bims-mesote 2024-11-03 papers

Issue of 2024–11–03
three papers selected by
Laura Mannarino, Humanitas Research

Am J Dermatopathol. 2024 Oct 31.

Metastatic Mesothelioma of the Tunica Vaginalis Presenting as Scrotal and Abdominal Nodules: A Case Report and Review of the Literature.

Aubre Gilbert, Rebekah Wieland, Natasha Zacher, Kerri Rieger, Gerald J Berry, Roberto Novoa.

ABSTRACT: Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

DOI: https://doi.org/10.1097/DAD.0000000000002848

Port J Public Health. 2023 Feb;40(3): 188-202

Asbestos Exposure and Malignant Pleural Mesothelioma: A Systematic Review of Literature.

Cátia Santos, Maria Dos Anjos Dixe, Ema Sacadura-Leite, Philippe Astoul, António Sousa-Uva.

Background: The relationship between exposure to asbestos and malignant pleural mesothelioma (MPM) is already well established. Nevertheless, much remains to be known about exposure thereto and the incidence and mortality from MPM.
Objective: This systematic review aims to map the relationship between asbestos and MPM by studying the exposure to asbestos and the incidence and mortality of MPM.
Methods: A systematic review was conducted relating asbestos and MPM. Exposure to asbestos, incidence, and mortality by MPM was reviewed. PubMed, Web of Science, Cochrane Library, RCAAP, DART-Europe, and the reference lists of included studies were searched, from January 1, 1960, to December 31, 2020. Methodological quality was checked, the risk of bias analysis was performed, a level of evidence grade was assigned, and descriptive data analysis was performed.
Results: 3,484 unique citations were identified, which included seventeen observational studies that met inclusion criteria with a total of 1,104 patients. Heterogeneity is present between the included studies which range from a case series of 16 retrospective studies and 1 prospective study. Studies were mostly conducted in Europe, particularly in Italy (6), and were published between 1969 and 2020. The mean age of patients is approximately 66 years with a latency period between the first exposure and diagnosis of approximately 42 years. 14 studies present data regarding the occupational context and chrysotile and crocidolite are the most studied types of fibre. The incidence of cases occurred between the interval 1966 and 2014 and in 9 studies the mortality rate was 100% of patients.
Conclusion: There is high evidence to support the relationships between asbestos and MPM. However, the relatively scant information provided by the studies reinforces the need for well-conducted research and implementation of National Mesothelioma Surveillance Centres at a global level.

Keywords: Asbestos; Exposure; Malignant pleural mesothelioma; Mortality

DOI: https://doi.org/10.1159/000527971

Sci Rep. 2024 10 29. 14(1): 25941

Antigen targeting and anti-tumor activity of a novel anti-CD146 212Pb internalizing alpha-radioimmunoconjugate against malignant peritoneal mesothelioma.

Kim Lindland, Marion Masitsa Malenge, Ruth Gong Li, Roxanne Wouters, Tina Bjørnlund Bønsdorff, Asta Juzeniene, Srdan M Dragovic.

Malignant mesothelioma, a highly aggressive cancer that primarily affects the serosal membranes, has limited therapeutic options, particularly for cavitary tumors, such as peritoneal and pleural malignant mesothelioma. Intracavitary administration of a radioimmunoconjugate to locally target mesothelioma cancer cells has been proposed as a treatment. CD146, upregulated in mesothelioma but not in healthy tissues, is a promising therapeutic target. This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212Pb (212Pb-TCMC-OI-3) in human mesothelioma cells. Flow cytometry showed that both chimeric (chOI-3) and murine (mOI-3) antibodies rapidly bound and internalized within 1-6 h in MSTO-211H cells. 212Pb-TCMC-chOI-3 exhibited 3.1- to 13.7-fold and 3.1- to 8.5-fold increased internalized 212Pb and 212Bi atoms per cell at 2 and 24 h, respectively, compared to isotype control, underscoring enhanced internalization efficiency. Intraperitoneal administration of 212Pb-TCMC-mOI-3 to mice with intraperitoneal MSTO-211H xenografts improved median survival by a ratio of 1.3 compared to non-binding 212Pb-TCMC-mIgG1. The ability of 212Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy's efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes.

Keywords: 212Pb; CD146 antigen; Internalization; Malignant peritoneal mesothelioma xenograft model; Radioimmunoconjugate; Targeted alpha therapy

DOI: https://doi.org/10.1038/s41598-024-76778-z