Mucoepidermoid Carcinoma arising from Warthin tumor/ Warthin-like Mucoepidermoid Carcinoma
Detailed case history:
- A 64-year-old female is presented with a painless, slowly progressive mass on her left cheek for 6 years. Patient had recent increasing the size of mass. On clinical examination a 6×5 cm size mass arising from the parotid gland is evident. CT scan showed left parotid neoplastic mass lesion involving superficial lobe.
- FNA cytology showed very few atypical cells with pale vacuolated cytoplasm and mild hyperchromatic nuclei. Few lymphoid cells were seen in the background. Conclusive features of malignancy were not seen. So, as per MILAN system of reporting of salivary gland cytology Atypia of Undetermined Significance was given. The patient was operated and superficial parotidectomy was performed.
Gross pathology:
- Multilobular mass with predominant cystic changes, containing mucinous material. Focal yellowish-brown areas are seen. Total size of mass is 6.5x4x3 cm with an irregular border. Necrosis is not seen.
Histopathology:
- Multiloculated cystically dilated gland structures with lining of double layer of cells (Inner columnar oncocytic cells and basal cells in the outer layer), which are surrounded by a prominent lymphoid stroma with germinal centers, which are typical of Warthin-like tumor. Few cystic spaces contain granular pink material.
- At high magnification, some areas of the double layer lining epithelial cells showed features of stratified squamoid cells and mucinous vacuoles, and focal complex architecture informs of epithlieal tufting and cribriform like look.
- At few places, mucin-filled microcytic structures are seen, with lining of mucinous cells mixed with oncocytic cells. Focal squamous differentiation are also seen.
- Mucinous glands show invasive growth within hyalinised-fibrous stroma, without lymphoid stroma.
- Lympho-vascular invasion and perineural invasion are not seen.
Practical Points of Pathoclinics:
- Warthin-like mucoepidermoid carcinoma is a newly recognized uncommon entity and could be misdiagnosed as a Warthin tumor. Here the coexistence of Warthin tumor and mucoepidermoid carcinoma need to rule out; however, the latter is very rare and distinction between these two has almost no practical implication.
- In the present case, parotid swelling present for 6 years also indicate the pre-existing Warthin tumor, in co-relation with double-layer oncocytic epithelium with lymphoid follicles as well as separate areas of an infiltrative mucinous and epidermoid component in a fibrous-hyalinized stroma. Such fetures are suggestive of mucoepidermoid carcinoma arising from warthin tumor. IHC is not much helpful in the distinction between these two.
- Lymphoid malignancy is common than carcinoma arising from warthin tumor. Carcinomas arsing from warthin tumors are squamous cell carcinoma (the most common), mucoepidermoid carcinoma, oncocytic carcinoma, adenocarcinoma and undifferentiated carcinoma.
- Both warthin-like mucoepidermoid carcinoma and mucoepidermoid carcinoma arising from Warthin tumor are low-grade, with relative good prognosis. Aggressive treatment should be reserved for cases with extensive capsular invasion, high grade features and presence of nodal metastasis.
- Helpful diagnostic features:
| Helpful diagnostic features | Warthin-like Mucoepidermoid Carcinoma | Mucoepidermoid Carcinoma arising from Warthin tumor | Warthin tumor with mucinous and squamous metaplasia due to infarction |
| Age | Young age | Middle-old age | Middle-old age |
| Clinical progression of swelling | Slow enlargement | Slow enlargement, later relative fast progression | Very slow enlargement with sudden pain |
| Fine needle aspiration cytology | Interpretation varies based on aspirated components | Interpretation varies based on aspirated components | Usually no difficulty, however prominence of squamous and mucinous areas on cytology may indicate the possibility of MEC |
| Tumor border | Relative circumscribed or irregular- infiltrative | Circumscribed or irregular or infiltrative, depending on the location of MEC component in Warthin tumor | Circumscribed |
| Cut surface of tumor | Solid-cystic brownish greyish with mucinous cysts | Solid-cystic brownish greyish with mucinous cysts | Solid-cystic brownish greyish. Mucin filled cysts are usually not seen. |
| Stromal reaction: fibrosis and hyalinization | Seen, suggestive of MEC component | Seen, suggestive of MEC component | Not seen |
| Infiltrative appearance of mucinous and squamous cells | Seen, suggestive of MEC component | Seen, suggestive of MEC component | Not seen |
| Mucinous cells, irregular mucous glands, mucin spillage | Seen, suggestive of MEC component | Seen, suggestive of MEC component | May be seen; metaplastic goblet cells are common. |
| Squamous cells | Seen, suggestive of MEC component | Seen, suggestive of MEC component | May be seen |
| Lymphoid stroma | Variable | Abundant with lymphoid follicles | Abundant with lymphoid follicles |
| Double layer lining the cysts and gland: basal cells and oncocytic columnar cells | The double layer epithelium may be seen but cells are less tall and less oncocytic. | The double layer epithelium may be seen but cells are less tall and less oncocytic. | Inner columnar cells have abundant granular pink cytoplasm. |
| Cytological atypia | Not seen | Not seen | Seen, common in squamous component |
| Ki-67 | Relatively increased | Relatively increased | Very low |
| Molecular alteration/FISH study | t(11;19)(q21;p13) translocation- CRTC1–MAML2 gene fusiont(11;15)(q21;q26) translocation-CRTC3–MAML2 gene fusion | t(11;19)(q21;p13) translocation- CRTC1–MAML2 gene fusiont(11;15)(q21;q26) translocation-CRTC3–MAML2 gene fusion | Not seen |
| Management | complete surgical excision. Neck node dissection usually not required | complete surgical excision. Neck node dissection usually not required | Resection of tumor only |
| Follow-up due to the possibility of recurrence or metastasis | Required | Required | Usually not required |
| Note: In case of diagnostic dilemma, it is necessory to go for gene fusion study. |
Reference:
- Zhang C, Gu T, Hu Y, Sun J, Xia R, Tian Z, Wang L, Li J. Reevaluation of Salivary Lymphadenoma: A Subgroup Identified as Warthin-like Mucoepidermoid Carcinoma Following Molecular Investigation for MAML2 Rearrangement. Arch Pathol Lab Med. 2021 Jun 1;145(6):744-752. doi: 10.5858/arpa.2019-0702-OA. PMID: 32960941.
- Yu C, Song Z, Xiao Z, Lin Q, Dong X. Mucoepidermoid carcinoma arising in Warthin’s tumor of the parotid gland: Clinicopathological characteristics and immunophenotypes. Sci Rep. 2016 Jul 15;6:30149. doi: 10.1038/srep30149. PMID: 27417276; PMCID: PMC4945913.
- 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.
