Schwannomas of the kidney are rare, with only a few reported cases. We report three additional cases with immunohistochemical analysis. All three tumors were from females (aged 27, 35, and 59 years) and ranged from 4.8 to 8 cm in diameter. All of the patients underwent nephrectomy. The tumors were totally or partially encapsulated; two were in the hilum and one was centered in the renal cortex. All tumors were diffusely positive for S100 protein. Two were positive for neuron-specific enolase. Immunostaining for neurofilament, HMB45, microphthalmia transcription factor, smooth muscle actin, CD34, cytokeratin AE1/3, cytokeratin 7, and CD10 were negative. Follow-up data were available for two patients; neither had tumor recurrence or metastasis. In conclusion, renal schwannoma is rare, usually arises centrally, impinging on the hilum or the pelvis, and is cured by resection. Sarcomatoid carcinoma and other spindle cell tumors should be considered in the differential diagnosis.
Schwannomas are uncommon tumors that originate from the neural sheath and are most common in the head and neck, extremities, and posterior mediastinum. Although 3% of schwannomas occur in the retroperitoneum, involvement of visceral organs is extremely uncommon.1 Schwannomas are rare in the kidneys, and only 19 cases have been reported.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 We report herein the clinicopathologic features of three additional cases of renal schwannoma.
Materials and methods
Clinical findings, operative data, and patient follow-up were obtained from medical records. Immunohistochemical preparations were performed on formalin-fixed, paraffin-embedded tissue in all cases. The antibodies, clones, dilutions, antigen retrieval methods, and vendors are listed in Table 1. Appropriate positive and negative controls for each antibody were run concurrently.
Clinical findings are summarized in Table 2. The patients were all women and were 27, 35, and 59 years old. None showed any sign of neurofibromatosis type 1. Clinical presentations included abdominal pain and nausea in one case; the other two patients were asymptomatic. Imaging revealed a renal mass suspicious for renal cell carcinoma in each case. Subsequently, two patients underwent radical nephrectomy and one had a laparoscopic nephrectomy. Short-term (4 and 8 months) follow-up data were available from two patients. Both were alive without recurrence or metastasis.
Macroscopically, case 1 showed a 4.8 × 4.2 × 4.2 cm well-circumscribed lobulated nodular lesion located in the hilum, compressing the renal pelvis, and distorting the surrounding vasculature. Its cut surface was gray–tan to yellow and fibrotic. Case 2 showed an 8.5 × 5.5 × 5 cm well-circumscribed, red–brown fibrous mass centered in the renal cortex in the middle and lower pole of the kidney. Its cut surface appeared myxomatous and fibrous. Case 3 showed a 7 × 4.8 × 4 cm multicystic, encapsulated, focally gelatinous-appearing mass involving the hilum of the kidney.
Histologically, all three tumors were encapsulated and showed characteristic features of schwannoma. In cases 1 and 3, the tumor was composed mainly of spindle cells with a loose textured pattern (Antoni B) and with microcyst formation, and some cellular areas with Verocay bodies (Antoni A). In case 2, the tumor showed extensive hyaline change in a predominantly Antoni B pattern composed of pleomorphic cells with smudged-appearing chromatin, consistent with degenerative changes. Vascular sclerosis, hemorrhage, and hemosiderin deposits were observed in case 3. Isolated or scattered nuclear atypia was present in cases 2 and 3. Rare mitotic figures were detected in case 1. Necrosis was not observed (Figure 1).
In each tumor, the neoplastic cells showed strong and diffuse immunoreactivity for S100 protein. Neuron-specific enolase was expressed in about 90% of the cells in cases 2 and 3 and in 10% of the cells in case 1. CD34 was expressed only in the endothelial cells. All other immunohistochemical reactions (neurofilament protein, cytokeratins (CK7 and AE 1/3), HMB45, microphthalmia transcription factor, smooth muscle actin, and CD10) were negative.
Schwannomas consist of a nearly pure population of cells showing schwannian differentiation, and arise eccentrically from the surface of their nerve of origin. The main nerves of the kidney consist of sympathetic and parasympathetic fibers that accompany the renal artery entering in the renal hilum. This could explain the more frequent location of schwannomas at the renal hilum. Schwannoma rarely arises from the kidneys with only 19 cases reported (Table 2).2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Clinical presentations include abdominal or flank pain (12 cases),2, 4, 5, 6, 8, 10, 11, 13 microhematuria (2 cases),3, 15 or fever (4 cases).4, 6, 10, 11 Sometimes patients are asymptomatic and the finding is incidental.2, 12, 14, 16 No patient has been reported to show any sign of neurofibromatosis type 1. All patients are adults and the mean age at diagnosis is 51 years (range, 18–84 years). The male-to-female ratio is 1:1.2. The mass is often located centrally in the kidney, impinging on the hilum and renal pelvis. Less commonly, the tumors appear to arise from the renal cortex or capsule. Two previously reported cases (9%) were diagnosed as ‘malignant schwannomas’ and those patients died with metastases 3 and 15 months after the diagnosis.9, 11 These cases probably represent malignant peripheral nerve sheath tumor since rarely does malignancy truly arise in a benign schwannoma.
The histologic appearance of schwannoma of the kidney is similar to that seen in other organs and includes the range of different morphologic patterns described in schwannomas. The classic schwannoma is characterized by a mixture of Antoni A and Antoni B patterns as seen in cases 1 and 3.17 Microcystic degeneration with hemorrhage and hemosiderin deposits associated with cells showing bizarre hyperchromatic nuclei are common degenerative features of large schwannomas usually seen in retroperitoneum.18 The tumor in case 2 showed the features of the so-called ancient schwannoma. Ancient schwannomas are not considered as a distinct subtype of schwannoma, but rather long-standing tumors with degenerative nuclear and architectural changes. They do not seem to differ clinically from conventional schwannomas.19 Cellular schwannoma is exclusively composed of spindle cells in the Antoni A pattern without Verocay bodies,17, 20 a pattern described in four of the reported renal schwannomas.2, 8
Differential diagnostic considerations include low-grade malignant peripheral nerve sheath tumor, renal angiomyolipoma, sarcomatoid carcinoma, synovial sarcoma, solitary fibrous tumor, leiomyoma, low-grade leiomyosarcoma, rhabdomyosarcoma, and angiosarcoma. The distinctive clinical, histologic, and immunohistochemical findings usually permit a definitive diagnosis.
S100 protein family is the largest subgroup of the EF-hand proteins, which consists of several members that display amino-acid sequence homology ranging from 25 to 65%. S100 protein has been studied in the spectrum of epithelial tumors of the kidney and has been proposed to be a useful tool in the differential diagnosis among renal cell neoplasms, particularly in the differential diagnosis of chromophobe renal cell carcinoma vs renal oncocytoma.20 Among renal tumors, S100 protein is expressed in oncocytoma, papillary renal cell carcinoma, and clear cell renal cell carcinoma, whereas they are negative in chromophobe renal cell carcinoma.20 In the current study, all three cases of renal schwannoma were positive for S100 protein.
Schwannomas rarely undergo malignant change, most often in the form of either malignant peripheral nerve sheath tumor or angiosarcoma.21, 22, 23 Malignant peripheral nerve sheath tumor is occasionally composed of epithelioid cells with vesicular nuclei and prominent nucleoli.24 Angiosarcoma is typically immunoreactive for endothelial markers, such as CD34.22 The presence of nuclear atypia or diffuse hypercellularity in a schwannoma may lead to an erroneous diagnosis of malignancy. It is critical to distinguish schwannoma of atypical or cellular type from malignant peripheral nerve sheath tumor. Unlike malignant peripheral nerve sheath tumors, schwannomas with degenerative nuclear atypia lack mitotic figures. Their large cells with pleomorphic nuclei and smudged chromatin are reminiscent of those seen in ancient schwannoma. Cellular schwannoma is distinguished from malignant peripheral nerve sheath tumor by the smaller cell size, infrequent mitotic figures and lack of significant cytologic atypia, nuclear pleomorphism, and necrosis. In the absence of definite cellular crowding, nuclear enlargement (≥3 times the size of ordinary schwannoma nuclei) and hyperchromasia, the finding of rare mitotic figures in a cellular schwannoma is not sufficient for a diagnosis of malignancy.
In summary, schwannoma rarely arises from the kidney, is usually located in the renal hilum or pelvis, and clinically behave in a benign fashion.
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