Small Cell Neuroendocrine of the Head and Neck: A Rare Presentation and Review of the Literature

Abstract

Head and neck tumors account for roughly 3% of malignancies in the United States and about 90% of these tumors are squamous cell cancers. Neuroendocrine neoplasms arise from neural crest cells and are commonly found in the gastrointestinal tract. Neuroendocrine neoplasms arising from the head and neck tend to be rare. In this article, we present a rare case of human papilloma virus-associated poorly differentiated small cell neuroendocrine carcinoma (NEC). Our patient was a 62-year-old African American man who presented with worsening left-sided neck pain and swelling that started 3 months prior to presentation, associated with an unintentional 20-pound weight loss over 6 months, hoarseness in his voice, in addition to dysphagia and odynophagia. Biopsy of left-sided tongue mass revealed poorly differentiated small cell NEC that was positive for HPV (E6/E7) RNA in situ hybridization. Patient was found to have metastatic disease at the time of diagnosis and given the aggressive nature of small cell NECs and the patient's symptomatic burden, chemotherapy with cisplatin and etoposide was initiated in the hospital. The patient was subsequently discharged from the hospital and is continuing treatment outpatient with cisplatin, etoposide, and atezolizumab.

Keywords: head and neck cancer; hematology oncology; neuroendocrine carcinoma; pathology.

Figure 1.

Computed Tomography (CT) soft tissue of neck. Enhancing mass lesion in the tongue, slightly lateralized to the left side measuring about the 4.4 x 3.7 x 4.3 in transverse, AP and CC directions. The lesion involves both vallecula with probable involvement of ventral surface of epiglottis. There is extensive necrotic lymphadenopathy on left side of the neck involving left level 2 through level 4 regions. Most of these lymph nodes measure about 3 to 4 cm in size.

Figure 2.

(A) Hematoxylin and eosin, Magnification 10x. Biopsy cores from the left neck mass shows tissue infiltrated by high-grade poorly differentiated carcinoma with a solid nested to trabecular pattern. (B) Hematoxylin and eosin, Magnification 40x. The tumor cells have high nuclear/cytoplasmic (N/C) ratio with increased mitotic activity and occasional molding. (C) Hematoxylin and eosin, Magnification 20x. Intermittent sheet-like segments of tumor cell necrosis are present. (D-F) Synaptophysin, P16, and pancytokeratin AE1/AE3 immunostains, Magnification 40x. The tumor cells are positive for synaptophysin, P16, and pancytokeratin AE1/AE3. The morphology and immunoprofile fit with small cell neuroendocrine carcinoma. The limited positive staining seen in the synaptophysin and pancytokeratin AE1/AE3 immunostains is expected since the tumor cells have limited cytoplasm.

Figure 3.

(A) Hematoxylin and eosin, Magnification 10x. Biopsy cores from the left base of tongue display mostly necrotic material and crushed cells. (B-D) Synaptophysin, CD56, and pancytokeratin AE1/AE3 immunohistochemical stains, Magnification 40x. The crushed cells show positivity for synaptophysin, CD56, and pancytokeratin AE1/AE3. The overall features fit with a neoplasm with neuroendocrine differentiation. The limited positive staining seen in the immunostains is expected since the tumor cells have limited cytoplasm.

Figure 4.

(A) Hematoxylin and eosin, Magnification 10x. Sections from the liver lesion biopsy contain liver parenchyma with extensive infiltration by small cell neuroendocrine carcinoma. (B) Hematoxylin and eosin, Magnification 40x. The tumor cells are small with fine chromatin and inconspicuous nucleoli. The majority of the tumor cells have scant to limited cytoplasm with occasional nuclear molding. Occasional slightly larger cells with mildly increased cytoplasm are seen and appear to be the same tumor cells with “intermediate” morphology. Scattered mitotic figures and single cell necrosis are present. (C-E) Synaptophysin, CD56, and pancytokeratin AE1/AE3 immunohistochemical stains, Magnification 40x.The tumor cells are positive for synaptophysin, CD56, and pancytokeratin AE1/AE3. The limited positive staining seen in the immunostains is expected since the tumor cells have limited cytoplasm.