1. Diagnostic Challenge Pathology for Neurosurgery & Neurology Residents Department of Pathology University of Oklahoma Health Sciences Center, Oklahoma City, OK, U.S.A. Case 15 History: The patient was a 65 year-old man who was admitted to the hospital with a lung mass. Further evaluation demonstrated also a solitary brain mass. Attempt to biopsy the lung mass was not successful. The brain mass was excised and submitted for pathologic examination. The followings are representative images. Contributor: Kar-Ming Fung, M.D., Ph.D., karming-fung@ouhsc.edu Last updataded: 3/6/2009karming-fung@ouhsc.edu

2. AB Cytologic Preparation

3.  CD Permanent Section

4. Cytokeratin 7Synaptophysin EF Other results: Thyroid transcription factor-1 (TTF-1) and cytokeratin 20 are both negative, mucicarmine stain is negative.

5. What is your diagnosis?

6. Diagnosis: Metastatic neuroendocrine carcinoma of uncertain origin. Discussion: This tumor has large atypical cells and is well demarcated from the adjacent brain. The tumor cells have well defined cytoplasmic membrane and moderate amount of cytoplasm. These features are most consistent with a metastatic neoplasm with metastatic carcinoma or malignant melanoma as the prime suspect. There is a lack of large nucleoli, pseudonuclear inclusions or melanin pigment to suggest metastatic metastatic melanoma. The negative mucicarmine stain does not support the possibility of an adenocarcinoma although it does not entirely rule out the possibility of an adenocarcinoma carcinoma. With synaptophysin (+), cytokeratin 20 (+), cytokeratin 7 (-), small cell carcinoma should be suspected. There are, however, features that are not characteristic for a small cell carcinoma and they are discussed on the next slide.

7. The tumor cells have a moderate amount of cytoplasm which is not a feature of small cell carcinoma (black arrow). The tumor cells have an organoid arrangement (white arrow) which a feature more characteristic of a carcinoma or neuroendocrine carcinoma rather than a small cell carcinoma. Small cell carcinoma is generally regarded as the poorly differentiated version of neuroendocrine carcinoma and does not have organoid arrangement. This tumor is CK7 (+) and CK20 (-) which is compatible with pulmonary origin, it is completely negative for TTF-1 which is often, but not always, positive in small cell carcinoma or lung origin. With all the features considered, the current pathologic findings are not classic for a metastatic small cell carcinoma of lung origin but the features do not entirely rule out this possibility. The lung mass can be a primary tumor but can also be a metastasis.