Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

INTRODUCTION: The aim of this study was to assess whether epidermal growth factor receptor (EGFR) overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC) and whether its prognostic significance was affected by immunohistochemical expression patterns. MATERIALS AND METHODS: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG) as low-NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2), or locally invasive (pT3, 4). Clinical disease was grouped by clinical stage as early stage (stage I, II), or late stage (stage III, IV). Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt), and membranous (EGFR Mem) staining. RESULTS: EGFR Cyt correlated with high NG (P = 0.001), lymphovascular invasion (P = 0.028), regional lymph node involvement (P = 0.027), metastasis (P = 0.001), late stage (P = 0.003), cancer-specific death (P = 0.036), and was a predictor for disease-specific survival (P = 0.012) whereas EGFR Mem correlated with only local invasion (P = 0.021) and perirenal invasion (P = 0.009) and did not show any correlation with cancer-specific death or disease specific survival. CONCLUSION: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.

Gelsolin, NF-κB, and p53 expression in clear cell renal cell carcinoma: Impact on outcome.

OBJECTIVES: To examine the prognostic significance of Gelsolin, NF-κB, and p53 in clear cell renal cell carcinoma (CRCC), which has an unpredictable behavior and tendency for recurrence and metastasis. MATERIALS AND METHODS: Immunohistochemistry was performed on 100 consecutive cases of CRCC using antibodies against Gelsolin, NF-κB, and p53. Tumors were grouped by nuclear grade (NG) as low NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2) or locally invasive (pT3, 4). Clinical stage was grouped as early stage (stage I, II) or late stage (stage III, IV). Evaluation was based on cytoplasmic (NF-κB(Cyt)) and nuclear (NF-κB(Nuc)) expression for NF-κB, nuclear expression for p53, membranous and cytoplasmic expression for Gelsolin. RESULTS: Gelsolin expression correlated with high NG (p = 0.001), metastasis (p = 0.003), late stage (p = 0.008), and cancer death (p = 0.001). NF-κB(Cyt) expression correlated with high NG (p = 0.002), perirenal invasion (p = 0.010), local invasion (p = 0.020), and late stage (p= 0.003). NF-κB(Nuc) expression failed to predict the prognosis of CRCC. p53 expression correlated with high NG (p = 0.045), lymphovascular invasion (p = 0.05), metastasis (p = 0.001), late stage (p = 0.028), and cancer death (p = 0.034). However, only Gelsolin was found to correlate with disease-specific survival, (p = 0.006), and neither NF-κB nor p53 showed such relation. CONCLUSION: Expressions of Gelsolin, NF-κB(Cyt), and p53 associated with aggressive behavior of CRCC, while Gelsolin expression specifically indicated poor disease-specific survival. The results of the present study served to determine biomarkers for predicting high-risk patients with CRCC, expected to show aggressive phenotype.

Acantholytic squamous cell carcinoma of the maxilla: unusual location and aggressive behavior of a rare histologic variant.

Acantholytic squamous cell carcinoma (ASCC) of the mucosal membranes has been documented sporadically. The highly aggressive behavior of a mucosal ASCC arising in the oral cavity has been recently reported. To the best of our knowledge, only 1 autopsy case of maxillary ASCC previously has been reported in the literature. We present what we believe is only the second case of maxillary ASCC. Our goal is to emphasize the aggressive behavior of this tumor in order to add weight to the argument that the prognosis is poor.

Primary malignant fibrous histiocytoma of the kidney: report of a case and literature review.

We report a 44-year-old woman with a malignant fibrous histiocytoma (MFH) of the kidney. Primary renal MFH is an extremely rare tumor with a poor prognosis. Renal MFH is differentiated from renal cell carcinoma, renal sarcoma, and sarcomatoid renal tumors only by histological and immunohistochemical studies. Because the therapeutic options for MFH are different, its early diagnosis is imperative.

An unusual cause of infantile gynecomastia: sertoli cell tumor.

Prepubertal testicular masses are relatively rare. Sertoli cell tumors account for 2% of prepubertal testicular tumors and very few have occurred in the first decade of life. Gynecomastia can be seen in approximately 5% of patients with testicular mass. We present an 8-month-old boy admitted with bilateral gynecomastia and unilateral testicular mass.

Melkersson-Rosenthal syndrome revisited as a misdiagnosed disease.

PURPOSE: We aimed to attract our college's attention to the Melkersson-Rosenthal syndrome (MRS), which has been an infrequently encountered subject in otolaryngology journals during the last 10 years. MATERIALS AND METHODS: A retrospective review of the last 10 years' patient database was performed to find patients with MRS. The medical files, treatment charts, and radiological and histopathological records of these patients were reviewed. RESULTS: The study group consisted of 3 MRS patients who had been misdiagnosed for 9, 10, and 16 years. Two of them have had the symptoms since adolescence. All of them presented orofacial edema and fissured tongue, whereas first two also had recurrent facial paralysis. Characteristic histopathological features were noted in 1 patient. Electromyography (EMG) was done in 1 patient who underwent facial decompressiom. All patients responded to either systemic or intralesional corticosteroid treatment. CONCLUSIONS: In the daily practice of an otolaryngologist, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this study will supply an additional aspect to otolaryngologists, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.

Actinomycosis in the etiology of recurrent tonsillitis and obstructive tonsillar hypertrophy: answer from a histopathologic point of view.

OBJECTIVE: To investigate the histopathologic profile and clinical presentation of tonsillar disease in the presence of Actinomycetes in children. DESIGN: A qualitative and quantitative histopathologic analysis of the palatine tonsil was performed. SETTING: Tonsillectomy specimens from patients who underwent tonsillectomy or adenotonsillectomy were searched for Actinomycetes. METHODS: Histologic evaluation of the specimens was done on hematoxylin and eosin-stained slides as blinded to patients' clinical category for disease groups. MAIN OUTCOME MEASURES: Four histologic compartments of the tonsil, including the surface epithelium, reticulated crypt epithelium (lymphoepithelium), lymphoid tissue, and interfollicular region, were examined. RESULTS: Actinomycetes was more prevalent in patients with obstructive symptoms treated with adenotonsillectomy. The number of subjectively quantitated total lymphoid follicles and small and medium-sized lymphoid follicles of the palatine tonsil were significantly increased in patients demonstrating "sulphur granules" in their crypts. Highly thick squamous metaplasia of the lymphoepithelium and dilatation of crypts were more prevalent in tonsil tissue revealing Actinomycetes. CONCLUSIONS: The presence of Actinomycetes in tonsillectomy specimens does not indicate active tissue infection. However, the histopathologic outcome may indicate the possible etiologic role of Actinomycetes in the development of prominent lymphoid hyperplasia and hypertrophy and, in turn, obstructive tonsillar hypertrophy.

Pathological staging of muscle invasive bladder cancer: is substaging of pT2 tumors really necessary?

OBJECTIVE: Compare clinical outcomes in patients having urothelial tumors invading less than one half of the depth of bladder muscle and greater than one half of bladder muscle and, to determine various clinical variables as predictive factors for survival. MATERIALS AND METHODS: According to our inclusion criteria, 57 patients among cases with T2 bladder tumor were selected. Thirty-five patients (61.4 percent) had pT2a (Group-1) and 22 patients (38.6 percent) had pT2b (Group-2) muscle invasive tumors. Mean follow up time was 7.3 years for Group-1, and 6.1 years for Group-2. Multivariate analysis was performed in order to identify possible correlation of clinical variables like age, gender, grade of primary tumor, appearance of local and/ or distant metastasis with patient outcome. RESULTS: Five year recurrence-free and overall survival rates were 69.1 percent and 44.3 percent for patients with pT2a tumor, whereas these ratios were 66.1 percent and 43 percent, respectively for patients with pT2b tumor (p = 0.896; p = 0.975). Mean overall and progression-free survival times were 87.7 ± 13.8 and 116 ± 13.12 months for Group-1, while they were 73.8 ± 13.7 and 88.85 ± 12.55 months for Group-2, respectively. On both univariate and multivariate analysis, age was noticed as an independent predictive factor for survival. CONCLUSIONS: The depth of muscle invasion in bladder tumors has no prognostic significance. Recurrence of the disease either locally or at distant sites dramatically shortens patients' life. Being older than 60 years old during the time of radical surgery, is also a bad prognostic factor for overall and progression-free survival.

Clinical importance of intratumoral and normal renal parenchymal inflammatory cell infiltration in renal cell carcinoma.

OBJECTIVE: To assess the relationship between inflammatory cell infiltration and tumor type, stage and grade, the presence of multifocality and survival in tumors and in tumor-free normal parenchyma. MATERIAL AND METHODS: A total of 99 patients who underwent radical nephrectomy for renal cell carcinoma (RCC) between 1995 and 2001 and were subsequently followed up were included in the study. Formalin-fixed, paraffin-embedded tissues from the patients were reassessed by a pathologist and inflammation in both tumor and normal renal tissue was scored using a five-point scale. We evaluated the relationship between these scores and tumor type, stage, grade, the presence of multifocality and survival. RESULTS: There were positive correlations between tumor grade and both the intratumoral inflammation score (IIS) and the extratumoral inflammation score (EIS) (p=0.001 and 0.01, respectively). There were no relations between pathological stage and either the IIS or EIS. We found higher multifocality rates in patients who died because of metastasis than those who survived (p=0.002). The EIS was 1.76+/-1.54 in the non-multifocality group and 2.64+/-1.15 in the multifocality group and this difference was statistically significant (p=0.03). There was no statistically significant relationship between the IIS and multifocality. Oncocytomas and chromophobe carcinomas did not show inflammatory infiltrates in either tumors or normal renal tissue. CONCLUSIONS: Higher EIS and IIS are associated with increasing tumor grade and a higher EIS is associated with multifocality in RCC. We propose to evaluate tumor tissue and normal renal parenchyma for the presence of inflammatory infiltration in RCC.

Amyloidosis of the larynx: a case report.

A 75-year-old female patient presented with hoarseness and foreign body sensation in the back of her throat of one-month history. Direct laryngoscopy showed bilateral, yellow, hyperemic masses on the left false vocal fold and laryngeal ventricle. Both true vocal folds were mobile. Excisional biopsies of the right false vocal fold and ventricle showed extracellular, insoluble, fibrillar protein accumulation, consistent with amyloidosis. There was no evidence for neoplasm. Serum and urine electrophoreses were negative. The work-up for systemic amyloidosis and multiple myeloma were negative. Treatment was limited to surgical excision. No complications developed within a six-month follow-up period.

Adenocarcinoma originating from a mature teratoma of the testis.

Malignant transformation in testicular teratomas has been reported very rarely in the literature. Although testicular teratomas in childhood are regarded as benign neoplasms, these tumors, if left untreated until advanced ages, may present the risk of malignant transformation. We report a case of differentiated adenocarcinoma originating from colonic glands in primary testicular teratoma.

Vitiligo associated with malignant melanoma and lupus erythematosus.

There exists several reports where malignant melanoma is associated with vitiligo, vitiligo with discoid lupus erythematosus and lupus erythematosus with urticaria. However, there are no reports in which vitiligo, malignant melanoma, lupus erythematosus and urticaria coexist in the same case. Herein, we report a case of a patient who developed lupus erythematosus, malignant melanoma, vitiligo and urticaria simultaneously.

Microvessel density and regulators of angiogenesis in malignant and nonmalignant prostate tissue.

The aim of this study was to investigate the relationship between microvessel density (MVD), positive and negative angiogenic factors, and established prognostic factors in prostate cancer (PC), and, to clarify the effect of angiogenic factors to angiogenesis. The vascularization of neoplastic, non-neoplastic prostate tissue was determined by CD34 immunostaining. Angiogenetic mediators VEGF, bFGF, TSP-1, and p53 were studied by immunohistochemistry. Neovascularization and p53, VEGF, and TSP-1 expressions of tumorous tissue were higher than non-tumorous tissue. The bFGF expression in these tissues was not different. The p53 expression was not correlated with the expressions of VEGF, bFGF, and TSP-1 in PC. Our results demonstrate a significant increase in MVD, VEGF, TSP-1, and p53 expressions in prostate tumorigenesis. The pretreatment sPSA was the only parameter demonstrating significant correlation with tumor grade and may have a value in the prediction of aggressive tumor behavior in PC.

Pathological staging of muscle invasive bladder cancer. Is substaging of pT2 tumors really necessary?

OBJECTIVE: Compare clinical outcomes in patients having urothelial tumors invading less than one half of the depth of bladder muscle and greater than one half of bladder muscle and, to determine various clinical variables as predictive factors for survival. MATERIALS AND METHODS: According to our inclusion criteria, 57 patients among cases with T2 bladder tumor were selected. Thirty-five patients (61.4 %) had pT2a (Group-1) and 22 patients (38.6%) had pT2b (Group-2) muscle invasive tumors. Mean follow up time was 7.3 years for Group-1, and 6.1 years for Group-2. Multivariate analysis was performed in order to identify possible correlation of clinical variables like age, gender, grade of primary tumor, appearance of local and/ or distant metastasis with patient outcome. RESULTS: Five year recurrence-free and overall survival rates were 69.1% and 44.3% for patients with pT2a tumor, whereas these ratios were 66.1% and 43%, respectively for patients with pT2b tumor (p = 0.896; p = 0.975). Mean overall and progression-free survival times were 87.7 +/- 13.8 and 116 +/- 13.12 months for Group-1, while they were 73.8 +/- 13.7 and 88.85 +/- 12.55 months for Group-2, respectively. On both univariate and multivariate analysis, age was noticed as an independent predictive factor for survival. CONCLUSIONS: The depth of muscle invasion in bladder tumors has no prognostic significance. Recurrence of the disease either locally or at distant sites dramatically shortens patients' life. Being older than 60 years old during the time of radical surgery, is also a bad prognostic factor for overall and progression-free survival.

Microscopic polyangiitis with unusual lung involvement.

Microscopic polyangiitis (MPA) is a non-granulomatous, systemic and small vessel vasculitis accompanied by segmental necrotizing glomerulonephritis with no evidence of other small vessel disease. We report a patient with weakness, fever, and arthralgia whose CXR and thoracic CT showed widespread nodular infiltration. His proteinase-3 anti-neutrophilic cytoplasmic antibody (c-ANCA) was positive. The serum creatinine was increased and haematuria subsequently developed. Renal biopsy revealed a focal segmental necrotizing glomerulonephritis which was compatible with MPA. He was treated with high-dose corticosteroid and cyclophosphamide. Because of a worsening CXR and hypoxaemia, mechanical ventilation was applied. Despite this he died of respiratory failure following 20 days of treatment. Nodular infiltration is an unusual radiological pattern in patients with MPA and is the reason for this report.

Solitary metastasis of renal cell carcinoma to the parotid gland 10 years after radical nephrectomy.

Renal cell carcinoma metastasis to the parotid gland after tumor nephrectomy is extremely rare. We report a case of solitary parotid metastasis from clear cell renal cell carcinoma in a 59-year-old woman, who presented 10 years after primary treatment. To our knowledge this is the first case in the published literature presenting with solitary parotid metastasis after such a long time. Superficial parotidectomy with preservation of the facial nerve was performed. One year after, the patient developed contralateral multiple kidney tumors and underwent left radical nephrectomy. She is currently on a dialysis program and no additional metastasis has been observed for 18 months.

Prostatic ductal adenocarcinoma showing Bcl-2 expression.

Prostatic ductal adenocarcinoma represents a rare histological variant of prostatic carcinoma with features of a papillary lesion at cystoscopy. There are conflicts regarding the existence, origin, staging, grading, treatment and clinical behavior of this tumor. The aim of the present study is to examine the expression of Bcl-2 and p53 in prostatic ductal adenocarcinoma and to evaluate its origin by analyzing prostate specific antigen, prostate specific acid phosphatase, cytokeratins, epithelial membrane antigen and carcinoembryonic antigen expressions. The results confirmed the expression of prostate specific antigen and prostate specific acid phosphatase in prostatic ductal adenocarcinoma. The demonstrated expression of Bcl-2 was predominant in the better-differentiated tumor. Bcl-2 expression appears not to be associated with neuroendocrine differentiation as assessed by chromogranin A reactivity. Thus, the first case of a prostatic ductal adenocarcinoma showing Bcl-2 expression is presented. The tumor was negative for p53.