Intraoral Pigmented Low-Grade Adenocarcinoma, Not Otherwise Specified: Case Report and Immunohistochemical Study

Abstract

Salivary adenocarcinoma, not otherwise specified (AdCaNOS) is a rare malignant tumor with potential diagnostic challenge, which mainly affects the parotid glands; however, the minor salivary glands can also be involved by AdCaNOS. This paper reports a case of a 45-year-old Afro-descendant woman complaining of a slow-growing mass with 6 months of evolution in the left superior vestibular fornix. Microscopic examination revealed an infiltrative epithelial neoplasm composed of predominantly solid growth pattern, arranged in a lobular configuration, admixed with glandular or ductal structures. Perineural invasion was evident. The tumor cells were polygonal or oval showing focally mild nuclear pleomorphism, and eosinophilic or clear cytoplasm. Notably, some areas exhibited intracytoplasmic pigment granules mainly in non-luminal cells, as well as sebaceous-like cells, discrete hyaline material deposition and foci of infiltration of residual salivary gland parenchyma. Tumor cells were negative for PAS, mucicarmine and Alcian blue stains. By immunohistochemistry, the tumor cells were diffuse and strongly positive for pan-cytokeratin (CK) AE1/AE3, 34betaE12 CK, vimentin, p63 and S100. CK7 and EMA strongly highlighted the ductal structures. Solid areas also showed diffuse and moderate expression of CD56. Podoplanin (D2-40), GFAP and Calponin, followed by DOG-1, were focally positive; whereas CK20, α-SMA, h-Caldesmon, CD57, ERBB2/HER2 and p53 were negative. Ki-67 was < 2%. Consecutive serial tissue sections using CD57 confirmed the perineural invasion. Positivity for HMB-45 and MART-1/Melan-A, as well as Fontana-Masson stain (and potassium permanganate bleaching-sensitive), identified the pigment granules as melanin. To the best of our knowledge, this is the first case of intraoral low-grade AdCaNOS with intracytoplasmic melanin granules.

Co-expression of Myoepithelial and Melanocytic Features in Carcinoma Ex Pleomorphic Adenoma

“…The presence of epithelial/myoepithelial markers allowed to exclude both metastatic and exceptionally rare primary MM of the salivary glands [ 12 , 13 ]. The most challenging aspect of the presented two cases and subject of numerous pathogenetic speculations is the widespread expression of multiple melanocytic markers, as well as the potential presence of melanin pigment in salivary gland tumors [ 2 – 11 ]. Salivary glands tumors can be “colonized” by the melanocytes resident in the salivary glands [ 2 – 8 ].…”

“…Melanocytes present in human oral mucosa and salivary glands of healthy patients can be activated and move to the adjacent tumor, injecting melanosomes in the neoplastic cells, similarly to what occurs with keratinocytes in the epidermis [ 2 – 6 ]. Melanocytic colonization can justify the aberrant expression of some melanocytic markers (HMB45 and MART-1) by salivary gland tumors [ 8 – 11 ]. Nevertheless, the present two cases did not show melanin pigment and/or cells with a clear-cut melanocytic morphology (large and dendritic cells, with an appearance similar to melanocytes found in the basal layer of the normal skin), but only an immunohistochemical melanocytic differentiation.…”

“…The alternative pathogenetic theory is a myoepithelial/melanocytic overlapping differentiation, justified by a common neural crest origin and proved by numerous shared immunohistochemical markers such as S-100 [ 7 ]. Myoepithelial cells are well-known for the potential acquisition of divergent phenotypes, as epithelioid, spindle, adipocytic, clear, plasmacytoid, squamous with or without keratin [ 7 , 10 , 11 ]. Desai SS et al .…”

“…It remains to be determined whether this apparently paradoxical differentiation is the result of the transformation of a cancer stem cell (histogenesis theory) rather than a trans-melanocytic differentiation occurring as a late-step change (dedifferentiation theory) [ 14 – 16 ]. The cases of salivary gland tumors with melanin pigment and/or melanocytic phenotype reported in the literature are too few to obtain data on the possible prognostic impact of the myoepithelial/melanocytic overlapping differentiation [ 2 – 11 ]. The reported cases were different in histological subtypes and AJCC clinical-pathological stages, which does not allow to obtain easily comparable data on the possible prognostic impact of this rare and intriguing phenomenon [ 2 – 11 ].…”

“…Multi-lineage differentiation can be observed in salivary glands carcinomas, especially in myoepithelial cell carcinoma [ 1 ]. At the best of our knowledge, only rare cases of salivary glands tumors with abundant melanin pigment and/or expression of multiple melanocytic markers (S-100, SOX10, HMB45, MART-1 and MITF) have been reported in the literature [ 2 – 11 ]. Several pathogenetic theories have been proposed to justify this aberrant phenotype, which could lead to a challenging differential diagnosis with metastatic and primary malignant melanoma (MM) [ 2 – 13 ].…”