Table of Contents
Definition / general | Prognostic factors | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Flow cytometry description | Electron microscopy description | Differential diagnosisCite this page: Jain D. Small cell carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungtumorsmallcell.html. Accessed February 18th, 2019.
Definition / general
- Also called oat cell carcinoma
- 10-20% all of lung carcinoma, 45,000 new cases per year in US
- Usually men, median age 60 years, 99% occur in smokers, very aggressive with early mediastinal lymph node involvement
- Apparently derived from primitive cells of basal bronchial epithelium with partial differentiation towards neuroendocrine cells
- Associated with paraneoplastic syndromes due to production of ACTH (Cushing's syndrome), ADH (hyponatremia), calcitonin (hypocalcemia), gonadotropins (gynecomastia), parathyroid hormone (hyperparathyroidism), serotonin (carcinoid syndrome); also encephalomyelitis, Lambert-Eaton syndrome, sensory neuropathy
- Two subtypes: pure or combined (Mod Pathol 2012;25:S18)
- Biopsies often crushed
- Cytology may be helpful
- Diagnosis based on H&E, not the presence of neuroendocrine markers
Prognostic factors
- Poor prognostic factors: elevated serum LDH, alkaline phosphatase, albumin, hemoglobin, white blood count
Treatment
- Chemotherapy, radiation
- Cure rates of 15-25% for limited disease
- Most live 1 year
- Preoperative chemotherapy and surgery if T1-2, N0-1, M0
Gross description
- Usually central / hilar
- White-tan, soft, friable, extensive necrosis
- Peripheral nodules have fairly well-defined border and fleshy cut surface
Microscopic (histologic) description
- Sheets, ribbons, clusters, rosettes or peripheral pallisading of small to medium sized (2-4x neutrophils) round / oval cells with minimal cytoplasm, salt and pepper chromatin without prominent clumps, hyperchromatic, indistinct nucleoli, nuclear molding, smudging, frequent mitotic figures
- Azzopardi phenomena (basophilic nuclear chromatin spreading to wall of blood vessels), indistinct cell borders
- Stroma is scanty, vascular, delicate
- No glands, replacement of epithelium is less common than subepithelial growth
- Necrosis and apoptotic debris are common
- More cytoplasm is present in cells in metastases or resections than in small biopsies
- May have larger cells with similar morphology, small mixtures of squamous cell carcinoma or adenocarcinoma (Am J Surg Pathol 2002;26:1184)
- Rarely scattered giant cells, prominent nucleoli
Microscopic (histologic) images
Positive stains
- Pan-keratin (100%, dot like pattern), TTF1 (89%); also neuron specific enolase (77%), CD117 (75%, 50% after chemotherapy, Mod Pathol 2003;16:1041), chromogranin (58%, may be weak), synaptophysin (57%), calretinin (49%), thrombomodulin (27%), keratin5 (27%), CD57 / Leu7 (variable), gastrin releasing peptide, N-CAM / CD56, bcl-2 (variable)
Negative stains
- CD3, CD20, CD45, CD99 / MIC2, pancreatic polypeptide, vimentin, mesothelin, p63
Flow cytometry description
- CD56+ (neural cell adhesion molecule), CD45-, which differentiates from lymphoma (Arch Pathol Lab Med 2003;127:461)
Electron microscopy description
- Occasional round, membrane bound, dense core neurosecretory granules, 100-200 nm in diameter
- May have bundles of tonofibrils
- May form glandular spaces
Differential diagnosis
- Atypical carcinoid tumor: less nuclear atypia, < 20 mitotic figures per 10 HPF, no extensive necrosis, more intense neuroendocrine staining
- Metastatic small cell carcinoma