Archives of Pathology & Laboratory Medicine

About the journal

Publisher: College of American Pathologists
Published: 1976 to the present, United States
Language: English
ISSN: 0003-9985 (print), 1543-2165 (electronic)
Continues: Archives of Pathology
Its record in the NLM Catalog

2020s

Molecular and Immunohistochemical Testing in Mesothelioma and Other Mesothelial Lesions. Y.P. Hung, L.R. Chirieac. 2024;148(5):e77-e89. Review PubMed · Publisher

Abstract

Context.—: Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.

Objective.—: To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.

Data Sources.—: We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.

Conclusions.—: Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.

© 2024 College of American Pathologists.
Molecular Characterization of Testicular Mesothelioma and the Role of Asbestos as a Causative Factor. A.J. Hocking, E.M. Thomas, S. Prabhakaran, et al. 2023;147(12):1446-1450. PubMed · Publisher

Abstract

Context.—: Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma.

Objective.—: To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos.

Design.—: We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time.

Results.—: The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations.

Conclusions.—: The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere.

© 2023 College of American Pathologists.
Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice. N. Le Stang, L. Burke, G. Blaizot, et al. 2020;144(4):446-456. Systematic review PubMed · Publisher

Abstract

Context.—: Pleural mesothelioma is a rare cancer with an often-challenging diagnosis because of its potential to be a great mimicker of many other tumors. Among them, primary lung and breast cancers are the 2 main causes of pleural metastasis. The development and application of targeted therapeutic agents have made it even more important to achieve an accurate diagnosis. In this setting, international guidelines have recommended the use of 2 positive and 2 negative immunohistochemical biomarkers.

Objectives.—: To define the most highly specific and sensitive minimum set of antibodies for routine practice to use for the separation of epithelioid malignant mesothelioma from lung and breast metastasis and to determine the most relevant expression cutoff.

Design.—: To provide information at different levels of expression of 16 mesothelial and epithelial biomarkers, we performed a systematic review of articles published between 1979 and 2017, and we compared those data to results from the Mesothelioma Telepathology Network (MESOPATH) of the standardized panel used in routine practice database since 1998.

Results.—: Our results indicate that the following panel of markers-calretinin (poly)/thyroid transcription factor 1 (TTF-1; clone 8G7G3/1) and calretinin (poly)/estrogen receptor-α (ER-α; clone EP1)-should be recommended; ultimately, based on the MESOPATH database, we highlight their relevance which are the most sensitive and specific panel useful to the differential diagnosis at 10% cutoff.

Conclusions.—: Highlighted by their relevance in the large cohort reported, we recommend 2 useful panels to the differential diagnosis at 10% cutoff.
Use of Programmed Death Ligand-1 (PD-L1) Staining to Separate Sarcomatoid Malignant Mesotheliomas From Benign Mesothelial Reactions. F. Derakhshan, D. Ionescu, S. Cheung, et al. 2020;144(2):185-188. PubMed · Publisher

Abstract

Context.—: The separation of benign from malignant mesothelial proliferations is a difficult morphologic problem. Some mesotheliomas stain for programmed death ligand-1 (PD-L1).

Objective.—: To determine whether PD-L1 staining can separate mesotheliomas from reactive mesothelial proliferations (RMPs).

Design.—: We stained 2 tissue microarrays containing in toto 62 malignant mesotheliomas and 88 RMPs, using anti-PD-L1 antibody 22C3. Staining was graded by using an immunoreactive score encompassing intensity/distribution and was divided into negative, weak, moderate, and strong. Because PD-L1 staining can be heterogeneous, we also stained 10 whole sections of sarcomatoid/desmoplastic mesotheliomas (SMMs) and 10 whole sections of spindled RMPs in the form of organizing pleuritis, the major morphologic differential of SMM. These 20 cases were not on the tissue microarrays.

Results.—: RMPs showed generally negative, or occasionally weak staining in either the epithelioid or spindle cell compartments, whereas moderate to strong staining was seen in 10 of 14 SMMs but only in 6 of 48 epithelioid mesotheliomas (EMMs). The difference between SMM and RMP staining was statistically significant (P < .001), but between EMM and RMP was not significant. Whole section cases of organizing pleuritis showed no staining (N = 8) or weak staining (N = 2), whereas moderate/strong staining was seen in 9 of 10 whole sections of SMMs, a statistically significant difference (P = .02). There were no "hot spots" of RMP staining, suggesting that heterogeneous staining of RMPs is not a confounder.

Conclusions.—: Strong diffuse PD-L1 staining using antibody 22C3 supports a diagnosis of SMM when the differential diagnosis is RMPs, but PD-L1 staining is not useful for separating EMMs from RMPs.

2010s

In Reply to "Malignant Mesothelioma and Its Nonasbestos Causes". R.L. Attanoos, A. Churg, F. Galateau-Salle, et al. 2019;143(8):911-914. Letter · Comment PubMed · Publisher

Summary

This letter was the authors' reply to correspondence from Dr Finkelstein about their 2018 review, "Malignant mesothelioma and its non-asbestos causes." Dr Finkelstein had questioned two statements in the review: that most mesotheliomas not clearly attributable to asbestos are spontaneous, and that in North America few mesotheliomas in women at any site are attributable to asbestos. The authors stated that he had cited no contrary peer-reviewed literature. Instead, they said, he relied on Statista market data on US body and baby powder purchasing between 2011 and 2017, and on a fiber burden database obtained through litigation and published without consent from one of the authors. They argued that a fiber burden result must be compared with a laboratory's control reference range before any significance is assigned. They noted that many female mesothelioma subjects in Roggli's data had fiber burdens within the control range. They explained the higher detection of talc and noncommercial amphiboles in women as a result of lower exposures combined with fiber-counting protocols. They also discussed aspect-ratio criteria for telling asbestiform fibers from cleavage fragments. They cited studies of cosmetic talc miners and millers with no confirmed mesothelioma cases, more than 300 talc pleurodesis patients followed for 14 to 40 years with no mesotheliomas, and rat and hamster experiments with no mesotheliomas. They concluded that they found no evidence that cosmetic talc causes malignant mesothelioma. The authors disclosed work as expert witnesses in asbestos and talc litigation.

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 and Its Nonasbestos Causes. M.M. Finkelstein. 2019;143(6):659-660. Letter · Comment PubMed · Publisher

Summary

In this letter to the editor, the author responded to a review by Attanoos and colleagues, which had concluded that most mesotheliomas not clearly attributable to asbestos exposure are spontaneous. The author argued that the review did not consider asbestos exposure from talcum powders. He cited earlier studies of consumer talc products. In 1976, Rohl et al reported that 10 of 20 products (50%) contained tremolite and anthophyllite, and other investigators had found asbestiform tremolite or anthophyllite in a popular baby powder ore and a popular body powder. He also cited market research reporting that some 100 million Americans used body and baby powders between 2011 and 2017. The author then drew on a lung fiber-burden database compiled by Victor Roggli, MD, at Duke University Medical Center, covering 566 people with pleural mesothelioma, 75 (13%) of them women. Talc fibers were detected in 332 of 491 men (68%) and 62 of 75 women (83%). Detection of tremolite (P < .001) and anthophyllite (P = .002) was significantly associated with the presence of talc. Talc and associated amphiboles were more common in women than men (odds ratio 3.24; 95% CI 1.65–6.35). The author concluded that, without accounting for amphibole asbestos exposure from baby and body powders, it was inappropriate to conclude that most mesotheliomas not clearly attributable to asbestos are spontaneous. He disclosed that he has served as a consultant to plaintiff's lawyers in asbestos and talc litigation.

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 and Its Nonasbestos Causes: Talcum Powder Does Not Create Occult Asbestos Exposure. S.J. Geyer. 2019;143(12):1439. Letter · Comment PubMed · Publisher
Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis. M. Regragui, N.B. Guebessi. 2019;143(4):531-533. Review PubMed · Publisher

Abstract

Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.
Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma: Ten Years of Clinical Experience in Relation to International Guidelines. A. Hjerpe, S. Abd-Own, K. Dobra. 2018;142(8):893-901. PubMed · Publisher

Abstract

Context: - Early diagnosis of malignant mesothelioma (MM) is urgently needed because life expectancies and treatment options are limited in advanced stages of the disease. Malignant mesothelioma often presents with recurrent hemorrhagic or inflammatory effusions, which might mask the incipient stages of the disease and thereby delay the diagnosis. Despite difficulties in recognizing the malignant cells present in those early effusions, they are often the first available biologic material for diagnosis. Therefore, awareness is needed, and efforts should be made to distinguish the malignant cells by well-defined morphological criteria, combined with ancillary methods.

Objectives: - To summarize the diagnostic criteria for the cytopathologic diagnosis of MM based on recently published guidelines and to evaluate the clinical utility of those criteria in clinical practice.

Data Sources: - The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM and data in recent literature constitute the sources of this review. Eighty-five epithelioid or mixed-type MMs diagnosed between 2004 and 2013 at the Department of Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge (Stockholm, Sweden), were evaluated to determine the clinical utility of the criteria defined by the guidelines.

Conclusions: - A conclusive diagnosis of MM can be obtained based on the criteria defined by the guidelines with high positive predictive value. When diagnosed in this way, subsequent therapy should be initiated without further delay. With the earlier diagnosis obtained by cytology, a better effect of chemotherapy can be expected, as shown by the longer overall survival in these patients compared with those with a histopathologic diagnosis.
Eighth Edition Staging of Thoracic Malignancies: Implications for the Reporting Pathologist. A.G. Nicholson, M.S. Tsao, W.D. Travis, et al. 2018;142(5):645-661. Review PubMed · Publisher

Abstract

Context The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, in conjunction with the International Mesothelioma Interest Group, the International Thymic Malignancy Interest Group, and the Worldwide Esophageal Cancer Collaboration, developed proposals for the 8th edition of their respective tumor, node, metastasis (TNM) staging classification systems. Objective To review these changes and discuss issues for the reporting pathologist. Data Sources Proposals were based on international databases of lung (N = 94 708), with an external validation using the US National Cancer Database; mesothelioma (N = 3519); thymic epithelial tumors (10 808); and epithelial cancers of the esophagus and esophagogastric junction (N = 22 654). Conclusions These proposals have been mostly accepted by the Union for International Cancer Control and the American Joint Committee on Cancer and incorporated into their respective staging manuals (2017). The Union for International Cancer Control recommended implementation beginning in January 2017; however, the American Joint Committee on Cancer has deferred deployment of the eighth TNM until January 1, 2018, to ensure appropriate infrastructure for data collection. This manuscript summarizes the updated staging of thoracic malignancies, specifically highlighting changes from the 7th edition that are relevant to pathologic staging. Histopathologists should become familiar with, and start to incorporate, the 8th edition staging in their daily reporting of thoracic cancers henceforth.
Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group. A.N. Husain, T.V. Colby, N.G. Ordóñez, et al. 2018;142(1):89-108. Guideline PubMed · Publisher

Abstract

Context: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.

Objective: - To provide updated, practical guidelines for the pathologic diagnosis of MM.

Data Sources: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks.

Conclusions: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.
Immunohistochemistry in Peritoneal Mesothelioma: A Single-Center Experience of 244 Cases. R.T. Tandon, Y. Jimenez-Cortez, R. Taub, et al. 2018;142(2):236-242. PubMed · Publisher

Abstract

Context: - Diagnosis of malignant mesothelioma is more common in the chest than it is in the abdomen. Most published immunohistochemistry data are more applicable to pleural than to peritoneal mesothelioma.

Objective: - To clarify the practical utility of 17 immunohistochemistry markers in the differential diagnosis of peritoneal mesothelioma with an emphasis on stains for which there is either contradictory information or a paucity of literature.

Design: - Consultation files of peritoneal mesothelioma diagnoses rendered from 1999 to 2014 were reviewed; 244 cases were identified. The results of immunohistochemistry markers performed were tabulated.

Results: - Immunohistochemistry markers positive in peritoneal mesothelioma in order of sensitivity were calretinin (244 of 244; 100%), WT1 (205 of 218; 94%), CK5/6 (173 of 194; 89%), mesothelin (132 of 150; 88%), and D2-40 (78 of 97; 80%). Markers used to differentiate carcinoma from mesothelioma showed immunoreactivity in peritoneal mesothelioma: estrogen receptor (2 of 84; 2%), B72.3 (6 of 196; 3%), CK20 (5 of 116; 4%), CD15 (7 of 192; 4%), p63 (3 of 62; 5%), carcinoembryonic antigen (9 of 199; 5%), PAX8 (12 of 191; 6%), progesterone receptor (5 of 71; 7%), Ber-EP4 (17 of 209; 8%), and CD138 (9 of 91; 10%). BAP1 loss, increasingly used in the differential diagnosis of benign versus malignant mesothelial proliferation, occured in 55% (99 of 181) of peritoneal mesothelioma cases.

Conclusions: - The results support the experience that there is no definitive marker to rule out malignant mesothelioma, including PAX8, estrogen receptor, progesterone receptor, and p63 immunoreactivity. The high rate of immunoreactivity for mesothelin may have a role as a predictive marker for immune targeting. BAP1 loss of 55% in this cohort of peritoneal mesothelioma confirms published observations, and BAP1 retention is seen in a significant proportion of neoplastic cases.
In Reply. L. Brcic, G. Vlacic, F. Quehenberger, et al. 2018;142(11):1311-1312. Letter · Comment PubMed · Publisher
Malignant Mesothelioma and Its Non-Asbestos Causes. R.L. Attanoos, A. Churg, F. Galateau-Salle, et al. 2018;142(6):753-760. Review PubMed · Publisher

Abstract

Context: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.

Objective: - To provide a review of non-asbestos causes for malignant mesothelioma.

Data Sources: - Review of relevant published literature via PubMed and other search engines.

Conclusions: - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 ( BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).
Malignant Mesothelioma in Individuals With Nonmesothelial Neoplasms. K.J. Butnor, E.N. Pavlisko, T.A. Sporn, et al. 2018;142(6):730-734. PubMed · Publisher

Abstract

Context: - Malignant mesothelioma (MM) is a component of the BAP1 tumor predisposition syndrome. Other than in BAP1 familial studies, nonmesothelial neoplasms in individuals with MM has not been comprehensively assessed.

Objective: - To assess the spectrum and prevalence of nonmesothelial neoplasms in individuals with MM.

Design: - Individuals with MM and second neoplasms were identified from a database of 3900 MM cases. The expected prevalence of each type of neoplasm was calculated and compared with the actual prevalence in the study population using available Surveillance, Epidemiology, and End Results data and other published data.

Results: - Two hundred seventy nonmesothelial neoplasms were identified in 241 individuals (6% of the study population) with MM. Prostate adenocarcinoma was most common. Non-Hodgkin lymphoma, Hodgkin lymphoma, lung carcinoma, urothelial carcinoma, breast carcinoma, chronic lymphocytic leukemia, clear cell renal cell carcinoma, head and neck squamous cell carcinoma, papillary renal cell carcinoma, multiple myeloma/plasmacytoma, meningioma, pleomorphic undifferentiated sarcoma, chronic myelogenous leukemia, ocular melanoma, hepatocellular carcinoma, liposarcoma, and Wilms tumor all were more prevalent than expected.

Conclusions: - Nonmesothelial neoplasms are uncommon in individuals with MM, but certain tumor types are increased in prevalence. In an unselected study population with respect to BAP1 status, the prevalence of several tumor types described in BAP1 mutation carriers, including lung carcinoma, clear cell renal cell carcinoma, breast carcinoma, meningioma, pleomorphic undifferentiated sarcoma, and ocular melanoma, was increased.
Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping. L. Brcic, G. Vlacic, F. Quehenberger, et al. 2018;142(6):747-752. PubMed · Publisher

Abstract

Context: - Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high.

Objective: - To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma.

Design: - One representative hematoxylin-eosin-stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and representative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists.

Results: - After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (κ, 0.36). The agreement was increased to substantial (κ, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM and for most epithelioid subtypes.

Conclusions: - Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnostic criteria, their strict application, and help from consensus-based illustrative images is needed.
Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping: Methodologic Issue. M. Naderi, S. Sabour. 2018;142(11):1311. Letter · Comment PubMed · Publisher

Summary

This letter to the editor commented on the statistical methods of a study by Brcic and colleagues on how reproducible the histologic subtyping of malignant pleural mesothelioma (MPM) is. That study had selected one hematoxylin-eosin-stained slide for each of 200 patients with MPM. Three pathologists independently classified the slides using the World Health Organization classification. The study reported agreement using the Cohen kappa statistic. Overall interobserver agreement was fair (kappa 0.36) and rose to substantial (kappa 0.63) in the second round. The letter writers argued that no kappa value is internationally accepted as a sign of good agreement. They said kappa has two weaknesses: it depends on the prevalence in each category, and it depends on the number of categories. To illustrate this, they gave hypothetical tables for two pathologists. In both tables, 90% of ratings agreed and 10% disagreed, yet the kappa values differed: 0.44 (moderate) when one category made up 90% of ratings and 0.80 (very good) when the two categories were equal. They suggested using weighted or Fleiss kappa, especially with more than two observers. They stated that the original conclusion, that moderate to substantial agreement in MPM typing and subtyping can be achieved, should be supported by addressing these statistical and methodologic issues.

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 Diagnosis of Pleural Tumors Other Than Mesothelioma. R.L. Attanoos, M.R. Pugh. 2018;142(8):902-913. Review PubMed · Publisher

Abstract

Context: - Pleural pathology has been dominated by discussions relating to the diagnosis, prognosis, etiology, and management of malignant mesothelioma. However, there exists a diverse group of other neoplasms that involve the pleura; the most common by far is metastatic carcinoma, usually of pulmonary origin. Other metastatic tumors of varied histogenesis do occur but are less common. Primary pleural neoplasms other than diffuse malignant mesothelioma are either uncommon or rare and have received less attention.

Objective: - To provide a review of those diverse tumors that can involve the pleura other than mesothelioma in order to facilitate their accurate diagnosis.

Data Sources: - Review of relevant literature published via PubMed and other search engines.

Conclusions: - A wide variety of tumors can involve the pleura. In most cases, the approach of considering the morphologic features with appropriate immunohistochemistry, in the correct clinical context, allows for a confident diagnosis. For a number of those soft tissue tumors that are well recognized in the pleura, such as solitary fibrous tumor, desmoid-type fibromatosis, synovial sarcoma, and epithelioid hemangioendothelioma, novel markers now exist based on an understanding of the individual tumors' molecular characteristics. Primary pleural lymphomas are rare with poor prognosis. They represent localized specific diffuse large B-cell lymphomas, with either post-germinal center B-cell or plasma cell lineage, arising in the context of either immunodeficiency or immune sequestration and with viral infection.
Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas. K.B. Berg, S. Dacic, C. Miller, et al. 2018;142(12):1549-1553. PubMed · Publisher

Abstract

Context.—: The separation of reactive from malignant mesothelial proliferations is often a difficult morphologic problem. There is contradictory information in the literature on whether methylthioadenosine phosphorylase (MTAP) immunohistochemistry can be used for this purpose.

Objective.—: To determine the utility of MTAP immunohistochemistry in distinguishing reactive from malignant mesothelial proliferations.

Design.—: We stained a tissue microarray containing 20 epithelioid malignant mesotheliomas and 17 reactive mesothelial proliferations. For the mesotheliomas, comparisons were made between MTAP staining and BRCA-associated nuclear protein 1 (BAP1) immunohistochemistry, cyclin-dependent kinase inhibitor 2A ( CDKN2A) fluorescence in situ hybridization, and neurofibromin 2 ( NF2) fluorescence in situ hybridization, which are established techniques for making this separation.

Results.—: Loss of MTAP was seen in 0 of 17 reactive mesothelial proliferations and 13/20 (65%) malignant mesotheliomas. Almost all cases with loss showed loss in 100% of mesothelial cells. Background inflammatory and stromal cells served as a positive internal control. CDKN2A fluorescence in situ hybridization on the mesotheliomas showed concordance with MTAP staining in 14 of 17 evaluable cases. BAP1 immunohistochemistry showed loss of nuclear staining in 11 of 20 mesotheliomas (55%). No cases showed loss of NF2. A total of 18 of 20 mesotheliomas (90%) showed loss of either MTAP or BAP1.

Conclusions.—: In the context of a mesothelial proliferation, loss of MTAP staining is 100% specific for malignant mesothelioma. In this study the combination of MTAP and BAP1 immunohistochemical staining allowed separation of reactive from epithelial malignant mesothelial proliferations in 90% of cases.
Common Fluorescence In Situ Hybridization Applications in Cytology. S. Savic, L. Bubendorf. 2016;140(12):1323-1330. Review PubMed · Publisher

Abstract

Context: - Fluorescence in situ hybridization (FISH) is a well-established method for detection of genomic aberrations in diagnostic, prognostic, and predictive marker testing.

Objective: - To review common applications of FISH in cytology.

Data Sources: - The published literature was reviewed.

Conclusions: - Cytology is particularly well suited for all kinds of FISH applications, which is highlighted in respiratory tract cytology with an increasing demand for predictive FISH testing in lung cancer. Fluorescence in situ hybridization is the gold standard for detection of predictive anaplastic lymphoma kinase gene (ALK) rearrangements, and the same evaluation criteria as in histology apply to cytology. Several other gene rearrangements, including ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), are becoming clinically important and share the same underlining cytogenetic mechanisms with ALK. MET amplification is one of the most common mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and can be targeted by crizotinib. As genomic aberrations are a hallmark of malignant cells, FISH is a valuable objective ancillary diagnostic tool. In urinary tract cytology, atypical urothelial cells equivocal for malignancy are a common diagnostic dilemma and multitarget FISH can help clarify such cells. Diagnosis of malignant mesothelioma remains one of the most challenging fields in effusion cytology, and ancillary FISH is useful in establishing the diagnosis. Fluorescence in situ hybridization is a morphology-based technique, and the prerequisite for reliable FISH results is a targeted evaluation of the cells in question (eg, cancer or atypical cells). Cytopathologists and cytotechnicians should therefore be involved in molecular testing in order to select the best material and to provide their morphologic expertise.
Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum: Recommendations From the International Collaboration on Cancer Reporting (ICCR). A. Churg, R. Attanoos, A.C. Borczuk, et al. 2016;140(10):1104-10. PubMed · Publisher · Free full text

Abstract

Context: -The International Collaboration on Cancer Reporting is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom; the College of American Pathologists; the Canadian Association of Pathologists-Association Canadienne des Pathologists, in association with the Canadian Partnership Against Cancer; and the European Society of Pathology. Its goal is to produce common, internationally agreed upon, evidence-based datasets for use throughout the world.

Objective: -To describe a dataset developed by the Expert Panel of the International Collaboration on Cancer Reporting for reporting malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of "required" (mandatory) and "recommended" (nonmandatory) elements.

Design: -Based on a review of the most recent evidence and supported by explanatory commentary.

Results: -Eight required elements and 7 recommended elements were agreed upon by the Expert Panel to represent the essential information for reporting malignant mesothelioma of the pleura and peritoneum.

Conclusions: -In time, the widespread use of an internationally agreed upon, structured, pathology dataset for mesothelioma will lead not only to improved patient management but also provide valuable data for research and international benchmarks.
Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations. B.S. Sheffield, J. Lorette, Y. Shen, et al. 2016;140(5):391. Letter PubMed · Publisher

Summary

This letter to the editor reported whether immunohistochemistry for NF2 (merlin), LATS2, and their downstream effector YAP/TAZ could help distinguish mesothelioma from benign mesothelial proliferations. The authors, from Vancouver, British Columbia, Canada, noted that NF2 and LATS1/2 alterations are frequent in mesotheliomas but that their diagnostic usefulness had not been widely explored. The study dates were not stated. The authors validated immunohistochemical assays in-house and applied all 3 markers to a previously characterized tissue microarray containing mesotheliomas and benign mesothelial proliferations. They also stained 2 published mesothelioma cases with comprehensive sequencing for NF2. NF2 loss was found in 1 of 25 mesotheliomas (4%) and 0 of 43 benign proliferations, giving 4% sensitivity and 100% specificity. LATS2 loss occurred in 6 of 22 mesotheliomas (27%) and 9 of 45 benign proliferations (20%), giving 27% sensitivity and 80% specificity. Nuclear YAP/TAZ staining was seen in 22 of 24 mesotheliomas (92%) and 37 of 46 benign proliferations (80%), giving 92% sensitivity and 20% specificity. Both sequenced tumors, one with a frameshift and one with a nonsense NF2 mutation, still stained positive for NF2. The authors concluded that, at least with the antibodies used, these stains were not helpful for separating mesothelioma from benign proliferations.

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New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet?. A. Churg, B.S. Sheffield, F. Galateau-Salle. 2016;140(4):318-21. PubMed · Publisher

Abstract

Context: The separation of benign from malignant mesothelial proliferations is crucial to patient care but is frequently morphologically difficult.

Objective: To briefly review adjunctive tests claimed to be useful in this setting and to examine in detail 2 new tests: p16 fluorescence in situ hybridization (FISH) and BRCA1-associated protein 1 (BAP1) immunohistochemistry.

Design: Literature review with emphasis on p16 FISH and BAP1 immunohistochemistry.

Results: Glucose transporter-1, p53, insulin-like growth factor 2 messenger RNA-binding protein 3 (IMP-3), desmin, and epithelial membrane antigen have all been claimed to mark either benign or malignant mesothelial processes, but in practice they at best provide statistical differences in large series of cases, without being useful in an individual case. Homozygous deletion of p16 by FISH or loss of BAP1 has only been reported in malignant mesotheliomas and not in benign mesothelial proliferations. BAP1 appears to be lost more frequently in epithelial than mixed or sarcomatous mesotheliomas. Homozygous deletion of p16 by FISH is seen in pleural epithelial, mixed, and sarcomatous mesotheliomas, but it is much less frequent in peritoneal mesothelioma. The major drawback to both these tests is limited sensitivity; moreover, failure to find p16 deletion or BAP1 loss does not make a mesothelial process benign.

Conclusions: In the context of a mesothelial proliferation, the finding of homozygous deletion of p16 by FISH or loss of BAP1 by immunohistochemistry is, thus far, 100% specific for malignant mesothelioma. The limited sensitivity of each test may be improved to some extent by running both tests.
Pathology of Asbestosis: An Update of the Diagnostic Criteria Response to a Critique. V. Roggli, A.R. Gibbs, R. Attanoos, et al. 2016;140(9):950-2. PubMed · Publisher

Summary

This article was the reply of the 2010 Asbestosis Committee of the College of American Pathologists and the Pulmonary Pathology Society to a published critique by Hammar and Abraham of the committee's 2010 update of the pathologic diagnostic criteria for asbestosis. The authors explained that the committee was formed after a 2007 request to update the 1982 standards. It included 12 pathologists from 8 countries on 4 continents, plus a radiologist, and limited its work to asbestosis.

The authors gave a point-by-point response. They stated that the committee decided unanimously to exclude fibrosis confined to bronchiolar walls from grade 1 asbestosis. Their reasons were that such fibrosis typically gives obstructive rather than restrictive lung function findings, occurs with other dusts, and was seen in 23% of 254 British persons without occupational exposure. They held that alveolar septal fibrosis is necessary for the diagnosis.

They defended the requirement of 2 asbestos bodies per square centimeter, which originated in the 1997 Helsinki criteria. They stated that it corresponds to 800, not 4000, asbestos bodies per gram of wet lung, which is 40 times the upper limit of background.

They said iron stains should be decided case by case. Cases with low asbestos body counts could still qualify by fiber analysis if the fiber burden exceeded the 5th percentile of the asbestosis range. Laboratories should compare results within their own methods. Finally, they stated that medical-legal issues were not the committee's focus and that NIOSH could endorse the 2010 document if it chose.

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Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A Clinicopathologic Study of 45 Cases. X. Li, N.A. Brownlee, T.A. Sporn, et al. 2015;139(9):1129-36. PubMed · Publisher

Abstract

Context: Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies.

Objective: To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy.

Design: From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure.

Results: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy.

Conclusions: Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy.
Malignant Mesothelioma Diagnosis. Q. Arif, A.N. Husain. 2015;139(8):978-80. Review PubMed · Publisher

Abstract

Context: Malignant mesothelioma is a relatively rare pleural tumor that may mimic benign mesothelial lesions and various other tumors including carcinomas and sarcomas. This makes the diagnosis challenging for the pathologist.

Objective: To provide a brief but useful update on the immunohistochemical, cytogenetic, and molecular markers that are currently available for the diagnosis of malignant mesothelioma.

Data Sources: Reference materials including peer-reviewed publications, text books, and consensus opinion reports among pathologists.

Conclusions: It is important to correlate histologic findings on adequate biopsy samples with clinical and radiologic features. Useful diagnostic mesothelial markers include calretinin, WT-1, cytokeratin 5/6, and D2-40 (podoplanin). It is recommended that at least 2 mesothelial and 2 carcinoma markers with greater than 80% sensitivity and specificity be used for the diagnosis of mesothelioma when all clinical, radiologic, and histologic features are concordant. p16 deletion is reported in up to 70% of primary epithelioid and 90% to 100% of sarcomatoid pleural mesotheliomas. Presence of this homozygous gene deletion is so far the best indicator of mesothelioma. To date, this deletion has not been reported in any benign mesothelial lesion. The impact of various histologic patterns on the clinical and prognostic aspects of mesothelioma is addressed. The pleomorphic pattern, when present in more than 10% of tumor, translates into a highly aggressive behavior and is associated with poor survival. Recent studies have shown that the high-grade subgroup of deciduoid mesothelioma with pleomorphic histologic pattern also has a more aggressive clinical course. Nuclear grade (combination of nuclear atypia and mitotic count) may also prove to be an independent prognostic factor.
The So-called Short-Fiber Controversy: Literature Review and Critical Analysis. V.L. Roggli. 2015;139(8):1052-7. Review PubMed · Publisher

Abstract

Context: Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 μm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers.

Objective: To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 μm in length, with particular attention to publications indicating that such fibers might be hazardous.

Data Sources: The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic.

Conclusions: Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 μm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 μm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhalational studies of whole animals or the epidemiological findings in humans.
Accurate diagnosis of mesothelioma: more important than ever. T.C. Allen. 2013;137(5):601-2. Editorial · Comment PubMed · Publisher

Summary

In this editorial, the author argued that accurate pathologic diagnosis of diffuse malignant mesothelioma (DMM) had become more important than ever. He described DMM as a diagnosis that is difficult to make with certainty and that carries heavy prognostic and legal weight. The disease is rare, its mimics are common, and few pathologists gain familiarity with it; even expert pathologists find some cases extremely challenging. He noted that only 20% of patients respond to cisplatin, that surgery and radiotherapy fare no better, and that conventional treatment often achieves no better result than supportive care. Survival rates remain extremely low, and reported long-term survival frequently reflects misdiagnosis. DMM incidence and mortality were predicted to continue to increase. The author pointed to several developments: research into the molecular mechanisms by which asbestos causes DMM, the search for molecular biomarkers, novel intrapleural and immune-based therapies, prevention efforts prompted by the long latency of asbestos-related DMM, and a trend toward standardized treatment, guidelines and registries. He argued that such studies and guidelines would be useless, or even dangerous, unless they were based on accurately diagnosed cases. He introduced the International Mesothelioma Interest Group's 2012 update of its 2009 guidelines for pathologic diagnosis of malignant mesothelioma, published in the same issue, and described it as a timely and welcome reference for pathologists.

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Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. A.N. Husain, T. Colby, N. Ordonez, et al. 2013;137(5):647-67. Consensus statement · Guideline PubMed · Publisher

Abstract

Context: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.

Objective: To provide updated practical guidelines for the pathologic diagnosis of MM.

Data Sources: Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Conclusions: There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.
p16 Deletion in sarcomatoid tumors of the lung and pleura. N. Tochigi, R. Attanoos, L.R. Chirieac, et al. 2013;137(5):632-6. PubMed · Publisher

Abstract

Context: The diagnosis of sarcomatoid neoplasms of the lung and pleura can be challenging. Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as the most common genetic alteration in malignant mesotheliomas that is of potential diagnostic and prognostic significance.

Objectives: To evaluate the frequency of 9p21 deletion by fluorescence in situ hybridization in the primary sarcomatoid neoplasms of the lung and pleura and to determine its potential diagnostic utility.

Design: Ninety-two sarcomatoid neoplasms of the lung and pleura (32 sarcomatoid mesotheliomas, 15 sarcomatoid carcinomas, 32 solitary fibrous tumors, and 13 high-grade sarcomas) were examined for 9p21 deletion by fluorescence in situ hybridization.

Results: Deletion of 9p21 was most frequently seen in malignant mesotheliomas (81%), followed by sarcomatoid carcinomas (53%), sarcomas (25%), and solitary fibrous tumors (12.5%). Malignant mesotheliomas showed mostly homozygous deletion, whereas sarcomatoid carcinomas showed either homozygous or hemizygous deletion. None of the sarcomas showed homozygous deletion. There was a trend toward more frequent occurrence of 9p21 deletion in recurrent solitary fibrous tumors, but this did not reach statistical difference.

Conclusions: Deletion of 9p21 is common in sarcomatoid tumors of the lung and pleura. Despite statistically significant differences in the frequency of 9p21 deletion, and because of the large overlap among the study groups, this genetic abnormality cannot be used as a reliable diagnostic tool in the assessment of sarcomatoid lesions of the lung and pleura. A potential use of p16 deletion in predicting the biology of solitary fibrous tumors should be further explored.
Diffuse malignant mesothelioma. S.P. Oviedo, P.T. Cagle. 2012;136(8):882-8. Case report · Review PubMed · Publisher

Abstract

Diffuse malignant mesothelioma (DMM) is an uncommon cancer with great clinical significance because it currently remains an incurable disease, and most patients die within months after diagnosis. Although DMM incidence is leveling off or decreasing in developed countries because of the strict control of asbestos use, it is increasing in countries without adequate asbestos control. In some settings, benign, reactive mesothelial hyperplasias and organizing pleuritis can be difficult to differentiate from DMM and vice versa, and the variety of DMM's histopathologic features generates an extensive list of differential diagnoses with other malignancies, particularly, metastatic malignancies, which are more frequent in the pleura than are primary malignancies. These two issues are the topic of discussion in this review, along with a brief presentation of a case of DMM that presented in a 66-year-old man with recurrent, right pleural effusions, and in whom, diagnosis of DMM had not been suspected clinically, radiographically, surgically, grossly, or initially, on frozen section. It was not until focal invasion into the skeletal muscle was discovered on permanent sections that a diagnosis of DMM could be established.
Epithelioid lesions of the serosa. S. Anttila. 2012;136(3):241-52. Review PubMed · Publisher

Abstract

Context: Diagnosing epithelioid serosal lesions remains a challenge because numerous different processes-primary or secondary, benign or malignant-occur in body cavities, some of which are very rare.

Objectives: To review the newest literature and to describe the morphologic criteria and immunohistochemical markers that are useful for distinguishing epithelioid serosal lesions.

Data Sources: Previously published literature concentrating on the newest research findings. Earlier reviews are principally referred to for established diagnostic criteria.

Conclusions: Immunohistochemistry with a panel of antibodies has made the diagnosis of epithelioid serosal lesions very reliable. When deciding on antibodies used in differential diagnosis, it is important to consider tumor location, clinical and radiologic information, and morphologic features. Immunohistochemistry is less useful in the differential diagnosis of benign versus malignant mesothelial lesions. The diagnosis of benign versus malignant mesothelial proliferations still relies on the histologic criteria of invasion.
Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma. P.G. Betta, C. Magnani, T. Bensi, et al. 2012;136(3):253-61. Review PubMed · Publisher

Abstract

Context: The pathologic approach to pleural-based lesions is stepwise and uses morphologic assessment, correlated with clinical and imaging data supplemented by immunohistochemistry (IHC), and more recently, molecular tests, as an aid for 2 main diagnostic problems: malignant mesothelioma (MM) versus other malignant tumors and malignant versus reactive mesothelial proliferations.

Objective: To present the current knowledge regarding IHC and molecular tests with respect to MM diagnosis, and in particular, the differentiation of the epithelioid type of MM from carcinoma metastatic to the pleural cavity.

Data Sources: A review of immunohistochemical features of 286 consecutive MMs from 459 cases of pleural pathology, diagnosed during routine practice from 2003 to 2009. A survey of biomedical journal literature from MedLine/PubMed (US National Library of Medicine) focused on MM and associated tissue-based diagnostic IHC markers and molecular tests.

Conclusions: The search for a single diagnostic marker of MM has so far been discouraging, given the biologic and phenotypic tumor heterogeneity of MM. The use of antibody panels has gained unanimous acceptance especially in the differential diagnosis between MM and metastatic carcinoma, whereas the usefulness of IHC is more limited when dealing with spindle cell malignancies or distinguishing malignant from reactive mesothelium. A great degree of interlaboratory variability in antibody combinations and clone selection within diagnostic panels still exists. Current investigations aim at selecting the most suitable and cost-effective combination of antibodies by using novel statistical approaches for assessing diagnostic performance beyond the traditional measures of sensitivity and specificity.
Lymphoproliferative conditions of the serosa. R. Attanoos. 2012;136(3):268-76. Review PubMed · Publisher

Abstract

Context: A diverse and complex variety of lymphoproliferative diseases may involve the serosa, with widely differing clinical outcomes encompassing a spectrum of benign and malignant conditions.

Objective: To review lymphoproliferative disease involving the serosa and to provide a practical approach to the evaluation of lymphoid and plasma cell infiltrates in the serosa, together with a review of various tumors and tumorlike conditions that may mimic lymphoproliferative disease.

Data Sources: Analysis of published literature.

Conclusions: All forms of hematologic malignancy may involve the various serosal sites, although this is usually observed as secondary involvement in persons with known lymph nodal, marrow-based, or extranodal disease. Primary pericardial, pleural, and peritoneal lymphomas are rare; many nonneoplastic conditions may mimic lymphoma and a variety of nonhematolymphoid tumors may simulate hematologic malignancies. An understanding of the role of ancillary tests, together with an appreciation of their limitations, will prevent misdiagnosis.
Malignant mesothelioma of the tunica vaginalis testis: diagnostic studies and differential diagnosis. S.S. Chekol, C.C. Sun. 2012;136(1):113-7. Review PubMed · Publisher

Abstract

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor representing 0.3% to 5% of all malignant mesotheliomas. Gross examination of testicular mesotheliomas typically reveals tumor nodules studding the thickened tunica vaginalis and, in some cases, infiltrating the testicular parenchyma, leading to diagnostic challenges. Microscopically, the tumor is characterized by epithelioid cells arising from the tunica vaginalis with papillary, tubulopapillary, or solid architectural patterns. The papillae are usually lined by a single layer of cells with relatively bland cytologic features. An epithelial cell phenotype admixed with a sarcomatoid pattern has also been described in a few cases. Immunohistochemically, the tumor is usually positive for calretinin, Wilms tumor-1, epithelial membrane antigen, D2-40, thrombomodulin, cytokeratin 7, and cytokeratin 5/6. Electron microscopic studies reveal epithelial cells joined by tight junctions, forming lumina, and displaying long microvilli with length to width ratios often greater than 10. The most important differential diagnostic considerations include florid mesothelial hyperplasia, adenomatoid tumor, carcinoma of the rete testis, and serous papillary tumors. In addition, the various types of testicular germ cell tumors should be considered, including seminomas, embryonal carcinomas, and intratubular germ cell tumors, particularly in tumors with testicular parenchymal involvement. Pleomorphic sarcomas should also be considered, particularly when dealing with the biphasic variant. The prognosis for this entity is grave, with a median survival of 23 months. Aggressive therapy with radical orchiectomy remains the mainstay of treatment.
Mesothelioma not associated with asbestos exposure. B. Jasani, A. Gibbs. 2012;136(3):262-7. Review PubMed · Publisher

Abstract

Context: Despite asbestos being identified as the single most important cause of malignant mesothelioma, the tumor is known to occur in only 10% to 20% of heavily exposed individuals. In addition, about 20% of the patients have no history of asbestos exposure even after detailed assessment. Therefore, there has been speculation for some time that asbestos alone may not be sufficient to cause mesothelioma and that other factors may be involved either as cocarcinogens or as independent mechanisms of cancer causation.

Objective: To give a brief review of nonasbestos fiber erionite and therapeutic radiation as 2 established examples of asbestos-independent mechanisms, of the potential emerging role of man-made fibers such as carbon nanotubes, and of polyoma virus SV40 (simian virus 40) as a potential example of the cocarcinogenic mode of involvement.

Data Sources: Relevant recent literature has been surveyed to portray and provide the evidence in favor of the examples.

Conclusions: Erionite has emerged as the most important example of nonasbestos-mediated cause of mesothelioma in regions such as Turkey where exposure to this type of fiber is highly prevalent. Recently, the polyoma virus SV40 has been unexpectedly discovered as an effective cocarcinogen of asbestos in the causation of animal mesothelioma, though despite considerable research, its potential role in human mesothelioma remains unproven.
Molecular changes in mesothelioma with an impact on prognosis and treatment. D. Jean, J. Daubriac, F. Le Pimpec-Barthes, et al. 2012;136(3):277-93. Review PubMed · Publisher

Abstract

Context: In recent decades, research on malignant pleural mesothelioma (MPM) has been developed to improve patients' outcomes by increasing the level of confidence in MPM diagnosis and prognosis.

Objective: To summarize data on genetic and epigenetic abnormalities in MPM that may be of interest for a better management of patients with MPM.

Data Sources: Data were obtained from scientific publications on genetic and epigenetic abnormalities in MPM by studying gene mutations, DNA methylation, and gene and microRNA expression profiling.

Conclusions: Molecular changes in MPM consist in altered expression and in activation or inactivation of critical genes in oncogenesis, especially tumor suppressor genes at the INK4 and NF2 loci. Activation of membrane receptor tyrosine kinases and deregulation of signaling pathways related to differentiation, survival, proliferation, apoptosis, cell cycle control, metabolism, migration, and invasion have been demonstrated. Alterations that could be targeted at a global level (methylation) have been recently reported. Experimental research has succeeded especially in abolishing proliferation and triggering apoptosis in MPM cells. So far, targeted clinical approaches focusing on receptor tyrosine kinases have had limited success. Molecular analyses of series of MPM cases have shown that defined alterations are present in MPM subsets, consistent with interindividual variations of molecular alterations, and suggesting that identification of patient subgroups will be essential to develop more specific therapies.
The separation of benign and malignant mesothelial proliferations. A. Churg, F. Galateau-Salle. 2012;136(10):1217-26. Review PubMed · Publisher

Abstract

Context: The separation of benign from malignant mesothelial proliferations is crucial to patient management but is often a difficult problem for the pathologist.

Objective: To review the pathologic features that allow separation of benign from malignant mesothelioma proliferations, with an emphasis on new findings.

Data Sources: Literature review and experience of the authors.

Conclusions: Invasion is still the most reliable indicator of malignancy. The distribution and amount of proliferating mesothelial cells are important in separating benignity from malignancy, and keratin stains can be valuable because they highlight the distribution of mesothelial cells. Hematoxylin-eosin examination remains the gold standard, and the role of immunochemistry is extremely controversial; we believe that at present there is no reliable immunohistochemical marker of malignancy in this setting. Mesothelioma in situ is a diagnosis that currently cannot be accurately made by any type of histologic examination. Desmoplastic mesotheliomas are characterized by downward growth of keratin-positive spindled cells between S100-positive fat cells; some cases of organizing pleuritis can mimic involvement of fat, but these fat-like spaces are really S100-negative artifacts aligned parallel to the pleural surface. Fluorescence in situ hybridization on tissue sections to look for homozygous p16 gene deletions is occasionally useful, but many mesotheliomas do not show homozygous p16 deletions. Equivocal biopsy specimens should be diagnosed as atypical mesothelial hyperplasia and another biopsy requested if the clinicians believe the process is malignant.
Utility of glucose transporter 1 in the distinction of benign and malignant thoracic and abdominal mesothelial lesions. S.M. Lagana, R.N. Taub, A.C. Borczuk. 2012;136(7):804-9. PubMed · Publisher

Abstract

Context: Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored.

Objective: To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax.

Design: Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions.

Results: The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%.

Conclusion: Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.
Asbestos fiber content of lungs with diffuse interstitial fibrosis: An analytical scanning electron microscopic analysis of 249 cases. F. Schneider, T.A. Sporn, V.L. Roggli. 2010;134(3):457-61. PubMed · Publisher

Abstract

Context: Asbestosis is one of many forms of diffuse interstitial pulmonary fibrosis. Its histologic diagnosis rests on the pattern of fibrosis and the presence of asbestos bodies by light microscopy in lung biopsies.

Objective: To determine the asbestos fiber burden in patients with diffuse pulmonary fibrosis (DPF) who had a history of asbestos exposure, but whose biopsies did not meet established criteria for asbestosis, and compare it with the fiber burden in confirmed asbestosis cases.

Design: Fiber burden analysis was performed using scanning electron microscopy and energy-dispersive x-ray analysis of lung parenchyma from 86 patients with DPF and 163 patients with asbestosis. The correlation of the number of asbestos fibers found for a quantitative degree of fibrosis was analyzed.

Results: The fibrosis scores of the asbestosis cases correlated best with the number of uncoated commercial amphibole fibers. Seven DPF cases fell within the 95% interval of asbestos body count by light microscopy and 3 cases within that of the total commercial amphibole fiber count.

Conclusions: Strict histologic criteria are useful for positive identification of asbestosis among cases of advanced pulmonary fibrosis. Few DPF patients with history of asbestos exposure whose biopsies did not meet the criteria for asbestosis may have asbestos fiber counts in the range seen in asbestosis, and fiber type identification by scanning electron microscopy with energy-dispersive x-ray analysis should be considered in these rare instances to avoid false-positive and false-negative diagnoses of asbestosis.
Pathology of asbestosis- An update of the diagnostic criteria: Report of the asbestosis committee of the college of american pathologists and pulmonary pathology society. V.L. Roggli, A.R. Gibbs, R. Attanoos, et al. 2010;134(3):462-80. PubMed · Publisher

Abstract

Unlabelled: Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms.

Differential Diagnosis: IDIOPATHIC PULMONARY FIBROSIS: The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis.

Differential Diagnosis: RESPIRATORY BRONCHIOLITIS: Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis.

Role Of Asbestos Bodies: Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5- mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests.

Role Of Fiber Analysis: Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.

2000s

Re: The "Helsinki Criteria" for attribution of lung cancer to asbestos exposure: how robust are the criteria?. V.L. Roggli, S.P. Hammar, J.C. Maddox, et al. 2008;132(9):1386-7; author reply 1387. Comment · Letter PubMed · Publisher
Cytology of nonneoplastic occupational and environmental diseases of the lung and pleura. R. Laucirica, M.L. Ostrowski. 2007;131(11):1700-8. Review PubMed · Publisher

Abstract

Context: Cytologic examination of the respiratory tract has been a useful diagnostic tool when evaluating neoplastic lesions of the respiratory tract. However, we have limited experience in the application of this technique in the management of nonneoplastic occupational and environmental diseases of the lung and pleura. This review focuses on the cytologic characteristics of a variety of occupational lung diseases, grouping them into 2 broad diagnostic categories: reactive cellular changes and noncellular elements. The former includes entities such as reactive mesothelial proliferation, goblet cell metaplasia, Creola bodies, and reserve cell hyperplasia, and the latter encompasses Curschmann spirals, Charcot-Leyden crystals, and asbestos bodies.

Objective: To illustrate the cytologic features of several nonneoplastic occupational and environmental diseases and correlate the cytology with various etiologic agents.

Data Sources: Case-derived material and literature review.

Conclusions: The role of cytology in the diagnosis of nonneoplastic occupational and environmental lung diseases is limited. This may be because more than one agent can elicit a similar host reaction and/or the offending agent can be associated with more than one pathologic process. However, in the appropriate clinical and radiographic setting, the cytology can render valuable diagnostic information. Examples include pulmonary alveolar proteinosis in patients with acute silicoproteinosis and asbestos bodies in bronchoalveolar lavage samples of patients with asbestos exposure.
The "Helsinki criteria" for attribution of lung cancer to asbestos exposure: how robust are the criteria?. A. Gibbs, R.L. Attanoos, A. Churg, et al. 2007;131(2):181-3. Editorial · Review PubMed · Publisher
The "Helsinki Criteria" for attribution of lung cancer to asbestos exposure: how robust are the criteria?. M. Greenberg. 2007;131(11):1630; author reply 1630. Comment · Letter PubMed · Publisher
Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. T.C. Allen, C. Moran. 2006;130(5):721-4. Case report PubMed · Publisher

Abstract

Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.
Ferruginous bodies on frozen section. D.M. Weinrach, K.L. Wang, W.R. Wiseman, et al. 2005;129(2):266. Case report PubMed · Publisher
Quality control analysis of the potential for asbestos contamination during tissue processing in pathology laboratories. R.F. Dodson, M. O'Sullivan, S.P. Hammar. 2004;128(7):781-4. PubMed · Publisher

Abstract

Context: Various quality assurance procedures are applied in pathology and analytical microscopy laboratories to ensure accurate results.

Objective: To assess the potential of cross-contamination of tissue with asbestos fibers and asbestos bodies during the fixation and washing process.

Design: Lung tissue from 10 patients with potential asbestos-related disease was evaluated. Samples of fixative, water, and lung tissue from each case were evaluated by light and analytical transmission electron microscopy for asbestos bodies and uncoated asbestos fibers.

Results: The lung samples tested contained a range of asbestos bodies and uncoated asbestos fibers. One wash water sample contained one asbestos body. No asbestos bodies or uncoated asbestos fibers were found in any other water or fixative samples.

Conclusions: The absence of uncoated asbestos fibers in wash water or fixative samples argues that the fixation process stabilizes asbestos fibers within tissue and the protocol used in this pathology laboratory protects against cross-contamination of tissue. The finding of one asbestos body in one water sample further supports the efficiency of the protective controls used in the testing methods, since this asbestos body was in the external solution that was being discarded before tissue sampling occurred.
Unusual clear cell variant of epithelioid mesothelioma. E. Dessy, M. Falleni, P. Braidotti, et al. 2001;125(12):1588-90. Case report PubMed · Publisher

Abstract

Clear cell mesothelioma is an extremely rare neoplasm of the pleura, which can easily be mistaken for a metastasis of clear cell carcinoma to the pleura. We report here the histochemical, immunohistochemical, and ultrastructural aspects of a new case of clear cell pleural mesothelioma in a 52-year-old man with no known asbestos exposure. He was admitted to the hospital for recurrent pleural effusion, which was negative for neoplastic cells at the cytologic examination. A partial decortication of the right pleura was performed. The morphologic, immunohistochemical, and ultrastructural features reported for this case are consistent with the diagnosis of clear cell mesothelioma. The differential diagnosis and immunohistochemical features in comparison with other clear cell neoplasms are discussed.

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