The American Journal of Surgical Pathology 24(8): 1097–1104, 2000 © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Primary Synovial Sarcoma of the Kidney Duck-Hwan Kim, M.D., Jin H. Sohn, M.D., Min C. Lee, M.D., Gilho Lee, M.D., Ghil-Suk Yoon, M.D., Hiroshi Hashimoto, M.D., Hiroshi Sonobe, M.D., and Jae Y. Ro, M.D. The authors present two cases of primary synovial sarcoma cytoma, hemangiopericytoma, osteosarcoma, rhabdo- of the kidney. Both patients had a mass in the upper part of myosarcoma, angiosarcoma, and malignant peripheral the right kidney without any primary extrarenal neoplastic le- nerve sheath tumor have been reported in this site. Fre- sions. Grossly, the tumors were soft to rubbery masses mea- suring 5.5 cm and 5 cm in diameter, respectively. Histologi- quently, the diagnosis of primary sarcoma of the kidney cally, both tumors were poorly differentiated synovial sarcoma. is difficult because sarcomatoid renal cell carcinomas The lesions exhibited a hypercellular solid or lobular growth of and primary retroperitoneal soft-tissue sarcomas with round, oval, or short spindle cells in variably solid sheets, in secondary renal invasion may mimic the primary renal intersecting fascicles, or in a haphazard fashion. Areas of solid sarcoma. To make a diagnosis of primary renal sarcoma, aggregation or fascicles of the tumor cells alternating with hypocellular myxoid tissues, together with areas displaying a the possibility of sarcomatoid renal cell carcinoma and prominent hemangiopericytoma-like pattern, were found. Im- primary retroperitoneal sarcoma as well as metastatic munohistochemically, vimentin was diffusely positive and a sarcoma to the kidney should be excluded. few tumor cells were positive for cytokeratin, epithelial mem- Synovial sarcoma is the fourth most common type of brane antigen, and neurofilament. The tumor cells were nega- soft-tissue sarcoma, and it occurs primarily in the ex- tive for S-100 protein, CD34, smooth muscle actin, and desmin, 10 whereas CD56 and CD99 were positive. In both cases, reverse tremities in young adults. Synovial sarcoma has been transcription–polymerase chain reaction using ribonucleic acid reported in a variety of unusual locations in which there extracted from formalin-fixed, paraffin-embedded tissues de- is no synovial structure, such as the head and neck,10 tected SYT-SSX2 fusion gene transcripts, which are character- third ventricle of the brain,25 peripheral nerve,35 heart,32 istic molecular findings of synovial sarcoma. One patient died pericardium,1 pleura,16,31 lung,20,22,44 intravascular 10 months after diagnosis. These tumors are unique cases of 29,36 43 12 primary synovial sarcoma of the kidney confirmed by molecu- space, mediastinum, abdominal wall, peritoneal 23 37 33 21 lar study. cavity, retroperitoneum, vulva, and prostate. Re- Key Words: Synovial sarcoma—Kidney—SYT-SSX— cently, three cases of primary synovial sarcoma of the RT-PCR. kidney, among seven cases of which previous diagnosis was embryonal renal sarcoma, were described in abstract Am J Surg Pathol 24(8): 1097–1104, 2000. form, and they were confirmed by the presence of SYT-SSX fusion transcripts or cytogenetic study.11 A reciprocal translocation, t(X;18)(p11.2;q11.2), has Primary sarcoma of the kidney is a rare neoplasm. The been shown to be specific for synovial sarcoma.6 Five most common renal sarcomas are leiomyosarcoma, lipo- variants of the SSX gene (SSX1, SSX2, SSX3, SSX4, sarcoma, and fibrosarcoma.30 Malignant fibrous histio- and SSX5) have been identified,18 but only SSX1 and SSX2 have been shown to fuse with the SYT gene in the 6,8 From the Department of Pathology (D.H.K., J.H.S.), Hallym translocation t(X;18) in synovial sarcoma. University College of Medicine, Seoul, Korea; the Departments of We describe two cases of primary renal synovial sar- Pathology (M.C.L.) and Urology (G.L.), Dankook University Hospital, coma, for which diagnosis was facilitated by detection of Cheonan, Korea; the Department of Pathology (G.S.Y., J.Y.R.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, SYT-SSX fusion transcripts using reverse transcription– Korea; the Department of Pathology and Oncology (H.H.), School of polymerase chain reaction (RT-PCR) analysis. Medicine, University of Occupational and Environmental Health, Kitakushu, Japan; and the Department of Pathology (H.S.), Kochi CLINICAL HISTORY Medical School, Japan. Address correspondence and reprint requests to Duck-Hwan Kim, Patient No. 1 MD, Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445 Gil-dong, Kangdong-gu, A 53-year-old man presented with a 10-day history of Seoul 134-701, Korea; e-mail: [email protected] right flank pain in February 1999. Physical examination 1097 1098 D.-H. KIM ET AL. was remarkable for right costovertebral angle tenderness. routine histopathologic processing and immunohisto- Abdominal computed tomography (CT) revealed a large, chemical study. Histologic sections 5 ␮m in thickness heterogeneous mass that arose in the anterosuperior side were prepared and stained with hematoxylin and eosin. of the right kidney, measured 5.5 cm in greatest dimen- Immunohistochemical stains were performed according sion, and was surrounded by subcapsular hematoma (Fig. to the labeled streptavidin–biotin complex method with 1). Radiologically, the mass was considered consistent primary antisera against pancytokeratin (CK; monoclo- with renal cell carcinoma. No local invasion or lymph- nal, 1:50; Dako, Glostrup, Denmark), high-molecular adenopathy was identified. The patient underwent a right weight cytokeratin (monoclonal, 1:50; Dako), low- radical nephrectomy without complication. He refused molecular weight cytokeratin (LMWCK; monoclonal, systemic chemotherapy and had an uneventful recovery 1:50; Dako), vimentin (monoclonal, 1:200, Dako), epi- during 6 months of follow up, after which he was lost to thelial membrane antigen (EMA; monoclonal, 1:200; follow up. Dako), CD34 (monoclonal, 1:50; Immunotech, Marseille, France), CD56 (monoclonal, 1:50; Zymed, Patient No. 2 San Francisco, CA, USA), CD99 (monoclonal, 1:50; A 47-year-old man presented with a 3-week history of Dako), neurofilament (NF; monoclonal, 1:50; Dako), gross hematuria and right flank pain in June 1997. On S-100 protein (monoclonal, 1:100; Dako), desmin physical examination, tenderness of the right costoverte- (mono-clonal, 1:50; Dako), smooth muscle actin (mono- bral angle was detected. Abdominal CT revealed a large, clonal,1:200; Dako), chromogranin (monoclonal, 1:200; heterogeneous mass that arose from the superolateral Dako), and synaptophysin (monoclonal, 1:80; Dako). side of the right kidney, measured 5 cm in greatest di- Diaminobenzidine was used as a chromogen. mension, and exhibited subcapsular hematoma and vena For the molecular analysis, to detect the SYT-SSX cava thrombosis. A right radical nephrectomy was per- fusion gene transcript characteristic of synovial sarcoma, formed with vena cava thrombectomy under the impres- RT-PCR analysis using ribonucleic acid (RNA) ex- sion of renal cell carcinoma. The hospital course of this tracted from the formalin-fixed, paraffin-embedded tis- patient was uneventful. He visited the urologic depart- sue of each patient was performed as described previ- 39 For positive control, two cases of conventional ment because of respiratory difficulty and hemoptysis 5 ously. soft-tissue synovial sarcoma, in which the existence of months after the nephrectomy. He showed multiple me- SYT-SSX1 and SYT-SSX2 were already confirmed, tastases to both lungs and received systemic chemo- were examined. For negative control, two cases of ma- therapy. The systemic disease progressed and the patient lignant peripheral nerve sheath tumor were examined.39 died 10 months after nephrectomy. Briefly, five 5-␮m-thick sections sliced from paraffin blocks were prepared from each representative tumor MATERIALS AND METHODS sample. To avoid cross-contamination of samples, the The material obtained at surgery from the two patients area of microtome around the blade was cleaned with was fixed in 10% formalin and embedded in paraffin for 70% ethanol before cutting each paraffin block. An ali- quot of the extracted RNA was reverse transcribed into complementary deoxyribonucleic acid (cDNA) using 1 ␮L of random primers and 200 U of reverse transcriptase (SuperScript II, Gibco BRL, Gaithersburg, MD, USA). PCR was performed using the primer set, which was designed to amplify both the junctional regions of the SYT-SSX1 and SYT-SSX2 gene transcripts reported previously.39 The primer sets used were as follows. The SYT-SSX consensus primer set, which amplifies a 98-base pair (bp) fragment of SYT-SSX messenger RNA (mRNA), is forward primer (FP) (SYT) 5Ј- CCAGCAGAGGCCTTATGGATA-3Ј and reverse primer (RP) (SSX) 5Ј-TTTGTGGGCCAGATGCTTC- 3Ј. The SYT-SSX1 primer set is FP (SYT) 5Ј- CCAGC- AGAGGCCTTATGGATA-3Ј and RP (SSX) 5Ј-GTGC- AGTTGTTTCCCATCG-3Ј, and the SYT-SSX2 primer set is FP (SYT) 5Ј-CCAGCAGAGGCCTTATGGATA- FIG. 1. An abdominal computed tomographic scan of pa- Ј Ј Ј tient no. 1 reveals a heterogeneous mass (arrows) in the 3 and RP (SSX) 5 -GCACAGCTCTTTCCCATCA-3 . anterior portion of the kidney with bulging into the anterior These primer sets similarly amplify a 118-bp fragment of perirenal space. Subcapsular hematoma is also noted. each fusion gene mRNA. PCR for ubiquitously ex- Am J Surg Pathol, Vol. 24, No. 8, 2000 SYNOVIAL SARCOMA OF KIDNEY 1099 The gross specimen from patient no. 2 consisted of kidney with a tumor on the superolateral portion. The tumor was an ill-defined, yellow-tan, soft-to-rubbery mass measuring 5 × 4 × 4 cm (Fig. 2). The tumor ex- hibited infiltrative growth with invasion into calices and peripelvic adipose tissue. Focal necrosis and hemorrhage were present in the tumor. A subcapsular hematoma around the tumor was demonstrated. There was tumor thrombus in the wall of the inferior vena cava and renal vein. Both tumors had a solid growth pattern with no obvi- ous epithelial components, despite extensive sampling.