VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Charlson score as a single pertinent criterion to select candidates for active surveillance among patients with small renal masses.

PURPOSE: The aim of the study was to assess the outcome after nephron-sparing surgery (NSS) of patients with small renal masses (SRMs) who would have been eligible for active surveillance (AS). METHODS: Data were collected retrospectively for 758 patients who underwent NSS over a 5-year period. Outcomes were assessed in two groups of patients who were eligible for AS according to different criteria. Group 1 criteria were as follows: age >75 years, renal mass ≤4 cm, significant comorbidities [Charlson Comorbidity Index (CCI) >2]. Group 2 criteria were as follows: any SRM ≤ 4 cm regardless of age, severe comorbidities with a 10-year mortality risk >50 % (CCI > 4). The two groups were not compared statistically because some patients were included in both. RESULTS: Fifty-five patients (7.3 %) were included in Group 1 and 62 (8.2 %) in Group 2. There was a significant proportion of benign tumours in Group 1 (N = 6; 11 %) and Group 2 (N = 6; 10 %). Six (11 %) positive margins were observed in Group 1 and 8 (13 %) in Group 2. The 2- and 5-year recurrence-free survival rates were 100 and 77.4 %, respectively, in Group 1, and 88.5 and 79.6 % in Group 2. The 2- and 5-year overall survival rates were 100 and 74.7 % in Group 1, and 96.7 and 78.1 % in Group 2. CONCLUSIONS: The majority of patients with SRMs who would have been eligible for AS had no recurrence after initial tumour removal. In these patients, a CCI > 4 appeared to be a pertinent criterion to identify those patients less likely to benefit from immediate surgery.

Reproducibilidad interobservador de un sistema de grado para el carcinoma de células renales tipo cromófobo / Interobserver Reproducibility of a Grading System for Chromophobe Renal Cell Carcinoma

Objetivos: Valorar la reproducibilidad interobservador y evaluar el sistema de gradación propuesto por Paner et al. para el carcinoma de células renales cromófobo. Material y métodos: Tras seleccionar 23 casos de carcinoma renal de tipo cromófobo de los hospitales Xeral-Cíes, Meixoeiro y POVISA de Vigo de los últimos 15 años se ha realizado una sesión informativa de los criterios del sistema de gradación de Paner et al. Posteriormente los patólogos observadores han aplicado dicho sistema a cada caso, valorando una laminilla seleccionada. Se ha calculado el índice Kappa de reproducibilidad interobservador, ponderado según la escala de Landis y Koch. Resultados: La distribución de grados en la mayoría de los 6 observadores participantes es similar, con predominio del grado 1 en 4 de los mismos. Los 2 observadores restantes consideraron una mayoría relativa de casos como grado 2. Los valores de Kappa oscilan entre 0,136 y 0,674, observándose un predominio de valores indicadores de reproducibilidad discreta-moderada (0,21-0,60). El mayor valor de Kappa (0,674) se ha dado entre un observador novel y el patólogo más experto. Entre los 2 observadores más veteranos se ha obtenido el índice más bajo (0,136). Conclusiones: La reproducibilidad interobservador en nuestros centros para el grado propuesto por Paner et al. es discreta-moderada. La asignación de los grados 1 y 2 no es homogénea entre los 6 observadores participantes. En espera de la existencia de una gradación consensuada por las sociedades científicas, creemos prudente no utilizar ningún sistema de gradación en los carcinomas de células renales de tipo cromófobo (AU)

Objectives: To evaluate interobserver reproducibility of a grading system proposed by Paner et al. for chromophobe renal cell carcinoma. Material and methods: After selecting 23 cases of chromophobe renal cell carcinoma from the Xeral-Cíes Hospital, Meixoeiro Hospital and POVISA Hospital from the last 15 years, an informative meeting on the Paner et al. grading system criteria was held. After, the participating pathologists applied the system to each case, evaluating one slide selected. Kappa index for interobserver reproducibility was calculated, and it was classified according to the Landis and Koch scale. Results: The grading distribution was similar for most of the 6 participating observers, with grade 1 predominance. The remaining 2 observers considered a relatively higher proportion of grade 2. Kappa index values ranged from 0.136 to 0.674, with a discrete-moderate reproducibility index predominance (0.21-0.60). Highest Kappa value (0.674) was obtained between the most novel and the most expert interobservers. The lowest Kappa value was obtained among the most veteran pathologists (0.136). Conclusions: Interobserver reproducibility for chromophobe renal cell carcinoma is discrete-moderate in our institutions when the novel grade proposed by Paner et al. is used. Labeling of grades 1 and 2 is not homogeneous among 6 participating observers. While awaiting a grading consensus on a new classification by the scientific societies, we consider that the routine use of a grading system for chromophobe renal cell carcinoma should not be used (AU)

Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential.

Expresión de MLH1, MSH2 y MSH6 en oncocitomas ycarcinomas de células cromófobas renales / MLH1, MSH2 and MSH6 expression in renal oncocytomas and chromophobe cell carcinomas

Objetivos: La alteraciones de los genes reparadores deADN llevan a la inestabilidad de microsatélites y caracterizanal adenocarcinoma familiar de colon no asociado a poliposisy al resto de tumores que se han descrito asociados aeste síndrome. Asimismo, aunque se han visto alterados enun número variable de casos de cáncer esporádico, han sidomuy raramente evaluados en los carcinomas de células renales.Material y métodos: Se han seleccionado 7 oncocitomasrenales y 7 carcinomas renales de células cromófobasmediante criterios histológicos e inmunohistoquímicos convencionales,para el estudio de los genes reparadores deADN mediante la expresión inmunohistoquímica de las proteínasMLH1, MSH2, y MSH6. Resultados: Existe un predominioclaro del sexo masculino, tanto entre los oncocitomas(2F/5M) como entre los carcinomas (3F/4M), con edadesmedias de presentación de 66,8 y 63,4 añosrespectivamente. Entre los oncocitomas renales se ha detectadopositividad para CK20 (4 casos) y CD15 (4 casos),negatividad para CK7 en todos los casos, y pérdida de laexpresión proteica de MLH1 en 1 caso, de MSH2 en 2casos, y de MSH6 en 1 caso. En los carcinomas de célulascromófobas se ha observado positividad para CK7 y negatividadpara CK20 y CD15 en todos los casos, y pérdida de laexpresión de MSH2 en 2 casos y de MSH6 en 3. Conclusiones:El patrón de expresión de las proteínas MLH1,MSH2 y MSH6 en oncocitomas y en carcinomas renales decélulas cromófobas es similar, apoyando la teoría vigente deun mismo origen para ambas entidades en la nefrona distal (AU)

Objectives: Mismatch repair gene disorders lead tomicrosatellite instability and characterise the nonpolyposishereditary colonic adenocarcinoma syndrome. Aside fromthat, the syndrome includes other carcinomas in differentlocations. Mismatch repair gene mutations have been alsodescribed in some sporadic carcinomas of diverse topographies,but only very occasionally in renal cortical carcinomas.Material and methods: Seven renal oncocytomas and7 chromophobe cell carcinomas have been selected followingconventional histological and immunohistochemicalmethods for the analysis of MLH1, MSH2 and MSH6 proteins.Results: There is a male predominance, both inoncocytomas and in carcinomas, with average ages of presentationof 66.8 and 63.4 years, respectively. Among theoncocytoma group, a positive immunostaining for CK20and CD15 has been seen in 4 cases each. Loss of MLH1expression has been detected in one case, loss of MSH2 in2, and loss of MSH6 in one. Among the chromophobe cellcarcinomas, CK7 was positive and CK20 and CD15 negativein all cases. Loss of MSH2 expression has been observedin 2 cases and loss of MSH6 in 3. Conclusions: The patternof MLH1, MSH2 and MSH6 expression is analogous inrenal oncocytomas and chromophobe cell carcinomas thussupporting the nowadays accepted theory of a similar originin the distal nephron for both pathological entities (AU)

Origin of renal cell carcinomas.

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition.

Pathologic features of renal cortical tumors.

Our better understanding of the morphologic spectrum of renal cortical tumors has resulted in a clinically more relevant classification of these tumor types. We now recognize that "granular cell" and "sarcomatoid" renal cell carcinoma are only nonspecific descriptors, and that such features are seen in a variety of types of renal tumors. The authors believe that the recently gained knowledge about molecular-driven antigen expression will play an important role in the characterization, development, and evaluation of targeted therapies in kidney cancer in the coming years.

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition (AU)

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Genética molecular del cáncer renal: utilidad en pronóstico y posibilidades terapéuticas / Molecular genetics of renal cancer: usefulness in prognosis and therapeutic possibilities

El cáncer renal tiene una incidencia del 3% del total de las neoplasias en adultos, y puede ser tanto de origen hereditario como esporádico. Histológicamente se clasifica en 5 tipos principales. Las técnicas actuales de citogenética y biología molecular han permitido conocer con más detalle algunos de los sucesos genéticos iniciales que causa la patogenia de los tipos mayoritarios como, por ejemplo, que un defecto en el cromosoma 3p está implicado en el desarrollo del carcinoma de células claras (ccRCC) o que en un 13% de los RCC de tipo papilar está mutado el gen c-MET (cromosoma 7), y en el resto de cánceres de este tipo existe duplicación de este mismo cromosoma, o que, en los oncocitomas la pérdida de los cromosomas 1 y/o 14 podría representar el suceso inicial. Aparte de estos defectos, el conocimiento de otros genes y alteraciones cromosómicas implicados, junto con otros factores, permite definir de manera aproximada el pronóstico en cada caso. Debido a que este tipo de cáncer desarrolla metástasis rápidamente, las terapias actuales, como la cirugía y el uso de interleucina (IL) 2, son poco eficaces y sólo consiguen alargar en unos meses la supervivencia del paciente. Aunque se están ensayando nuevas terapias, es necesario un conocimiento más profundo de los procesos moleculares implicados para obtener el éxito deseado tanto en el diagnóstico precoz como en el pronóstico y el tratamiento de la enfermedad(AU)

Renal cancer has a 3% incidence of all neoplasms in adults and it can be of hereditary or sporadic origin. Histologically, it is classified into 5 main types. The current cytogenetic and molecular biology techniques allow some of the initial genetic events responsible for the main types of pathogenesis to be studied in more detail, such as the implication of a defect in chromosome 3p in the development of clear cell renal cell carcinoma (ccRCC), or the presence of the mutated c-MET gene (chromosome 7) in 13% of papillary RCCs and the presence of the same chromosome duplication in the rest of these types of cancer, or the loss of chromosomes 1 and/or 14 which could represent the initial event in oncocytomas. Apart from these defects, knowledge other genes involved and chromosomic defects, as well as other factors, may enable an approximate prognosis to be made in each case. As the metastatic process in this cancer type develops very early, the current therapies, such as surgery and the use of IL-2, are not very effective and they only manage to extend patient survival by a few months. Although newer therapies are being assessed, a deeper knowledge about the molecular processes involved is necessary to obtain the desirable success both in the early diagnosis, as well as the prognosis and treatment of the disease(AU)

Expression of adrenocorticotropic hormone, prolactin and transcriptional factors in clinically nonfunctioning pituitary adenoma.

We describe here a case of a clinically nonfunctioning pituitary adenoma, but with expression of ACTH and PRL. A 42-year-old woman was referred to our department for further evaluation of pituitary tumor. She had no acromegaloid features, and no typical Cushingoid features. She had no galactorrhea, and had regular menses. GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were all within the normal ranges, while PRL levels were mildly elevated. Both ACTH and cortisol levels were adequately increased in response to CRH, and both were suppressed by a small dose of dexamethasone. Plasma ACTH and cortisol levels were decreased at night, suggesting the circadian rhythms for plasma ACTH levels were undisturbed. Based on these findings we did not clinically suspect ACTH-producing tumor, however immunohistochemistry revealed ACTH immunoreactivity in the pituitary adenoma. Therefore, the tumor was considered a silent corticotroph adenoma. PRL was co-expressed in a significant subpopulation of ACTH-immunoreactive tumor cells. Ptx1, Neuro D1, and T pit were densely expressed and Pit-1 was sparsely expressed in the nuclei of adenoma cells. It is therefore possible that a tumor originating in an immature or uncommited adenohypophysial stem cell may later differentiate into different cell types due to a combination of certain specific transcriptional factors.

Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness.

BACKGROUND: Prognostic markers for renal cell carcinoma (RCC), such as patient symptoms, tumor stage, tumor size, and tumor grade, are useful for determining appropriate follow-up and selecting patients for adjuvant therapy. Histologic coagulative tumor necrosis, also reported to be a prognostic marker for RCC, has not previously been extensively described or investigated. Hence, the objective of the current study was to characterize tumor necrosis as a prognostic feature of RCC. METHODS: The authors of the current study identified 3009 patients treated surgically for RCC between 1970 and 2002 from the Mayo Clinic Nephrectomy Registry (Rochester, MN). Associations of tumor necrosis with clinical, laboratory, and pathologic features were examined with chi-square, Fisher exact test, and Wilcoxon rank-sum tests. Cancer-specific survival was estimated with the Kaplan-Meier method, and associations with outcome were assessed with Cox proportional hazard models. RESULTS: Tumor necrosis was present in 690 of 2445 (28%) clear cell, 196 of 421 (47%) papillary, and 28 of 143 (20%) chromophobe RCCs. The risk ratio for death from RCC in patients with necrotic compared with non-necrotic tumors was 5.27 (95% confidence interval [CI]: 4.56-6.09; P < 0.001) for clear cell, 4.20 (CI: 1.65-10.68; P < 0.001) for chromophobe, and 1.49 (CI: 0.81-2.74; P = 0.199) for papillary RCC. The survival difference for clear cell RCC persisted even after multivariate adjustment for tumor stage, size, and grade (risk ratio 1.90; P < 0.001). CONCLUSIONS: Histologic coagulative tumor necrosis is an independent predictor of outcome for clear cell and chromophobe RCC, and it should be routinely reported and used in clinical assessment.

[Adult renal neoplasms in the material of the Pathology Department of the Szeged University]. / Felnottkori vesedaganatok a Szegedi Tudományegyetem Patológiai Intézetének anyagában.

AIMS: The authors investigated the frequencies of the various histological types of adult renal tumours. METHODS: The slides of 469 nephrectomies performed in the Department of Urology, Szeged University between 1990 and 2003 were revised according to the 1997 Heidelberg and 2004 WHO classification schemes. RESULTS: 86.7% of all the tumours (n = 407) were malignant. Among the malignant tumours, the frequency of renal cell carcinomas was 91.1% (n = 371). 88.4% of the renal cell carcinomas (n = 328) were of conventional type, 5.6% (n = 21) were papillary and 4% (n = 15) were chromophobe. The authors observed 3 Bellini duct, 1 mucinous tubular and 3 non-classifiable carcinomas, with a combined incidence of 1.8%. 84.5% of the conventional carcinomas were clear cell (n = 277), 8.8% were eosinophilic granular (n = 29), 3.9% were multilocular cystic (n = 13) and 2.7% were sarcomatoid carcinomas (n = 9). The median age of the patients with conventional carcinoma was 60 (median, range: 25-84), in the papillary group it was 62 (43-78), and in the chromophobe group was 59 (17-77). The median age of patients affected by transitional cell carcinoma was 64 (range: 45-81). As far as benign tumours are concerned (13.2%, n = 62), oncocytomas (n = 37, 7.8% of all the tumours) affected mainly females, whereas angiomyolipomas (n = 21, 4.4% of all the tumours) occurred in females only. In 13 oncocytoma cases, the tumours were initially diagnosed as malignant. CONCLUSIONS: Adult malignant renal tumours affect mainly patients around the age of 60. The commonest diagnosis was clear cell carcinoma of conventional type. The incidence of clear cell carcinoma was 5% higher than that reported in the literature (84.5% vs 70-80%) whereas that of papillary carcinoma was 5% lower (5% vs 10-15%). In comparison with the literature data, oncocytomas were relatively common (8% instead of 3%), and not rarely, it was difficult to distinguish them from renal cell carcinomas.

Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses.

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.

Extracerebral subdural manifestation of Chester-Erdheim disease associated with a giant adenoma of the pituitary.

Chester-Erdheim disease is a rare non-Langerhans histiocytosis, affecting within the CNS mainly the neurohypophyseal unit, the retrobulbar space and the parenchyma of cerebellum, cerebrum and brainstem. Here we present a case of a 55-year-old woman who developed an exophthalmus, edema and dyspnea, finally leading to death 4 months post admission to the hospital. A cMRI showed a retrobulbar fibrosis, a tumor in the sella turcica, and further tumor formation expanding from the pons to the spinal cord, but without involvement of the dural sheet. Autopsy revealed multiple tumors attached to the pituitary gland, the tentorium, and the brainstem as well as a diffuse thickening of the dura. Histologically, the tumor tissue consisted of densely packed lipid-laden foamy macrophages positive for CD68 and intervening fibrillary cords. Interestingly, tumor cells did not infiltrate/affect the parenchyma but showed a strictly extracerebral/ subdural location. In addition, sections of the pituitary tumor revealed a chromophobe giant adenoma of the pituitary gland. As to our knowledge this is the first detailed description of an exceptional case of intracranial CED presenting with strictly extracerebral/subdural tumor masses accompanied by a giant adenoma of the pituitary gland.

Synchronous subarachnoid drop metastases from a pituitary adenoma with multiple recurrences. Case report.

The authors report the case of a 49-year-old man with synchronous drop metastases from a multiply recurrent somatotroph pituitary adenoma. The metastatic lesions were found in the subarachnoid space of the cauda equina and foramen magnum 18 years after the initial diagnosis of the disease. Five transsphenoidal resections had previously failed to cure the sellar tumor. Two of these, performed 4 and 5 years before the patient's current presentation, had been complicated by cerebrospinal fluid rhinorrhea that necessitated lumbar drainage. Resections of the two subarachnoid lesions, separated by 14 months, removed pathologically aggressive pituitary adenomas. There were no signs of local recurrence or subarachnoid dissemination of disease during the postoperative follow-up periods, which lasted 18 and 4 months, respectively. Previous cases of subarachnoid spread of a pituitary adenoma have been associated with multiple intracranial metastases, multiple intraspinal metastases, or widely disseminated disease. This case demonstrates that subarachnoid metastasis of a pituitary adenoma, particularly when it follows multiple operations, is not invariably widely disseminated or associated with a very poor prognosis.

Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma.

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.

Prognostic features of pathologic stage T1 renal cell carcinoma after radical nephrectomy.

OBJECTIVES: To assess the effect of renal cell carcinoma (RCC) subtype, tumor size, and Fuhrman grade on clinical outcome in patients with pathologic T1 (pT1) RCC treated with radical nephrectomy. METHODS: Between 1970 and 1998, 840 patients underwent radical nephrectomy for pT1 RCC. Tumors were subtyped and graded. Univariate and multivariate Cox proportional hazards models were fitted to assess the features associated with metastasis-free survival (MFS) and cancer-specific survival (CSS). We identified a range of tumor sizes of clear cell RCC in which a transition occurred from low to high risk. Cox proportional hazards models were then fitted by using size cutoffs. RESULTS: The mean follow-up (+/- SD) was 9.4 +/- 6.6 years among the patients alive at latest follow-up. At 10 years, the CSS and MFS for clear cell RCC (n = 682) were 89.1% and 88.6%, respectively; for papillary RCC (n = 122), they were 95.5% and 93.8%; and for chromophobe RCC (n = 33), they were both 100%. The differences in CSS (P = 0.013) and MFS (P = 0.023) between clear cell RCC and the other subtypes were statistically significant. For clear cell RCC, tumor size and Fuhrman grade were independently associated with CSS and MFS (P <0.001). A transition in risk occurred for tumor sizes between 4.5 and 5.0 cm, and the tumor size cutoff of 5.0 cm had the highest concordance index for predicting CSS and MFS. CONCLUSIONS: RCC subtype is a strong independent prognostic variable for patients with pT1 RCC treated with radical nephrectomy. For clear cell RCC, Fuhrman grade and tumor size are independently associated with CSS and MFS.