Immunohistochemical characterization of neuroendocrine and squamous differentiations in squamous cell carcinomas of the head and neck region

O carcinoma espinocelular (CEC) é a neoplasia maligna mais comum (>90%) na região de cabeça e pescoço (CECCP). Apesar dos avanços científicos nos seus mecanismos moleculares e protocolos terapêuticos, a taxa de sobrevida global em 5 anos permanece em 90%) in the head and neck region (HNSCC). Despite scientific advances in its molecular mechanisms and therapeutic protocols, the overall 5-year survival rate remains at <50%. In addition to the classic prognostic factors, there are histopathological variants of the HNSCC showing differences in its biological behavior and prognosis. Notably, some studies show that HNSCC can show neuroendocrine differentiation (NEd); however, the significance of this finding and its prognostic impact must be described in detail in a wide range of cases. According to the World Health Organization (WHO, 2017), neuroendocrine carcinoma (NEC) poorly differentiated from the head and neck region is an aggressive neoplasm, which may show association with human papillomavirus (HPV) or Epstein-Barr virus (EBV). Therefore, the NEC must be differentiated from the SCC NEd, aiming at diagnostic, therapeutic and prognostic criteria. Thus, in the present study 386 CECCPs were evaluated using the tissue microarray technique (TMA), using immunohistochemical analysis (IHQ), using the antibodies chromogranin-A, synaptophysin, CD56, CD57, CD99, Fli-1, p16INK4a, p40, CD10, vimentin, cyclin D1 and Ki-67; and by in situ hybridization (HIS) aiming at the detection of high-risk HPV (HRHPV) and EBV (EBER1 / 2). Our results showed a predominance of men (70%), white blood cells (74%), smokers (83%) and alcoholics (76%). The mean age was 59.4 ± 11.64 years, with no gender differences. The most affected sites were the oropharynx (n = 125), larynx (n = 121) and oral cavity (n = 103), followed by paranasal sinuses (n = 15), nasopharynx (n = 12) and others (n = 10). dNE (A-chromogranin and / or synaptophysin positive) was detected in 27/386 (7%) cases (larynx, n = 12; oropharynx, n = 8; oral cavity, n = 4; paranasal sinuses, n = 2; others, n = 1). Considering viral agents, 54 cases (oropharynx, n = 23; larynx, n = 21; oral cavity, n = 8; nasopharynx, n = 1; others, n = 1) and 3 cases (all of nasopharynx) were positive for HPV -AR and EBER1 / 2, respectively. p16INK4a was uniformly positive in HPV-AR positive cases. Seven cases simultaneously presented dNE / HPV-AR (oropharynx, n = 4; larynx, n = 2; mouth, n = 1). All CD99 positive cases were Fli-1 negative. CD10 and vimentin showed variable expression in cases with (53.9% and 12.5%) or without (31.8% and 9.6%) NEd, or with (33.9% and 5.6%) or without (32.8% and 10.2%) association with HPV-AR, respectively. Similarly, Ki-67 and cyclin D1 showed variable expression in cases with (39.1% and 9.6%) or without (38.6% and 5.9%) dNE, or with (42.1% and 7, 2%) or without (38.8% and 5%) association with HR-HPV, respectively. The 5-year overall survival (OS) for CgA (p = 0.79), SNF (p = 0.44) and HR-HPV (p = 0.93) in the oral cavity; CgA (p = 0.96), SNF (p = 0.13) and HR-HPV (p = 0.06) in the oropharynx; CgA (p = 0.83), SNF (p = 0.57) and HR-HPV (p = 0.46) in the larynx; no statistically significant differences over 5-years in OS considering dNE or association with HR-HPV. The OS at 5-years was statistically significant for staging III / IV in the oral cavity (p = 0.02) and larynx (p = 0.03); for surgical treatment in oral cavity (p = 0.03), oropharynx (p <0.01) and larynx (p <0.01); for radiotherapy (p