Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome

Our plain-English summary of Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome, by Z. Marušić, M. Buljan, K.J. Busam (Journal of Cutaneous Pathology, 2015).

The study

• Authors: Z. Marušić, M. Buljan, K.J. Busam
• Journal: Journal of Cutaneous Pathology
• Published: 2015;42(6):406-12
• Type of article: Case report
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms.

Methods: We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome.

Results: The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up.

Conclusions: We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In plain English

This was a report of a small series of cases from Croatia. The authors examined six skin growths of pigment-producing cells (melanocytic neoplasms), three each from a father aged 81 and his daughter aged 52. In these growths, the large epithelioid pigment cells lacked BAP1 protein in their nuclei, as did the melanoma cells, while lymphocytes (immune cells) mixed in with them kept it. The family had a history of cancers that included pleural mesothelioma, renal carcinoma, cholangiocarcinoma, cutaneous melanoma and leukemia. The article did not study asbestos or any other exposure. The growths were mainly in the deeper skin layer (dermal nevi), made of large epithelioid cells, and measured 3 to 11 mm. Five of six contained nuclear pseudoinclusions, and all showed focal adipocytic metaplasia (fat-cell change). In two growths, one from each patient, a nodular melanoma had developed within a nevus. Both patients were alive without recurrence or spread 6 and 3 years after diagnosis. The authors concluded that adipocytic metaplasia and nuclear pseudoinclusions may be additional clues to a BAP1-deficient nevus. They said larger studies 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 series: pathology review of six skin tumors from two members of one family
• Who was studied: A father (patient A, 81 years old) and his daughter (patient B, 52 years old) from a Croatian family with BAP1-associated cancer susceptibility syndrome
• Exposure: No asbestos or environmental exposure was studied. The subject was a family cancer history the authors considered indicative of BAP1-associated tumor predisposition syndrome. Close relatives had pleural mesothelioma, renal carcinoma, cholangiocarcinoma, cutaneous melanoma and leukemia.
• Main results:
  • The six tumors ranged in size from 3 to 11 mm
  • Five of the six nevi contained melanocytes with nuclear pseudoinclusions
  • All six nevi showed focal adipocytic metaplasia
  • The father's melanoma measured 4.5 mm in thickness, had a mitotic rate of 10/mm2 and was not ulcerated
  • The daughter's melanoma measured 2.5 mm in thickness, had a mitotic rate of 3/mm2 and was not ulcerated
  • The large epithelioid melanocytes lacked BAP1 protein in their nuclei
  • The melanomas showed the same staining pattern. Lymphocytes mixed in with the melanoma kept nuclear BAP1, while the melanoma cells did not.
  • Lesional melanocytes in all six tumors expressed BRAFV600E
  • Sentinel lymph node biopsy was negative. Both patients were alive without recurrence or metastasis 6 and 3 years after diagnosis, respectively.
• The authors' conclusion: The authors concluded that adipocytic metaplasia and nuclear pseudoinclusions may be additional clues to a BAP1-deficient nevus. They said it remains to be seen whether these features are more common in familial than in sporadic lesions.
• Limitations the authors state:
  • The authors said studies of a larger number of cases are needed to judge whether adipocytic metaplasia and nuclear pseudoinclusions help tell familial from sporadic tumors
  • The authors said future studies are needed to learn whether melanomas arising in familial BAP1-deficient nevi have a similar or different outlook from sporadic melanomas
  • Slides of the father's earlier superficial spreading melanoma were not available for review

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Neoplasm, Germline Mutation, Carcinoma, Mesothelioma, Epithelioid.

Related studies

• Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome — A. Louw, J. Creaney, et al. (2020)
• 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)
• Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy — P. Star, A. Goodwin, et al. (2018)
• Dual Screen for Efficacy and Toxicity Identifies HDAC Inhibitor with Distinctive Activity Spectrum for BAP1-Mutant Uveal Melanoma — J.N. Kuznetsoff, D.A. Owens, et al. (2021)
• Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations — M.G. Zauderer, G. Jayakumaran, et al. (2019)

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