Salivary glands

Cytology

Milan system

Atypia of undetermined significance (AUS)


Editorial Board Members: Ricardo R. Lastra, M.D., Marc Pusztaszeri, M.D.
Umamaheshwari Golconda, M.D.
Sadia Sayeed, M.D.

Last author update: 2 May 2023
Last staff update: 2 May 2023

Copyright: 2022-2024, PathologyOutlines.com, Inc.

PubMed Search: Salivary glands atypia of undetermined significance

Umamaheshwari Golconda, M.D.
Sadia Sayeed, M.D.
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Cite this page: Golconda U, Sayeed S. Atypia of undetermined significance (AUS). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsmilanAUS.html. Accessed February 22nd, 2024.
Definition / general
Essential features
  • Category is heterogeneous in nature
  • Differential includes nonneoplastic and neoplastic entities
  • Risk of malignancy is ~20%; the implied risk of malignancy was estimated to be ~20% in the 1st edition of the Milan system but was found to be higher (~30% on average) in subsequent studies with surgical follow up
  • It is recommended that no more than 10% of FNAs should be interpreted as atypia of undetermined significance
CPT coding
  • 88172 - determination of adequacy of specimen, first pass
  • 88177 - determination of adequacy of specimen, subsequent pass
  • 88173 - FNA interpretation
  • 88305 - cell block
Sites
  • Major salivary glands (parotid, submandibular, sublingual), less frequent in minor salivary glands
Case reports
Treatment
Cytology description
  • Atypia in a scant cellularity specimen which may represent reactive or reparative atypia but is indeterminate for a neoplastic process
  • Epithelial cells which have squamous, oncocytic or metaplastic changes but have limited cellularity and are indeterminate for a neoplastic process
  • Scant cellularity specimens which are suggestive of but not diagnostic of a neoplasm
  • Poorly preserved specimens which preclude determination of a neoplastic versus nonneoplastic diagnosis
  • A predominantly cystic lesion with a mucinous background with rare or absent epithelial cells
  • A lymphoid predominant aspirate in which a hematolymphoid neoplasm cannot be excluded
  • Rare atypical cells present when the differential includes a basaloid neoplasm
  • Reference: Faquin: The Milan System for Reporting Salivary Gland Cytopathology, 1st Edition, 2018
Cytology images

Contributed by Umamaheshwari Golconda, M.D.
Rare atypical cells

Rare atypical cells

Lymphoid rich aspirate

Lymphoid rich aspirate

Abundant extracellular mucin

Abundant extracellular mucin

Sample pathology report
  • Parotid, right, fine needle aspiration smears:
    • Atypia of undetermined significance
    • Scant histiocytes in a background of abundant mucin (see comment)
    • Comment: The specimen is limited by scant cellularity. The differential includes a mucinous cyst, though a low grade mucoepidermoid carcinoma is not entirely excluded. Clinical and radiologic correlation is suggested.

  • Submandibular, left, fine needle aspiration smears:
    • Atypia of undetermined significance
    • Heterogenous lymphoid elements (see comment)
    • Comment: Insufficient material was available for flow cytometry. Additional sampling with dedicated material for flow cytometry is suggested if clinical suspicion for a lymphoproliferative disorder persists.

  • Parotid, right, fine needle aspiration smears:
    • Atypia of undetermined significance
    • Rare atypical cells (see comment)
    • Comment: The specimen is limited by scant cellularity. The differential includes reactive atypia, though a neoplastic process cannot be entirely excluded. Clinical and radiologic correlation is suggested.
Differential diagnosis
  • Differential diagnosis of lymphocyte rich aspirates includes:
    • Nonneoplastic:
      • Chronic sialadenitis:
        • Hypocellular aspirate with basaloid (atrophic) or metaplastic ductal cells and few / absent acinar cells
        • Chronic inflammation (lymphocytes and plasma cells)
      • Lymphoepithelial sialadenitis:
        • More common in parotid gland (~90% of cases), in women and associated with autoimmune conditions like Sjögren syndrome
        • Cellular aspirate with large sheets of reactive ductal cells with or without squamous metaplasia and percolating mature lymphocytes
      • Lymphoepithelial cyst (HIV associated) cyst:
        • Associated with autoimmune disease (e.g., Sjögren syndrome) or young HIV+ individuals (usually multiple and bilateral) (Diagn Cytopathol 2012;40:684)
        • Proteinaceous and keratin debris with squamous cells (without significant atypia), lymphocytes and lymphohistiocytic aggregates
    • Neoplastic:
      • Warthin tumor:
        • FNA with predominant dirty granular background material and scant epithelial component can be falsely interpreted as necrosis
      • False negative rate: 1.3% (4/304) (Cancer Cytopathol 2021;129:43)
      • Mucoepidermoid carcinoma:
        • Predominantly mucus cells floating in extracellular mucin (low grade)
          • High grade nuclear features with pleomorphic nuclei, prominent nucleoli, intermediate cells and mucous cells are rare
      • Acinic cell carcinoma:
        • Cells are large but morphologically resemble normal acinar cells
          • Round nuclei with small nucleoli
          • Abundant finely vacuolated to granular cytoplasm
      • Malignant lymphoma:
        • Lymphomas originating from the salivary glands are rare, accounting for ~3% of all malignant tumors which more commonly affect the parotid glands
  • Differential diagnosis of lesions that can yield cystic fluid includes:
    • Nonneoplastic:
      • Obstructive sialoadenopathy
      • Neoplastic:
        • Warthin tumor:
          • Sheets of oncocytes and mixed population of lymphocytes in a characteristic dirty proteinaceous background
        • Pleomorphic adenoma:
          • Mixture of myoepithelial cells, ductal cells and extracellular stroma
        • Mucoepidermoid carcinoma:
          • Predominantly mucus cells floating in extracellular mucin (low grade)
            • High grade nuclear features with pleomorphic nuclei, prominent nucleoli, intermediate cells and mucous cells are rare
        • Acinic cell carcinoma:
          • Cells are large but morphologically resemble normal acinar cells
            • Round nuclei with small nucleoli
            • Abundant finely vacuolated to granular cytoplasm
          Cystadenoma:
          • Cyst wall with simple lining of glandular cells, oncocytic cells or squamous cells
        • Secretory carcinoma:
          • Cohesive clusters or sheets of epithelial cells with variable eosinophilic, granular to vacuolated cytoplasm and uniform nuclei with single nucleoli
Board review style question #1

This aspirate smear contains abundant extracellular mucin without epithelial cells. Under which category should this be placed according to the Milan system for reporting salivary gland cytopathology?

  1. Atypia of undetermined significance
  2. Nondiagnostic
  3. Salivary gland neoplasm of uncertain malignant potential
  4. Suspicious for malignancy
Board review style answer #1
A. Atypia of undetermined significance. The image shows abundant extracellular mucin. The differential diagnosis of mucin containing cysts includes mucocele, mucus retention cysts and low grade mucoepidermoid carcinoma. Therefore, atypia of undetermined significance is the correct interpretation on FNA.

Comment Here

Reference: Atypia of undetermined significance (AUS)
Board review style question #2
What is the implied risk of malignancy on excision if a diagnosis of atypia of undetermined significance is rendered on a fine needle aspiration (FNA) of the parotid?

  1. < 5%
  2. 20%
  3. 45%
  4. 90%
Board review style answer #2
B. 20%. The implied risk of malignancy is ~20% as per the Milan system for reporting salivary gland cytopathology (1st edition 2018), based on a limited number of studies. However, subsequent studies using the Milan system criteria have found the risk of malignancy for a diagnosis of atypia of undetermined significance with surgical follow up to be significantly higher (30% on average) with wide variations across institutions that reflect different types of practices.

Comment Here

Reference: Atypia of undetermined significance (AUS)
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