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. 2024 Nov 1;160(11):1220-1224.
doi: 10.1001/jamadermatol.2024.3315.

Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants

James J Abbott  1 , Angela J Jiang  2 , Rama Godse  3 , Sarah Ahmed  4 , Stephen C Senft  4 , Melissa A Wilson  5 , Justine V Cohen  6 , Tara C Mitchell  7 , Temitayo A Ogunleye  3 , H William Higgins 2nd  3 , Thuzar M Shin  3 , Christopher J Miller  3 , Jacquelyn J Roth  8 , Salvatore F Priore  8 , Leslie Castelo-Soccio  9 , Rosalie Elenitsas  3 , John T Seykora  3 , Katherine L Nathanson  10 , Emily Y Chu  3
Affiliations

Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants

James J Abbott et al. JAMA Dermatol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mitchell reported personal fees from BMS Scientific advisory board participant, personal fees from Merck Scientific advisory board participant, and personal fees from Pfizer Scientific advisory board participant outside the submitted work. Dr Shin reported grants from Regeneron outside the submitted work. Dr Roth reported personal fees from Genomics Organization for Academic Laboratories in the form of a Consultant, personal fees from Eli Lilly in the form of Stocks, and personal fees from Pfizer in the form of Stocks outside the submitted work. Dr Priore reported consulting fees paid from Palmetto GBA and MCG Health; honoraria paid from Bayer, and Thermo Fisher Scientific; Support to attend a meeting from Thermo Fisher; and stock or stock options from Moderna, Eli Lilly, Amgen, and Johnson & Johnson. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Clinical Images
A, Patient 1, numerous skin-colored papules on the central face for several years. B, Closer view of papules on the central face for patient 1. C, Patient 2, sister of patient 1, who demonstrates similar clinical findings with scattered skin-colored papules on the central face. D, Patient 3, with a longstanding history of skin-colored papules on the face. E, Patient 4, a woman in her 60s who has a long-standing history of basal cell carcinomas on her face for at least 10 to 15 years. F, Patient 5, a woman in her 60s with facial papules that initially began to appear in her 20s.
Figure 2.
Figure 2.. Histopathology of SUFU Pathogenic Variant–Associated Basaloid Neoplasms
A and B, Biopsies taken from the glabella and nasal ala of patient 1, demonstrating basaloid follicular hamartomas. Endophytic basaloid neoplasms with follicular differentiation arise from the epidermis (hematoxylin-eosin stains). C, A basaloid neoplasm with follicular differentiation from patient 2 shows similar findings to those seen in her sister (patient 1), but was diagnosed as infundibulocystic basal cell carcinomas (BCCs). D, A biopsy from patient 3 shows an infundibulocystic BCC with areas of peripheral palisading, anastomosing epithelial strands, and follicular differentiation (hematoxylin-eosin stain). E, Infundibulocystic basal cell carcinoma from patient 4 (hematoxylin-eosin stain). F. Infundibulocystic BCC showing a basaloid neoplasm with follicular differentiation from patient 5 (hematoxylin-eosin stain).
See this image and copyright information in PMC

References

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