Giant cell hepatitis with autoimmune hemolytic anemia in a nine month old infant.

Giant cell hepatitis (GCH) with autoimmune hemolytic anemia is a rare entity, limited to young children, with an unknown pathogenesis. We report the case of 9-mo old who presented with fever, diarrhea and jaundice four days before hospitalization. Physical examination found pallor, jaundice and hepatosplenomegaly. The laboratory workup showed serum total bilirubin at 101 µmol/L, conjugated bilirubin at 84 µmol/L, hemolytic anemia, thrombocytopenia and immunoglobulin G (IgG) and anti-C3d positive direct Coombs' test. The antinuclear, anti-smooth muscle and liver kidney microsomes 1 non-organ specific autoantibodies, antiendomisium antibodies were negative. Serological assays for viral hepatitis B and C, cytomegalovirus, herpes simplex and Epstein Barr virus were negative. The association of acute liver failure, Evan's syndrome, positive direct Coomb's test of mixed type (IgG and C3) and the absence of organ and non-organ specific autoantibodies suggested the diagnosis of GCH. The diagnosis was confirmed by a needle liver biopsy. The patient was treated by corticosteroids, immunomodulatory therapy and azathioprine but died with septicemia.

Reproductibilité des classifications OMS 1973 et OMS 2004 des tumeurs urothéliales papillaires de la vessie.

UNLABELLED: RéSUMé: OBJECTIF : Déterminer les taux d'accord et la reproductibilité intra et inter-observateurs des classifications OMS 1973 et OMS 2004 des tumeurs urothéliales papillaires de la vessie. MATéRIEL ET MéTHODES : Cent deux cas de tumeurs urothéliales papillaires de stade pTa/pT1 ont été étudiés. Deux pathologistes ont revu les lames et ont établi le grade tumoral selon les deux classifications OMS 1973 et OMS 2004. En cas de désaccord, les deux évaluateurs ont procédé à une lecture commune au microscope en double tête afin d'aboutir à un grade consensuel selon les deux classifications. La variabilité intra-observateur a été étudiée chez l'un des deux évaluateurs qui a procédé à la relecture des lames un mois après sa première lecture. Les taux d'accord entre les deux pathologistes pour chaque catégorie de grade ont été déterminés et la reproductibilité des deux classifications a été évaluée à l'aide du coefficient kappa. Une valeur de 0 à 0,2 était interprétée comme un désaccord absolu, de 0,21 à 0,4, un accord faible, de 0,41 à 0,6, un accord modéré, de 0,61 à 0,8, un accord considérable, et de 0,8 à 1, un accord absolu. RéSULTATS : Selon la classification OMS 1973, les proportions des grades G1, G2 et G3 étaient respectivement de 40,2 %, 50 % et 9,8 %. Selon la classification OMS 2004, les proportions respectives des tumeurs de faible potentiel de malignité, des carcinomes de bas grade et des carcinomes de haut grade de malignité étaient de 23,5 %, 60,8 % et 15,7 %. La reproductibilité intra-observateur était excellente pour les deux classifications (accord absolu). Les taux d'accord entre les deux pathologistes étaient meilleurs pour la classification OMS 2004 (kappa = 0,7) que pour la classification OMS 1973 (kappa = 0,51). CONCLUSIONS: La reproductibilité entre observateurs de la classification OMS 2004 est supérieure à celle de 1973. La reproductibilité intra-observateur est excellente pour les deux classifications.

Colorectal cancer in Central Tunisia: increasing incidence trends over a 15-year period.

INTRODUCTION: Significant variation in colorectal cancer incidence rates and trends has been observed across countries. Data from Tunisia are sparse. In this paper, we analyzed trends in incidence rates of the colorectal cancer over a 15-year period, 1993-2007, in Central Tunisia. DESIGN: Five-year age-specific rates, crude incidence rates, world age-standardized rates, and annual percent change were calculated using annual data on population size and its estimated age structure. RESULTS: A total of 1,443 incident cases of colorectal cancer were registered, with a male to-female sex ratio of 1.1:1. The world age-standardized rate was 10.0 per 100,000 among females and 11.7 among males. Over time, there were significant increasing trends by +2.6% (95% CI: 0.1%, 5.1%) and +5.3% (95% CI: 2.7%, 7.9%) for females and males, respectively. CONCLUSION: The absence of a screening program for colorectal cancer could explain the increasing trends observed among males and females in Central Tunisia. Our findings point the need to plan and develop effective programs aimed at the control and prevention of the spread of colorectal cancer in Tunisia.

Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix.

Aberrant DNA methylation is an early event in carcinogenesis and could serve as an additional molecular marker for the early diagnosis. The study was performed to investigate the promoter methylation of DAPK1, CDH13, and TWIST1 genes in uterine cervix lesions in an effort to examine whether this epigenetic event is involved in the process of cervical carcinogenesis, and whether it might be used as a molecular marker of cervical lesions. We conducted a retrospective study of 60 uterine cervix specimens, including 8 normal tissue samples, 10 benign lesions, 28 precancerous lesions (CIN1-3), and 14 squamous cell carcinomas (SCC). DNA hypermethylation was investigated using methylation-specific PCR. Immunohistochemistry was used to find p16(INK4A) overexpression. No hypermethylated promoters were detected in normal tissues and benign lesions. However, promoter hypermethylation of CDH13, TWIST1, and DAPK1 increased progressively from CIN1 to cancer, reaching values higher than 50% for cancer. DAPK1 and CDH13 displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia (p<0.05). A statistically significant association was observed between p16(INK4A) expression and hypermethylation of DAPK1, TWIST1, and CDH13 (p<0.0001). Hypermethylation of CDH13, DAPK1, and TWIST1 promoters is an early event in the initiation and progression of cervix neoplasia. CDH13, DAPK1, and TWIST1 genes are potential biomarkers of cervical cancer risk.

Validation of nomograms to predict the risk of non-sentinels lymph node metastases in North African Tunisian breast cancer patients with sentinel node involvement.

INTRODUCTION: In approximately half of patients with breast cancer and lymph node metastases, the sentinel node (SN) is the only involved axillary node. Scoring systems have been developed to predict probability of non-SN metastases among those with a positive SN. The goal of the present study was to determine whether the five models (Memorial Sloan-Kettering Cancer Center (MSKCC), Stanford, Tenon, Cambridge and the Turkish model) accurately predicted non-SN involvement in a North African Tunisian population. METHODS: During a five years period, we identified 87 cases of invasive breast cancer which had a positive SN biopsy and complete axillary lymph node dissection (CALND). The MSKCC, Stanford, Tenon, Cambridge and Turkish models were tested. Results were compared using the area under the curve (AUC) of the receiver operating characteristics for each model. False negative and false positive rates were also calculated. RESULTS: The AUC of the MSKCC, Stanford, Tenon, Cambridge and Turkish models was respectively 0.73 (95% CI 0.6-0.86), 0.76 (95% CI 0.65-0.87), 0.75 (95% CI 0.63-0.87), 0.67 (95% CI 0.53-0.82) and 0.75 (95% CI 0.63-0.88). The threshold for a 10% false negative of non-SN involvement was obtained with a cut off value of 10% for MSKCC, 25% for Stanford, a score of 3 for Tenon, 6% for Cambridge and 15% for the Turkish nomogram. CONCLUSIONS: Meaningfully applied to our population, although AUC values had overlapping of 95% confidence intervals but combined our data suggest that the Stanford nomogram may be the most accurate. Before prospective trials validate these nomograms, CALND remains the standard for patients who have SN metastases.

Cervical adenocarcinoma and squamous cell carcinoma incidence trends among Tunisian women.

INTRODUCTION: Uterine cervix cancer is an important public health problem in Tunisia. In this study, we report trends in the incidence of adenocarcinoma and squamous cell carcinoma of the cervix uteri in the central region of Tunisia during 1993-2006. DESIGN: Data were obtained from the Cancer Registry of the Center of Tunisia which registers invasive cancer cases by active methods. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual population data. RESULTS: Among all women cancers, cervix uteri cancer accounted for 5.9% and ranked the fourth during the study period with an ASR of 6.9 per 100,000. The ASRs decreased notably with an APC of -6.7% over the whole period. However, incidence rates of adenocarcinomas have increased during the last years (APC: +14.4%). CONCLUSION: The introduction of cytological screening programs has led to a marked decrease of the incidence rates of cervix uteri cancer among Tunisian women. The data underline the fact that the population-based cancer registry is an indispensable tool for providing data for planning and evaluation of programs for cancer control.

Distribution of molecular breast cancer subtypes among Tunisian women and correlation with histopathological parameters: a study of 194 patients.

According to the immunohistochemical test of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2), breast cancer can be divided into 4 molecular subtypes: luminal A, luminal B, Her-2, and basal-like. The purpose of this study is to correlate these subtypes with clinicopathological features. We have selected from the files of our Pathology Department 194 breast carcinomas which had already been studied for ER, PR, and Her-2, diagnosed between January 2008 and October 2009. The cases were classified into 4 molecular subtypes. The clinicopathological characteristics of each subtype were compared. The luminal A subtype was the most prevalent (51.5%). The basal-like and Her-2 subtypes were significantly correlated to a large tumor size, a high tumor grade, and a high-volume nodal involvement (≥4). On multivariate analysis, patients with the Her-2 and basal-like subtypes were 4.2 (95% CI, 1.3-13.5) times more likely to have developed metastases in four or more lymph nodes than those with luminal tumors. Our analysis revealed that the Her-2 and basal-like subtypes are correlated with factors associated with a poor prognosis. The luminal A subtype is the commonest subtype, showing that breast cancer in Tunisia has no aggressive phenotype.

Cervix cancer in Tunisia: clinical and pathological study.

INTRODUCTION: Uterine cervix cancer is the second most commonly diagnosed cancer among women worldwide. DESIGN: In order to review the clinical and pathological features of cervix cancer in the center of Tunisia, a retrospective study was carried out on 410 cancer cases diagnosed in the Pathology Department, Farhet Hached University Hospital, Sousse, Tunisia (1993-2006). RESULTS: The mean age was 52.1 years. Of the 410 patients, 90.5% had squamous cell carcinoma and 7.3% had adenocarcinoma. One hundred thirty-eight patients were identified as being in early stages (0 and I) (33.6%) and 58.2% in advanced stages (II-IV). Therapy consisted mainly in combination of radiotherapy and surgery in early stages (28.8%), and radiotherapy alone or associated with the chemotherapy in advanced stage (29.7%). Surgery was the only treatment in 29.5% of cases. CONCLUSION: A relatively large proportion of patients presented in stages II to IV, as compared to only 36% with early stages, emphasizing the need to reinforce the early detection of this cancer and its precursor lesions in the center of Tunisia.

Trends in the incidence of cancer in the Sousse region, Tunisia, 1993-2006.

In this article, we analyzed trends in incidence rates of the major cancer sites for a 14-year period, 1993-2006, in the Sousse region localized in the centre of Tunisia. Five-year age-specific rates, crude incidence rates (CR), world age-standardized rates (ASR), percent change (PC) and annual percent change (APC) were calculated using annual data on population size and its estimated age structure. A total of 6,975 incident cases of cancer were registered, with a male to-female sex ratio of 1.4:1. ASRs showed stable trends (-0.1% in males, and +1.0% in females). The leading cancer sites in rank were lung, breast, lymphoma, colon-rectum, bladder, prostate, leukemia, stomach and cervix uteri. For males, the incidence rates of lung, bladder and prostate cancers remained stable over time. While, cancers of colon-rectum showed a marked increase in incidence (APC: +4.8%; 95% CI: 1.2%, 8.4%) and non-Hodgkin's lymphoma (NHL) showed a notable decline (APC: -4.4%; 95% CI: -8.2, -0.6). For females, cancers of the breast (APC: +2.2%; 95% CI: 0.4%, 4.0%) and corpus uteri (APC: +7.4%; 95% CI: 2.8%, 12.0%) showed a marked increase in incidence during the study period, while the cervix uteri cancer decreased significantly (APC: -6.1%; 95% CI: -9.2%, -3.0%). The results underline the increasing importance of cancer as a cause of mortality and morbidity in Tunisia. Our findings justify the need to develop effective program aiming at the control and prevention of the spread of cancer amongst Tunisian population.

[Prevalence of HPV infection in precancerous and cancerous lesions of the uterine cervix in Tunisia]. / Prévalence des infections à papillomavirus (HPV) dans les lésions précancéreuses et cancéreuses du col utérin en Tunisie.

OBJECTIVES: To investigate the distribution of HPV genotypes inuterine cervical lesions in Central Tunisia in order to predict the impact ofHPV vaccines and HPV-based screening tests among Tunisian women. MATERIAL AND METHODS: We performed a retrospective study of 146 fixed tissues including 30 benign lesions, 36 low-grade cervical intraepithelial neoplasias (CIN1), 45 high-grade cervical intraepithelial neoplasias (CIN2/3), 26 invasive squamous cell carcinomas (SCC) and 9 adenocarcinomas. HPV infection detection and typing were investigated by PCR technique using consensus GP5/GP6 primers and type specific primers for HPV6/11, 16, 18, 31 and 33. RESULTS: Among our patients, overall HPV prevalence was 73.6% (p = 0.0001). HPV infection was associated to 84% of precancerous lesions and 83.9% of cancers. High-risk HPV infection (HPV16 and 18) was detected in 17.4% of CIN1, 74.3% of CIN2/3 (p = 0.002) and 73.1% of cancers (p = 0.001). HPV16 was the most common type among CIN2/3 (51.2%, p < 0.001), invasive SCC (47.6%, p = 0.001) and adenocarcinomas (80%, p < 0.001). CONCLUSION: This study supports previous population-based studies in which similar HPV detection rates were found among random samples of women. HPV-based screening tests and HPV vaccination would be efficient in uterine cervix cancer prevention among women in the Central Tunisia.

p16INK4A overexpression in precancerous and cancerous lesions of the uterine cervix in Tunisian women.

Uterine cervix cancer is an important public health problem in developing countries. However, there is a substantial lack of inter-observer diagnostic reproducibility for its precursor lesions (CIN1). The study was performed to evaluate the usefulness of p16(INK4A) overexpression as a surrogate marker for uterine cervix precancerous lesions and high-risk human papillomavirus (HPV) infection. We conducted a retrospective study of 87 uterine cervix specimens, including 7 normal tissue samples, 17 benign lesions, 34 precancerous lesions, 22 invasive squamous cell carcinomas (SCC), and 7 adenocarcinomas. Immunohistochemistry was used to find p16(INK4A) overexpression. HPV infection was detected by PCR. No immunoreactivity for p16(INK4A) was detected in normal tissue or benign lesions. p16(INK4A) immunoreactivity was focal in CIN1, whereas strong and diffuse immunoreactivity for p16(INK4A) was uniformly observed in both the nucleus and the cytoplasm of all CIN2 and 3, as well as in those of invasive SCC and adenocarcinomas. A statistically significant association was observed between p16(INK4A) overexpression, lesion grade, and high-risk HPV infection (p<0.0001). p16(INK4A) overexpression is a useful additional marker for the interpretation of problematic uterine cervical lesions and can help to reduce the variability during evaluation of suspicious biopsies of the uterine cervix.

Extra ocular sebaceous carcinoma of the thigh: A case report.

CONTEXT: Sebaceous cell carcinoma is a malignant neoplasm, rarely recognized in extra ocular sites. His prognosis depends of the precocity of the diagnosis. This neoplasm is aggressive in 29%; lymph node and visceral metastasis aren't rare. CASE REPORT: An 80-year-old male had an ulcerated and infected nodule located on the left thigh. The lesion appeared after five months ago. It suspected a squamous cell carcinoma. The histologic findings revealed an extra ocular sebaceous carcinoma. The patient died one month later due to heart insufficiency. CONCLUSION: extra ocular sebaceous carcinoma is a rare neoplasm. It has more difficulties of diagnosis because it has diverse clinical presentations as well as a variety of histologic patterns. We will discuss the incidence, clinical, histological and the prognosis of this aggressive neoplasm.

Mucinous carcinoma with axillary lymph node metastasis in a male breast: A case report.

CONTEXT: Pure mucinous carcinoma of the male breast is an extremely rare neoplasm. It is characterized by a lower incidence of metastatic nodal involvement and a higher survival rate than invasive ductal carcinomas. CASE REPORT: We report the case of a 75-year-old male who presented with a retroareolar mass of the right breast. The patient underwent radical mastectomy including right axillary lymph node dissection. The tumor was well demarcated and had a friable consistency with a gelatinous appearance. Histologically, the diagnostic of pure mucinous carcinoma with lymph node metastasis was performed. After surgery, the patient received chemotherapy, radiotherapy, and hormonotherapy (Tamoxifen). The patient remained free of disease for 36 months after surgery. CONCLUSION: Pure mucinous carcinoma of the male breast is a very rare tumor; in which axillary nodal disease is exceptional.

Synovial Sarcoma: A Clinicopathological and Radiological Study of 12 Cases Seen Over 18 Years.

BACKGROUND: Synovial sarcoma is a rare malignant soft tissue tumor characterized by a poor outcome. We report herein our experience concerning synovial sarcoma and review its diagnosis, histology, treatment and prognosis. METHODS: This is a retrospective review, from 1990 to 2007, of cases of synovial sarcoma diagnosed at the Department of Pathology, Farhat Hached hospital, Sousse, Tunisia. The clinical, radiological and pathological features as well as treatment modalities and patient's outcome were recorded. RESULTS: From 1990 to 2007, 12 cases of synovial sarcoma have been diagnosed in our department. Patients' mean age at the time of diagnosis was 21 years. There was no sex predominance and the lower extremity was the most commonly involved. A painful tumefaction was the most common presenting symptom. The duration of symptoms ranged from 6 months to 6 years. Malignancy was suspected on radiological findings in only 2 cases. Ten patients underwent surgery, in association with adjuvant chemotherapy in 4 cases, one of whom underwent post-operative radiotherapy. Histological subtypes included monophasic synovial sarcoma in 8 cases, biphasic synovial sarcoma in 3 cases and poorly differentiated synovial sarcoma in one case. At the time of analysis, 6 patients were dead with an average follow-up of 18 months. CONCLUSIONS: Synovial sarcoma is a rare malignancy with a propensity for young adults and a poor prognosis. Its symptomatology is non-specific and it is characterized by histopathological diversity. Diagnosis can be suggested by radiology and definitive diagnosis is achieved after pathological analysis.

In Situ and Invasive Ductal Carcinoma Within a Borderline Phyllodes Tumor.

A rare case of a borderline phyllodes tumor with simultaneous intraductal and infiltrating duct carcinoma is reported. The patient was a 52-year-old woman with a breast tumor detected by physical examination. A simple mastectomy was performed. The excised tumor had a macroscopic appearance of a phyllodes tumor. After histological examination, the diagnosis of ductal carcinoma within a borderline phyllodes tumor was made. Immunohistochemical staining revealed that the epithelial component was positive for Epithelial Membrane Antigen and cytokeratin. No metastasis was detected in the axillary lymph nodes and the patient didn't receive any adjuvant therapy. No recurrence or metastasis has been observed 38 months after the surgery.

Synchronous Bilateral Benign Phyllodes Tumor of the Breast in a 32-year-old Woman.

Bilateral phyllodes tumors are distinctly uncommon. As some previous reports have described, most of them are malignant and asynchronous. We report a new case of bilateral synchronous phyllodes tumor in a 32-year-old women. Both tumors were classified as benign after large bilateral excision. No tumor recurrence was noted during the 10 months follow-up.

Lymphoepithelial Carcinoma of the Nasal Cavity With EBV Infection in a North African Man.

We report the case of a 58-year-old Tunisian man who presented with a 2 months' history of left nasal obstruction and one episode of epistaxis. Nasal endoscopy revealed a polypoid mass of the left nasal septum. Magnetic resonance imaging showed a left nasal cavity tumor with erosion of the orbit. Diagnosis of nasal cavity lymphoepithelial carcinoma EBV positive was performed on biopsy. The patient was treated by chemotherapy and radiotherapy. No tumor recurrence has been reported with a follow-up of 12 months.

Phyllodes Tumors of the Breast: A Review of 26 Cases.

BACKGROUND: Phyllodes tumors of the breast are rare and locally aggressive neoplasms. Our study aimed to report the experience of the Farhat Hached Hospital (Sousse, Tunisia) acquired during a 7-year period and to give an additional review of the available literature. METHODS: The authors analyzed retrospectively clinical, radiological, histopathological and therapeutic features as well as outcome in a series of 26 cases diagnosed as phyllodes tumors of the breast at the Pathology Department of Farhat Hached Hospital, Sousse, Tunisia, from 2003 to 2009. The slides were reviewed in order to classify the tumors into benign, borderline and malignant on the basis of the criteria proposed by the World Health Organization. RESULTS: All the cases occurred in women. The analysis of this series showed the following characteristics: mean age at diagnosis was 40 years (19 - 66), tumor size was 1.5 - 40 cm (mean: 7.8 cm); the chief complaint was a mammary mass; the right breast was affected in 14 cases, the upper outer quadrant was the most commonly involved site (42.3%); surgical treatment was used in all cases, 21 patients (80.8%) were treated conservatively (13 benign, 6 borderline, and 2 malignant) and 5 (19.2%) by radical surgery (1 borderline and 4 malignant); seven patients underwent post-operative radiotherapy; in 14/19 cases (73.7%), a good correlation was observed between intraoperative frozen section analysis and definitive histology; the tumor was classed as benign in 13 cases (50%), borderline in 7 cases (27%) and malignant in 6 cases (23%); follow-up data was available in 22 cases; the rate of recurrence was 23% (1 benign, 3 borderline, and 2 malignant) after a mean follow-up of 13.6 months; all the recurrent tumors were initially treated by lumpectomy and were close to margin at the initial pathologic examination; the treatment of recurrences consisted of simple mastectomy in 5 cases, and local excision in one case; three patients developed metastases, one of whom after recurrence; three patients have died. CONCLUSIONS: This is a substantial single institution experience of a rare tumor. Phyllodes tumors of the breast have an unpredictable outcome, thus a wide local excision, with an adequate margin of normal breast tissue, is the preferred initial therapy.

Pure Small Cell Carcinoma of the Bladder: A Case Report.

Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases.