## **Supplemental Online Content**

Lebensohn A, Ghafoor A, Bloomquist L, et al. Multiple onychopapillomas and BAP1 Tumor predisposition syndrome. *JAMA Dermatol*. Published online May 17, 2024. doi:10.1001/jamadermatol.2024.1804

- **eFigure 1.** Polydactylous Onychopapillomas in a Female Age 40s
- **eFigure 2.** Polydactylous Onychopapillomas in a Female Age 60s
- **eFigure 3.** Polydactylous Onychopapillomas in a Female Age 40s
- **eFigure 4.** Onychopapilloma in a Male Age 30s
- **eFigure 5.** Polydactylous Onychopapillomas in a Male Age 70s
- **eFigure 6.** Polydactylous Onychopapillomas in a Male Age 50s
- **eFigure 7.** Severe Fingernail Dystrophy in a Female Age 60s

This supplemental material has been provided by the authors to give readers additional information about their work.

**eFigure 1. Polydactylous onychopapillomas in a female (age 40's) with BAP1 TPDS.** 

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_1_Picture_1.jpeg)

A. Multiple discrete longitudinal bands with variable leukonychia, erythronychia and splinter hemorrhage on 1st digits of patient with BAP1 TPDS. B. Hyponychial view of nail margin demonstrates subungual columns of hyperkeratotic nail material corresponding to the bands of nail plate discoloration.

**eFigure 2. Polydactylous onychopapillomas in a female (age 60's) with BAP1 TPDS.** 

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_2_Picture_1.jpeg)

A. Broad area of central nail leukonychia and longitudinal ridging on the left thumb. The right thumb has a more subtle band of longitudinal erythronychia and a small area of distal nicking. B. Multiple areas of near contiguous subungual keratinous material are visible at the distal nail margin of L. thumb hyponychium.

**eFigure 3. Polydactylous onychopapillomas in a woman (age 40's) with BAP1 TPDS.** 

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_3_Picture_1.jpeg)

A. Splinter hemorrhage and thin band of leukonychia on right thumb and parallel leukonychia bands on left thumb [white arrows] correspond to areas of subungual hyperkeratosis [black arrows] (B).

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_4_Picture_0.jpeg)

**eFigure 4. Onychopapilloma in a male (age 30's) with BAP1 TPDS.** 

Leukonychia with column of subungual hyperkeratosis on 1st digit left foot.

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_5_Picture_0.jpeg)

**eFigure 5. Polydactylous onychopapillomas in a male (age 70's) with BAP1 TPDS.** 

A-B. Diffuse leukonychia with distal onycholysis, distal nicking and subungual hyperkeratosis on bilateral thumbs.

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_6_Picture_0.jpeg)

**eFigure 6. Polydactylous onychopapillomas in a male (age 50's) with BAP1 TPDS.** 

A-B. Subtle leukonychia and splinter hemorrhage with focal columns of subungual hyperkeratosis on right hand 1st digit.

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2024.1804/_page_7_Picture_0.jpeg)

**eFigure 7. Severe fingernail dystrophy in a female (age 60's) with BAP1 TPDS.** 

A-C. Diffuse destruction of nails attributed by patient to a history of paronychia and history of artificial nail use. Biopsy was not performed, and the nail findings were considered non-diagnostic for onychopapilloma. D-E. The toenails were unaffected.

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>

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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

Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome

Clinical Summary

What was studied

Key findings

Study limitations

Clinical implications

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