Ayman Tawil

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

Background.The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis.Methods.We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25–.49, .50–.74, .75–1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS.Results.On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25.Conclusions.Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Metastastic rhabdomyosarcoma to the breast

Abstract Rhabdomyosarcoma is a common extramammary primary malignancy in childhood that rarely metastasises to the breast. We present a patient with primary sinonasal rhabdomyosarcoma who was in remission when she developed breast metastases. We describe particular imaging findings of this disease, using ultrasound and MR imaging. To our knowledge, MR findings have only been described in one previous case report in the literature.

Prediction of celiac disease at endoscopy

BACKGROUND AND STUDY AIMS Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

Mammary carcinoma with osteoclastlike giant cells cytologically mimicking benign breast disease. A case report.

BACKGROUND Mammary carcinoma with osteoclastlike giant cells (OCLGCs) is a rare tumor. Few reports on the fine needle aspiration (FNA) findings are available. This case had cytologic findings overlapping with benign breast disease. CASE A 50-year-old woman presented with multiple masses in her right breast and a 2-cm right axillary lymph node. Cytologic scrapings and FNA of the same breast mass showed large cohesive, two-dimensional epithelial cells with a uniform distribution of small, bland nuclei. Discohesion, single cells with features of malignancy, cytologic atypia and mitosis were lacking. Many OCLGCs were present. CONCLUSION The cytologic features of this rare type of breast carcinoma need to become familiar to pathologists to avoid a false negative diagnosis.

PERIOSTEAL OSTEOBLASTOMA OF THE CALVARIA MIMICKING A MENINGIOMA

While osteoblastoma of the cranial vault is rare, the periosteal form of the tumor is highly unusual, with only one case reported in the English literature. We report on a 24-year-old woman presenting with headache and tinnitus. Magnetic resonance imaging of the brain showed an extra-axial temporal mass with findings that were suggestive of a meningioma. The mass was excised completely, and histological examination revealed a periosteal osteoblastoma arising from the inner surface of the temporal bone and adhering to the dura. The tumor was strongly positive for epithelial membrane antigen, a feature not previously described in osteoblastoma, and one that could lead to a mistaken diagnosis of metaplastic meningioma in a limited sample. A detailed literature review of 40 other reported cases of calvarial osteoblastoma is presented. Apart from being slightly more common in females, calvarial osteoblastoma is similar in all other respects to that arising at conventional skeletal sites. Accurate histological diagnosis of a calvarial osteoblastoma requires adequate sampling of the tumor, including its interface with adjacent structures. Correlation with the radiological findings is crucial for the diagnosis in most cases; however, it is not helpful in differentiating the rare intracranial periosteal variant from a meningioma.

Abdominal Manifestations of Multiple Myeloma : A Retrospective Radiologic Overview

BACKGROUND Abdominal manifestations of multiple myeloma (MM) are rare. Herein, the authors study the radiologic characteristics of such involvement because these findings are usually missed by the radiologist and oncologist. PATIENTS AND METHODS We retrospectively reviewed the medical records of 202 patients with MM treated at our institution. A total of 192 patients underwent > or = 1 abdominal imaging studies (ultrasound, computed tomography, magnetic resonance imaging), which were correlated with histopathology, when available. RESULTS Eleven patients (5.72%) had lesions within 13 abdominal sites: liver (n = 4); pancreas (n = 3); peritoneum (n = 2); kidney, stomach, adrenal gland, and retroperitoneum (n = 1), respectively. Cytopathologic diagnosis was available in 5 cases. The remaining cases were considered to have myeloma deposits as a result of previous normal studies and the absence of other primary disease. The imaging findings were nonspecific. CONCLUSION Myeloma deposits within the abdomen are rare. Although the imaging findings are nonspecific, oncologists and radiologists should be aware of their common characteristics.

Modulation of Ceramide Content and Lack of Apoptosis in the Chronically Hypoxic Neonatal Rat Heart

To assess the effect of chronic hypoxia on cardiomyocyte apoptosis, we used an animal model that mimics cyanotic heart disease. Rats were placed in a hypoxic environment at birth, and oxygen levels were maintained at 10% in an air-tight Plexiglas chamber. Controls remained in room air. Animals were killed, and the hearts were harvested at 1 and 4 wk. Significant polycythemia developed in the hypoxic rats at 1 and 4 wk. Right ventricular mass in the hypoxic rats was 192% and 278% that of controls, and hypoxic left ventricular mass was 140% and 178% that of the controls at 1 and 4 wk, respectively. The increase in cardiac mass was paralleled by only mild hypertrophy (10 to 20%). Contrary to previous reports showing increased apoptosis in response to hypoxia in cultured cardiomyocytes, there was no difference in the number of apoptotic cardiomyocytes between the chronically hypoxic rats and controls, as assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Hoechst staining. We then examined the role of the sphingolipid ceramide because of its reported role in the stress response, growth suppression, and apoptosis. We found that the right ventricular ceramide content was significantly decreased in the hypoxic rats to 73% of control levels at the age of 4 wk. We suggest that the decrease in the ceramide content in the hypoxic right ventricular rat heart may be an adaptive response to chronic hypoxia and pulmonary hypertension. Lower ceramide levels may help suppress apoptosis and allow compensatory right ventricular cardiomyocyte proliferation.

Clinicopathologic and immunohistochemical characteristics of male breast cancer: a single center experience.

Abstract:  Male breast cancer (MaleBC) is a rare tumor that has been insufficiently described in the Middle East. The purpose of this study is to report the first MaleBC series in Lebanon, describing its clinicopathologic and immunohistochemical phenotype, and how it compares with MaleBC in the West and with female breast cancer in Lebanon and the Middle East. Forty‐seven cases of MaleBC were reviewed. Results showed younger ages at presentation (62 years versus 67 years), higher incidence of lobular carcinoma (6% versus 1%), and more frequent p53 positivity and axillary node metastases in our series than in those reported about MaleBC. Other results such as higher estrogen receptor (ER) positivity and lower HER‐2/neu over‐expression were comparable to the literature. These findings suggest that MaleBC in our region may represent a biologically different tumor with potentially distinct prognostic and therapeutic implications.

Long-term remission in a patient with hepatosplenic gammadelta T cell lymphoma treated with bortezomib and high-dose CHOP-like chemotherapy followed by autologous peripheral stem cell transplantation.

Dear Editor, Hepatosplenic gammadelta (HSG) T cell lymphoma (TCL) is a distinct clinicopathological entity among peripheral TCL with an extremely poor prognosis [1]. We report the case of a 33-year-old woman with HSG TCL who was treated with bortezomib and high-dose CHOP-like chemotherapy followed by autologous peripheral blood stem cell transplantation (APSCT). She remained disease free for 27 months and died after disease relapse. The patient is a 33-year-old woman previously healthy who presented with a 2-week history of dizziness, fatigue, palpitations, and pallor. Laboratory studies showed pancytopenia with white blood cell of 1,900 per microliter, hemoglobin of 6.2 g/dL, and platelets of 125,000 per microliter. Chemistry showed elevated lactate dehydrogenase and bilirubin. Her physical examination was significant for general pallor and splenomegaly. Computerized tomography (CT) scan of the chest, abdomen, and pelvis showed hepatosplenomegaly with no focal lesions. Bone marrow aspirate, biopsy, and flow cytometry were negative for lymphoma. Cytogenetic testing was normal. Splenectomy revealed expansion of the red pulp with dilatation of the sinusoids by atypical lymphoid cells and abundant hemophagocytosis. Liver biopsy revealed diffuse sinusoidal dilatation containing the same atypical lymphoid cells which were strongly positive for CD3 and CD45RO while CD5, CD20, and CD79a were negative. On flow cytometry of the splenic tissue extract, the abnormal T cells showed dim CD2, CD3, CD56, TIA-1, and CD45 expression with deletion of CD5, CD7, CD4, and CD8. Human leukocyte antigen-DR was also positive. Molecular testing confirmed the rearrangement of the gammadelta chains of the T cell receptor and the diagnosis of HSG TCL. The patient received four cycles of platinum-cytarabinebased chemotherapy. Repeat liver biopsy showed partial response. After her consent, she received bortezomib (Velcade 1 mg/m per day on days 1 and 5) with modified high-dose CHOP chemotherapy (ACVB) with granulocytecolony-stimulating factor (G-CSF) support every 2 weeks for four cycles. ACVB consisted of Adriamycin 75 mg/m, cyclophosphamide 1,200 mg/m, vincristin 1.2 mg/m (2 mg maximum), bleomycin 15 mg, and prednisone 60 mg/m/day for 5 days. Because of potential additive peripheral neurotoxicity with bortezomib, vincristine was deleted from the first two cycles. This treatment was well tolerated. Laparoscopic liver biopsy showed almost complete remission with persistence of a single small atypical lymphoid infiltrate (Fig. 1). The patient then underwent stem cell mobilization with high-dose cyclophosphamide plus G-CSF followed by stem cell collection and cryopreservation. She then received BEAM conditioning regimen followed by APSCT. She remained free of disease for 27 months after transplantation (37 months after diagnosis). She then presented with abdominal pain. CT scan showed enlarged liver with new Ann Hematol (2008) 87:1023–1024 DOI 10.1007/s00277-008-0523-7

Programmed Death-Ligand 1 Expression in Muscle-Invasive Bladder Cancer Cystectomy Specimens and Lymph Node Metastasis: A Reliable Treatment Selection Biomarker?

BACKGROUND The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have shown activity in several tumor types with preliminary data suggesting a relationship between PD-L1 expression and response. The aim of this study was to establish the frequency of PD-L1 expression in muscle-invasive bladder cancer and associated lymph node metastasis using immunohistochemistry and to investigate the feasibility of using PD-L1 expression as a biomarker to select patients for PD-1-directed therapy. PATIENTS AND METHODS Cases of radical cystectomy for muscle-invasive bladder cancer with no exposure to previous chemotherapy were identified and representative slides from archived paraffin-embedded blocks stained with anti-PD-L1 antibody (5H1 clone) were identified. PD-L1 positivity was defined by a 5% expression threshold. RESULTS Fifty-two radical cystectomy specimens were reviewed. PD-L1 was overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in tumor-infiltrating immune cells. Discordance was observed between PD-L1 expression in lymph node metastasis and the primary tumor. CONCLUSION Standard assays for PD-L1 expression have yet to be established. The observation of discordance between PD-L1 expression in metastatic sites and primary tumors suggests that prospective biomarker studies should aim to acquire material immediately before treatment initiation rather than archived tissue from resected specimens that might not reflect the current immune-active microenvironment.