Microsecretory adenocarcinoma of the skin harboring recurrent SS18 fusions: A cutaneous analog to a newly described salivary gland tumor

Abstract

Background Microsecretory adenocarcinoma (MSA) is a newly described salivary gland neoplasm characterized by MEF2C::SS18 fusions. MSA was previously thought to occur exclusively in salivary glands. Here, we expand the spectrum of known primary sites of this tumor by describing a series of cutaneous tumors with analogous findings. Methods We identified four cutaneous primary tumors with histopathologic features identical to MSA of the salivary glands. These cases were evaluated by immunohistochemistry, fluorescence in situ hybridization (FISH) for SS18 rearrangement and targeted RNA‐sequencing. We also queried a pan‐tumor database of advanced carcinomas for MEF2C::SS18. Results The cases occurred in men ranging from 61 to 74 years (mean, 68). They arose from the skin of the nose, chin, scalp, and external auditory canal. All included cords/microcysts of eosinophilic cells with bland oval nuclei and bluish mucin within fibromyxoid stroma. The scalp tumor also exhibited high‐grade transformation (marked atypia, elevated mitotic rate, and necrosis), a feature unreported in salivary MSA. By immunohistochemistry, all cases were positive for S100. Two showed a myoepithelial component positive for p40 and smooth muscle actin or calponin. Three cases harbored MEF2C::SS18 by RNA sequencing, while one with limited tissue had SS18 rearrangement via FISH. Two patients had no evidence of recurrence or metastasis in limited follow‐up (3 and 6 months). The pan‐tumor database query also did not identify MEF2C::SS18 in any advanced cutaneous carcinomas. Conclusion This report expands the sites that can be involved by MSA. Similar to salivary cases, MEF2C::SS18 represents a recurrent fusion in MSA of the skin. Unusual features in cutaneous cases not seen in salivary MSA include one case with high‐grade transformation and two cases with a myoepithelial cell component. Identification of this fusion expands the spectrum of salivary‐analog cutaneous tumors and aids in precise tumor classification.

Microsecretory adenocarcinoma: Cutaneous counterpart of a newly described salivary gland tumor with recurrent MEF2C::SS18 fusion

“…In summary, the works of Bishop et al 1 and Dibbern et al 2 describe cutaneous MSA that highlight similar findings to those seen in MSA of salivary gland origin. They also highlight some distinct features including the presence of a myoepithelial lining in some examples and the rare occurrence of high‐grade morphologic features.…”

“…This case further emphasizes the reproducible morphological, immunohistochemical, and genetic features of this rare tumor. It is interesting to note that the tumor in this case was located in the EAC, where two other reported cases of MSA have occurred 1,9 . The common origin in the EAC, presumably arising from the ceruminous glands, may reflect a common extraoral site for MSA.…”

“…In this issue of the Journal of Cutaneous Pathology , Bishop et al 1 and Dibbern et al 2 describe a total of five cases of cutaneous microsecretory adenocarcinoma (MSA), a recently described salivary gland tumor with a novel MEF2C::SS18 fusion.…”

“…In the current issue of The Journal of Cutaneous Pathology , Bishop et al 1 describe four cases of MSA limited to skin, involving the nose, chin, scalp, and the external auditory canal (EAC) (Table 1). In their series, the authors confirm that the findings of cutaneous MSA are similar to those seen in their salivary gland counterparts.…”

“…It is interesting to note that the tumor in this case was located in the EAC, where two other reported cases of MSA have occurred. 1,9 The common origin in the EAC, presumably arising from the ceruminous glands, may reflect a common extraoral site for MSA.…”