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Infiltrating, moderately differentiated neuroendocrine tumor of the larynx: A brief report. (Original Article).


We report a rare case of moderately differentiated neuroendocrine carcinoma of the larynx. We describe the clinical and pathologic findings relevant to this case, and we review the literature on the pathologic features of this malignancy. We also discuss treatment options.


Primary neuroendocrine tumors of the larynx account for fewer than 1% of all laryngeal malignancies. (1) Since these tumors were first described by Goldman et al (2) in 1969, numerous advances have occurred that have improved the histologic and immunochemical analysis of these lesions. These advances have contributed to our understanding of the characteristics of these malignancies, and they have enhanced our expertise in diagnosis and treatment. Proper histologic classification is crucial because the treatment, clinical course, and response to therapy are all determined by the tumor's cellular subtype. In this article, we describe a case of an infiltrating, moderately differentiated neuroendocrine tumor of the larynx, and we correlate the clinical and histologic findings with the therapeutic intervention and clinical course.

Case report

A 34-year-old white woman came to us in the summer of 2001 with a 7-month history of a left sore throat, odynophagia, and left referred otalgia. She admitted to smoking three or four cigarettes per day, and she denied alcohol intake. She worked in a beauty salon.

Fiberoptic laryngoscopy detected a 0.5-cm exophytic and erythematous mass arising from the left laryngeal surface of the epiglottis. No cervical lymphadenopathy was evident. Contrast-enhanced fine-cut computed tomography of the larynx and neck failed to identify the small epiglottic lesion or any cervical lymphadenopathy. Findings on chest x-ray were normal.

The patient was taken to the operating room on Sept. 4 for microlaryngoscopy and esophagoscopy. Biopsy specimens of the mass were obtained, and they were later interpreted to represent an infiltrating, moderately differentiated neuroendocrine carcinoma (figure 1). On special staining, chromogranin and CAM 5.2 were strongly positive (figure 2), synaptophysin and neuron-specific enolase were positive, and S-100 was negative.

The patient was returned to the operating room on Oct. 18, and she underwent a supraglottic laryngectomy and bilateral anterior neck dissections (figure 3). The final pathologic analysis identified residual nests of an infiltrating, moderately differentiated neuroendocrine carcinoma. There was no infiltration of the tumor into the cartilage, and there were no positive nodes on either side of the neck. All surgical margins were free of tumor. The immunohistochemical markers in the surgical specimen were identical to those in the biopsy specimen. At follow-up 1 year postoperatively, the patient was disease-free.


Although neuroendocrine carcinomas of the larynx are rare, they do account for 59% of all nonsquamous cancers of the larynx. (3) They can arise from either argyrophilic Kulchitsky's cells or pluripotential salivary stem cells. (4)

The three subtypes of neuroendocrine cancers of the larynx are designated as well differentiated, poorly differentiated, and moderately differentiated.

Well-differentiated neuroendocrine carcinomas (carcinoid tumors) are the rarest of the three ([less than or equal to]4% of cases). They usually appear in older men as a supraglottic mass, and they are associated with hoarseness. Histologically, these tumors contain uniform small cells with round or ovoid nuclei arranged in a trabecular pattern. (5) Electron microscopy reveals abundant neurosecretory granules. These cancers have an indolent course and are effectively treated with surgery.

Poorly differentiated neuroendocrine carcinomas (small-cell or oat-cell tumors) also occur in older men in the supraglottis; patients frequently have hoarseness, a neck mass, and a distant metastasis. Histologically, poorly differentiated neuroendocrine carcinomas appear much the same as oat-cell tumors of the lung. Specimens feature small cells, arranged in sheets or ribbons, that contain hyperchromatic nuclei and indistinct nucleoli; mitosis and necrosis are common. (6) These tumors frequently metastasize to the bone, liver, lung and pleura, brain, and adrenal glands. (7) The treatment of choice for these lesions is a combination of chemotherapy and radiation, but the mean duration of survival is less than 1 year. (7)

Moderately differentiated neuroendocrine carcinomas (atypical carcinoid or large-cell tumors) are the most common subtype (90% of cases). They tend to occur in younger patients, and they are accompanied by glossopharyngeal neuralgia. Histologically, these tumors contain more cytologic atypia, and they feature larger cells, cellular pleomorphism, and increased mitotic activity. (8) Because neuroendocrine markers are usually positive, they are a helpful adjunct in making the diagnosis. Patients with moderately differentiated neuroendocrine carcinomas have a poorer prognosis than do patients with well-differentiated neuroendocrine carcinomas because the former exhibit a greater tendency toward local recurrence and metastatic spread. Cutaneous and subcutaneous spread is seen in 9 to 28% of cases, which is unusual. (9) The overall 5-and 10-year survival rates for patients with these tumors have been reported to be 48 and 30%, respectively. (9)

Because moderately differentiated neuroendocrine carcinomas are radio-and chemoresistant, surgery is the mainstay of treatment. However, conservation procedures should be performed whenever possible, as we did for our patient, because these tumors permeate focally rather than through the paraglottic space. Endoscopic resection or supraglottic laryngectomy with prophylactic neck dis sections are reliable options for eradicating these tumors. (10,11)


(1.) Ferlito A, Friedmann I. Review of neuroendocrine carcinomas of the larynx. Ann Otol Rhinol Laryngol 1989;98:780-90.

(2.) Goldman NC, Hood CI, Singleton GT. Carcinoid of the larynx. Arch Otolaryngol 1969;90:64-7.

(3.) Woodruff JM, Huvos AG, Erlandson RA, et al. Neuroendocrine carcinomas of the larynx. A study of two types, one of which mimics thyroid medullary carcinoma. Am J Surg Pathol 1985; 9:771-90.

(4.) Hartley C, Birzgalis AR, Lyons TJ, Farrington WT. Neuroendocrine carcinoma of the larynx. J R Coil Surg Edinb 1996;41:333-5.

(5.) Batsakis JG, el-Naggar AK, Luna MA. Neuroendocrine tumors of larynx. Ann Otol Rhinol Laryngol 1992;101:710-4.

(6.) Gnepp DR. Small cell neuroendocrine carcinoma of the larynx. A critical review of the literature. ORL 3 Otorhinolaryngol Relat Spec 1991;53:210-9.

(7.) Machens A, Holzhausen HJ, Dralle H. Minimally invasive surgery for recurrent neuroendocrine carcinoma of the supraglottic larynx. Eur Arch Otorhinolaryngol 1999;256:242-6.

(8.) Woodruff JM, Senie RT. Atypical carcinoid tumor of the larynx. A critical review of the literature. ORL J Otorhinolaryngol Relat Spec 1991;53: 194-209.

(9.) Wenig BM, Hyams VJ, Heffner DK. Moderately differentiated neuroendocrine carcinoma of the larynx. A clinicopathologic study of 54 cases. Cancer 1988;62:2658-76.

(10.) Curran AC, McDermott N. Leader M, Walsh M. Neuroendocrine carcinoma of the larynx. Ir J Med Sci 1997;166:44-6.

(11.) Gripp FM, Risse EK, Leverstein H, et al. Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma. Eur Arch Otorhinolaryngol 1995;252:280-6.

From the Department of Surgery (Dr. Shemen, Dr. Petratos, and Dr. Patel) and the Department of Pathology (Dr. Horowitz), New York Hospital Medical Center of Queens, Flushing, N.Y.

Reprint requests: Larry Shemen, MD, 233 E. 69th St., Suite 1D, New York, NY 10021. Phone: (212) 472-8882; fax: (212) 472-3077; e-mail:

Originally presented at a research forum at the New York Hospital Medical Center of Queens; June 7, 2002; Flushing N.Y.
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Article Details
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Author:Horowitz, Laurie
Publication:Ear, Nose and Throat Journal
Geographic Code:1USA
Date:Mar 1, 2003
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