Case prepared by Dr Asmita Nakum. Edited by Dr Jitendra Nasit
Clinical Case Details:
- A some around 60 years old female presented with a painless, slowly progressive mass of parotid gland for six years. Clinically and radiologically, the mass was approximately 6×5 cm sized, arising from the superficial lobe of the parotid gland.
- Fine needle aspiration cytology showed very few scattered pale vacuolated cells with mild hyperchromatic nuclei. Conclusive features of malignancy are not seen. So, according to the MILAN system of reporting of salivary gland cytology, atypia of undetermined significance was given (category 3).
Gross Pathology:
A grossly multilocular cystic mass was received, measuring 6.5x4x3 cm.
























Warthin-like Mucoepidermoid Carcinoma of the Parotid gland
Histopathology:
- Multi-cystic areas with dense lymphoid cells in the stroma and adjacent unremarkable salivary gland.
- Multi-cystic spaces are lined by mucinous epithelium (single to few layers of mucinous cells, with foci of papillary-like structures), admixed with oncocytic appearing pale cells within dense lymphoid stroma with germinal center formation.
- Areas of squamous cells, intermediate cells, and mucous cells are seen in an infiltrating manner in the dense fibrosclerotic stroma.
- Few areas have large cells, with abundant pink granular cytoplasm (true oncocytic cells, marked in yellow area) seen in the dense sclerotic stroma.
Practical Points of Pathoclinics:
- Mucoepidermoid carcinoma can show variable morphology like sclerosing, unicystic, oncocytic, sebaceous, clear cell, goblet cell rich and mix pattern. Recently Warthin-like mucoepidermoid carcinoma is a newly recognized entity. It could be misdiagnosed as a benign Warthin tumor, leading to improper management.
- In the present case, the important differential is Warthin tumor. Classically Warthin tumors have a well-defined border, and prominent cystic changes with a double layer of oncocytic cells within dense lymphoid follicles. Mucinous cells are not seen in Warthin tumors. However, metaplastic squamoid and goblet cells are very rarely seen in the Warthin tumor, which could be misinterpreted as evidence of mucoepidermoid carcinoma. Mucoepidermoid carcinoma has a mixture of mucous cells, intermediate cells, and squamous-like cells. Mucous cells of mucoepidermoid carcinoma are positive carcinoembryonic antigen and PAS staining. Key features favoring Warthin-like mucoepidermoid carcinoma are (1) presence of both mucinous and squamous areas, (2) infiltrative growth pattern, (3) dense lymphoid stroma, (4) absence of double layered densely oncocytic tall cells while the presence of mucous cells mixed with oncocytic looking pale cells, and (5) perineural invasion and necrosis (uncommonly seen). In the above case, distinctive mucous glands with squamous areas in an infiltrative pattern and the absence of doubled-layered oncocytic cells favor Warthin-like mucoepidermoid carcinoma.
- The second point is to look for squamous metaplasia in Warthin tumor. Metaplastic squamous areas can be extensive and commonly due to infarction within tumor. In such situation, differentiation from mucoepidermoid carcinoma can be difficult. In addition, Infarction and metaplastic process may induce of multilayering proliferation of epithelium, with both mucinous and squamous metaplasia. Features like bilayered oncocytic epithelium (at least focally), and absence of infiltrative growth favours non-malignant process.
- Another third but very uncommon differential of Warthin-like mucoepidermoid carcinoma is malignant transformation of Warthin tumor. Malignant components can be squamous cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, undifferentiated, poorly differentiated, and anaplastic carcinoma. Conclusive evidence for carcinoma ex Warthin tumor requires the presence of pre-existing benign Warthin tumor, areas of transition zones from benign to malignant component, infiltrating growth in the surrounding lymphoid tissue, and exclusion of metastases to the lymphoid stromal component of a primary extra salivary tumor. The coexistence of Warthin tumor and mucoepidermoid carcinoma is very rare and have a distinct component of each lesion.
- Warthin-like mucoepidermoid carcinoma have specific t(11:19) translocation resulting in CRTC1- MAML2 gene fusion exhibiting a better prognosis than conventional mucoepidermoid carcinoma. Fluorescence in situ hybridization for mastermind-like transcription coactivator 2 (MAML2) rearrangement may be required in problematic cases. All Warthin tumors are negative for MAML2 gene fusions.
- Complete local excision is the adequate treatment for Warthin-like mucoepidermoid carcinoma. It has a very indolent behavior and is unlikely recur. No metastasis has been reported.
- In the presence of keratinization, diagnosis of mucoepidermoid carcinoma should be in big question. It is necessary to rule out squamous cell carcinoma.
References:
- Balasubiramaniyan V, Sultania M, Sable M, Muduly D, Kar M. Warthin-like mucoepidermoid carcinoma of the parotid gland: a diagnostic and therapeutic dilemma. Autops Case Rep. 2019 Sep 30;9(4):e2019122. doi: 10.4322/acr.2019.122. PMID: 31641663; PMCID: PMC6771442.
- Zhang D, Liao X, Tang Y, Meyer RG, VAN Dyke DL, Liu X, Islam MN, Lai J. Warthin-like Mucoepidermoid Carcinoma of the Parotid Gland: Unusual Morphology and Diagnostic Pitfalls. Anticancer Res. 2019 Jun;39(6):3213-3217. doi: 10.21873/anticanres.13461. PMID: 31177170.
- Lei R, Yang H. Warthin-like mucoepidermoid carcinoma of the parotid gland: a clinicopathological analysis of two cases. J Int Med Res. 2022 Jul;50(7):3000605221101329. doi: 10.1177/03000605221101329. PMID: 35879827; PMCID: PMC9340346.