Adenocarcinoma, not otherwise specified

Definition

 Adenocarcinoma, not otherwise specified, is a malignant salivary gland tumour that exhibits ductal differentiation but lacks any of the histomorphologic features that characterize the other defined types of salivary carcinoma. The modifying term “not otherwise specified” should be included because most other epithelial salivary gland malignancies are also adenocarcinomas.

ICD-O code 8140/3

Synonyms

These tumours have often been reported as miscellaneous or unclassified adenocarcinomas or, simply, as adenocarcinoma {1662,1815,2447}. It appears that many reports include cases that should be classified as one of the more specific carcinoma types {668}. They should not be grouped together with tumours that arise from the seromucous glands of the nasal cavity, paranasal sinuses or larynx because in these sites they appear to have a more aggressive biologic behaviour {2447}.

Epidemiology

 The inconsistent reporting of these tumours limits our understanding of them. In one report they are second in frequency only to mucoepidermoid carcinoma among malignant salivary gland tumours and account for about 17% of the carcinomas {668}. Women outnumber men slightly and the average patient age is 58 years. They are extremely rare in children.

Localization

About 60% and 40%, respectively, occur in the major and minor glands. The vast majority that involve the major glands occur in the parotid, and the minor gland tumours most often arise from the glands in the hard palate, buccal mucosa, and lips.

 Clinical features

 Most patients with tumours of major glands present with solitary, asymptomatic masses, but about 20% have pain or facial weakness {2447}. Pain is more often associated with tumours of the submandibular glands. Minor gland tumours may be ulcerated and about 25% of palatal tumours involve the underlying bone. Tumour duration ranges from one to 10 years {2447}.

Macroscopy

Adenocarcinoma, NOS, is often partially circumscribed but in many areas the periphery is irregular and ill defined. Areas of necrosis or haemorrhage may contrast with the white or yellowish cut surface.

Histopathology

Shared by all tumours in this group are the presence of glandular or duct-like structures, infiltrative growth into parenchyma or surrounding tissues, and lack of features that characterize other salivary adenocarcinomas. There is considerable variability in the architectural structure. Some have small confluent nests or cords of tumour cells, others large discrete islands with intervening trabeculae of fibrous connective tissue, and still others large solid, densely cellular sheets. This latter group reveals very limited stromal connective tissue. Ductal differentiation is widespread in low and intermediate grade tumours but usually much more subtle in high-grade tumours. Small cysts are occasionally present in those with numerous ducts. Cuboidal or ovoid cells predominate in most tumours but scattered clear and oncocytic cells are occasionally evident. Small deposits of eosinophilic acellular material and extracellular mucin may be present. Unlike most other salivary adenocarcinomas, the cytologic variability is useful for grading these tumours {2447}. Low-grade   tumours demonstrate minimal variability of nuclear size, shape, or staining density, and rare mitoses. In some, the bland nuclear morphology suggests benignity and determination of their malignant nature is based largely on the identifi cation of invasive growth. Intermediate grade tumours show nuclear variability and more frequent mitoses. High-grade tumours have enlarged, pleomorphic, hyperchromatic nuclei, focal necrosis, and frequent and atypical mitoses. The presence of ductal differentiation helps in the distinction from undifferentia ted carcinoma.

Differential diagnosis

 Because these tumours do not have pathognomonic histopathologic features, the possibility of metastatic adenocarcinoma should be considered. While immunohistochemical studies may be useful in this evaluation {2370} it should be remembered that immunoreactivity with prostate-specific antigen has been reported {2571,2574}.

Prognosis and predictive factors

Limited data suggest that the clinical stage, site of involvement and grade of tumour influence prognosis {1662,2447, 2708}. Minor gland tumours have a better prognosis than those of the major glands. Distant metastases may occur despite regional control and recurrence is more frequent with high-grade tumours {2447}. In one study, the 15-year survival for low, intermediate and high-grade tumours was 54, 31, and 3%, respectively, and the cure rate of the low-grade tumours was similar to that of acinic cell adenocarcinoma {2447}.