Microcitoma (Small Cell Lung Cancer)- 2° paragraph

2. PATHOLOGY and BIOLOGY

2.1 Biological data

2.1.1 Neuroendocrine phenotype
SCLC is a form of lung cancer characterised by a neuroendocrine phenotype. This is shown by the presence of neurosecretory granules in the cytoplasm which are visible ultrastructurally. These granules contain peptide hormones such as ADH, gastrin releasing peptide, neuromedin. The neural cell adhesion molecule is found on the cell surface. Other antigens on the cell surface are linked with other forms of lung cancer.

2.1.2 Chromosomal abnormality
A constant chromosomal abnormality is deletion of part of the short arm of chromosome 3 (3p21-24). Also on chromosome 17 p53 mutations are almost always present in cell lines. In tissue culture the cells grow either as tight spheres or, less commonly, as open cords of cells ("variant" appearance). In tissue culture the tumour cells show some degree of autocrine growth regulation, being stimulated by gastrin releasing peptide and blocked by its binding inhibitors such as analogues of substance P.

2.2 Histological types

2.2.1 Pathological data
The relationship to other histological types is not well understood but it seems likely that the initial cancer-inducing events occur in cells which have the capacity to differentiate into a variety of histotypes. The tumour is characterised by small round cells with nuclei staining deep blue and a small ring of cytoplasm. It is mainly a submucosal malignancy. Crush or traction artefact is often present on biopsy samples. Areas of adenocarcinomatous or squamous differentiation are occasionally present, which can lead to diagnostic errors on small samples and on cytology. A combined histology of small cell cancer and non small cell cancer is observable in approximately 2% of specimens. These patients tend to have a more favourable prognosis.

2.2.2 Pathological variant type
In 4% of cases a large cell component may be present (variant type). There is no definite evidence that the presence of a large cell component confers a worse prognosis. Some autopsy and post-chemotherapy pathological studies have suggested that large cell change is often present in drug resistant tumours.

2.2.3 ICD-O codes
Morphology codes of the ICD-O ("International Classification of Diseases for Oncology") are provided in brackets.
small cell carcinoma, NOS (M-8041/3)
small cell carcinoma, fusiform cell (M-8043/3)
oat cell carcinoma (M-8042/3)
small cell-large cell carcinoma (M-8045/3)

2.3 Accuracy and reliability of pathological diagnosis

2.3.1 Accuracy and reliability of pathological diagnosis
In the presence of a typical clinical presentation and bronchoscopy finding there is little likelihood of diagnostic confusion. Cytological accuracy is 70-80%. Diagnostic reproducibility is around 90%. Isolated metastases have to be distinguished from other small round cell tumours.

References

2.I
Abeloff MD, Eggleston JC, Mendelsohn G, et al. Changes in morphologic and biochemical characteristics of small cell carcinoma of the lung. A clinicopathologic study. Am J Med 1979; 66: 757-764.

2.II
Bepler G, Neumann K, Holle R, et al. Clinical relevance of histologic subtyping in small cell lung cancer. Cancer 1989; 64:74-79.

2.III
Brambilla E, Moro D, Gazzeri S, et al. Cytotoxic chemotherapy induces cell differentiation in small cell lung carcinoma. J Clin Oncol 1991; 9: 50-61.

2.IV
Gazdar AF. Molecular markers for the diagnosis and prognosis of lung cancer. Cancer 1992; 69: 1592-1599.

2.V
Rygaard K, Moller C, Bock E, Spang-Thomsen M. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts. Br J Cancer 1992; 65: 573-577.

2.VI
Schuller HM. Receptor-mediated mitogenic signals and lung cancer. Cancer Cells 1991; 3: 496-503.

2.VII
Souhami RL, Beverley PCL, Bobrow LG, Ledermann JA. Results of central data analysis: 2nd International Workshop on Small Cell Lung Cancer Antigens. J Natl Cancer Inst 1991; 83: 609-612.

2.VIII
Watkin SW. Temporal demographic and epidemiologic variation in histologic subtypes of lung cancer: a literature review. Lung Cancer 1989; 5:69-81

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