Anatomic Pathology / JUXTAGLOMERULAR CELL TUMOR

We studied 4 new cases of juxtaglomerular cell tumor and compared their morphologic and immunohistochemical features with 2 renal hemangiopericytomas and 5 cutaneous glomus tumors. The juxtaglomerular tumors were resected from 2 males and 2 females (mean age at diagnosis, 23 years). Three patients manifested with severe hypertension. Tumors ranged from 2.2 to 8.0 cm and were well circumscribed. The tumors consisted of solid sheets and nodules of variably sized tumor cells with round, oval, and spindled nuclei alternating with edematous microcystic foci. Nuclear atypia, present in all tumors, was a prominent feature in 2. Mitotic activity was not identified. All cases showed hemorrhage, numerous mast cells, and thick-walled blood vessels. Unusual features included coagulative tumor necrosis, a hemangiopericytoma-like vascular pattern, and hyalinized stroma. All tumors were immunoreactive for CD34 and actin. Ultrastructural analysis revealed the presence of rhomboid-shaped renin protogranules. Patients were treated by partial or radical nephrectomy and followed up for 14 to 48 months. There were no recurrences or metastases. The characteristic clinical and morphologic features of juxtaglomerular cell tumor permit distinction from renal hemangiopericytoma and other renal tumors. Juxtaglomerular cell tumor of the kidney is a rare renal neoplasm that was first described by Robertson et al1 in 1967. This tumor typically is found in young adults, with a peak incidence in the second and third decades.2-4 Patients have hypertension, hyperaldosteronism, and hypokalemia secondary to tumor renin secretion.5,6 In addition to the typical light microscopic findings, these tumors contain characteristic rhomboid-shaped renin protogranules that are evident by electron microscopy,7-9 and renin also has been demonstrated by immunofluorescence5,6,10-12 and immunoperoxidase methods.13-15 There have been 66 previously reported cases in the English literature, the vast majority as single case reports.1-62 Because of their rarity, the immunohistochemical profile and morphologic features of this tumor have not been clearly established. We report the clinicopathologic features of 4 cases of juxtaglomerular cell tumor of the kidney that to the best of our knowledge is the largest series of these rare tumors reported in the pathology literature. We reviewed the literature to better define the morphologic and immunohistochemical profile of juxtaglomerular cell tumor. In addition, we compared the immunophenotypic findings of juxtaglomerular cell tumor with 2 renal hemangiopericytomas and 5 cutaneous glomus tumors, both tumors that share morphologic features with juxtaglomerular cell tumor. Materials and Methods Four cases of renal juxtaglomerular cell tumor were identified in a search of the Mayo Clinic (Rochester, MN) Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2001;116:854-863 855 © American Society of Clinical Pathologists surgical pathology files (1 case) and consultation files (3 cases) for the years 1985 to 2001. Four-micrometer-thick, formalin-fixed, paraffin-embedded sections were stained with H&E for routine microscopic examination, and a mean of 3.5 slides per case (range, 2-5) were examined. Tumors were assessed for growth pattern, nuclear atypia, mitotic activity, and necrosis. Nuclear atypia was defined as greater than 3-fold variation in nuclear size. Mitotic activity was determined by counting 50 consecutive high-power fields (×400). Paraffin blocks were available for all cases for immunohistochemical study. In addition, 2 renal hemangiopericytomas and 5 cutaneous glomus tumors were selected for immunohistochemical analysis. All cases were immunostained with the following antibodies using standard avidin-biotin complex techniques: smooth muscle actin, muscle-specific actin, desmin, cytokeratins (CAM 5.2, AE1/AE3), S-100, HMB-45, CD34, CD31, c-kit, synaptophysin, chromogranin, and factor VIII–related antigen ❚Table 1❚. Slides were processed using a Biotek autostainer (Ventana Medical Systems, Tucson, AZ). Ultrastructural analysis was performed in all cases using glutaraldehyde-fixed tissues. Electron microscopy was performed on 3 cases at the Mayo Clinic and at 1 outside submitting institution. Information about clinical manifestations and follow-up was obtained by reviewing the medical records or by correspondence with outside physicians. Results