Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report

Our plain-English summary of Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report, by K. Minami, N. Jimbo, Y. Tanaka, et al (Virchows Archiv, 2020).

The study

• Authors: K. Minami, N. Jimbo, Y. Tanaka, D. Hokka, Y. Miyamoto, T. Itoh, Y. Maniwa
• Journal: Virchows Archiv
• Published: 2020;476(3):469-473
• Type of article: Case report
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

In plain English

This case report described one patient, a 73-year-old man with a history of asbestos exposure, who had cough and chest pain. The article gives no details of the exposure. Scans showed a large fluid build-up around the right lung without nodules, and slight pleural thickening on the left. During keyhole chest surgery on the right side, surgeons drained 1500 mL of fluid, saw multiple plaques and took five biopsies. Under the standard microscope stain these showed only a single layer of mildly atypical lining (mesothelial) cells, with no invasion. However, all five biopsies showed loss of the protein MTAP, and a genetic test (FISH) found homozygous deletion of the CDKN2A (p16) gene in at least 15 of 50 cells analyzed. Left-side biopsies showed none of these changes. The right side was diagnosed as malignant mesothelioma in situ, and the left as benign. Nine months later there was no sign of progression, and the patient was untreated. The authors said it remains unclear whether such in situ lesions become invasive, and that more cases are needed.

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 report (single patient)
• Who was studied: One 73-year-old man with a history of asbestos exposure who presented with cough and chest pain. The authors are from Kobe University and Hyogo-Chuo National Hospital in Japan. Dates of care are not given.
• Exposure: A history of asbestos exposure, with no fiber type, job, product or dose given. Multiple pleural plaques seen during surgery were described as consistent with that history.
• Main results:
  • Right side: 1500 mL of mildly turbid pleural fluid was collected. Fluid cytology showed small clusters of atypical epithelioid cells suggesting malignant pleural mesothelioma.
  • Right-side biopsies (hematoxylin and eosin stain) showed a single layer of cuboidal mesothelial cells with mild cytologic atypia and no infiltration into the adipose layer.
  • BAP1 expression was preserved, but MTAP loss was found in the mesothelial cells of all five right-side biopsies, without invasive lesions.
  • FISH on 50 right-side mesothelial cells found homozygous CDKN2A (p16) deletion in at least 15 cells (more than 30%). The threshold used was loss of both signals in more than 20% of nuclei.
  • Left-side biopsies showed no cytologic atypia. BAP1 and MTAP were preserved and no homozygous CDKN2A (p16) deletion was detected.
  • The right pleural thickening was diagnosed as malignant mesothelioma in situ and the left as a benign lesion.
  • Nine months after the first surgery, whole-body imaging showed no disease progression. The patient was being observed without treatment because the patient was reluctant to receive surgery or chemotherapy.
• The authors' conclusion: The authors stated that, to their knowledge, this was the first case of malignant mesothelioma in situ diagnosed on the basis of MTAP loss by immunohistochemistry and homozygous CDKN2A (p16) deletion by FISH. They said more cases are needed to establish diagnostic criteria and treatment strategies.
• Limitations the authors state:
  • It remains unclear whether a single-layer mesothelium without invasive lesions can definitely be diagnosed as malignant pleural mesothelioma.
  • It is unclear whether in situ lesions invariably become invasive or simply represent surface spread of invasive mesothelioma.
  • There are no guidelines on diagnosis and treatment of mesothelioma in situ. Its invasive potential and the time needed to become invasive are unknown.
  • Very few cases of mesothelioma in situ have been reported.

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: Malignant Mesothelioma, Homozygous Deletion, CDKN2A, Pleural Mesothelioma, Asbestos Exposure, Fluorescence In Situ Hybridization (FISH), Immunohistochemistry, Pleural Effusion.

Related studies

• 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, et al. (2018)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in malignant pleural mesothelioma — D.B. Chapel, A.M. Dubuc, et al. (2021)
• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre — K. Marshall, S. Jackson, et al. (2020)
• CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival — A.M. Krasinskas, D.L. Bartlett, et al. (2010)

Browse more research in Virchows Archiv, or return to medical research.