Sclerosing mucoepidermoid carcinoma of salivary glands

Abstract

Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs.

Keywords: MAML2 rearrangement; IgG4; Keloid-like stromal fibrosis; SMEC; Salivary gland; Sclerosing mucoepidermoid carcinoma; Sclerosis; Tissue eosinophilia.

Fig. 1

SMECs were well circumscribed and only partially encapsulated by hyalinized pseudocapsule with tumor-associated lymphoid tissue at the periphery including lymphatic follicles with germinal centers and displaying a paucicellular zone of hyalinized collagen in the center A. The inflammatory component was mixed, predominantly composed of lymphocytes and plasma cells with only a few cells of acute inflammation (neutrophils/mast cells) B. The stromal component was always pronounced and revealed fibrohyaline sclerotic features resembling storiform collagenoma with tumor cells entrapped in a single fashion or as small clusters of cells C, D. Higher magnification of scattered tumor cells dispersed in collagen bundles D and highlighted by AE1/3 E on the left of both pictures with entrapped nerve. Occasionally there were characteristic structures of MEC arranged in cystic spaces with intermediate and mucoid cell differentiation F

Fig. 2

Three cases with typical SMEC-histology characterized by entrapped lesional structures in dense hyalinosclerotic stroma with intense inflammatory (mainly lymphoplasmacytic) infiltrate A showed an increased number of IgG4-positive plasma cells B

Fig. 3

SMECEs were highly cellular with the accumulation of chronic inflammatory cells, in particular lymphocytes that create lymphatic follicles with germinal centers A. The lesions were arranged in variably sized nests, thin strands, and anastomosing cords of large polygonal ganglion-like cells; their nuclei were round to oval with prominent nucleoli, vesicular chromatin, and eosinophilic or vacuolized cytoplasm B with neural involvement (arrow). Cystic spaces with squamoid cells and evidence of abrupt keratinization C and sometimes with multiple eosinophils in their lumen D. The stromal component consisted of thin hyalinized membranes and/or fibrous septa that surrounded tumor cells with a retraction phenomenon at their periphery. Occasionally they create larger fibrous fascicles E. Tumor cells were positive for p63 F