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Salivary glands

Cytology

Milan system

Suspicious for malignancy


Rebecca Tian Mei Au, M.B.B.S.
Manish Mahadeorao Bundele, M.B.B.S., M.D.

Last author update: 23 October 2023
Last staff update: 21 November 2023

Copyright: 2021-2025, PathologyOutlines.com, Inc.

PubMed Search: Suspicious for malignancy

Rebecca Tian Mei Au, M.B.B.S.
Manish Mahadeorao Bundele, M.B.B.S., M.D.
Table of Contents
Definition / general | Essential features | Terminology | CPT coding | Sites | Clinical features | Laboratory | Radiology description | Cytology description | Cytology images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Au RTM, Bundele MM. Suspicious for malignancy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsmilansuspicious.html. Accessed January 16th, 2025.
Definition / general
Essential features
  • FNA that shows cytologic features suggestive of malignancy and meets some but not all of the criteria for malignancy
  • FNA should be subcategorized if possible (e.g., suspicious for a primary salivary gland malignancy, suspicious for metastasis, suspicious for lymphoma)
Terminology
  • Suspicious for malignancy (category V)
CPT coding
  • 88172 - determination of adequacy of specimen
  • 88173 - FNA interpretation
Sites
Clinical features
  • Frequency among all the Milan system categories: 4%
  • Risk of malignancy (ROM) is 83% in the 2nd edition of Milan System, with a large study demonstrating a ROM of 83.3% (Cancer Cytopathol 2018;126:94)
Laboratory
Radiology description
Cytology description
  • FNA should be subcategorized if possible (e.g., suspicious for a primary salivary gland malignancy, suspicious for a metastasis, suspicious for lymphoma) (Diagn Cytopathol 2017;45:820)
  • Significant proportion will be suboptimal samples of a high grade carcinoma
  • Reasons that a salivary gland FNA leads to an interpretation of suspicious for malignancy include
    • Presence of markedly atypical cells with poor smear preparation, cell preservation, fixation artifact or obscuring blood or inflammation
    • Presence of limited cytologic features of a specific type of malignancy
    • Scant cellularity but presence of markedly atypical or suspicious cytologic features (prominent nucleoli, anisonucleosis, increased N:C ratio, nuclear molding, prominent nuclear pleomorphism, atypical mitoses and coarse chromatin)
    • Scant sample with features suggestive of a neuroendocrine neoplasm
    • Scant sample with features suggestive of a metastatic lesion
  • Many of the aspirates of lymphoma classified as suspicious for malignancy lack sufficient material for ancillary studies; some of the cytomorphologic features suggestive of lymphoma include
    • Prominent population of large atypical lymphocytes with coarse chromatin and prominent nucleoli, seen in large cell lymphomas
    • Monomorphic population of small to intermediate sized lymphocytes, seen in follicular lymphoma, mantle cell lymphoma, small lymphocytic lymphoma
    • Heterogeneous lymphoid population with atypical forms, seen in extranodal marginal zone lymphomas (EMZL), in particular in patients with history of Sjögren syndrome
Cytology images

Contributed by Manish Mahadeorao Bundele, M.B.B.S., M.D. and Rebecca Tian Mei Au, M.B.B.S.
Suspicious for acinic cell carcinoma   Suspicious for acinic cell carcinoma

Suspicious for acinic cell carcinoma

Suspicious for adenoid cystic carcinoma   Suspicious for adenoid cystic carcinoma

Suspicious for adenoid cystic carcinoma


Suspicious for mucoepidermoid carcinoma   Suspicious for mucoepidermoid carcinoma

Suspicious for mucoepidermoid carcinoma

Suspicious for large cell lymphoma   Suspicious for large cell lymphoma

Suspicious for large cell lymphoma


Suspicious for metastatic carcinoma   Suspicious for metastatic carcinoma

Suspicious for metastatic carcinoma

Suspicious for high grade basal cell adenocarcinoma   Suspicious for high grade basal cell adenocarcinoma   Suspicious for high grade basal cell adenocarcinoma

Suspicious for high grade basal cell adenocarcinoma

Sample pathology report
  • Parotid, right, fine needle aspiration smears:
    • Satisfactory for evaluation
    • Suspicious for malignancy
    • Rare markedly atypical cell clusters, suspicious for high grade carcinoma

  • Parotid, right, fine needle aspiration smears:
    • Satisfactory for evaluation
    • Suspicious for malignancy
    • Atypical cell clusters in a mucinous background, suspicious for low grade mucoepidermoid carcinoma

  • Parotid, right, fine needle aspiration smears:
    • Satisfactory for evaluation
    • Suspicious for malignancy
    • Monomorphic population of small lymphoid cells, suspicious for non-Hodgkin lymphoma (see comment)
    • Comment: Additional tissue sampling either by repeat FNA or other tissue biopsy is recommended for further evaluation with ancillary studies, including flow cytometry.

  • Parotid, right, fine needle aspiration smears:
    • Evaluation limited by low yield of well preserved cells
    • Suspicious for malignancy
    • Cyst contents with atypical squamous cells with enlarged hyperchromatic nuclei / dyskeratotic cells, suspicious for metastatic keratinizing squamous cell carcinoma
Differential diagnosis
  • Aspirates with scant cellularity but presence of markedly atypical cells:
    • Benign
      • Reactive and reparative atypia
      • Squamous, oncocytic or other metaplastic changes
    • Malignant
      • Salivary duct carcinoma:
        • Highly cellular with 3 dimensional clusters and single discohesive cells in a dirty / necrotic background and with overtly malignant cytologic features with abundant finely granular cytoplasm, nuclear pleomorphism, prominent nucleoli and frequent mitoses
      • Metastasis:
        • Metastatic cystic keratinizing squamous cell carcinoma:
          • Cyst contents with atypical squamous cells and dyskeratotic cells
      • Melanoma:
        • Wide range of cytomorphologic appearances; classically shows discohesive pleomorphic cells with eccentric nuclei, prominent nucleoli and fine to coarsely granular cytoplasmic melanin pigment
  • Lymphoid rich aspirates:
  • Cellular aspirates with oncocytic / oncocytoid cells or vacuolated cells:
  • Cellular aspirates with basaloid cells:
    • Benign
      • Cellular Pleomorphic adenoma:
        • Cellular basaloid neoplasm with absent to scant fibrillary matrix
      • Basal cell adenoma:
        • Cellular basaloid neoplasm with absent to scant hyaline stroma
        • Nonspecific cytomorphologic features; will need histological evaluation to exclude invasive features
      • Myoepithelioma:
        • Cellular basaloid neoplasm with minimal to no matrix
        • Nonspecific cytomorphologic features; will need histological evaluation to exclude invasive features
    • Malignant
      • Adenoid cystic carcinoma:
        • Monotonous, small basaloid cells with dark angulated nuclei and indistinct cytoplasm
        • Arranged in sheets or tubular pattern
        • Homogenous acellular nonfibrillary and intensely metachromatic matrix
      • Carcinoma ex pleomorphic adenoma:
        • Focal component of classic pleomorphic adenoma may be seen
        • Carcinomatous component most often salivary duct carcinoma or high grade adenocarcinoma, NOS
      • Epithelial myoepithelial carcinoma:
        • Variable proportions of ductal and myoepithelial cells
        • Predominant population of clear myoepithelial cells
        • Laminated acellular stromal cores
      • Myoepithelial carcinoma:
        • Cells with myoepithelial differentiation with cell types including plasmacytoid, spindled, clear and epithelioid forms
        • Metachromatic stromal material
        • Will need histological evaluation to demonstrate invasive features
      • Basal cell adenocarcinoma:
        • Cellular basaloid neoplasm with absent to scant hyaline stroma
        • Nonspecific cytomorphologic features; will need histological evaluation to demonstrate invasive features
      • Polymorphous adenocarcinoma:
        • Cytomorphologic features which lack specificity for a definitive diagnosis
        • Ductal phenotype with cellular monotony and architectural heterogeneity
  • Mucin containing aspirates:
    • Benign
      • Mucocele / mucus retention cyst:
        • Pooled mucin surrounded by a simple cyst lined by an intact, attenuated, cuboidal, columnar or squamous epithelium lining
      • Warthin tumor with focal mucinous metaplastic change:
        • Mucinous background with sheets of oncocytes and small lymphocytes
    • Malignant
    • Board review style question #1
    What is the risk of malignancy on excision if a diagnosis of suspicious for malignancy is given on a fine needle aspiration (FNA) of the parotid?

    1. < 20%
    2. ~40%
    3. ~60%
    4. > 80%
    Board review style answer #1
    D. > 80%. The risk of malignancy is 83%, as per the Milan System for Reporting Salivary Gland Cytopathology. Answers A - C are incorrect because the risk on excision is higher than 80% if reported as suspicious for malignancy on FNA.

    Comment Here

    Reference: Suspicious for malignancy
    Board review style question #2


    This is a representative image from a parotid gland fine needle aspiration. On cell block immunostaining, the epithelial cell clusters are positive for GATA3, AR and negative for DOG1, while the spindle cells are positive for p63 and SOX10. What category should this aspirate be placed in according to the Milan System for Reporting Salivary Gland Cytopathology?

    1. Atypia of undetermined significance
    2. Benign neoplasm
    3. Malignant
    4. Suspicious for malignancy
    Board review style answer #2
    D. Suspicious for malignancy. As mentioned above, on cell block immunostaining the atypical epithelial cell clusters are positive for GATA3, AR and negative for DOG1. These features raise the possibility of carcinoma with oncocytoid / apocrine features, such as salivary duct carcinoma. The background bland spindle myoepithelial cells are positive for p63 and SOX10 suggests a pleomorphic adenoma component. Given the limited cluster of cells with carcinoma morphology and admixed with bland myoepithelial cells, the correct answer is suspicious for malignancy. Answer B is incorrect because atypical cells are seen. Answer A is incorrect because the degree of atypia seen in these few atypical cell clusters is of high grade and is generally beyond this category. Answer C is incorrect because qualitative and quantitative features of atypical cells are insufficient for this category.

    Comment Here

    Reference: Suspicious for malignancy
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