A 50-year-old male with a 30-pack-year smoking history, hyperthyroidism, and hypertension presented with a 5-month history of globus sensation, bilateral nasal obstruction, and foul odor. No cervical mass was noted initially. Flexible endoscopy revealed an extensive ulceroinfiltrative mass involving the soft palate, bilateral palatine tonsils, uvula, epiglottis, pre-epiglottic space, and left aryepiglottic fold (Fig. 1).

Uvular punch biopsy revealed nests and rosette-like glandular structures of mixed large and small tumor cells with geographic necrosis and brisk mitoses (Fig. 2). Immunohistochemistry showed diffuse positivity for cytokeratin 7, CD56, and synaptophysin, while chromogranin A and p16 showed focal positive staining. TTF-1, C-kit, p40, and S-100 protein stains were negative. Ki-67 reached 80%. The tumor was diagnosed as NEC with mixed small and large cell features.

Contrast-enhanced neck MRI showed multilevel cervical and retropharyngeal lymphadenopathy (Fig. 3). Whole-body FDG PET-CT revealed hypermetabolic uptake at the primary and bilateral cervical nodes (Fig. 4), a 7.5 cm hepatic mass, and multiple pulmonary nodules (Fig. 5). Ultrasound-guided biopsies of a left level Ib node and the hepatic mass showed histopathology identical to the uvular lesion.

Given multifocal regional and distant metastases, palliative carboplatin-etoposide was initiated. After eight cycles, progressive disease prompted a switch to second-line FOLFIRI. The patient subsequently received palliative radiotherapy to the oropharynx concurrent with second-line chemotherapy for pain control, and is currently receiving third-line topotecan therapy. The detailed treatment course and response evaluation over an 11-month follow-up period are summarized in Table 2.

A 64-year-old male (40-pack-year smoker) presented with a 3-month history of progressive throat discomfort and odynophagia. He had undergone laryngeal microsurgical biopsy at a prior institution. At our institution, laryngoscopy confirmed a 2.4 cm mass at the left aryepiglottic fold without vocal fold fixation (Fig. 6A).

The laryngeal microsurgical biopsy from the referring institution revealed a carcinoma suggestive of NEC. Immunohistochemistry showed positivity for p16, CD56, and synaptophysin, with focal p63 expression. Chromogranin A was negative, and the Ki-67 index was approximately 40%-50%.

Neck MRI showed a well-circumscribed lesion at the left aryepiglottic fold without adjacent invasion, and a 1.6 cm left level III lymph node without extranodal extension (Fig. 7). FDG PET-CT confirmed hypermetabolic uptake at both sites and identified a 1.2 cm hypermetabolic nodule in the right upper lobe (Fig. 8). Fine needle aspiration of the cervical node revealed metastatic carcinoma.

Following multidisciplinary discussion, the pulmonary nodule was considered likely metastatic given its solitary appearance and the absence of features suggesting primary lung malignancy, although histologic confirmation was required for staging. Combined CO₂ laser-assisted supraglottic partial laryngectomy and video-assisted thoracoscopic surgery wedge resection of the right upper lobe was therefore planned for airway protection, curative-intent resection with negative margins, and staging confirmation. Neck dissection was considered a conditional component, to be reassessed based on intraoperative frozen section. Intraoperatively, malignancy was confirmed on pulmonary frozen-section analysis, establishing M1 disease. At this point, platinum-etoposide systemic chemotherapy was anticipated as the treatment backbone regardless of histologic subtype. Given NEC’s biological similarity to small cell lung cancer (in which widely metastatic disease is not surgically curable), and timely initiation of systemic therapy is the principal determinant of outcome [7,8], the added surgical burden of neck dissection was judged likely to delay systemic therapy without commensurate oncologic benefit. Neck dissection was not performed; cervical lymph node management was deferred to systemic therapy.

Final histopathology of the supraglottic specimen confirmed NEC, small cell type, with nests of small cells showing high mitotic activity; immunohistochemistry was positive for CD56, synaptophysin, and TTF-1, focally positive for p63, negative for chromogranin A, with Ki-67 of 40%-50% (Fig. 9). The pulmonary specimen was a poorly differentiated carcinoma with neuroendocrine features and focal squamous differentiation (metastasis vs. synchronous primary), showing focal TTF-1, p40, and p63 positivity with CD56 and synaptophysin negativity, plus lymphovascular emboli and spread through air spaces. Both resection margins were negative (supraglottic 0.1 cm, pulmonary <0.1 cm). Although differing marker profiles precluded pathology-based confirmation, the lesion was clinically interpreted as metastatic based on 1) absent primary lung features, 2) shared neuroendocrine differentiation, and 3) the known propensity of head and neck NEC for early distant metastasis.

Postoperatively, six cycles of palliative cisplatin-etoposide achieved complete response. Subsequent surveillance revealed recurrence at the left level III node and two new pulmonary nodules; palliative radiotherapy (5500 cGy each to the neck and lung over 1 month) was followed by second-line FOLFIRI. The primary surgical site remained free of recurrence at 6 months (Fig. 6B). The patient continues on systemic therapy. The detailed treatment course and response evaluation over a 21-month follow-up period are summarized in Table 2.

This study was approved by the Institutional Review Board of Korea University Ansan Hospital (IRB No. 2026AS0058), and informed consent was waived.