BRCA1-associated-protein-1 inactivated melanocytic tumours: characterisation of the clinicopathological spectrum and immunohistochemical expression pattern of preferentially expressed antigen in melanoma

Our plain-English summary of BRCA1-associated-protein-1 inactivated melanocytic tumours: characterisation of the clinicopathological spectrum and immunohistochemical expression pattern of preferentially expressed antigen in melanoma, by Y. Xu, A.A. Gru, T. Brenn, et al (Histopathology, 2025).

The study

• Authors: Y. Xu, A.A. Gru, T. Brenn, K. Wiedemeyer
• Journal: Histopathology
• Published: 2025;86(2):294-301
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aims: BRCA1-associaed protein-1 (BAP1) inactivated tumours (BIMT) are rare melanocytic tumours that may be mistaken for Spitz tumours or melanoma. They occur sporadically or in association with the BAP1 tumour predisposition syndrome (BAP1-TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. The aim of this study was to characterise the clinicopathological features and the immunohistochemical expression pattern of preferentially expressed antigen in melanoma (PRAME) of BIMT in a large patient cohort.

Methods And Results: Ethical approval was obtained, haematoxylin and eosin-stained slides were reviewed, PRAME immunohistochemistry was performed and clinical follow-up was obtained from patient records. Sixty-five BIMT from 38 patients (F:M = 4.4:1) were identified. BIMT were typically located on the trunk and head and neck (median size = 0.5 cm). Seven patients with BAP1-TPDS (range = 16-66 years, median = 25) had multiple BIMT (median = 5), while sporadic BIMT were solitary (median patient age = 39 years). One of seven patients with BAP1-TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive without recurrence of BIMT (median follow-up = 42 months). BIMT presented as intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity and moderate to severe cytological atypia in 63% of cases. A background conventional naevus was present in 64%. PRAME immunohistochemistry showed negative or weakly patchy positive staining in all BIMT.

Conclusions: BIMT are more common in a sporadic setting and behave indolently, despite worrying cytological atypia. PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma.

© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.

In plain English

This study looked at BAP1-inactivated melanocytic tumours (BIMT), rare skin growths that can be mistaken for Spitz tumours or melanoma. The authors searched pathology archives in Calgary, Canada, from 2010 to 2022. They reviewed 65 tumours from 38 patients (31 female, 7 male) and stained them for PRAME, a marker used to help identify melanoma. The study did not examine asbestos or any other exposure. Seven patients (18.4%) carried an inherited (germline) BAP1 mutation. They were younger (median 25 years) and often had several tumours. Many tumours looked worrying under the microscope: 41 (63%) showed moderate to severe cell atypia. Even so, no tumour recurred or spread during follow-up of 4 to 111 months (mean 44). One male patient with a germline BAP1 mutation, who had earlier had a melanoma, died of complications of mesothelioma at age 69. The article does not say where in the body the mesothelioma arose. PRAME staining was negative or weak and patchy in all tumours. The authors concluded that BIMT behave indolently and that PRAME is a reassuring tool for telling BIMT apart from melanoma.

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: Retrospective review of tumours from a pathology archive (case series), with immunohistochemical staining and follow-up from patient records
• Who was studied: 65 BAP1-inactivated melanocytic tumours from 38 patients (31 female, 7 male), Calgary health zone, Alberta, Canada, archives searched 2010 to 2022
• Exposure: No asbestos or environmental exposure was studied. The study compared tumours in patients carrying a germline BAP1 mutation (7 patients) with sporadic tumours, and assessed PRAME staining.
• Main results:
  • Patients with a BAP1 germline mutation presented at a younger age (range 16 to 66, median 25 years)
  • Patients with BAP1 germline mutations often had multiple BIMT (range 1 to 8 per patient, mean 6)
  • No recurrences or metastases of BIMT were seen in the whole cohort (follow-up 4 to 111 months, mean 44 months)
  • One male patient with a BAP1 germline mutation died of complications of mesothelioma at age 69, 42 months after diagnosis of one BIMT
  • Moderate to severe cytological atypia was present in 41 of 65 tumours (63%)
  • Low mitotic activity was seen in 7 tumours (10.8%)
  • A conventional background naevus was present in 50 tumours (76.9%) according to the results text
  • PRAME staining was negative or weakly, patchily positive in all BIMT; the quantity score ranged from 0 to 40% of tumour cells and intensity from 0 to 2
• The authors' conclusion: The authors concluded that BIMT are more common in a sporadic setting and behave indolently despite worrying cytological atypia, and that PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, BAP1 Tumor Predisposition Syndrome, Mesothelioma, Carcinoma, Immunohistochemistry, Spindle Cell, Epithelioid.

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