Salivary glands

Primary salivary gland neoplasms

Malignant

Sclerosing microcystic adenocarcinoma


Editorial Board Member: Marc Pusztaszeri, M.D.
Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.
Treeva Jassim, M.D.
Derek Allison, M.D.

Last author update: 13 June 2023
Last staff update: 13 June 2023

Copyright: 2021-2024, PathologyOutlines.com, Inc.

PubMed Search: Sclerosing microcystic adenocarcinoma

Treeva Jassim, M.D.
Derek Allison, M.D.
Page views in 2023: 1,806
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Cite this page: Jassim T, Allison D. Sclerosing microcystic adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/salivaryglandssclerosingmicrocysticadeno.html. Accessed June 16th, 2024.
Definition / general
  • Sclerosing microcystic adenocarcinoma (SMA) is an exceedingly rare tumor of presumed minor salivary gland origin that closely resembles cutaneous microcystic adnexal carcinoma (MAC)
  • It arises in mucosal sites in the head and neck region
  • SMA is made up of deeply infiltrative, variably sized bland ducts, tubules, cords and nests that contain a biphasic population of myoepithelial cells and cuboidal cells within an abundant, densely sclerotic stroma (Head Neck Pathol 2019;13:215, Surg Pathol Clin 2021;14:137)
Essential features
  • Sclerosing microcystic adenocarcinoma (SMA) is a unique and rare tumor of presumed salivary origin in the head and neck region that shows significant morphologic overlap with microcystic adnexal carcinoma (MAC) of the skin (Surg Pathol Clin 2021;14:137, Diagnostics (Basel) 2022;12:1288)
  • It is composed of a biphasic population of inner cuboidal and outer myoepithelial cells that form highly infiltrative and variably sized ducts, tubules, cords and nests within a dense collagenous stroma; perineural invasion and skeletal muscle involvement is prominent
  • Myoepithelial cells are often attenuated but are occasionally clear while the cuboidal component is relatively monomorphic with eosinophilic cytoplasm and round nuclei with even chromatin, occasional nucleoli and no increase in mitosis
  • Although follow up data are limited, patients with SMA have had uniformly good outcomes without locoregional recurrence or distant metastases (Surg Pathol Clin 2021;14:137)
Terminology
ICD coding
  • ICD-O:
    • 8000/3 - salivary gland neoplasm, malignant
    • 8140/3 - salivary gland adenocarcinoma, NOS
Epidemiology
Sites
Pathophysiology
  • Pathophysiology is still under investigation
  • SMA may show morphologic overlap with cutaneous MAC because normal intraoral minor salivary glands have morphologic and functional overlap with normal eccrine sweat glands
  • Recently, whole exome sequencing of a single case revealed a moderate tumor mutational burden, a putative loss of function mutation in CDK11B and no molecular overlap with mutations previously identified in MAC, though more work needs to be done (Anticancer Res 2020;40:6375)
Etiology
  • Like MAC, immunosuppression may play a role in the pathogenesis of SMA (several of the cases described have had a history of immunosuppressive therapy for autoimmune disorders, chemotherapy or radiation)
Clinical features
  • Typically painless, slow growing mass or submucosal lump (Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125:e94)
  • Both SMA and MAC exhibit an infiltrative growth pattern and a highly aggressive local behavior with perineural invasion that can cause numbness (Hum Pathol Rep 2021;26:300577)
  • Due to extensive perineural invasion, clear surgical margins may be difficult; patients with positive margins are recommended to undergo adjuvant radiation therapy
Diagnosis
  • Tumors may be visualized or palpated on the physical exam while imaging, such as CT and MRI, can be utilized to examine the extent of disease
  • Definitive diagnosis will typically be made on an excisional biopsy specimen
Radiology description
Radiology images

Images hosted on other servers:

Tongue tumor

Floor of mouth mass and enlarged lymph node

Prognostic factors
Case reports
Treatment
Clinical images

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Ulcerated palate tumor

Gross description
Gross images

Images hosted on other servers:

Tongue tumor

Frozen section description
  • Assessment of surgical margins, especially during intraoperative evaluation, is extremely challenging if not impossible due to the paucicellular and low grade nature of the tumor (Head Neck Pathol 2019;13:215)
Microscopic (histologic) description
  • SMA has a distinctive low power appearance of a relatively paucicellular tumor with clearly invasive variably sized ducts, tubules, cords and nests within densely sclerotic or desmoplastic stroma
  • Invasive component is composed of a biphasic population of inner cuboidal and outer myoepithelial cells
  • Myoepithelial cells are often attenuated and flattened but are occasionally more prominent and clear
  • Cuboidal cells are relatively monomorphic with eosinophilic cytoplasm and round nuclei with even chromatin, occasional nucleoli and no increase in mitosis
  • No significant nuclear atypia or necrosis (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:284)
  • No dysplasia is noted in the overlying mucosa (Diagnostics (Basel) 2022;12:1288)
  • Ducts and tubules are frequently filled with eosinophilic secretions that stain positively with mucicarmine (Surg Pathol Clin 2021;14:137)
  • Tumor infiltrates skeletal muscle (Head Neck Pathol 2019;13:215)
  • Perineural invasion is common (AJSP: Reviews & Reports 2021;26:329)
Microscopic (histologic) images

Contributed by Marc Pusztaszeri, M.D.
Infiltrative tubules and poorly formed glands Infiltrative tubules and poorly formed glands

Infiltrative tubules and poorly formed glands

Perineural invasion Perineural invasion

Perineural invasion

Perineural invasion

Perineural invasion


CK7 and p63 CK7 and p63

CK7 and p63

CK5/6 and p40

CK5/6 and p40

CK AE1 / AE3 and SOX10

CK AE1 / AE3 and SOX10

Cytology description
  • Distinct population of basaloid epithelial cells arranged in branching sheets and clusters with minimal nuclear pleomorphism
  • Biphasic appearance is apparent
  • Some of the cell clusters are bordered by a layer of flattened cells with ovoid bland nuclei
  • Occasional intranuclear inclusions are seen
  • Hyaline globular matrix, fibrillary metachromatic stroma and mucin are not identified
  • Mitotic activity, significant nuclear atypia and necrosis are absent (Ann Diagn Pathol 2021;54:151806)
Positive stains
Molecular / cytogenetics description
  • Recently, whole exome sequencing of a single case revealed a moderate tumor mutational burden, a putative loss of function mutation in CDK11B and no molecular overlap with mutations previously identified in MAC (Anticancer Res 2020;40:6375)
  • However, the molecular landscape of SMA is largely unknown at this point in time
Sample pathology report
  • Tongue, partial glossectomy:
    • Sclerosing microcystic adenocarcinoma (2.4 cm), margins uninvolved by carcinoma (see synoptic report and comment)
    • Comment: Sections show deeply infiltrative nests, cords and tubules of tumor cells embedded in prominent desmoplastic to densely collagenous stroma. The tumor is composed of a biphasic population of peripheral, flattened myoepithelial cells with central, bland cuboidal ductal cells with round nuclei, evenly dispersed chromatin and occasional nucleoli. Significant atypia and necrosis are not identified and mitotic figures are not conspicuous. Lumens of various sizes containing occasional dense, globular eosinophilic secretory material are present. The tumor infiltrated into skeletal muscles and multiple foci of perineural invasion are identified. On immunohistochemistry, the outer myoepithelial population stains positively for p63 and SMA while the inner cuboidal ductal cells stain positively for CK7. This immunohistochemical staining pattern supports the diagnosis.
Differential diagnosis
Board review style question #1

Which of the following immunohistochemical staining patterns support a diagnosis of sclerosing microcystic adenocarcinoma?

  1. CK7 in central ductal / epithelial component; p63 in peripheral myoepithelial cell population
  2. p63 in central ductal / epithelial component; CK7 in peripheral myoepithelial cell population
  3. S100 in central ductal / epithelial component; pancytokeratin in peripheral myoepithelial cell population
  4. SMA in central ductal / epithelial component; pancytokeratin in peripheral myoepithelial cell population
Board review style answer #1
A. CK7 in central ductal / epithelial component; p63 in peripheral myoepithelial cell population. The central ductal component showing positivity for pancytokeratin and CK7 and the peripheral myoepithelial cell population expressing smooth muscle actin, S100, p63 and p40 (Surg Pathol Clin 2021;14:137). Answers B - D are incorrect because these are not the immunohistochemical staining patterns for sclerosing microcystic adenocarcinoma.

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Reference: Sclerosing microcystic adenocarcinoma
Board review style question #2
Sclerosing microcystic adenocarcinoma (SMA) has been seen in association with which of the following?

  1. Alcohol
  2. HPV infection
  3. Immunosuppression
  4. Smoking
Board review style answer #2
C. Immunosuppression. SMA frequently arises in the context of immunosuppression (Anticancer Res 2020;40:6375). Answers A, B and D are incorrect because alcohol, HPV infection and smoking have not been reported as associations with this tumor.

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Reference: Sclerosing microcystic adenocarcinoma
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