Small Cell Carcinoma of the Larynx:
Report of a Case and Review of the Literature

M Gairola,¹ S Jayalakshmi,¹ DN Sharma,¹ MC Sharma,²
A Thakkar,³ BK Mohanti,¹
Departments of ¹Radiation Oncology, ²Pathology,
and ³Otorhinolaryngology and Head and Neck Surgery,
All India Institute of Medical Sciences,
New Delhi-110029, India

Abstract

Small cell neuroendocrine carcinoma in the bronchus is well recognised as a highly malignant tumour with a high mortality rate. However, this tumour in the larynx is unusual with an aggressive biological behaviour. We present a report of a patient with small cell carcinoma of the larynx who presented with stage IV disease with metastasis.

Key words: Larynx, Radiotherapy, Small cell

Introduction

Anaplastic small cell carcinoma or oat cell carcinoma is a neoplasm commonly arising in the lungs. However, it may also occur, although rarely, in the larynx. The incidence rate has been reported to be slightly lower than 1% of all carcinomas.¹ Small cell neuroendocrine carcinoma is an important tumour in the larynx,² and was first described by Olofsson and van Nostrand in 1972.³ These tumours are biologically aggressive, with a mortality rate of at least 73%, with widespread tumour metastases. A combination of chemotherapy and radiotherapy forms the mainstay of treatment.²

Case Report

A 30-year-old male presented to the head and neck clinic at the All India Institute of Medical Sciences with chief complaints of hoarseness of 6 months duration, difficulty in swallowing of 4 months duration, and difficulty in breathing of 3 days duration. On examination, the patient was of average build, with a Karnofsky performance score of 60. Loco-regional examination of the neck revealed a 3 x 3 cm, level III lymph node on the left side of the neck that was hard in consistency, mobile, and non-tender with the overlying skin being normal. Indirect laryngoscopic examination revealed a bilateral supraglottic growth on the left side more than the right side. The endolarynx could not be seen due to a poor view. In view of the breathlessness and stridor, the patient underwent emergency tracheotomy. Direct laryngoscopy revealed an extensive clot around the growth in the supraglottic area, obscuring the endolarynx. Bilateral pyriform sinuses were involved in the medial part of the growth, while the post cricoid area was free of tumour. Histopathological examination of a biopsy specimen showed a poorly differentiated malignant tumour, possibly a small cell carcinoma (figure 1).

Figure 1. Photomicrograph showing stratified squamous epithelium with a sheet of small round cells in the subepithelial region. These cells have a scant amount of cytoplasm and hyperchromatic nuclei. (H&E, x40.)

Figure 2. Immunochemical staining showing positivity for synaptophysin antibody. (Magnification, x100.)

In view of this report, histopathological slides were sent for immunochemistry to test for leukocyte common antigen, which confirmed the diagnosis as small cell carcinoma (figure 2). All other investigations, including complete haemogram, renal and liver function tests, chest X-ray (postero-anterior and lateral views), X-ray of the soft tissue of the neck, and ultrasound of the abdomen, were well within normal limits.

The patient started combined modality treatment with chemotherapy and radiotherapy. He received 6 cycles of chemotherapy comprising intravenous cisplatin 20 mg/m² on days 1 to 5 and etoposide 100mg/m² on days 1 to 3, after which he was referred for radiotherapy. At the time of the radiotherapy planning, the patient was reassessed and found to have multiple, bilateral cervical lymph nodes and a low Karnofsky performance status of 50. He was therefore given palliative radiotherapy to the primary site and the neck by 2 lateral opposing fields by Co 60 teletherapy, to a total dose of 20 Gy/5 fractions/1 week. The patient tolerated the treatment well and was advised to attend the head and neck tumour clinic after 3 weeks.

Discussion

Small cell carcinoma of the larynx is a rare tumour.⁴ It is thought to arise from Kulchitsky cells or argyrophilic cells located in the bronchial wall. However, despite the common embryonic origin of the lung and larynx from the medial diverticulum of the foregut, small cell carcinomas of the larynx are extremely uncommon tumours.⁴

The majority of patients with laryngeal small cell neuroendocrine carcinoma are older than 50 years and tend to be men who have been heavy cigarette smokers. A 2:1 male:female predominance has been noted.⁵ The patient in this report was comparatively younger (30 years) and did not have a history of heavy cigarette smoking. The youngest reported patient in the literature is 23 years old. The tumour usually arises submucosally and predominantly from the supraglottic larynx.

In a review of 54 patients with small cell carcinoma of the larynx, Aguilar et al. found that 35% were transglottic and 27% were supraglottic.⁶ Small cell carcinomas present with the same type of symptoms as other laryngeal tumours. The commonest presenting symptom is hoarseness, followed by a neck mass. Mills et al. have observed that 50% of patients presented with cervical metastasis.⁵ The patient reported here presented with a bilateral neck mass and stridor, for which he underwent emergency tracheostomy. Small cell neuroendocrine carcinoma of the larynx may be associated with paraneoplastic syndrome, which may be a presenting feature. Although the metastatic lymph nodes were large, no areas of low attenuation indicating necrosis were seen on the computed tomography scan.⁷

Histologically, the tumour can be divided into 3 types, as for pulmonary tumours. These are oat cell, intermediate, and combined tumours. Laryngeal tumours showing squamous, glandular, neuroendocrine, exocrine, chondrosarcomatous, and rhabdomyosarcomatous differentiation have also been reported.⁸ The tumour may be cytokeratin and carcinoembryonic antigen positive and stains with general neuroendocrine markers, including chromogranin neuron specific enolase, protein gene product 9.5, neurofilament, and synaptophysin.⁹

Because of the aggressive nature of laryngeal small cell neuroendocrine carcinoma, treatment should be based on the assumption of disseminated disease. The tumour metastasises widely, spreading to the lungs, liver, and bone as well as the regional lymph nodes. In a review of 15 patients, Mills et al. found that 43% developed regional metastases and 71% developed distant metastases.⁵ Therefore, the treatment of choice for laryngeal small cell carcinoma remains a combined modality approach with radiotherapy and chemotherapy^2,4,6,10 as was pursued for the patient reported here. Surgery has a limited role in view of the prognosis, laryngectomy is rarely justified. The prognosis of laryngeal small cell carcinoma is poor, with a 2-year survival rate of 16% and 5-year survival of only 5%.¹¹

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