Cellular Classification of Small Cell Lung Cancer

Before initiating treatment of a patient with small cell lung cancer (SCLC), an experienced lung cancer pathologist should review the pathologic material.

Pathologic Classification

The current classification of subtypes of SCLC includes the following:[1]

• Small cell carcinoma.
• Combined small cell carcinoma (i.e., SCLC combined with neoplastic squamous and/or glandular components).

SCLC arising from neuroendocrine cells forms one extreme of the spectrum of neuroendocrine carcinomas of the lung.

Neuroendocrine tumors include the following:

• Low-grade typical carcinoid.
• Intermediate-grade atypical carcinoid.
• High-grade neuroendocrine tumors including large-cell neuroendocrine carcinoma (LCNEC) and SCLC.

Because of differences in clinical behavior, therapy, and epidemiology, these tumors are classified separately in the World Health Organization (WHO) revised classification. The variant form of SCLC called mixed small cell/large cell carcinoma was not retained in the revised WHO classification. Instead, SCLC is now described with only one variant, SCLC combined, when at least 10% of the tumor bulk is made of an associated non-small cell component.

SCLC presents as a proliferation of small cells with the following morphological features:[2]

• Scant cytoplasm.
• Ill-defined borders.
• Finely granular "salt and pepper" chromatin.
• Absent or inconspicuous nucleoli.
• Frequent nuclear molding.
• A high mitotic count.

Combined small cell carcinoma includes a mixture of small cell and large cell or any other non-small cell component. Any cases showing at least 10% of SCLC are diagnosed as combined SCLC, and SCLC is limited to tumors with pure SCLC histology. SCLC associated with LCNEC is diagnosed as SCLC combined with LCNEC.

Nearly all SCLC are immunoreactive for keratin, thyroid transcription factor 1, and epithelial membrane antigen. Neuroendocrine and neural differentiation result in the expression of dopa decarboxylase, calcitonin, neuron-specific enolase, chromogranin A, CD56 (also known as nucleosomal histone kinase 1 or neural-cell adhesion molecule), gastrin-releasing peptide, and insulin-like growth factor 1. One or more markers of neuroendocrine differentiation can be found in approximately 75% of SCLC.[3]

Although preinvasive and in situ malignant changes are frequently found in patients with non-small cell lung cancer, these findings are rare in patients with SCLC.[4]

References:

1. Travis WD, Colby TV, Corrin B, et al.: Histological typing of lung and pleural tumours. 3rd ed. Berlin: Springer-Verlag, 1999.
2. Brambilla E, Travis WD, Colby TV, et al.: The new World Health Organization classification of lung tumours. Eur Respir J 18 (6): 1059-68, 2001.
3. Guinee DG Jr, Fishback NF, Koss MN, et al.: The spectrum of immunohistochemical staining of small-cell lung carcinoma in specimens from transbronchial and open-lung biopsies. Am J Clin Pathol 102 (4): 406-14, 1994.
4. Kumar V, Abbas A, Fausto N, eds.: Robins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia, Pa: Elsevier Inc, 2005.