Prognostic Value of Soluble Death Receptor Ligands in Patients with Transitional Cell Carcinoma of Bladder.

BACKGROUND: The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer. METHODS: The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively. RESULTS: Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form. CONCLUSION: The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer.

Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.

BACKGROUND: The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. METHODS: Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity. RESULTS: T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p < 0.0001) is significantly higher than in invasive bladder tumors and in patients with high-grade bladder carcinoma, respectively. In addition, heavy smokers, whose tumors express low levels of GATA-3 and Bcl-6, are poor responders to BCG (p = 0.01 and p = 0.03). Finally, better patient survival correlated with GATA-3 (p = 0.04) and Bcl-6 (p = 0.04) but not T-bet expression. CONCLUSIONS: Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.

Akt activation correlates with the tumor aggressiveness in Tunisian patients with bladder cancer.

Various studies in western countries found Akt amplification to be a frequent event in human cancers, including bladder, but the correlation with clinicopathological features is controversial. Such studies have not been reported in African populations, including Tunisians. The purpose of this study was to assess expression of the phosphorylated/activated forms of Akt in tumors from Tunisian patients with bladder cancer and to correlate its expression with pathological and clinical parameters of the disease. The study included 72 patients of whom 34 were diagnosed as low- to medium-grade and 35 as high-grade; 30 were muscle stage and 39 non-muscle stage. Primary tumors from these patients, normal adjacent tissues, or bladder cancer cell-lines were analyzed for Ser473 phosphorylated Akt expression by Western blot. Seventy-two percent of primary tumors from patients with bladder cancer had increased levels of p-Akt. The p-Akt levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer. In invasive carcinoma, the p-Akt level was significantly higher than in superficial non-invasive bladder tumors. Concerning the influence of tobacco on Akt activation, no significant differences of p-Akt expression were found between non-smoker and smoker patients. Altogether, our results suggest that Akt activation can provide useful prognostic information and that tobacco represents a serious risk factor for recurrence in a cohort of Tunisian patients.

Over-expression of EGFR is closely correlated to poor prognosis in Tunisian patients with non-small cell lung adenocarcinoma.

We studied epidermal growth factor receptor (EGFR) expression profile with the aim of an individualized therapy for patients with non-small cell lung cancer (NSCLC) from whom tumor materials are not sufficient for molecular investigations. Using immunohistochemistry, we found a markedly increased EGFR expression with significant difference in term of intensity and distribution from normal mucosa to primary tumors (p < 0.05). Furthermore, patients with EGFR positive tumors had significantly shorter survival than those with EGFR negative tumors (p = 0.0001). Thus, EGFR over-expression is a valuable prognostic marker to predict poor outcome in Tunisian patients with NSCLC.

[Immunohistochemical analysis of mismatch repair proteins in colorectal adenomas]. / Analyse immunohistochimique des protéins de réparation de I'ADN dans les adénomes colorectaux.

BACKGROUND: The deficiency of mismatch repair system is one of the main pathways in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2, MSH6 and PMS2. Colorectal cancer develops in the majority of cases from precancerous lesions called adenomas. Only few studies have reported on the deficiencies of these proteins in adenomas. AIM: In this study we used immunohistochemistry staining in colorectal adenomas to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins. METHODS: 102 adenomas from 93 patients were collected in our institution during six years (2007-2012). The immunohistochemical technique was performed with 4 antibodies: MLH1, MSH2, MSH6 and PMS2. The loss of expression was retained if adenomatous cells were not stained with positive internal control. Staining was considered as abnormal if nucleus of adenomatous cells showed low nuclear staining and / or heterogeneous one, while positive internal control had normal staining. RESULTS: Loss of expression of MSH2 and MSH6 in adenomatous cells was found in only 1 case which was a tubular adenoma 3mm high-grade dysplasia. Abnormal staining of the adenomatous cells was noted in 23 cases (22.5%) for MSH2 and in 8 cases (7.8%) for MSH6. No cases showed loss of expression of MLH1 and PMS2. Abnormal expression of MSH2 and MSH6 was not correlated with sex of patients, the location of the adenoma, its grade of dysplasia and its histological type. CONCLUSIONS: Loss of Mismatch repair proteins expression is a rare event in adenomas. However, the abnormal expression levels are higher in our study compared to those reported in the literature. This could reflect a higher rate of microsatellite instability in our patients. Multicenter and larger studies with molecular biology techniques are needed.

Prognostic value of Pheochromocytoma of the Adrenal Gland Scaled Score (Pass score) tests to separate benign from malignant neoplasms.

BACKGROUND: Differentiating malignant from benign pheochromocytoma has been challenging when based on histologic features. This is due to the definition of malignant pheochromocytoma which are defined by the presence of metastases. A PASS score was developed and according to many authors, a PASS score> =4 identified potentially malignant tumors. AIM: To assess the prognostic value of PASS score in differentiating benign pheochromocytomas from malignant ones. METHODS: The records of 11 patients with tumors diagnosed as "pheochromocytoma" were identified from 1970 to 2010 in the files of the pathology, intern medicine and biochemistry departments of the Charles Nicolle hospital and Pasteur Institute. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic performance of PASS. The logistic model was developed using the 11 predictive variables. Its performance was evaluated by calculating the area under the ROC curve and comparing it with that of the PASS. RESULTS: In benign tumors, The PASS score was <4 in 3 cases and >=4 in 6 cases. In malignant tumors, the PASS score was >=4 in both cases. According to the ROC curve analysis, a PASS equal or superior to 4 identifies malignant pheochromocytoma with a sensitivity of 50% and a specificity of 45%. CONCLUSION: I think that PASS score, despite its low sensitivity, may help to reserve the more aggressive treatment and narrow follow up for potentially malignant tumors. Widespread of this called score with complete clinical data will help to validate these findings and to add other prognostic factors of value that could be a part of this scaled score such as immunohistochemical findings.

Primary testicular non-Hodgkin lymphoma. a 10-year Tunisian single-institute experience.

BACKGROUND: Primary testicular non-Hodgkin lymphoma (NHL) is an uncommon extra nodal presentation, accounting for 1% of all NHL and 1 to 9% of testicular neoplasms. Median age at time of presentation is 60 years old. Anthracycline based chemotherapies are most frequently used. AIM: To analyze baseline characteristics, treatment modalities and survival of six cases of primary testicular non-Hodgkin lymphoma. METHODS: We screened 46 testicular neoplasm cases registered from January 1999 to January 2009 and found six primary testicular lymphoma patients. These six cases were analyzed for baseline clinical features, investigations, treatment and outcome variables. RESULTS: Median age was 50 years old and median duration of symptoms was 4 months. All patients had testicular swelling. Four patients had abdominal lymphadenopathy. Most patients had diffuse large B-cell histology. All patients underwent high inguinal orchidectomy and five were treated with anthracycline based chemotherapy. Four patients completed therapy and one of them relapsed two years later. CONCLUSION: Primary testicular NHL is an uncommon entity and with current combined modality treatment, the outcome may be as good as nodal NHL.

Postvaccination morphea profunda in a child.

We report a new case of postvaccination morphea profunda (MP) in a child and discuss its different clinical presentations, prognosis, and therapy and its relationship with "solitary morphea profunda." A 2-year-old healthy girl presented with an induration of the anterior aspect of the left thigh of 9 months duration. The lesion had appeared 3 months after a third dose of diphtheria-tetanus-pertussis vaccine. Cutaneous examination showed an induration of 7 × 7 cm with an "orange peel" texture after pinching the skin. Histologic examination confirmed the diagnosis of MP. Systemic steroids (1 mg/kg/day) led to the stabilization of the lesion. After 4 months of treatment, we began the concomitant use of oral methotrexate (10 mg/wk) for 2 months. Methotrexate was then continued alone for 10 months, leading to a significant regression of the induration with no relapse.

A case of multiple epithelioid angiomatous nodules.

Cutaneous epithelioid angiomatous nodule (CEAN) is a distinct type of epithelioid vascular tumor that is usually solitary. Herein we present a 31-year-old man with multiple, rapidly growing nodules on the scalp.

Pigmented lesion in the inguinal region.

Pigmented Bowen disease (PBD) is a rare tumor characterized by increased melanin pigment in the epidermis or papillary dermis in addition to the typical findings of Bowen disease. We report the case of a 60-year-old woman who presented with a 6-month history of a gradually enlarging solitary dark brown plaque in her right inguinal region. Histopathology showed hyperkeratosis with parakeratosis, acanthosis, disorganization of epidermal architecture, atypical keratinocytes, and increased melanin pigment of the papillary dermis. Considering the clinical and the histological evidence, a diagnosis of PBD was established. Complete resection confirmed the diagnosis. Pigmented Bowen disease is an unusual form of squamous carcinoma in situ. Other tumors in the differential diagnosis include pigmented basal cell carcinoma and superficial spreading melanoma.

Erythema elevatum diutinum: an "idiopathic" case.

Erythema elevatum diutinum (EED) is a rare condition with an unclear pathogenesis. Initially classified within neutrophilic dermatoses, it is now considered as a leukocytoclastic vasculitis accordingly to its histopathologic pattern. Several clinical presentations as well as many associated diseases are reported in the literature. We report a new case of EED in a 58-year-old man who presented with a three-month history of plaques and nodules on the extensor surfaces of hands, elbows, knees, ankles, forearms, and buttocks. Histology showed a leucocytoclastic vasculitis, suggestive of the diagnosis of EED. Screening for an associated pathology, namely a paraproteinemia or a solid cancer, was negative. Treatment with dapsone leads to amelioration within few weeks.

Giant trichoblastoma of the scalp.

BACKGROUND: Trichoblastoma is a rare and benign adnexial tumor with characteristic histological features. It occurs on any hair folliclebearing location, and usually presents as a solitary lesion most often less than 2 cm in size. Giant trichoblastoma has been rarely reported in the literature. AIM: To report a new case of giant trichoblastoma, misleading for malignancy. CASE REPORT: A 57-year-old woman presented with a 5 cm-solitary asymptomatic nodular lesion of the scalp, of 28 years. It had been previously excised with recurrence and progressive regrowth. On examination, it was a dome-shaped, erythematous, firm, papillomatous, non infiltrated nodule. Full body work up revealed no metastases. Cutaneous biopsy concluded to trichoblastoma but failed to eliminate malignancy. After excision with secondary skin graft, histological examination confirmed the benignity with clear margins. There was no evidence of recurrence after a 5 year-follow-up period. CONCLUSION: This case illustrates a rare clinical variant of trichoblastoma with an unusual important size. This can be misleading for malignancy, but the slowly progressive course of the tumour in our patient, together with histological benignity led to the correct diagnosis. This tumour is considered as a distinct entity by some authors.

Xeroderma pigmentosum skin: an immune privilege site for tumor development.

A unique feature of the skin immune system is its proximity to cells continuously exposed to sun rays, as it is located in the interface between the body and the environment. In this study, we aimed to determine the impact of DNA damaged keratinocytes on the expression of apoptotic-related molecules, in T-cells of the inflammatory component of the tumor environment. Immunohistochemistry was performed on tissue sections derived from skin biopsies of basal cell carcinomas (BCCs) of xeroderma pigmentosum (XP) patients, non-XP patients and nevoid basal cell carcinoma syndrome (NBCCS) patients, using antibodies against B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), CD95, CD3, CD8 and CD56. Our results showed significantly lower levels of expression of the antiapoptotic Bcl-2 molecule, in XP, in comparison with non-XP and NBCCS T-lymphocytes, leading to the highest Bax/Bcl-2 ratio for XP T-cells. For the CD95 receptor expression levels, there were significant differences among T-cells of the three patient subgroups as well. The higher propensity of XP T-cells to undergo apoptosis may have evolved in individual XP patients, apparently during the course of their disease, to maintain a special skin as an immune privilege site for tumors' development.

Vulvoperineal Crohn's disease: response to metronidazole.

A 46-year-old woman with a medical history of chronic juvenile arthritis with bilateral prosthetic hips presented with vulvoperineal ulcerations of 3 years' duration. There was no diarrhea or recent weight loss. Cutaneous examination showed asymmetrical vulvar edema of the labia minora and labia majora with deep and linear ulcerations having verrucous borders located on the inguinocrural regions and the buttocks fold (Figure 1). On physical examination there was bilateral limited mobilization of the hips. A biopsy specimen was taken from the border of the vulvar ulceration and histologic examination showed under a hyperplasic epidermis an epithelioid granuloma with multinucleated giant cells of the dermis without caseification. Laboratory analyses and results from chest x-ray were normal. Results for Koch bacilla in the spittle, microbiologic studies (staining for microorganisms and cultures), and tuberculin intradermoreaction were negative. There was no Crohn's disease aspect on colonoscopy, and there was normal small bowel enterography. Systematic intestinal biopsies were also with normal aspect. Based on the clinical data and granulomatous histologic characteristics, the diagnosis of metastatic Crohn's disease without digestive involvement was obtained. The patient was started on metronidazole 1 g/d. After 6 months of treatment, there was an almost-complete healing of ulcerations (Figure 2). Treatment was well-tolerated.

[Odontogenic myxoma: About four cases and review of the literature]. / Le myxome odontogénique : étude de quatre cas et revue de la littérature.

OBJECTIVE: Odontogenic myxoma is an uncommon tumor that represent less than 0,5% of all bone tumors and only 3 to 6% of odontogenic tumors. The aim of this article was to catalogue the clinical cases diagnosed microscopically as odontogenic myxoma and to describe their clinical and radiographic characteristics, comparing these to the data found in the current literature. DESIGN: Histological and immunocytochemical examinations were performed on odontogenic myxomas from four Tunisian patients in a period of 23 years. RESULTS: In the present series, two were male and two female. The age at diagnosis ranged from 19 to 38 years. Three tumors involved the mandible and one occurred in the maxilla. In all cases with radiographic records, lesions presented with a multilocular and osteolytic appearance. Histologically, odontogenic myxomas were mainly composed of spindled or stellate-shaped cells in a mucoid-rich intercellular and alcian blue positive matrix. All cases were treated by tumor-enucleation. There was no evidence of recurrence after 2 to 8 years. CONCLUSION: Clinical and radiological aspects of odontogenic myxomas are not conclusive; a histopathological examination of the lesion is mandatory in order to make the right diagnosis. Because of its high rate of recurrence, surgical treatment through bone resection is the most indicated treatment modality, and the patient must be followed-up closely for years.

Multiple keratoacanthoma centrifugum marginatum.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma characterized by a progressive peripheral growth with concomitant central healing. We report here a case of multiple KCM of the lower legs in a 48-year-old man. The lesions had progressively evolved over 3 years. They were multiple asymptomatic and confluent annular plaques of 5 to 20 cm, having papulo-nodular with hyperkeratotic and crusted borders and cicatricial center. Within the centers were numerous firm and pigmented minipapules of 1 to 2 mm. The typical clinical aspect, together with characteristic histological features confirmed the diagnosis of KCM. Herein we will highlight the clinical and histological features of KCM, as well as the different effective treatments. We will also briefly discuss KCM among the other types of keratoacanthomas.

The utility of alpha-methyl CoA racemase (P504S) expression as a marker of renal cell carcinomas.

BACKGROUND: Renal cell tumours are numerous and heterogeneous. Because of their clinicopathological heterogeneity, their accurate diagnosis may be challenging. In case of an equivocal diagnosis, immunohistochemistry may be a useful mean of diagnosis. Recently, alpha-methyl CoA racemase has been identified as a useful marker in kidney cancers. AIMS: Our objectives are to highlight the role of alpha-methyl CoA racemase (AMACR) as a diagnostic marker in papillary renal carcinoma and to assess its utility in the other tumour types. METHODS: Aretrospective review was performed on 62 patients who were treated for renal tumours between January 1994 and November 2005. Immunoreactivity was evaluated with a qualitative manner. Positive AMACR staining was defined as a coarse dense cytoplasmic granularity. RESULTS: The 62 renal tumours were diagnosed as papillary tumours in 22 cases, clear cell tumours in 18 cases, chromophobe carcinoma in 12 cases and oncocytoma in 10 cases among the 22 cases of papillary tumours, all the cases (100%) showed cytoplasmic immunoreactivity staining. 4 cases between the 18 clear cell carcinomas (22%) showed positivity with AMACR. The 12 cases of chromophobe carcinoma didn't express AMACR by immunohistochemistry. Only one case between the oncocytomas (1%) expressed AMACR. CONCLUSION: This study confirms the high sensitivity of AMACR for papillary renal cell carcinomas but we must keep in mind that weak focal AMACR staining could be present in other renal cell carcinomas.

Rosacea: 244 Tunisian cases.

BACKGROUND: Rosacea is a common, chronic facial dermatosis of uncertain etiology, several well-defined types and variable progression. There is a paucity of epidemiologic studies from North African countries especially in Tunisia. AIM: to determine epidemiological, clinical, histological features, treatment and outcome of rosacea in a Tunisian study. METHODS: A retrospective study of all rosacea cases diagnosed in the outpatient Dermatology Department of Charles Nicolle hospital of Tunis was conducted between 1990, January and 2003, May. RESULTS: Our study included 244 patients. The diagnosis of rosacea was made on symptoms and clinical features in 185 cases and on histological findings in 59 patients. The hospital prevalence of rosacea was 0.2%. The sex ratio M/F was 0,4. Patient's Mean age was of 49 years. Triggered factors mentioned included most often: sun exposure (64%) and thermal stimuli (25%). Mean duration between the onset of symptoms and the first consultation was about 20 months. The rosacea subtypes were: erythematotelangiectatic type (12%), papulopustular rosacea (69%), and rhinophyma (3.7%). Granulomatous rosacea was diagnosed in 8 patients and steroid rosacea in 28 cases. Ocular rosacea was observed in 41 cases. Treatment modalities included: topical treatment (1.6%), systemic treatment (85%), systemic and topical treatment (5%) and surgical procedures (1.2%). CONCLUSIONS: Rosacea seems to be a frequent dermatosis in Tunisia where most of the population is phenotype IV-V. It affects mostly middle-aged women. Most of our patients present with papulopustular rosacea (69%). More epidemiological and clinical studies in North African countries should be conducted to emphasize these results.

[Microcystic serous pancreatic cystadenoma]. / Cystadénome séreux microkystique du pancréas.

BACKGROUND: The pancreatic cystic serous neoplasms are divided into two categories: benign serous cystadenoma (SCA) and malignant serous cystadenocarcinoma. Furthermore, based on the macroscopic appearances, SCAs are subdivided into serous microcystic adenomas (SMAs) and serous oligocystic or macrocystic adenomas. AIM: Report of a new case of SMA in which we emphasize on the diagnostic difficulties encountered against such tumor despite its relatively radiological easiness compared to the other variants. CASE REPORT: We report the case of 84 year-old-woman with a microcystic serous cystadenoma of the pancreas which was identified on pathologic examination of the surgical specimen, after unconclusive abdominal ultrasound and computed tomography (CT)- scan. CONCLUSION: This case describes this rare entity and emphasizes that the diagnosis of such entity is still based on pathological examination after tumor removal.