Multidisciplinary approach in diagnosis of lung carcinoma

Kontic M., Stojsic J., Kacar-Kukric V., Jekic B., Bunjevacki V.

Summary. Aim: To employ multidisciplinary approach in order to make the correct diagnosis of lung carcinoma clinically and morphologically mimicking lymphoma. Methods: Immunostaining was performed by incubating tissue sections with appropriate antibodies, using the streptavidin-biotin technique. Antigen-antibody complexes were visualized with 3-amino-9-ethylcarbasole or diaminobenzidine hydrochloride substrate solution. We have investigated p53 gene mutations by polymerase chain reaction and DNA sequence analysis of exons 5, 6, 7, 8 and 9. Results: Tumor cells expressed cytokeratin AE1/AE3, epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF-1) without thyreoglobulin positivity. Further, tumor cells expressed neuroendocrine mar kers: synaptophysin, chromogranin A, neuron-specific enolase (NSE), CD56/NCAM, CD57/Leu-7 and protein gene product 9.5 (PGP9.5). P53 was also expressed. Diffuse large cell lymphomas of B and T cell origin were excluded. Direct sequencing analysis of exon 6 of the p53 gene revealed ATC to ACC mutation at codon 195. Final diagnosis of large cell lung neuroendocrine carcinoma (LCNEC) was established. Conclusions: Morphological pattern of tumor complied with large cell non-Hodgkin’s lymphoma, but large cell lung carcinoma with neuroendocrine differentiation was proved immunohistochemically and confirmed by genetic analysis of p53 mutations in tumor tissue sample. Multidisciplinary approach in diagnosis of lung carcinoma is useful for its final diagnosis.

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