Primary cutaneous adenoid cystic carcinoma with MYB aberrations: report of three cases and comprehensive review of the literature

Abstract

Adenoid cystic carcinoma (ACC) is a relatively rare slow growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22–23;p23–24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report 3 additional cases of PCACC harboring MYB aberrations. The tumors presented in 3 males aged 43, 81 and 55 years old and affected the extremities in the first 2 patients and the scalp in the third one. None of the patients had history of prior or concurrent ACC elsewhere. Lesions exhibited the classic ACC morphology of nests of basaloid cells arranged in cribriform and adenoid patterns. Sentinel lymph node biopsy was performed in two cases with one case showing lymph node positivity. Fluorescence in situ hybridization with break-apart probes for MYB and NFIB loci revealed that 2 cases showed MYB rearrangements while one case showed loss of one MYB signal. None of the cases showed NFIB rearrangements. We contribute with 3 additional cases of PCACC exhibiting MYB aberrations, the apparent driving genetic abnormality in these tumors.

Homeobox transcription factor engrailed homeobox 1 is a possible diagnostic marker for adenoid cystic carcinoma and polymorphous adenocarcinoma

“…We recently reported that En1 is expressed in normal eccrine gland cells from the secretory coil to the acrosyringium and in the tumor cells with eccrine gland differentiations, but not in the normal hair follicles, sebaceous glands, apocrine glands or neoplasms with respective differentiations 12 . AdCC very rarely occurs in the skin originating from sweat glands 13,14 and we were aware that a case of AdCC in the skin expressed En1 (unpublished results). The expression of En1 in AdCC was previously reported through the screening of hypermethylated genes 15 and transcription profiling with microarrays; 16 however, the utility of En1 in histopathological diagnosis remains to be clarified.…”

Analysis of Characteristics and Survival of Primary Cutaneous Adenoid Cystic Carcinoma of the Head and Neck

“…One report highlights a case where a slowly growing scalp nodule progressed for 3 years before diagnosis, 9 while a literature review of cases, not limited to the head and neck, found a mean time to diagnosis of 84.5 months. 12 It has been shown that generally, being uninsured is associated with higher mortality. 17 Approximately one-third of the patients in our study presented with more advanced stage III and stage IV disease, which differs from previous literature showing PCACC to only rarely have nodal involvement or distant metastasis.…”

“…Most examinations of this tumor have been included in studies looking at PCACC arising from any primary site on the body or have been limited to case series, case reports, and components of literature reviews. 3,4,7-14 As a result, there is little documented insight into demographic characteristics of this tumor or factors that can impact survival and mortality. There is also little known about the ideal treatment modality for PCACC of the head and neck.…”

Fusion‐positive skin/adnexal carcinomas

“…Almost half of cases (46%) involved the head and neck, mainly the scalp, followed by the chest wall. 53 Involvement of the trunk, extremities, and the genito-perineal area is much less frequent. 53 Targeted RNA sequencing revealed no gene fusions (however, the PRKD1/2/3 genes are not included in the panel used so that a polymorphous adenocarcinoma could not be ruled out) and metastases (18%), even after complete local excision.…”

“…53 Involvement of the trunk, extremities, and the genito-perineal area is much less frequent. 53 Targeted RNA sequencing revealed no gene fusions (however, the PRKD1/2/3 genes are not included in the panel used so that a polymorphous adenocarcinoma could not be ruled out) and metastases (18%), even after complete local excision. 53 About 40% of cases harbor the canonical MYB::NFIB fusion.…”