Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma

PURPOSE: Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology. MATERIALS AND METHODS: We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease. RESULTS: The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm. CONCLUSIONS: von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.     

Rapid isolation of cell-type-specific protein tyrosine kinases by degenerate polymerase chain reaction combined with differential hybridization technique

To identify protein tyrosine kinase (PTK) genes preferentially expressed in renal cell carcinoma cell line, we screened a PTK-cDNA-enriched library constructed from RNA of an renal cell carcinoma cell line with a PTK probe, each produced from renal cell carcinoma, gastric cancer or esophageal cancer cell lines by degenerate polymerase chain reaction. Two cDNA fragments of PTK genes, FRK and FLT-3, were isolated from the PTK-cDNA-enriched library of the renal cell carcinoma cell line by differential hybridization technique. The FRK cDNA clone represented 15.8% of the PTK-cDNA-enriched library from the renal cell carcinoma cell line, while the FLT-3 cDNA clone was 2.8% of the same library. Both of the two PTK genes were expressed preferentially in renal cell carcinoma cell lines. This method, described here, is useful for the rapid isolation of PTK cDNA fragments, including a low abundant cDNA, preferentially expressed in a specific cell line.     

Thymic carcinoma. Five distinctive histological variants

Five histologically distinct variants of thymic carcinoma are described: mixed small cell undifferentiated squamous cell carcinoma (three cases), basaloid carcinoma (two cases), mucoepidermoid carcinoma (one case), clear cell carcinoma (one case), and sarcomatoid carcinoma (one case). While forming a heterogeneous group, these tumors bear the common features of an anterior mediastinal location and lack of evidence of a primary tumor elsewhere, marking them as primary thymic neoplasms. All except the sarcomatoid variant are morphologically related to similar malignant neoplasms of other organs. These tumors should be recognized as morphological variants of primary thymic carcinoma and demonstrate the ability of thymic epithelium to differentiate toward a variety of different cell types.     

Atypical squamous cell carcinoma of the larynx and hypopharynx: radiologic features and pathologic correlation

The objective of this study was to analyze the radiologic features of atypical forms of squamous cell cancer and correlate them with clinical, endoscopic, and histopathologic findings. The CT and MRI images of 31 patients with atypical forms of squamous cell carcinoma were reviewed retrospectively and the radiologic findings were correlated with clinical, endoscopic, and histopathologic findings. Histopathologic diagnoses included undifferentiated carcinoma of nasopharyngeal type (n = 8), verrucous carcinoma (n = 18), spindle cell carcinoma (n = 3), and basaloid cell carcinoma (n = 2). Undifferentiated carcinoma of nasopharyngeal type was located in the supraglottis or piriform sinus beneath an intact mucosa and initial endoscopic biopsy was most often negative. The discrepancy between an intact mucosa at endoscopy and a solid mass with homogenous enhancement at CT or MRI was characteristic for these tumors and warranted further investigations to obtain the definitive histologic diagnosis. Verrucous carcinoma displayed characteristic clinical, radiologic, and pathologic features, namely, an exophytic tumor arising from the glottic level displaying a rugged surface with finger-like projections but with only minor submucosal infiltration. Spindle cell carcinoma appeared as a polypoid mass with a thin stalk arising from the supraglottis. Basaloid cell carcinoma displayed a distinct lobulated enhancement pattern which was observed on contrast-enhanced T1-weighted SE images. Although the MR and CT features of atypical forms of squamous cell carcinoma cannot be considered pathognomonic they should raise the differential diagnosis even if endoscopic biopsy has been negative. The radiologist's awareness of the appearance of these unusual tumors on CT and MR images may greatly facilitate the diagnostic work-up and helps to guide the endoscopist to the adequate biopsy site in order to establish the correct diagnosis.     

Soluble CD27 in thyroid disorders

Central acinic cell carcinoma is extremely rare; only six cases have been reported in the literature. An unusual case of central acinic cell carcinoma of the mandible in an 84-year-old Japanese woman is presented. This is thought to be the seventh case of central acinic cell carcinoma described in the English literature.     

The effects of steroid instillations and hematomas on the pseudosheaths around miniature breast implants in rats

The syndrome of hypercalcemia in patients with renal cell carcinoma without metastasis to bone, in association with elevated levels of immunoreactive prostaglandin E and normal parathyroid hormone levels, prompted the investigation of an etiologic relationship of increased prostaglandin in this syndrome. Ethyl acetate extracts of tissue culture effluents, primary and metastatic renal cell carcinoma, and plasma were chromatographed on silicic acid columns and assayed by double antibody immunoprecipitative methods for immunoprecipitative methods for immunoreactive prostaglandins A and E. Increased levels of immunoreactive prostaglandins A and E were found 1) to be generated in parallel with cell growth during a period of time by renal cell carcinoma in monolayer growth, 2) in extracts of primary and metastatic renal cell carcinoma tissue and 3) in the venous effluent of a kidney bearing a renal cell carcinoma. These findings support the hypothesis that renal cell carcinoma can produce prostaglandins. Furthermore, reported syndromes of patients with renal cell carcinoma associated with elevated prostaglandin levels may result from the autonomous production of prostaglandins in vivo by the tumor.     

Compare and contrast

We report a patient with squamous cell carcinoma that developed at the ureteroileal anastomosis and extended into the ileal conduit 11 years after a radical cystectomy for transitional cell carcinoma of the bladder. To our knowledge, this is the first report to document the development of a squamous cell carcinoma in an ileal conduit after a radical procedure for bladder cancer.     

Follicular and Hurthle cell carcinomas of the thyroid: a comparative study

University of Texas M. D. Anderson Cancer Center cases filed as Hurthle cell and follicular carcinoma were reviewed. Requirements for including a case in the study were that the diagnosis of Hurthle cell or follicular carcinoma be confirmed, that histologic material and clinical information be adequate, and that there be at least 9 years of follow-up. The study group included 18 cases of Hurthle cell carcinoma and 33 cases of follicular carcinoma. Ten of the Hurthle cell carcinomas had extrathyroid invasion, three had intrathyroid invasion, and five were encapsulated (i.e., they had intracapsular invasion only). In the follicular carcinoma group, 5 tumors had extrathyroid invasion, 14 had intrathyroid invasion, and 14 were encapsulated. When the cases were stratified according to extent of invasion in this manner, there was no statistically significant difference in rate of local recurrence, rate of metastasis (either regional lymph node or distant), or patient survival between Hurthle cell carcinoma and follicular carcinoma. Other variables including patient age and sex, treatment differences, tumor size, vascular invasion, predominant growth pattern (follicular versus solid-trabecular), nuclear size and pleomorphism, mitotic rate, and tumor necrosis did not provide significant additional prognostic information. Metastases of both Hurthle cell and follicular carcinoma were mostly distant and predominantly involved bone and lung. Behavioral differences between Hurthle cell and follicular carcinoma that were not statistically significant included a higher rate of local recurrence in Hurthle cell carcinoma with intrathyroid invasion, more frequent occurrence of regional lymph node metastasis in Hurthle cell carcinoma with extrathyroid invasion, and absence of distant metastasis and death caused by tumor in encapsulated Hurthle cell carcinoma. Five follicular carcinomas and one Hurthle cell carcinoma appeared to have arisen within an adenoma.     

Trichomonas foetus meningoencephalitis after allogeneic peripheral blood stem cell transplantation

The authors report a case of adrenal metastasis contralateral to a renal cell carcinoma in a 74-year-old patient who had undergone right radical nephrectomy for renal cell carcinoma. Nine months later, computed tomography revealed a hypervascular mass considered to be an aneurysm of the splenic artery. Arteriography led to the diagnosis of hypervascular adrenal tumour. Left adrenalectomy was performed. Histological examination showed a metastasis from renal cell carcinoma. This is an unusual form of renal cancer metastasis. Its treatment and prognosis are discussed.     

Effects of incubation temperature on the energetics of embryonic development and hatchling morphology in the Brisbane river turtle Emydura signata

AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.     

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.     

Different techniques of internal fixation applied in lumbosacral fusion: 83 cases analysis

To characterize the cytologic spectrum of small cell carcinoma of the urinary bladder, a review of 42 urinary cytology specimens from 13 patients with histologically proven tumors was conducted. Patients ages ranged from 45 to 81 yr (mean 68.9). In four tumors, small cell carcinoma was the sole malignant cellular component: all 11 urinary specimens in these patients harbored cells with features of an undifferentiated small cell carcinoma. In the remaining nine tumors, small cell carcinoma appeared with transitional, squamous cell or adenocarcinoma, but in four, small cell carcinoma was the sole invasive component. Almost one third of urinary specimens in this group lacked a small cell component. Neuroendocrine differentiation was confirmed by immunopathology in eleven cases (neuron specific enolase positive in 11 of 12, synaptophysin in 2/11, chromogranin in 2/13, Leu 7 in 2/7), and by ultrastructural analysis in two. Small cell carcinoma is a cytologically recognizable variant of bladder cancer, but admixture with other malignant components may mask its appearance in urinary specimens.     

Drug resistance to 5-aza-2''-deoxycytidine, 2'',2''-difluorodeoxycytidine, and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into murine cells

Squamous metaplasia can be demonstrated in about 4% of all invasive carcinomas of the breast. Primary squamous cell carcinomas of the breast are rare, since they occur in less than 1% of all primary invasive breast carcinomas. In order to classify a breast tumor as a primary squamous cell carcinoma one must exclude an epidermal origin, especially from the nipple region and the possibility of metastatic infiltration of the breast by a squamous cell carcinoma from a different location. Causative and formal pathogenesis of primary squamous cell carcinoma of the breast is not clear. A pluripotent embryonal stem cell origin is discussed, considering the phylogenetic descent of the mammary gland from skin appendages. Squamous metaplasia is also suggested to be a precursor of squamous cell carcinoma. Here endocrine stimulation and chronic inflammation may both play an inductive role. The number of published cases of squamous cell carcinomas developing years and decades after implantation of silicon prostheses has increased in recent years. These tumors probably develop on top of squamous metaplasia induced by the inflammatory pseudocapsule. Estimating the prognosis and therapeutic management in patients with squamous cell carcinoma of the breast should follow the same guidelines as for other squamous cell cancers.     

Hereditary papillary renal cell carcinoma

We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes.     

Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma

BACKGROUND/AIMS: Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma. METHODS: Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34. RESULTS: In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor. CONCLUSIONS: This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.     

Merkel cell carcinoma in the nasal cavity: a case report

Merkel cell carcinoma is an aggressive dermal neoplasm of neuroendocrine origin with a predilection for the head-and-neck region in elderly patients. We present a case of Merkel cell carcinoma of the nasal fossa. Local wide excision was performed.     

Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized primarily by multiple basal cell carcinomas, odontogenic keratocysts, and pits of the palms and soles. Tumor deletion studies and linkage analysis in Caucasians have revealed that the gene is on chromosome 9q. To further refine the location of the nevoid basal cell carcinoma syndrome locus, we tested linkage to this region in three families. Evaluation of recombinants suggested that the nevoid basal cell carcinoma syndrome locus lies in the interval defined distally by D9S127. Our data, together with existing published data defining D9S12 as a proximal flanking marker, refine the location of nevoid basal cell carcinoma syndrome to an 8.3-cM interval. Two of the families studied were African-American and show a notable variation in phenotypic expression in which affected individuals developed few skin cancers. However, despite clinical heterogeneity, our data are consistent with the hypothesis that the same locus is involved in these African-American families.     

Large cell neuroendocrine carcinoma of the thymus

AIM: We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus. CASE DETAILS: A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later: Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma. CONCLUSIONS: Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.     

Use of prostaglandin E1 for treatment of erectile dysfunction

Metastatic tumors to the head and neck are uncommon. We report a case of renal cell carcinoma that presented as an epidermal inclusion cyst on the forehead. The forehead is an exceedingly uncommon site for renal cell metastases. We review the biology of tumor metastases and explore the pathways by which infraclavicular tumors spread to the head and neck. We then discuss the clinical appearance and management of metastatic renal cell carcinoma.