Summary This paper presents health outcomes and associated socioeconomic factors of 41 children admitted to a tertiary care institution in south‐east Nigeria with Burkitt's lymphoma (BL) between 1987 and 2004. BL responds well to chemotherapy and does not pose a significant threat to health in industrialized nations. However, in resource‐poor settings where it is endemic, socioeconomic factors significantly affect access to care for affected children, making this readily treatable condition a cause of considerable distress and early death in affected children. Half of the children reported in this paper presented with late stage disease. Although laboratory facilities were available, they were not accessible to all the children. Nearly a quarter of parents of these children could not afford the cost of confirmatory tests, and about a fifth (n = 8; 19.5%) of the children received no chemotherapy because of their parents’ inability to pay. Only 21 of 41 children (51.2%) remained on treatment long enough (at least 12 weeks) to enable them to be confirmed either as short‐term cure (n = 9; 64.3%), or as early relapse (n = 2; 4.9%). Owing to financial constraint, 13 of the parents (31.7%) withdrew their children against medical advice (n = 7; 17.1%) or left the hospital (n = 6; 14.6%). To address the challenge posed by these factors, we call for the establishment of a regional BL programme in Africa to help establish a critical mass of resources (human and material) to facilitate the development of an effective and accessible control programme in the region.
Three hundred cases of invasive breast carcinoma from the University of Calabar Teaching Hospital, Nigeria were subjected to evaluation of proliferative activity by mitotic counts. The prognostic significance and association with other prognostic factors were evaluated. The mitotic activity was expressed as mitotic activity index (MAI), and standardized mitotic index (SMI). Pearson's correlation and univariate and multivariate Cox's regression were used. The mean follow-up time was 25.9 months. The mean values of SMI and MAI were 42.6 mitotic figures per square millimeter and 30.5 mitotic figures per 10 high-power fields, respectively, and these were much higher than values reported for Europe or other Western countries. The SMI had a positive correlation with tumor size (r ؍ 0.31, P < .0001), histologic grade (r ؍ 0.68, P < .0001), nuclear area (r ؍ 0.45, P < .0001), and negative correlation with fraction of fields with tubular differentiation (FTD; r ؍ ؊0.56, P ؍ <0.0001). There was no statistically significant difference in the mitotic activity between the postmenopausal and the premenopausal patients. Also, lymph node-positive patients had higher counts than did lymph node-negative patients. Earlier determined grading associated decision thresholds divided the patients into groups of favorable and unfavorable prognosis. However, the statistically optimal thresholds for Nigerian material were different (32 and 92 mitotic figures per square millimeter for SMI). Tumor size of 5 cm, SMI, and MAI were independent prognostic factors. Nigerian breast cancers are high-grade, high-stage, and high-proliferating cancers occurring in a younger population than those of the Western countries. Proliferation is also more active. Evaluation of SMI or MAI can improve the distinction between aggressive and less aggressive variants of breast cancer.
Extranodal marginal zone lymphomas (EMZL) are the most common lymphomas in the ocular adnexa. The etiology and potential role for antigenic stimulation in these lymphomas are still controversial. We have examined IGHV gene usage and mutations in 67 Chlamydophila psittaci-negative ocular adnexal EMZL. Clonal IGHV gene sequences were identified in 43 tumors originating from the orbit (19), conjunctivae (18) and lacrimal gland (6). Forty four potentially functional clonal IGHV gene sequences were detected with overrepresentation of the IGHV4 family and IGHV4-34 gene. All but 3 sequences were mutated with the average percent homology to the germ line of 93.5±6.1. Multinomial model and Focused binomial test demonstrated evidence for positive and/or negative antigen selection in 59% of the potentially functional IGHV genes. Intraclonal variation was detected in 8 of 11 tumor specimens. Overall our findings demonstrate that C. psittaci-negative ocular adnexal EMZL exhibit biased usage of IGHV families and genes with evidence for intraclonal heterogeneity and antigen selection in multiple tumors, implicating B-cell receptor-mediated antigen stimulation in the pathogenesis of these lymphomas.
The etiology and pathogenesis of ocular adnexal extranodal marginal zone lymphoma (OAEMZL) are still unknown and the association with Chlamydophila psittaci (C. psittaci) has been shown in only some geographic regions. Herein we comprehensively examined the frequency of chromosomal translocations as well as CARD11, MYD88 (L265P) and A20 mutations /deletions in 45 C. psittaci negative OAEMZLs. t(14;18)(q32;q21) IGH-MALT1 and t(11;18)(q21;q21) API2-MALT1 were not detected in any of the analyzed tumors while 3 tumors harbored IGH translocations to an unidentified partner. CARD11 mutations were not found in all the analyzed tumors while MYD88 L265P mutation was detected in 3 (6.7%) tumors. A20 mutations and deletions were each detected in 7(15.6%) and 6(13.3%) of the tumors, respectively. Therefore, the observed genetic aberrations could account for the activation of NF-kB signaling pathway in only a minority of the cases. Further studies are needed to identify the molecular mechanisms underlying the pathogenesis of OAEMZL.
The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar's test and Bowker's symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number ≥3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification.
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