ALK-rearranged renal cell carcinoma (ALK-RCC): Evaluation of histomorphological and immunohistochemical features by analysis of 276 renal cell carcinoma cases in Turkey.

Anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) is characterized by ALK fusion at chromosome 2p23. It has recently been included as a recognized entity with the 5th edition of the WHO classification urinary and male genital tumor. However, our knowledge about ALK-RCC is limited due to the small number of reported cases. In our study, we aimed to contribute the histomorphological and immunohistochemical features of ALK-rearranged renal cell carcinoma cases. We reviewed 276 cases diagnosed as RCC in order to detect ALKRCCs.We used immunohistochemistry to screen ALK rearrangement and then confirmed the ALK rearrangement by fluorescence in situ hybridization (FISH) method. ALK was immunohistochemically positive in 8 of 276 cases. ALK rearrangement was detected by FISH in 3 of 8 cases. These cases were previously diagnosed as clear cell renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (ChRCC). Their histomorphological findings were diverse, and all three cases exhibited different immunohistochemical findings. Survival of these patients ranged between 6 and 24 months. ALK immunohistochemical findings were also different in each case as perinuclear, weak cytoplasmic, and membranous.ALK RCCs appear to be very rare tumors with heterogeneous histomorphological and immunohistochemical features. Although immunohistochemistry may be useful to detect ALK positivity, genetic evaluation is required to confirm the diagnosis. With identifying ALK-RCCs, ALK inhibitors, which are currently used in the treatment of lung adenocarcinomas, can be used as a targeted therapy option in ALK-RCCs.

A Signet Ring Cell Carcinoma Presented as Refractory Acquired Thrombotic Thrombocytopenic Purpura.

Microangiopathic hemolytic anemia (MAHA) can be observed as a paraneoplastic syndrome (PS) in certain tumors. MAHA-related signet ring cell carcinoma (SRCC) of an unknown origin is very infrequent. Herein we present a SRCC case presented with refractory acquired thrombotic thrombocytopenic purpura (TTP). A 35-year-old man applied to the emergency service with fatigue and headache. His laboratory tests resulted as white blood cell 9,020/µL, hemoglobin 3.5 g/dL, platelet 18,000/µL. Schistocytes, micro-spherocytes, and thrombocytopenia were observed in his blood smear. MAHA was present and he was considered as having TTP. Plasma exchange treatment was initiated; however, he was refractory to this treatment. Thorax and abdomen computerized tomography revealed thickening of minor curvature in stomach corpus with hepatogastric and paraceliac lymphadenopathy. Bone marrow (BM) investigation by our clinic resulted as the metastasis of adenocarcinoma. Ulceration and necrosis were observed by gastric endoscopy procedure. Biopsy was taken during endoscopic intervention, which resulted as SRCC. MAHA may be seen as a PS in some tumors, especially gastric cancers. Tumor-related MAHA is generally accompanied by BM metastases. As a result, BM investigation may be used as the main diagnostic method to find the underlying cancer. The clinical course of cases with tumor-related MAHA is usually poor, and these cases are usually refractory to plasma exchange treatment. In conclusion, physicians should suspect a malignancy and BM involvement when faced with a case of refractory TTP.