Respiratory Tract Cytology

Specimen Collection - Catching Culprits

• Key Goal: Obtain adequate, representative cells for diagnosis.
• Methods Overview:

⭐ For suspected pulmonary TB, 3-5 consecutive early morning sputum samples are recommended for AFB smear/culture to maximize diagnostic yield.

Benign & Reactive - The Usual Suspects

• Normal Cellular Components:
  • Ciliated columnar (benign indicator), goblet (mucin), basal (reserve) cells.
  • Alveolar macrophages (dust cells, phagocytic).
• Reactive Atypia & Inflammation:
  • Inflammatory cells: Neutrophils, lymphocytes, eosinophils.
  • Epithelial changes: Nuclear enlargement, prominent nucleoli. Ciliocytophthoria.
  • Creola bodies: 3D clusters of reactive bronchial cells; benign mimic of malignancy.
• Common Infections - Key Features:
  • Aspergillus: Septate hyphae, acute (45°) angle branching.
  • Candida: Pseudohyphae, budding yeasts.
  • CMV: Large cells, "Owl's eye" basophilic intranuclear inclusions.
  • HSV: Multinucleation, nuclear molding, ground-glass chromatin (Cowdry A).

⭐ Creola bodies are benign reactive bronchial cell clusters that can significantly mimic adenocarcinoma due to their 3D structure and atypia.

Squamous Lesions - From Mild to Malignant

• Squamous Metaplasia: Benign; flat, polygonal cells, small regular nuclei, normal N/C ratio.
• Dysplasia (Squamous Intraepithelial Lesion - SIL):
  • Low-grade (LSIL): Mildly ↑N/C ratio, slight hyperchromasia, smooth nuclear outlines.
  • High-grade (HSIL): Moderately to markedly ↑N/C ratio, hyperchromasia, irregular nuclear outlines, coarse chromatin.
• Squamous Cell Carcinoma (SCC): Malignant cells, often individual or in poorly cohesive sheets.
  • Key Features: Dense, often orangeophilic/eosinophilic cytoplasm (keratinization), bizarre cell shapes (tadpole, spindle cells 📌 "Tadpoles swim in keratin seas"), hyperchromatic, irregular nuclei. Necrotic/inflammatory background common.
  • Keratinizing SCC: Obvious keratin (dense orangeophilia, pearls).
  • Non-keratinizing SCC: Less keratin, prominent nucleoli.

⭐ SCC is the most common lung cancer type linked to smoking; centrally located, often cavitates. P63 and CK5/6 are positive IHC markers for SCC (though typically for histology).

Glandular & Large Cell - Adeno & Beyond

• Adenocarcinoma (ADC):

  • Cytologic features: 3D clusters, acini, papillae; vacuolated cytoplasm; prominent nucleoli. Signet rings (rare in cytology).
  • Adenocarcinoma in situ (AIS)/Lepidic: May show bland, cohesive clusters or flat sheets.

• Large Cell Carcinoma (LCC):

  • Diagnosis of exclusion.
  • Features: Large undifferentiated cells, prominent nucleoli, moderate cytoplasm; no glandular/squamous differentiation.

⭐ TTF-1 and Napsin A are crucial immunohistochemical (IHC) markers for identifying pulmonary adenocarcinoma.

Neuroendocrine & IHC - Tiny Terrors, Tell-Tale Stains

• SCLC (Small Cell Lung Carcinoma):
  • Cells 2-3x lymphocyte size, scant cytoplasm, nuclear molding.
  • "Salt & pepper" chromatin, high N:C ratio, Azzopardi effect (DNA on vessel walls).
• Carcinoid Tumors:
  • Uniform, round/plasmacytoid cells; "salt & pepper" chromatin.
  • Less atypia/mitoses than SCLC.
• Key IHC Markers:
  • Adeno: TTF-1, Napsin A.
  • Squamous: p40, p63.
  • Neuroendocrine (SCLC, Carcinoid): Synaptophysin, Chromogranin, CD56.
• Common Lung Metastases (Key IHC):
  • Breast: GATA3; Colon: CDX2, CK20; Melanoma: S100, SOX10.

⭐ > SCLC is notorious for paraneoplastic syndromes (e.g., SIADH, Lambert-Eaton).

High‑Yield Points - ⚡ Biggest Takeaways

• Sputum cytology is best for central lung tumors; BAL for peripheral lesions and diffuse diseases.
• Charcot-Leyden crystals and Curschmann spirals are key findings in bronchial asthma.
• Ferruginous bodies (asbestos bodies) are diagnostic markers for asbestosis.
• Small cell carcinoma shows nuclear molding, salt-and-pepper chromatin, and scant cytoplasm.
• Adenocarcinoma often presents with glandular clusters, prominent nucleoli, and intracytoplasmic mucin.
• Squamous cell carcinoma is characterized by keratinization, intercellular bridges, and dense cytoplasm.