MDR1 gene polymorphisms and imatinib response in chronic myeloid leukemia: A meta-analysis.

BACKGROUND: Our study aimed to investigate the association between multidrug resistance (MDR1) C1236T, C3435T and G2677T/A polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML). MATERIALS AND METHODS: An electronic databases in PubMed, Embase, Web of Knowledge, Scopus and Cochrane were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using strict inclusion and exclusion criteria. RESULTS: In total, 37 studies were initially identified, and 17 studies, involving 4494 CML patients, were eventually included in this meta-analysis.Results of our study revealed significant association between MDR1 G2677T/A and C3435T polymorphisms and response to IM in Caucasian population under recessive model (T or A vs G; OR = 1.43,95%CI [1;06-1.93]; T vs C;OR = 1.13; 95%IC [0.79; 1.63]), dominant (T or A vs G; OR = 0.94; 95%CI [0.74-1.21]; T vs C; OR = 1.49; 95%CI [1.02-2.17]) and heterozygous models (T or A vs G; OR = 0.83; 95%CI [0.64; 1.09]; T vs C; OR = 1.52; 95%CI [1.01-2.28]); respectively. However, never significative association was found between IM response and the MDR1 C1236T polymorphism (OR = 1.25; 95%CI [0.46; 3.33]). CONCLUSION: The MDR1 G2677T/A and C3435T polymorphisms might be a risk factor for resistance to IM in Caucasian CML patients.

Penconazole alters redox status, cholinergic function, and membrane-bound ATPases in the cerebrum and cerebellum of adult rats.

Pesticides exposure causes usually harmful effects to the environment and human health. The present study aimed to investigate the potential toxic effects of penconazole, a triazole fungicide, on the cerebrum and cerebellum of adult rats. Penconazole was administered intraperitoneally to male Wistar rats at a dose of 67 mg kg-1 body weight every 2 days during 9 days. Results showed that penconazole induced oxidative stress in rat cerebrum and cerebellum tissues. In fact, we have found a significant increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, as well as an alteration of the antioxidant status, enzymatic (superoxide dismutase and catalase) and nonenzymatic (glutathione), the cholinergic function, and membrane-bound ATPases (Na+/K+-ATPase and Mg2+-ATPase). Penconazole also provoked histological alterations marked by pyknotic and vacuolated neurons in the cerebrum and apoptosis and edema in the cerebellum Purkinje cells' layer. Therefore, the use of this neurotoxicant fungicide must be regularly monitored in the environment.

[Primary neuroendocrine tumors of the breast: a retrospective study of 21 cases and literature review]. / Tumeurs neuroendocrines primitives du sein: étude rétrospective de 21 cas et revue de la littérature.

PURPOSE: The aim of the present study was to discuss the epidemiology, clinical and pathologic features, treatment, and prognosis of primary neuroendocrine carcinomas of the breast. PATIENTS AND METHODS: We report 21 cases diagnosed over a period of 12 years (1995-2011) at the university hospital of Sfax. A review of the clinical data with pathology and immunohistochemistry study was carried out for all the cases. RESULTS: The average age was 62 years (34-86 years). At the time of the diagnosis, tumours were classified T1 and T2 (16 cases), N1 (11 cases) and M1 in two cases. The histological examination has shown 13 cases of solid neuroendocrine carcinoma, six cases of large cell type and two cases of atypical carcinoid. Grade I and II SBR were found in 18 cases. Eighty-one percent of the tumours were reactive for synaptophysin; all tumours were positive for chromogranin. Thirteen (61.9%) tumours were estrogen receptor-positive and 12 (57.5%) progesterone receptor-positive. Nineteen (90.5%) tumours were negative for HER2/neu. Overall five-year survival was 72.7%. All patients had surgical treatment with modified radical mastectomy in 13 cases. Adjuvant treatment was indicated according to histopronostic elements. CONCLUSION: For primary neuroendocrine carcinoma of the breast, multivariate analysis identified three predictive factors for mortality: disease stage, histological grade and lymph node involvement.

[Auto-immune hepatitis in chronic granulomatous disease in a 2-year-old girl]. / Hépatite auto-immune associée à une granulomatose septique chronique chez une fille de 2 ans.

BACKGROUND: Chronic granulomatous disease is a rare inherited primary immune deficiency disease characterized by recurrent infection and an increased susceptibility to autoimmunity disorders. We report on the case of a girl with autoimmune hepatitis in chronic granulomatous disease to describe the clinical and biological features and treatment implications for patients with chronic granulomatous disease associated with autoimmune disorders. CASE REPORT: An 18-month-old girl was referred to our department for investigation of hepatomegaly. She was the third child of non-consanguineous parents. Her two elder sisters had died from infectious diseases at an early age. She had elevated liver transaminase levels with a normal gamma globulin concentration. Negative results were found for all autoimmune markers (antinuclear antibody, anti-smooth muscle, anti-liver-kidney microsomal, anti-liver cytosol and anti-soluble liver antigen). Her liver biopsy showed features of interface hepatitis with portal fibrosis. The diagnosis of seronegative autoimmune hepatitis was established. Treatment with corticosteroids and azathioprine led to clinical improvement with normalization of transaminases. Six months after initial presentation, at the age of 2 years, she was readmitted for fever. Staphylococcus aureus bacteremia was identified with multiple foci of infection (skin infection, arthritis of the right elbow, pneumonia, buttock abscess). The immunological workup revealed chronic granulomatous disease. The course was marked by a fatal outcome despite appropriate antibiotics and intensive care. CONCLUSION: Early diagnosis of the association between chronic granulomatous disease and autoimmune disorders allows for appropriate treatments, improves the quality of life for affected patients, and reduces the risk of mortality.

Uterine tumour resembling ovarian sex cord tumours presenting as multiple endometrial and cervical uterine polyps: a case report.

BACKGROUND: Uterine tumours resembling ovarian sex-cord tumours (UTROSCT) are very rare, benign uterine tumours, composed solely of sex cord elements. These tumours have a polyphenotypic immunophentype that favours a derivation from uterine mesenchymal stem cells. CASE REPORT: A 43-year-old female presented with recurrent vaginal bleeding. On hysteroscopy, she had multiple endometrial and cervical polyps that were removed endoscopically. Histologically, the specimen contained epithelioid cells arranged in tubules, trabeculae and anastomosing cords, without significant cellular atypia or mitotic activity. Immunohistochemical studies were performed. The tumour was found to be diffusely positive for vimentin, calretinin and desmin, focally positive for cytokeratin, CD99 and inhibin and negative for chromogranin and CD10. A subsequent total hysterectomy was performed and revealed neoplastic infiltration of the myometrium. CONCLUSION: A polyphenotypic immunophenotype is a characteristic feature of UTROSCT, and may be helpful in diagnosis and in exclusion of other lesions. Familiarity with this tumour by gynaecologists and pathologists is essential to avoid misdiagnosis:correct diagnosis of this neoplasm is important in patient management.

[Crohn's disease or intestinal tuberculosis: a diagnostic challenge]. / Tuberculose intestinale ou maladie de Crohn : un défi diagnostique.

Distinguishing intestinal tuberculosis from Crohn disease is difficult and can result in misdiagnosis, especially when active pulmonary infection is absent. A 13-year-old girl was admitted to our hospital with a 2-month history of watery diarrhea, abdominal pain, and 12-kg weight loss. Based on clinical, radiological, endoscopic, and histological findings, she was initially misdiagnosed as having Crohn disease and treated with glucocorticosteroids, with a poor response after 4 weeks. Intestinal tuberculosis was then suspected. Improvement was observed during the 1st week of antituberculous treatment. The differentiation of intestinal tuberculosis from Crohn disease may be very difficult in some patients. A positive response to antituberculous treatment associated with clinical, endoscopic, and histological features argue in favor of the diagnosis of intestinal tuberculosis.

Mixed stromal and smooth muscle tumours of the uterus: a report of two cases.

Mixed stromal and smooth muscle uterine tumours, defined as those containing at least 30% of each component as seen by routine light microscopy, are rare. This report describes the morphological features of two such tumours diagnosed in 44-year-old and 50-year-old females complaining from recurrent uterine bleeding that was unresponsive to medical treatment. Morphological and immunohistochemical evaluations were performed, and a final diagnosis of mixed endometrial stromal nodule and smooth muscle tumour of the uterus was rendered in both cases.

Localisation nasosinusienne des tumeurs plasmocytaires

Introduction : Les tumeurs plasmocytaires representent 3 a 4 des tumeurs des cavites naso-sinusiennes. Elles necessitent un bilan diagnostique specifique et une prise en charge adequate. Nous nous proposons d'etudier les particularites diagnostiques et therapeutiques des plasmocytomes naso-sinusiens. Materiel et methodes : Notre etude est retrospective comportant 5 cas de plasmocytomes naso-sinusiens confirmes histologiquement. Resultats : Il s'agit de 3 hommes et 2 femmes ages de 32 a 77 ans. Le plasmocytome avait une localisation sphenoidale dans un cas; nasale dans 2 cas; ethmoido-nasale dans un cas et naso-maxillaire dans le cas restant. Il s'agissait d'un myelome multiple dans un cas. Trois patients ont eu une radiotherapie. Celle-ci etait associee a une chimiotherapie dans le cas du myelome multiple et a une exerese chirurgicale dans les 2 autres cas La chirurgie a ete seule dans un cas. La chimiotherapie exclusive a ete proposee dans un cas de plasmocytome localement avance mais le patient a ete perdu de vue. Pour les patients suivis; une seule recidive a ete notee a 18 mois. Conclusion : La presentation clinique des plasmocytomes nasosinusiens est aspecifique. Le diagnostic est confirme par l'histologie. Le pronostic est domine par la presence ou non d'un myelome multiple et par la taille tumorale. Un suivi prolonge est necessaire

Type 2 autoimmune hepatitis overlapping with primary sclerosing cholangitis in a 10-year-old boy.

BACKGROUND: Overlap syndrome of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is considered when the patient presents with the diagnostic criteria of both diseases at some stage of the medical history, either simultaneously or consecutively. AIM: To report on a new case of overlap syndrome and describe the clinical presentation, progression, radiological studies, histological characteristics, and therapeutic options of this rare association. CASE REPORT: A 10-year-old boy presented with jaundice and hepatosplenomegaly. Levels of plasma aminotransferases, gamma-glutamyl transferase, serum alkaline phosphatase and gammaglobulins were elevated. Anti-liver cytosol and perinuclear antineutrophilic cytoplasmic antibodies were positive. Liver biopsy showed features of interface hepatitis with ductopenia. Magnetic resonance cholangiography revealed bile duct stenosis and dilations. Serological findings associated with radiological and histological features confirmed the diagnosis of overlap syndrome of AIH with PSC. Treatment with prednisone, azathioprine, and ursodeoxycholic acid led to a good response. CONCLUSION: The possibility of AIH-PSC overlap syndrome should be considered in all children with AIH and, with clinical, biochemical, or histological signs of PSC, complementary investigations should be done to confirm the diagnosis so as to urgently initiate appropriate treatment with immunosuppressive medication and ursodeoxycholic acid.

[Clinical aspects of brain metastases from nasopharyngeal carcinoma]. / Aspects anatomocliniques des métastases cérébrales des carcinomes nasopharyngés.

Metastasis to the central nervous system, either through a hematogenous route or through the cerebrospinal fluid, is extremely rare in nasopharynx cancer. We aim to expose clinical aspects, therapeutic features and prognosis of nasopharyngeal carcinoma with brain metastases. We retrospectively reviewed the medical history of about 420 patients with nasopharyngeal carcinoma treated during 17 years at the university hospital of Sfax (Tunisia). Among them, three patients had brain metastasis. We excluded patients with direct extension to the brain. Tumours of the nasopharynx were locally advanced. The first patient had brain metastases at the initial diagnosis. The two other patients had brain metastases at 10 and 16 months during the follow-up. Ocular signs were the symptoms. Lesions were unique in two patients. Synchronous bone metastases were recorded in the three cases. All patients had whole brain radiation therapy and palliative chemotherapy. All patients had a progression of the disease and died. Brain metastases in nasopharynx cancer represent a rare event. Prognosis is poor, depending on age, surgical excision and synchronous metastases. Survival does not exceed 6 months.

Primary mucinous carcinoma of the thyroid gland: case report with review of the literature.

Primary mucinous thyroid carcinoma (PMTC) are extremely rare lesions that are histologically indistinguishable from mucinous carcinoma of other sites. We describe the clinicopathological, histological and immunohistochemical features of this rare tumour with a review of the literature. We describe a case of thyroid tumour, in 56-year-old Tunisian man, composed of small nests and sheets of malignant epithelial cells associated with extensive extracellular mucin that entrapped the follicular parenchyma of thyroid. Thyroglobulin and thyroid-specific-transcription factor 1 (TTFl) were focally positive. Follow-up did not reveal another neoplasm at other sites. Based on these features, we classified this tumour as PMTC. Mucinous carcinoma of the thyroid gland can be a cause of pitfall in differential diagnosis. For correct diagnosis, complete clinical history, restricted histological criteria and immunohistochemical panel are necessary.

Mammary myofibroblastoma with leiomyomatous differentiation: case report and literature review.

INTRODUCTION: Myofibroblastoma of the breast (MFB) is an unusual benign tumour that belongs to the family of benign spindle cell tumours of the mammary stroma. The detection of smooth muscle cells in MFB is explained by its histogenesis from CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle. AIMS: The purpose of this case is to highlight characteristics of this rare neoplasm. Immunohistochemical features, in MFB with predominant leiomyomatous differentiation, are provided to offer a practical approach to a correct diagnosis. CASE REPORT: We report a right MFB in a 60-year-old male. The tumour was unusual due to its morphological features, with predominant leiomyomatous differentiation. Immunohistochemical findings, based on the negativity of h-caldesmon, helped in reaching a diagnosis. CONCLUSION: The detection of leiomyomatous rather than myofibrolastic features in MFB may reflect only the predominant cell types of examined area, and this is not necessarily representative of the remaining tumour which may have a different basic cellular composition. Immunohistochemical expression of h-caldesmon is a reliable marker in distinguishing smooth muscle versus myofibrolastic cellular differentiation in spindle cells lesions of the breast.

Primary sinonasal meningioma.

INTRODUCTION: Primary meningiomas of the sinonasal tract are rare tumors. Their positive diagnosis is difficult to establish. From one case observation, we report the clinical features, the diagnosis difficulties and the therapeutic modalities of primary meningioma of the sinonasal tract. CASE REPORT: A seventeen-year-old girl consulted for a left unilateral nasal obstruction with progressive evolution without episodes of epistaxis, smell disorder or headaches over a year. Physical examination revealed a grayish polypoid tumor in the left nasal fossa. CT scan evidenced an isodense lesion of the left nasal fossa slightly enhanced pushing back the lateral nasal wall without invasion or intracranial connection. Biopsy was in favour of an inverted papilloma. The tumor was resected via endoscopic approach. Pathological examination established the diagnosis of meningothelial menigioma. The prognosis was favourable without recurrence after a six-month follow-up. CONCLUSION: The positive diagnosis of primary sinonasal meningioma is difficult to establish because of their infrequent occurrence in this ectopic site and of their non-specific clinical appearance. The final diagnosis rests on the histological examination. Immunohistochemical studies are helpful to establish the accurate diagnosis. Imaging confirms the primitive nature of these tumors. Prognosis is excellent after complete surgical extirpation without the necessity of adjuvant therapy.

Congenital infantile fibrosarcoma of the forearm.

Congenital infantile fibrosarcoma is a rare soft tissue neoplasm in the infant of which only a few cases are reported as congenital. This tumor has a rapid growth and extensive local invasion, but metastasis rarely occurs. Distal extremities involvement is more common and metastasis are rare. We report a case of a congenital infantile fibrosarcoma of the forearm, which was initially confused with a hemangioma, treated successfully by surgical resection.

Ganglion cyst of the carpal navicular. A case report and review of the literature.

Intraosseous ganglion (IOG) cyst of the scaphoid is an infrequent cause of hand and wrist pain. Intraosseous ganglia located in the scaphoid have rarely been described in the literature. We report the case of a 30-year-old right-handed woman who presented with a more than 24-month history of progressive right-wrist pain. No history of trauma was reported.Conservative treatment with anti-inflammatory medications before referral was unsuccessful. Examination revealed a small palpable mass in the carpal navicular region with no limitation of normal wrist motion. An IOG cyst of the scaphoid was found on standard radiograph and CT-scan of the wrist. Treatment consisted in curettage of the cyst followed by packing of the defect with autologous cancellous bone graft harvested in the distal end of the radial metaphysis. Satisfactory functional recovery was achieved. The clinical, radiographic and therapeutic aspects of this rare condition are discussed by the authors.