Salivary glands
Cytopathology (Milan system)
Neoplasm: benign

Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Jen-Fan Hang, M.D.

Topic Completed: 21 May 2020

Minor changes: 21 May 2020

Copyright: 2020,, Inc.

PubMed Search: Milan system benign neoplasm salivary

Jen-Fan Hang, M.D.
Page views in 2020 to date: 69
Cite this page: Hang JF, Bychkov A. Milan system - Neoplasm: benign. website. Accessed May 24th, 2020.
Definition / general
Essential features
  • Salivary gland FNA diagnostic of a benign neoplasm (pleomorphic adenoma 60 - 70%, Warthin tumor 20 - 30%, other tumors 10%)
  • 30 - 40% of all salivary gland FNA
  • Estimated risk of malignancy (ROM) by the Milan system: < 5%
  • Neoplasm: benign (category IVA)
  • Specific diagnosis of a benign neoplasm should be provided in this category
  • Parotid gland: 65 - 80% of all salivary gland tumors, 70 - 85% are benign (Kumar: Robbins and Cotran Pathologic Basis of Disease, 9th Edition, 2014)
  • Submandibular gland: 10% of all salivary gland tumors, 55 - 60% are benign
  • Minor salivary glands (including sublingual glands and seromucinous glands of the upper aerodigestive tract): 20% of all salivary gland tumors, 10 - 30% of sublingual gland tumors and 50% of minor salivary gland tumors are benign
Clinical features
Radiology description
Case reports
  • 12 year old boy with a parotid juvenile sclerosing polycystic adenosis, cytologically mimicking a Warthin tumor (Diagn Cytopathol 2019;47:1208)
  • 41 year old woman with a glandular schwannoma in submandibular region, cytologically mimicking a pleomorphic adenoma (Diagn Cytopathol 2015;43:395)
  • 53 year old women with Warthin-like variant of mucoepidermoid carcinoma of parotid glands, cytologically mimicking a Warthin tumor (Diagn Cytopathol 2017;45:1132)
  • 61 year old man with an epithelioid schwannoma of the facial nerve, cytologically mimicking a parotid pleomorphic adenoma (Diagn Cytopathol 2014;42:58)
  • 70 year old man with a cystic pleormophic adenoma of parotid gland, cytologically mimicking a mucoepidermoid carcinoma (Diagn Cytopathol 2005;32:229)
  • 78 year old woman with a pleomorphic adenoma of hard palate, showing predominant plasmacytoid myoepithelial cells and cytologically mimicking a poorly differentiated carcinoma (Diagn Cytopathol 2009;37:56)
  • Surgery or clinical and radiological follow up
Cytology description
  • Pleomorphic adenoma: 60 - 70% of all benign salivary gland FNA
    • Mixture of myoepithelial cells, ductal cells and extracellular stroma
    • Myoepithelial cells are usually the predominant cell type with various cytomorphology, including round, polygonal, plasmacytoid, spindle, etc.
    • Ductal cells show bland cytologic features with organized honeycombing or ductal arrangement
    • Extracellular matrix shows characteristic feathery / fibrillary borders and bright magenta color on Romanowsky type stain and gray-green chondromyxoid features on Papanicolaou stain
  • Warthin tumor: 20 - 30% of all benign salivary gland FNA
    • Sheets of oncocytes and mixed population of lymphocytes in a characteristic dirty proteinaceous background
    • Oncocytic sheets show an organized honeycombing or papillary arrangement and are typically cyanophilic at the periphery and bright orange at the center on Papanicolaou stain
    • Oncocytes show densely granular cytoplasm, centrally located nuclei and small nucleoli
    • Lymphocytes are mostly small mature cells
  • Oncocytoma:
    • Cellular oncocytic aspirates with very clean background
    • Oncocytes show abundant finely granular cytoplasm, centrally placed or eccentric nuclei and occasional distinct nucleoli
    • Cellular arrangement can be irregular sheets, small clusters or single cells
  • Most FNA of basal cell adenoma, myoepithelioma and cystadenoma should be better classified as salivary gland neoplasm of uncertain malignant potential (SUMP) due to overlapping cytomorphology with other malignant tumors
  • Other benign mesenchymal neoplasms:
    • Schwannoma: spindle shaped cells with wavy nuclei and bipolar cytoplasmic processes in syncytium-like fragments
    • Lipoma: fragments of benign adipocytes with clear cytoplasm and small nuclei
    • Hemangioma: bloody aspirates with few groups of bland spindle shaped endothelial cells
Cytology images

Contributed by Jen-Fan Hang, M.D.

Pleomorphic adenoma (PA): fibrillary extracellular matrix

PA: plasmacytoid
myoepithelial cells

PA with squamous metaplasia

Warthin tumor



Dr. Faquin on the Milan system - benign neoplasms

Sample pathology report
  • Satisfactory for evaluation. Neoplasm: benign. Pleomorphic adenoma.
  • Satisfactory for evaluation. Neoplasm: benign. Warthin tumor.
  • Satisfactory for evaluation. Neoplasm: benign. Oncocytoma.
Differential diagnosis
Board review style question #1

A 45 year old man presented with a 2.8 cm, slow growing mass at left parotid region. He underwent ultrasound guided FNA for evaluation. What is the best diagnosis?

  1. Basal cell adenoma
  2. Oncocytoma
  3. Pleomorphic adenoma
  4. Warthin tumor
Board review answer #1
C. Pleomorphic adenoma

Magenta colored extracellular matrix with feathery / fibrillary borders and intermingled bland myoepithelial cells are characteristic features for a pleomorphic adenoma.

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Reference: Milan system - Neoplasm: benign
Board review style question #2
Which of the following salivary gland tumors is not recommended to be reported as a benign neoplasm in fine needle aspiration?

  1. Basal cell adenoma
  2. Oncocytoma
  3. Pleomorphic adenoma
  4. Warthin tumor
Board review answer #2
A. Basal cell adenoma

Basal cell adenoma shows overlapping morphological features with basal cell adenocarcinoma in FNA. The distinction between these 2 tumors depends on the histological examination to demonstrate tumor invasion. Moreover, pleomorphic adenoma with predominant basal cells and solid / tubular variant of adenoid cystic carcinoma can also cytologically mimic a basal cell adenoma. Therefore, it is recommended to report FNA with basal cell feature as "SUMP with basaloid features" in the Milan system.

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Reference: Milan system - Neoplasm: benign
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