Head and neck cytopathology

Micrograph showing a pleomorphic adenoma. Pap stain.

Head and neck cytopathology is a small part of cytopathology. Non-cytopathology head & neck pathology is dealt with in the head and neck pathology article.

Thyroid cytopathology is dealt with in the thyroid cytopathology article. An introduction to cytopathology is in the cytopathology article.

Salivary gland cytopathology and salivary gland cytology redirect to here.

Proposed Milan system for reporting salivary gland cytopathology

Milan system and Milan classification redirect here.

Category	Typical management	Comments
Nondiagnostic	repeat FNA
Nonneoplastic	follow-up/discharge
Atypia of undetermined significance (AUS)	repeat FNA	use should be minimized - like FLUS and ASCUS
Neoplasm	excision	subdivided into: (a) benign (b) salivary gland neoplasm of uncertain malignant potential (SUMP)
Suspicious for malignancy	wide excision +/-lymph nodes (?)
Malignant	wide excision & lymph nodes (?)

Notes:

• This classification is still evolving. The preliminary version (above) was presented by Dr. William Faquin at USCAP 2016 in Seattle.
• The goal is to complete the reporting system by the summer of 2017.

Normal

Depends on the structure that is needled.

Parotid:

• Acini - small globoid clusters.
  • Separated by adipose tissue.
• Granular cytoplasm.
• Nucleus:
  • Dispersed chromatin.
  • Indistinct nucleolus.
• Low NC ratio cells.

Sticky lymphoid tissue:

• Irregular globs of tissue with small cells.

Skeletal muscle:

• Round red staining globs +/-apparent striations.
• Nuclei more at edges (peripheral).

Images

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  SM - intermed. mag.

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  SM - high mag.

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  SM - very high mag.

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  SM - very high mag.

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  SM - high mag.

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  SM - high mag.

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  SM - very high mag.

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  SM - very high mag.

Salivary gland tumours - summary

Benign

Diagnosis	Architecture	Cytoplasm	Nucleus	Main DDx	Used to diff. from main DDx	Image
Pleomorphic adenoma	Fluffy fibromyxoid material & cells and single (plasmacytoid-like) myoepithelial cells	?	Myoepithelial cells - plasmacytoid appearance	DDx (?)	?	Pleomorphic adenoma. (WC)
Warthin tumour (papillary cystadenoma lymphomatosum)	Sheets of uniformly spaced oncocytes, lymphocytes, necrotic debris	Oncocytes (abundant, granular, eosinophilic tinge), well-defined cell borders	Oncocytes have nucleolus	Acinic cell carcinoma (AcCC), oncocytoma	AcCC: irregular spaced cells, lack well-defined cell borders	Warthin tumour - high mag. (WC)

Malignant

Diagnosis	Architecture	Cytoplasm	Nucleus	Main DDx	Used to diff. from main DDx	Image
Mucoepidermoid carcinoma	Clumps of cells	Abundant whispy cytoplasm	Small oval nucleus, +/-distinct nucleolus	Mucocele ?	Nuclear atypia	Mucoepidermoid carcinoma. (WC)
Adenoid cystic carcinoma (AdCC)	Circular islands of abundant very small cells	Scant cytoplasm	Small nucleus - may have carrot shape	AcCC	Basement membrane material - PAS-D+ve	Adenoid cystic carcinoma. (WC)
Acinic cell carcinoma (AcCC)	3-D clusters of small cells	Abundant orangeophilic granular cytoplasm	Stippled chromatin	Warthin tumour	AcCC missing lymphocytic background; irreg. spacing of cells	Acinic cell carcinoma. (WC)

Salivary gland

Main article: Salivary gland

Sialoadenitis

Main article: Chronic sialadenitis

Cytology

Features:

• Inflammatory cells - lymphocytes, plasma cells - key features.
• +/-Squamous metaplasia.
• +/-Necrotic debris.
• Benign ductal epithelium.

DDx:

• Squamous carcinoma.
• Mucoepidermoid carcinoma.

Crystals in salivary gland specimens

General

• Uncommon in general.
  • Typical location is: parotid (>85% salivary gland specimens with crystals).
• May be seen in the context of any diagnostic category (non-diagnostic, benign, neoplastic, malignant).
  • Approximately 40% of cases with crystals are benign or non-diagnositic.
  • Approximately 10% of cases with crystals are suspicious or malignant.

DDx:

• Amylase crystalloids ~ 75%.
• Tyrosine crystalloids ~ 11%.
• Collagenous crystalloids ~ 3%.
• Undetermined type ~ 11%.

Cytology

Features:

• Amylase crystalloids: rhomboid (or polygonal) +/- "pointy" ends, nonbirefringent.
• Tyrosine crystalloids: floret-like structures, refractile.
• Collagenous crystalloids: needle-shaped, radially arranged.

Images

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  Amylase crystals - parotid - intermed. mag.

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  Amylase crystals - parotid - intermed. mag.

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  Amylase crystals - parotid - high mag.

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  Amylase crystals - parotid - high mag.

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  Amylase crystals - parotid - very high mag.

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  Amylase crystals - parotid - very high mag.

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  Amylase crystals - parotid - very high mag.

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  Amylase crystals - parotid - animation - high mag.

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  Amylase crystals - parotid - animation - very high mag.

Sign out

Crystalloid material is present and has a rhomboid/polygonal shape with occasional "pointy" ends; this is in keeping with amylase crystals.

Pleomorphic adenoma

Main article: Pleomorphic adenoma

• Abbreviated PA.

General

• Common benign tumour.

Cytology

Features (MEC):

1. Myoepithelial cells.
   • Plasmacytoid-like cells.
     • Single cells (very common) or small clumps - oval shape.
2. Epithelial cells.
3. Chondromyxoid stroma.
   • Whispy/fluffy groups of spindle cells that overlap (fibromyxoid tissue) - blue-ish.

DDx:

• Adenoid cystic carcinoma.
  • Big circular globs (cysts) - common in AdCC.

Images

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  PA - high mag. (WC)

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  PA - high mag. (WC)

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  PA - very high mag. (WC)

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  PA - very high mag. (WC)

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  Pleomorphic adenoma. (WC)

Warthin tumour

• AKA papillary cystadenoma lymphomatosum.

General

• Usual smokers.
• May be bilateral.

Cytology

Features:

• Oncocytes.
  • • Well-defined cell border.
    • Granular cytoplasm.
    • Nucleoli.
  • Oncocytes are often associated with mast cells, i.e. on "top of" oncocytes.
    • Mast cells: very granular dark staining cytoplasm (on smears).
• Lymphocytes.
• Necrotic material (cyst contents).

DDx:

• Acinic cell carcinoma.
  • Spacing of tumour in AcCC is more irregular and appear more crowded.
  • The cell borders in AcCC is less obvious.
• Oncocytoma.
  • Oncocytoma (vis-a-vis Warthin tumour) has more cells, more cytoplasm, more granularity of cytoplasm, more complex architecture.

Images

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  Warthin tumour - high mag. (WC)

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  Warthin tumour - intermed. mag. (WC)

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  Warthin tumour - surgical specimen. (WC)

Oncocytoma

Main article: Oncocytoma of the salivary gland

General

• May be confused with Warthin tumour.

Cytology

Features:

• Oncocytes.
  • • Well-defined cell border.
    • Granular cytoplasm.
    • Nucleoli.

Vis-a-vis Warthin tumour:

• Oncocytoma has:
  • More cells,
  • More cytoplasm,
  • More granularity of cytoplasm,
  • More complex architecture.

Mucoepidermoid carcinoma

Main article: Mucoepidermoid carcinoma

General

• A challenging FNA diagnosis.

Cytology

Features:

• Sheets of cells.
• Cells have a small oval nucleus with nucleolus.
• Fluffy cytoplasm with a pink tinge (on Pap stain) - key feature.
  • Cytoplasm not seen in 3-D clusters - look for single layer of cells.
  • Cell borders are often distinct.

DDx:

• Squamous cell carcinoma - extensive keratinization and squamous pearls.

Images

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  Mucoepidermoid carcinoma. (WC)

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  Mucoepidermoid carcinoma - very high mag. (WC)

Acinic cell carcinoma

Main article: Acinic cell carcinoma

General

• Uncommon.

Cytology

Features:

• Abundant granular cytoplasm.
• Stippled chromatin.
• +/-Nucleolus.

Notes:

• Often accompanied by stripped nuclei; may mimic lymphocytes (may lead to confusion with Warthin tumour).
• Lack:
  • Adipocytes between acini (differentiates from normal).
  • Ductal structures (differentiates from normal).

Memory device:

• AcCC - lots of "C"s: lots of cytoplasm, carcinoid-like (stippled chromatin, granular cytoplasm).

Image

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  Acinic cell carcinoma - cytology. (WC)

Adenoid cystic carcinoma

General

• Usu. distinctive.
• May be painful due the presence of perineural invasion.

Cytology

Features:

• Solid circular islands that are well-circumscribed.
  • Classically forms cystic structures.
• Very cellular.
• Small cells - key feature.
• Nucleus - large relative to cell (high NC ratio)
  • Often oval/triangular - may be carrot-shaped.
  • +/-Nucleolus. (???)
  • Chromatin NOT stippled.
• Scant cytoplasm - key feature.

Notes:

• Memory device: AdCC = lotsa DNA in relation to cell.

Image

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  Adenoid cystic carcinoma - cytology. (WC)

Epithelial-myoepithelial carcinoma

Main article: Epithelial-myoepithelial carcinoma

Cytology

Features:

• Single cells/stripped nuclei.
• 3-dimensional clusters.
• Two cell population:
  • Dark small cells.
  • Light large cells.

Common

Squamous carcinoma

Main article: Squamous cell carcinoma

• AKA squamous cell carcinoma.

Cytopathology

Features:

• Mix of spindle cells/epithelioid cells, present in clusters, +/-small number of single cells.
• Keratinization:
  • Orange/red staining on Pap stain.
    • Poorly differentiated SCC = not orange/red.
  • "Intense" (blue) staining of cells on rapid Romanowsky + pyknotic (small shriveled) nucleus.
• "Dense" appearing cytoplasm.
  • +/-Laminae (layers)/lines in the cytoplasm.
• Nuclear features of malignancy (required for diagnosis):
  1. Irregular nuclear membrane, e.g. notches, sharp discontinuities.
  2. Nuclear hyperchromasia - "jet-black" nuclei on Pap stain key feature.
  3. Increased NC ratio.
  4. Variation of nuclear size from cell-to-cell.
  5. Granular chromatin.

Notes:

1. One should see abnormal squamous cells to call it SCC.
2. Poorly differentiated SCC may look like adenocarcinoma.

Melanoma

Main article: Malignant melanoma

Features:

• Usually mixed population of:
  • Spindle cells.
    • Often single/detacted cells.
  • Epithelioid cells - usually predominant.
    • Nucleus typically eccentric.
• Brown granular cytoplasm; usually fine granularity.
• Large red nucleoli (classic finding).
• +/-Intranuclear inclusions.
• +/-Binucleation.

Minimal (for morphologic diagnosis):

1. Nuclear features of malignancy in epithelioid cells (with an eccentric nucleus) or spindle cells.
2. Brown granular cytoplasm.

Notes:

1. IHC stains are needed in many cases (S-100, HMB-45, Melan A).
2. The classic appearance of melanoma without pigment is closest to adenocarcinoma (which may have red nucleoli, large cells, abundant cytoplasm, occasional binucleation).
   • Differentiating morphologic features: adenocarcinoma - 3-D clusters of cells, no spindle-shaped cells.

Lymph nodes

Normal lymph node

Cytology

• Mixed population of lymphoid cells.
• +/-Lymphoglandular bodies.

Image

• Lymphoglandular bodies in a DLBCL (ouhsc.edu).

Non-Hodgkin's lymphoma

• AKA lymphoma.

Cytology

Features:

• Population of monomorphous lymphoid cells - usu. ~2x the size of a RBC.
• Lymphoglandular bodies - blue-grey bodies.
  • Often about 1/2 the size of a RBC.
    • These may be seen in benign tissue.

Note:

• Small cell lymphomas cannot be diagnosed definitively from cytology.

Image

• DLBCL with lymphoglandular bodies (ouhsc.edu).

Hodgkin's lymphoma

Main article: Hodgkin lymphoma

Cytology

Features:

• Reed-Sternberg cell (diagnostic).
  • Classically binucleated.
  • Huge cell with macronucleus.
  • Each nucleus has a huge macronucleolus.
    • Macronucleolus approximately the size of a RBC.
• Commonly seen with eosinophils.

Note:

• RSCs are usually found at the edge of smears.

Images

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  HL - higher mag. (WC)

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  HL - lower mag. (WC)

www:

• HL (ouhsc.edu).

Cystic lesions of the neck

General

• One should never sign-out a cytology specimen as: "branchial cleft cyst" or "thyroglossal duct cyst".
  • The proper verbiage is "cystic squamous lesion".

DDx

Lateral:

• Branchial cleft cyst.
• Cystic hygroma.

Medial:

• Thyroglossal duct cyst.

Both:

• Epidermoid cyst.
• Cystic squamous cell carcinoma.

See also

• Cytopathology.
• Thyroid.
• Head and neck pathology.