Resected cytokeratin-negative small cell lung carcinoma

Small cell lung carcinoma (SCLC), a malignancy of neuroendocrine origin, can show varied morphologies and patterns but is typically positive for at least one neuroendocrine marker and almost always for cytokeratins. It is essential to distinguish this tumour due to its characteristic genetic features, aggressive behaviour, propensity for metastasis and responsiveness to chemotherapy. We hereby present a rare case of a pulmonary mass that showed morphological features of an SCLC but lacked cytokeratin expression on biopsy as well as resection specimens. Various cytokeratins were tested on multiple blocks and at different laboratories. A broad differential diagnosis was considered and ruled out including small round blue cell tumours, non-SCLC and metastasis. After performing an extensive work-up to identify the origin of this tumour, it was finally diagnosed as SCLC with expression of neuroendocrine markers synaptophysin and CD56, and intracytoplasmic electron dense neurosecretory granules (250-350 nm) however lacked cytokeratin expression.