Poorly differentiated neuroendocrine tumor of the larynx: challenging and highly aggressive.

Neuroendocrine tumors are the second most common pathologic type of laryngeal tumor, following only squamous cell carcinoma. Even so, they account for fewer than 1% of all laryngeal neoplasms. (1) Among these epithelial tumors are poorly differentiated carcinoma (also called small-cell undifferentiated carcinoma), oat-cell carcinoma, and anaplastic small-cell carcinoma, (2) and more than 90% of patients with these aggressive carcinomas develop metastatic disease. (2) In this article, we describe an atypical case.

The patient was a 25-year-old, nonsmoking Hispanic woman who presented with a 4-month history of gradually progressive hoarseness. Endoscopic examination detected a small, fleshy tumor along the subglottic aspect of the left true vocal fold: no evidence of local or distant invasion was seen. Computed tomography (CT) of the neck confirmed these findings (figure, A). The mass was locally resected. The lesion was pathologically and immunohistochemically consistent with a poorly differentiated carcinoma of neuroendocrine differentiation. The patient underwent both radiation and chemotherapy with cisplatin and etoposide.

After 14 months without systemic signs of disease, the patient was readmitted for evaluation of worsening headaches and lethargy. Imaging studies revealed widespread metastatic disease. CT and T1-weighted magnetic resonance imaging (MRI) of the head (figure, B) revealed the presence of two enhancing masses consistent with metastatic disease. T2-weighted MR1 showed associated surrounding edema and a moderate mass effect. CT of the chest, abdomen, and pelvis identified numerous metastatic lesions. Surgical biopsy of the largest intracranial mass and bronchoscopic biopsy identified the masses as metastatic, undifferentiated neuroendocrine carcinomas: they were strongly positive for cytokeratin and synaptophysin. The patient had no obvious evidence of recurrence of the primary laryngeal tumor. She underwent another course of chemotherapy. Her clinical course progressively deteriorated over the next 18 months, and she died.

The most common sites of metastatic spread of poorly differentiated or small-cell neuroendocrine carcinoma are the regional cervical lymph nodes, liver, lung, and bone. Only 8% of poorly differentiated neuroendocrine carcinomas of the larynx have been reported to metastasize to the central nervous system as a preterminal event. (2)

Most affected patients are men with a history of smoking. Approximately half of all patients have already developed a cervical metastasis at the time of presentation, and approximately two-thirds die of widespread metastatic disease (survival range: 1 to 26 mo). (2) Because this tumor is believed to undergo early hematogenous spread, a metastatic workup is warranted. Therapy protocols include a combination of radiation and chemotherapy. Surgery is most effective when performed during the early stages of disease and in patients with no evidence of metastasis. (2,3)

The atypical aspect of this case is that our patient was a female nonsmoker with a relatively small laryngeal tumor who developed late metastatic dissemination to the brain, lungs, and pelvis.

References

(1.) Gillenwater A, Lewin J, Roberts D, El-Naggar A. Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the larynx: A clinically aggressive tumor. Laryngoscope 2005:115:11915.

(2.) Ferlito A, Rinaldo A. Small cell neuroendocrine carcinoma of the larynx: A preventable and frustrating disease with a highly aggressive lethal behavior. ORL J Otorhinolaryngol Relat Spec 2003:65:131-3.

(3.) Ferlito A, Barnes L, Rinaldo A, et al. A review of neuroendocrine neoplasms of the larynx: Update on diagnosis and treatment. J Laryngol Otol 1998;112:827-34.

Sherley Valdez Arroyo, MD; Paul Rosel, MD; Enrique Palacios, MD, FACR 

From the Department of Neurology (Dr. Valdez Arroyo) and the Department of Radiology (Dr. Rosel and Dr. Palacios), Tulane University Medical Center, New Orleans.