Spinal hemangioblastoma containing metastatic renal cell carcinoma in von Hippel-Lindau disease. Case report and review of the literature

The authors describe the case of a patient with von Hippel-Lindau (VHL) disease in which a spinal hemangioblastoma contained metastatic renal cell carcinoma (RCC). The literature on tumor-to-tumor metastasis associated with VHL disease of the central nervous system (CNS) is reviewed. Midthoracic back pain developed in this 43-year-old man with a left-sided radicular component 2 years after he underwent resection of a left RCC. Radiological findings demonstrated a T6-7 intradural intramedullary lesion. A T5-8 laminectomy and gross-total resection of the spinal cord mass were performed. Light and electron microscopic examination showed features of hemangioblastoma, which contained metastatic foci of RCC. Genetic analysis demonstrated the presence of a deleting mutation in the first exon (nt. 394-406) of the VHL locus, truncating 16 amino acids (N61-77) from the first beta sheet in the VHL protein. A review of the literature revealed that RCC-to-CNS hemangioblastoma is the second most common donor-recipient tumor association among the tumor-to-tumor metastases.     

Sarcomatoid renal cell carcinoma with von Hippel-Lindau disease: a case report

We report a 68-year-old woman who had bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease. Surgical resection of a central nervous system hemangioblastoma had been done previously. This time, synchronous bilateral RCCs were found in her kidneys, with metastases to lungs and liver. Right radical nephrectomy was performed to remove the primary tumor in the right kidney. Histopathological examination of the tumor revealed clear cell RCC with a sarcomatoid component. After surgery, transcatheter arterial embolization was performed for the tumor in the left kidney and interferon therapy was commenced. The left renal tumor decreased in size and interferon therapy was effective against the metastatic lung tumors. However, 4 years after resection of the right RCC, the tumor in the left kidney increased progressively in size and partial left nephrectomy was performed. Histopathological examination of the resected tumor also showed clear cell type RCC with a sarcomatoid component. The patient eventually died of her disease at 5 years after resection of the right RCC. RCC associated with VHL is usually of the clear cell type has a relatively good prognosis. Sarcomatoid RCC is rare in VHL patients and, to our knowledge, the present report is the first case of sarcomatoid RCC associated with VHL in the Japanese literature.     

A case of renal cell carcinoma associated with von Hippel-Lindau disease and the necessity for family genetic diagnosis

We report a 47-year-old man who had bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease. Surgical resection of hemangioblastomas and left nephrectomy for RCC had been done previously. This time, a small RCC was found in his right kidney and enucleation was performed to preserve renal function. His mother had retinal angioma, hemangioblastoma, and bilateral RCC. Hemangioblastoma was also found in his daughter. Genetic diagnosis was performed in his family and a germline VHL mutation was recognized. For improvement of the prognosis of VHL disease, genetic diagnosis and early clinical assessment are important.     

Bilateral renal cell carcinoma associated with von Hippel-Lindau disease

A 52-year-old man was referred to the department of neurosurgery of our hospital for evaluation of left occipital pain on September 27, 1982. Brain CT and arteriography showed midcerebellar tumor and an operation was performed on October 7, 1982. Histopathologically, the tumor was hemangioblastoma (solid type). His whole-body CT showed bilateral multiple renal tumors but no angioma retinae were found. Angiography revealed that the lesions were bilateral multiple (more than 20) renal tumors, bilateral adrenal tumors and left retroaortic renal vein. The patient underwent bilateral radical nephrectomy and lymphadenectomy on December 15, 1982. Renal cell carcinoma (grade II greater than III) with adrenal and left renal vein involvement were noted on the pathologic specimen. Postoperatively, he received supplement therapy with hydrocortisone and hemodialysis, but died of bleeding from the recurrent hemangioblastoma on July 7, 1983.     

VHL病一例报告并文献复习

目的 探讨von Hippel-Lindau(VHL)病的临床和影像学特点,提高对本病的认识.方法 VHL患者1例.患者男,50岁,因无痛性全程肉眼血尿伴视物模糊5个月入院.影像学及眼底镜检查诊断双肾多发性肿瘤,肾囊肿,胰腺囊肿,肝囊肿,右眼视网膜血管瘤.12年前有小脑血管母细胞瘤手术史,无家族史.结果 行左侧保留肾单位肿瘤切除术(肿瘤5枚),肿瘤最大约3.5cm×3.5 cm,病理报告肾多发性透明细胞癌.术后口服索尼替尼治疗.随访4个月,肾功能正常,右肾肿瘤缩小.结论 VHL病是一种家族性常染色体显性遗传性肿瘤病,病变表现为中枢神经系统血管母细胞瘤、内脏肿瘤和内脏多发囊肿等.全面的影像学检查是诊断和随访的重要手段.

Abstract：

Objective To investigate the clinical and imaging features of von Hippel-Lindau disease to raise awareness of the disease. Methods The clinical and imaging data of a case of VHL patient were analyzed retrospectively and discussed with relative literature review. The patient was a 50-year-old man, who was admitted with the chief complaints of painless gross hematuria and blurred vision for 5 months. Imaging data and ophthalmoscopy examination showed bilateral multiple renal tumors, renal cysts, pancreatic cysts, hepatic cysts and retinal angioma in his right eye. He suffered a surgical operation for his cerebellar hemangioblastoma 12 years ago without family history. Results The patient underwent nephron- sparing surgery (NSS) in the left kidney. Five renal tumors were removed, and the largest tumor was 3.5 cm× 3.5 cm. Postoperative oral administration of Sorafenib agents was applied. Followed up for 4 months, the renal function was normal and the right kidney tumor reduced. Pathology confirmed the diagnosis of multiple renal clear cell carcinoma. Conclusions VHL disease is a familial autosomal dominant hereditary syndrome, with the performance of hemangioblastorna in central nervous system, visceral tumors and multiple visceral cysts. Comprehensive imaging examination plays a major role in both the diagnosis and the follow-up of VHL disease.     

A case of von Hippel-Lindau disease associated with bilateral renal cell carcinoma

A case of von Hippel-Lindau disease associated with bilateral renal cell carcinoma is presented. A 27-year-old female noticed myodesopsia and underwent laser coagulation of right retinal hemangioma in 1973. In addition, cerebellar hemangioblastomas were removed in 1977, 1978, 1983 and 1987. The patient was referred to the department of urology for further examination of bilateral renal masses which were incidentally found on abdominal computed tomography (CT) and magnetic resonance-CT. Fine needle biopsy performed and microscopic examination revealed the presence of clear cell type renal cell carcinoma (grade 1). Renal arteriography demonstrated multiple neovascularity in the bilateral masses. Complete tumor excision was impossible to retain the minimum of renal function, the patient was conservatively subjected to a follow-up study.     

Secretory breast carcinoma--case report and review of the medical literature

Secretory breast carcinoma (SBC) is a rare type of invasive breast cancer. Since little is known about the biology of this rare tumour, it is useful to report every such case, in order to make as much information as possible available in the medical literature. We present the case of an 18-year-old woman with a SBC treated by mastectomy (Madden) and axillary node dissection (stage pT3N1M0) followed by chemotherapy (FEC regimen) and radiotherapy. The patient has meanwhile completed 4 years of follow-up with no evidence of recurrence. The authors review the literature and summarize relevant findings concerning definition, pathology, clinical picture, treatment, and follow-up.     

A case of renal cell carcinoma and bladder carcinoma associated with von Hippel-Lindau disease

A case of renal cell carcinoma and bladder carcinoma associated with von Hippel-Lindau disease is reported. A 31-year-old female was referred to the Department of Urology for further examination of right renal mass which was incidentally found on abdominal computed tomography (CT). The patient was operated on spinal hemangioma in May 19 and July 8, 1975, on cerebellar hemangioblastoma in July, 1976 and June 10, 1981 and on cerebellar cyst in June 20, 1988. Angiography revealed three hypervascular renal tumors in the right kidney. Cystoscopy revealed a papillary bladder tumor (TCC Grade 1). Transurethral resection of bladder carcinoma was performed on July 28, 1988. Right radical nephrectomy and lymphadenectomy were performed on August 2, 1988. Histopathologically, the tumor was renal cell carcinoma of clear cell type (Grade 1). Postoperative course was uneventful and the residual kidney is being followed up in the outpatient clinic.     

von Hippel-Lindau病肾癌的自然病程研究

目的 探讨von Hippel-Lindau(VHL)病肾癌的自然病程. 方法 初诊后未立即手术的VHL病肾癌患者11例,男5例,女6例,平均年龄45岁.共32个肿瘤,肿瘤直径平均2.5(0.5～6.2)cm.采用积极监测策略对其进行临床管理.对患者临床资料、随访结果及肿瘤生长速度进行分析. 结果 中位随访时间70(32～258)个月.双肾实性占位6例;行手术治疗8例,包括保留肾单位手术7次,根治性肾切除6次;肿瘤复发4例.死于肿瘤转移2例,死于非肿瘤因素1例.32个肿瘤中位随访时间51(19～106)个月.肿瘤平均生长速度0.55 cm/年;直径＞3 cm、≤3 cm肿瘤生长速度分别为0.55、0.44 cm/年,差异无统计学意义(P=0.40).肿瘤生长快3个(1.13～1.75cm/年),肿瘤生长慢29个(0.17～0.88 cm/年).肿瘤进展转移2例.随访结束时,肿瘤＞3 cm者27个(84%),直径≤4 cm肿瘤未发现转移.结论 多数VHL病肾癌生长缓慢,不发生转移;肿瘤直径≤4 cm者很少转移;对≤4 cm VHL病肾癌采用积极监测策略可行.     

von Hippel-Lindau病肾癌的诊治特点分析

目的 总结yon Hippel-Lindau(VHL)病肾癌的诊治经验. 方法 VHL肾癌患者28例.男16例,女12例.平均年龄45岁.双肾癌15例(同时11例、异时4例),单侧肾癌13例.行VHL基因检测25例.行保留肾单位手术或肾癌根治术24例,观察等待2例,保守治疗2例.结果 25例受检者均有VHL基因胚系突变,其中无症状患者14例.9例患者中有29个实性肿瘤曾被观察,平均44(12～86)个月,肿瘤平均生长速度0.531 cm/年;观察结束时,19个(65.5%)肿瘤生长>3 cm,仅1个肿瘤转移.24例手术切除实性肿瘤87个,其中肿瘤剜除术62个(71.3%)、肾下极切除1个、根治性肾切除术24个.术后病理报告24例均为肾透明细胞癌.TNM分期T1a8例、T1b7例、T2 8例、T3 1例.肿瘤86个,Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个,钙化结节1个.28例患者平均随访50(5～237)个月,存活26例,死亡2例,肿瘤局部复发4例. 结论 基因检测可早期发现无症状VHL患者;VHL病肾癌多生长缓慢,>3 cm的肿瘤多数不发生转移,可随访观察;保留肾单位手术是治疗VHL病肾癌安全有效的方法.     

Von Hippel—Lindau病肾癌的临床特征分析

目的 探讨Von Hippel-Lindau（VHL）病肾癌的临床特点。方法回顾分析28例VHL病肾癌患者的临床资料。就初诊年龄、肿瘤部位、同时或异时癌、肿瘤的组织病理等与散发性肾癌进行比较。结果VHL肾癌初诊年龄44．6岁，双肾癌15例、多灶性肾癌16例、伴双侧多发肾囊肿20例。共切除87个实性肿瘤。术后病理：透明细胞癌86个，Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个；钙化结节1个。TNM分期ⅠA期、ⅠB期、Ⅱ期、Ⅲ期分别为8例、7例、8例和1例。与散发性肾癌组相比，VHL病肾癌组患者发病年龄早（P〈0．05），双肾多灶性肾癌及伴双侧多发肾囊肿比例高（P〈O．001），高级别肿瘤比例低（P〈O．05）。结论VHL病肾癌不同于散发性肾癌，有其独特的临床病理特征，这对该病诊断治疗具有一定指导价值。     

Bilateral pheochromocytomas and asynchronous bilateral renal cell carcinomas associated with von Hippel-Lindau disease: a case report

A 38-year-old man who had been followed with diagnosis of dilated cardiomyopathy and retinal angioma was referred to our hospital because of incidentally detected bilateral adrenal masses. Although he was normotensive, levels of catecholamine in urine were elevated and I131-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Screening of central nervous system by MRI revealed cerebellar hemangioblastoma. Right adrenalectomy and left partial adrenalectomy were performed, both of which tumors pathologically diagnosed as pheochromocytoma, followed by resection of the cerebellar hemangioblastoma. Five months later, abdominal CT revealed a left renal tumor and underwent left partial nephrectomy, being diagnosed as renal cell carcinoma. A right renal tumor was detected on follow up CT at 1 year after the partial nephrectomy. Since cardiac function was deteriorated, we have followed with careful observation. This is the second documented case of bilateral renal cell carcinomas and bilateral pheochromocytomas with VHL in Japan.     

Report of aggressive renal cell carcinoma in two patients with von Hippel-Lindau disease

Renal cell carcinoma is relatively common in patients with von Hippel-Lindau disease, yet characteristically follows a less aggressive course compared with sporadic renal cell carcinoma. We report on 2 patients with von Hippel-Lindau disease and atypically aggressive renal tumors. In these patients, more rigorous screening guidelines may help to identify the more aggressive variants.     

Juvenile renal cell carcinoma as first manifestation of von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome characterized by germline mutations in the VHL tumor suppressor gene located at chromosome 3p25-26 and pleomorphic clinical picture. The major clinical manifestations include retinal angiomas, central nervous system hemangioblastomas, pheopleochromocytoma, pancreatic cysts, epididymal cystoadenomas and renal lesions. Recently, we observed a 58-year-old male patient with macrohematuria and a history of nephrectomy due to renal cell carcinoma (RCC). The patient showed retinal angiomatosis, cerebellar hemangioblastomas, multiple pancreatic cysts, right kidney with polycystic features plus two RCC. The patient's offspring, two females and one male, showed VHL lesions, such as retinal angiomatosis, cerebellar hemangioblastomas and polycystic kidney disease (PKD). The affected family members were screened for mutations in the VHL gene. Data suggested the presence of a deletion encompassing exon 1 of the VHL gene. Early diagnosis of VHL disease in patients and their relatives is important for clinical and geneticreasons. VHL disease patients have an increased incidence of malignant carcinomas and the syndrome can mimic the presentation of other cystic kidney diseases. Early diagnosis and molecular genetic testing of family members is essential to improve the clinical management of patients and to allow an accurate risk assessment in asymptomatic individuals. In conclusion, nephrologists and urologists must carefully evaluate patients with PKD and RCC to confirm or exclude VHL disease, and physicians must play a crucial role in the clinical process of therapeutical decisions and choices for VHL patients.     

Von Hippel-Lindau病并发肾癌的诊断和治疗

目的 提高von Hippel-Lindau病(VHL)并发肾癌的诊断和治疗水平。方法 回顾分析7例VHL病并发肾癌患者临床资料并结合文献复习讨论。男4例，女3例，平均年龄42岁。手术治疗6例，共切除肿瘤34个，其中5个肾脏行肿瘤切除术，切除肿瘤13个；切除肾脏4个，发现肿瘤21个。结果 随访8-76个月，平均45个月。1例术后26个月肾脏肿瘤复发，行肾脏切除。1例双肾切除者，半年后行肾移植，随访18个月未见肿瘤复发，移植肾功能良好。4例患者肿瘤无复发和转移，肾功能正常。1例患者拒绝治疗，随访25个月肿瘤局部有进展，未发现远处转移。结论 肾癌是VHL病主要病变之一，具有多中心、双侧发病、易复发等特点。薄层CT是主要的诊断和随访手段。手术治疗方式包括双肾切除，肾肿瘤剜除和肾部分切除等，保留肾单位术后应密切随访，及时发现再发的病变。     

Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study: case report and review of the literature

BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare.CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs.CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.     

A forme fruste of von Hippel-Lindau disease: a combination of adrenal pheochromocytoma and ipsilateral renal cell carcinoma--a case report

A patient with the combination of pheochromocytoma and renal cell carcinoma is reported, matching a forme fruste of von Hippel-Lindau disease. A review of the literature on this combination is given and a possible relation between the overlap syndrome, von Hippel-Lindau disease and the combination pheochromocytoma-renal cell carcinoma, is discussed.     

Percutaneous renal cryoablation of renal tumors in patients with von Hippel-Lindau disease

PURPOSE: We determine the feasibility and safety of performing percutaneous cryoablation of renal tumors in patients with von Hippel-Lindau disease. MATERIALS AND METHODS: We selected 2 men and 2 women with von Hippel-Lindau disease and radiographic determined solid renal tumors were selected to undergo percutaneous cryoablation. All patients underwent standard preoperative evaluation. An interventional magnetic resonance imaging unit was used for probe guidance and ice ball monitoring. The cryoablation procedure was performed with a 2 or 3 mm. cryoprobe using a pressurized argon gas system for ice ball formation. The patients were hospitalized overnight for observation and discharged home the following day. A followup computerized tomogram or magnetic resonance imaging scan was performed at 1 week, 1, 3, 6 and 12 months and every 6 months thereafter, along with physical examination, urinalysis, serum blood urea nitrogen and creatinine. RESULTS: A total of 5 tumors were treated ranging from 2.8 to 5.0 cm. in diameter. All patients underwent the procedure without difficulty with 2 requiring re-treatment due to residual tumor for a total of 7 treatments. At followup from 2 to 23 months there has been no radiographic evidence of recurrence at the cryoablated areas. CONCLUSIONS: Percutaneous cryoablation of renal tumors in patients with von Hippel-Lindau disease proved to be successful in this initial series. Although 2 patients had residual tumor after the initial cryoablation procedure re-treatment was performed with no adverse sequela. This minimally invasive therapy may allow patients with von Hippel-Lindau disease to avoid the necessity of multiple open surgical procedures.     

Bilateral renal cell carcinoma associated with polycystic kidney disease: case report and literature review

A 56-year-old Japanese man consulted a urologist because of urethral bleeding. He had been undergoing hemodialysis for the past 15 years due to polycystic kidney disease. Computed tomography revealed an irregular cyst wall in the left kidney. Since a neoplasm could not be ruled out, we removed the left kidney, by laparoscopic radical nephrectomy after obtaining the patient's consent. Histopathologic diagnosis was renal cell carcinoma. Fourteen months after the operation, urethral bleeding recurred. Further examination of the bladder and the urethra revealed no significant abnormalities. The patient insisted on right nephrectomy. Therefore, laparoscopic radical nephrectomy was performed. Histopathologic diagnosis was also renal cell carcinoma. Renal cell carcinoma in patients with end-stage renal disease is fairly common and is associated with acquired cystic kidney disease. However, renal cell carcinoma associated with polycystic kidney disease is extremely rare.