Detection of Anaplastic Lymphoma Kinase-Rearranged Mesothelioma Cells in Ascites by Companion Diagnostics

Our plain-English summary of Detection of Anaplastic Lymphoma Kinase-Rearranged Mesothelioma Cells in Ascites by Companion Diagnostics, by M. Konishi, T. Kanyama, K. Maeno, et al (Acta Cytologica, 2020).

The study

• Authors: M. Konishi, T. Kanyama, K. Maeno, C. Miyagawa, S. Minamiguchi, H. Katsushima, T. Shimada
• Journal: Acta Cytologica
• Published: 2020;64(4):378-385
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: A case of peritoneal mesothelioma with an anaplastic lymphoma kinase (ALK) translocation was identified, and we conducted further studies to obtain diagnostic and therapeutic insights. We believe that this is the first report describing the cytology of this new tumor type.

Case: A teenage woman was referred for severe pleural effusion. Enhanced computed tomography indicated an abdominal mass with ascites. Laparoscopy revealed tumor dissemination from the pelvis to the upper abdomen. Because a high-grade serous carcinoma was suspected, ascitic cytology and biopsy were performed. Cytologically, the tumor displayed characteristics of both adenocarcinoma and reactive or neoplastic mesothelial cells. After extensive pathological evaluation, the tumor was diagnosed as malignant peritoneal mesothelioma. To verify the diagnosis and aid in developing a therapeutic strategy, several companion diagnostics were tried. Surprisingly, the tumor was ALK-positive, and ALK recombination was confirmed by an ALK break-apart test. Retrospectively, cells and tissue specimens were stained with ALK intercalated antibody-enhanced polymer. Tumor cells were clearly distinguished from the nonneoplastic background. Recombination in ALK was reconfirmed by the National Cancer Center Japan, and the patient was enrolled in a clinical trial for alectinib.

Conclusion: Companion diagnostics-based cytology may provide a useful means of monitoring and evaluating a molecular-targeted therapy.

© 2019 S. Karger AG, Basel.

In plain English

This article was a case report from Japan about one patient, a female in her late teens with no asbestos exposure. She was referred because of a large build-up of fluid around the lungs. Scans and laparoscopy then found a tumor spreading through the pelvis and abdomen, with abdominal fluid (ascites). Because a type of ovarian-like cancer was suspected, the authors examined cells from the ascites and a tumor biopsy using stains, immunohistochemistry and electron microscopy. They diagnosed malignant peritoneal mesothelioma. Markers for typical adult mesothelioma did not show the usual changes: BAP1 and MTAP were normal, and an EWSR1 test was negative. A companion diagnostic stain for the ALK protein was positive (score 3). An ALK break-apart FISH test showed 86% positive cells, confirming an ALK gene rearrangement. In ascites smears and cell blocks, ALK staining separated tumor cells from non-cancerous background cells. The patient was enrolled in a clinical trial of the drug alectinib. The article does not report treatment results. The authors concluded that this staining approach may be applicable for monitoring molecular-targeted therapy.

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 female patient in her late teens with no relevant medical history and no asbestos exposure, seen in Japan (Osaka Red Cross Hospital and collaborating hospitals)
• Exposure: The patient had no asbestos exposure. The study concerned diagnostic testing (ALK iAEP companion diagnostic stain and ALK break-apart FISH), not an exposure.
• Main results:
  • In this patient, the ascites contained elevated hyaluronic acid (20,200 ng/mL) and CA125 (3,206.8 U/mL)
  • The tumor was positive for the mesothelioma markers calretinin, vimentin and WT-1, and negative for adenocarcinoma markers CEA and TTF-1
  • Electron microscopy showed well-developed desmosomes and intracellular tonofilaments. On this basis the tumor was diagnosed as malignant peritoneal mesothelioma rather than low-grade serous carcinoma.
  • BAP1 and MTAP levels were normal by immunohistochemistry in this tumor
  • EWSR1 FISH split signal was negative (5/55 cells)
  • The ALK iAEP companion diagnostic test was positive, score 3
  • The ALK break-apart FISH test showed 86% positive cells, confirming ALK recombination
  • Ascitic fluid cytology and cell-block specimens were ALK iAEP-positive, and tumor cells were clearly distinguished from reactive background cells
  • ALK recombination was reconfirmed by the National Cancer Center Japan, and the patient was enrolled in a clinical trial of alectinib (TACKLE)
• The authors' conclusion: The authors concluded that ALK iAEP positivity in cytological and histological specimens may be applicable for monitoring molecular-targeted therapy.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Ascites, Peritoneal Mesothelioma, Translocation, Cytology, Pleural Effusion, Carcinoma, Biopsy.

Related studies

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• Case report: targeted therapy of malignant pleural mesothelioma with anaplastic lymphoma kinase receptor tyrosine kinase gene fusion mutation by crizotinib — Y. Wu, Y. Zhao, et al. (2024)
• Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report — J. Hu, B. Zhang, et al. (2020)
• Improving the cytological diagnosis of high-grade serous carcinoma in ascites with a panel of complementary biomarkers in cell blocks — X. Zhang, L. Chen, et al. (2018)
• Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases — P. Argani, D.W.Q. Lian, et al. (2021)

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