Diagnosis -- Mucoepidermoid Carcinoma, Low Grade with Oncocytic Features (with Cilia)

FINAL 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:

  1. AFIP grading system [7]
  2. Modified Healey system [8]
  3. Brandwein system [9]
  4. 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).

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.

MULTIPLE CHOICE QUESTIONS

1. The most common fusion occurring in mucoepidermoid carcinoma (MEC) is:

  1. CRTC3::MAML2 fusion
  2. CRTC1::MAML2 fusion
  3. EWSR1::POU5F1 fusion
  4. EWSR1::MAML2 fusion

2. Which of the following is true:

  1. CRTC1::MAML2 fusion may be seen in low, intermediate or high grade MECs
  2. Low grade MECs show high-level copy number alterations
  3. Low grade MECs typically show TP53 and/or POU6F2 somatic mutations

3. Entities that enter the differential diagnosis of low grade MEC include:

  1. Poorly differentiated squamous cell carcinoma
  2. Salivary duct carcinoma
  3. Warthin tumor with oncocytic or squamous metaplasia
  4. Adenosquamous carcinoma

4. Entities that enter the differential diagnosis of high grade MEC include:

  1. Mucocele
  2. Sclerosing sialadenitis with mucous metaplasia
  3. Cystadenoma
  4. Salivary duct carcinoma

5. Mucoepidermoid carcinomas of the head and neck most commonly occur in the:

  1. Submandibular gland
  2. Sublingual gland
  3. Parotid gland
  4. Palate
  5. Mandible

REFERENCES

  1. Seethala, R.R., An update on grading of salivary gland carcinomas. Head Neck Pathol, 2009. 3(1): p. 69-77.
  2. Ilmo Leivo, J.A.B., Philippe Vielh, Hiroshi Inagaki, Nicole A. Cipriani, Valerie Costes-Martineau, Salivary Gland. Malignant epithelial tumours. Mucoepidermoid carcinoma., in WHO Classification of Tumours Editorial Board. Head and neck tumours, M.D.H. Alena Skalova, Ravi Mehrotra, Editor. 2022, Lyon (France): International Agency for Research on Cancer: [Internet; beta version ahead of print].
  3. Garcia, J.J., et al., Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test. Hum Pathol, 2011. 42(12): p. 2001-9.
  4. Juan C. Hernandez-Prera, P.E.W., Jr., Lisa M. Rooper, Brittany J. Holmes, Tumours and tumour-like lesions of the neck and lymph nodes. Cyst and cyst-like lesions. Lymphoepithelial cyst., in WHO Classification of Tumours Editorial Board. Head and neck tumours, M.D.H. Bruce M Wenig, Editor. 2022, Lyon (France): International Agency for Research on Cancer: [Internet; beta version ahead of print].
  5. Abbas Agaimy, R.S., Roderick Howard, Wallace Simpson, Masato Nakaguro, Salivary Gland. Benign Epithelial tumours. Cystadenoma of salivary glands., in WHO Classification of Tumours Editorial Board. Head and neck tumours, M.D.H. Alena Skalova, Ravi Mehrotra, Editor. 2022, Lyon (France): International Agency for Research on Cancer: [Internet; beta version ahead of print].
  6. Bishop, J.A., et al., MAML2 Rearrangements in Variant Forms of Mucoepidermoid Carcinoma: Ancillary Diagnostic Testing for the Ciliated and Warthin-like Variants. Am J Surg Pathol, 2018. 42(1): p. 130-136.
  7. Goode, R.K., P.L. Auclair, and G.L. Ellis, Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer, 1998. 82(7): p. 1217-24.
  8. Batsakis, J.G. and M.A. Luna, Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. Ann Otol Rhinol Laryngol, 1990. 99(10 Pt 1): p. 835-8.
  9. Brandwein, M.S., et al., Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol, 2002. 122(7): p. 758-64.
  10. Katabi, N., et al., Prognostic features in mucoepidermoid carcinoma of major salivary glands with emphasis on tumour histologic grading. Histopathology, 2014. 65(6): p. 793-804.
  11. Ilmo Leivo, J.A.B., Philippe Vielh, Hiroshi Inagaki, Nicole A. Cipriani, Valerie Costes-Martineau, Salivary Gland. Malignant epithelial tumours. Mucoepidermoid carcinoma., in WHO Classification of Tumours Editorial Board. Head and neck tumours, M.D.H. Alena Skalova, Ravi Mehrotra, Editor. 2022, Lyon (France): International Agency for Research on Cancer: [Internet; beta version ahead of print].

Contributed by Rayan Rammal, MD, and Raja Seethala, MD



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