Introduction

Extrapulmonary neuroendocrine small cell carcinoma is a relatively rare disease, with the larynx the most frequently affected organ in the head and neck. They can occur in any region of the larynx with the supraglottis the most commonly reported site. Small cell carcinomas are highly aggressive and should be considered as a disseminated disease at the time of initial presentation. [₆] Nearly half the patients will have cervical metastasis at the time of presentation. A full metastatic workup is therefore important. [₇] Because of the rarity of these tumours in the larynx, no large studies are available to accurately guide management. In contrast to squamous carcinoma of the larynx, single modality therapy is not advised for neuroendocrine small cell carcinoma. Radiotherapy or surgery should be combined with systemic chemotherapy as primary treatment. Surgery is most effective in the early stages of the disease when there is no evidence of metastatic disease. [₇] Reported survival rates for patients with small cell carcinoma are 16% 2-year and 5% 5- year survival. [₁] This paper will discuss a case of neuroendocrine small cell carcinoma of the larynx and review the world literature.

Case study

A 52-year-old man presented to our department with a four-month history of hoarseness. He did not report any loss of weight or coughing and swallowing was normal. Apart from a fifteen pack-year smoking history he had no relevant medical history.

His nasal cavity, oral cavity and ears were normal, and there were no palpable cervical lymph nodes. Indirect laryngoscopy revealed a submucosal firm mass involving the right true and false vocal cords extending to the right aryepiglottic fold. The right vocal cord was immobile. Chest X-ray was normal.

Diagnostic rigid laryngoscopy and biopsy revealed infiltrates of fragile small round hyperchromatic malignant cells with the prominent smear artefact typical of this tumour (medium and high power, Figs A, B) [₁]. These cells were also seen intravascularly.

Figure 1

Figure 1a

Figure 2

Figure 1b

There was accompanying focal necrosis. In keeping with this diagnosis, the cells stained positively for cytokeratin antigens (AE1/AE3, Fig C, in which the normal overlying squamous epithelium is seen acting as a positive control) and for neural cell adhesion molecule antigens (CD56, Fig D).

Figure 3

Figure 1c

Figure 4

Figure 1d

A diagnosis of neuroendocrine small cell carcinoma of the larynx was made. Full metastatic work up did not reveal any metastases.

Discussion

Extrapulmonary neuroendocrine small cell carcinoma is a relatively rare disease, comprising 2.5% to 4% of all small cell carcinomas. [₂] These tumours occur in multiple sites throughout the head and neck with the larynx most frequently affected, followed by the salivary glands and the sinonasal region. [₃] These tumours account for less than 1% of laryngeal neoplasms [₄]. They can occur in any region of the larynx with the supraglottic region the most commonly reported site. [₂]

Neuroendocrine tumours constitute a morphologically heterogeneous group and include poorly differentiated carcinoma (also called small-cell undifferentiated carcinoma), oat-cell carcinoma and anaplastic small-cell carcinoma [₅]. Accurate histopathological diagnosis is often very difficult, but correct diagnosis is of utmost importance to ensure correct treatment.

Small cell carcinomas are highly aggressive and should be considered as a disseminated disease at the time of initial presentation. [₆] A full metastatic workup is therefore important. [₇] As with pulmonary small cell carcinoma, prognosis is poor and nearly half the patients have cervical metastasis at the time of presentation. The most common site of metastatic spread is to regional cervical lymph nodes, followed by liver, lung and bone. [₅] Two thirds of patients die of widespread metastatic disease.

Because of the rarity of these tumours in the larynx, no large studies are available to accurately guide management. In contrast to squamous carcinoma of the larynx, single modality therapy is not advised for neuroendocrine small cell carcinoma. Radiotherapy or surgery should be combined with systemic chemotherapy as primary treatment. Commonly used chemotherapeutic agents include cisplatin, carboplatin, etoposide, cyclophosphamide, doxorubicin, vincristine and methotrexate. [₆] An encouraging result was reported in a patient with an advanced laryngeal small cell carcinoma treated with Irinotecan hydrochloride (CPT-11). This agent has been associated with excellent efficacy in treatment of extensive small cell lung cancer. [₈] Surgery is most effective in the early stages of the disease when there is no evidence of metastatic disease. [₇]

Reported survival rates for patients with small cell carcinoma are 16% 2-year and 5% 5- year survival. [₁] The median survival for patients with primary small cell carcinoma of the larynx, hypopharynx, and trachea is between 7 and 11 months. [₉,₁₀]

Correspondence to

Dr Nico Jonas Division of Otolaryngology University of Cape Town Medical School H-53 Old Main Building, Groote Schuur Hospital Observatory, Cape Town 7925 South Africa Tel: +27 21 4066420 Fax: +27 21 4488865 Email: nicojonas@gmail.com