陳昱光¹、張延驊^1,2,3、林登龍^1,2,3

¹台北榮民總醫院泌尿部；²國立陽明大學醫學院泌尿學科；³書田泌尿科學研究中心

Yu-Kuang Chen¹, Yen-Hwa Chang^1,2,3, Alex T.L. Lin^1,2,3

¹Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.

²School of Medicine and ³Shu-Tien Urological Institute, National Yang-Ming University, Taipei, Taiwan.

 

 

Subunits of SWI/SNF (switch/sucrose nonfermentable) complex have been recognized as tumor suppressors in malignancies recently, approximately 20% of human cancers are related to their genomic alterations. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1, abbreviated as SMARCB1, encoding INI-1 (integrase interactor 1), is located on chromosome 22q11.2. Rhabdoid tumors in children with SMARCB1 loss was the first SWI/SNF genomic alteration noted in cancer. Other SMARCB1 loss induced tumors such as epithelioid sarcoma, renal medullary carcinoma and sinonasal carcinoma were also reported.

A 45-year-old woman with peptic ulcer history under proton-pump inhibitors (PPI), denied family history of cancer. She initially presented with right flank soreness and radiation to lower back for several months. Abdominal CT scan revealed irregular infiltrative lesion about 5 cm at left kidney lower pole, with extensive para-aortic and aorto-caval lymphadenopathy. Image-guided biopsy for left kidney tumor reported SMARCB1 (INI-1)-deficient carcinoma. Chest CT further disclosed lymphadenopathy over bilateral lower neck and right upper paratrachea, whole body bone scan (WBBS) showed suspected bone metastasis to L-5, left iliac bone and right acetabulum. Left radical nephrectomy was performed on Jan 15^th, 2018. We also consulted hematologist for Hemoglobin electrophoresis, replying no hemoglobin S (Hb S). Blood smear reported no suspicious clues such as sickle cells or Howell-Joly bodies of red blood cell (RBC). The permanent pathology reported tumor stains focally positive for GATA3 while negative for INI-1, OCT3/4, PAX8, and CD138. Therefore, she was diagnosed as SMARCB1 (INI-1)-deficient urothelial carcinoma, high grade, with two para-aortic lymph node metastases, pT3N2, cM1. Adjuvant therapy with 3 courses pembrolizumab 100 mg, 1 course cisplatin and gemcitabine, as well as salvage radiotherapy to L5 spine, left iliac, right acetabulum metastasis and para-aortic lymphadenopathy were administered. Unfortunately, lower back pain radiation to right leg with numbness and coldness developed gradually after last immunotherapy on Mar 13^th, 2018. Spine MRI showed S2-4 spine metastasis with Right side root epidural compression, neurosurgeon has been consulted and surgical intervention is under discussion.

Complete SMARCB1 loss urothelium carcinoma is a novel and rare subgroup of urinary system cancer, which seems to occur in younger patient and have female predominance. The differential diagnosis includes renal medullary carcinoma (occurs nearly 75% on the right side and in patient with sickle cell hemoglobulinopathy), unclassified renal cell carcinoma with renal medullary phenotype (always PAX8 and mostly OCT3/4 stain positive) and renal rhabdoid tumor (almost occurs in infancy), were all less likely the diagnosis. Wilson et al has reported inhibition of EZH2 (enhancer of zeste homolog 2) prevents tumor formation in SMARCB1-deficient cells, and EZH2 inhibitor related clinical trials are undergoing.