Definition

 Small cell carcinomas of the salivary glands are rare, malignant epithelial tumours characterized by a proliferation of small anaplastic cells with scant cytoplasm, fine nuclear chromatin, and inconspicuous nucleoli.

ICD-O code 8041/3

 Synonyms

 Small cell undifferentiated carcinoma, small cell anaplastic carcinoma, oat cell carcinoma, neuroendocrine carcinoma.

 Epidemiology

They account for less than 1% of all salivary gland tumours and approximately 2% of salivary gland malignancies {668}.

Most patients are older than 50 years at the time of initial diagnosis; however, these tumours have been described in younger patients {668,902}. The tumour has a slight predilection for males.

Localization

The tumours can involve major and intraoral minor salivary glands, and are most common in the parotid gland.

Clinical features

Patients typically present with a painless, rapidly growing mass of several months duration. Cervical lymphadenopathy and facial nerve palsy are common findings. Paraneoplastic syndromes accompanied by the production of ectopic hormones are unusual {1746}. 

 Macroscopy

It is a firm, poorly circumscribed tumour that often infiltrates the surrounding salivary gland parenchyma and adjacent soft tissues. The tumour is usually grey to white and commonly accompanied by necrosis and haemorrhage.

 Histopathology

 Small cell carcinoma is characterized by sheets, cords, or irregular nests of anaplastic cells and a variable amount of fibrous stroma. The tumour cell nests may exhibit a peripheral palisading pattern. Rosette-like structures are occasionally seen. Tumour cells are usually 2- 3 times larger than mature small lymphocytes and have round to oval nuclei with scant cytoplasm. Fusiform or polygonal cells as well as occasional larger cells are sometimes observed. Nuclear chromatin is finely granular, and nucleoli are absent or inconspicuous. Cell borders are ill defined, and nuclear moulding is common. Mitotic figures are numerous. A tumour may have small foci of ductal differentiation {902}. Focal areas of squamous differentiation also have been described {1030,2196}. Extensive necrosis and vascular and perineural invasion are common. Immunoprofile In most small cell carcinomas, the tumour cells express at least one neuroendocrine marker such as chromogranin A, synaptophysin, CD57 (Leu-7), CD56 (neural cell adhesion molecule) and neurofilament {907,1818}. However, immunoreactivity for neuron-specific enolase alone is insufficient evidence for confirming the neuroendocrine differentiation of the tumour. Most small cell carcinomas are positive for cytokeratins, which often have a characteristic paranuclear dotlike pattern of reactivity {372,1818}. The majority of the tumours are also positive for epithelial membrane antigen {907,1818}. Similar to Merkel cell carcinoma, but unlike pulmonary small cell carcinoma, three out of four salivary small cell carcinomas are cytokeratin 20 positive {1818}. Also, small cell carcinomas are negative for S-100 protein and HMB-45. Electron microscopy Electron microscopic examination shows membrane-bound neuroendocrine granules in about one-third of small cell carcinomas {907}. The tumour cells contain sparse cytoplasmic organelles, and either poorly or well-formed desmosomes interconnect the cells. Multidirectional differentiation with the presence of myofilament-like microfilaments and tonofilaments has been reported {1030,2628,2836}.

Prognosis and predictive factors

 Local recurrence and distant metastases develop in more than 50% of patients after the initial diagnosis. Cervical lymph node involvement is less common than haematogenous metastasis. The 5-year survival rate for patients with small cell carcinomas arising in the major salivary glands ranges from 13 to 46% {902, 1818,2042}. Overall survival is reduced for patients with a primary tumour larger than 3 cm, negative immunostaining for cytokeratin 20 and decreased immunoreactivity for neuroendocrine markers {1818}.