distinguishing features of small cell carcinoma

Introduction

Histological features

• scant cytoplasm
• small, hyperchromatic nuclei with fine chromatin
• indistinct nucleoli
• diffuse sheets of cells

Neuroendocrine properties

• dense core granules
• L-dopa decarboxylase activity
• chromogranin
• synaptophysin
• neuron-specific enolase
• creatine kinase BB isozyme
• CD56 & CD57 antigens

Peptide hormone production

• gastrin-releasing peptide gene products
• ACTH
• arginine vasopressin (AVP)
• calcitonin
• atrial natriuretic factor (ANF)

Other markers

• low or absent HLA & beta-2 microglobulin
• neurofilaments
• opioid receptors*
• nicotinic receptors*
• EGF receptors few or absent
• mucin is absent (present in adenocarcinoma)
• surfactant-associated proteins are absent
• carcinoembryonic antigen (CEA) is present*

Genetic aberrations:

• aberrations affecting recessive genes
  • 3p deletions* > 90% (> 80% non-small cell CA)
  • Rb mutations 90% (20% non-small cell CA)
  • MTS1 (CDKN2A) mutations 10% (> 50% non-small cell CA)
  • p53 mutations > 90% (> 50% non-small cell CA)
  • 5q, 8p, 11p & other allele losses*
  • microsatellite instability*
• aberrations affecting dominant genes
  • ras mutations < 1% (30% non-small cell CA)
  • myc family overexpression* > 50%
  • bcl-2 overexpression > 75% (> 50% non-small cell CA)
  • Her-2/neu overexpression < 10% (30% non-small cell CA)
  • telemorase overexpression* > 90%

Response to radiotherapy:

• objective shrinkage in 80-90% (30-50% non-small cell CA)
• often complete response

Response to combination chemotherapy:

• overall regression rate 90% (30-40% non-small cell CA)
• complete regression 50% (5% non-small cell CA)

* NOT a distinguishing feature

PTH-like substance produced by squamous cell carcinoma

mucin is present in adenocarcinoma

Additional terms

• small cell carcinoma