Salivary glands

Primary salivary gland neoplasms


Carcinoma ex pleomorphic adenoma

Topic Completed: 1 September 2012

Minor changes: 16 April 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Carcinoma ex pleomorphic adenoma[TIAB] salivary

Adriana Handra-Luca, M.D., Ph.D.
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Cite this page: Handra-Luca A. Carcinoma ex pleomorphic adenoma. website. Accessed September 16th, 2021.
Definition / general
  • Usually defined as carcinoma that develops in association with benign primary or recurrent pleomorphic adenoma
  • Rare spectrum of carcinomas demonstrating abrupt transition from benign tumor (usually pleomorphic adenoma); often adenocarcinoma, NOS, myoepithelial, salivary duct, terminal duct or undifferentiated carcinomas, usually with benign stroma
  • Also called malignant mixed tumor
Clinical features
  • 4% of salivary neoplasms, 12% of salivary malignancies but only 1% of intraoral salivary gland or minor salivary gland neoplasms
  • 5% of parotid tumors but 18% of malignant parotid tumors
  • Median age 55 years, average age 60 years, but also children (9% of salivary gland neoplasms in children), teenagers
  • Associated with pleomorphic adenomas: 2% risk of malignant transformation if present < 5 years, 10% risk if 15 years
  • Note: prior history of pleomorphic adenoma may be difficult to obtain but necessary for diagnosis unless benign tumor coexists with malignant tumor
  • Note: must rule out malignant mixed tumor if a high grade carcinoma of salivary glands is difficult to classify, by vigorous searching for a benign mixed tumor (may be 5 mm or less)
  • Clinically, have sudden increase in growth, pain or facial paralysis, facial tingling, trismus
  • 23% have recurrence, 56% regional or nodal metastases, 44% distant metastases (lung, bone / vertebral column, abdominal organs, CNS, kidney), 30 - 50% survival at 5 years
Prognostic factors (must thoroughly sample tumor)
  • Stage, extent of invasion beyond the capsule (< 8 mm is associated with benign behavior)
  • Histologic type and grade of carcinoma, proliferation index, proportion of carcinoma
  • Extent of invasion, vascular invasion, atypical mitoses
  • Pathological stage, tumor size, proliferation index (Arch Pathol Lab Med 2009;133:1763)
Case reports
  • Surgery, radiotherapy, chemotherapy
  • Possibly WT1 peptide based immunotherapy, trasuzamab / capecitabine
Gross description
  • Widely infiltrative with hemorrhage and necrosis
  • Average size 4 cm, mean size 6 cm
  • May be encapsulated
Microscopic (histologic) description
  • Abrupt transition from benign tumor (usually pleomorphic adenoma); often adenocarcinoma, NOS, myoepithelial, salivary duct, terminal duct, undifferentiated, usually with benign stroma (rarely stroma is chondrosarcoma)
  • Extensively infiltrative with marked atypia, necrosis, frequent mitotic figures, perineural and vascular invasion
  • Occasionally benign pleomorphic adenoma is present with hyalinization and hypocellularity
  • Malignant component: adenoid cystic carcinoma, carcinosarcoma (with chondro, lipo, rhabdomyo and spindle cell sarcoma component), clear cell carcinoma, epithelial myoepithelial carcinoma, giant cell tumor, mucoepidermoid carcinoma, salivary duct carcinoma, sarcomatoid carcinoma, sebaceous carcinoma, small cell carcinoma, squamous cell carcinoma
  • May have ossification, increased lymphatic vessels
  • Current classification / prognostic subtypes: in situ carcinoma (earliest stage, intracapsular), noninvasive (intracapsular, including in situ carcinoma), minimally invasive (< 1.5 mm) and invasive (Hum Pathol 2010;41:927)
  • Note: clinical malignant behavior is associated only with cytologically malignant foci beyond the capsule of original tumor
Cytology description
  • Poorly differentiated carcinoma, macronucleoli, irregular nuclear membranes
Positive stains
Negative stains
Molecular / cytogenetics description
  • Associated with 8q12-13 and 12q13-15 rearrangements
  • Diploid or aneuploid
  • Abnormal karyotype
  • LOH at 3p, 6q, 8p, 8q, 12q, 8q, 9p, 17p
  • Amplification of MYC, MDM2, HMGA2, MGC2177, PLAG1, PMSC6P, LYN, WIF1 rearrangement and loss of other allele
  • qMSP abnormal methylation, RASSF1 methylation and the epigenotype panel p16 / hTERT / RASSF1 / WT1 related to malignancy
Differential diagnosis
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