Single case of renal cell carcinoma and endocrine pancreatic head cancer occurring with von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease in which various neoplastic lesions occur in multiple organs. Reported here is a case of VHL disease with concurrent renal cell carcinoma and endocrine pancreatic cancer. The patient was a 43-year old woman. On this occasion, the patient had sought treatment from her local physician, complaining chiefly of yellowing of the skin and bulbar conjunctiva. Abdominal ultrasound and computed tomography scans revealed a mass in the right kidney and a mass in the pancreatic head. Peripheral blood genetic analysis revealed an Arg/stop heteroconjugative mutation in codon 113 in exon 1 of the VHL gene on the short arm of chromosome 3 (p25–26). After various tests were performed, the patient was diagnosed with right renal cell carcinoma, malignant tumor of the pancreatic head, and multiple pancreatic cysts accompanying von Hippel-Lindau disease. Right nephrectomy and pancreatoduodenectomy were performed. Based on the histopathological results, the patient was diagnosed with right renal cell carcinoma and highly differentiated endocrine pancreatic cancer. Immunohistologically, a large number of atypical cells were found to be positive for both anti-chromogranin and anti-synaptophysin antibodies in the endocrine tumor. Immunostaining for each type of gut hormone was also performed, but all results were negative. Based on the above findings, nonfunctioning, highly differentiating endocrine cancer was diagnosed. This is the first confirmed case of renal cell carcinoma and endocrine pancreatic cancer occurring concurrently with VHL. This is an important case, so it is presented here along with a short discussion of the literature.     

A family with von Hippel-Lindau disease revealed by pheochromocytoma.

Von Hippel-Lindau (VHL) disease is an inherited neoplastic disease characterized by a predisposition to develop retinal angiomas, central nervous system hemangioblastomas, renal cell carcinomas, pancreatic cysts and pheochromocytomas. Recently, we encountered three members of the same family who each had both VHL disease and pheochromocytoma. As in all three patients we suspected pheochromocytoma, the diagnosis of VHL disease should be considered. The possible presence of VHL disease was initially investigated in all three patients based on the presence of pheochromocytoma. A mutational analysis of the VHL gene revealed the presence of a missense mutation, consisting of a G to A transversion, at nucleotide 713 in all three patients. This germline point mutation in the VHL gene is often detected in type 2 VHL disease with pheochromocytoma. Genetic analysis seems to be useful for early detection of VHL disease, even when the formal criteria for diagnosis of this disease are lacking.     

The association of neurofibromatosis, bilateral pheochromocytoma and primary hyperparathyroidism.

Neurofibromatosis (NF) is a hereditary disease and carries increased risk of both benign and malignant tumor development. Pheochromocytoma or hyperparathyroidism have been reported to be associated with NF type 1 (NF1). However, the coexistance of pheochromocytoma and parathyroid adenoma in a patient with NF1 is very rare. We report a case of a 37-year-old male with NF1, bilateral pheochromocytoma and parathyroid adenoma. This association sould be kept in mind in patients with NF1 in initial evaluation as well as during follow-up.     

A case of primary hyperparathyroidism, primary hyperaldosteronism and Cushing's disease

The rare association of parathyroid adenoma with primary hyperaldosteronism, occurring in each of 2 patients, was recently reported from this unit. The present communication records the subsequent development, in one of these patients, of Cushing's syndrome with an anterior pituitary adenoma. Screening for other endocrine abnormalities was negative. A literature search failed to produce any other cases of the association of these three conditions in one patient.     

Pancreatic metastasis from renal cell carcinoma causing massive gastrointestinal bleeding in von Hippel-Lindau disease.

Patients with von Hippel-Lindau disease (VHLD) may develop pancreatic lesions, including cysts, serous cystadenomas and islet cell tumors. However, only a few cases of pancreatic metastasis have been reported. We present a case of VHLD with multiple pancreatic metastases from renal cell carcinoma. One of the metastases invaded the duodenum, causing massive bleeding.     

Case of von Hippel-Lindau disease diagnosed by detection of multiple pancreatic endocrine tumors and renal tumor 13 years after bilateral adrenalectomy

von Hippel-Lindau (VHL) syndrome is an inherited neoplastic syndrome caused by abnormity of the VHL gene found on the short arm of the chromosome 3. We reported a case of VHL disease diagnosed by the detection of multiple pancreatic endocrine tumors and renal tumor 13 years after bilateral adrenalectomy. A 40-year-old man presented with multiple pancreas tumors (maximum size 42 mm in diameter) detected by screening abdominal ultrasonography. A 23 mm renal tumor was detected by contrast computed tomography scan at that time. His past history included left retinal angioma (age 15) and bilateral adrenal pheochromocytoma (age 27). VHL was diagnosed by genetic testing. Endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreas tumor was performed, and tumor was diagnosed as an endocrine tumor. After diagnosis, distal pancreatectomy (body-tail) was performed. This was a didactic case indicating that we should suspect VHL syndrome based on past history and family history and follow such cases up strictly.     

A rare case of primary hyperparathyroidism with clear cell adenoma

We report a 52-year-old woman who was noted to have elevated alkaline phosphatase (ALP), hypercalcemia (Ca: 11.7 mg/dL), and intact parathyroid hormone (intact PTH: 643.1 pg/mL), and then referred to our hospital with suspected hyperparathyroidism. Ultrasound examination of the neck and magnetic resonance imaging showed a mass region in the posterior aspect of the left lobe of the thyroid, and Tl-Tc subtraction scintigraphy showed Tl uptake at the same location. Based on laboratory and imaging studies, she was diagnosed with primary hyperparathyroidism. The excised parathyroid was a large mass measuring 6.8 x 2.8 x 1.9 cm in diameter and weighing 15.4 g. It was soft, covered with a thin capsule, did not infiltrate the thyroid parenchyma, and showed no evidence of malignant process. Histopathological examination showed that it was clear cell adenoma. There was no evidence of metastasis from the parathyroid tumor in other organs. The post-operative course was excellent, and serum PTH, Ca, and ALP levels returned to normal. Among parathyroid tumors, large adenomas are commonly considered to be more likely malignant, but in this case it was benign despite measuring more than 6 cm in diameter. The histopathological type of the adenoma was clear cell adenoma, a very rare type. We report a clear cell adenoma of the parathyroid gland, which has not been described previously in Japan.     

Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.     

A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma

A 72-year-old woman with von Recklinghausen's disease was referred to our hospital because of pain and muscle weakness in her thighs. She had elevated serum values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a diagnosis of polymyositis was made. Treatment with prednisolone improved muscle strength, and laboratory values returned to normal. Computed tomography, magnetic resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left adrenal gland. Endocrinologic investigation disclosed elevation of serum and urine catecholamines. Since the blood pressure was normal, nonfunctioning pheochromocytoma was diagnosed clinically. The nonhypertensive course was attributed to reduced vascular response to noradrenaline. Serum lactate dehydrogenase. alkaline phosphatase. and asparate aminotransferase became elevated, and abdominal computed tomography showed a well-defined mass measuring 13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of elongated spindle-shaped atypical cells arranged in intersecting bundles. Immunohistochemically, the cells of this tumor were reactive for alpha-smooth muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the liver. Eight months after onset of symptom, the patient developed hepatic coma and died. The mean age at presentation with pheochromocytoma in von Recklinghausen's disease patients age is 42 years. Our patient was considerably older. To the best of our knowledge this is the first report of a patient with von Recklinghausen's disease developing polymyositis. asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to remain aware of the possibility of cancer in von Recklinghausen's disease.     

Cardiovascular disease,hypertension and renal function in primary hyperparathyroidism

OBJECTIVES: Patients with primary hyperparathyroidism run an increased risk of death in cardiovascular disease. Long ago, hypertension was found to frequently occur in these patients. The aim of this study was to compare the death risk after surgery for hyperparathyroidism of hypertensive patients with that of normotensive ones, and to investigate relations between variables of cardiovascular disease and variables of hyperparathyroidism and renal function. METHODS: A series of 845 patients with primary hyperparathyroidism and serum creatinine 相似文献   

Renal cell carcinoma in von Hippel-Lindau disease: another piece of the puzzle

The association of von Hippel-Lindau disease and renal call carcinoma is well recognized. However, the most appropriate surgical approach in patients with von Hippel-Lindau disease and renal carcinoma remains controversial. We examine this controversy and report on our experience. Our cohort consisted of 28 affected members of three von Hippel-Lindau kindreds. Screening of these individuals consisted of an abdominal ultrasound (US) in their early teens and a baseline computerized axial tomography (CT) scan in their late teens. To date, nine patients have been found to have renal cell carcinoma. In three of these patients, the surgical specimen revealed multiple small foci of "clear cells" characteristic of renal cell carcinoma that had not been detected by careful radiological assessment prior to surgery. In two patients, these lesions were located at the opposite pole from the radiologically-detected tumor. Nephron-sparing surgery, therefore, risks leaving potential tumor that may be responsible for mortality. Conversely, radical procedures condemn a patient to life-long dialysis and/or transplantation with associated risk and morbidity. The potential for the metachronous emergence of contralateral renal cell carcinoma, however, justifies efforts to preserve normal tissue in patients harboring radiologically-detected lesions; however, we need to know with some certainty the natural history of the correct management of this disorder.     

A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma

Von Hippel-Lindau (VHL) syndrome is a neoplastic syndrome caused by a mutation in the VHL gene. There is a discrepancy between the phenotypes of human VHL syndrome and VHL gene-disrupted mouse models. A heterozygous VHL gene-disrupted model (vhl +/-) developed hepatic vascular lesions; in contrast, hepatic hemangioma is a rare manifestation of human VHL syndrome. We identified a novel mutation (P154S) in the VHL gene in a Japanese family with pheochromocytoma. One of the members demonstrated hepatic hemangiomas, suggesting that there may be a relationship between the mutation of the VHL gene and hepatic vascular lesions, even in humans.     

Nephron-sparing surgery and renal transplantation in patients with renal cell carcinoma and von HippelLindau disease

Goldfarb DA (Cleveland Clinic Foundation, Cleveland, Ohio, USA). Nephron-sparing surgery and renal transplantation in patients with renal cell carcinoma and von HippelLindau disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 5637.
Renal cell carcinoma is a common manifestation of von HippelLindau disease and an important cause of mortality in these patients. A contemporary approach to the treatment of localized renal cell carcinoma is outlined based upon several recently conducted multicentre reviews. When technically feasible nephron-sparing surgery can preserve renal function without compromising long-term survival in most patients. For those who develop end-stage renal failure as a result of treatment for renal cell carcinoma, excellent results with a limited risk for development of recurrence can be obtained with renal transplantation.     

Diagnosis and management of pancreatic neuroendocrine tumor in von Hippel-Lindau disease

The pancreatic manifestations seen in patients with von Hippel-Lindau(VHL) disease are subdivided into 2 categories:pancreatic neuroendocrine tumors(NET),and cystic lesions,including simple cyst and serous cystadenoma.The VHL-associated cystic lesions are generally asymptomatic and do not require any treatment,unless they are indistinguishable from other cystic tumor types with malignant potential.Because pancreatic NET in VHL disease are non-functioning and have malignant potential,it is of clinical importance to find and diagnose these as early as possible.It will be recommended that comprehensive surveillance using dynamic computed tomography for abdominal manifestations,including pancreatic NET,should start from the age of 15 years in VHL patients.Unlike sporadic non-functioning NET without VHL disease,in which surgical resection is generally recommended,VHL patients at lower metastatic risk of pancreatic NET should be spared the risks of operative resection.     

胰腺多发转移性肾透明细胞癌1例报告

正1病例资料患者男性,57岁,因"发现胰腺占位性病变1个月"入院。既往20年前因肾癌行左肾切除术,术后病理提示透明细胞癌。入院查体:右侧腹部可见长约15 cm手术瘢痕,余无阳性体征。增强多排螺旋CT检查提示:右肾确如,胰腺形态正常,胰管未见明显扩张;胰头及胰体尾部见结节状稍低密度灶,大小约     

A case of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT)

We report a rare case of ACTH-independent macronodular adrenal hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT). A 57-year-old woman was admitted to our hospital for further examination of secondary hypertension and bilateral adrenal macrotumors. Midnight serum cortisol elevation with undetectable plasma ACTH, increased 24-hour urinary free cortisol excretion, and loss of the normal circadian rhythm in cortisol secretion established the diagnosis of Cushing's syndrome. Total resection of the enlarged left adrenal gland was performed with subsequent steroid replacement. Her general condition improved but serum calcium level increased 3 weeks after surgery. PHPT was diagnosed on the basis of endocrinological examination, although imaging studies failed to detect parathyroid lesion. In summary, we believe this to be the first report of a case of AIMAH with PHPT.