Salivary glands

Cytology

Milan system

Malignant


Editorial Board Member: Marc Pusztaszeri, M.D.
Deputy Editor-in-Chief: Andrey Bychkov, M.D., Ph.D.
Jen-Fan Hang, M.D.

Topic Completed: 9 August 2021

Minor changes: 14 October 2021

Copyright: 2021, PathologyOutlines.com, Inc.

PubMed Search: Malignant[TIAB] salivary gland cytopathology Milan system

Jen-Fan Hang, M.D.
Page views in 2021 to date: 243
Cite this page: Hang JF. Malignant. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsmalignant.html. Accessed December 3rd, 2021.
Definition / general
Essential features
  • FNA showing diagnostic features of malignancy
  • 10 - 15% of all salivary gland FNA
  • Estimated risk of malignancy (ROM) by the Milan system: 90%
Terminology
  • Malignant (category VI)
  • An attempt should be made to grade the tumor as low, intermediate or high grade (Cancer Cytopathol 2020;128:392)
  • Specific tumor type should be provided if possible
CPT coding
  • 88172 - determination of adequacy of specimen
  • 88173 - FNA interpretation
Epidemiology
Sites
  • Parotid gland: 65 - 80% of all salivary gland tumors (Kumar: Robbins & Cotran Pathologic Basis of Disease, 10th Edition, 2020)
    • 15 - 30% are malignant
  • Submandibular gland: 10% of all salivary gland tumors
    • 40 - 45% are malignant
  • Minor salivary glands (including sublingual glands and seromucinous glands of the upper aerodigestive tract): 20% of all salivary gland tumors
    • 70 - 90% of sublingual gland tumors and 50% of minor salivary gland tumors are malignant
Clinical features
Radiology description
  • High grade carcinoma: ill defined, infiltrative border, heterogeneous internal signal with cystic change and necrosis (Eur J Radiol 2008;66:419)
  • Low grade carcinoma: overlapping features with benign salivary gland tumors
Case reports
Treatment
  • Surgical excision with or without lymph node dissection
Cytology description
  • Low grade carcinoma
    • Acinic cell carcinoma
      • Second most common (10 - 15%) malignant salivary gland tumor
      • Sheets or loosely cohesive cells without regular acinar organization
      • Plump tumor cells with abundant granular to vacuolated cytoplasm, indistinct cell borders and variable zymogen secretory granules best seen on Romanowsky type stain
      • Minimal nuclear atypia and frequent naked nuclei
      • Marked nuclear pleomorphism, prominent nucleoli, high nuclear/cytoplasmic ratio, necrotic background and loss of acinic differentiation in high grade transformation (Cancer Cytopathol 2021;129:318)
      • Ancillary testing:
    • Secretory carcinoma
      • Characterized by morphological resemblance to mammary secretory carcinoma and ETV6-NTRK3 fusion
      • Cellular smear with 2 different architectural patterns (Cancer Cytopathol 2013;121:228)
        • Papillary or sheet-like fragments
        • Dispersed or dissociated single cells
      • Polygonal tumor cells with abundant finely granular cytoplasm, occasional to prominent cytoplasmic vacuoles and rare eosinophilic secretory globules and intracytoplasmic mucin (Cancer Cytopathol 2013;121:234)
      • Mild to moderate nuclear atypia with distinct nucleoli and occasional multinucleation
      • Ancillary testing (Cancer Cytopathol 2018;126:627):
        • Positive for S100, mammaglobin, SOX10 and pan-TRK immunocytochemistry
        • Positive for ETV6 FISH
  • High grade carcinoma
    • Salivary duct carcinoma
      • Most common in elder males (peak in the seventh decade)
      • Sheets or crowded 3 dimensional clusters of overtly high grade malignant cells resembling invasive ductal carcinoma of the breast
      • Polygonal cells with enlarged, pleomorphic nuclei and prominent nucleoli
      • Frequent mitoses and necrosis
      • Ancillary testing: positive for androgen receptor and GATA3 immunocytochemistry (Cancer Cytopathol 2018;126:627)
      • Evaluation of AR and HER2 status is recommended for potential targeted therapy (Cancer Cytopathol 2020;128:693)
    • Due to overlapping cytomorphology among various high grade salivary gland carcinomas or salivary gland tumors with high grade transformation, classification of a specific tumor type might not be the most relevant and diagnosis of high grade carcinoma alone should be sufficient for most of the cases regarding the clinical decision making
  • Carcinoma with intermediate or multiple grades
    • Mucoepidermoid carcinoma
      • Most common malignant salivary gland tumors (40 - 50%) in both children and adults
      • 3 tiered grading system for histopathology and most often graded as low grade and high grade in FNA
      • Admixture of epidermoid, intermediate and mucus cells
      • Cystic background with abundant extracellular mucin
      • Low grade mucoepidermoid carcinoma: bland epithelial cells and abundant extracellular mucin
      • High grade mucoepidermoid carcinoma: predominantly epidermoid cells with marked cytologic atypia
      • Lymphocytes can be present in 20% of the cases and sometimes are abundant
      • Ancillary testing (Cancer Cytopathol 2018;126:627):
        • Positive for p63 / p40 and negative for SOX10 immunocytochemistry in epidermoid and intermediate cells
        • Positive for mucicarmine stain in the intracytoplasmic mucin of mucus cells
        • Positive for MAML2 FISH
    • Adenoid cystic carcinoma
      • Malignant basaloid tumor consisting of epithelial and myoepithelial cells in various histologic configurations, including cribriform, tubular and solid
      • Uniform basaloid cells with scant cytoplasm, oval to angulated hyperchromatic nuclei and indistinct nucleoli
      • Various architecture patterns, including microcystic, tubular and syncytial clusters
      • Characteristic extracellular hyaline globules or cylinders of acellular metachromatic stroma with sharp borders best seen on Romanowsky type stain
      • Marked nuclear pleomorphism, prominent nucleoli, high nuclear/cytoplasmic ratio and necrotic background in high grade transformation (Cancer Cytopathol 2021;129:318)
      • Ancillary testing (Cancer Cytopathol 2018;126:627):
        • Positive for MYB and KIT immunocytochemistry
        • Positive for MYB or MYBL1 FISH
    • Carcinoma ex pleomorphic carcinoma
      • Approximately 7% of all pleomorphic adenoma
      • Peak incidence at the sixth to seventh decade
      • Most of the carcinoma components are high grade salivary duct carcinoma
      • Features of classic pleomorphic adenoma in various proportions, depending on the sampling
  • Lymphoma
    • Low grade lymphoma: monotonous population of atypical small to medium sized lymphocytes (ex: extranodal marginal zone lymphoma, follicular lymphoma)
    • High grade lymphoma: diffuse proliferation of large atypical cells (ex: diffuse large B cell lymphoma)
    • Ancillary testing:
      • Immunocytochemistry for CD3, CD20, etc.
      • Flow cytometry if necessary
Cytology images

Contributed by Jen-Fan Hang, M.D.

Mucoepidermoid carcinoma

Acinic cell carcinoma

Salivary duct carcinoma


Adenoid cystic carcinoma

Secretory carcinoma

Videos

Malignant category 1

Malignant category 2

Sample pathology report
  • Submandibular gland, right, fine needle aspiration:
    • Satisfactory for evaluation
    • Malignant
    • Low grade mucoepidermoid carcinoma
  • Parotid gland, left, fine needle aspiration:
    • Satisfactory for evaluation
    • Malignant
    • High grade carcinoma, consistent with salivary duct carcinoma
  • Parotid gland, left, fine needle aspiration:
    • Satisfactory for evaluation
    • Malignant
    • High grade carcinoma (see comment)
    • Comment: Presence of scant chondromyxoid matrix, suggestive of carcinoma ex pleomorphic adenoma.
Differential diagnosis
Additional references
Board review style question #1

Which histological diagnosis most likely corresponds to this cytologic aspirate?

  1. Acinic cell carcinoma
  2. Adenoid cystic carcinoma
  3. Mucoepidermoid carcinoma
  4. Secretory carcinoma
Board review style answer #1
C. Mucoepidermoid carcinoma. A fragment of intermediate cells with intermingled mucous cells containing orange colored intracytoplasmic mucin is characteristic for a mucoepidermoid carcinoma.

Comment Here

Reference: Malignant
Board review style question #2

Which histological diagnosis most likely corresponds to this cytologic aspirate?

  1. Acinic cell carcinoma
  2. Adenoid cystic carcinoma
  3. Mucoepidermoid carcinoma
  4. Secretory carcinoma
Board review style answer #2
B. Adenoid cystic carcinoma. Basaloid tumor cells with prominent hyaline globules arranging in cribriform pattern are characteristic for an adenoid cystic carcinoma.

Comment Here

Reference: Malignant
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