Pulmonary cytopathology

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Pulmonary cytopathology is a subset of cytopathology.

This article deals only with pulmonary cytopathology (FNAs, sputum samples). An introduction to cytopathology is in the cytopathology article.

Normal

  • Cells with cilia = good.
  • Cells with "terminal bar" (apical red band-like region associated with cilia) = good.

Specimens

  1. Bronchial brushings.
  2. Bronchial washing (contain airway cells).
  3. Bronchoalveolar lavage (BAL).
  4. Endobronchial ultrasongraphic transbronchial needle aspiration (EBUS-TNA).

Adequacy

  • Want to see pulmonary macrophages (large cells with bubbly green/brown cytoplasm, eccentric reniform nucleus).
    • Ciliated cells may be from the nasopharynx - not proof of lung parenchymal tissue.

There is no generally accepted standard for pulmonary specimens. An in-house standard is:[1]

  • Sputum: >= 10 pulmonary macrophages.

Pulmonary hamartoma

Histology:

  • No cytologic features of malignancy.
  • Fat.

Non-specific inflammation

  • A very common finding in BALs.

Types:

  • Eosinophilia
    • If you notice eosinophils... you probably have eosinophilia.
      • One in several HPFs (40x obj. with 22 mm eye piece) is enough.
  • Acute - neutrophils.
    • ~10/HPF (40xo 22mm ep).
  • Chronic - lymphocytes + occ. plasma cells.
    • ~5 small lymphocytes/HPF (40xo 22 mm ep).
  • Mixed acute & chronic inflammation.

Infection

If you see lotsa lymphocytes think tumour.[2]

Pneumocystic carinii pneumonia (PCP)

Features:

  • Casts of frothy material/large proteinaceous debris - approximately the size of an alveolus.

Aspergillosis

Features:

  • Hyphae... branching at 45 degrees.

Image:

Zygomycosis

  • AKA mucormycosis.

Features:

  • Hyphae... with variable width.

Image:

Crytococcus

Features:

  • Prominent (i.e. thick polysaccharide) capsule.
    • Seen well on Pap stain... harder to see on rapid Romanowsky stain.
  • Spherical - 5-15 micrometres.

Image:

DDx:

  • Bastomycosis.
    • Doesn't have thick capsule
    • Has broad based budding.
  • Coccidioidomycosis - larger (20-60 micrometers).

Cancer

Approaches to lung cancer

Lung cancer in a table

Small cell carcinoma Adenocarcinoma Squamous cell carcinoma Value
Cellular cohesion Single cells/stripped nuclei common Cohesive Cohesive Cohesive (only) suggests NSCLC
Nuclear moulding Present Absent Absent R/i & r/o: small cell carcinoma and carcinoid
Small nucleoli (difficult to see on Field stain) Multiple pseudo-nucleoli may be seen in occ. cells Many be present Often present Weak discriminative valuable
Large nucleoli Never Present Rarely R/i adenocarcinoma; should prompt consideration of melanoma briefly
Location of nucleus Eccentric Eccentric Central Useful for SCC vs. adenocarcinoma
Cytoplasm Scant Abundant, bubbly Abundant, "dense" Abundant r/o small cell
Streaming Absent Absent Present - "stretched yeast dough" R/i squmaous (weak)
Keratin (difficult to see on Field stain) Absent Absent Present Present r/i squamous (strong)

Criteria list

Neuroendocrine tumours - look for:

  1. Nuclear moulding (not seen in NSCLC).
  2. Singular bare nuclei/single cells - often very abundant in small cell lung carcinoma (SCLC).
    • Size ~2X neutrophil (PMN) - SCLC is large relative to most haematologic cancers (which are approx. the size of a PMN)... small in relation to other carcinoma.[3]
  3. Stippled chromatin.
  4. Negatives: Abundant cytoplasm - virtually excludes SCLC.
  5. Carcinoid vs. atypical carcinoid vs. SCLC (list from good to bad) - degree of nuclear atypia, presence of necrosis and smoking history.
    • One should never sign-out small cell carcinoma without looking at the history.[4]

Adenocarcinoma:

  1. Nucleolus.
    • Good ones are visible with 10X objective (excludes SCLC).
    • Look for subtle large ones - at higher power.
    • Neuroendocrine tumours occasionally may appear to have nucleoli - one should see good nucleoli in 3-4 cells in one field.
  2. Abundant cytoplasm - virtually excludes small cell carcinoma.
  3. Vacuoles with mucin (pink discolouration) - virtually diagnostic, though only seen occasionally.
  4. Eccentric nucleus.
  5. Negatives: NO moulding.
    • Important if no nucleolus obvious.

Squamous cell carcinoma:

  1. Small nucleolus - not visible at 10X.
  2. Coarse chromatin.
  3. "Streaming" - think stringy yeast dough.
  4. Keratin (orange) - on Pap stain.

Adenocarcinoma

  • Most common type of lung cancer.

Cytology

Features:

  • Nucleolus.
    • Good ones are visible with 10X objective (virtually excludes SCLC).
    • Look for subtle large ones - at higher power.
  • Abundant cytoplasm - virtually excludes small cell carcinoma.
  • Vacuoles with mucin (pink discolouration) - virtually diagnostic.
  • Eccentric nucleus.
  • Negatives: NO moulding.
    • Important if no nucleolus visible.

Notes:

  • May be subtle, i.e. have minimal cytologic changes.

DDx:

  • Benign mesothelium (also sheets of cells).
  • Atypical adenomatous hyperplasia (AAH) - thought to be the precursor to adenocarcinoma.[5]
    • AAH has a size criterion, ergo not really possible to diagnose on cytopathology specimen.

Neuroendocrine tumours

  • This is a group of tumours that has benign (e.g. carcinoid tumour of the lung) to malignant (e.g. small cell lung carcinoma) behaviour.[6]

The grouping can be divided into four types:[7]

  • Small cell carcinoma.
  • Large cell neuroendocrine carcinoma.
  • Typical carcinoid.
  • Atypical carcinoid.

Cytologic features useful for differentiation:

  • Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
  • Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB-1: scant staining).
  • Atypical carcinoid: higher mitotic rate/MIB-1 than typical carcinoid,[8] no necrosis.

Notes:[7]

  • Large cell and small cell tumours behave in a similar fashion; large cell can be considered a morphological variant of small cell.
  • 9/10 of carcinoids are typical and usually have a good prognosis, i.e. do not metastasize.
    • Central location (vis-a-vis peripheral location) tends favours typical carcinoid over atypical carcinoid.

Small cell lung carcinoma

  • Is the most easy lung cancer to miss, as one is usually looking for large cells.

Histology:

  • Morphologic features of malignancy:
    • Irregular nuclear membrane.
    • Chromatin clumping.
    • Marked nuclear size variation.
  • Bare nuclei common - very useful if present.
  • Nuclear moulding - key feature.
  • Stippled chromatin - key feature.
  • Small cells ~ 2x RBC.
  • Scant cytoplasm - so scant it often near impossible to see.

Notes:

  • The Azzopardi phenomenon (smudging of nuclei) is not present on cytology specimens - it is processing artifact.
  • Small cell carcinoma should not be diagnosed without a clinical history; if there is no smoking history... think about the possibility of carcinoid and atypical carcinoid.
  • Small cell leukemias may mimic small cell carcinoma; difference: leukemias typically have smaller cells (~size of RBC vs. ~2x of RBC), and lymphoglandular bodies.

Image:

Squamous cell carcinoma

Microscopic

  • 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.[9]
  • "Dense" appearing cytoplasm.
    • +/-Laminae (layers)/lines in the cytoplasm.
  • Nuclear features of malignancy (required for diagnosis):
    • Irregular nuclear membrane, e.g. notches, sharp discontinuities.
    • Nuclear hyperchromasia - "jet-black" nuclei on Pap stain key feature.
    • Increased NC ratio.
    • Variation of nuclear size from cell-to-cell.

Image(s):

Notes:

  • One should see abnormal squamous cells to call it SCC.
    • The default diagnosis is usually adenocarcinoma.
  • Poorly differentiated SCC may look like adenocarcinoma.

Malignant melanoma

Classic features:

  1. Loosely cohesive cells and single cells.
  2. Mixure of epithelioid cells and spindle cells.
  3. Malignant cells have:
    • Prominent red nucleolus.
    • Pigmented cytoplasm - key feature (often not pigmented).
    • Pigment may only be present in macrophages
    • Occasional large binucleated cells (bug-eyed monster cell).
      • Nuclei are often at opposite poles of the cell, i.e. the nuclei are as far apart as possible ("divorce cells").[10]
    • Intranuclear inclusions.
  4. Pigmented macrophages (useful feature - but less specific for melanoma than pigment in malignant looking cells).

Notes:

  1. Large nucleolus - may Vaguely resemble adenocarcinoma.
    • Prominent red nucleolus common in: serous carcinoma.
  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.
  3. Bug-eyed monster cells - may vaguely resemble a Reed-Sternberg cell (RSC) - diagnostic of Hodgkin's lymphoma (HL).
    • RSCs do not have the granular cytoplasm typical of melanoma.
    • Nuclei usually adjacent, i.e. not at opposite poles of the cell.
    • Background of melanoma different than HL.

Images:

See also

References

  1. UHN PCY50001.08 P.11.
  2. Attributed to SM. 6 January 2010.
  3. WG. 20 January 2010.
  4. WG. 20 January 2010.
  5. Mori, M.; Rao, SK.; Popper, HH.; Cagle, PT.; Fraire, AE. (Feb 2001). "Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung.". Mod Pathol 14 (2): 72-84. doi:10.1038/modpathol.3880259. PMID 11235908. http://www.nature.com/modpathol/journal/v14/n2/full/3880259a.html.
  6. URL: http://emedicine.medscape.com/article/426400-overview. Accessed on: 20 January 2010.
  7. 7.0 7.1 http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp
  8. WG. February 2010.
  9. GS. 24 February 2010.
  10. GS. 24 February 2010.

External links