Salivary Gland FNA ATYPICAL : Criteria and Controversies
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1 Salivary Gland FNA ATYPICAL : Criteria and Controversies W.C. Faquin, M.D., Ph.D. Director, Head and Neck Pathology Massachusetts General Hospital Massachusetts Eye and Ear Infirmary Harvard Medical School Boston, MA USA
2 CASE A 45 yo man with a 6 month history of an enlarging left parotid gland mass.
3 Case: A CT scan revealed a 3.7 cm mass in the superficial lobe of the left parotid gland. An FNA was performed.
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8 What is your FNA Diagnosis?
9 CASE CYTOLOGIC DIAGNOSIS: NEOPLASTIC: UNCERTAIN MALIGNANT POTENTIAL Basaloid neoplasm with mild atypia. See note. Note: The differential diagnosis includes basal cell adenoma and other basaloid salivary gland tumors.
10 CASE SURGICAL RESECTION: Superficial parotidectomy was performed. A frozen section performed at the time of surgery favored a basal cell adenoma.
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13 CASE HISTOLOGIC DIAGNOSIS: BASAL CELL ADENOCARCINOMA, 3.7 CM, SOLID TYPE. Clinical follow-up: The patient has been free of disease for 10 years.
14 BASAL CELL ADENOCARCINOMA Low-grade salivary gland neoplasm 2% of malignant salivary gland tumors Malignant counterpart of basal cell adenoma Parotid gland, rarely in submandibular gland Average age: 60 years (range: years) Good prognosis: Local recurrence (35%), infrequent metastatic disease (10%), and low mortality (3%) Complete surgical excision with disease-free margins
15 Basal Cell Adenoma & Adenocarcinoma Immunohistochemistry: Positive for keratin 7, CEA, EMA Positive for myoepithelial markers Nuclear beta-catenin +
16 Basal Cell Adenoma & Adenocarcinoma CTNNB1 mutation 3p21 Beta-Catenin overexpression Present at cell junctions Part of WNT signaling pathway
17 Nuclear Beta-Catenin in Basal Cell Adenoma Jo et al. AJSP 2016;40:
18 The Key DDX for Basaloid Neoplasms: Basal Cell Adenoma/Adenocarcinoma Adenoid Cystic Carcinoma Cellular Pleomorphic Adenoma
19 The Milan System for Reporting Salivary Gland Cytopathology Proposed Classification Scheme 1) Non-Diagnostic 2) Non-Neoplastic 3) Atypia of undetermined significance 4) Neoplastic: a) Benign b) Uncertain malignant potential 5) Suspicious for Malignancy 6) Malignant
20 Salivary Gland FNA With an expanded array of IHC and new molecular advances, FNA and small biopsies are becoming more effective.
21 Increasing Availability of Molecular Markers For Salivary Gland Tumors Mammary analogue secretory carcinoma: ETV6-NKRT; t(12:15) Pleomorphic adenoma & Ca ex PA: PLAG1; t(3;8) HMGA2 rearrangement Clear cell carcinoma: EWSR1-ATF1; t(12:22) Mucoepidermoid carcinoma: MECT1/MAML2; t(11:19) Cribriform Adenocarcinoma: PRKD rearrangement Adenoid cystic carcinoma: MYB-NFIB; t(6:9) Basal Cell Adenoma CTNNB1 mutations
22 Most Pleomorphic Adenomas Are Accurately Diagnosed by FNA
23 Cellular Pleomorphic Adenoma: Can be difficult to distinguish from other basaloid neoplasms
24 Pleomorphic Adenoma Immunohistochemistry: Positive for keratin 7, CEA, EMA Positive for myoepithelial markers PLAG1 +
25 Pleomorphic Adenoma Cytogenetics: PLAG1 rearrangements (50-60%) Present in PAs in different tissues Nuclear localization Functions to activate transcription (Zn finger) HMGA2 rearrangements (10%)
26 PLAG-1 Immunoreactivity: Overexpressed in 94% of PA Contributed by Dr. J. Krane, BWH
27 Adenoid Cystic Carcinoma: Classic Cribriform Pattern often Recognizable by FNA
28 Solid Adenoid Cystic Carcinoma: Difficult to diagnose by FNA
29 Adenoid Cystic Carcinoma Immunohistochemistry: Positive for keratin 7, CEA, EMA Positive for myoepithelial markers CD117 (KIT) + MYB +
30 Immunoreactivity for CD117 (KIT) in AdCC Luminal Cells +
31 Adenoid Cystic Carcinoma: Recent Advance MYB Translocation Cytogenetics: t(6:9) MYB oncogene-nfib transcription factor In salivary gland, this finding by FISH is specific for AdCC FISH contributed by Dr. Joaquin Garcia, Mayo Clinic
32 MYB immunostaining is a useful ancillary test for distinguishing adenoid cystic carcinoma from pleomorphic adenoma in FNAB specimens FNA BIOPSY
33 A Challenging DDX in the Salivary Gland: PA vs AdCC vs BCA PA Chondromyxoid/ embedded cells PLAG1+, GFAP + Myoep predominant AdCC Matrix spheres acellular MYB+, CD117+ Small basaloid cells BCA Peripheral matrix ribbons Nuclear b-catenin+ 2 basaloid cell populations
34 Key Points FNA of basaloid neoplasms may be the single most difficult diagnostic problem in the salivary gland Milan System: Neoplastic - UMP A descriptive diagnosis and DDX is often used New immunohistochemical and molecular markers may increase the accuracy of FNA for basaloid tumors
35 Thank You!
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