SummaryDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0Á015 and P = 0Á005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0Á001) and EFS (P = 0Á0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.

The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B-and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/Tcell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences. (Blood. 2012;120(24):4795-4801) IntroductionNeoplasms of the lymphoid system are very diverse with different clinical presentations, morphologic appearances, and biologic behaviors. 1 Furthermore, the non-Hodgkin lymphoma (NHL) category includes numerous different subtypes. The incidence of NHL is increasing worldwide and, although this increase began to slow in the 1990s, significant variations in temporal trends have been noted for individual NHL subtypes. 2,3 Epidemiologic studies of risk factors for NHL have contributed significantly to our understanding of the pathogenesis of these neoplasms. [2][3][4][5] In numerous epidemiologic studies investigators also have analyzed the distribution of NHL subtypes in North America (NA), Europe, the Far East, and Middle East. 3,[6][7][8][9][10][11][12] These studies have shown substantial differences in the relative frequencies of NHL subtypes in different geographic regions. Furthermore, it has become clear that subtype-specific NHL frequency patterns in different geographic regions may be indicative of environmental or host risk factors in a particular region. [2][3][4]7 Moreover, comparison of the incidence rates and frequency patterns of specific NHL subtypes may provide critical clues to guide future epidemiologic studies. 3 Although studies of individual NHL subtypes have been conducted in several Central and South American (CSA) countries, [13][14][15][16] in only a few epidemiologic studies have authors examined the distribution of NHL subtypes in individual countries. [17][18][19] However, to our knowledge, a large-scale, wellorganized, systematic study of the distribution of NHL subtypes in CSA has not been undertaken. The aim of this study was to assess the clinical features and distribution of NHL su...

Objectives Exosomes are important mediators in intercellular communications and play a role in cancer progression and metastasis. Exosomal membranes are enriched in endosome-specific tetraspanins (CD9 and CD63). Here, we explored the expression of CD63 and CD9 utilizing immunohistochemistry in malignant and non-malignant cells in 29 resected pancreatic specimens (RPS) of mixed racial background. Methods The pathologic tissues (PTs) and adjacent normal tissues (ANTs) in each RPS were stained for CD63 and CD9. Two pathologists independently scored the expression of CD63 and CD9. Staining intensity was graded from 1–3. Staining percentage was estimated in 10% increments. An average Q score (Intensity X Percentage of staining) was calculated. Unpaired t test was used for statistical analysis. Results The mean multiplicative Quick-score (Q-score) for CD63 and CD9 expression is higher in PTs (209 and 72) compared to ANTs (154 and 24) (p= 0.0041; p=0.0018). The Mean Q score for CD63 and CD9 expression is higher in the malignant PTs (231 and 85) compared to ANTs (129 and 25) (p<0.0001 and p < 0.0124). Conclusions Exosomal markers (CD63 and CD9) expression assessment using IHC is feasible in RPS. The expression of CD63 and CD9 is higher in PTs and malignant PTs compared to their ANT.

Gastrointestinal tract involvement by neurofibromatous lesions is rare and occurs most frequently as one of the systemic manifestations of generalized neurofibromatosis type 1 (NF1). In this setting, the lesions may manifest as focal scattered neurofibromas or as an extensive diffuse neural hyperplasia designated ganglioneuromatosis. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. Rarely, cases of isolated neurofibromatosis of the large bowel with no prior or subsequent evidence of generalized neurofibromatosis have been documented. We present the case of a 52 year-old female with abdominal pain and alternating bowel habits. Colonoscopic evaluation revealed multiple small polyps in the cecum and the presence of nodular mucosa in the colon and rectum. Pathologic evaluation of the biopsies from the cecum, descending colon, sigmoid colon, and rectum revealed tangled fascicles of spindle cells expanding the lamina propia leading to separation of the intestinal crypts. Immunohistochemical stains helped confirm the diagnosis of diffuse intestinal neurofibromatosis. A thorough clinical evaluation failed to reveal any stigmata of generalized neurofibromatosis. This case represents a rare presentation of isolated intestinal neurofibromatosis in a patient without classic systemic manifestations of generalized neurofibromatosis and highlights the need in such cases for close clinical follow-up to exclude neurofibromatosis type I or multiple endocrine neoplasia type II.

Few studies have examined the value of a mandatory second review of outside pathology material for haematological malignancies. Therefore, we compared diagnoses on biopsies referred to an academic medical centre to determine the rate and therapeutic impact of revised diagnoses resulting from a second review. We reviewed 1010 cases referred for lymphoma during 2009-2010. For each case, referral diagnosis and second review diagnosis were compared. Revised diagnoses were grouped into major and minor discrepancies and all major discrepancies were reviewed by a haematologist to determine the effect the diagnostic change would have on therapy. There was no change in diagnosis in 861 (85·2%) cases. In 149 (14·8%) cases, second review resulted in major diagnostic change, of which 131 (12·9%) would have resulted in a therapeutic change. The highest rates of revision were for follicular, high-grade B-cell, and T-cell lymphomas. We found higher rates of major discrepancy in diagnoses from non-academic centres (15·8%) compared to academic centres (8·5%; P = 0·022), and in excisional biopsies (17·9%) compared to smaller biopsies (9·6%; P = 0·0003). Mandatory review of outside pathology material prior to treatment of patients for lymphoma will identify a significant number of misclassified cases with a major change in therapy.