Familial papillary carcinoma of the thyroid

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.     

Deletion mapping of 18q in conventional renal cell carcinoma

Loss of heterozygosity (LOH) is frequently associated with the inactivation of tumor suppressor genes. 18q LOH has been frequently reported in colorectal cancer and lung cancer; however, allelic loss on 18q has not been investigated in renal cell carcinoma (RCC). We evaluated LOH on 18q using nine microsatellite markers in 126 with conventional RCC (cRCC). LOH was observed in more than one 18q microsatellite locus in 24 cRCC (19%). We found the highest frequency of LOH (13.5%) at 18q21.3, where the DCC gene is located. We also assessed the relationship between LOH frequency and patient clinical parameters. Patients with a family history of cancer had a significantly higher frequency of 18q LOH than those without such a history (P=0.0017). No associations were found with other parameters, including gender, tumor grade, tumor stage, smoking status, and body mass index. The results suggest that inactivation of tumor suppressor genes at 18q21.3, including DCC and SMAD4 as candidates, may be involved in the tumorigenesis of some conventional RCCs.     

Topographical and histological presentation of mammographic pathology in breast cancer.

Between 1979 and 1985 surgical resections from 680 cases of primary breast cancer were examined histologically. The patients were divided into four groups: (i) patients aged between 45 and 69 years who had been screened (n = 316); (ii) those younger than 45 who had not been screened (n = 55); (iii) those aged between 45 and 69 who had not been screened (n = 104); and (iv) those older than 69 who had not been screened (n = 205). The material was compared in terms of the association between in situ and invasive carcinoma. There was a low incidence of lobular carcinoma in situ (LCIS) in all groups and a high incidence of ductal carcinoma in situ (DCIS) which declined with age. Ninety nine group i patients had in situ carcinoma or early invasive carcinoma (less than 1 cm in diameter) compared with 19 of group iii cases. Screened patients had fewer multicentric cancers and a lower incidence of large invasive cancer compared with unscreened patients. Group ii patients had a higher incidence of whole quadrant in situ carcinoma, multiple cancer, and lymph node metastases. Group iv patients had a lower incidence of in situ cancer, and more low grade cancer than the other groups. Cases were divided into four types on the basis of this analysis.     

Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and renal cell cancer. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. A Finnish family with nine closely related women with uterine leiomyomas was detected by an alert gynecologist. No cutaneous or renal cell tumors were reported in the family when it was referred to genetic analyses. Samples were available from seven patients, and a novel germline FH mutation was detected in five of them. Mutation carriers were symptomatic, had multiple tumors and were diagnosed at an early age. This study emphasizes the importance of considering FH mutation screening when gynecologists encounter families with multiple severe uterine leiomyoma cases. Due to possibility of phenocopies more than one patient should be tested. Early mutation detection allows regular screening of the mutation carriers and enables early detection of possible highly aggressive renal tumors. It may also affect family planning as multiple myomas at early age may significantly reduce fertility.     

Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and this pattern of genetic abnormality is not present in renal oncocytoma.

That chromophobe renal cell carcinoma has an uncommon eosinophilic variant has been recognized for more than a decade. In sections stained with hematoxylin and eosin, the eosinophilic variant of chromophobe renal cell carcinoma and renal oncocytoma are similar in appearance. While it is well established that chromophobe renal cell carcinoma and renal oncocytoma have different patterns of genetic anomalies, little is known of the genetics of the eosinophilic variant of chromophobe renal cell carcinoma. This study was undertaken to elucidate the genetic lesions of eosinophilic chromophobe renal cell carcinoma and to compare them with those found in classic chromophobe renal cell carcinoma and in renal oncocytoma. A total of 29 renal neoplasms--nine eosinophilic chromophobe renal cell carcinomas, 10 classic chromophobe renal cell carcinomas, and 10 oncocytomas--were investigated by fluorescence in situ hybridization on 5 microm paraffin-embedded tissue sections with centromeric probes for chromosomes 1, 2, 6, 10, and 17. Signals were counted in 100-200 neoplastic nuclei from each tumor. Chromophobe renal cell carcinomas frequently showed loss of chromosomes 1 (70% of classic, 67% of eosinophilic), 2 (90% classic, 56% eosinophilic), 6 (80% classic, 56% eosinophilic), 10 (60% classic, 44% eosinophilic), and 17 (90% classic, 78% eosinophilic); Among the classic chromophobe renal cell carcinomas, only one had no loss of any of the chromosomes, while 50% had loss of all five chromosomes. Among the eosinophilic chromophobe renal cell carcinomas, one of nine had no loss and 44% had loss of all five chromosomes. One oncocytoma had loss of chromosome 1. No other chromosomal loss was detected in the oncocytomas. In conclusion, losses of chromosomes 1, 2, 6, 10, and 17 are frequent in both eosinophilic and classic chromophobe renal cell carcinomas. Loss of chromosome 1 occurs occasionally in oncocytoma but losses of chromosomes 2, 6, 10, and 17 are not found in oncocytomas. When the differential diagnostic problem is oncocytoma vs eosinophilic chromophobe renal cell carcinoma, detection of losses of chromosomes 2, 6, 10, or 17 effectively excludes the diagnosis of oncocytoma and supports the diagnosis of chromophobe renal cell carcinoma.     

Long-term follow-up after partial removal of a solitary kidney

BACKGROUND. The removal of more than one kidney in animals leads to proteinuria and progressive renal failure due to focal segmental glomerulosclerosis. This injury may be the result of chronic glomerular hyperfiltration. The purpose of this study was to determine the effect of a reduction in renal mass of more than 50 percent on residual renal function and morphology in humans. METHODS. We evaluated long-term renal function in 14 patients with a solitary kidney who had undergone partial nephrectomy for renal-cell or transitional-cell carcinoma. In 12, the first kidney had been removed 2 months to 21 years previously for the same type of cancer; in 2, the other kidney was congenitally atrophic. Before surgery, no patient had clinical or histopathological evidence of primary renal disease. All 14 patients underwent partial nephrectomy to remove a localized tumor, with 25 to 75 percent of the solitary kidney being excised. They were evaluated 5 to 17 years after surgery (mean, 7.7). RESULTS. Twelve patients had stable postoperative renal function, and end-stage renal failure developed in two. There were no changes in blood pressure in any patient during follow-up. Nine patients had proteinuria, which was mild (0.15 to 0.8 g of urinary protein per day) in five. The extent of proteinuria was inversely correlated with the amount of remaining renal tissue (P = 0.0065) and directly correlated with the duration of follow-up (P = 0.0005). Four patients with moderate-to-severe proteinuria had renal biopsies, which revealed focal segmental glomerulosclerosis in three patients and global glomerulosclerosis in one. CONCLUSIONS. Long-term renal function remains stable in most patients with a reduction in renal mass of more than 50 percent. These patients are, however, at increased risk for proteinuria, glomerulopathy, and progressive renal failure.     

CHARACTERIZATION OF RENAL ANGIOMYOLIPOMA BY SCANNING ACOUSTIC MICROSCOPY

A scanning acoustic microscope system was used to differentiate renal angiomyolipoma from renal cell carcinoma. The ultrasonic frequency used ranged from 100 to 200 MHz, and the attenuation constant and sound speed were measured on a two-dimensional distribution. The sound speed was significantly lower for lipoma cells than for vessels, smooth muscle fibres, clear cell renal cancer or granular cell renal cancer. The attenuation constant was significantly lower for lipoma cells than for vessels or clear cells. Both acoustic parameters for smooth muscle fibres were significantly lower than for vessels. The heterogeneity of the microacoustic field in renal angiomyolipoma is closely related to the high intensity echo observed on clinical echography. Renal angiomyolipoma and renal cell carcinoma can thus be distinguished by acoustic examination. © 1997 by John Wiley & Sons, Ltd.     

Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma

The high‐throughput method using microarray is an easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. We identified two genes (HOXA5 and MSH2) with β‐value differences of more than 0.3 between cancer and normal tissues. The high methylation group in HOXA5 had high Fuhrman's nuclear grade (P= 0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P > 0.05). Survival curve of the high methylation group in HOXA5 was slightly lower than that of the low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P > 0.05). We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.     

Serum concentrations of immunoglobulins E and G and α2-macroglobulin in childhood renal disease

Serum concentrations of IgE, IgG, and α₂-macroglobulin (α₂M) were determined in 67 children with renal disease and in appropriate controls. IgE concentrations were significantly elevated in patients with renal disease and proteinuria, including those with minimal change nephrotic syndrome (MCNS). IgG concentrations were lower and α₂M concentrations higher in patients with proteinuria than in patients without proteinuria. In 16 patients with nephrotic syndrome who had a decrease in proteinuria with therapy, there was a concomitant decrease in mean serum IgE level. All nine with MCNS had a decrease in serum IgE following therapy whereas eight of the nine had a concomitant increase in serum IgG. The findings suggest the possibility that IgE may play an etiologic role in the proteinuria of childhood nephrotic syndrome, and that both elevated serum IgE and proteinuria may represent unusual responses to antigens that are seldom identified. Elevations of IgE secondary to lowered IgG or to entirely nonspecific alterations in IgE metabolism in proteinuric renal disease are other possibilities. Further studies to elucidate the role of IgE in renal disease, including the nature of the altered metabolism of this immunoglobulin, are warranted.     

Relation between skin cancer and HLA antigens in renal-transplant recipients

BACKGROUND. Recipients of renal allografts are at an increased risk for skin cancer. It is also known that recipients who are homozygous for HLA antigens are at an increased risk for certain cancers, as are those who are mismatched with their donors for these antigens. In a case-control study we assessed the relation between skin cancer in renal-transplant recipients and HLA homozygosity and mismatching. METHODS. Of 764 patients who received renal transplants between 1966 and 1988, 66 had squamous-cell carcinoma or basal-cell carcinoma of the skin after transplantation. HLA homozygosity was assessed in all 66 recipients, and HLA mismatching in 39; the results were compared with those in 124 recipients without skin cancer. We also investigated the relation between skin cancer and the use of immunosuppressive drugs. In separate case-control analyses we investigated the influence of exposure to the sun and keratotic skin lesions on the risk of skin cancer. RESULTS. The risk of squamous-cell carcinoma was increased in recipients mismatched for HLA-B antigens; the relative risks were 2.6 (95 percent confidence interval, 1.1 to 6.5) and 5.0 (95 percent confidence interval, 1.3 to 19.0) with mismatching for one and two antigens, respectively, as compared with no mismatching. Mismatching for HLA-A or HLA-DR antigens had no effect on the risk of squamous-cell carcinoma, and there was no association between mismatches at any of the HLA loci and the occurrence of basal-cell carcinoma. The total doses of azathioprine and prednisone were not associated with the occurrence of skin cancer or with HLA matching. Exposure to sunlight and keratotic skin lesions were strongly associated with skin cancer but not with HLA mismatching. Homozygosity for HLA-DR was more frequent among the patients with squamous-cell carcinoma (relative risk, 2.5; 95 percent confidence interval, 0.95 to 4.6) and among patients with 100 or more keratotic skin lesions (relative risk, 4.8; 95 percent confidence interval, 1.5 to 15.1). CONCLUSIONS. HLA-B mismatching is significantly associated with the risk of squamous-cell carcinoma in renal-transplant recipients, as is HLA-DR homozygosity. An indirect effect on the level of immunosuppression does not appear to explain these findings, nor does exposure to sunlight or the number of keratotic skin lesions account for this observation.     

Preferential involvement of chromosome 1q in a primary breast carcinoma

The cytogenetic findings by G- and C-banding in a primary breast carcinoma are reported. The tumor is characterized by a high modal number of chromosomes (79) and 14 markers of ten different origins. Chromosome #1 is more frequently involved in structural and numerical aberrations than is any other chromosome; nine copies of 1q were present in each cell examined. This observation supports the hypothesis that duplication of chromosome 1q may play an important role in the progression of malignant tumors.     

Incidental renal neoplasms: is there a need for routine screening? A Danish single‐center epidemiological study

On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty‐nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients. In the incidental group, the size (p < 0.05), pathological stage (p < 0.001), Fuhrman grading (p < 0.0001) and Leibovich score (p < 0.0001) were lower than in those causing symptoms. Significantly less in the incidental group had metastasis at follow‐up (p < 0.0001). Incidentally discovered RCC constitute a major part of kidney tumors. They have a more favorable prognosis than symptomatic tumors and seem to be discovered in an earlier phase. Needle core biopsy is an accurate technique for distinguishing between malignant and benign tumors and is recommendable for smaller incidental tumors. Screening may help detect RCC at an earlier stage.     

Cytogenetic analysis of 62 transitional cell bladder carcinomas

Chromosome analysis of biopsy material obtained after vinblastine pretreatment was carried out in 108 specimens from 89 patients with transitional cell carcinoma of the urinary bladder. Analyzable metaphases were obtained in 62 tumors, but only in nine tumors could karyotypes be analyzed by banding; a conventional technique was used in all others. Ploidy and occurrence of markers corresponded with tumor morphology and invasion and sometimes aided in the clinical evaluation; chromosome anomalies specific for bladder cancer were not revealed. In noninvasive tumors of WHO grade 1 and 2, near-diploid karyotypes with occasional marker chromosomes dominated. Grade 3 tumors showed a variety of grossly aneuploid karyotypes, with an almost constant occurrence of different markers. Superficially invasive G2 tumors had moderately pronounced aberrations with more deviations than noninvasive tumors but without the great variety of G3 tumors.     

182例肺癌病人癌症家族史的分析

本文调查了182例肺癌病人及200例非肿瘤病人及200例非肿瘤病人（对照组）的癌症家庭史，分析结果：①肺癌组家庭患癌率为19.2%，其中直系亲属占94%，对照组家庭患癌率为20%，其中直系亲属占85%，肺癌组直系亲属患癌比例大于对照组，提示：肺癌的发病与遗传因素可能有相关性。②将三种不同组织类型肺癌病人的家庭患癌率作了比较，小细胞肺癌（Sclc）组最高为26.6%，其次是腺癌21%，鳞癌最低为10%，提示Sclc很可能与癌遗传因素有关。     

Collecting duct meningeal carcinomatosis.

Collecting duct carcinoma (CDC) is an aggressive primary renal neoplasm that represents a distinct subtype of renal cell carcinoma. Histochemical (eg, mucicarmine) and immunohistochemical (eg, Ulex europaeus) studies, taken in concert with the gross and histologic findings, allow differentiation of CDC from the conventional varieties of renal cell carcinoma in most cases. Collecting duct carcinoma generally pursues a more aggressive course than conventional renal cell carcinoma. Metastases to regional lymph nodes, bone, adrenal glands, lung, and skin have been reported in CDC. We describe the case of a 26-year-old man who presented with a clinical and radiologic impression of multifocal meningioma. Biopsies of the meninges and extracranial soft tissues revealed metastatic adenocarcinoma; subsequent studies suggested metastatic CDC. Ultrasound-guided biopsy was performed on a subsequently identified renal mass, which showed features consistent with CDC. To our knowledge, this is the first reported case of meningeal carcinomatosis due to CDC. The diagnostic features of this tumor are discussed.     

Resection of pancreatic metastasis from renal cell carcinoma and an early gastric cancer.

An 81-year-old woman, who had undergone left radical nephrectomy for renal cell carcinoma 17 years previously, was found to have a mass approximately 5cm in diameter in the body of the pancreas and an early gastric cancer. The patient was suspected of having pancreatic metastasis from renal cell carcinoma and an early gastric cancer and underwent distal pancreatectomy, splenectomy, and distal gastrectomy. Histologic examination showed that the pancreatic tumor was a clear cell renal cell carcinoma that had metastasized to the body of the pancreas and that the gastric cancer was a well-differentiated adenocarcinoma that had invaded the mucosa. Twenty months after the operation, the patient was well, without any evidence of recurrence. Renal cell carcinoma metastatic to the pancreas with gastric cancer rarely occurs, and surgical resection might have improved the quality of life in this patient. Careful long-term follow-up is necessary for patients who have undergone surgery for renal cell carcinoma.     

Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma

Fumarate hydratase (FH) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring with another FH germline alteration. However, a sufficiently large dataset has been lacking to conclusively determine its clinical significance to cancer predisposition in the heterozygous state. We reviewed a series of 7,571 patients with cancer who received germline results through MSK‐IMPACT testing at the Memorial Sloan Kettering Cancer Center. The FH c.1431_1433dupAAA (p.Lys477dup) variant was detected in 24 individuals, none of whom was affected with renal cancer. Eleven of the 372 patients with renal cancer were identified to carried pathogenic FH variants associated with HLRCC. None of these 372 patients with renal cancer carried the FH c.1431_1433dupAAA variant. Our data indicate the FH c.1431_1433dupAAA is not associated with cancer including renal cell carcinoma.     

Glomerulocystic Disease and Lupus Glomerulonephropathy

A renal biopsy demonstrated the presence of both glornerulo-cystic disease (GCD) and lupus glomerulonephropathy in a patient who was admitted for an unrelated disease and was found to have proteinuria and renal failure. Of 12 adult pa- tients with GCD reported in the literature, some form of glomerulonephropathy was demonstrated in 3. One of the 3 had the membranous type of lupus glornerulonephropathy. When family members of previously reported cases of GCD have been examined, “occult” cases of GCD were frequently identified. GCD is probably a much more frequent disease than the relatively small number of published cases would lead one to believe. In adults GCD is often asymptomatic and will only become symptomatic if another renal disease, such as lupus glomerulonephropathy, is superimposed.