Low-grade cribriform cystadenocarcinoma

 Definition

A rare, cystic, proliferative carcinoma that resembles the spectrum of breast lesions from atypical ductal hyperplasia to micropapillary and cribriform lowgrade ductal carcinoma in-situ.

Synonym

Low-grade salivary duct carcinoma

Epidemiology

To date, all but one tumour have been diagnosed in the parotid gland and one in the palate {259,578,899,2562}. There is a female predominance of 2:1.

 Clinical features

Patients are usually elderly and all but one patient presented with cystic parotid tumours. Histopathology

Low-grade cribriform cystadenocarcinomas (LGCCC) are unencapsulated, consisting of single or multiple cysts, accompanied by adjacent intraductal proliferation. The cysts are lined by small, multilayered, proliferating, bland ductal cells with finely dispersed chromatin and small nucleoli. Within the cystic areas, they typically are arranged in a cribriform pattern and frequently have anastomosing, intracystic micropapillae lining the cavity, which may contain fibrovascular cores. Separate, smaller ductal structures are variably filled by proliferating ductal epithelium with cribriform, micropapillary and solid areas. The overall appearance is very similar to breast atypical ductal hyperplasia and lowgrade ductal carcinoma in-situ. Many superficial cells contain cytoplasmic apocrine-type microvacuoles (PAS- positive/ diastase-resistant) and/or fine yellow to brown pigment resembling lipofuscin. Focal invasion into the surrounding tissue can be seen, characterized by small solid islands and reactive inflammation and desmoplasia. Perineural or vascular invasion typically is not present. Cellular pleomorphism and mitotic figures are usually absent and necrosis is extremely uncommon. Occasional tumours may demonstrate transition from low to intermediate or high-grade cytology, with scattered mitotic figures and focal necrosis.

Immunoprofile

These tumours demonstrate strong, diffuse S100 positivity. Myoepithelial markers (calponin or smooth muscle actin) highlight cells rimming the cystic spaces, confirming the intraductal nature of most, or all, of each tumour. No myoepithelial cells are admixed within the proliferative cellular component. Those tumours studied for HER2-neu antigen are uniformly negative. Variants Originally, this tumour was reported as a low-grade variant of salivary duct carcinoma. However, as no data have accumulated definitely relating this entity to ductal carcinoma and since there frequently is a prominent cystic component, for the purposes of this WHO classification, the tumour is listed as a variant of cystadenocarcinoma.

Differential diagnosis

 The following tumours require exclusion: papillary cystic variant of acinic cell carcinoma, (PCVACC) and other variants of cystadenocarcinoma. PCVACC contains vacuolated cells similar to the microvacuolated cells of LGCCC. However the vacuoles of the latter are smaller, refractile, and associated with a yellow to brown pigment, while areas with PAS positive diastase resistant fine cytoplasmic granules will be found in the former. Conventional cystadenocarcinoma differ from LGCCC by the lack of intraductal proliferation, golden brown pigment, solid cellular foci, and overall resemblance to atypical hyperplasia or carcinoma- in-situ of the breast. Cystadenocarcinoma tends to be an invasive tumour, whereas LGCCC is usually contained within cysts {790}.

Prognosis and predictive factors

 Treatment is complete surgical excision. Although the number of cases with followup is small, none of the cases, to date, have recurred. Greater experience and longer follow-up periods are necessary to substantiate the excellent prognosis.