Canonical Nuclear Factor κB Pathway Links Tumorigenesis of Synchronous Mantle-Cell Lymphoma, Clear-Cell Renal-Cell Carcinoma, and GI Stromal Tumor
Authors: Robin Guo, Lufen Chang, Zheng Liu, Arthur X. Li, Qin Huang, David K. Ann, Hao-Chien Wang, Chung-Wu Lin, Xiwei Wu, Yate-Ching Yuan, Yun Yen
Journal: Journal of Clinical Oncology (2011)

A 74-year-old man was admitted to National Taiwan University Hospital (Taipei, Taiwan) complaining of a 1-week history of abdominal pain and night sweats.The patient had no diarrhea or vomiting, but was hypotensive.An abdominal computed tomography (CT) scan revealed hemoperitoneum and a ruptured spleen.Laboratory results revealed elevated lactate dehydrogenase (1,256 U/L), WBC of 9.28 K/L, RBC of 3.67 M/L, a hemoglobin level of 11.2 g/dL, and a platelet count of 412 K/L.The patient's prior medical history was unremarkable, but one of the patient's daughters was reported to suffer from lupus.From a clinical standpoint, a spleen rupture as a result of splenomegaly (1,260 g) indicated surgery.In the course of a laparotomy, a 0.4-cm gastric serosal tumor and a 4-cm renal tumor at the upper right pole of the kidney were revealed.Lymphadenopathies in the bilateral supraclavicular, mediastinal, and abdominal regions, as well as in the junction of the cystic duct, common bile duct, and group 13 lymph nodes were noted.Splenectomy, right partial nephrectomy, gastric biopsy, cholecystectomy, and liver biopsy were performed.After surgery, immunohistochemical analysis performed on spleen tissues showed the expression of CD5, CD20, and cyclin D1.Fluorescent in situ hybridization also detected t(11;14) translocation, which suggested mantlecell lymphoma (MCL).Samples taken from the gastric serosal tumor were diffusely positive for c-KIT staining, focally positive for S100 staining, and showed scanty mitotic activity (Ͻ 1 mitotic figure/10 high-power field), which suggested a low-grade GI stromal tumor (GIST).The resected kidney tumor showed clear cells with small nuclei and indistinct nucleoli; this finding suggested Fuhrman grade 1 clear-cell renal-cell carcinoma (ccRCC).To complete the staging work-up, bone marrow aspiration was performed and revealed involvement of the lymphoma.A positron emission tomography scan revealed diffuse multiple viable malignancies in the nasal cavity, left oropharynx, and nodes of the bilateral cervical, bilateral supraclavicular, pretracheal, anterior mediastinal, bilateral paratracheal, aortopulmonary window, bilateral hila, bilateral axilla, abdominal para-aortic, hepatic, pancreatic, iliac chain, and bilateral inguinal regions.Ann Arbor stage IV MCL was suggested.Subsequent positive CD20 and Ki67 staining and additional investigation suggested blastoid MCL.No mutation in the p53 gene was detected.After surgery, the patient underwent treatment involving a regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.Follow-up CT scans performed after the third cycle of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy revealed partial responses in the mediastinal, para-aortic, and both inguinal lymph nodes.Kidney and stomach tumors were undetectable.