【Abstract】Objective To explore the diagnosis and treatment strategy of hereditary renal cancer. Methods The clinical data of 11 patients with double kidney cancer were retrospectively analyzed, 8 males and 3 females, aged 32-62 years, mean 47.5 years. 3 cases had double kidney cancer, 4 cases had multiple. 2 cases were diagnosed with VonHippel-Lindau syndrome, 6 cases were diagnosed with familial kidney cancer, and 3 cases were diagnosed with hereditary papillary kidney cancer. As a result, 10 patients underwent surgery to preserve the renal unit and or radical nephrectomy for renal cancer. 1 case was not operated. At 12-114 months follow-up, 4 cases had tumor recurrence, 1 case died of tumor metastasis, 2 cases died of other causes, and 4 cases survived tumor-free. Conclusion Hereditary renal cancer has an early age of onset, family aggregation phenomenon, and a high incidence of bilateral and multicenter tumors, and should be operated with preserved renal units as much as possible. Patients and their relatives should be followed up closely.
[Keywords] Hereditary renal cancer; vonHippel-Lindau syndrome; hereditary papillary renal cancer; Birt-Hogg-Dube syndrome; familial renal clear cell carcinoma; renal unit preserving surgery
Hereditary renal carcinoma has been reported less frequently and has certain diagnostic and therapeutic features. From January 1993 to January 2004, a total of 1025 cases of kidney cancer were admitted to our hospital, including 11 cases of hereditary kidney cancer, accounting for 1.1% of kidney cancer in the same period, as reported below.
Materials and methods
Clinical data
There were 11 cases in this group, 8 males and 3 females. The age was 32-62 years old, with an average of 47.5 years old. The clinical symptoms included: 3 cases of carnal hematuria, 3 cases of lumbar pain, 1 case of carnal hematuria with lumbar pain, 1 case of carnal hematuria with fever; 3 cases of no obvious symptoms; 4 cases of anemia, 4 cases of abnormal liver function, 3 cases of accelerated blood sedimentation. One case was diagnosed as retinal vascular reticulocytoma and later found to be left kidney cancer and multiple cysts in right kidney; one case was found to be right adrenal pheochromocytoma after laser treatment of left retinal hemangioma, and then found to be double kidney cancer during follow-up after adrenalectomy. The above two cases were diagnosed as VonHippel-Lindau syndrome, six cases were diagnosed as familial renal cancer, and three cases were diagnosed as hereditary papillary renal cancer.
All 11 cases were examined by ultrasound and CT, 8 cases by IVU, 9 cases by renal ECT, 4 cases by CT angiography and 3D reconstruction. CT examination showed isointense or hypointense, well-defined round-like masses with uniform or heterogeneous internal echogenicity, and obvious enhancement effect after enhancement. 10 tumors showed irregular areas of liquefied necrosis of different degrees in the center. The CT values of the tumors ranged from 18 to 61 HU, with a mean of 35 HU, and the enhanced CT values ranged from 35 to 86 HU, with a mean of 62 HU. The IVU and ECT examinations showed that the renal tumor was an occupying lesion, and the CT angiography and 3D reconstruction of four cases could clearly show the main trunk of the renal artery and grade 1 to 3 branches, including one case showing the collateral renal artery.
Results
Six cases of unilateral renal cancer: three cases were radical nephrectomies; three cases were partial nephrectomies, and two cases were radical nephrectomies after recurrence.
Four cases of double kidney cancer: 2 cases of simultaneous double kidney cancer underwent partial nephrectomy, and 1 case underwent radical nephrectomy after recurrence on one side; 1 case of heterochronic double kidney cancer underwent radical nephrectomy first, and the contralateral kidney cancer was found in the postoperative follow-up, and partial nephrectomy was performed, and no surgery was performed after recurrence; 1 case of radical nephrectomy for double kidney cancer was treated with long-term dialysis after surgery.
Metastasis occurred in 1 case, no kidney surgery was performed, and the metastases were pathologically confirmed as renal cancer.
Pathology: 8 cases were clear cell carcinoma; 3 cases were papillary carcinoma.
In 11 patients, the follow-up period was 12-114 months, with an average of 72.1 months. 4 cases had tumor recurrence, 1 case died of uremia, 1 case died of tumor metastasis, 1 case died of other diseases, and 4 cases survived tumor-free.
Discussion
I. Epidemiology
Hereditary renal cancer includes.
(1) vonHippel-Lindau (VHL) syndrome
(2) hereditary papillary renal carcinoma (HPRC),
(3) Birt-Hogg-Dube syndrome (BHDS)
(4) familial renal clear cell carcinoma [1]. There is a lack of exact statistics at home and abroad, and the incidence rate is estimated to be less than 3% of kidney cancer in the same period [2]. Due to the lack of knowledge of this particular type of kidney cancer, there are more domestic case reports, and in our group, hereditary kidney cancer accounts for 1.1% of kidney cancer in the same period.
VHL syndrome is a group of familial, multiple, multi-organ involved benign and malignant tumor syndromes, which is an autosomal dominant disorder caused by mutations in VHL gene, with an incidence rate of 1/58100-1/13000. [3]. 50% of patients present with renal cell carcinoma, the mean age of onset of renal cell carcinoma is 37 years (16-67 years) and 75% of patients have bilateral, multifocal lesions with a clear cell type of pathology. In our two cases of VHL syndrome, bilateral renal carcinomas accounted for 50% of the renal carcinomas in the same period and renal carcinomas accounted for 2/3 of the VHL syndrome in the same period [4]. Clinically, only 25% of the patients were able to confirm the diagnosis. The reasons for the difficulty in confirming the diagnosis may be.
(1) About 50% of patients present with only one symptom of the disease, leaving a significant number of VHL syndromes undiagnosed.
(2) Insufficient knowledge of the disease, leading to clinical underdiagnosis or misdiagnosis [4].
Hereditary papillary renal carcinoma is also an autosomal dominant disease, and mutations in the MET gene on chromosome 7 are associated with the development of this disease, with patients often presenting with bilateral, multifocal disease onset at an average age of 45 years [5]. Unlike the VHL syndrome, this disease is not associated with tumors of other systems. It is pathologically low-graded, relatively unvascularized, often with eosinophils, and has a relatively good prognosis. There were three cases of papillary renal carcinoma in our group, distributed in one family.
BHD syndrome is an autosomal dominant tumor syndrome caused by mutations in the BHD gene located on chromosome 17p11.2, and patients often present with benign skin tumors, renal tumors and spontaneous pneumothorax [6]. The pathological type of renal cell carcinoma is mostly of the suspicious cell type.PavlovichCP [7] reported 30 patients from 19 families with a total of 130 renal tumors found, with a mean of 6.5 per patient and a mean age of onset of 50.7 years. The disease is rare and no case of this disease was found in our group.
Familial renal clear cell carcinoma is clinically characterized by a tendency for familial aggregation of heredity, unlike other clinical syndromes with involvement of other organs. The age of diagnosis is relatively late, the tumors are mostly isolated, solitary lesions, and the study of related genes is currently being explored [8]. In our group, there were 6 cases, distributed in 2 families.
II. Key points of diagnosis and treatment
Hereditary renal cancer has unique epidemiological, clinical, imaging and biological features.
(1) The age of onset is early, mostly concentrated in the age group of 30-50 years, and the average age of 11 cases in this group was 47.5 years. the age of onset of kidney cancer in patients with VHL syndrome was the youngest, followed by hereditary papillary kidney cancer, BHD syndrome, and familial clear cell carcinoma.
(2) There is a family aggregation phenomenon. The possibility of hereditary renal cancer is highly suspected when someone in the family is diagnosed with hereditary renal cancer syndrome and renal cancer is found in relatives.
(3) Multi-organ involvement is more common in VHL syndrome and BHD syndrome, which often show multi-organ involvement, and those who are found to have renal occupancy with related organ lesions or previous syndrome-related organ lesions are highly likely to have hereditary renal cancer. Two patients with VHL syndrome in our group had lesions in three organs successively.
(4) In addition to familial clear cell carcinoma, bilateral and multicentric growth of tumor is more common. The incidence of bilateral and multicentric cases in this group accounts for 45.5%, while the incidence of bilateral non-hereditary renal cancer is only 2-4%. Even if a single kidney cancer is diagnosed at the time of diagnosis, its risk of developing heterochronic double kidney cancer is higher.
(5) Hereditary kidney cancer has associated genetic alterations. Clinical diagnosis can now be confirmed by genetic testing, with mutations in the VHL gene in VHL syndrome, in the MET gene in hereditary papillary renal carcinoma, and in the BHD gene in BHD syndrome [2].
Surgery is still an important treatment for hereditary renal carcinoma, and surgery to preserve the renal unit is preferred, and surgery can still be performed after recurrence [1]. If both tumors are large, radical bilateral renal cancer surgery should be used and postoperative treatment with dialysis. The reasons for preferring surgery to preserve the renal units are.
(1) Patients with family history of kidney cancer, VHL syndrome and BHD syndrome, because the risk of heterochronous bilateral kidney cancer and multiple tumors is higher, often after radical surgery for kidney cancer on one side, the tumor on the other side is found, which increases the difficulty of treatment, and at present, foreign scholars mostly advocate that even if the kidney function on the opposite side is normal, surgery to preserve the renal unit should be actively performed.
(2) Hereditary renal cancer has a low grade and slow growth [9], and most tumors are less than 3 cm in diameter. A group of studies on 96 patients with VHL syndrome and 23 patients with hereditary papillary renal cancer showed that the largest tumor diameter was less than 3 cm at diagnosis in 52 patients with VHL syndrome and 10 patients with hereditary papillary renal cancer, and no metastatic foci were found in patients with diameters less than 3 cm [ 10]. A study of 65 patients with VHL syndrome kidney cancer showed that tumor-specific survival rates of 100% and 81% at 5 and 10 years were achieved by performing kidney unit-preserving surgery [11].
There are recent foreign applications of radiofrequency and cryotherapy to treat smaller VHL and hereditary papillary renal carcinoma, which can achieve avoidance or delay of surgery.
CT angiography and 3D reconstruction techniques developed in recent years can clearly show the anatomy of intersegmental vessels, segmental localization of renal cancer, the presence of arteriovenous malformations and the relationship between the tumor and hilar vessels, collecting system and renal parenchyma, thus helping to develop a partial nephrectomy plan, which is conducive to intraoperative control of tumor vessels, avoiding damage to the collecting system of the kidney and maximizing tumor removal [12]. One case in our group showed a variant of renal vascularity.
III. Prognosis and follow-up
Although the grading of hereditary renal cancer is low, the recurrence rate of tumor is high due to the high chance of multicenter and bilateral incidence, and the recurrence rate of this group reached 36.4% (4/11), which should be followed up closely. Hereditary renal cancer is mostly one of the manifestations of genetic syndromes and has an overall poor prognosis due to multi-organ involvement.
If genetic abnormalities are confirmed in a family with a prior witness, genetic screening should be performed for relatives at risk, and those found to be carriers of mutated genes should be followed up closely, including imaging of the kidney and related organs to facilitate early detection of lesions [8]. There are still some difficulties in applying genetic screening in China, and some genetic studies of hereditary kidney cancer (familial clear cell carcinoma) are still being explored, and it is recommended that all patients with hereditary kidney cancer and their relatives should be closely followed up.