Diagnostic Cytopathology

About the journal

Publisher: Wiley-Liss
Published: 1985 to the present, United States
Language: English
ISSN: 8755-1039 (print), 1097-0339 (electronic)
Its record in the NLM Catalog

2020s

Cytopathologic Features of Metastatic Malignant Mesothelioma With SMARCB1 (INI-1) Deficient Diagnosed by Ultrasound-Guided Fine-Needle Aspiration: A Case Report. J. Yang, J. Liu, J. Jin, et al. 2026;54(4):E87-E92. Case report PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare yet aggressive neoplasm that arises from mesothelial cells lining the thoracic and abdominal cavities, the pericardium, and the tunica testis. Characterized by rapid progression, high invasiveness, and a poor prognosis, MM poses significant clinical challenges. SMARCB1, also referred to as INI-1, hSNF5, or BAF47, is located on chromosome 22q11.2 and serves as a critical subunit of the SWI/SNF chromatin remodeling complex. INI-1 functions as a tumor suppressor and plays a vital role in DNA damage repair and regulation of cell growth. Case Presentation: A 37-year-old Chinese male with no history of asbestos exposure but a 10-year smoking history (30 cigarettes per day) presented with a cough lasting one month and a fever persisting for one day. Computed tomography (CT) showed multiple enlarged supraclavicular lymph nodes measuring up to 30 × 15 mm bilaterally. An ultrasound-guided fine-needle aspiration (FNA) of the left supraclavicular lymph nodes was subsequently performed. The SurePath-prepared liquid-based cytopathology (LBC) using Papanicolaou-staining revealed tumor cells organized in clusters with indistinct borders. The cells exhibited abundant cytoplasm and pleomorphic round nuclei, which displayed prominent nucleoli and mitotic activity. Additionally, scattered lymphoid fragments were observed in the background. The FNA sample was formalin-fixed and paraffin-embedded for cell block; 4-μm thick sections were prepared. Histological examination using HE-stained cell block revealed a solid sheet-like tumor growth characterized by minimal stroma and the absence of fibrovascular cores. The neoplastic cells had well-defined borders, abundant eosinophilic (partially clear) cytoplasm, and round-to-oval nuclei displaying focal atypia, finely dispersed chromatin, and prominent nucleoli. Immunohistochemistry (IHC) demonstrated positive staining for CK(pan), calretinin, D2-40, and SMARCA4, whereas NapsinA, TTF-1, P40, NUT, and WT-1 yielded negative results. The confirmed loss of INI-1 expression ultimately led to the diagnosis of metastatic INI-1 deficient MM. Conclusion: This case highlights the cytomorphological features and immunophenotype of INI-1 deficient MM diagnosed through FNA. An accurate diagnosis requires a thorough clinicopathological correlation and a comprehensive IHC panel.

© 2025 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.
The Diagnostic Value of Immunohistochemistry and Biomarkers in the Diagnosis of Mesothelioma in Pleural/Peritoneal Effusions. S.M. Selvaggi. 2026;54(9):631-636. PubMed · Publisher · Free full text

Abstract

Background: Mesothelioma is a rare tumor that arises from the serosal cells lining the serous cavities, most commonly the pleura followed by the peritoneum. Presenting symptoms include pleuritic pain and bloody effusions that recur. Although cytologic analysis cannot determine the mesothelial subtype or in situ from invasive disease, the application of biomarkers to serous effusions has aided in distinguishing benign from malignant mesothelial cells. This study evaluates the diagnostic value of specialized techniques in the cytologic diagnosis of mesothelioma pre- and post-implementation of biomarkers and a robust immunohistochemical (IHC) panel.

Methods: From January 1, 2013, through December 31, 2025, 26 effusions (20 pleural, six peritoneal) from 16 males and four females (mean, 72 years; median, 75 years) were evaluated and contained atypical mesothelial cells. In each case, ThinPrep slides were made for cytologic analysis and cell blocks were prepared for IHC and biomarker evaluation. Prior to 2017, the IHC markers were limited, whereas after that time, biomarkers including BAP1 and MTAP were available.

Results: Cytologically the effusions were cellular and contained atypical, enlarged mesothelial cells arranged singly and in clusters with a normal nuclear/cytoplasmic ratio. Five effusions (2013-2015) were diagnosed as suspicious for mesothelioma based on the cytologic findings and a limited IHC panel (calretinin, CK 5/6, TTF-1). The diagnosis was confirmed on biopsy/resection specimens. For 17 effusions (2017-2025), an expanded IHC and biomarker panel aided in the cytologic diagnosis of mesothelioma. Three effusions were from patients with a known history of pulmonary mesothelioma, so IHC stains were not performed. Histologic confirmation was done in 23 cases.

Conclusions: The application of IHC and biomarkers in combination with cytomorphology aids in the diagnosis of mesothelioma on fluid cytology.

© 2026 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.
Cytology of malignant pleural mesothelioma: Diagnostic criteria, WHO classification updates, and immunohistochemical staining markers diagnostic value. N. Shaker, D. Wu, A.M. Abid. 2022;50(11):532-537. PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy with a poor prognosis. Because of this tumor rarity and overlapping histologic features with other malignancy types, the histopathological findings and diagnostic immunohistochemical workup are essential in establishing the final diagnosis of MPMs. We aimed to review the diagnostic criteria, WHO tumor classification updates, and immunohistochemical staining markers diagnostic value to achieve an appropriate clinical diagnosis.

© 2022 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.
A rare case of primary effusion lymphoma in HIV negative patient: Diagnostic challenges and literature review. P. Malik, S.N. Khader, S. Asiry. 2021;49(6):785-789. Case report · Review PubMed · Publisher

Abstract

We present a rare case of primary effusion lymphoma (PEL) in a 75 year old, HIV-negative male patient with multiple comorbidities. Imaging studies revealed a massive right pleural effusion and a significant lung collapse with multiple plural soft tissue nodules. Immediate thoracentesis was performed. Cytologic evaluation of the pleural fluid showed abnormally large cell with increased nuclear to cytoplasmic ratio, irregular nuclear contours and prominent nucleoli, with phenotypic expression of HHV-8, CD138, CD30, and MUM1 markers and negative staining for epithelial and mesothelial markers. PEL is a rare and aggressive large B-cell lymphoma often affecting immunocompromised adults and is mostly associated with human herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV). However, cases in immunocompetent elderly patients have been reported. The cytomorphologic features of PEL overlaps with those of aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, and anaplastic large-cell lymphoma. Also, mesothelioma, metastatic carcinoma or melanoma should be considered in the differential diagnosis. Hence, PEL should be kept in mind in the diagnostic algorithm of cytological evaluation of serosal fluid not only in HIV positive patients but also HIV-negative elderly patients. In this report, we aim to highlight the cytologic and immunohistochemical staining pattern of this rare entity to increase awareness of this entity among cytopathologists.

© 2021 Wiley Periodicals LLC.
Effusion cytology of malignant mesothelioma enables earlier diagnosis and recognizes patients with better prognosis. S. Abd Own, J. Höijer, G. Hillerdahl, et al. 2021;49(5):606-614. PubMed · Publisher

Abstract

A conclusive diagnosis of malignant mesothelioma (MM) can be based on effusion cytology using the guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM. Briefly, the diagnosis is obtained when the mesothelial phenotype of malignant cells is established by ancillary techniques. This study is based on the comparison of the overall survival rates of patients with MM when diagnosed by effusion cytology, histopathology, or a combination of both. A total of 144 patients were diagnosed with epithelioid and mixed-type pleural MM at Karolinska University Hospital between 2004 and 2013. The diagnosis was obtained by histopathology in 74 cases and by cytological examination of pleural effusion in 70 cases. In 29 of the latter cases, a diagnostic biopsy was obtained simultaneously. A total of 104 patients received chemotherapy. All diagnoses were supported by clinical findings, including computer tomography scans. The median time between first symptoms and diagnosis was similar for cytology and histopathology. However, a delay of more than 6 months after first symptoms was seen in many patients in the histopathology group, resulting in late onset of treatment. The overall survival and proportion of long-term survival were significantly better for cases diagnosed by cytology. Similarly, a better survival, following a cytological diagnosis, was also seen in patients who were only provided the best supportive care. Accurate cytological diagnosis enables conclusive diagnosis of MM. Our finding enables the initiation of treatment as soon as the cytological diagnosis is established, avoiding further delay and deterioration of patient survival and possibilities for treatment.

© 2020 The Authors. Diagnostic Cytopathology published by Wiley Periodicals, Inc.
HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. K. Hiroshima, D. Wu, S. Hamakawa, et al. 2021;49(5):622-632. PubMed · Publisher

Abstract

Background: The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion.

Methods: Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization. Staining scores were calculated for IHC by adding the number of categories for the staining intensity and the staining extension.

Results: HEG1 was positive in all (41/41) MMs, but negative in carcinomas, except for ovarian carcinomas. Overall 76.9% (20/26) of RMCs and 28.6% (6/21) of ovarian carcinomas expressed HEG1. BAP1 loss was found in 71.1% of MMs, but none was found in RMCs. MTAP loss was found in 76.2% of MMs, but none was found in RMCs. 73.9% of MMs harbored HD of CDKN2A. There was concordance between loss of MTAP and HD of CDKN2A in 95% of MMs.

Conclusion: HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following methods: IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.

© 2020 Wiley Periodicals LLC.
Immunochemistry in the work-up of mesothelioma and its differential diagnosis and mimickers. W.S. Mneimneh, Y. Jiang, A. Harbhajanka, et al. 2021;49(5):582-595. Review PubMed · Publisher

Abstract

The differential diagnosis in cellular effusions with cytological atypia often includes malignant mesothelioma (MM), reactive mesothelial proliferation, and malignancies of metastatic origin, particularly carcinomas. The International Reporting System for Serous Fluid recently established guidelines for reporting MM. In conjunction with the cytomorphologic evaluation, the role of immunochemistry (IC) was emphasized as a very useful tool in the workup of serous fluids, especially with the availability of novel markers. Utilizing a panel of markers, IC allows the characterization of the cells, whether mesothelial or not, and when mesothelial origin is established, IC can frequently assist in delineating its benign or malignant nature. IC can also confirm metastatic disease, allowing the identification of the primary origin in most cases. This review summarizes the current status of IC and its role in the diagnosis of MM and its differential diagnosis in serous fluids.

© 2021 Wiley Periodicals LLC.
Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena. A. Re, D. Shersher, A. Allen, et al. 2021;49(6):E234-E237. Case report PubMed · Publisher

Abstract

Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.

© 2020 Wiley Periodicals LLC.
Osteosarcoma pleural effusion: A diagnostic challenge with some cytologic hints. B. AbdullGaffar. 2021;49(1):E40-E44. Case report PubMed · Publisher

Abstract

Pleural effusions can be the first manifestation, recurrence, or metastasis of small round cell sarcomas in children. The most common are Ewing sarcoma, neuroblastoma, and rhabdomyosarcoma. The cytomorphology is variable, the cells can be cohesive, single cells, small or large, morphologically mimicking lymphomas, carcinomas, melanomas, and mesothelioma depending on the sarcoma involved. Osteosarcomas are rare. Their rarity, variable histomorphologic features, immunophenotypic heterogeneity, being of osseous or extraosseous origin and focality of malignant osteoid matrix make their cytologic recognition a diagnostic challenge. They can be confused with small round cell sarcomas, may be misinterpreted as degenerative inflammatory cells, or masked by florid reactive mesothelial hyperplasia particularly in pleural effusions. However, attention to certain cytomorphologic features in smears and cellblock sections should raise suspicion. We report a case of a 9-year-old child who presented with cough, chest pain and breathing difficulty, left pleural effusion, a collapsed consolidated lower lung lobe, and a clinical impression of pneumonia. Pleural fluid cytology was initially reported as inflammatory effusion with florid reactive mesothelial hyperplasia. Tissue biopsy of the lung mass showed histomorphologic features consistent with osteosarcoma. A careful look at the cytology materials and cellblock sections showed helpful cytomorphologic features that were masked by florid reactive mesothelial cells and misinterpreted as degenerative inflammatory lymphocytes. An extracellular matrix was a helpful hint. Malignant pleural effusion secondary to osteosarcoma is rare. Cytologic examination may help reach the correct diagnosis if the smears and cellblock sections are carefully evaluated for certain helpful cytomorphologic features, particularly osteoid matrix.

© 2020 Wiley Periodicals LLC.
Root cause analysis of indeterminate diagnoses in serous fluids cytopathology. H.N. Gokozan, A. Harbhajanka, S. Lyden, et al. 2021;49(5):633-639. PubMed · Publisher

Abstract

Introduction: The International System for Reporting Serous Fluid Cytopathology proposed five diagnostic categories: Nondiagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM) and Malignant (MAL) (Primary or Metastatic). The indeterminate (AUS/SFM) categories are challenging for management. The goal of this study is to reveal the root causes contributing to indeterminate diagnoses (ID).

Materials And Methods: We searched our archives between 1 January 2017 and 30 June 2019, and performed a root cause analysis (RCA) using the "5 whys" method to determine the contributing factors of ID.

Results: Nine hundred eleven specimens were evaluated and diagnosed: ND (9, 1%), NFM (667, 73.2%), AUS (51, 5.6%), SFM (27, 3%) and MAL (157, 17.2%). More than one factor contributed to 38/78 ID. Low volume (<50 cc), and low cellularity were identified in 31 and 51 cases, respectively. Three cases were simply deferred to concurrent biopsy. Eleven cases were called atypical, favor reactive mesothelium despite confirmatory IHC. Atypical lymphoid population was reported in seven cases. Cellblocks (CB) were low in cellularity despite volume >1000 mL in 13 cases. Two mesotheliomas were underdiagnosed as suspicious.

Conclusions: Low cellularity and low volume were the most common contributing factors, highlighting the importance of adequate sample collection. Adequate volume specimens with low cellularity may benefit from a close inspection and a second CB. Some IDs can be switched to NFM or MAL with careful consideration of clinical, radiologic findings and ancillary testing, and concurrent surgical pathology correlation when available.

© 2021 Wiley Periodicals LLC.
Alveolar rhabdomyosarcomas involving serous cavity fluid specimens exhibit diverse cytomorphologies: A case report and review of the literature. R.M. Jones, C.J. VandenBussche. 2020;48(11):1155-1161. Case report · Review PubMed · Publisher

Abstract

Involvement of serous cavity specimens by alveolar rhabdomyosarcoma (ARMS) is a rare event and only a few case reports have been reported in the literature, with conflicting cytomorphologic patterns. Herein, we report on a 41-year-old man with no significant past medical history who presented with pancytopenia and shortness of breath and was found to have widely metastatic sinonasal alveolar rhabdomyosarcoma, including involvement of the pleura. The pleural fluid specimen was cellular and contained ARMS cells in small-to-medium sized three-dimensional fragments that resembled an adenocarcinoma or mesothelioma, and numerous single cells were seen in the background. The individual tumor cells demonstrated variable morphology; all were large, with varying degree of cytoplasm, and multinucleated cells were commonly seen in the background. The cells were negative for calretinin and claudin-4 and were positive for myogenin, confirming the diagnosis. Given the cytomorphologic diversity of ARMS seen in serous fluid specimens, patient history and the use of confirmatory immunostains are essential.

© 2020 Wiley Periodicals LLC.
Categorical systems for reporting of cytology specimens: Following the footsteps of Bethesda-like reporting systems. L.J. Layfield, Z. Baloch. 2020;48(10):859-861. Editorial PubMed · Publisher
Current applications of molecular testing on body cavity fluids. D. Pinto, F. Schmitt. 2020;48(9):840-851. PubMed · Publisher

Abstract

Introduction: Effusion cytology has a high sensitivity for the diagnosis of malignancy and provides abundant material for molecular testing. Effusion draining is a minimally invasive procedure with few complications.

Materials And Methods: We performed a review of publications regarding the use of molecular testing in serous effusions.

Results: In diagnostics, BAP-1 IHC and CDKN2A FISH are powerful tools for the diagnosis of malignant mesothelioma. FISH, PCR, and EBER-ISH work well in lymphomas. RT-PCR may enhance the diagnosis of secondary epithelial malignancies. In theranostics, molecular testing on serous effusions is widely reported for the detection of alterations in genes related to lung carcinomas, such as EGFR, ALK, ROS1, and BRAF. PD-L1 expression testing by immunohistochemistry (IHC) also seems to be viable in this type of sample. HER2 FISH and IHC provide actionable results in the context of breast malignancies. Results in serous effusions seem to be equivalent to tissue biopsies for most applications and across different molecular techniques. The most interesting technology is next-generation sequencing (NGS), given its ability to sequence multiple genes on a single sample and the decreasing costs that have closely followed increasing throughputs. Cell-free DNA from effusion supernatants might be the most promising area for future research, showing superiority to serum and even to cell-block samples in limited studies.

Conclusions: Molecular tests are viable in serous effusion specimens when sufficient material is available. Given the rising importance of molecular testing we expect this to be an active field of research in the near future.

© 2020 Wiley Periodicals, Inc.
Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating. M. Sheaff. 2020;48(10):877-879. PubMed · Publisher

Abstract

The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma produced by the International Mesothelioma Interest Group and which are endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology are reviewed and discussed. This (predominantly) evidence-based document provides a robust and useful framework for diagnosticians and guideline producers to emphasise and promote the value, power and role of cytology in mesothelioma diagnosis and management with comments and suggestions about how the guidelines can be updated and improved in the future.

© 2019 Wiley Periodicals, Inc.

2010s

A case of malignant mesothelioma pleural effusion with MOC-31, BerEP4, and calretinin expression. P. Zhao. 2019;47(12):1321-1323. Case report · Letter PubMed · Publisher
Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions. I. Cozzi, F.A. Oprescu, E. Rullo, et al. 2018;46(1):9-14. PubMed · Publisher

Abstract

Background: The important diagnostic challenge facing the cytopathologist is whether a mesothelial proliferation on effusions represents a malignant mesothelioma (MM) or a benign mesothelial hyperplasia (MH). Here, we evaluated the diagnostic utility of BAP1 immunohistochemistry (IHC) in distinguishing between reactive and neoplastic mesothelial cells.

Methods: In pleural and peritoneal effusions from 147 patients with diagnosed MM or with a differential diagnosis of MM and MH, the expression of BAP1 was examined by IHC on paraffin-embedded cell blocks (n = 121) and biopsies (n = 44). Included were also synchronous and methacronous cytology/biopsy pair samples. BAP1 IHC was evaluated for nuclear staining as positive or negative on target mesothelial cells, with appropriate internal control.

Results: In MM cases, loss of BAP1 nuclear staining was observed in 76.5% of the cell blocks and 47.5% of the biopsies. All BAP1-negative cases with a differential diagnosis of benign and malignant mesothelial proliferations were MM at follow-up. All MH cases, the 29% of epithelial MM and the 90% of nonepithelial MM, retained BAP1 expression. Synchronous and methacronous biopsy/cytology pairs showed matching BAP1 results.

Conclusion: In effusions with mesotheliomatous cells or atypical mesothelial cells of uncertain significance, negative BAP1 IHC strongly supports a diagnosis of MM. With prudence in interpreting immunostaining, BAP1 may be included in IHC panels for MM cytodiagnosis, given its high specificity and sensitivity.

© 2017 Wiley Periodicals, Inc.
Pleural fluid cytology samples in cases of suspected lung cancer: An experience from a tertiary care centre. G. Kaur, R. Nijhawan, N. Gupta, et al. 2017;45(3):195-201. PubMed · Publisher

Abstract

Objective: Pleural effusion is present in some patients with lung carcinoma. This study was undertaken to evaluate the role of pleural fluid cytology in suspected cases of lung carcinoma.

Methods: In this prospective study, 86 cases of suspected primary lung carcinoma associated with pleural effusion were included. Cytomorphology of conventional smears was combined with LBC smears and a cytomorphological diagnosis was offered. An immunopanel of CK7, CK5/6, p63, TTF1, calretinin, and CD56 was applied on cell blocks. Additional immunochemical markers were performed based on clinical details and cytomorphology, wherever indicated.

Results: The mean age of the patients was 56.8 years. The female to male ratio was 2.1:1. Lung nodule/mass could be detected in 70.9% cases by CECT chest. Cytomorphology was evaluated in all the 86 cases and IHC was used to refine the cytomorphological diagnosis. After IHC along with clinico-radiological details, 61/86 (71%) cases were confirmed as metastasis from lung primary, 5/86 (5.8%) were diagnosed as metastatic adenocarcinoma of extrapulmonary origin, and 6/86 (7%) were metastatic SCC. A diagnosis of adenosquamous carcinoma was suspected in five cases. Other cases included small cell carcinoma (n = 2), large cell carcinoma (n = 2), large cell neuroendocrine carcinoma (n = 3), and mesothelioma (n = 1). One case remained "uncategorized" even after IHC.

Conclusions: Immunohistochemistry (IHC) performed on the pleural fluid sample can accurately diagnose and subtype primary lung carcinoma even in cases where radiology failed to identify a definite lung lesion. IHC can further help in delineating primary site in tumors of extrapulmonary origin. © 2017 Wiley Periodicals, Inc. Diagn. Cytopathol. 2017;45:195-201. © 2016 Wiley Periodicals, Inc.

© 2017 Wiley Periodicals, Inc.
Significance of flower pot cells in effusion cytology. V. Bharani, P. Singh, N. Gupta, et al. 2017;45(10):925-927. Case report PubMed · Publisher

Abstract

Cells with long polar hair-like processes referred to as 'flower pot cells' are a rare but beautiful morphological feature observed in effusions of diverse etiologies. This report describes these cells in effusions seen in ovarian borderline serous tumours, malignant mesothelioma and in reactive mesothelial cells with or without accompanying malignant cells. These processes were better appreciated in air-dried May-Grunwald-Giemsa stained smears.

© 2017 Wiley Periodicals, Inc.
The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions. C. Sadullahoglu, D. Nart, A. Veral. 2017;45(2):118-124. PubMed · Publisher

Abstract

Background: All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC-31 and EZH2) in serosal effusions.

Methods: The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC-31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow-up in the absence of any surgical material of the patient in the hospital archive system.

Results: None of the benign cases showed MOC-31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases.

Conclusion: In conclusion, it could be considered cost-effective to use a double immunohistochemical antibody kit for these two markers, MOC-31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118-124. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens. Z. McCroskey, G. Staerkel, S. Roy-Chowdhuri. 2017;45(4):312-319. PubMed · Publisher

Abstract

Background: Loss of BAP1 has recently been described as a highly specific marker for distinguishing malignant mesotheliomas (MM) from benign mesothelial proliferations (BMP). The aim of this study was to evaluate the utility of BAP1 in cytospin and cell block (CB) preparations.

Methods: We searched the database at our institution for cases of MM (n = 21) and BMP (n = 11). A Papanicolaou stained cytospin preparation and CB section from each case were selected for BAP1 staining. The results were scored as nuclear BAP1 staining, absent or present. Positive staining in non-neoplastic cells was noted as internal control.

Results: In the study group, MM cells showed a loss of BAP1 staining in 18/21(86%) cytospin and 19/21(90%) CB preparations. All cytospins showed appropriate positive nuclear staining in the "internal control" inflammatory cells. However, only 17/21(81%) of CB sections showed good internal control with positive nuclear staining in inflammatory cells. The intensity of BAP1 nuclear staining varied across cases. Overall, the intensity of staining was higher in cytospins, providing sharper contrast between the malignant cells with loss of stain and the benign inflammatory cells with retained stain in cases of MM. Sensitivity/specificity for cytospins when compared with CB was 86/100 and 88/100%, respectively.

Conclusions: Cytospin preparations have comparable sensitivity and specificity to CB with greater intensity and better contrast between negative and positive nuclei making the interpretation easier. We advise to interpret BAP1 IPOX stain results with caution with careful attention to staining of background nonmalignant "internal control" cells. Diagn. Cytopathol. 2017;45:312-319. © 2016 Wiley Periodicals, Inc.

© 2017 Wiley Periodicals, Inc.
BAP1 Immunostain and CDKN2A (p16) FISH Analysis: Clinical Applicability for the Diagnosis of Malignant Mesothelioma in Effusions. A.E. Walts, K. Hiroshima, S.M. McGregor, et al. 2016;44(7):599-606. PubMed · Publisher

Abstract

Background: Loss of BAP1 by immunohistochemistry (IHC) and CDKN2A(p16) deletion by fluorescence in situ hybridization (FISH) have been proposed to distinguish malignant mesothelioma (MM) from atypical reactive mesothelial proliferations (ARMP) in effusions but it is uncertain whether both tests are needed routinely.

Methods: Paraffin embedded blocks from 67 effusions (32 MM, 35 ARMP) were evaluated with BAP1 IHC. 38 of them (17 MM, 21 ARMP) were also analyzed with CDKN2A (p16) FISH. Criteria for MM were absence of BAP1 nuclear staining in >50% of atypical mesothelial cells in the presence of a positive internal control, and/or CDKN2A(p16) homozygous or hemizygous deletion pattern in >15% or >41.5% of atypical mesothelial cells, respectively. Sensitivity (SS), specificity (SP), positive, and negative predictive values (PPV, NPV) for MM were calculated.

Results: 17 of 32 MM were correctly diagnosed by IHC (SS 53.1%, SP 85.7%, PPV 77.3%, NPV 64.3% for MM). In the subset of 38 cases studied by IHC and FISH, the SS, SP, PPV, and NPV of IHC for MM were 41.2, 81.0, 63.6, and 63.0%, respectively. 7 of 17 MM were diagnosed by FISH (SS 41.2%, SP 100%, PPV 100%, NPV 67.7% for MM).

Conclusion: BAP1 IHC and CDKN2A(p16) FISH yield similar sensitivities for MM in paired samples but FISH has a higher specificity. To diagnose effusions with atypical mesothelial cells, use of both tests is optimal. However, BAP1 IHC alone may be sufficient to diagnose MM when clinical, imaging, and cytological findings strongly suggest MM. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc. Diagn. Cytopathol. 2016;44:599-606. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16. K. Hiroshima, D. Wu, M. Hasegawa, et al. 2016;44(7):591-8. PubMed · Publisher

Abstract

Background: Mesothelioma patients often present with serosal effusions, which are ideal for cytopathological diagnoses. However, the morphological overlap between malignant and benign mesothelial proliferation can make a conclusive cytological diagnosis of mesothelioma elusive because immunohistochemical staining does not discriminate definitively between the two in this setting. p16 is deleted in up to 80% of pleural mesotheliomas. The aim of this study was to establish the correlation between the p16 deletion status of the cell block with that of its corresponding tumor using fluorescence in situ hybridization (FISH) analysis for individual patient tumors.

Methods: Twenty-two biopsies and 24 corresponding cell blocks, containing serosal effusions with atypical mesothelial cells from 22 patients with histologically confirmed pleural mesotheliomas, were analyzed with p16 FISH. Seventeen cell blocks consisting of serosal effusions with reactive mesothelial cells from nonmesothelioma cases were also analyzed. Combined immunofluorescence and FISH were also performed.

Results: Seventeen of the 22 mesothelioma patients (77.3%) showed homozygous deletions of p16 in the tumor tissue and in the atypical mesothelial cells from the cell blocks. p16 FISH followed by immunofluorescence with EMA was helpful towards identifying the mesothelioma cells in the cell blocks.

Conclusion: We confirmed that the p16 FISH results obtained from the cell blocks are as reliable as those from the tissue sections. Cell block analysis is recommended for patients with serosal effusions of unknown origins with the following methods: immunohistochemistry should be performed to validate the mesothelial origin, and p16 FISH should be performed to confirm malignancy. Diagn. Cytopathol. 2016;44:591-598. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
Cytomorphologic findings of malignant mesothelioma in FNA biopsies and touch preps of core biopsies. A. Paintal, K. Raparia, R. Nayar. 2016;44(1):14-9. PubMed · Publisher

Abstract

Background: Given the lack of recent literature regarding the aspiration cytology of immunohistochemically confirmed malignant mesothelioma (MM), we were interested in reviewing the experience of our institution and establishing useful morphologic criteria.

Methods: Seventeen aspiration and touch preparation specimens with a diagnosis of MM obtained between 2002-2013 were reviewed along with 20 cases of adenocarcinoma and 16 cases of squamous cell carcinoma. The utility of a number of morphologic features was evaluated.

Results: In most cases of MM, a consistent pattern emerged. Aspirates and touch preps were cellular with irregularly shaped 2 and 3 dimensional clusters. The individual cells were predominantly angulated and had dense cytoplasm with eccentric nuclei. In every case, a minority of tumor cells contained prominent microvacuoles. The chromatin pattern tended to be fine with small nucleoli. While most cases were cytologically monotonous, five cases displayed striking pleomorphism and three cases contained occasional large atypical cells. Two cases contained metachromatic background material. Features which were most useful in discriminating MM from adenocarcinoma were angulated cell shape(P = 0.0002), dense cytoplasm(P = 0.0001), and cytoplasmic microvacuoles(P = 0.0001). In our material, cases of squamous cell carcinoma were often difficult to distinguish from MM. Useful discriminatory features present in squamous cell carcinoma included ink dot nuclei(P = 0.0003), a "dirty" cystic, necrotic background (P = 0.0027) and tumor balls with peripheral spindling(P = 0.0041).

Conclusion: Most cases of MM have a consistent appearance in core biopsy touch preps and FNAs. Distinguishing MM from adenocarcinoma and squamous cell carcinoma can be facilitated by evaluating a few key morphologic features.

© 2015 Wiley Periodicals, Inc.
Direct comparison of liquid-based and smear-based cytology with and without rapid on-site evaluation for fine needle aspirates of thoracic tumors. A. Mfokazi, C.A. Wright, M. Louw, et al. 2016;44(5):363-8. PubMed · Publisher

Abstract

Background: Liquid-based cytology (LBC) and rapid on-site evaluation (ROSE) are proposed to improve the quality of fine needle aspirates (FNA) and their diagnostic yield compared with conventional smear cytology (CSC). This prospective study directly compared outcomes of sonar-guided FNA of thoracic tumors supported by LBC, CSC, or CSC with ROSE.

Methods: Three aspirates each for both LBC and CSC with separate 22G spinal needles in a randomized, alternating sequence during 64 transthoracic FNA of thoracic tumors were collected. Smears were prepared by cytology staff on site but evaluated with ROSE only when all six samples had been collected. If no diagnostic material was found on the first three CSC additional needle passes guided by ROSE were performed.

Results: Final diagnoses were non-small cell lung cancer in 50 (78.1%), small cell lung cancer in 11 (17.2%), mesothelioma in 1 (1.6%), and inflammation in 2 cases (3.1%), respectively. LBC and CSC were diagnostic in 42 (65.6%) and 49 (76.6%) cases, respectively (P = 0.039), with both methods diagnostic in 41 cases (64.1%). Fifteen cases (23.4%) remained undiagnosed following three passes for CSC but 9 (14.1%) of these were diagnosed using FNA and ROSE with a total yield of 58 cases (90.6%; P < 0.001).

Conclusion: The diagnostic yield of transthoracic FNA submitted for LBC is significantly lower than with CSC when slides are prepared professionally. ROSE significantly increases the yield of transthoracic FNA.

© 2016 Wiley Periodicals, Inc.
Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology. T. Oda, S. Ogata, S. Kawaguchi, et al. 2016;44(6):499-504. PubMed · Publisher

Abstract

Background: Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology.

Methods: In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores).

Results: In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively).

Conclusions: Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
Small cell mesothelioma: A rare entity and diagnostic pitfall mimicking small cell lung carcinoma on fine-needle aspiration. Y. Zhang, A. Afify, R.F. Gandour-Edwards, et al. 2016;44(6):526-9. Case report PubMed · Publisher

Abstract

Small cell mesothelioma (SCM) is an extremely rare variant of epithelioid mesothelioma that can be mistaken for other forms of small round blue cell tumors, particularly small cell lung carcinoma (SCLC). Here, we describe a fine-needle aspiration (FNA) from a pleural lesion in a 75-year-old man with a history of known asbestos exposure. The FNA revealed cohesive clusters of uniform small round blue cells with high nuclear-to-cytoplasmic ratio, finely powdery chromatin, small inconspicuous nucleoli, and scant amount of cytoplasm. Mitoses were infrequent and nuclear molding was absent. Immunochemical profile supported a mesothelial origin, which was later confirmed by pleurectomy with a diagnosis of SCM. This report demonstrates the difficulties in cytologic evaluation of lung FNAs in differentiating SCM from SCLC or other small round blue cell tumors. As therapy differs for SCM, early recognition of the cytologic features is essential in making the correct diagnosis needed for appropriate clinical management. Diagn. Cytopathol. 2016;44:526-529. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations. K. Nabeshima, S. Matsumoto, M. Hamasaki, et al. 2016;44(9):774-80. Review PubMed · Publisher

Abstract

Because most of malignant pleural mesothelioma (MPM) patients first present with pleural effusion, detection of mesothelioma cells on effusion smears is critical for early diagnosis. Recently, accumulating evidence indicating that the cytological diagnosis of MPM supported by ancillary techniques is as reliable as that based on histopathology has led to new guidelines for the cytopathologic diagnosis of MPM. Based on the guidelines, a combination of cytomorphological criteria and verification by ancillary techniques is required for the cytologic diagnosis of MPM. Detection of p16 homozygous deletion by fluorescence in situ hybridization (FISH) is the most reliable ancillary technique for differentiating MPM from reactive mesothelial cells (RMC) because of its relatively high sensitivity and extremely high specificity. We showed that the p16 deletion status of MPM cells in pleural effusions reflected that of the underlying invasive MPM tissues, indicating the usefulness of p16 FISH in effusion smear cytology for MPM diagnosis. Thus, for differentiating MPM from RMC, we propose to perform p16 FISH as often as possible. A positive p16 homozygous deletion supports the diagnosis of MPM. However, a negative result does not rule out the possibility of MPM. In such cases, a morphological assessment is critical. Therefore, we analyzed the morphological characteristics of p16 deletion-positive mesothelioma cells using a combination of virtual microscopy and p16 FISH, and identified three morphological characteristics useful for the differentiation, including cell-in-cell engulfment with or without hump formation, multinucleate cells, and larger berry-like cell aggregates. Diagn. Cytopathol. 2016;44:774-780. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.
An update on pleuro-pulmonary cytopathology: Part i: Cytological diagnosis of mesothelioma and molecular cytology of lung cancer with an historical perspective. C.W. Bedrossian. 2015;43(7):513-26. Editorial · Historical article · Review PubMed · Publisher
Desmoplastic small round cell tumor with sphere-like clusters mimicking adenocarcinoma. Y. Hattori, A. Yoshida, N. Sasaki, et al. 2015;43(3):214-7. Case report PubMed · Publisher

Abstract

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere-like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients.

© 2014 Wiley Periodicals, Inc.
Excessive lipid-phagocytosis of neutrophils in a patient with mesothelioma. C. Morales-Indiano, M. Carbonell Prat, E. Castellà Fernández, et al. 2015;43(10):830-2. Case report PubMed · Publisher
Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. A. Hjerpe, V. Ascoli, C.W. Bedrossian, et al. 2015;43(7):563-76. PubMed · Publisher

Abstract

Objective: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.

Data Sources: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Rationale: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

© 2015 Wiley Periodicals, Inc.
Preoperative cytological diagnosis of malignant mesothelioma of tunica vaginalis. A. Bandyopadhyay, S. Bhattacharya, K. Konar. 2015;43(10):850-4. PubMed · Publisher

Abstract

Malignant mesothelioma of tunica vaginalis testis is a rare aggressive neoplasm with ∼200 cases reported so far. A correct preoperative diagnosis of this rare tumor is difficult. Fine-needle aspiration cytology (FNAC) is a rapid and inexpensive diagnostic tool that may prove helpful in such cases. Very few cases have been diagnosed on cytology so far, and the descriptions of the cytological features have rarely been described in the literature. In this report we present the cytological features of malignant mesothelioma of tunica vaginalis testis which was diagnosed by FNAC and subsequently confirmed by histopatholoy and immunohistochemical (IHC) studies.

© 2015 Wiley Periodicals, Inc.
Adenomatoid mesothelioma with intranuclear inclusion bodies: a case report with cytological and histological findings. T. Kawai, K. Kawashima, H. Serizawa, et al. 2014;42(5):436-40. Case report PubMed · Publisher

Abstract

We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball-like clusters, with a tubular pattern, composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S(8) . Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology.

Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.
CD147 immunohistochemistry discriminates between reactive mesothelial cells and malignant mesothelioma: an expanded analysis of the data. S.J. Geyer. 2014;42(8):734. Letter · Comment PubMed · Publisher
EZH2, a unique marker of malignancy in effusion cytology. H. Jiang, R. Gupta, J. Somma. 2014;42(2):111-6. PubMed · Publisher

Abstract

Distinguishing reactive mesothelial cells from metastatic disease, typically adenocarcinoma, in effusion cytology can be challenging at times. We currently use a panel of immunocytochemical markers for select cases including MOC-31 and BerEp4, but difficulties still exist. Enhancer of zeste homologue 2 (EZH2) plays important roles in epigenetic silencing and cell cycle regulation and is upregulated in a wide variety of malignancies. Thus, we hypothesized that EZH2 immunocytochemistry, which to our knowledge has not yet been reported on cytology material, might serve as a unique marker of malignancy in morphologically equivocal effusion specimens by highlighting aberrant protein expression in malignant cells. A total of 96 (48 benign and 48 malignant) effusion cases were selected retrospectively from our department archives. All malignant cases were metastatic adenocarcinomas except for three high grade neuroendocrine carcinomas (two lungs and one ovary), one cervical squamous cell carcinoma, and one epithelioid endometrial stromal sarcoma. The 48 benign cases were all negative for EZH2, and 43 of 48 malignant effusions were positive. As a solitary marker, EZH2 exhibited a sensitivity of 90% and a specificity of 100% (P < 0.0001). EZH2 functioned as a unique and accurate marker of malignancy in this series of effusions. Relative to published data, EZH2 demonstrated a sensitivity comparable to MOC-31 and superior to BerEp4, and a specificity superior to both of these commonly used immunostains. Thus, EZH2 is likely to be of great value as an adjunct to morphology in diagnosing malignancy in effusion specimens.

Copyright © 2013 Wiley Periodicals, Inc.
Telomerase activity analyzed with TRAP in situ provides additional information in effusions remaining equivocal after immunocytochemistry and hyaluronan analysis. E. Adell, A. Dejmek. 2014;42(12):1051-7. PubMed · Publisher

Abstract

Cytology is central in the diagnosis of malignancy in effusions. Ancillary techniques, mainly immunocytochemistry, have considerably improved the sensitivity but some 10% of all cases remain equivocal and require the addition of new diagnostic modalities. We have previously shown that strong nuclear telomerase activity determined with Telomere Repeat Amplification Protocol (TRAP) in situ is specific for malignant cells and could be a candidate for an additional test. Thirty effusions remaining diagnostically equivocal after the use of immunocytochemistry and the determination of the hyaluronan content were reviewed and their TRAP in situ reactivity was related to the definitive diagnoses based on all available data. There were seven effusions from patients with definitive benign diagnoses and 23 effusions from patients with definitive malignant diagnoses. Strong telomerase activity was seen only in effusions from patients with definitive malignant diagnosis, all effusions from patients with benign disease lacking strong telomerase activity, whereas eight of the malignant cases, including three cases of epithelial mesothelioma, showed strong reactivity. Strong nuclear TRAP in situ reactivity was demonstrated only in effusions from patients with verified malignant disease. Although the study is small, it suggests that TRAP in situ activity provides diagnostic information in about one-third of effusions remaining cytologically equivocal after the use of current ancillary techniques. The most striking diagnostic improvement appears to be gained in epithelial mesotheliomas.

© 2014 Wiley Periodicals, Inc.
"Cannonballs" and psammoma bodies: unusual cytologic features of metastatic pulmonary small-cell carcinoma in a pleural effusion. A.B. Conway, M.K. Hart, J. Jessurun, et al. 2013;41(3):247-52. Case report PubMed · Publisher

Abstract

Large three-dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small-cell carcinoma occurring in an 88-year-old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three-dimensional neoplastic cell aggregates ("cannonballs"), associated with rare psammoma bodies. Although the crowded three-dimensional tumor-cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small-cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic "cell-in-cell" and "stack-of-coins" arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound-guided fine-needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small-cell carcinoma. Metastatic pulmonary small-cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three-dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall.

Copyright © 2011 Wiley Periodicals, Inc.
Cytomorphologic features of metastatic urothelial carcinoma in serous effusions. C.C. Huang, A. Attele, C.W. Michael. 2013;41(7):569-74. PubMed · Publisher

Abstract

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, "windows" between the cells, two-tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the "cell wrapping" of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel.

Copyright © 2012 Wiley Periodicals, Inc.
Deciduoid mesothelioma: cytologic presentation and diagnostic pitfalls. C.C. Huang, C.W. Michael. 2013;41(7):629-35. Case report PubMed · Publisher

Abstract

We report two cases of malignant deciduoid mesothelioma (MDM), a very rare variant of malignant mesothelioma (MM). Case 1: An 18-year-old male with no history of asbestos exposure presented with worsening abdominal pain, anorexia, and vomiting after a motor vehicle accident. A CT scan showed small amount of ascites and abdominal mass. An exploratory laparotomy revealed multiple yellow tan, firm nodules on the peritoneum and omentum. He received palliative treatment and died 5 months after the diagnosis. Case 2: A 64-year-old female with history of asbestos exposure initially presented with abdominal distension. CT scan showed abdominal mass with a large amount of ascites. A diagnostic laparoscopy revealed multiple peritoneal nodules. She underwent several regimens of chemotherapy over a period of 69 months and is still alive to date. In both cases, features of mesothelial origin were subtle and the smears showed predominantly single cells with marked nuclear atypia. The second case also contained few two-dimensional loose cell clusters with scalloped or hobnail borders. The clusters often exhibited a pseudoacinar structure surrounding a globular extracellular material. Groups of three to four cells often formed doublets and triplets with cell-to-cell windows. Our results show that MDM may not present with the traditional cytological features described in MM and can manifest with more nuclear pleomorphism resulting in erroneous diagnosis. Recognition of the subtle mesothelial features along with the appropriate ancillary tests is essential for accurate diagnosis.

Copyright © 2012 Wiley Periodicals, Inc.
Distinguishing benign from malignant mesothelial cells in effusions by Glut-1, EMA, and Desmin expression: an evidence-based approach. M. Kuperman, R.R. Florence, L. Pantanowitz, et al. 2013;41(2):131-40. PubMed · Publisher

Abstract

Distinguishing malignant mesothelioma (MM) from reactive mesothelial hyperplasia (RM) may be difficult in effusions. This study tested the hypothesis that immunocytochemistry (IC) in effusion cell blocks (CB) can distinguish MM from RM and that the results may be applied to individual specimens. External validation of a risk score (RS) model associating sensitivity and specificity was applied to an external set of MM and RM specimens from a separate institution. Forty three effusion cytology CBs of 25 confirmed malignant mesotheliomas were compared to CBs of 23 benign mesothelial effusions without inflammation and 13 reactive mesothelial proliferations associated with inflammation. Glut-1, EMA, and Desmin expression were evaluated by immunocytochemistry on CBs. Each antibody was compared using ROC values, where the area under the curve (AUC) was 0.90, 0.82, and 0.84 for Glut-1, EMA, and Desmin, respectively. Logistic regression (LR) analysis was applied to a combination of Glut-1 and EMA. A combined ROC curve was modeled for Glut-1 and EMA (AUC = 0.93). A RS = 2 × (Glut-1%) + 1 × (EMA%) was created from this ROC curve. When applied to an external set of MM and RM, the RS resulted in an ROC with AUC = 0.91. In conclusion, a RS derived from a LR of Glut-1 and EMA IC greatly improves the distinction between MM from RM cells in individual effusions. The study illustrates principles of evidence-based pathology concerning internal and external test performance in the differential diagnosis of MM versus RM.

Copyright © 2011 Wiley Periodicals, Inc.
Familial mesothelioma in first degree relatives. A.M. Kalogeraki, D.J. Tamiolakis, E.D. Lagoudaki, et al. 2013;41(7):654-7. PubMed · Publisher

Abstract

Occupational asbestos exposure is believed to be the primary etiologic link to mesothelioma. However, in the evaluation of familial mesothelioma, it is important to consider the possibility of household exposure to asbestos. In this study, we report a family in which the father with prolonged occupational asbestos exposure developed malignant pleural mesothelioma and his daughter 14 years later mesothelioma in situ with focally early invasion. Several reports of familial aggregations of mesothelioma strongly support that genetic factors in collaboration with environmental exposure may contribute etiologically to an as yet unknown fraction of occurrence of this disease.

Copyright © 2012 Wiley Periodicals, Inc.
Lymphohistiocytoid mesothelioma of the pleura: a case report with cytological findings. F. Tresserra, M. Castella, G. Fabra, et al. 2013;41(6):546-9. Case report PubMed · Publisher

Abstract

Lymphohistiocytoid malignant mesothelioma is an infrequent variant of sarcomatoid mesothelioma representing approximately 0.5-3.3% of malignant mesotheliomas. It has been related to asbestos exposure. The tumor is characterized by a diffuse large histiocyte-like cells proliferation mixed with an inflammatory infiltrate of lymphocytes and plasma cells. Its cytological diagnosis is difficult. We present a case of a 67-year-old female with lymphohistiocytoid mesothelioma involving the left pleura. The cytological, histological, and immunohistochemical features are discussed.

Copyright © 2011 Wiley Periodicals, Inc.
Malignant biphasic peritoneal mesothelioma in a child: consideration of other diagnostic possibilities. S.J. Geyer. 2013;41(7):658. Letter · Comment PubMed · Publisher
Metastatic proximal epithelioid sarcoma in pleural effusion: cytopathologic findings and differential diagnosis. H. Guan, F. Haque, S.Z. Ali. 2013;41(6):542-5. Case report PubMed · Publisher

Abstract

We present a rare occurrence of metastatic proximal epithelioid sarcoma (PES) in the pleural effusion of a 23-year-old man, developed within one year of diagnosis in his gluteal soft tissue. The cytologic and immunoperoxidase findings are described. PES, due to its epithelioid morphology, can be confused with more common cancers in effusions such as adenocarcinoma and mesothelioma. PES is an aggressive neoplasm that differs clinically and pathologically from conventional epithelioid sarcoma. Knowledge of its cytomorphology in serous cavity effusions, a patient's clinical history and ancillary studies may lead to an accurate diagnosis.

Copyright © 2011 Wiley Periodicals, Inc.
The application of immunocytochemistry to direct smears in the diagnosis of effusions. S.M. Knoepp, J. Placido, K.L. Fields, et al. 2013;41(5):425-30. PubMed · Publisher

Abstract

Metastatic malignancy represents a common cause of effusions. Immunocytochemistry (ICC) is useful in confirming malignancy and gaining insight into the site of origin. Cell blocks are commonly utilized for this purpose; nonetheless, when the malignant cells are sparse, they may not be represented in cell blocks thereby precluding immunophenotypic characterization. Thus, we sought to investigate the utility of direct smear preparations as a platform for ICC in the diagnosis of effusions. Air-dried, unstained direct smears were prepared from 49 malignant effusions and 17 reactive effusions for comparison. ICC for EMA and MOC-31 highlighted the tumor cells in 91 and 98% of the malignant effusions tested, respectively. EMA immunoreactivity was focally observed within the calretinin-positive mesothelial cell population in 1 (6%) of the 17 reactive effusions. ICC for MOC-31 was negative in all reactive effusions. Site-specific immunomarkers were also evaluated. Immunoreactivity for Napsin-A and TTF-1 were observed in 78 and 67% of metastatic lung adenocarcinomas, respectively. ICC for PAX8 highlighted metastatic Müllerian and thyroid carcinomas in 100% of cases tested. CDX-2 immunoreactivity was observed in 25, 60, and 100% of metastatic gastric, pancreatic, and colorectal adenocarcinomas, respectively. Positivity for p63 was observed in 75% of metastatic urothelial cell carcinomas and the one case of pulmonary squamous cell carcinoma examined. Calretinin ICC highlighted the tumor cells in both malignant mesothelioma cases tested as well as the benign mesothelial cells in the reactive effusions. In conclusion, direct smears represent an effective platform for the performance of ICC in the diagnosis of malignant effusions.

Copyright © 2012 Wiley Periodicals, Inc.
CD147 immunohistochemistry discriminates between reactive mesothelial cells and malignant mesothelioma. C. Pinheiro, A. Longatto-Filho, T.R. Soares, et al. 2012;40(6):478-83. PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a rare form of cancer. Its histopathological diagnosis is very difficult, as it exhibits a number of different appearances that can be misinterpreted as metastatic invasion or atypical hyperplasia. Thus, there is an urgent need to identify adequate markers to distinguish between benign and malignant cells, allowing the implementation of appropriate therapies and, possibly, specific directed therapies. MM, like other tumors, show an increase in glucose uptake, due to high rates of glycolysis, inducing an intracellular overload of acids. In this context, monocarboxylate transporters (MCTs) emerge as important players, by mediating the transmembranar co-transport of lactate with a proton, thereby, regulating pH and allowing continuous glycolysis. Importantly, proper MCT expression and activity depend on its co-expression with a chaperone, CD147, which is associated with poor prognosis in cancer. Twenty-two samples including reactive mesothelial cells, MM, and atypical mesothelial hyperplasias were evaluated for immunoexpression of MCT1, MCT4, and CD147. Expression of these proteins was compared with GLUT1 as a new promising marker for MM. Although MCT isoforms were not differentially expressed in the two types of cytological specimens, CD147, as GLUT1, was almost exclusively expressed in MM. Both MCT1 and MCT4 are not able to discriminate between mesothelial reactive cells and mesothelial malignant cells, while CD147 was able to distinguish these two proliferations. If confirmed, besides being a good marker for identification of MM, CD147 may also be a target for therapeutical strategies in this rare type of tumor.

Copyright © 2012 Wiley Periodicals, Inc.
Malignant biphasic peritoneal mesothelioma in a child: fine-needle aspiration cytology, histopathology, and immunohistochemical features along with review of literature. S.K. Arora, R. Srinivasan, R. Nijhawan, et al. 2012;40(12):1112-5. Case report PubMed · Publisher

Abstract

Peritoneal mesotheliomas in children are of rare occurrance. We herein report the clinical, radiological, and pathological findings of a rare case of malignant peritoneal mesothelioma occurring in nine-year-old female child. The child presented with abdominal distension and awareness of a painless mass in the abdomen which on radiology appeared as a large heterogeneous pelvic mass with peritoneal deposits at multiple sites. To the best of our knowledge, this is the first case of a peritoneal malignant mesothelioma on which fine needle aspiration (FNA) was performed as first line investigation of the primary tumor. The cytological features, major differential diagnoses, and the pitfalls therein are discussed. Histopathology revealed biphasic pattern of mesothelioma which is again a rare pattern. Immunochemistry was carried out on the cell block made from the FNA as well as the biopsy specimen essentially showed the same features. There was positivity for vimentin, EMA, and cytokeratin 5/6 while WT1, calretinin, and CEA were negative; however, D2-40 showed diffuse membranous positivity in the epithelial areas and cytoplasmic positivity in the spindle areas confirming a mesothelioma. We emphasize the use of immunochemistry on cell block material for a confident diagnosis of mesothelioma in such cases.

Copyright © 2011 Wiley Periodicals, Inc.
Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry. X.Y. Su, G.D. Li, W.P. Liu, et al. 2011;39(12):900-8. PubMed · Publisher

Abstract

The objective of the study is to estimate the expression of some antibodies in the metastatic adenocarcinomas, malignant epithelial mesotheliomas, and reactive mesothelial cells in serous effusions and to choose effective panel to the differential diagnosis. Totally 113 effusion cytology samples (80 pleural fluid, 30 ascitic, and 3 pericardial fluid) from 60 cases of metastatic adenocarcinoma (ACA), 18 cases of malignant epithelial mesothelioma (MM), and 35 cases of reactive mesothelium (RM) were included in this study. The cytological diagnoses of these cases were confirmed by histopathology or clinical datas. Smears and cell blocks were prepared for each case. Immunocytochemical study was performed on the cell block sections. The sensitivity of E-cadherin, CEA, MOC-31, and Ber-EP4 for adenocarcinoma was 86.7%, 80%, 70%, and 76.4%, respectively. The specificity was 98.1%, 96.2%, 92.5%, and 86.8%, respectively. The sensitivity of calretinin, HBME-1, and thrombomodulin for RM/MM was 83%, 79.2%, and 47.2% respectively. The specificity was 88.3%, 21.7%, and 70%, respectively. The expression of E-cadherin, CEA, MOC-31, Ber-EP4, calretinin, and thrombomodulin showed significant difference between ACA and RM/MM (P < 0.01). The reactivity of EMA and Des showed significant difference between RM and MM (P < 0.01). In our opinion, the antibody panel that consists of E-cadherin, CEA, calretinin, and thrombomodulin should be the best for differential diagnosis between metastatic adenocarcinomas and RM/MM in serous effusions. EMA and Des should be used to differentiate malignant epithelial mesothelioma and reactive mesothelial cells. EMA positive and Des negative favor MM, while Des positive and EMA negative favor RM.

Copyright © 2010 Wiley Periodicals, Inc.
Diagnostic usefulness of EMA, IMP3, and GLUT-1 for the immunocytochemical distinction of malignant cells from reactive mesothelial cells in effusion cytology using cytospin preparations. K. Ikeda, G. Tate, T. Suzuki, et al. 2011;39(6):395-401. PubMed · Publisher

Abstract

To differentiate reactive mesothelial cells (RMs) from metastatic carcinoma and malignant mesothelioma (MM) in effusion cytology is crucial for the cytologic diagnosis and the management of the patients. In the present study, the immunocytochemical staining profile of the epithelial membrane antigen (EMA), the insulin-like growth factor-II mRNA-binding protein 3 (IMP3), and the glucose transporter-1 (GLUT-1) was examined to distinguish RMs from malignant cells. A total of 171 pleural (n = 87) and peritoneal (n = 84) effusion specimens, including 50 benign effusions with RMs, 11 MM effusions, and 110 metastatic malignant effusions, were evaluated for immunocytochemistry. EMA, IMP3, monoclonal GLUT-1, and polyclonal GLUT-1 immunoreactivity were observed in 26.0%, 6.0%, 20.0%, and 18.0% of RMs, respectively. In contrast to RMs, the immunoreactivity in MM was 100%, 36.4%, 100%, and 90.9%; adenocarcinoma (AC) was 100%, 80.8%, 81.7%, and 72.1%; squamous-cell carcinoma was 83.3%, 83.3%, 83.3%, and 66.7%. EMA, IMP3, mGLUT-1, and pGLUT-1 expressions were observed in 98.4%, 65.6%, 88.5%, and 75.4% in the pleural effusion with malignant cells, and 100%, 88.3%, 78.3%, and 71.7% in ascites containing malignant cells, respectively. The findings of the present study indicate that the immunocytochemical staining for EMA, IMP3, and GLUT-1 is a useful diagnostic tool for distinguishing effusions containing malignant cells from those that contain benign cells, and in particular, we suggest that the combination of mGLUT-1 and EMA, and IMP3 and EMA are extremely useful in pleural effusion and in ascites, respectively.

Copyright © 2010 Wiley-Liss, Inc.
Primary malignant deciduoid peritoneal mesothelioma: a report of the cytohistological and immunohistochemical appearances. H. Ustun, H.M. Astarci, N. Sungu, et al. 2011;39(6):402-8. Case report PubMed · Publisher

Abstract

Malignant deciduoid mesothelioma (MDM) is a rare variant of epithelioid mesothelioma. This type of tumor might be associated with the asbestos exposure and carries a poor prognosis in general. MDM was first described by Nascimento et al. in 1994 in a peritoneal lesion of a young woman. And its diagnosis is frequently mistaken with florid mesothelial hyperplasia and peritoneal deciduosis. There are 44 MDM cases reported in the literature up today. A 59-year-old woman patient referred to our clinic was identified with an abdominal mass. Computed tomography of whole abdomen of the patient showed a mass with the widest transverse dimension of 65 × 60 mm at abdominal bifurcation in the mesenteric region. The patient was diagnosed with MDM after the cytopathological examination of the fine needle aspiration biopsy performed from the mass. Consequently, she received a total mass excision and right hemicolectomy under general anesthesia. The cytomorphological appearance of the ascitic fluid is detailed for the first time by Gillespie et al. and is described only in two manuscripts. In the present study, we aimed to report a case of a 59-year-old woman since she was diagnosed with MDM and because her cytological findings were further supported by histomorphological and immunohistochemical evaluations of the operation material obtained from the patient.

Copyright © 2010 Wiley-Liss, Inc.
Usefulness of Claudin 4 in the cytological diagnosis of serosal effusions. S. Lonardi, C. Manera, R. Marucci, et al. 2011;39(5):313-7. PubMed · Publisher

Abstract

The identification of metastatic cells in serous effusions has prognostic and therapeutic implications, thus leading to a continuous search for improvement of the existing diagnostic procedures, including immunocytochemistry. To evaluate the usefulness of an antibody recognizing the tight junction-associated protein Claudin 4 in detecting metastatic tumor cells and in the differential with reactive and neoplastic mesothelium, we stained 345 cases of benign and neoplastic serous effusions obtained from pleura, peritoneum, and pericardium. Two-hundred and twenty-eight of 230 cases (99.1%) of epithelial metastasis of different origin were strongly stained by anti-Claudin 4, whereas all cases of reactive mesothelitis (78) and malignant mesothelioma (37) were negative. With the exception of a single case of ovarian carcinoma hypercalcemic-type, all tumors originating from the anatomical sites that most frequently metastasize to the serosae, including lung (61), breast (23), female genital tract (67), gastrointestinal tract (27), and peritoneum (6), were found to be positive. Claudin 4 was also extremely useful in detecting single-tumor cells dispersed among heavy inflammatory reaction. Because of its high sensitivity (99.1%) and specificity (100%), Claudin 4 might be used as an ideal "single-shot" marker for the identification of metastatic epithelial cells in serous effusions.

Copyright © 2010 Wiley-Liss, Inc.
"Signet-ring" cells--a caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report. B. Rekhi, S. Pathuthara, D. Ajit, et al. 2010;38(6):435-9. Case report PubMed · Publisher

Abstract

A diffuse peritoneal mesothelioma is a rare tumor. Exfoliative cytology forms the first step in the diagnosis of mesothelioma, since most of these cases presented with effusion. Despite well established cytomorphological features, a challenge exists in differentiating mesothelial cells, including reactive and malignant types from carcinoma cells and macrophages. Presence of "signet-ring" cells increases the diagnostic challenge as these can be forms of benign and malignant cells. Ancillary techniques like immunohistochemical (IHC) markers and ultrastructural analysis form useful adjunct in substantiating exact diagnosis. We report an unusual case study of a diffuse peritoneal mesothelioma in a 57-years-old lady, with no history of asbestos exposure, presenting with recurrent ascites, diagnosed on ascitic fluid cytology and on histology as an adenocarcinoma, based upon the presence of "signet-ring" cells. On review, clinicopathological correlation with IHC was helpful in forming correct diagnosis.

(c) 2009 Wiley-Liss, Inc.
Cytomorphologic characteristics of fine needle core biopsy of multicystic peritoneal mesothelioma: a case report and review of the literature. A.M. Kemp, R. Nayar, D. De Frias, et al. 2010;38(3):192-7. Case report PubMed · Publisher

Abstract

Multicystic peritoneal mesothelioma (MPM) is an uncommon cystic mesothelial proliferative lesion. It occurs predominantly in women of reproductive age and most commonly arises in the pelvis. The preoperative diagnosis of MPM is difficult to establish based on clinical and radiographic findings, and has therefore traditionally been diagnosed following surgical resection. Due to differing management of MPM and its differential diagnoses including both benign and malignant lesions, it would be beneficial to diagnose MPM preoperatively. We report a case of MPM in a middle aged female that was diagnosed by fine needle core biopsy and touch preparations, allowing for appropriate clinical management. The cytomorphologic features of needle core biopsy, immunocytochemical studies and differential diagnosis are discussed. Furthermore, despite its infrequency, the current case emphasizes the importance of the inclusion of this entity in the differential diagnosis of cystic lesions of the abdomen and pelvis at the time of on-site evaluation and final diagnosis, in order to avoid misinterpretation of strips of benign mesothelial cells as inadequate for diagnosis.
Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: pleural effusions with malignant epithelioid cells. D.E. Westfall, X. Fan, A.M. Marchevsky. 2010;38(1):9-14. PubMed · Publisher

Abstract

There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005-2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 +/- 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed.

(c) 2009 Wiley-Liss, Inc.
Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case report. V. Samedi, S. White, M.J. Zimarowski, et al. 2010;38(9):675-81. Case report PubMed · Publisher

Abstract

Malignant peritoneal mesothelioma is uncommon but rapidly fatal with a median survival of less than 1 year. The diagnosis of this entity is often delayed because of the nonspecific presenting symptoms and nonspecific cytological features of the mesothelial cells in the peritoneal fluids. A 72-year-old man who had no known history of exposure to asbestos and had longstanding refractory ascites thought to be secondary to alcoholic cirrhosis was found to have widespread metastatic malignant mesothelioma involving the lung, liver, pancreas, peritoneal, and pelvic wall, skin and subcutaneous tissue.

Copyright 2009 Wiley-Liss, Inc.
Podoplanin is a useful marker for identifying mesothelioma in malignant effusions. A. Hanna, Y. Pang, C.W. Bedrossian, et al. 2010;38(4):264-9. PubMed · Publisher

Abstract

The diagnosis of malignant mesothelioma in serosal effusions continues to be a major challenge because some of its cytomorphological features closely resemble adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single antibody has demonstrated absolute sensitivity or specificity. In this study, we evaluated the value of immunostaining pattern for podoplanin to differentiate mesothelioma from adenocarcinomas of various origins.Cell blocks from previously collected paraffin-embedded cell blocks of 86 effusions (18 mesothelioma, 35 reactive mesothelium, 9 breast adenocarcinoma, 14 ovarian adenocarcinoma, and 10 lung adenocarcinoma) were retrieved from the file of the Department of Pathology at University of Michigan and Lund University in Sweden and were used for the study. Slides prepared from the cell blocks were stained for podoplanin. The percentage of immunostained cells was recorded as follows: 1+ (5-25%), 2+ (26-50%), and 3+ (>50%). A stain result involving <5% of cells was considered negative. The intensity of positive results was evaluated as strong, moderate, or weak.Podoplanin is expressed in 94% of malignant mesothelioma cases (17/18), 97% (30/31) of cases of reactive mesothelial, 0% of lung adenocarcinoma cases (0/9), 0% of breast adenocarcinoma (0/9), and 7% of ovarian adenocarcinoma (1/14). All positive cases of malignant mesothelioma and reactive mesothelium showed strong membranous reactivity to podoplanin. The one positive case of ovarian adenocarcinoma showed a weak membranous podoplanin immunostaining.On the basis of our results and published data, we believe that membranous podoplanin immunoreactivity, in conjunction with calretinin, would be more specific than CK5/6 and WT-1 in differentiating epithelioid malignant mesothelioma from adenocarcinoma of the lung, breast, and ovary.

Copyright 2009 Wiley-Liss, Inc.
Significance of cell proliferation markers (Minichromosome maintenance protein 7, topoisomerase IIalpha and Ki-67) in cavital fluid cytology: can we differentiate reactive mesothelial cells from malignant cells?. F. Kimura, J. Kawamura, J. Watanabe, et al. 2010;38(3):161-7. PubMed · Publisher

Abstract

The aim of this study was to evaluate whether immunocytochemical expressions of proliferation markers, such as minichromosome maintenance protein 7 (MCM 7), topoisomerase IIalpha (topo IIalpha), and Ki-67, in reactive mesothelial cells and malignant cells obtained from cavital fluids could be useful for their differential diagnosis. Samples diagnosed as reactive mesothelial cells (14 cases) or malignant tumors (28 cases) in cavital fluids were examined. Immunocytochemical staining of MCM 7, topo IIalpha, and Ki-67 was performed with the universal immunoperoxidase polymer method. In reactive mesothelial cells, MCM 7 was stained in a fine granular pattern and its distribution was uniform in the nuclei. Topo IIalpha and Ki-67 were stained in a coarse granular pattern and the distributions were the same as MCM 7. In contrast, in malignant cells, MCM 7 was stained in an irregular and fine granular pattern, and topo IIalpha and Ki-67 were stained in a uniform and coarse granular pattern. Labeling indices of MCM 7 (cut-off value; 30%, sensitivity; 100%, and specificity; 100%), topo IIalpha (cut-off value; 15%, sensitivity; 89.3%, and specificity; 92.9%) and Ki-67 (cut-off value; 30%, sensitivity; 64.3%, and specificity; 92.9%) of malignant cells were significantly higher than those of reactive mesothelial cells. MCM 7, topo IIalpha, and Ki-67 are different types of cell proliferation markers. MCM 7 and topo IIalpha, in particular, could be reliable tools for differential diagnosis between reactive mesothelial cells and malignant cells.
The sensitivity of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma. E.A. Rakha, S. Patil, K. Abdulla, et al. 2010;38(12):874-9. PubMed · Publisher

Abstract

Pleural malignant mesothelioma (MM), which is an aggressive neoplasm with a high mortality, frequently manifests initially as pleural effusions. The sensitivity of cytologic examination for its diagnosis varies widely in literature and most of the figures are from earlier studies with conventional cytologic preparations. The objective of this study was to provide the current evidence on the role and sensitivity of cytologic examination of pleural fluid in the diagnosis of MM. We reviewed the cytologic findings in pleural effusions of a large series of histologically proven MM (234 cases) diagnosed in our institution between 2001 and 2008. Of all cases, 154 (66%) had cytologic material examined. A specific diagnosis of MM was rendered or suspected in 53% (79 patients). The lowest sensitivity (20%) was noticed in sarcomatoid MM cases. MM was favored over adenocarcinoma in 97% of patients with positive cytologic findings that have been confirmed with immunohistochemistry. In this series, five cases were inadequate and five cases were initially reported as atypical, whereas 65 cases (44%) were reported as negative for malignancy. On review of the cytology slides, only four cases were upgraded from benign to suspicious compared to four cases downgraded from suspicious to atypical but no significant improvement to the diagnosis could be made on revision. These data suggested that a cytologic diagnosis contributed useful information in patients with epithelioid and biphasic pleural MM. Limitations of the cytologic examination of MM should also be acknowledged.

Copyright © 2010 Wiley-Liss, Inc.

2000s

Fine-needle aspiration of a well-differentiated papillary mesothelioma in the inguinal hernia sac: A case report and review of literature. Y.Y. Wheeler, F. Burroughs, Q.K. Li. 2009;37(10):748-54. Case report · Review PubMed · Publisher

Abstract

Well-differentiated papillary mesothelioma (WDPM) is an uncommon subtype of epithelioid mesothelioma. In contrast to malignant epithelioid mesothelioma, WDPM has a low malignant potential and an indolent clinical course. WDPM may be difficult to diagnose and differentiate from benign reactive mesothelial cells and other malignant neoplasm on cytology specimens due to the presence of papillary or tubulopapillary clusters of tumor cells. We report a case of a 63-year-old Asian male with a slowly growing left inguinal hernia mass for several years and a concurrent 8 cm mass in the peritoneal wall. The cytology of ultrasound-guided fine-needle aspiration (FNA) of the left inguinal hernia and peritoneal masse reveal cellular specimens with numerous individual and tubulopapillary clusters of epithelioid mesothelial cells in a background of scant hyalinized material. Tumor cells show minimal cytological atypia. The differential diagnoses are broad and include reactive mesothelial cells, WDPM, and other malignant neoplasm. The follow-up surgical resection of masses reveals features of WDMP. It is important to recognize this entity in the differential diagnosis, because the clinical management of WDPM is quite different from that of malignant neoplasm. On the basis of the published data in the literature, it suggests that in male patients, the WDPM occurs predominantly in pleural cavity of older men in their 50s, and about half of the patients have history of asbestos exposure. However, the data is limited and insufficient for a definitive conclusion.

(c) 2009 Wiley-Liss, Inc.
Pleural mesothelioma: an unusual case diagnosed on pleural fluid cytology and immunocytochemistry. V.K. Arora, S. Aggarwal, S. Mathur, et al. 2009;37(7):509-12. Case report PubMed · Publisher

Abstract

Mesothelioma is a rare neoplasm with relationship to occupational and environmental exposure to asbestos. Its accurate and early diagnosis is often difficult. We present an unusual clinical presentation and diagnostic dilemma in a 30-year-male, who presented with neck pain and diffuse edema of left upper limb. The color Doppler ultrasound revealed venous thrombosis. The right supraclavicular lymph node biopsy revealed a poorly differentiated carcinoma. The patient had mild bilateral pleural effusion, the characteristic cytomorphological features of mesothelioma on fluid cytology were helpful in establishing the diagnosis.

2009 Wiley-Liss, Inc.
Fine-needle aspiration of malignant mesothelioma with unusual morphologic features: a case report. U. Kapur, E.M. Wojcik. 2007;35(3):174-8. Case report PubMed · Publisher

Abstract

Malignant mesothelioma is an aggressive neoplasm linked to asbestos exposure. Most mesothelioma patients present with pleural effusion and the fluid is typically sent for cytological examination. Therefore, cytopathologists are most familiar with features of mesothelioma in fluid preparations. We present here a case of malignant mesothelioma with unusual cytological features diagnosed on FNA. The diagnosis was confirmed by immuno-histochemical and electron microscopic studies. In addition, we compare the cytomorphological features observed in malignant effusion versus fine-needle aspiration.
Mesothelioma: you do not have to work for it. E.J. Ampleford, J. Ohar. 2007;35(12):774-7. Case report PubMed · Publisher

Abstract

Asbestos pollution is a global problem. Asbestos exposure induced mesothelioma does not require an 'occupational' type of exposure. Bystander exposures may result in earlier age of disease onset and more aggressive disease progression as described in the following 3 case reports.

Copyright 2007 Wiley-Liss, Inc.
Percutaneous image-guided fine-needle aspiration of peritoneal lesions. L.J. Layfield, E.V. Gopez. 2003;28(1):6-12. PubMed · Publisher

Abstract

Fine-needle aspiration (FNA) is a widely accepted technique for the initial tissue diagnosis of a variety of lesions arising within retroperitoneal and intraabdominal viscera. Fear of complications secondary to perforation of the bowel wall has limited the use of FNA in the diagnosis of gastrointestinal and peritoneal masses. A variety of primary and secondary neoplasms involving the peritoneum may present as multiple nodules, as masses, or as diffuse involvement of the peritoneum. When these lesions are associated with mass lesions or areas of significant peritoneal thickening, they become amenable to percutaneous image-guided FNA. We report on our experience with a series of 23 peritoneal lesions investigated by FNA for which subsequent histologic confirmation was available in 19, along with an additional 4 cases without histologic confirmation. One to four passes were made into each lesion, and immediate assessment for adequacy was performed by a cytopathologist in all cases. All 17 cases with a specific cytologic diagnosis and histologic confirmation represented either primary or metastatic neoplasms (5 gastrointestinal stromal tumors, 4 metastatic melanomas, 2 mesotheliomas, 1 lymphoma, 1 example of Kaposi's sarcoma, 1 serous papillary carcinoma of ovarian origin, 1 mucinous adenocarcinoma of ovarian origin, 1 intraabdominal desmoplastic small-cell tumor, and 1 solitary fibrous tumor of the peritoneum). In an additional 4 cases, the aspirates were judged as insufficient for diagnosis, with the smears containing only blood and benign mesothelial cells and/or inflammatory cell elements. These four smears were associated with both neoplastic and nonneoplastic lesions. Surgical confirmation was obtained in only 2 of these cases (1 metastatic melanoma and 1 example of omental and peritoneal involvement by an ovarian adenocarcinoma). Two cases without histologic confirmation were associated with clinically confirmed metastases. In our series, no acute or chronic postprocedural complications were identified, indicating that FNA in this setting is a safe technique. Accurate cytologic diagnosis was achieved in 74% of cases. The overall insufficiency rate was 26%.

Copyright 2003 Wiley-Liss, Inc.
Fine-needle aspiration biopsy of axillary lymph nodes. S. Jaffer, M. Zakowski. 2002;26(2):69-74. PubMed · Publisher

Abstract

To assess the efficacy of fine-needle aspiration biopsy (FNAB) of axillary lymph nodes (ALN), we retrospectively analyzed 140 FNAB of ALN at Memorial Sloan-Kettering Cancer Center, examining technique and cytologic-histologic correlation. Of the 140 FNAB, 124 were performed by the conventional method and 16 by ultrasound guidance (USG). The diagnoses included: unsatisfactory, 20; negative, 38; positive, 72; suspicious, 6; and indeterminate, 4. Positive diagnoses included: carcinoma, 44.4%; melanoma, 43.0%; lymphoma, 5.6%; sarcoma, 5.6%; and mesothelioma, 1.4%; one of which was false-positive, attributed to misinterpretation. All indeterminate and most false-negative cases were due to lymphoproliferative conditions. The sensitivity and specificity of FNAB of ALN were 94.7% and 97.1% and the adequacy rate was 85.7%. The sensitivity, specificity, and adequacy rates of USG FNAB were 100%. Our study shows that FNAB of ALN is an excellent method for diagnosing reactive conditions as well as neoplasms.
Peritoneal washing cytology findings of disseminated myxoid leiomyosarcoma of uterus: report of a case with emphasis on possible differential diagnosis. W.K. Ng, P.C. Lui, L. Ma. 2002;27(1):47-52. Case report PubMed · Publisher

Abstract

We report the cytology findings of a rare case of myxoid leiomyosarcoma of the uterus with intraabdominal dissemination. The cytology showed uniformly dispersed spindly to polygonal "epithelioid" tumor cells focally linked by background matrix. Spindly tumor cells attaching to and radiating from branching capillary structures were also present. Occasionally, scattered "signet-ring" cells were found, mimicking metastatic poorly differentiated adenocarcinoma. The background mucoid substance was more conspicuous in the cell block sections. Gross and histologic examination of the surgical specimen revealed a large uterine leiomyosarcoma with prominent myxoid change. Ultrastructural study showed that the "signet-ring" appearance was mainly due to degenerative cytoplasmic change with ballooning of mitochondria, dilatation of endoplasmic reticulum, and elevation of outer nuclear membrane. In contrast to other spindle cell malignancies such as sarcomatoid mesothelioma, sarcomatoid carcinoma, or malignant melanoma, true sarcoma cells in general carry a distinctive cytologic appearance in washing/effusion fluid. In a correct clinical setting, the peculiar association with mucoid matrix and absence of classic lipoblasts should also raise the suspicion of metastatic myxoid leiomyosarcoma.

Copyright 2002 Wiley-Liss, Inc.
Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an immunocytochemical study. A. Simsir, P. Fetsch, C.W. Bedrossian, et al. 2001;25(4):203-7. PubMed · Publisher

Abstract

Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase chain reaction in 40-80% of malignant mesothelial proliferations. However, the role of immunohistochemistry (IHC) in demonstrating the nuclear localization of Tag is controversial. We sought to determine the clinical utility of SV-40 Tag IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong and consistent immunoreactivity in positive controls, no nuclear immunostaining was observed in any case. We believe the small sample size in cytology cell block sections, the low viral copy number in infected cells, and the effect of formalin fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further studies reliably show its detection.

Copyright 2001 Wiley-Liss, Inc.
Changing clinical course of patients with malignant mesothelioma: implications for FNA cytology and utility of immunocytochemical staining. G.H. Yu, L. Soma, S. Hahn, et al. 2001;24(5):322-7. PubMed · Publisher

Abstract

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.

Copyright 2001 Wiley-Liss, Inc.
Comparison of antibodies to HBME-1 and calretinin for the detection of mesothelial cells in effusion cytology. P.A. Fetsch, A. Simsir, A. Abati. 2001;25(3):158-61. PubMed · Publisher

Abstract

The distinction of mesothelial cells in cytologic samples is often a diagnostic challenge. This is particularly true in potentially malignant effusions in which reactive mesothelial cells may simulate adenocarcinoma (ACA) cells, and in the differentiation of ACA vs. mesothelioma. We sought to determine the superior antibody for the positive identification of mesothelial cells in these circumstances. Cell block sections of 25 reactive and 8 malignant mesothelioma effusions were immunostained with an avidin-biotin procedure, using antibodies to HBME-1 and calretinin. No pretreatment of samples was necessary for the HBME-1-stained slides; microwave antigen retrieval was performed on all slides stained for calretinin. A negative control was performed on each sample. The staining intensity of tumor cells was scored on a scale of 0-3+, with the proportion of immunoreactive cells categorized as <25%, 25-50%, 50-75%, and >75%. The predominant staining pattern for HBME-1 was surface, with rare samples also exhibiting cytoplasmic staining as well. The calretinin-staining pattern was cytoplasmic, with peripheral condensation/prominence and accompanying nuclear staining. All samples were immunoreactive with both antibodies. Fifty-five percent (18/33) of samples showed significantly stronger immunoreactivity with calretinin than with HBME-1; 45% (15/33) of samples showed equivalent staining with the two markers. None of the samples in this study showed stronger immunoreactivity with HBME-1 than with calretinin. Sixty-one percent (20/33) of samples stained with HBME-1 at a moderate (2+) intensity. Fifty-five percent (18/33) of samples stained with calretinin at a strong (3+) intensity. While only 12% of samples showed >75% immunoreactivity for HBME-1, 58% of samples showed >75% of cells immunoreactive for calretinin. Calretinin is the preferred marker in identifying mesothelial cells in cytologic samples, showing the highest sensitivity for mesothelial cells, as evidenced by a more intense staining reaction in a higher percentage of cells than with HBME-1. Published 2001 Wiley-Liss, Inc.
Thoracic splenosis diagnosed by fine-needle aspiration cytology: a case report. S. Syed, P. Zaharopoulos. 2001;25(5):321-4. Case report PubMed · Publisher

Abstract

A case of thoracic splenosis diagnosed by fine-needle aspiration (FNA) of subpleural lung lesions is presented. The patient, a 49-yr-old male with a history of gunshot wound to his trunk with splenic rupture and splenectomy several years previously, presented with recent hemoptysis and multiple subpleural solid nodules shown in the left lung field by CT scan. As the possibility of a metastatic malignancy vs. mesothelioma was entertained, an FNA was performed on one of these lesions, revealing lymphoid tissue with abundant vascularity simulating the structure of splenic tissue. In view of this finding, supported by the absence of splenic outline in the CT radiograph, the diagnosis of splenosis was made. This is the fourth reported case of thoracic splenosis in which FNA cytology was utilized for diagnosis, yet the first in which the diagnosis was based exclusively on the FNA cytologic findings. Clinical, pathologic, and diagnostic aspects of this entity are discussed.

Copyright 2001 Wiley-Liss, Inc.
Mesothelial hyperplasia with reactive atypia: diagnostic pitfalls and role of immunohistochemical studies-a case report. A. Lee, Z.W. Baloch, G. Yu, et al. 2000;22(2):113-6. Case report PubMed · Publisher

Abstract

The cytomorphologic features of highly reactive mesothelial cells can be difficult to distinguish from malignant cells. We report on an unusual case of mesothelial hyperplasia in a pericardial effusion. The specimen contained bizarre-shaped cells and large tissue fragments in a patient with a history of lung carcinoma. The atypical cells were negative for CEA and LeuM-1 and positive for cytokeratins (AE1/3) and HBME-1. Strong HBME-1 positivity supported a mesothelial origin of the atypical cells and led to the diagnosis of reactive mesothelium. While HBME-1 cannot be used as the sole marker to establish an mesothelial origin; its use in a immunohistochemistry panel may be useful in individual cases to distinguish reactive mesothelial cells from carcinoma in effusion cytology. Diagn. Cytopathol. 2000;22:113-116.

Copyright 2000 Wiley-Liss, Inc.

1990s

Cytopathology of malignant mesothelioma of the pleura in fine-needle aspiration biopsy. G.K. Nguyen, M.R. Akin, R.R. Villanueva, et al. 1999;21(4):253-9. PubMed · Publisher

Abstract

The cytologic findings in fine-needle aspiration biopsy (FNAB) of 9 histologically, immunohistochemically, and ultrastructurally confirmed malignant mesotheliomas of the pleura were reviewed. There were 4 epithelial malignant mesotheliomas (EMM), 3 sarcomatous mesotheliomas (SM), 1 mixed malignant mesothelioma (MMM), and 1 poorly differentiated malignant mesothelioma (PDMM). In FNAB, three EMMs yielded polygonal malignant cells with oval nuclei and prominent nucleoli, singly, in small sheets, and in tridimensional clusters with smooth or lobulated contours. In one EMM, only atypical mesothelial cells with prominent nucleoli were seen singly and in loose aggregates. In FNAB, two SM showed malignant spindle-shaped cells (MSC) with scant, ill-defined cytoplasm singly and in loose clusters. Cohesive clusters of elongated and polygonal cells with ill-defined, clear cytoplasm and pleomorphic nuclei containing small or prominent nucleoli were observed in one SM, with extensive clear-cell changes. In needle aspirates, the MMM showed polygonal malignant cells in clusters admixed with MSC. The PDMM displayed single and clustered large pleomorphic malignant cells, with prominent single or multiple nucleoli. Electron microscopic examination of minute tissue fragments retrieved from the FNAB in 2 cases of EMM revealed epithelial mesothelial cells with well-formed desmosomes and long slender microvilli (LSM) on the free tumor cell surfaces. In one case, LSM in direct contact with collagen fiber bundles in the tumor tissue matrix were observed, supporting the diagnosis of an invasive EMM. Diagn. Cytopathol. 1999;21:253-259.

Copyright 1999 Wiley-Liss, Inc.
Cytopathological features of solitary fibrous tumor of the pleura: a study of 5 cases. B. Weynand, P. Collard, C. Galant. 1998;18(2):118-24. Case report PubMed · Publisher

Abstract

Solitary fibrous tumor is a rare lesion of serosal membranes. In a pleural location, it may be confused clinically with a localized mesothelioma or a peripheral lung tumor. A transthoracic needle aspiration can be done to obtain material for a diagnosis in these easily accessible tumors. In the literature, there are only sporadic reports of cytology of solitary fibrous tumor in pleural fluid or in material obtained by percutaneous fine-needle aspiration. We had the opportunity to study five such cases by cytology and biopsy and in four cases we could study the resected specimen as well. We want to emphasize the possibilities of approaching diagnosis by cytologic material. A more precise diagnosis can be made if immunohistochemistry can be applied on a cell block or a concomitant biopsy specimen. We shall discuss the differential diagnosis of these tumors on cytologic material and/or biopsy and the usefulness of the CD34 antibody.
Diagnostic problems in serous effusions. C.W. Bedrossian. 1998;19(2):131-7. Review PubMed · Publisher

Summary

This narrative review, presented at an IAP Symposium in Budapest in October 1996, described diagnostic challenges and pitfalls in the cytologic examination of pleural, pericardial and peritoneal fluids. The author outlined how the mesothelium responds to injury and repair, and listed common causes of mesothelial hyperplasia, including infection, infarction, liver disease, radiation, chemotherapy and foreign substances such as talc and asbestos. Reactive mesothelial cells were described as able to mimic malignancy, and the author advised against using the term "atypical" without a clarifying comment. For malignant mesothelioma, the author noted attention arising from the medico-legal implications of asbestos exposure. Suspicion was advised in the setting of a history of asbestos exposure, appropriate X-ray findings and an unexplained bloody effusion. Approximately 90% of mesotheliomas were stated to be pleural in origin. Cytologic features of mesothelioma were described, along with special stains, immunostains (CEA, keratin, EMA, Ber-Ep4, Leu M1, B72.3) and hyaluronic acid testing for separating mesothelioma from adenocarcinoma. In the author's experience, electron microscopy was the most reliable method of diagnosing mesothelioma. The review also covered metastatic malignancies, clues to the primary site, and antibody panels. Proliferative markers (AgNOR, PCNA, Ki-67, MIB-1) were reported to help separate malignant effusions from mesothelial hyperplasia, but PCNA and Ki-67 did not distinguish mesothelioma from carcinoma.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Hyaluronate binding probe and CD44 in the differential diagnosis of malignant effusions: disappointing results in cytology material. A.C. Filie, A. Abati, P. Fetsch, et al. 1998;18(6):473-4. Letter PubMed · Publisher

Summary

In this letter, the authors examined whether a biotinylated hyaluronate binding probe and an antibody to CD44, the cell surface receptor for hyaluronan, could help distinguish malignant mesothelioma from metastatic adenocarcinoma in cytology material from malignant effusions. An earlier study had found the probe highly predictive of mesothelioma in surgical pathology material. Cell block preparations from 21 mesotheliomas, 22 metastatic adenocarcinomas, 1 case of reactive mesothelial cells and 1 mesothelioma cell line were retrieved from the files of the Cytopathology Section, National Cancer Institute (Bethesda, Maryland). Sections were stained with the probe and for CD44, and three observers reviewed them without knowing the final diagnosis. Two cases were not scored because of absent or scanty tumor cells. The probe stained 19 of 20 mesotheliomas (95%) and 19 of 21 adenocarcinomas (90.5%). CD44 showed membranous staining in 18 of 20 mesotheliomas (90%) and 9 of 21 adenocarcinomas (43%). The reactive mesothelial cells stained focally for CD44. The authors suggested that hyaluronic acid in the effusion fluid may stick to or be taken up by floating adenocarcinoma cells. They concluded that neither the probe nor CD44 was useful for this distinction in effusion cell blocks, although the probe appeared to work well in surgical tissue sections. They stated that the small number of benign samples did not allow conclusions about separating benign from malignant mesothelial cells.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Detection of aneuploidy in mesothelioma cell lines by fluorescence in situ hybridization (FISH). A. Abati, J. Sanford, P. Fetsch, et al. 1997;16(4):375-7. Letter PubMed · Publisher

Summary

In this letter, the authors examined whether fluorescence in situ hybridization (FISH) could detect aneuploidy in mesothelioma cell lines. They studied ten mesothelioma cell lines, nine of which had previously been reported to have numerical karyotypic abnormalities. For each cell line, three cytospin preparations were made: one air-dried, one fixed in 95% ethanol, and one fixed in Carnoy's solution. They applied probes for chromosome 9 and chromosome 3, chosen because numerical abnormalities of these chromosomes are common in mesothelioma, and evaluated 200 mononucleated cells per cell line. Normal mesothelial cells served as controls. Initial results on control slides were unsatisfactory. Doubling the probe concentration gave slightly improved results, and increasing the detection time from 5 to 15 minutes gave strong signals for both probes. Cells were counted on ethanol-fixed samples, which gave the best signal intensity with the least fragmentation and retained cytoplasmic integrity. Carnoy's-fixed material gave weak chromosome 3 signals and lost cytoplasmic integrity. Air-dried material was satisfactory, but its chromosome 3 signals were less concise. All ten cell lines showed more than the expected two signals for both chromosomes, ranging from 2.2 to 4.8. The authors concluded that several fixation methods can optimize results with probes of variable signal intensity, that longer detection time can enhance weak signals, and that FISH can reliably detect aneuploidy in interphase nuclei in malignant mesothelioma.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Pleural effusion cytology of embryonal rhabdomyosarcoma. K.S. Thompson, J.D. Jensen, N. Bhoopalam, et al. 1997;16(3):270-3. Case report PubMed · Publisher

Abstract

This case report concerns an embryonal rhabdomyosarcoma of the testis in a 31-yr-old white male patient who underwent radical left orchiectomy, followed by combined irradiation and chemotherapy, and who 2 yr later presented with dyspnea at rest, nonproductive cough, and lower back pain for 1 wk. Chest radiographs demonstrated a bilateral pleural effusion and diffuse infiltrating lesion of the pleurae, mimicking a mesothelioma. The pleural fluid displayed noncohesive, malignant, small, round cells about 2-5 times larger than mature lymphocytes. They had large, darkly stained, pleomorphic nuclei and bubbly cytoplasm with poorly defined borders. The diagnosis of embryonal rhabdomyosarcoma was supported by a positive myosin immunostaining and ultrastructural findings of intracytoplasmic actin and myosin-type microfilaments. Our case is also notable in that the tumor was a pure rhabdomyosarcoma involving a testicular origin, and the patient is the oldest reported in the literature.
Concomitant malignant mesothelioma of the pleura, peritoneum, and tunica vaginalis testis. V. Ascoli, F. Facciolo, S. Rahimi, et al. 1996;14(3):243-8. Case report PubMed · Publisher

Abstract

We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.
Cytopathology of serous neoplasia of the ovary and the peritoneum: differential diagnosis from mesothelial proliferations. L.R. Pisharodi, C.W. Bedrossian. 1996;15(4):292-5. PubMed · Publisher

Abstract

Serous neoplasia of the ovary ranges from benign adenomas through serous borderline tumors to invasive serous adenocarcinoma. This spectrum of neoplasia is at least partially reflected in the cytomorphologic features of the lesions. The objective of this study is to review the cytopathology of serous neoplasia of the ovary. In addition, cytologic features of serous surface papillary carcinoma and its distinction from peritoneal mesothelial proliferations are discussed.
Inflammatory and neoplastic processes of the lung: differential diagnosis and pitfalls in FNA biopsies. J.F. Silverman. 1995;13(5):448-62. Review PubMed · Publisher
Summary

This review, from the Department of Pathology and Laboratory Medicine at East Carolina University School of Medicine, discussed sources of diagnostic error in fine-needle aspiration (FNA) biopsy of the lung. The author described the institution's technique. Lung lesions were aspirated percutaneously with a 22-gauge Chiba needle under fluoroscopic, ultrasound or CT guidance, and smears were stained with Papanicolaou and rapid Diff-Quik stains for immediate interpretation.

The review covered benign processes that can mimic malignancy and lead to false-positive diagnoses. These included reactive mesothelial cells, inflammatory atypia, squamous metaplasia, repair in pulmonary infarct, type II pneumocyte hyperplasia in organizing pneumonia, degenerating histiocytes, radiation and chemotherapy effects, inflammatory pseudotumor, vegetable material, inadvertently sampled liver cells, and granulomas. It also described neoplasms that can cause false-negative diagnoses, such as squamous-cell carcinoma with abscess-like necrosis and inflammation.

Four diagnostic challenges among lung neoplasms were discussed:
- small-cell carcinoma versus carcinoid, poorly differentiated squamous-cell carcinoma and lymphoma;
- primary lung carcinoma versus metastasis;
- pleomorphic large-cell malignancies, including sarcoma;
- peripheral adenocarcinoma versus mesothelioma, which the author noted has a very strong association with asbestos exposure.
Tables summarized cytologic, immunocytochemical and electron microscopic features. The author stressed several ways to avoid misdiagnosis: immediate examination of rapid stains, attention to low-power cell architecture, ancillary studies such as immunocytochemistry and electron microscopy, and correlation with clinical and radiologic findings.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
OV632 as a possible marker for malignant mesothelioma: high expectations; low specificity. A. Abati, P.A. Fetsch. 1995;12(1):81-2. Editorial PubMed · Publisher

Summary

In this letter, the authors, at the National Cancer Institute in Bethesda, Maryland, reported a small trial of the monoclonal antibody OV632 as a marker for malignant mesothelioma. Earlier reports had stated that OV632 selectively stained nonmucinous ovarian adenocarcinomas and malignant mesotheliomas, rarely stained other tumours, and did not stain reactive mesothelial cells. Over a 6-week period the authors selected cases offering a range of diagnoses from body fluids and fine-needle aspirates. These included metastatic breast and ovarian adenocarcinomas, mesothelioma, reactive mesothelial cells, melanoma, squamous cell carcinoma and lymphoma. They stained two kinds of preparation with OV632 using the avidin-biotin peroxidase method, with negative controls: air-dried cytospins that had been stored frozen and fixed in acetone, and formaldehyde-fixed paraffin cell blocks. On cytospins, one breast adenocarcinoma was technically unsatisfactory, and four of five metastatic breast adenocarcinomas stained positive. Positive staining was also seen in the mesothelioma, reactive mesothelial cells, malignant melanoma, squamous cell carcinoma and large-cell lymphoma. The single metastatic ovarian adenocarcinoma was negative. Cell block sections could not be interpreted because of uniformly high background staining. The authors had no explanation for results contrary to expectations, since reagents were fresh and the manufacturer's procedure was followed. They did not add OV632 to their routine panel for suspected mesothelioma in male patients. They asked other laboratories to report their experience and said they would use OV632 only on an experimental basis.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Utility of cytokeratin 20 in identifying the origin of metastatic carcinomas in effusions. V. Ascoli, S. Taccogna, C.C. Scalzo, et al. 1995;12(4):303-8. PubMed · Publisher

Abstract

Using a commercially available monoclonal antibody (Ks20.1) and the avidin-biotin peroxidase method on cytospins and cell blocks, we analyzed cytokeratin (CK) 20 expression in 169 serous effusions. Cytoplasmic staining was observed in 44/151 malignant fluids. Colon, gastric, and pancreatic adenocarcinomas and mucinous ovarian tumors were most frequently positive. Single cases of transitional-cell and squamous cell carcinomas were reactive as well. Lung and breast cancers were mostly negative. Nonmucinous ovarian tumors were invariably unlabeled as were mesotheliomas and normal mesothelial cells. The study shows that CK 20 is valuable in distinguishing tumor cell origin in effusions. In particular, it identifies a set of carcinomas with the majority arising from the gastrointestinal tract, and represents a highly characteristic marker for colorectal cancer.
Cytopathology of malignant mesothelioma: a study of its patterns and histological bases. L. DiBonito, G. Falconieri, I. Colautti, et al. 1993;9(1):25-31. PubMed · Publisher

Abstract

We have reviewed the effusion cytology of 51 cases of histologically proven malignant mesothelioma of the pleura (49 cases) and the peritoneum (2 cases). The patient group included 45 males and 6 females, aged 45-83 yr. A cytological diagnosis of malignancy had been rendered on 43 cases, and in 30 of them it was consistent with, or at least suggestive of, a mesothelioma. Diagnostic clues, especially evident in epithelial and biphasic tumors were hypercellularity and/or morular aggregates of malignant cells showing scalloped borders and nuclei with dense chromatin and evident nucleoli. Cytomegaly with multinucleation was also frequently observed. Reactive mesothelial cells were often present along with other non specific features such as red blood cells, fibrin, necrotic debris. In 13 cases, a diagnosis of malignancy was entertained but mesothelioma, although considered, was not reported out because of scantiness of material. In four cases, adenocarcinoma was erroneously diagnosed for the presence of deceptive cell vacuoles. In eight cases, no diagnostic cells were recovered in repeated effusions. The first diagnosis was a cytologic one in 37 patients, Tissue study was performed on autopsy (35 patients) and surgical material. The latter was the only source of histology in six cases. Immunocytochemical investigation was negative for carcinoembryonic antigen in all but one tested cases (1/21) and positive for human milk fat globulin in about one-half of the epithelial and biphasic tumors. In 18 of 21 cases, positivity for combined high- and low-molecular-weight keratins was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Fine-needle aspiration cytology of localized fibrous tumor of pleura. D. Dusenbery, M.M. Grimes, W.J. Frable. 1992;8(5):444-50. Case report PubMed · Publisher

Abstract

Fine-needle aspiration (FNA) biopsy findings are presented in three cases of localized fibrous tumor of pleura (LFTP). Clinically, two of the tumors behaved benignly, although one showed frequent mitoses and foci of necrosis. The third tumor exhibited local aggressiveness as evidenced by rib destruction. Cytologically, these tumors exhibited a wide range of cellularity, composed mainly of small, bland oval to spindle cells with moderate numbers of stripped nuclei. Small bits of collagen were seen in the smears. In all cases, cell blocks were instrumental in making the diagnosis. Previous cytologic descriptions of the tumor are briefly reviewed and the cytologic differential diagnosis is discussed. The peripheral location of this uncommon tumor makes it an ideal target for FNA biopsy.
Fine-needle aspiration cytology of multicystic mesothelioma. K. Devaney, P.J. Kragel, E.J. Devaney. 1992;8(1):68-72. Case report PubMed · Publisher

Abstract

This report details the cytologic findings from a case of peritoneal multicystic mesothelioma (MCM). Fine-needle aspiration of a 20 cm abdominal mass in a 31-year-old man yielded a specimen which consisted of a monomorphous population of mesothelial cells lacking cytologic atypia which were arranged in three patterns: monolayered sheets, single cells, and two-cell-thick strands of mesothelial cells with little or no intervening stroma. The background was clean, without necrotic debris or abundant inflammatory cells. The mesothelial cells were not arranged in prominent papillary formations; mitotic figures were not found. The mesothelial cells were cytokeratin positive and vimentin positive, and negative for carcinoembryonic antigen (CEA) and factor VIII. The FNA findings from MCM should be distinguished from those of a variety of other abdominal lesions, including cystic lymphangioma, ovarian and primary peritoneal epithelial tumors, necrotic tumors with cystic degeneration, developmental cysts, and infectious cysts.
Rounded atelectasis: diagnosis by fine-needle aspiration cytology. W.T. Miller, P.K. Gupta, M.A. Grippi, et al. 1992;8(6):617-20. Case report PubMed · Publisher

Abstract

Rounded atelectasis, a rare, benign mass lesion, is most often seen in association with asbestos-related pleural changes. Often a presumptive diagnosis can be made on the basis of characteristic CT and chest radiographic findings. However, not infrequently radiographic imaging fails to differentiate rounded atelectasis from primary bronchogenic carcinoma, a disease which is seen with increased frequency in patients with asbestos exposure. We describe two cases where the diagnosis of rounded atelectasis was made by fine-needle aspiration (FNA) cytology. The cytologic features included abundant pulmonary parenchymal material with thickened alveolar walls containing pulmonary macrophages and connective tissue. It is important to realize that this is a useful positive finding indicating rounded atelectasis, rather than a negative finding suggesting the absence of neoplasm. Needles with a cutting action may be necessary to obtain sufficient material to make the diagnosis of rounded atelectasis.
The utility of ancillary techniques in effusion cytology. K.V. Nance, J.F. Silverman. 1992;8(2):185-9. Review PubMed · Publisher

Abstract

We believe that, in general, immunocytochemical studies when used as a panel are the most helpful of the ancillary techniques in the workup of a difficult effusion cytology case. Routine histochemical stains for mucin should also be employed due to their low cost and simplicity, but suffer from lack of sensitivity and specificity. EM examination is especially helpful in the differentiation of metastatic carcinoma from mesothelioma, but lacks specificity due to overlapping ultrastructural features, and is both costly and labor intensive. Immunophenotyping by flow cytometry is useful in the workup of problematic lymphoid proliferations, but DNA analysis by flow cytometry is not useful as a screening technique. Fortunately, most effusion cytology cases will not need the use of ancillary studies, since the diagnosis will be accurately rendered based on the cytomorphologic findings. However, occasional cases will benefit from the use of specific ancillary studies, which can aid in making an accurate, specific, and rapid diagnosis in an otherwise challenging case.

1980s

Ultrastructural histochemistry of mesotheliomas and adenocarcinomas in malignant effusions. P. Barsotti, A.O. Muda, V. Ascoli, et al. 1989;5(2):154-61. PubMed · Publisher

Abstract

The results of electron microscopic examination of cytologic specimens from six cases of mesothelioma and 10 cases of metastatic carcinoma of different origins are presented. The formation of cell clusters in malignant effusions from the two neoplasms has been thoroughly investigated: in mesotheliomas, cells had longer, more slender microvilli than in carcinomas and more abundant bundles of intermediate filaments; the central cavity often seen in the clusters frequently contained collagen and showed basement membrane production. The application of periodic acid-silver methenamine (PASM) and phosphotungstic acid (PTA) demonstrated a peculiar ultrastructural difference in cell coat staining in the two tumor types: in mesotheliomas, PTA and PASM were consistently negative along the outer surface of the cell aggregates, while carcinomas displayed a positive reaction either on the outer surface or on both inner and outer surfaces of the clusters. The diagnostic significance of the above-mentioned difference between the two neoplasms will require further investigation in a larger number of cases.
Value of immunocytochemistry in the study of malignant effusions. M.R. Mason, C.W. Bedrossian, C.A. Fahey. 1987;3(3):215-21. PubMed · Publisher

Abstract

Recognition of malignant effusion relies heavily on cytologic examination despite the difficulty of distinguishing atypical mesothelial hyperplasia from metastatic carcinoma. The combination of CEA, EMA, vimentin, keratin, high-molecular-weight cytokeratin (HMWK), low-molecular-weight cytokeratin (LMWK), and Alcian blue was tested in 51 cytologic specimens of pleural, peritoneal, and pericardial effusions. These showed metastatic carcinoma in 38 cases (ovary, 14; lung, 8; breast, 7; GI, 4; endometrium, 4; bladder, 1) and mesothelial processes in 13 (hyperplasia, 9; mesothelioma, 4). Strong positivity for EMA (92%), CEA (90%), and Alcian blue (71%) was noted in metastatic carcinoma but not in the mesothelial processes. Keratin was positive in all cases of mesothelioma but occurred also in mesothelial hyperplasias (44%) and metastatic carcinomas (47%). In mesothelial cells, HMWK was consistently stronger than LMWK, whereas in adenocarcinoma the reverse was true. There was no difference in the degree or distribution of positivity of any of the markers among the various primary sites of the neoplasms. Our findings are consistent with the view that immunocytochemistry with a battery of antibodies is useful in the recognition of malignant effusions but cannot, as yet, determine the site of origin of metastatic neoplasms.
Asbestos-associated pulmonary disease. K.L. Myrent. 1986;2(2):179. Letter PubMed · Publisher
Malignant mesothelioma cells in sputum. D. Whitaker, G. Sterrett, K. Shilkin, et al. 1986;2(1):21-4. Case report PubMed · Publisher

Abstract

In five patients with malignant mesothelioma of pleura, malignant cells, presumably derived from intrapulmonary deposits, were found in sputum specimens. The cells presented mainly as papillary aggregates of epithelial-like cells, in most cases without specific identifiable mesothelial cell features. In one patient, the specimen was received early in the diagnostic work-up and led to a strong consideration of the diagnosis of adenocarcinoma. In the remainder, the finding was incidental, occurring after the diagnosis of mesothelioma had been established. The cases are reported to draw attention to this phenomenon, previously unreported in the cytologic literature, and to emphasize that the finding of malignant cells in sputum does not preclude the diagnosis of malignant mesothelioma.
Cytopathology of asbestos-associated pulmonary disease. S.D. Greenberg. 1985;1(3):177-82. PubMed · Publisher

Abstract

The goal of this investigation was to determine the practical role of cytopathology in the clinical and laboratory diagnosis of asbestos-related pulmonary diseases. For this purpose, sputum, bronchial washings, lung tissues, and pleural fluids were obtained from asbestos workers and controls. The asbestos-associated pulmonary diseases studied were: (1) asbestosis, (2) carcinoma, and (3) mesothelioma. The cytology smears were prepared with both Papanicolaou and iron stains. Lung tissues were digested by the Chlorox (5.25% sodium hypochlorite solution) technique for quantitation of asbestos bodies. Asbestos bodies within the sputum were found to be highly specific markers for past asbestos exposure, indicating a heavy residual pulmonary asbestos load (greater than 900 asbestos bodies/g wet lung weight). Asbestos bodies in sputum were also found to have a highly significant relationship (P less than 0.001) with the degree of accompanying atypia of bronchial epithelial cells. Bronchial washings appeared to be more sensitive than sputum for the detection of asbestos bodies. Asbestos bodies were not found within the pleural fluids of malignant mesotheliomas. It is concluded that sputum cytology screening represents a practical, noninvasive, and inexpensive approach to the diagnosis and study of asbestos exposure.
Ultrastructural studies of malignant cells in fluids. G.A. Herrera, J.A. Wilkerson. 1985;1(4):272-85. PubMed · Publisher

Abstract

An ultrastructural study was performed on 104 sequential fluids in which more than eight malignant cells per ten high-power fields were found by routine light microscopy. The study included fluids associated with mesotheliomas, melanomas, lymphomas, squamous-cell carcinomas, small-cell anaplastic (oat-cell) carcinomas, and adenocarcinomas. Electron microscopic examination reliably separated lymphoid from epithelial malignancies and benign from reactive and malignant mesothelial cell proliferations. It also suggested or identified a primary site for the adenocarcinomas. Ultrastructural examination of fluids can be a valuable adjunct to routine light microscopy of cytology specimens. No false-positive diagnoses were encountered. Sampling was the most significant limitation for this technique.

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