LOW-GRADE CRIBRIFORM CYSTADENOCARCINOMA (LGCCC) (aka "low-grade salivary duct carcinoma")
Low-grade cribriform cystadenocarcinoma is a rare tumor that was first reported by Delgado et. al. in 1996. It was originally termed "low-grade salivary duct carcinoma" and recognized as a variant of salivary duct carcinoma; however, there is no data linking it to this much more aggressive tumor. In order to avoid confusion, the World Health Organization has recently recommended a change in the name to "low-grade cribriform cystadenocarcinoma."
LGCCC are rare entities. All that have been diagnosed to date have been in the parotid (with the exception of one in the submandibular gland), and these generally present as a cystic parotid tumor. The female to male ratio is 2:1.
Histologically, LGCCC are unencapsulated and consist of one or more cystically enlarged ducts associated with intraductal proliferations. The cysts are lined by a thick layer of proliferating, small ductal cells with anastomosing intracystic micropapillae, or with a looser cribriform pattern. Some papillae have fibrovascular cores. Smaller separate ductal structures have similar features; these may be filled with a typical cribriform pattern, or may exhibit solid growth. Proliferating ductal cells are small and bland with finely dispersed chromatin and small nucleoli. Overall, the appearance mimics breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Superficial cells often contain cytoplasmic apocrine type microvacuoles (PAS- positive/ diastase resistant), and/ or fine yellow- brown pigment that resembles lipofuscin. Cellular pleomorphism and mitoses are rare, as is necrosis. Infrequently, a transition from low- to intermediate- or high- grade cytology may be seen. These lesions may also have focal invasion into surrounding tissue, seen with small solid islands, reactive inflammation and desmoplasia. There is usually no perineural or vascular invasion.
LGCCC are strongly and diffusely positive for S100 protein. Myoepithelial markers such as calponin and smooth muscle actin highlight the myoepithelial cells rimming the ducts. Tumor cells are negative for Her-2-neu.
The differential diagnosis for LGCCC includes papillary cystic variant of acinic cell carcinoma (PCVACC) and conventional cystadenocarcinoma. PCVACC contains PAS-positive, diastase-resistane zymogen granules and is typically negative for S-100 proteins. Cystadenocarcinoma does not resemble breast lesions, and tends to be more invasive.
Treatment is complete surgical excision. To date, none of the cases with follow-up have recurred.
This case of low-grade cribriform cystadenocarcinoma represents a classic example of a rare tumor. Despite its rarity, its striking resemblance to breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ makes it a morphologically distinct salivary gland lesion.
Contributed by Melina Flanagan, MD, MSPH, and Leon Barnes, MD