Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome

Our plain-English summary of Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome, by A. Louw, J. Creaney, A. Thomas, et al (The American Journal of Dermatopathology, 2020).

The study

• Authors: A. Louw, J. Creaney, A. Thomas, C. Van Vliet, N.T. Harvey, B.A. Wood, N. Mesbah Ardakani
• Journal: The American Journal of Dermatopathology
• Published: 2020;42(11):872-875
• Type of article: Case report
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

BRCA1-associated protein-1 (BAP1)-deficient cutaneous tumors are common in patients with BAP1 tumor predisposition syndrome, frequently presenting before other associated neoplasms, and can serve as an early marker to identify individuals with this disease. The typical lesions are dermal based and composed of a combination of larger epithelioid melanocytes with abundant glassy cytoplasm and smaller cells resembling those of a conventional nevus. There is often a component of interspersed lymphocytes. However, BAP1-deficient melanocytic tumors can show a spectrum of histologic appearances, ranging from lesions with pure epithelioid, pure conventional nevus, or rhabdoid cells and tumors with an intraepidermal component. To demonstrate such morphologic variation, we present a case of a 50-year-old woman with multiple histologically diverse BAP1-deficient melanocytic tumors and germline BAP1 mutation, identified after a diagnosis of pleural mesothelioma. We also discuss the pathogenesis and potential histopathological and clinical indications of germline versus sporadic etiology in the assessment of BAP1-deficient melanocytic tumors.

In plain English

This case report described one 50-year-old woman with BAP1 tumor predisposition syndrome, an inherited condition caused by BAP1 gene changes. She came to medical attention with a persistent cough and fluid around the right lung. Testing of the fluid suggested malignant mesothelioma, and a later pleural biopsy confirmed it. The article does not say whether she had ever been exposed to asbestos. Several pigmented skin growths had been removed earlier, and one more after the mesothelioma diagnosis. Under the microscope all five were benign pigment-cell (melanocyte) growths that looked different from one another. One was made mostly of large epithelioid cells. Two mixed ordinary mole cells with rhabdoid cells. Two looked like ordinary moles. All five showed BAP1 protein loss; in the two mixed growths, only the rhabdoid cells had lost it. Genetic testing of a blood sample found an inherited BAP1 change. The authors concluded that BAP1-deficient skin tumors in such patients can look varied. They suggested there may be value in BAP1 staining of lesions without typical features in patients who have already had one such lesion.

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 50-year-old woman with pleural malignant mesothelioma and five skin lesions; the authors are based in Perth, Western Australia; dates are not given
• Exposure: No asbestos exposure is reported in the article. The factor examined was an inherited (germline) change in the BAP1 gene, reported as p.Arg213Pro.
• Main results:
  • Malignant mesothelioma was suspected from cells in the pleural fluid and confirmed on a later pleural biopsy; the tumor cells in the fluid had lost BAP1 staining
  • All 5 skin lesions were benign melanocyte growths, mainly within the skin's deeper layer, with varied cell appearances
  • Lesion 1 (foot) was made almost entirely of large epithelioid cells
  • Lesions 2 and 3 (neck) were combined nevi with ordinary mole cells and rhabdoid cells; lesions 4 (shoulder) and 5 (forearm) looked like ordinary intradermal moles
  • None of the lesions showed a significant intraepidermal component or mitotic activity
  • All 5 lesions stained positive with the BRAF VE1 antibody
  • BAP1 was completely lost in lesions 1, 4 and 5; in lesions 2 and 3 it was lost only in the rhabdoid cells, not in the ordinary mole cells
• The authors' conclusion: The authors concluded that this patient's skin tumors all showed BAP1 loss despite their varied appearances. They suggested there may be value in BAP1 staining of lesions without typical features in patients who have had one such lesion identified.
• Limitations the authors state:
  • The authors note that the effect of this patient's BAP1 variant on protein function has not been tested in functional studies

Topics

Medical terms in this study, explained in our Lexicon: BAP1, BAP1 Tumor Predisposition Syndrome, Neoplasm, Epithelioid, Rhabdoid, Pleural Mesothelioma, Etiology.

Related studies

• Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome — Z. Marušić, M. Buljan, et al. (2015)
• Post-thoracotomy neuralgic amyotrophy in a patient with BAP1 tumor predisposition syndrome: Multimodality longitudinal follow-up — N. Jazebi, N. Dargah-Zada, et al. (2021)
• Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases — R. Pilarski, C.M. Cebulla, et al. (2014)
• Clinical Implications of Real-time Integrative Sequencing in Management of Patients With Suspected Germline BAP1 Mutations — S. Sengupta, A.C. Weyand, et al. (2019)
• Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases — K. Rai, R. Pilarski, et al. (2016)
• Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist — L.M. Martorano, R.R. Winkelmann, et al. (2014)

Browse more research in The American Journal of Dermatopathology, or return to medical research.