216 Tumours of the salivary glands

 Acinic cell carcinoma

Definition Acinic cell carcinoma is a malignant epithelial neoplasm of salivary glands in which at least some of the neoplastic cells demonstrate serous acinar cell differentiation, which is characterized by cytoplasmic zymogen secretory granules. Salivary ductal cells are also a component of this neoplasm.

ICD-O code 8550/3 Synonyms Acinic cell adenocarcinoma, acinous cell carcinoma. Acinic cell tumour is an inappropriate synonym since the malignant biologic behaviour of this neoplasm is well-established {2304}.

Epidemiology Slightly more women than men are affected. There is no predilection for any ethnic group. Affected patients range from young children to elderly adults with a fairly even distribution of patients from the second to the seventh decades of life. Four percent of the patients are under 20 years old {668,1304,1954}.

Localization The overwhelming majority, almost 80%, of acinic cell carcinomas occur in the parotid gland, and about 17% involve the intraoral minor salivary glands. Only about 4% develop in the submandibular gland, and less than 1% arise in the sublingual gland {668,2711,2886}. Clinical features They typically manifest as slowly enlarging, solitary, unfixed masses in the parotid region, but a few are multinodular and/or fixed to skin or muscle. A third of patients also experience pain, which is often vague and intermittent, and 5-10% develop some facial paralysis. While the duration of symptoms in most patients is less than a year, it can be up to several decades in some cases {478,668,670, 1435,2445}.

 Macroscopy Most are 1-3 cm in largest dimension. They are usually circumscribed, solitary nodules, but some are ill-defined with irregular peripheries and/or multinodula - rity. The cut surface appears lobular and tan to red. They vary from firm to soft and solid to cystic.

Tumour spread Usually, acinic cell carcinomas initially metastasize to cervical lymph nodes and subsequently to more distant sites, most commonly the lung {670,960}.

Histopathology While serous acinar cell differentiation defines acinic cell carcinoma, several cell types and histomorphologic growth patterns are recognized. These are acinar, intercalated ductal, vacuolated, clear, and non-specific glandular and solid/lobular, microcystic, papillary-cystic, and follicular growth patterns {161, 478,668,1492,2290,2304}. Acinar cells are large, polygonal cells with lightly basophilic, granular cytoplasm and round, eccentric nuclei. The cytoplasmic zymogen-like granules are PAS positive, resistant to diastase digestion, and weakly stained or non-stained with mucicarmine. However, the PAS positivity can sometimes be very patchy and not immediately obvious. Intercalated duct type cells are smaller, eosinophilic to amphophilic, cuboidal with central nuclei, and surround variably sized luminal spaces. Vacuolated cells contain clear, cytoplasmic vacuoles that vary in number and size. The vacuoles are PAS negative. Clear cells are similar in size and shape to acinar cells but have non-staining cytoplasm that is non-reactive with PAS staining. Non-specific glandular cells are round to polygonal, amphophilic to eosinophilic cells with round nuclei and poorly demarcated cell borders. They often develop in syncytial sheets. Tumour cells are closely apposed to one another in sheets, nodules, or aggregates in the solid/lobular growth pattern. Numerous small spaces that vary from several microns to a millimetre or more in size characterize the microcystic pattern. Prominent cystic lumina, larger than the microcystic spaces that are partially filled with papillary epithelial proliferations characterize the papillary-cystic pattern. This variant, in particular, may be very vascular and haemorrhagic and sometimes phagocytosis of haemosiderin by luminal tumour cells is a conspicuous feature. In the follicular pattern, multiple, epithelial-lined cystic spaces are filled with eosinophilic proteinaceous material, which produces a thyroid follicle-like appearance. Psammoma bodies are occasionally seen and are sometimes numerous. They are not restricted to the papillary-cystic variant and have been reported in FNA specimens. Although a single cell type and growth pattern often dominate, many tumours have combinations of cell types and growth patterns. Acinar cells and intercalated duct-like cells often dominate while the other cell types seldom do. Clear cells are seen in only 6% of all acinic cell carcinomas {670}. They are usually focal and only rarely cause diagnostic confusion. The solid/lobular and microcystic patterns are most frequent, followed by the papillary-cystic and follicular pat - terns. A prominent lymphoid infiltrate of the stroma is associated with many acinic cell carcinomas {83,1717}. Whereas a heavy lymphoid infiltrate by itself has no prognostic significance, some tumours are well-circumscribed masses arranged in a microfollicular growth pattern and with a low proliferation index. They are completely surrounded by the lymphoid infiltrate (with germinal centre formation) and a thin fibrous pseudocapsule. These tumours appear to constitute a subgroup that behaves far less aggressively than other acinic cell carcinomas {1717}.