肾脏淀粉样变性的临床病理分析

目的：探讨肾脏淀粉样变性病（amyloidosis,AL）的临床病理特点、诊断及鉴别诊断。方法回顾性分析9例肾脏淀粉样变性病患者的临床表现,并对其肾活检组织进行光镜、特殊染色、免疫荧光、免疫组化及超微结构观察。同时对患者进行随访获取预后信息。结果9例肾脏淀粉样变性病患者的临床上主要表现为肾病综合征伴进行性肾功能不全并逐渐恶化。肾活检组织光镜观察,早期淀粉样变光镜表现轻微,可有系膜轻度增生或基底膜空泡变性及轻度增厚,PASM染色可见节段性睫毛状结构;后期,肾小球系膜区明显增宽、基底膜增厚,毛细血管腔闭塞,呈无细胞结节硬化状态。免疫荧光表现不一,部分病例全部阴性,部分表现免疫球蛋白及补体沿系膜区或毛细血管壁不同程度的沉积。刚果红染色呈砖红色,甲基紫染色呈紫红色。免疫组化显示,5例来源于轻链λ,1例来源于轻链κ,全阴性者有3例。电镜观察下,肾小球毛细血管基底膜部分节段无明显病变,部分节段不规则增厚,肾小球基底膜外侧和（或）内皮下可见淀粉样纤维沉积;系膜轻、中度无细胞性增生,其内可见不规则排列淀粉样纤维沉积,直径8~10 nm,无分支,僵硬,排列紊乱。足突大部分融合,肾间质纤维化,其内亦可见淀粉样纤维沉积。结论肾脏淀粉样变性多见于中老年,根据光镜的典型病理学改变,并结合刚果红和甲基紫染色,可明确诊断。电镜检查是早期诊断肾淀粉样变的重要手段。     

Perimembranous-type renal amyloidosis: a peculiar form of AL amyloidosis

Six cases of perimembranous-type renal amyloidosis were reported. This type of renal amyloidosis was characterized by amyloid deposition predominantly involving the epithelial aspect of the glomerular capillary wall. Florid spicular arrangement was another representative feature. This type of amyloid deposition was found in 8% of autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations.     

Chromophobe renal cell carcinoma: a clinicopathological study of 16 cases

Pathological characteristics, patient outcome, and preoperative examinations of 16 cases (4.1%) of chromophobe renal cell carcinoma (RCC) observed among 389 patients with RCC treated at Yokohama City University Hospital and Yokohama City University Medical Center between 1991 and 2004 were analyzed. The age distribution was 16 to 74 years old (average age; 50.9 +/- 17.0). Pathologically, 14 patients had pure chromophobe RCC, and two patients had chromophobe RCC coexisting with aggressive pathological elements, that is, sarcomatoid change in one patient and collecting duct carcinoma in the other. The average tumor size was 7.1 +/- 4.1 cm. On preoperative imaging studies with enhanced computed tomography or angiography, all cases showed a hypovascular pattern. C-reactive protein (CRP) and immunosuppressive acidic protein (IAP) were increased specifically in the two cases coexisting with aggressive pathological elements. Fourteen cases showing pure chromophobe RCC did not metastases on preoperative examination. Thirteen cases were treated by nephrectomy, and another was treated by partial nephrectomy. To date there have been no recurrences during the 6 to 160 months postoperative follow-up. The patient with a mixture of chromophobe RCC and sarcomatoid change (pT3aN0M0) died of multiple lung metastases 18 months after nephrectomy. The patient showing a mixture of chromophobe RCC and collecting duct carcinoma demonstrated metastases to the paraaortic lymph nodes at preoperative examination (pT1bN2M0), and died of multiple lung and bone metastases and carcinomatous peritonitis 8 months after nephrectomy. The patients with pure chromophobe RCC had a favorable prognosis, but those with a mixed type including aggressive elements such as sarcomatoid change or collecting duct carcinoma, showed a poor clinical course. The increase in CRP or IAP could predict poor prognosis in such cases.     

Prognosis of acute renal failure in children: a multivariate analysis

Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P <0.05) and associated with cardiac surgery (90.9%, P <0.01). Anuria (67.6% vs. 43.5%, P <0.05), need for dialysis (85.3% vs. 56.5%, P <0.05), neurological complications (50% vs. 6.3%, P <0.01), and respiratory complications (35.2% vs. 2.1%, P <0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors. Received May 2, 1995; received in revised form August 28, 1996; accepted September 13, 1996     

MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. The definition of the mutated gene has allowed molecular diagnosis of the disease. The most important complication of FMF is the development of AA type secondary amyloidosis. In a group of patients clinically designated as phenotype II amyloidosis patients, renal amyloidosis develops without being preceded by typical attacks of the disease. In this study, the mutations of the MEFV gene were analysed in a group of patients clinically recognized as phenotype II. METHODS: DNA samples were obtained from tissue samples of the subjects. PCR-RFLP methods were used to analyse the M694V, M680I, V726A and E148Q mutations that have been previously defined by us to be the most common mutations in our Turkish cohort. RESULTS: The distribution of the four most common mutations among phenotype II patients was 38% for M694V, 8% for M680I, 4% for V726A and 4% for E148Q. CONCLUSIONS: In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. We therefore suggest that secondary genetic or environmental factors are operative in the development of secondary amyloidosis in patients with FMF.     

A clinical evaluation of renal amyloidosis in the Japan renal biopsy registry: a cross-sectional study

Background and aim

The available clinical data are limited in a rare glomerular disease, renal amyloidosis. We aimed to clarify the clinical features of renal amyloidosis from database of the Japan Renal Biopsy Registry (J-RBR).

Methods

We performed a cross-sectional study with database of the J-RBR of the Japanese Society of Nephrology. We identified 281 cases of renal amyloidosis from 20,997 cases enrolled into the J-RBR from 2007 to 2014. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared among the levels of ages, amount of urine protein excretion (AUPE) or CKD G stages.

Results

The prevalence of renal amyloidosis was 1.3 % (281/20,997). DBP significantly decreased in higher age quartiles (P = 0.034). SBP and DBP did not increase in the progression of AUPE levels and CKD G stages. In multiple regression analysis, eGFR was a significant independent factor for SBP in all cases and a subgroup without hypertensive agents. There was a reverse significant relationship between SBP and eGFR.

Conclusion

Blood pressure did not significantly increase in elderly and much proteinuric condition in renal amyloidosis. The progression of CKD and decrease of eGFR did not produce the higher SBP. The mechanism underlying these results remains unclear; however, they are unique features of renal amyloidosis. The couple of hypotensive and hypertensive conditions might produce no relationship between blood pressure and CKD stages.

     

Differentiation between renal allograft rejection and cyclosporine toxicity: a clinicopathological study

The differentiation between cyclosporine nephrotoxicity (CyN) and acute rejection (AR) still remains a matter of intensive research. In a retrospective study over the last 2 years, we assessed the clinical and histopathological data of 43 episodes of renal dysfunction in 39 renal transplant recipients immunosuppressed with cyclosporine (CyA). Ten episodes (23.2%) were identified as AR and 10 (23.2%) as acute CyN; in six cases (13.9%), signs of both AR and CyN were found. Fever (80%), oliguria (50%), and edema (50%) were prominent features in AR, but not in CyN. Renal blood flow was higher in the nephrotoxicity group and for corresponding degree of renal dysfunction. Significant hyperuricemia (greater than 8 mg/dL) was a prominent finding in CyN (80%) and to a lesser extent in AR (20%). The helper to suppressor cell ratio in the peripheral blood remained stable or slightly decreased in all cases with CyN, but increased in 70% of the cases with AR. CyN was associated with significantly higher whole blood CyA levels (P less than 0.005) and there was a positive correlation between plasma creatinine and CyA levels during the nephrotoxicity episodes (P less than 0.02). Diffuse mononuclear cell infiltrate was observed in 90% of the biopsies with AR and only in 20% with CyN (P less than 0.005). Concerning the extent of the tubular lesions, no significant differences were observed between the two groups. In contrast, vascular lesions such as arterial endothelial proliferation (P less than 0.05), hyalinosis (P less than 0.05), and glomerular capillary thrombi (P less than 0.05) were more commonly seen in nephrotoxicity biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)     

SDH-deficient renal cell carcinoma: a clinicopathological analysis highlighting the role of genetic counselling

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) accounts for 0.05–2% of all RCCs. The majority of patients have germline mutations, most frequently in the SDHB gene. People with these mutations are predisposed to developing paragangliomas, phaeochromocytomas and gastrointestinal stromal tumours. Patients should be referred to genetic services for further workup and close surveillance imaging due to the risk of development of further tumours. We present a woman with SDH-deficient RCC and review the literature associated with this uncommon entity.     

Papillary renal cell carcinoma: A clinicopathological study of 35 cases

AIM: The objective of the present study was to characterize the clinicopathological features of histologically defined papillary renal cell carcinoma (RCC). METHODS: The present study included a total of 35 patients who were treated by radical surgery and subsequently diagnosed as having papillary RCC between April 1995 and June 2004. Clinicopathological data of these patients were retrospectively reviewed according to the previously reported classification system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%) and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively. Despite the lack of significant differences in clinical parameters between these two groups, including age, gender, clinical stage and metastasis, the incidence of symptomatic disease in patients with type 2 papillary RCC was significantly higher than that in those with type 1 papillary RCC. Pathological examinations demonstrated that there were no significant differences between these two groups in pathological stage, tumor grade or vascular invasion. Furthermore, there was no significant difference between these two groups in overall or recurrence-free survival. CONCLUSIONS: Although the present study included a small number of patients with short follow-up period, the clinicopathological features including prognoses were almost similar between patients with type 1 and type 2 papillary RCC; therefore, careful postoperative follow-up should be considered for patients with papillary RCC irrespective of morphological subtype.     

Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study

Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF.     

True thymic hyperplasia: a clinicopathological study

In this report, we describe the clinicopathological features of 4 patients with true thymic hyperplasia. This controversial thymic lesion has only recently been defined as a variable, often massive enlargement of the thymus characterized by a nearly normal microscopic structure. Our study of 4 patients and review of the literature indicate that true thymic hyperplasia has a well-defined clinicopathological profile: prevalence in children or young male patients, absence of associated autoimmune diseases, and often presence of respiratory distress or peripheral blood lymphocytosis, or both. True thymic hyperplasia should be considered in the differential diagnosis of anterior mediastinal masses in children and young adolescents.     

Renal neuroendocrine tumours: a clinicopathological study

OBJECTIVES: To report cases of primary neuroendocrine tumours (NETs) of the kidney, including carcinoid tumour, large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCC), which show a wide range of NE differentiation and biological behaviour, and are exceedingly rare. PATIENTS AND METHODS: The clinicopathological features of all nine renal NETs diagnosed during a 7-year period were reviewed. RESULTS: Six carcinoids, two SCC and one LCNEC were identified from 2780 kidney tumours. No patient had carcinoid syndrome or other NE symptoms. Three of six carcinoids and no SCC/LCNEC arose in horseshoe kidneys. The mean size of the six carcinoids and three SCC/LCNEC was 4.8 cm and 12.2 cm, respectively. No carcinoid had tumour necrosis or mitosis. By contrast, three SCC/LCNEC had extensive tumour necrosis and brisk mitosis. All renal NETs were positive for synaptophysin but were variably positive for chromogranin and CD56. Three of six carcinoid tumours were confined to the kidney, and four of five patients were disease-free at a mean (range) of 26 (6-74) months. One patient with nodal metastases has had no recurrence and another died with liver metastases. Three patients with SCC/LCNEC each presented with locally advanced disease and extensive lymphadenopathy; two of them died from distant metastasis or local tumour progression, and the third is currently alive with disease. CONCLUSIONS: Various NETs can occur in the kidney, but rarely. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. The diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical NE markers.     

Outcome of kidney transplantation for renal amyloidosis:a single-center experience

The aim of this retrospective study was to investigate the results of kidney transplantation in patients with renal amyloidosis. We analyzed the results of renal transplantation in 13 amyloidotic transplant recipients compared with those in a control group of 13 nonamyloidotic patients. While the etiology of amyloidosis was rheumatoid arthritis in one patient, in all of the others it was secondary to familial Mediterranean fever. Acute rejection episodes developed once in six and twice in one patient. The renal function in these patients was improved by antirejection treatment. Chronic rejection did not develop in any patient. However six patients (46%) died due to various complications despite functional grafts. The others are still being followed with well-functioning grafts. Among the control group, acute and chronic rejection were diagnosed in three and two patients, respectively: one patient returned to hemodialysis after 26 months of transplantation, while the others are still alive with functional grafts. There was no death in the control group. The 5- and 10-year actuarial patient survival rates of the amyloidosis and control groups were 52.2%, 26.6%, and 100%, 100%, respectively (P = .002). However, the graft survivals of the amyloidosis versus control groups were 100%, 100%, versus 87.5%, 87.5, respectively (P = .47). In conclusion, we observed a high rate of early mortality among recipients with amyloidosis associated with infectious complications. Moreover, patient survivals were lower among amyloidotic renal recipients.     

芬兰型肾淀粉样变性合并膜性肾病一例

本文报道1例芬兰型淀粉样变性合并膜性肾病,53岁女性,肾病综合征起病,血抗磷脂酶A2受体(PLA2R)抗体阳性,肾活检提示肾淀粉样变性合并膜性肾病,肾组织多种物质染色不能明确淀粉样变性分型,基因检测提示凝溶胶蛋白(GSN)基因c.640G>A杂合突变,最终明确为芬兰型淀粉样变性。对于分型不明的淀粉样变性,基因检测可以辅助诊断。     

男性泌尿生殖系统淋巴瘤临床病理分析

目的:探讨男性泌尿生殖系统淋巴瘤的临床病理特征和免疫表型。方法:回顾性分析35例男性泌尿生殖系统淋巴瘤的病理形态学和免疫组化标记,结合文献对其临床病理特点进行分析。结果:35例淋巴瘤患者的年龄4～83岁,平均年龄56.5岁,≥50岁者28例(80%)。发生于睾丸者最多,28例(80%),其次是前列腺3例(8.6%),精索、精囊、阴茎和附睾各1例(各2.9%)。组织学类型包括:弥漫性大B细胞淋巴瘤(DLBCL)22例(62.9%)、粘膜相关淋巴组织(MALT)淋巴瘤6例(17.1%)、Burkitt淋巴瘤4例(11.4%)、外周T细胞淋巴瘤2例(5.7%)和浆细胞瘤1例(2.9%)。结论:男性泌尿生殖系统淋巴瘤少见,多发生于中老年人,大多是B细胞淋巴瘤,以DLBCL最常见,其次是MALT淋巴瘤、Burkitt淋巴瘤,T细胞淋巴瘤和浆细胞瘤罕见,男性泌尿生殖系统淋巴瘤的确诊依赖组织病理学,免疫组化标记对明确诊断、分型和鉴别诊断具有肯定价值。     

Dense renal papillae: a quantitative study using computed tomography

The attenuation of the renal papillae has been compared with that of the cortex/outer medulla (COM) in 100 consecutive patients undergoing abdominal computed tomography (CT). In most patients (73%) there were areas within the papillae measuring more than 5 Hounsfield units (HU) higher than the COM. In 11% of the patients this increase in papillary attenuation was even more marked (15 or more HU). Increased papillary attenuation was most marked in patients with newly diagnosed widespread malignancy; it was also common in thin patients and in those who were in-patients. The region of the papilla has been shown to have a slightly higher CT attenuation than the rest of the renal parenchyma and such density seems especially noticeable in sick patients.