Cytopathology

Our medical research library holds 34 studies published in Cytopathology (1990–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 24 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 5 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Blackwell Scientific Publications
• Published: 1990 to the present, England
• Language: English
• ISSN: 0956-5507 (print), 1365-2303 (electronic)
• Its record in the NLM Catalog

2020s

• Performance of the Monoclonal Antibody B72.3 in Diagnosis of Malignant Carcinomatous Serous Effusions-A Systematic Review and Meta-Analysis of Diagnostic Performance. A.H. Lin, M. Hsu, J.K.M. Ng, et al. 2025;36(4):399-407. Systematic review · Meta-analysis PubMed · Publisher · Free full text

  Abstract

  Objectives: Immunocytochemistry is often required in the cytologic assessment of malignant serous effusion, particularly for differentiating metastatic carcinoma from mesothelioma. To summarise the diagnostic performance of the monoclonal antibody B72.3, a systematic review and meta-analysis was conducted.

  Methods: Five databases were searched for relevant studies and reviewed for data extraction and risk of bias assessment. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under curve of summary receiver operating characteristics (AUC-SROC) were calculated for the diagnostic performance of B72.3. Heterogeneity and publication bias were assessed by the I2 index and Deeks' funnel plot.

  Results: In total, 19 studies (1159 cases) were included. Overall pooled sensitivity and specificity were 0.76 (0.72-0.79) and 0.90 (0.74-1.00), respectively. The NLR, PLR and DOR were 0.27 (0.21-0.34), 7.66 (< 0.001-20.46) and 28.26 (0-75.96), respectively. The AUC-SROC was 0.98, indicating a good overall diagnostic accuracy for B72.3. Subgroup analysis for adenocarcinoma (0.75, 0.71-0.79), mesothelioma (0.92, 0.85-0.98) and benign/reactive mesothelial cells (0.96, 0.93-1.00) showed similar sensitivity and specificity, while the sensitivity for adenocarcinomas of the gastrointestinal/hepatobiliary tract (0.56, 0.41-0.71) and breast (0.55, 0.38-0.71) was significantly lower. High heterogeneity was observed in the majority of our analyses, while no evidence of publication bias was identified.

  Conclusions: B72.3 has an acceptable performance with low sensitivity. With a good specificity, B72.3 may find use in an immunocytochemical panel for excluding benign mesothelial processes.

  © 2025 The Author(s). Cytopathology published by John Wiley & Sons Ltd.

• Practical Approach to Reporting Based on the International System for Serous Fluid Cytopathology. E. Viljanen, I. Kholová, A. Chandra. 2025;36(1):12-22. Review PubMed · Publisher · Free full text

  Abstract

  The International System for Serous Fluid Cytopathology (TIS) is intended for reporting cytological specimens from serous cavities: pleural, abdominal and pericardial cavities. TIS is being adopted into practice in cytology laboratories worldwide. In this system, there are six diagnostic categories: non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, malignant-primary and malignant-secondary. Malignant-primary category almost always implies malignant mesothelioma and malignant-secondary usually refers to metastasis from carcinoma but also to involvement of serous cavity by haematolymphoid and other malignancies. When evaluating effusion cytological specimen adequacy, the factors that must be considered are sample volume, cellular content and cellular preservation. In the diagnostic analysis and interpretation, it is helpful to consider systematically all basic cytomorphological components in a sample. The basic components are architecture, cell populations, cell size, cytoplasm, nuclei and background elements. One important requirement for a successful evaluation of an effusion cytological specimen is sufficient clinical and radiological information in a referral. Clinical information may guide ancillary testing. In the present review, we provide a practical and educational approach to reporting serous effusion cytology based on the TIS.

  © 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.

• Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology. A. Louw, Y.C.G. Lee, N. Acott, et al. 2022;33(1):84-92. PubMed · Publisher

  Abstract

  Objective: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.

  Methods: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.

  Results: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.

  Conclusions: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.

  © 2021 John Wiley & Sons Ltd.

• State-of-the-art cytology of pleural fluid, focusing on the diagnosis of mesothelioma. S.E. Monaco, L. Brcic, S. Dacic. 2022;33(1):57-64. Review PubMed · Publisher

  Abstract

  Mesothelioma has always been a challenging diagnosis to render in body cavity cytology samples. This review is a timely update on pleural fluid cytology and ancillary studies that should be considered in the diagnosis of mesothelial proliferations, specifically mesotheliomas. Information about new diagnostic approaches and ancillary studies in mesothelioma was obtained from the peer-reviewed literature and the authors' experiences. Although the morphological diagnosis of mesothelioma is fraught with numerous challenges given the overlap with other diagnostic entities, there are a variety of immunohistochemical and fluorescence in situ hybridization studies available to help in determining mesothelial origin and in distinguishing malignant proliferations from the more common benign or reactive mesothelial proliferations. Although ancillary studies can be helpful, there are important pitfalls to be aware of when interpreting these cases, and this review highlights some of the challenges that require caution.

  © 2021 John Wiley & Sons Ltd.

• The value of cytology in distinguishing malignant mesothelioma: An institutional experience of 210 cases reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC). P. Straccia, D. Magnini, R. Trisolini, et al. 2022;33(1):77-83. PubMed · Publisher

  Abstract

  Objective: Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC).

  Methods: A total of 450 cases were identified. Cytological analysis was present in 210 patients (164 pleural and 46 peritoneal effusions). All cases were reviewed and reclassified according to the proposed ISRSFC scheme. A comparison among the cytomorphological features was made throughout the different diagnostic categories.

  Results: The 210 cases were histologically diagnosed as follows: 192 (91.4%) cases had an epithelioid type and 18 (8.6%) had a sarcomatoid subtype of MM. The cytological cases were reclassified as follows: 2 (0.9%) as non-diagnostic (ND), 81 (38.6%) as negative for malignancy (NFM), 4 (1.9%) as atypia of undetermined significance (AUS), 11 (5.2%) as suspicious for malignancy (SFM), 112 (53.4%) as malignant (MAL). Sarcomatoid cells in the MAL category were characterised cytomorphologically by more pronounced discohesion. In comparison with the epithelioid subtype, the tumour cells appeared solitary with moderate or marked nuclear pleomorphism, and irregular chromatin.

  Conclusions: It is important to recognise the cytological characteristics of this aggressive entity to suggest an early and precise possible diagnosis. Morphological features, coupled with clinico-radiological data may help the clinicians in adequately managing the patients.

  © 2021 John Wiley & Sons Ltd.

• The phosphatase PTPN1/PTP1B is a candidate marker of better chemotherapy response in metastatic high-grade serous carcinoma. B. Davidson, A.J. Bock, A. Holth, et al. 2021;32(2):161-168. PubMed · Publisher

  Abstract

  Objective: To analyse the expression and clinical role of the phosphatase PTPN1 (PTP1B) in serous effusions.

  Methods: PTPN1 mRNA expression by quantitative RT-PCR was analysed in 83 high-grade serous carcinoma (HGSC) and 15 malignant mesothelioma (MM) effusions. PTP1B and phospho-PTP1B (pPTP1B) protein expression by immunohistochemistry was analysed in 62 HGSC and 44 MM effusions.

  Results: PTPN1 mRNA (P = .048), PTP1B protein (P = .047) and pPTP1B protein (P < .001) were overexpressed in HGSC compared to MM effusions. PTPN1 mRNA was additionally overexpressed in post-chemotherapy HGSC effusions compared to chemo-naïve effusions (P = .005). However, pPTP1B protein expression was higher in effusions from patients with FIGO stage III compared to stage IV (P = .006), and higher expressions of both PTPN1 mRNA (P = .041) and PTP1B protein (P = .035) in HGSC effusions were associated with better (complete) chemotherapy response at diagnosis. PTPN1 RNA and protein expression was unrelated to survival in HGSC, whereas a trend for shorter overall survival (P = .06) was found for MM patients whose tumours expressed pPTP1B protein.

  Conclusion: PTPN1 is overexpressed in HGSC compared to MM effusions, and may be a marker of better chemotherapy response in the former. Whether PTPN1 activation is informative of adverse outcome in MM merits further investigation.

  © 2020 John Wiley & Sons Ltd.

• Expression of palladin is associated with disease progression in metastatic high-grade serous carcinoma. B. Davidson, A.J. Bock, A. Holth, et al. 2020;31(6):572-578. PubMed · Publisher

  Abstract

  Objective: To analyse the expression and clinical role of the actin-associated molecule palladin in serous effusions.

  Methods: PALLD mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction in 83 high-grade serous carcinoma (HGSC) effusions. Fifteen malignant mesothelioma (MM) effusions and 18 surgical HGSC specimens from the ovary were studied for comparative purposes. Palladin protein expression by immunohistochemistry was analysed in another series consisting of 261 HGSC effusions.

  Results: PALLD mRNA was significantly overexpressed in HGSC compared to MM effusions (P < .001). Palladin expression by immunohistochemistry was found in HGSC cells in 106/261 (41%) effusions, most commonly focally (<5% of cells). PALLD expression was additionally higher in ovarian HGSC specimens compared to HGSC effusions (P < .001). However, immunohistochemistry showed only stromal expression of this protein in surgical specimens. PALLD mRNA expression in HGSC effusions was unrelated to clinicopathological parameters, chemotherapy response or survival. Palladin protein expression was higher in post-chemotherapy, mainly disease recurrence, specimens compared to chemo-naïve effusions tapped at diagnosis (P = .018), although it was unrelated to other clinicopathological parameters or survival.

  Conclusion: PALLD mRNA is overexpressed in HGSC compared to MM effusions, and its protein product is overexpressed in post-chemotherapy compared to pre-chemotherapy HGSC effusions, suggesting upregulation along tumour progression. The presence of this molecule in HGSC effusions, at the mRNA or the protein level, is unrelated to disease outcome.

  © 2020 John Wiley & Sons Ltd.

• MGMT promoter methylation is a rare epigenetic change in malignant effusions. M. Brunetti, I. Panagopoulos, F. Micci, et al. 2020;31(1):12-15. PubMed · Publisher

  Abstract

  Objective: The aim of this study was to analyse the promoter methylation status of the gene O6-methylguanine-DNA methyltransferase (MGMT) in malignant effusions, with focus on serous carcinoma.

  Methods: Fresh-frozen cell pellets from 81 effusions (42 peritoneal, 38 pleural, one pericardial), consisting of 71 carcinomas of different origin (33 ovarian, 23 breast, six lung, five uterine corpus and four cervical carcinomas) and 10 malignant mesotheliomas, were analysed for MGMT methylation using pyrosequencing analysis.

  Results: MGMT methylation at all four cytosine-guanine dinucleotide sites examined was detected in only 2/81 (2%) specimens, consisting of a high-grade serous carcinoma with high frequency of methylation, and a breast carcinoma with low methylation frequency.

  Conclusion: The findings in the present study suggest that MGMT methylation is a rare epigenetic change in malignant effusions of different origin.

  © 2019 The Authors. Cytopathology published by John Wiley & Sons Ltd.

• Number of mesothelial cells as a measure of adequacy criteria for pleural effusions: A multi-institutional study. E.F. Rodriguez, P.C. Morris, V. Calsavara, et al. 2020;31(3):223-227. PubMed · Publisher

  Abstract

  Background: The development of a terminology system is essential to allow uniformity in reporting serous fluid specimens. An important topic to cover is the issue of specimen adequacy. In the present study, we aimed to evaluate whether there is a correlation between number of mesothelial cells and overall improved sensitivity and adequacy control of tests.

  Methods: Cases of negative pleural fluids with concomitant positive pleural biopsies were selected from two referral institutions, with observation of the number of mesothelial cells in 10 high-power fields, comparing the results with a control group (cases with negative biopsies, ie, true negatives). Comparisons were conducted using the nonparametric Mann-Whitney U test. Data were analysed for sensitivity and specificity derived from the receiver operating characteristics curve. For the choice of an optimal cut-off of mesothelial cells, receiver operating curve analysis was constructed and the Youden index was calculated.

  Results: A total of 112 pleural effusions with paired pleural biopsies were studied. There was no difference in distributions of the number of mesothelial cells between cases with a positive biopsy (false negatives) and the control group (median = 39 vs median = 30, respectively, P-value = .974). However, simple logistic regression found a cut-off of 750 cells per 10 high-power fields as an optimal number for improved sensitivity (72.7%), with fair discriminatory power.

  Conclusions: Enumeration of mesothelial cells may improve the sensitivity of the cytological diagnosis of malignant pleural effusion, serving as an internal quality control for the test's overall accuracy.

  © 2020 John Wiley & Sons Ltd.

• The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens. W. Althakfi, S. Gazzo, M. Blanchet, et al. 2020;31(1):5-11. PubMed · Publisher

  Abstract

  Objective: Diffuse malignant peritoneal mesothelioma (DMPM), represents 30% of all malignant mesothelioma, and is characterised by a difficult diagnosis and different presentations. Immunohistochemistry has improved the diagnostic sensitivity and specificity in the differential diagnosis between metastatic adenocarcinoma and malignant mesothelioma, and loss of BRCA-1-associated protein 1 (BAP1) expression is correlated with BAP1 somatic or constitutional genetic defects. Furthermore, cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently lost in DMPM. In the present study, we assessed the value of integrating BAP1 in the panel of antibodies used for the diagnosis of DMPM in cytological samples. Since p16 fluorescent in situ hybridisation (FISH) assay could constitute an additional useful adjunct, results of BAP1 immunostaining and p16 FISH assays have been compared.

  Methods: Forty-eight DMPM patients and 71 peritoneal carcinomatosis patients were included. BAP1 immunohistochemical and CDKN2A FISH techniques were performed on tissue specimens of DMPM (n = 48) and peritoneal carcinomatosis (n = 71) then on cell-block of DMPM (n = 16), peritoneal carcinomatosis (n = 25) and peritoneal benign effusion (n = 5).

  Results: Loss of BAP1 expression was observed in 56.3% of DMPM while none of the peritoneal carcinoma specimens showed BAP1 loss of expression. CDKN2A loss was observed in 34.9% DMPM and 2.1% peritoneal carcinoma. Although BAP1 immunostaining was successful in 100% of cytological DMPM samples, CDKN2A deletion status could be obtained for 75% of DMPM cases.

  Conclusion: BAP1 immunostaining represents an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens and should be preferred to CDKN2A FISH analysis on these precious samples.

  © 2019 John Wiley & Sons Ltd.

2010s

• Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens. M. Vojtek, M.D. Walsh, D.J. Papadimos, et al. 2019;30(6):614-619. PubMed · Publisher

  Abstract

  Objective: To evaluate the utility of claudin-4 as a pan-carcinoma marker in cell-blocks of effusion specimens and compare results with Ber-Ep4 staining.

  Methods: Effusion cell-blocks (n = 284) were stained for claudin-4 and results compared with Ber-Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas.

  Results: All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin-4. Claudin-4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin-4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin-4 outperformed Ber-Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin-4 compared with Ber-Ep4, respectively. Only two cases were claudin-4-/Ber-Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin-4 (131/137; 95.6%) than Ber-Ep4 (117/137; 86.2%). Claudin-4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin-4 and Ber-Ep4.

  Conclusions: Claudin-4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber-Ep4.

  © 2019 John Wiley & Sons Ltd.

• Diagnostic value of BRCA1-associated protein-1, glucose transporter-1 and desmin expression in the discrimination between reactive mesothelial proliferation and malignant mesothelioma in tissues and effusions. S. Önder, E. Özogul, D. Koksal, et al. 2019;30(6):592-600. PubMed · Publisher

  Abstract

  Objective: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations.

  Methods: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies.

  Results: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%).

  Conclusions: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.

  © 2019 John Wiley & Sons Ltd.

• Aquaporin-1 expression in fluoro-edenite-induced mesothelioma effusions: An approach by cell-block procedure. G. Angelico, A. Ieni, R. Caltabiano, et al. 2018;29(5):455-460. PubMed · Publisher

  Abstract

  Objective: Aquaporin 1 (AQP-1) is a water channel protein found in cell membranes, whose expression has been considered an independent favourable prognostic factor in pleural malignant mesothelioma (MM). The aim of this study was to evaluate the expression of AQP-1 and its prognostic value in a series of pleural MM effusions, from a geographical area with high concentrations of fluoro-edenite (FE).

  Methods: We selected 25 MM cases from Biancavilla (Italy), an area with high environmental concentrations of FE. Cytological samples, cell-blocks (CB), clinical and follow-up data were available for all cases. Immunohistochemistry for calretinin, CK5/6, WT1, CK7 and TTF1 was used on CB sections to confirm the cytological diagnosis of MM. Immunohistochemistry for AQP-1 was performed and high expression was defined when ≥50% of tumour cells showed linear and circumferential membranous staining.

  Results: The cohort included 16 men and nine women (median age: 67.5 years; range: 49-88 years). The median survival was 14 months (range 1.5-60 months), with a significant value (P = 0.006). All cases have been histologically confirmed and classified as epithelioid (16 cases), biphasic (seven cases) and sarcomatoid (two cases). AQP-1 high expression has been observed in 16 cases. Comparing AQP-1 high expression to the survival of corresponding patients, a significant association with a slight increased overall survival of 12 months has been demonstrated. Nine patients with a AQP-1 score less than 50% showed a shorter median overall survival (7 months).

  Conclusions: AQP-1 high expression is detectable on cytological samples of FE-induced MM with a prognostic value.

  © 2018 John Wiley & Sons Ltd.

• Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks. X. Zhang, L. Chen, Y. Liu, et al. 2018;29(3):247-253. PubMed · Publisher

  Abstract

  Introduction: Precise cytological diagnosis of pelvic high-grade serous carcinoma (HGSC) in ascites is important for tumour staging, therapeutic decision-making and prognostic evaluation. However, it can often be difficult to distinguish metastatic HGSC cells from reactive mesothelial cells based on morphology alone. Immunocytochemical analysis of ascites cell blocks has been used to obtain accurate diagnosis and provide a reliable basis for treatment decisions in the clinic. This study was performed to determine whether a panel of antibodies is necessary to achieve high specificity and sensitivity for the identification of HGSC cells.

  Methods: Ascites samples from 70 cases (70/253, 27.7%) of histologically confirmed HGSC were postoperatively collected from 2012 to 2015 and were immunocytochemically analysed.

  Results: The sensitivity and specificity of Ber-EP4 (a marker of HGSC) for detecting HGSC was 85.7% and 82.1%, respectively, whereas the sensitivity and specificity of HBME-1 for identifying mesothelial cells was 100% and 68.3%, respectively. To improve the rate of detection further of HGSC, 29 cases of ascites were also stained for E-cadherin (a marker of HGSC) and calretinin (a marker of mesothelial cells). The combination of Ber-EP4 and E-cadherin as markers of adenocarcinoma cells increased the sensitivity and specificity for HGSC detection to 100% and 88.9%, respectively. Meanwhile, the sensitivity and specificity for mesothelial cell identification increased to 100% and 90%, respectively, when HBME-1 and calretinin were combined.

  Conclusion: This panel of complementary biomarkers is valuable and ideal for the differential diagnosis of HGSC based on ascites cytology.

  © 2017 The Authors. Cytopathology Published by John Wiley & Sons Ltd.

• Metastatic pleural mesothelioma presenting in a breast fine needle aspiration specimen. P.W. Shield, D.L. Ribu. 2017;28(5):429-431. Case report PubMed · Publisher

• Cytomorphology of ovarian clear cell carcinomas in peritoneal effusions. D. Damiani, V. Suciu, C. Genestie, et al. 2016;27(6):427-432. PubMed · Publisher

  Abstract

  Objective: To investigate and describe the cytomorphology of malignant effusions from ovarian clear cell carcinomas (OCCC).

  Methods: Five cases of malignant peritoneal effusions from OCCC histologically confirmed were analysed and compared.

  Results: Among the malignant peritoneal effusions exhibiting clear cell features, a characteristic feature of OCCC was the presence of large deposits of a hyaline matrix. This matrix may be typically arranged either in 'raspberry bodies' or 'globule-like' structures. Other rare neoplasms composed of clear cells must be considered in the differential diagnosis such as yolk sac tumour of the ovary, clear cell subtype of endometrial carcinoma and, less frequently, malignant peritoneal mesothelioma as well as metastatic renal cell carcinoma.

  Conclusions: Ovarian clear cell carcinomas have distinct morphological features that are helpful in making a cytological diagnosis of this entity. The role of cytological examination in ovarian neoplasms is of paramount importance, as stated by The International Federation of Gynecology and Obstetrics (FIGO) recommendations.

  © 2016 John Wiley & Sons Ltd.

• Pulmonary acantholytic squamous cell carcinoma with focal signet ring cell morphology mimicking malignant mesothelioma on fine needle aspiration cytology: a case report. S.E. Choi, H.S. Park. 2016;27(2):131-3. Case report · Letter PubMed · Publisher

  Summary

  The authors, from the Department of Pathology at Gangnam Severance Hospital in Seoul, South Korea, described the cytological features of a lung squamous cell carcinoma (SCC) with both acantholytic and signet ring cell components, and discussed its differential diagnosis. They stated that the signet ring cell variant of SCC had not been reported in the lung. A 64-year-old man was a 35-pack-year ex-smoker with hypertension. A chest X-ray taken during a regular medical examination showed a nodule, and computed tomography showed a 2.8-cm mass with an irregular margin in the left upper lobe. CT-guided fine needle aspiration (FNA) was performed, followed by left upper lobe lobectomy with mediastinal lymph node dissection. The FNA smears showed loose aggregates and scattered round tumour cells. These cells had central nuclei, prominent nucleoli, dense cytoplasm and endoplasmic–ectoplasmic demarcation. Some contained intracytoplasmic vacuoles that were negative for periodic acid-Schiff with diastase. Cell-to-cell opposition with windows, linear arrangement and cell-in-cell engulfment were also seen. All tumour cells were positive for p63 and p40 and negative for TTF-1, napsin-A, calretinin, WT-1 and D2-40. The final diagnosis was acantholytic SCC with signet ring cell features. The cytological differential diagnosis had included poorly differentiated adenocarcinoma, non-keratinizing SCC and intrapulmonary epithelioid malignant mesothelioma. The authors concluded that this tumour's cytological features can resemble epithelioid malignant mesothelioma, and that immunostaining including squamous and mesothelial cell markers may be required to confirm it.

  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.

• The role of endobronchial ultrasound-guided fine needle aspiration in the diagnosis of pleural mesothelioma. M.R. Ghigna, A. Crutu, V. Florea, et al. 2016;27(4):284-8. PubMed · Publisher

  Abstract

  Objective: The aims of the present study were to investigate the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of malignant pleural mesothelioma (MPM), and to identify specific clinical settings in which this procedure can be recommended.

  Methods: We retrospectively reviewed the clinical and pathological files of patients having undergone EBUS-TBNA from February 2011 to October 2014 to investigate thoracic lesions. Among 736 patients, we identified four of them with a diagnosis of MPM achieved primarily through EBUS-TBNA. The diagnosis was made on formalin-fixed paraffin-embedded cell blocks, by checking the expression of mesothelial and carcinomatous-specific markers.

  Results: In all patients, the collected tissue was adequate, and the histological analysis in association with immunohistochemistry led us to the diagnosis of malignant pleural mesothelioma. In three patients, the diagnosis of mesothelioma was clinically suspected, as patients presented with diffuse pleural thickening. In two patients, videothoracoscopy was not possible owing to the 'dry' presentation of the pleural disease and the site of thickening. In this setting, EBUS-TBNA was considered, at a multidisciplinary consensus meeting, as the most adequate available method to obtain a histological diagnosis.

  Conclusion: EBUS-TBNA may be a valuable diagnostic technique in the field of pleural pathology in selected clinical settings. More specifically 'dry' mesothelioma forming para-tracheal nodules or masses not accessible by surgery or by computed tomography/ultrasonogaphy-guided needle biopsy constitutes a good indication to perform EBUS-TBNA.

  © 2015 John Wiley & Sons Ltd.

• Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: a secondary publication. A. Hjerpe, V. Ascoli, C.W. Bedrossian, et al. 2015;26(3):142-56. Guideline 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 John Wiley & Sons Ltd.

• The evolving role of effusion cytology in the diagnosis of malignant mesothelioma. A. Paintal. 2015;26(3):137-8. Editorial · Comment PubMed · Publisher

• Cytomorphological features of metastatic squamous cell carcinoma in serous effusions. C.C. Huang, C.W. Michael. 2014;25(2):112-9. PubMed · Publisher

  Abstract

  Objective: To study the cytomorphological features of squamous cell carcinoma (SCC) in serous effusions.

  Methods: Conventional smears from 23 SCC were reviewed for the following features: cellularity, single cells, cell clusters, long cords, squamous pearls, cell-in-cell, 'windows', polygonal cells, anucleated cells, tadpole cells, fibre cells, third-type cells, refractile cytoplasmic ring, two-tone cytoplasm, cytoplasmic density, cytoplasmic vacuoles, signet ring cells, nuclear/cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleolus, anaplastic cells and mitosis. Subsequently, we also reviewed 15 reactive mesothelium, 18 mesotheliomas and 24 adenocarcinomas for comparison.

  Results: Most SCC smears comprised mixed populations of single cells and cell clusters. Keratinized squamous cells and squamous pearls were diagnostic for well-differentiated SCC. Squamous eddies, appreciated on the cell block sections appearing as two-dimensional cell clusters with a swirling pattern, were characteristic for SCC. Poorly differentiated/third-type cells with atypical cytoplasmic keratinization, manifest as two-tone cytoplasm with a well-defined border and occasionally a refractile central ring, were an important clue for the squamous origin of the cells. Features including cell-in-cell, cytoplasmic vacuolation, double or multinucleated cells, anaplastic cells and mitotic figures were present in various degrees, and were not of diagnostic value.

  Conclusions: Certain cytological features are diagnostic for SCC, whereas other features of poorly differentiated SCC often overlap with those of reactive mesothelial cells, mesothelioma, metastatic adenocarcinoma or urothelial carcinoma in serous effusions. The combination of clinical history, appropriate immunohistochemical panel and cytomorphological features are important to ensure a correct diagnosis.

  © 2013 John Wiley & Sons Ltd.

• Fine needle aspiration cytology in malignant mesothelioma of the tunica vaginalis testis. R. Gupta, P. Dey, R.K. Vasishtha. 2011;22(1):66-8. Case report · Letter PubMed · Publisher

• Flow cytometric measurement of cellular FLICE-inhibitory protein (c-FLIP) in ovarian carcinoma effusions. H.P. Dong, A.K. Ree Rosnes, A.J. Bock, et al. 2011;22(6):373-82. PubMed · Publisher

  Abstract

  Objective: The objective of this study was to establish a flow cytometry assay for measuring c-FLIP in serous effusions. In addition, we studied the clinical relevance in ovarian carcinoma effusions of this inhibitor protein in the death receptor signalling pathway of apoptosis.

  Methods: Two c-FLIP antibodies were tested using Western blotting and the best performing one was used for titration of c-FLIP expression in a panel of five cell lines, consisting of ovarian carcinoma, breast carcinoma and malignant mesothelioma. The concentration that provided the best signal-to-noise ratio was used for comparison of the performance of three fixation and permeabilization protocols. The best performing protocol was chosen for analysis of 69 ovarian carcinoma effusions. c-FLIP expression was analysed for association with clinicopathological parameters and survival.

  Results: Rabbit polyclonal c-FLIP by Abcam and the IntraStain kit by Dako performed best. c-FLIP expression was detected in tumour cells in all 69 effusions (expression range 21-100%, median = 80%). No association was found between c-FLIP expression and clinicopathological parameters, including chemoresponse and survival. However, an inverse correlation was found between c-FLIP levels and expression of the previously studied apoptosis marker cleaved caspase-3 (P = 0.029).

  Conclusions: An assay for measuring c-FLIP in cytology specimens is presented. c-FLIP is frequently expressed in ovarian carcinoma effusions, but its expression appears to be unrelated to disease aggressiveness.

  © 2011 Blackwell Publishing Ltd.

• PINCH-2 expression in cancers involving serosal effusions using quantitative PCR. Y. Yuan, H.P. Dong, D.A. Nymoen, et al. 2011;22(1):22-9. PubMed · Publisher · Free full text

  Abstract

  Objective: The PINCH-2 gene was previously shown to be overexpressed in malignant mesothelioma compared with ovarian/peritoneal serous carcinoma in Affymetrix array analysis. The objective of the present study was to validate this finding at the mRNA and protein level.

  Methods: Effusions (n = 91; 71 ovarian and 10 breast carcinomas, 10 malignant mesotheliomas) were assayed for PINCH-2 mRNA expression using quantitative PCR. PINCH-2 protein expression was analysed in 37 effusions using flow cytometry.

  Results: Quantitative PCR analysis showed significantly higher PINCH-2 mRNA levels in mesotheliomas compared with carcinomas (P = 0.004). Values of <10 copies were found exclusively in carcinoma effusions (25.4% of ovarian and 50% of breast carcinomas). However, PINCH-2 protein expression by flow cytometry did not differ significantly between the three cancer types. No association was observed between PINCH-2 levels and patient survival or expression of previously-studied molecules related to adhesion, metastasis and apoptosis inhibition in ovarian carcinoma.

  Conclusions: Our data suggest that PINCH-2 mRNA is overexpressed in malignant mesothelioma compared with carcinomas involving serosal cavities, and that low levels of this gene argue against the diagnosis of mesothelioma. The frequent PINCH-2 protein expression in all three studied cancers suggests a role for this molecule in cancer cell biology in effusions and merits further research.

  © 2010 Blackwell Publishing Ltd.

• Should cytology be an acceptable means of diagnosing malignant mesothelioma?. M. Sheaff. 2011;22(1):3-4. Comment · Editorial PubMed · Publisher

  Summary

  This editorial accompanied a review article by Davidson in the same issue and discussed whether cytology should be an acceptable means of diagnosing malignant mesothelioma. The author noted that reactive mesothelial cell proliferations and other cancers can closely resemble mesothelioma in cytological preparations, so the definitive diagnosis is usually based on histology, which can also confirm tissue invasion. He stated that most agree the diagnosis can at least be suspected from a fluid sample. This matters for treatment, and because cytology may be the only pathological material available for people with mesothelioma from occupational asbestos exposure who are seeking compensation. British, European, international and American guidelines were described as acknowledging a role for cytology while favouring tissue diagnosis for final confirmation. The author identified the lack of a marker specific for mesothelioma as a central problem, particularly for separating reactive from malignant mesothelium and for distinguishing peritoneal mesothelioma from serous adenocarcinoma in women. He described a female patient whose pleural serous adenocarcinoma was later traced to an endometrial primary. He used this case to stress close clinical and radiological correlation and to note that serous carcinomas are not usually considered asbestos-related. He concluded that immunocytochemistry on cell blocks is widely available and that molecular research might one day identify a unique marker supporting a dependable cytological diagnosis.

  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.

• The diagnostic and molecular characteristics of malignant mesothelioma and ovarian/peritoneal serous carcinoma. B. Davidson. 2011;22(1):5-21. Review PubMed · Publisher

  Abstract

  Malignant mesothelioma and ovarian/peritoneal serous carcinoma are two of the most common tumours affecting the serosal cavities. Unlike other malignant tumours diagnosed at this anatomical site, such as lung and breast carcinoma, malignant mesothelioma and serous carcinoma share a common histogenesis, may be difficult to differentiate morphologically, and co-express many of the diagnostic markers used by cytopathologists in effusion diagnosis. Selected markers have nevertheless shown sufficient sensitivity and specificity to differentiate serous carcinoma from malignant mesothelioma effectively. Recently, our group applied high throughput technology to the identification of new markers that may aid in differentiating these two cancer types and validated several of these markers in follow-up studies. This review will present current data regarding the diagnostic and biological aspects of malignant mesothelioma and ovarian/peritoneal serous carcinoma.

  © 2010 Blackwell Publishing Ltd.

2000s

• Lung squeeze: a helpful adjunct in diagnosis. L. Gupta, J. Elder. 2005;16(5):269-70. Case report · Letter PubMed · Publisher

• Deciduoid peritoneal mesothelioma. A report of the cytological appearances. F.R. Gillespie, J.D. van der Walt, N. Derias, et al. 2001;12(1):57-61. Case report PubMed · Publisher

  Summary

  The authors (Guy's and St Thomas' Hospitals, London) reported a case of deciduoid malignant mesothelioma of the peritoneum. This variant had previously been described in young females unexposed to asbestos. They described, for the first time, the cytological appearances of the ascitic fluid. A 50-year-old woman presented with a 5-month history of generalized abdominal pain and occasional episodes of rectal bleeding. At laparoscopy, 300 mL of straw-coloured fluid was aspirated. At laparotomy, 500 mL of ascites and an inflamed, indurated omentum were found, and the omentum, both ovaries and both tubes were removed. Ascitic fluid cytology and the intraoperative frozen section were initially considered to show reactive mesothelial proliferation. Examination of the omental mass, including immunocytochemistry and electron microscopy, established a diagnosis of deciduoid malignant mesothelioma. Small numbers of malignant cells were found on the surface of the ovaries and tubes. The fluid contained a single population of large, rounded mesothelial cells with abundant dense cytoplasm, prominent nucleoli and slightly coarser chromatin, with a background of inflammatory cells. The authors noted that the patient fell within the usual age group for malignant mesothelioma and had no history of asbestos exposure. She was referred for chemotherapy and remained well over a year later. They concluded that peritoneal mesothelioma in non-asbestos-exposed females of a wide age range must be borne in mind in the differential diagnosis of ascitic fluid cytopathology.

  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.

• Malignant mesothelioma mimicking squamous carcinoma in a pleural fluid aspirate. J.S. Johnson, J.M. Edwards. 2001;12(1):54-6. Case report PubMed · Publisher

• The cytology of malignant mesothelioma. D. Whitaker. 2000;11(3):139-51. Review PubMed · Publisher

  Summary

  This invited review described the introduction, development and state of the art of cytopathology in diagnosing malignant mesothelioma. The author, from a cytology unit in Perth, Western Australia, noted that mesothelioma incidence had increased worldwide over 30 years, mainly in association with asbestos dust exposure. His institution saw a new case each week on average. Published sensitivities of effusion cytology ranged from 0 to 93%, with better results from laboratories with more experience. Other series reported 76% (51 cases) and 32% (29 cases), the latter attributed to sampling problems. The author reported a 100% predictive value for a positive diagnosis in serous effusions and a 73% sensitivity for fine needle aspiration. A history of asbestos exposure was described as helpful but not essential. The review covered key features of the cells and cell clusters, including collagen cores, and the use of special stains. In the author's experience, 98% of mesotheliomas showed strong EMA staining. In 16 adenocarcinomas and 26 mesotheliomas tested, all adenocarcinomas were negative and all mesotheliomas positive for calretinin and cytokeratin 5/6. The author recommended a five-antibody panel, electron microscopy in selected situations (including litigation), and a standard protocol. Problem areas included sparsely cellular fluids, often from sarcomatous mesotheliomas, and well-differentiated and desmoplastic tumours. The author concluded that the standardized approach gave a high degree of sensitivity and specificity.

  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.

1990s

• Utility of HBME-1 immunostaining in serous effusions. V. Ascoli, C. Carnovale-Scalzo, S. Taccogna, et al. 1997;8(5):328-35. PubMed · Publisher

  Abstract

  HBME-1 is an anti-mesothelial cell monoclonal antibody derived from human mesothelioma cells. We investigated 227 body cavity effusions to test its utility in differentiating mesothelioma from adenocarcinoma. HBME-1 outlined cell membranes in non-neoplastic mesothelial cells. Thick surface staining was observed on all mesotheliomas. HBME-1 reactivity was also detected in 24% of metastatic carcinomatous effusions. Most ovarian carcinomas (83%) reacted with this antibody, showing surface staining. Cytoplasmic HBME-1 immunoreactivity was observed in a small proportion of non-ovarian adenocarcinomas (14%). Despite its limited specificity, HBME-1 might be added to the battery of other markers of epithelial and/or mesothelial differentiation to be used in cases of suspected mesothelioma. Evaluation of suspicious cells should include careful study of the pattern of immunostaining.

• Malignant peritoneal mesothelioma with squamous metaplasia. T. Matsuo, H. Ito, M. Anami, et al. 1993;4(6):373-8. Case report PubMed · Publisher

  Summary

  The authors described a case of malignant peritoneal mesothelioma that partly showed the histological features of squamous carcinoma, in a man with past asbestos exposure, from Nagasaki, Japan. The 48-year-old man had worked continuously with asbestos, lagging pipes, from age 17 to 30. He was admitted with a 6-month history of lower abdominal distention. Computed tomography showed ascites and a mass of the omentum, and cytology of the fluid showed malignant cells compatible with mesothelioma. At laparotomy, about 1000 ml of bloody fluid was found, along with massive omental tumour and thickening of the entire peritoneum. As much tumour as possible was removed. Histology confirmed peritoneal mesothelioma. After chemotherapy with cisplatin, doxorubicin and cyclophosphamide, he stayed free of ascites for 6 months. He then developed paralytic ileus, renal failure and metastatic tumour, and died 7 months later. The ascitic fluid contained atypical mesothelial cells and a few cells resembling keratinizing squamous carcinoma. At autopsy, the tumour was mixed epithelial and sarcomatous mesothelioma. One nodule contained squamous cells with intercellular bridging and keratinization that merged with mesothelioma. Both lungs and the hilar lymph nodes showed asbestosis. The squamous areas stained for high molecular weight cytokeratins. The authors could not entirely exclude two separate tumours, but found no independent primary squamous carcinoma. They suggested that multipotential subserosal cells can undergo squamous metaplasia.

  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.

• Immunocytochemical staining of serous effusions with the monoclonal antibody Ber-EP4. M. De Angelis, I.D. Buley, A. Heryet, et al. 1992;3(2):111-7. PubMed · Publisher

  Abstract

  Cytospin preparations were made from 102 serous effusions for immunocytochemical staining using a panel of monoclonal antibodies including a new monoclonal antibody Ber-EP4. On cytological examination, 32 fluids were reported to contain tumour cells consistent with metastatic adenocarcinoma; 66 contained benign cells only and three were reported to contain cells suspicious of malignancy. One effusion contained tumour cells consistent with malignant mesothelioma. Positive staining of the tumour cells with Ber-EP4 was observed in the 32 effusions (100%) which contained adenocarcinoma cells. No staining of the mesothelial cells in these 32 specimens was observed. Carcinoembryonic antigen, epithelial membrane antigen Ca2 and CD15 staining of tumour cells was noted in 53%, 50%, 50% and 9% of these cases, respectively. None of the mesothelial cells in the benign effusions stained with Ber-EP4. Nor did the malignant mesothelial cells in the only case of malignant mesothelioma. These findings suggest that Ber-EP4 is a valuable addition to antibodies available for the differential diagnosis of mesothelial cells and adenocarcinoma cells in serous effusions.

• Cytopathology of malignant mesothelioma. Reappraisal of the diagnostic value of collagen cores. M. Delahaye, A.A. de Jong, M.A. Versnel, et al. 1990;1(3):137-45. PubMed · Publisher

  Abstract

  The identification of malignant mesothelial cells in cytological smears prepared from serous effusions is still hampered by the lack of features specific for mesothelial differentiation. We examined the diagnostic value of collagen cores within clusters of tumour cells in cytological smears prepared from effusions from 43 patients with malignant mesothelioma and of 62 cases of metastatic adenocarcinoma. In Giemsa-stained smears collagen cores were detected in 51% of the cases of malignant mesothelioma and in none of the smears with metastatic adenocarcinoma. Using the Azan stain, collagen cores were detected in 64% of the malignant mesotheliomas and 4% of the adenocarcinomas. Immunoelectron microscopy demonstrated that the collagen cores are largely composed of collagen type III fibrils and some elastin embedded in a homogenous extracellular matrix. It can be concluded that the presence of collagen cores within clusters of tumour cells is highly suggestive of mesothelial differentiation and a common finding in malignant mesothelioma.

Browse every journal in the library or the library by type of article, or return to medical research.