JAMA Dermatology

<jats:sec id="ab-doi240020-4"><jats:title>Importance</jats:title><jats:p><jats:italic>BRCA1</jats:italic>-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk.</jats:p></jats:sec><jats:sec id="ab-doi240020-5"><jats:title>Objective</jats:title><jats:p>To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in <jats:italic>BAP1</jats:italic>.</jats:p></jats:sec><jats:sec id="ab-doi240020-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>In this prospective cohort study, individuals who were known carriers of pathogenic <jats:italic>BAP1</jats:italic> germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center.</jats:p></jats:sec><jats:sec id="ab-doi240020-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization.</jats:p></jats:sec><jats:sec id="ab-doi240020-8"><jats:title>Results</jats:title><jats:p>Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]).</jats:p></jats:sec><jats:sec id="ab-doi240020-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the <jats:italic>BAP1</jats:italic> gene.</jats:p></jats:sec>

BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization.

Cancer Res

Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide.

J Natl Cancer Inst

Medical and surgical care of patients with mesothelioma and their relatives carrying germline BAP1 mutations.

J Thorac Oncol

Germline mutations in BAP1 predispose to melanocytic tumors.

Nat Genet

What’s new in dermatopathology 2023: WHO 5th edition updates.

J Pathol Transl Med

BRCA1-associated protein (BAP1)-inactivated melanocytic tumors.

J Cutan Pathol

Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: results of a multicenter case-control study by the International Dermoscopy Society.

J Am Acad Dermatol

BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs.

J Transl Med

Localized multinucleate distal subungual keratosis.

Br J Dermatol

Longitudinal erythronychia with distal subungual keratosis: onychopapilloma of the nail bed and Bowen’s disease.

Longitudinal erythronychia: suggestions for evaluation and management.

Clinical and histopathological features of onychopapilloma in an Australian setting: a case series of 50 patients.

Australas J Dermatol

Clinical, dermoscopic, and pathologic features of onychopapilloma: a review of 47 cases.

Longitudinal erythronychia: retrospective single-center study evaluating differential diagnosis and the likelihood of malignancy.

Dermatol Surg

Onychopapillomas: a 68-case series to determine best surgical procedure and histologic sectioning.

J Eur Acad Dermatol Venereol

Matrix biopsy of longitudinal melanonychia and longitudinal erythronychia: a step-by-step approach.

Cosmetic Dermatology

Hailey-Hailey disease: the clinical features, response to treatment and prognosis.

Acral lesions in tuberous sclerosis complex: insights into pathogenesis.

Subungual squamous cell carcinoma in a BAP1 germline pathogenic variant carrier.

Malignant onychopapilloma.

Loss of BAP1 expression in basal cell carcinomas in patients with germline BAP1 mutations.

Am J Clin Pathol

Germline BAP1 mutations also predispose to cutaneous squamous cell carcinoma.

Pathology

Combined genetic and genealogic studies uncover a large BAP1 cancer syndrome kindred tracing back nine generations to a common ancestor from the 1700s.

PLoS Genet

BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk.
To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1.
In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center.
Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization.
Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]).
This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome.

Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome

Papers