[Cystic tubulopapillary adenoma with apocrine differentiation and BRAF V600E mutation. A case report and review of the literature]. / Adenoma tubulopapilar quístico con diferenciación apocrina: descripción de un caso con mutación de BRAF V600E y revisión de la literatura.

Syringocystadenoma papilliferum (SCAP), tubular adenoma (TA) and hydrocystoma (HC) are benign adnexal tumors. Recently it has been suggested that these lesions belong to the same morphological spectrum: Tubulopapillary cystic adenoma with apocrine differentiation (TPCAa). BRAF and K-Ras (KRAS) mutations have been described in SCAP and TA, but not in HC. Moreover, verrucous epithelial proliferations have been observed in TPCAa. We present a case of TPCAa with BRAF V600E mutation and BRAF VE1 immunohistochemical expression in the SCAP, AT, HC and verrucous hyperplasia components.

Syringocystadenoma papilliferum associated with verrucous carcinoma of the skin in the same lesion: Report of four cases.

The association of syringocystadenoma papilliferum (SCAP) with verrucous carcinoma (VC) of the skin in the same lesion is a rare, but well-documented event. Although human papillomaviruses (HPV) have been proposed to have an etiologic role in the development of the verrucous proliferations associated with SCAP, most of the immunohistochemical and molecular studies have failed to show the presence of their genomic material in these lesions. We report a series of four cases of SCAP associated with VC in anogenital lesions. In two of the cases, we demonstrated the presence of the BRAF V600E mutation by polymerase chain reaction and immunohistochemistry, both in the glandular and in the squamous component. No HPV-related histopathologic changes were found, nor could the presence of viral DNA be showed.

Several genotypes, one phenotype: PIK3CA/AKT1 mutation-negative hidradenoma papilliferum show genetic lesions in other components of the signalling network.

About 60-70% of hidradenoma papilliferum (HP), a benign tumour of the anogenital region, were recently described to harbour mutations in major driver genes of the PI3K/AKT/MAPK-signalling pathways. However, the underlying genetic defects of the non-mutant cases are still unknown. Using a 409 gene panel, we employed targeted next generation sequencing to investigate the mutational landscape in a cohort of seven PI3K/AKT-negative cases and five cases with known hotspot mutations in either PIK3CA or AKT1. In total, we identified 29 mutations in 22 of 409 genes. The four cases with PIK3CA hotspot mutations carried no or only few additional mutations. The AKT1 hotspot mutated case harboured additional mutations in four genes (SYNE1, ADAMTS20, EP400 and CASC5). At least two of these genes are involved in or contribute to the PI3K/AKT-pathway. In the seven non-hotspot mutated cases we observed 18 mutations. Each case carried at least one mutation in a gene contributing to or involved in PI3K/AKT-signalling. Affected genes were PIK3CA (n=1, non-hotspot mutation), PIK3R1 (n=3), SYNE1, AR, IL6ST, PDGFRB, KMT2C, AR, BTK, DST, KAT6A, BRD3, RNF213, USP9X, ADGRB3, MAGI1, and IL7R (each gene mutated once). The identified PIK3CA and PIK3R1 mutations lead to constitutive activated PI3K/AKT-signalling. In conclusion, we demonstrate the genetic basis of HP in all cases. Our data suggest that tumourigenic alterations in the PI3K/AKT-pathway are indispensable in HP and establish a homogenous morphomolecular entity with a functionally converging and selecting tumourigenic mechanism.

Syringocystadenoma Papilliferum of the Anogenital Area and Buttocks: A Report of 16 Cases, Including Human Papillomavirus Analysis and HRAS and BRAF V600 Mutation Studies.

Syringocystadenoma papilliferum (SCAP) is a benign tumor most commonly located on the head and neck area often associated with nevus sebaceus. In its usual location, the human papillomavirus (HPV) DNA and mutations in the RAS/mitogen-activated protein kinase signaling pathway have been detected in SCAP. We studied 16 cases of SCAP in the anogenital areas and buttock where this neoplasm is rare and attempted to find out whether SCAP in these sites have different histopathological and molecular biological features. It seems that there is no significant difference between the morphology of anogenital SCAP and SCAP in other locations. Several tumors in our cohort demonstrated features resembling those seen in warts, but HPV DNA was not found in these lesions. On the contrary, we identified DNA of HPV high-risk types in some tumors without HPV-related morphology. Our study confirms the role of HRAS and BRAF V600 mutations in the pathogenesis of SCAP, including SCAP in the anogenital areas and buttock.

Contiguous verrucous proliferations in syringocystadenoma papilliferum: A retrospective analysis with additional evaluation via mutation-specific BRAFV600E immunohistochemistry.

BACKGROUND: Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal proliferation. There have been several reports describing collision lesions of SCAP and verruca, although little is known about the frequency of this association. Molecular testing has revealed the BRAFV600E mutation in a large proportion of SCAP cases, although its expression pattern has not been previously evaluated. METHODS: In this retrospective analysis, we explored the potential histopathological association between verruca and SCAP. We also evaluated mutation-specific BRAFV600E expression in these lesions by immunohistochemistry. Cases of SCAP diagnosed over a 7-year period were closely reviewed for the presence of contiguous verrucous proliferations. Additional sections were cut and stained using the BRAFV600E-specific clone VE1 antibody. RESULTS: Contiguous verrucous proliferations were identified in 9 out of 12 identified cases. Furthermore, expression of the BRAFV600E mutation was identified in 7 out of 12 cases. Interestingly, in SCAP associated with endophytic verrucous proliferations (n = 4), expression of BRAFV600E was found in both the glandular and the contiguous hyperplastic squamous epithelium. CONCLUSION: Overall, these findings suggest that contiguous verrucous proliferations in SCAP are common. Both components of the neoplasm may express the BRAFV600E mutation, which is suggestive of a common origin.