Mesothelioma with signet-ring cell features: report of 23 cases

Our plain-English summary of Mesothelioma with signet-ring cell features: report of 23 cases, by N.G. Ordóñez (Modern Pathology, 2013).

The study

• Author: N.G. Ordóñez
• Journal: Modern Pathology
• Published: 2013;26(3):370-84
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signet-ring cell mesotheliomas were positive for calretinin, keratin 5/6, keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features.

In plain English

The author studied 23 mesotheliomas with at least 10% signet-ring-like cells, selected as epithelioid though two were classed biphasic in surgical specimens. Twenty-one were pleural, two peritoneal; patients were 20 men and 3 women aged 43 to 74. Twelve had a history of asbestos exposure and 16 of smoking. Two were first diagnosed as signet-ring cell adenocarcinoma. Twenty-two died of disease 3 to 42 months after diagnosis. All tested mesotheliomas were positive for calretinin, keratin 5/6, keratin 7 and mesothelin; 20 of 22 for WT1, 14 of 15 for podoplanin. None were positive for adenocarcinoma markers such as MOC-31 (0 of 22), CEA (0 of 22) or TTF-1 (0 of 10). Seven comparison signet-ring cell lung adenocarcinomas were all positive for MOC-31 and CEA and negative for calretinin, keratin 5/6, WT1 and podoplanin. By electron microscopy, mesothelioma cells' signet-ring look came mainly from spaces inside them. In the one lung adenocarcinoma examined, it came mainly from mucin granules, though some cells had such spaces. The author concluded that this variant can potentially be confused with other signet-ring tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case series (pathology study using immunohistochemistry and electron microscopy), with a comparison group of signet-ring cell lung adenocarcinomas
• Who was studied: 23 mesotheliomas from MD Anderson Cancer Center files, selected as epithelioid mesotheliomas in which at least 10% of the tumor consisted of signet-ring-like cells (21 pleural, 2 peritoneal; two later classified as biphasic on pneumonectomy specimens); compared with 7 signet-ring cell lung adenocarcinomas; study dates not given
• Exposure: A history of asbestos exposure was recorded in 12 of the 23 mesothelioma patients and smoking in 16; no fiber types, products, jobs or doses were reported
• Main results:
  • The mesothelioma patients were 20 men and 3 women aged 43 to 74 years (mean 60)
  • The mesothelioma arose in the pleura in 21 cases and in the peritoneum in 2
  • In the 15 patients who had extrapleural pneumonectomy, the tumor in the surgical specimen was classified as epithelioid in 13 and biphasic in 2
  • Two of the mesothelioma patients (cases 19 and 21) were initially diagnosed as having signet-ring cell adenocarcinoma
  • 22 of the 23 mesothelioma patients died of disease 3 to 42 months (mean 15 months) after diagnosis; no follow-up was available for the remaining patient
  • All 23 mesotheliomas were positive for calretinin
  • All mesotheliomas stained for keratin 5/6 (22/22), keratin 7 (21/21) and mesothelin (13/13) were positive
  • In the mesotheliomas, 20 of 22 (91%) were positive for WT1 and 14 of 15 (93%) for podoplanin
  • No mesothelioma tested was positive for MOC-31 (0/22), CEA (0/22), TAG-72 (0/18), CD15 (0/16), TTF-1 (0/10), napsin A (0/8), keratin 20 (0/17) or CDX2 (0/8)
  • In the signet-ring cell lung adenocarcinomas, all stained were positive for keratin 7 (7/7), MOC-31 (7/7), CEA (7/7) and napsin A (4/4), and 6 of 7 were positive for TTF-1
  • None of the lung adenocarcinomas tested was positive for keratin 5/6, keratin 20, calretinin, WT1, podoplanin or CDX2
  • None of the seven mesothelioma cases stained with Mayer's mucicarmine (a mucin stain) was positive
  • In the 12 mesotheliomas studied by electron microscopy, the signet-ring appearance was mainly caused by one or more spaces (lumina) inside the cell cytoplasm
  • In some mesothelioma cells, electron microscopy showed that the signet-ring appearance was instead caused by widening of the space between two adjacent cells
  • In the one lung adenocarcinoma studied by electron microscopy, the signet-ring appearance was mainly caused by accumulated mucin granules inside the cell
  • The author described the appearance in that lung adenocarcinoma as resulting from spaces inside the cells (intracytoplasmic lumina) and/or many mucin-containing granules
• The authors' conclusion: The author concluded that pathologists should be aware that mesotheliomas can occasionally show prominent signet-ring-like features and can therefore potentially be confused with other tumors of similar appearance, particularly signet-ring cell carcinomas

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Carcinoma, Immunohistochemistry, Pleura, Peritoneum, Differential Diagnosis, Lung Adenocarcinoma, Calretinin.

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