Primary Combined Neuroendocrine and Squamous Cell Carcinoma of the Maxillary Sinus: Report of a Case with Immunohistochemical and Molecular Characterization

Abstract

Neuroendocrine neoplasms represent a rare subset of tumors in the sinonasal tract. Combined tumors, with an endocrine and a non-neuroendocrine component, are exceedingly rare, and mainly consist of a combination of neuroendocrine carcinoma with adenocarcinomas. We present the clinico-pathologic and immunohistochemical features of a neuroendocrine carcinoma combined with squamous cell carcinoma, arising in the maxillary sinus. In addition, we evaluated the clonal origin of the two components through analysis of TP53 gene status. Both components were positive for cytokeratins AE1/AE3, while the squamous cell carcinoma was positive for cytokeratin 5/6 and p63, and the neuroendocrine carcinoma showed immunoreactivity for neuron specific enolase, chromogranin, synaptophysin and CD56. In situ hybridization for human papilloma virus and Epstein-Barr virus were negative in both components. A missense mutation in TP53 exon 7 (c.734G>C) and strong nuclear immunostaining for p53 were detected only in the neuroendocrine carcinoma. This suggests that the tumor either derived from one precursor cell with squamous differentiation, which underwent TP53 mutation and acquisition of a neuroendocrine phenotype, or it derived from two separate clones, one with mutated TP53 and neuroendocrine differentiation, and the other with wild type TP53 and squamous differentiation (collision tumor).

Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading

“…Kao et al [24] also found p53 overexpression in 92% of their high-grade NECs whereas none of their WD-NEC or MD-NECs exhibited p53 increased expression. In a single case report of a combined NEC and SCC of the maxillary sinus, Frachi et al found a missense mutation of TP53 the NEC component but not in the SCC component [32]. In contrast, Halmos et al [29] found no p53 overexpression in a study of 10 laryngeal NECs.…”

“…The coexistence of neuroendocrine and non-neuroendocrine components in carcinomas of the head and neck is a known but rare phenomenon [32][33][34]. Whereas the WHO classifications of endocrine organs and GI system recommend that mixed neoplasms are those in which either component represent at least 30% of the tumor, no such recommendation exists for mixed neuroendocrine-nonneuroendocrine carcinomas of the head and neck.…”

An Update on Sinonasal Round Cell Undifferentiated Tumors

“…Positivity for cytokeratins allows the distinction from other undifferentiated tumors, which may show neuroendocrine differentiation, including olfactory neuroblastoma and melanoma. Finally, sinonasal neuroendocrine carcinoma may occur in combination with squamous cell carcinoma or adenocarcinoma [20,21].…”

Primary Neuroendocrine Carcinoma Combined with Squamous Cell Carcinoma of the Soft Palate: A Case Report and Review of Literature

“…Staining of SCCs and BSCCs is strongly positive for 34βE12, while NECs are negative [6] [23]. p63 is also useful to identify basal and stem cells of the squamous epithelium and could be helpful to differentiate NECs from SCCs and BSCCs, as staining is positive for SCCs and BSCCs, but negative for NECs [6] [23]. In our case, tumor cells of the squamous cell differentiated area and a few basaloid nests were positive for 34βE12 and p63, but negative for the neuroendocrine markers.…”