Diagnosis: Mucoepidermoid Carcinoma, Low Grade with Oncocytic Features (with Cilia)
ANCILLARY STUDIES
MAML2 is positive for rearrangement by fluorescence in situ hybridization.
Figure 3
Discussion:
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is histologically comprised of a mixture of mucous cells, intermediate cells and squamoid/epidermoid cells but may also demonstrate clear cell, oncocytic or columnar cells [1]. Approximately half of MECs occur in major salivary glands, predominantly in the parotid gland [2]. Most MECs harbor a tumor type-specific translocation at t(11;19)(q21;p13) expressing CRTC1::MAML2 fusion gene [2].
While most oncocytic MEC with lymphoid stroma (i.e. “Warthin like” MEC) raise Warthin tumor as a differential diagnostic consideration, here, given the attenuated almost single layered appearance of the majority of the lesion, lymphoepithelial cyst is a closer differential diagnostic consideration [3]. In contrast to this MEC, lymphoepithelial cyst tends to be more squamous, with only rare mucous cells. In lymphoepithelial cyst, the epithelium is often infiltrated by lymphocytes, rather than surrounded by sclerosis with lymphoplasmacytic infiltrates [4].
Cystadenoma of salivary gland is another entity in the differential diagnosis and may show a lining similar to that of this case. Although mucinous subtype is uncommon, it may mimic a purely cystic mucoepidermoid carcinoma. Cystadenomas, however, lack invasive growth and also lack complex arborizing and hierarchical papillary tufting [5]. Ciliated epithelium is not uncommon in MEC in our experience, and likely underreported given the recent interest in this topic, though it is only rarely prominent [6]. Thus, ciliated epithelium does not automatically equate to a benign diagnosis.
Finally, the impression of mucoepidermoid carcinoma was confirmed by our fluorescence in situ hybridization for MAML2 gene rearrangements.
Mucoepidermoid carcinomas are currently graded using a three-tiered system as: low, intermediate and high grade, based on a constellation of cytomorphologic and architectural features including cystic component, border, mitoses, anaplasia, perineural and angiolymphatic invasion among others [1].
Grading in mucoepidermoid carcinoma is important for prognosis and therapy. The reported 5-year overall survival rate for low grade MEC is 92-100%. Low grade MECs generally require only surgical treatment, while high grade MECs require adjuvant radiation and neck dissection [1].
Different grading systems have been adopted for mucoepidermoid carcinomas and the four most popular grading systems are:
- AFIP grading system [7]
- Modified Healey system [8]
- Brandwein system [9]
- MSK Grading system [10] (Table [1]).
Both the AFIP and Brandwein system are point-based, with each adverse histologic parameter being assigned a point value and higher scores equating to higher grades, while in the modified Healey and MSK grading system, a tumor is graded based on its predominant morphologic features with certain histologic parameters characterizing a particular grade. The MSK grading system shares some similarities with the modified Healey system in that it takes into account predominant growth pattern, but for high grade MEC criteria become more discrete (i.e. mitotic count and tumor necrosis).
Table: Comparison of grading systems for mucoepidermoid carcinoma.
Footnote: The Brandwein grading scheme has been simplified to remove microstaging prognostically redundant parameters (angiolymphatic invasion, perineural invasion, bone invasion) and resolved to a simpler criteria based scheme with no adverse remaining parameters equating to low grade; one adverse to intermediate grade, and two or more adverse parameters to high grade.
The case presented here would be considered low grade by all commonly utilized grading systems and surgical excision would likely be curative.
References