Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma

Kushitani, Kei; Amatya, Vishwa Jeet; Okada, Yasukazu; Katayama, Yuya; Mawas, Amany Sayed; Miyata, Yoshihiro; Okada, Morihito; Inai, Kei; Kishimoto, Takumi; Takeshima, Yukio

doi:10.1111/his.13073

Cited by 30 publications

(64 citation statements)

References 37 publications

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“…For neoplastic and reactive mesothelium we used a panel of three antibodies. The combination of markers that distinguish the cells of reactive mesothelium, adenocarcinoma, and mesothelioma have been considered a gold standard in the cytologic diagnostics of effusions in people for more than 30 years . A recent study of canine and feline effusions used a combination of CK (AE1/AE3) and vimentin to try and differentiate mesothelial and carcinomatous cells .…”

Section: Discussionmentioning

confidence: 99%

“…Immunostains that can distinguish between mesothelial, both reactive or neoplastic, and epithelial cells in effusions continue to be evaluated in human pathology . Such a comprehensive evaluation has never been performed in the veterinary field, although its importance is well recognized .…”

Section: Introductionmentioning

confidence: 99%

“…However, this could raise problems since vimentin‐positive neoplastic cells other than mesothelial cells can appear in effusions, as in the case of other mesenchymal tumors, such as osteosarcomas . The use of more than one marker or panel of antibodies for mesothelial cells has been long proposed in human pathology, while in veterinary medicine, a few markers, such as calretinin, Hector Battifora Mesothelial cell‐1 (HBME‐1), and desmin have been studied with mediocre results …”

Section: Introductionmentioning

confidence: 99%

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The cell tube block technique and an immunohistochemistry panel including Wilms tumor 1 to assist in diagnosing cavitary effusions in dogs and cats

Marcos

Marrinhas

Malhão

et al. 2019

Veterinary Clinical Pathol

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Background: Cell blocks and immunohistochemistry (IHC) are increasingly recognized as being complementary tools for cytologic diagnostics, especially for neoplastic diseases. Objectives:The study aimed to evaluate the utility of cell tube block (CTB) IHC for refining the diagnosis of effusions in dogs and cats.Methods: Cavitary effusions (n = 25) from dogs and cats classified by cytology as reactive, neoplastic, borderline (suspicious of neoplasia), and chylous were studied.CTB sections were stained with H&E, and immunostained with PAX-5, CD3, pancytokeratin (CK), vimentin, and Wilms tumor 1 protein (WT1) antibodies, according to the cytologic diagnoses. A histologic case series of confirmed normal, reactive, and neoplastic mesothelium and several different carcinomas were included to test the utility of WT1 as a marker of mesothelial cells. Results:CTBs had a layered appearance with reduced background staining. CD3 and PAX5 immunolabeling allowed immunophenotype assessment in all of the lymphoma cases. In carcinomatous effusions, neoplastic cells were CK-positive, WT1negative, and vimentin-negative (except for two cases). Wilms tumor 1 protein was positive in the nuclei of normal, reactive, and neoplastic mesothelial cells, and ovarian carcinomatous cells. Other carcinomas and lymphomas were negative. Conclusions:CTBs are valuable tools to assist in making a diagnosis of cavitary effusions in dogs and cats, and WT1 is a promising marker to differentiate mesothelial from carcinomatous cells. K E Y W O R D Scell blocks, cytology, effusion, immunohistochemistry, mesothelial cells

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The cell tube block technique and an immunohistochemistry panel including Wilms tumor 1 to assist in diagnosing cavitary effusions in dogs and cats

Marcos

Marrinhas

Malhão

et al. 2019

Veterinary Clinical Pathol

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“…To date, the most common problem in the diagnosis of mesothelioma has been to differentiate it from pulmonary adenocarcinoma and metastatic adenocarcinoma from other organs . In contrast, only a few reports have focused on the differential diagnosis between epithelial pleural mesothelioma and squamous cell carcinoma . Here, we report the autopsy findings of a case of malignant mesothelioma with extensive squamous differentiation, mimicking a squamous cell carcinoma.…”

Section: Introductionmentioning

confidence: 94%

“…5 In contrast, only a few reports have focused on the differential diagnosis between epithelial pleural mesothelioma and squamous cell carcinoma. 7,8 Here, we report the autopsy findings of a case of malignant mesothelioma with extensive squamous differentiation, mimicking a squamous cell carcinoma.…”

Section: Introductionmentioning

confidence: 97%

Malignant mesothelioma with squamous differentiation

et al. 2018

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To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.

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Comprehensive epithelial biomarker analysis of malignant mesothelioma: EpCAM positivity is a potential diagnostic pitfall

Zhu

Moore

Wang

et al. 2023

Cancer Cytopathology

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Background: Epithelial cell adhesion molecule (EpCAM) is frequently used to distinguish carcinoma from background mesothelial cells during cytologic examination of body cavity fluids. Previously, the authors identified one malignant mesothelioma case with strong and diffuse membranous EpCAM staining, making it indistinguishable from carcinoma. Methods: In this study, the authors evaluated all available effusion specimens from patients with malignant mesothelioma, including the above-mentioned index case, obtained at Stanford Health Care, from 2011 to 2021 (N = 17) as well as control cases (N = 5). Analyses included an immunohistochemistry (IHC) assay for EpCAM and claudin-4, a multiplexed immunofluorescent (IF) assay for EpCAM, and an RNA in situ hybridization assay targeting EpCAM. Results: The authors detected EpCAM positivity of variable intensity and percentage in four malignant mesothelioma cases (23.5%; although only two showed positivity for the epithelial-specific IHC marker MOC31 in ≥40% of cells) and claudin-4 negativity in all cases, with two cases displaying focal and weak claudin-4 staining in <1% of cells. Multiplexed IF staining on the cases with EpCAM IHC positivity showed strong, membranous EpCAM staining in one of four cases. RNA in situ hybridization also was used to assess the correlation between EpCAM positivity by IHC/IF and RNA expression levels. Strong EpCAM RNA expression was detected in the three malignant mesothelioma cases. Conclusions:The current findings revealed that a subset of epithelioid malignant mesothelioma cases mimic or exhibit the immunophenotypic features of carcinoma when evaluating for EpCAM only. Additional biomarker testing, such as claudin-4, may help avoid this potential pitfall to yield accurate diagnoses.

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Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma

Abstract: We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.

Cited by 30 publications

References 37 publications

The cell tube block technique and an immunohistochemistry panel including Wilms tumor 1 to assist in diagnosing cavitary effusions in dogs and cats

The cell tube block technique and an immunohistochemistry panel including Wilms tumor 1 to assist in diagnosing cavitary effusions in dogs and cats

Malignant mesothelioma with squamous differentiation

Comprehensive epithelial biomarker analysis of malignant mesothelioma: EpCAM positivity is a potential diagnostic pitfall

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