Inherited Basaloid Neoplasm Associated with SUFU Pathogenic Variants

Authors

James J. Abbott, Department of Dermatology, Billings Clinic, Billings, Montana
Angela J. Jiang, Department of Dermatology, Oregon Health and Sciences University, Portland
Rama Godse, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Sarah Amhmed, Department of Dermatology, St Luke’s University Health Network, Easton, Pennsylvania
Stephen C. Senft, Department of Dermatology, St Luke’s University Health Network, Easton, Pennsylvania
Melissa A. Wilson, Division of Medical Oncology, St Luke’s University Health Network, Easton, Pennsylvania
Justine V. Cohen, Dana Farber Cancer Institute, Boston, Massachusetts
Tara C. Mitchell, Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia
Temitayo A. Ogunleye, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
H. William Higgins II, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Thuzar M. Shin, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Christopher J. Miller, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Jacquelyn J. Roth, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Salvatore F. Priore, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Leslie Castelo-Soccio, Cutaneous Microbiome and Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
Rosalie Elenitsas, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
John T. Seykora, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Katherine L. Nathanson, Division of Medical Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Emily Y. Chu, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia

Document Type

Article

Abstract

Importance: Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated.

Objective: To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.

Design, Setting, and Participants: This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.

Main Outcomes and Measures Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.

Results: All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.

Conclusions and Relevance: Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

First Page

1220

Last Page

1224

DOI

doi:10.1001/jamadermatol.2024.3315

Publication Date

11-1-2024

Recommended Citation

Abbott JJ, Jiang AJ, Godse R, Ahmed S, Senft SC, Wilson MA, Cohen JV, Mitchell TC, Ogunleye TA, Higgins HW, Shin TM. Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants. JAMA dermatology. 2024 Nov 1;160(11):1220-4.