Morphological Characteristics of 9p21 Homozygous Deletion-Positive Malignant Pleural Mesothelioma Cells Detected by FISH

Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.

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Diagnostic Challenges in Epithelioid Pleural Mesothelioma: Case Series with Support from Electron Microscopy

Diagnostics ◽

10.3390/diagnostics11050841 ◽

2021 ◽

Vol 11 (5) ◽

pp. 841

Author(s):

Francesco Fortarezza ◽

Mila Della Barbera ◽

Federica Pezzuto ◽

Francesca Lunardi ◽

Eleonora Faccioli ◽

...

Keyword(s):

Electron Microscopy ◽

Malignant Pleural Mesothelioma ◽

Rare Variants ◽

Case Series ◽

Morphological Characteristics ◽

Pleural Mesothelioma ◽

Ultrastructural Examination ◽

Specific Diagnosis ◽

Final Interpretation ◽

Definition Of

The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist’s armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.

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Short 57 kb CDKN2A FISH probe effectively detects short homozygous deletion of the 9p21 locus in malignant pleural mesothelioma

Oncology Letters ◽

10.3892/ol.2021.13074 ◽

2021 ◽

Vol 22 (6) ◽

Author(s):

Yuzo Oyama ◽

Makoto Hamasaki ◽

Shinji Matsumoto ◽

Ayuko Sato ◽

Tohru Tsujimura ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Homozygous Deletion ◽

Pleural Mesothelioma ◽

9P21 Locus

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Update on Diagnosing and Reporting Malignant Pleural Mesothelioma

Acta Medica Academica ◽

10.5644/ama2006-124.335 ◽

2021 ◽

Vol 50 (1) ◽

pp. 197

Author(s):

Ivana Savic ◽

Jeffrey Myers

Keyword(s):

Malignant Pleural Mesothelioma ◽

Malignant Tumors ◽

Tumor Grade ◽

Homozygous Deletion ◽

Diagnostic Tools ◽

Pleural Mesothelioma ◽

Methylthioadenosine Phosphorylase ◽

Diffuse Malignant Pleural Mesothelioma ◽

Tissue Specimens ◽

Immunohistochemical Stains

In this review, we summarize current approaches to diagnosis of malignant pleural mesothelioma, focusing on the distinction from benign mesothelial proliferations and other malignant tumors. Current recommendations for reporting histological sub-type and tumor grade are also reviewed. Particular emphasis is placed on immunohistochemical and molecular tools that may help in establishing the diagnosis of mesothelioma with greater confidence. Immunohistochemical stains for BRCA1-associated protein (BAP1) and methylthioadenosine phosphorylase (MTAP) and homozygous deletion of p16 using fluorescence in situ hybridization (FISH) are emphasized as important methods for distinguishing benign from malignant mesothelial prolifera- tions.Conclusions. Diffuse malignant pleural mesothelioma is a heterogeneous group of aggressive pleural tumors for which histological classification plays an increasingly important role in patient management. Stage and resectability remain key drivers of therapeutic strategies and outcomes. There is an increasingly robust suite of diagnostic tools, including immunohistochemical stains for BAP1 and MTAP and p16 FISH, for differentiating benign from malignant mesothelial proliferations in cytology and tissue specimens.

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Malignant pleural mesothelioma with heterologous elements

Journal of Clinical Pathology ◽

10.1136/jclinpath-2021-207575 ◽

2021 ◽

pp. jclinpath-2021-207575

Author(s):

Toshiaki Kawai ◽

Reishi Seki ◽

Kuniharu Miyajima ◽

Hiroshi Nakashima ◽

Takayuki Takeda ◽

...

Keyword(s):

Median Survival ◽

Malignant Pleural Mesothelioma ◽

In Situ Hybridisation ◽

Homozygous Deletion ◽

Fish Analysis ◽

Pleural Mesothelioma ◽

Fluorescence In Situ Hybridisation ◽

Surgical Operation ◽

Methylthioadenosine Phosphorylase

AimsMalignant pleural mesothelioma with heterologous elements (such as osseous, cartilaginous or rhabdomyoblastic differentiation) is very rare. We tried to differentiate such mesothelioma cases from extraskeletal pleural osteosarcoma, which is very challenging.MethodsWe compared 10 malignant pleural mesotheliomas (three biphasic and seven sarcomatoid types) with two pleural osteosarcomas using clinicopathological and immunohistochemical methods, and also fluorescence in situ hybridisation (FISH) to examine for homozygous deletion of p16.ResultsThe median age was 72 years for mesotheliomas, and 69 years for osteosarcoma. For mesothelioma, eight cases were male and two were female. Growth was diffuse in all mesothelioma cases except case 10, where it was localised, as it was for the two osteosarcomas. Among mesothelioma cases, 80% displayed osteosarcomatous and 60% chondromatous elements, while 10% exhibited rhabdomyoblastic ones. Immunohistochemical labelling for calretinin and AE1/AE3 was present in 8/10 and 7/10 mesotheliomas, respectively, but in only one osteosarcoma. Loss of methylthioadenosine phosphorylase was seen in 5/7 mesotheliomas. FISH analysis revealed homozygous deletion of p16 in 5/8 mesothelioma and 2/2 osteosarcoma. Median survival was 6.5 months after biopsy or surgical operation in mesothelioma, and 12 months after operation in osteosarcoma.ConclusionsAlthough median survival was longer for osteosarcoma than for malignant mesothelioma, we could not differentiate mesothelioma from pleural osteosarcoma on the combined basis of clinicopathological and immunohistochemical data, and FISH analysis. However, diffuse growth was more frequent in mesothelioma than in osteosarcoma.

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