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Background: Esophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa., Methods: A total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software., Results: Of the 118 patients' samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29-88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001)., Conclusion: A substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region., (© 2024. The Author(s).)

Although the approval of new drugs has improved the clinical outcome of multiple myeloma (MM), it was widely regarded as incurable over the past decades. However, recent advancements in groundbreaking immunotherapies, such as chimeric antigen receptor T cells (CAR-T), have yielded remarkable results in heavily pretreated relapse/refractory patients, instilling hope for a potential cure. CAR-T are genetically modified cells armed with a novel receptor to specifically recognize and kill tumor cells. Among the potential targets for MM, the B-cell maturation antigen (BCMA) stands out since it is highly and almost exclusively expressed on plasma cells. Here, we review the currently approved BCMA-directed CAR-T products and ongoing clinical trials in MM. Furthermore, we explore innovative approaches to enhance BCMA-directed CAR-T and overcome potential reasons for treatment failure. Additionally, we explore the side effects associated with these novel therapies and shed light on accessibility of CAR-T therapy around the world.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Introduction: Bladder cancer is a possible outcome of chronic urinary schistosomiasis in many endemic countries. In Tanzania, the Lake Victoria area is one of the areas with the highest prevalence of urinary schistosomiasis and higher incidences of squamous cell carcinoma (SCC) of the urinary bladder. A previous study in the area over one decade (2001-2010) showed SCC to be common in patients aged below 50 years. With various prevention and intervention programs there are likely to be notable changes in schistosomiasis-related urinary bladder cancer, which is currently unknown. Updated information on the status of SCC in this area will be useful for giving an insights into efficacy of control interventions implemented and help guide the initiation of new ones. Therefore, this study was done to determine the current trend of schistosomiasis-related bladder cancer in lake zone, Tanzania., Methods: This was a descriptive retrospective study of histologically confirmed urinary bladder cancer cases diagnosed at the Pathology Department of Bugando Medical Centre over 10 years period. The patient files and histopathology reports were retrieved and information was extracted. Data were analyzed using Chi-square and student t-test., Results: A total of 481 patients were diagnosed with urinary bladder cancer during the study period whereby, 52.6% were males and 47.4% were females. The mean age regardless of histological type of cancer was 55 ± 14.2 years. The SCC was the commonest histological type accounting for 57.0%, followed by transitional cell carcinoma 37.6%, and 5.4% were adenocarcinomas. The Schistosoma haematobium eggs were observed in 25.2% and were commonly associated with SCC (p = 0.001). Poorly differentiated cancers were observed mostly in females (58.6%) compared to males (41.4%) (p = 0.003). Muscular invasion of the urinary bladder by cancer was observed in 11.4% of the patients, and this was significantly higher in non-squamous than in squamous cancers (p = 0.034)., Conclusion: Schistosomiasis-related cancers of the urinary bladder in the Lake zone of Tanzania is still a problem. Schistosoma haematobium eggs were associated with SCC type indicating the persistence of infection in the area. This calls for more efforts on preventive and intervention programs to reduce the burden of urinary bladder cancer in the lake zone., (© 2023. The Author(s).)

Introduction: breast lump is the commonest presentation for both benign and maligant breast conditions. Both ultrasound guided and conventional fine needle aspiration cytology (FNAC) have been used for diagnosing of breast malignancy among patients with palpable breast lumps. This study compared diagnostic utility of ultrasound guided versus conventional FNAC in diagnosing breast malignancies among patients with palpable breast lumps at Bugando Medical Centre., Methods: this was a hospital based cross sectional study with a follow up component that combined both retrospective data (from January 2017 to June 2018) and prospective data (from July 2018 to June 2019)., Results: during the study, total of 354 patients (male; female = 1: 32) were enrolled in the study. A total of 134 (37.9%) patients had malignant lesions while 220 (62.1%) of patients had benign lesions confirmed on histology. The diagnostic utility (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) for conventional FNAC was 86.7%, 95.7%, 93.5%, 91.1% and 92.0% with an 8% error margin versus ultrasound guided FNAC all were 100% with a 0% error margin respectively., Conclusion: both ultrasound guided and conventional FNAC show almost perfect agreement with histology. However, ultrasound guided FNAC has a higher diagnostic utility relative to conventional FNAC in diagnosing breast malignancies., Competing Interests: The authors declare no competing interests., (Copyright: Tresphory Bonephace Kamushaga et al.)

CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high-level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut-off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high-level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut-off for IHC to predict CCNE1 high-level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high-level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high-level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38-2.26, p < 0.0001). CCNE1 high-level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high-level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors., (© 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons Ltd.)

Background: Ovarian cancer is a spectrum of several histologically distinct tumor types that differ in etiology, response to therapy, and prognosis. In resource-limited settings, the diagnosis of ovarian cancer can be challenging. This study describes the distribution of ovarian cancer tumor types in East Africa as well as assessing the diagnostic accuracy by using contemporary methods., Methods: Data from 210 women identified from the records with a diagnosis of ovarian cancer in a period of 15 years were included. Two tissue microarrays were constructed and stained with 20 antibodies relevant to ovarian cancer subtyping. An integrated diagnosis was reached by the review of full Haematoxylin and Eosin stained sections, with consideration of immunohistochemical results. The integrated diagnoses were compared with the original diagnoses, and the degree of agreement was evaluated by percentage and Kappa statistics., Results: Though limited by selection bias, the results suggest lower rates of ovarian cancer in East Africa compared to a North American population from Alberta, Canada. There was a higher proportion of sex cord stromal tumors and germ cell tumors in the East African population. Diagnostic accuracy for main ovarian tumor type categories was substantial (Kappa 0.70), but only fair for specific ovarian carcinoma histotypes (Kappa 0.34). Poor Haematoxylin and Eosin stain was the main factor hindering the correct diagnosis, which was not related to tissue processing., Conclusions: In a resource-limited setting, where immunohistochemistry is not routinely carried out, diagnostic accuracy for the main categories of ovarian carcinoma is substantial and could be further improved by standardization of the basic Haematoxylin and Eosin stain.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7 - /CK20 + /CDX2 + /PAX8 - . This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

Purpose: Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches., Experimental Design: To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, n = 10; endometrioid carcinoma, n = 10). Eight candidate protein biomarkers specific to endometrioid carcinoma were validated by IHC using tissue microarrays representing 361 cases of either endometrioid carcinoma or HGSC., Results: More than 500 proteins were differentially expressed ( P < 0.05) between endometrioid carcinoma and HGSC tumor proteomes. A ranked set of 106 proteins was sufficient to correctly discriminate 90% of samples. IHC validated KIAA1324 as the most discriminatory novel biomarker for endometrioid carcinoma. An 8-marker panel was found to exhibit superior performance for discriminating endometrioid carcinoma from HGSC compared with the current standard of WT1 plus TP53 alone, improving the classification rate for HGSC from 90.7% to 99.2%. Endometrioid carcinoma-specific diagnostic markers such as PLCB1, KIAA1324, and SCGB2A1 were also significantly associated with favorable prognosis within endometrioid carcinoma suggesting biological heterogeneity within this histotype. Pathway analysis of proteomic data revealed differences between endometrioid carcinoma and HGSC pertaining to estrogen and interferon signalling., Conclusions: In summary, these findings support the use of multi-marker panels for the differential diagnosis of difficult cases resembling endometrioid carcinoma and HGSC., (©2019 American Association for Cancer Research.)

Aims: Ovarian endometrioid carcinoma (EC) generally has a good prognosis. Adjuvant chemotherapy can be spared in low-stage disease, but prognostic biomarkers are needed to refine the treatment threshold. Wnt/β-catenin signalling is commonly altered in EC. We examined immunohistochemical expression of nuclear β-catenin and CDX2 as prognostic biomarkers for EC; both are mediators of the Wnt pathway., Methods and Results: We evaluated two ovarian EC cohorts, discovery set (n = 183) and validation set (n = 174), with ovarian cancer-specific survival (OCSS) as the primary end-point. In univariable analysis, nuclear β-catenin expression was significantly associated with longer OCSS in the discovery set [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.16-0.74, P = 0.004] and the validation set (HR = 0.35, 95% CI = 0.11-0.89, P = 0.006). Similar significant associations were observed with CDX2 expression in the discovery set (HR = 0.25, 95% CI = 0.11-0.50, P < 0.001) and validation set (HR = 0.27, 95% CI = 0.07-0.75, P = 0.020). In multivariable analysis, combined positivity of both markers was significantly associated with longer OCSS in the discovery set (HR = 0.20, 95% CI = 0.06-0.49, P < 0.001) and in the validation set (HR = 0.33 95% CI = 0.07-0.1.06, P = 0.047). In a stratified analysis for stage IC/II EC, combined positivity identified a subset of patients with a significantly longer OCSS in the discovery cohort but only a non-significant trend in the validation cohort., Conclusions: Nuclear β-catenin and CDX2 expression individually or in combination are validated prognostic markers for ovarian EC. However, their full potential to stratify low risk patients at adjuvant threshold awaits further multimarker study., (© 2018 John Wiley & Sons Ltd.)

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition., (© 2018 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Although infrequently encountered, the diagnosis of ovarian high-grade endometrioid carcinoma remains a diagnostic challenge with potential consequences for targeted therapies and genetic counselling. We studied the clinical, morphologic, and immunohistochemical features of ovarian high-grade endometrioid carcinomas and their diagnostic reproducibility compared with tuboovarian high-grade serous carcinomas. Thirty cases confirmed as International Federation of Gynecology and Obstetrics grade 3 endometrioid carcinomas were identified from 182 ovarian endometrioid carcinomas diagnosed in Alberta, Canada, between 1978 and 2010, from the population-based Alberta Ovarian Tumor Types cohort. Cases of lower grade endometrioid and high-grade serous carcinoma served for comparison. Ten immunohistochemical markers were assessed on tissue microarrays. Clinical data were abstracted and survival analyses performed using Cox regression. Interobserver reproducibility for histologic type was assessed using 1 representative hematoxylin and eosin-stained slide from 25 randomly selected grade 3 endometrioid carcinomas and 25 high-grade serous carcinomas. Histotype was independently assigned by 5 pathologists initially blinded to immunohistochemical WT1/p53 status, with subsequent reassessment unblinded to WT1/p53 status. Patients diagnosed with grade 3 endometrioid carcinoma had a significantly longer survival compared with high-grade serous carcinoma in univariate analysis (hazard ratio [HR]=0.34, 95% confidence interval [CI]=0.16-0.67, P=0.0012) but not after adjusting for age, stage, treatment center, and residual tumor (HR=1.01, 95% CI=0.43-2.16, P=0.98). Grade 3 endometrioid carcinoma cases (N=30) were identical to grade 2 endometrioid carcinoma cases (N=23) with respect to survival in univariate analysis (HR=1.07, 95% CI=0.39-3.21, P=0.89) and immunohistochemical profile. Using histomorphology alone, interobserver agreement for the diagnosis of grade 3 endometrioid or high-grade serous carcinoma was 69%, which significantly increased (P<0.0001) to 96% agreement with the knowledge of WT1/p53 status. Our data support the diagnostic value of WT1/p53 status in differentiating between grade 3 endometrioid carcinoma and high-grade serous carcinoma. However, grade 3 and grade 2 endometrioid carcinomas showed no differences in immunophenotype or clinical parameters, suggesting that they could be combined into a single group.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival., Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong)., Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively)., Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths. Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing. Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8 + tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival. Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. Clin Cancer Res; 24(3); 569-80. ©2017 AACR See related commentary by Peng and Mills, p. 508 ., (©2017 American Association for Cancer Research.)

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors., Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer., Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years., Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines., Main Outcomes and Measures: Overall survival time., Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form., Conclusions and Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

Purpose: Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry., Methods: We included patients with endometrioid (n = 180) and clear cell (n = 165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher's exact test., Results: Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR = 0.45, 95% CI = 0.23-0.87, p = 0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR = 2.17, 95% CI = 0.92-5.13, p = 0.08) and lower pre-treatment CA125 levels (OR = 0.17, 95% CI = 0.02-1.32, p = 0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p ≤ 0.03)., Conclusions: Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.

The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.

Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.

Aims: The clinical courses of patients with low-grade serous carcinoma (LGSC) can be substantially different. The purpose of this study was to explore whether molecular or pathological features could identify patients who follow a more aggressive course., Methods and Results: Twenty-six primary LGSCs (11 with an aggressive clinical course, and 15 with an indolent clinical course) and five paired recurrences were assessed for non-synonymous somatic mutations in 18 MAPK pathway genes and in 42 other classic cancer 'hotspot' genes by use of a custom-designed AmpliSeq panel based on the AmpliSeq Cancer hotspot panel v2. Copy number alterations for 94 target genes were assessed with the nCounter v2 Cancer CN assay. Immunohistochemistry for 12 proteins was performed. We detected 16 mutations in 13 of 26 cases (50%), affecting five genes that signal through the MAPK pathway, and one ESR1 mutation implicated in resistance to endocrine therapy in breast cancer. Recurrent samples were concordant with the primary tumour with respect to the mutational status, but all five cases showed additional alterations at the copy number or protein expression level. The absence of progesterone receptor (PR) expression and the presence of myometrial lymphovascular invasion were associated with an unfavourable outcome (log-rank P = 0.016 and P < 0.0001, respectively), but none of the other molecular features assessed showed an association., Conclusion: Despite limited case numbers, it appears that current molecular testing is inferior to a pathological parameter or protein expression in predicting the outcome of LGSCs. Prediction of outcome based on the primary tumour may be confounded by additional changes acquired over time., (© 2016 John Wiley & Sons Ltd.)

Background: In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant., Results: Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 ( P  = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses)., Conclusion: This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions.

There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.

Aims: Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types., Methods and Results: Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age <50 years, synchronous endometrial endometrioid carcinoma, a higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A, and at least 20 CD8-positive intraepithelial lymphocytes per high-power field, but was not associated with cancer-specific death. Age <50 years, higher CA125 levels at diagnosis and at least 20 CD8-positive intraepithelial lymphocytes per high-power field remained significant after adjustment for multiple testing, but their sensitivity for identifying dMMR remained insufficient., Conclusion: Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas., (© 2016 John Wiley & Sons Ltd.)

Objective: To assess the association of hormone receptor expression with outcome in high-grade endometrial carcinomas., Methods: This study included three sites participating in the Canadian High Risk Endometrial Cancer (CHREC) consortium. Sections from tissue microarrays containing cases with a diagnosis of endometrioid grade 3 (EC3) and endometrial serous carcinoma (ESC) were assessed for estrogen (ER) and progesterone receptor (PR) expression by immunohistochemistry. Expression was considered present if >1% of tumor cell nuclei were labeled. Associations with overall survival were assessed., Results: ER expression was present in 168/216 (78%) of EC3 and 124/192 (65%) of ESC. PR expression was present in 148/212 (70%) of EC3 and 83/196 (42%) of ESC. PR expression was significantly associated with favorable overall survival in EC3 and ESC (log rank, p=0.018 and p=0.0024) but ER expression was not. PR expression was significantly associated with favorable overall survival in EC3 independent of age, stage, center and lymph-vascular invasion (hazard ratio=0.457, 95% CI 0.257-0.811, p=0.0075) as well as in stage I and II ESC (hazard ratio=0.266, 95% CI 0.094-0.750, p=0.0123)., Conclusion: Our data provide support for the assessment of the PR expression status in EC3 and ESC. Future work will be required to determine how PR expression may be incorporated into management of patients with EC3 and ESC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Head and neck cancer (HNC) is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding head and neck cancers in Tanzania, and Bugando Medical Centre in particular. This study describes the clinicopathological profile of HNC in our local setting and highlights the challenges in the management of this disease., Methods: This was a retrospective study of histopathologically confirmed cases of head and neck cancers treated at Bugando Medical Center between January 2009 and December 2013., Results: A total of 346 patients (M:F = 2.1:1) were studied representing 9.5 % of all malignancies. The median age of patients was 42 years. Cigarette smoking (76.6 %) and heavy alcohol consumption (69.9 %) were the most frequently identified risk factors for head and neck cancer. The majority of patients (95.9 %) presented late with advanced stages. Twenty-five (7.2 %) patients were HIV positive with a median CD4+ count of 244 cells/μl. The oral cavity (37.3 %) was the most frequent anatomical site affected. The most common histopathological type was carcinomas (59.6 %) of which 75.7 % were squamous cell carcinoma. A total of 196 (56.6 %) patients underwent surgical procedures for HNC. Radiotherapy and chemotherapy was reported in 9.5 and 16.8 % of patients, respectively. Only 2 (0.6 %) patients received chemo-radiation therapy. The mortality rate was 24.4 %. The overall 5-year survival rate (5-YSR) was 20.6 %. The predictors of overall 5-YSR were age of patient at diagnosis, stage of disease, extent of lymph node involvement, HIV seropositivity and CD4+ count <200 cells/μl (P < 0.001). Local recurrence was reported in 22 (23.4 %) patients and this was significantly associated with positive resection margins, stage of the tumor and presence of metastasis at diagnosis and non-adherence to adjuvant therapy (P < 0.001)., Conclusion: Head and neck cancers are not uncommon at Bugando Medical Centre and show a trend towards a relative young age at diagnosis and the majority of patients present late with advanced stage cancer. Therefore, public enlightenment, early diagnosis, and effective cost-effective treatment and follow-up are urgently needed to improve outcomes of these patients in our environment.

Background: Vascular anomalies pose major diagnostic and therapeutic challenges among pediatricians and pediatric surgeons practicing in resource limited countries. There is paucity of published data regarding this subject in Tanzania and Bugando Medical Centre in particular. This study describes our experiences on the challenges and outcome of surgical management of childhood vascular anomalies in our environment., Methods: Between January 2009 and December 2013, a prospective study on the surgical management of vascular anomalies was undertaken at Bugando Medical Centre., Results: A total of 134 patients (M; F = 1:2.5) were studied. The median age at presentation was 6 years. Of the 134 patients, 101 (75.4%) were diagnosed as having vascular tumors and 33 (24.6%) had vascular malformations. The head and the neck were the most frequent anatomical site recorded as having a tumor (56.7% of patients). Out of 134 patients, 129 (96.3%) underwent surgical treatment. Failure to respond to non-operative treatment (86.8%), huge disfiguring/obstructing mass (4.7%), infection (3.1%), ulceration (3.1%) and hemorrhage (2.3%) were indications for surgical intervention. Tumor excision and primary wound closure was the most common type of surgical procedure performed in 80.6% of patients. Surgical site infection was the most frequent complications accounting for 33.8% of cases. Mortality rate was 1.5%. Tumor excision and primary wound closure gave better outcome compared with other surgical options (p < 0.001). Outcome of injection sclerotherapy in 3 (3.7%) children, serial ligation of feeder vessels employed in 2 (1.6%), and conservative treatment in 5 (3.7%), were poor and required conversion to surgical excision. Despite low mortality rate recorded in this study, but ugly scar, 14 (20.6%) and limb deformity, 6 (8.8%) were problems. The overall result of surgical treatment at the end of follow up period was excellent in 108 (87.1%) patients., Conclusion: Surgical excision and primary wound closure gave good outcome which could be employed in complicated and vascular anomalies which failed to respond to other treatment in regions with limited resources.

Background: Kaposi's Sarcoma is the most common sarcoma and second most prevalent cancer seen in Tanzania. Little is known about Kaposi's sarcoma in our setting as there is paucity of recent published data regarding this condition. This study describes the clinicopathological pattern and treatment outcome of Kaposi's sarcoma at Bugando Medical Centre, a tertiary care hospital in northwestern Tanzania., Methods: This was a prospective study of histologically confirmed Kaposi's sarcoma that was conducted at Bugando Medical Center between July 2004 and June 2014., Results: A total of 248 patients (M:F = 1.4:1) representing 2.4% of all malignancies during the study period were enrolled into the study. The median age at presentation was 36 years. Females were younger than males (p = 0.04). Out of 248 patients, 122 (49.2%) were HIV positive. Of these, 46 (37.7%) were males and 76 (62.3%) females. AIDS-related Kaposi's sarcoma were younger than HIV negative Kaposi's sarcoma patients (p = 0.011). Median duration of symptoms was 6 months. Kaposi's sarcoma was the AIDS defining disease in 82 (67.2%) patients while in the remaining 40 (32.8%) it was diagnosed between 1 and 14 months after the initial diagnosis of AIDS. The lower limb was most frequently involved site in 28.9% of patient. Females had more disseminated lesions compared with more localized lesions in the males (p = 0.001). The treatment modalities in this study included chemotherapy, radiotherapy, surgery and highly active antiretroviral therapy. Overall 126 (53.4%) patients had significant improvement in quality of life at the end of 1 year follow up. Treatment related complication and mortality rates were 25.8 and 24.2% respectively. Poor ACTG stage, CD4+ count <200 cells/µl, associated co-morbid illness, disseminated disease and poor adherent to chemotherapy were the significant independent factors associated with deaths (p < 0.001). Patient's follow-up was generally poor and data on long-term survivals were not available as more than two-thirds of patients were lost to follow up., Conclusion: Kaposi's sarcoma is the most common malignant vascular tumor and HIV/AIDS- related cancer in our region. There is an urgent need to develop health education programmes to enhance the understanding of this disease and how it spreads, particularly among the younger generation.

Background: Penile cancer is an uncommon malignancy in developed countries, but the incidence is as high as 10% to 20% of all male cancers in some developing countries. There is a paucity of published data on this subject in our setting. This study describes the clinicopathological presentation and treatment outcome of this condition in our environment, and highlights challenges associated with the care of these patients and proffers solutions for improved outcome., Methods: This was a retrospective study of histologically confirmed cases of penile cancer seen at Bugando Medical Centre between January 2004 and December 2013., Results: There were 236 penile cancer patients representing 2.2% of all male malignancies during the study period. The median age was 47 years with a modal age group of 41 to 50 years. Of the 236 patients, 147 (62.3%) had severe phimosis. The majority of patients (89.8%) were uncircumcised. A history of human papilloma virus (HPV) was reported in 12 (5.1%) cases. One hundred eighty-two (77.1%) patients reported history of cigarette smoking. Seven (6.7%) patients were human immunodeficiency virus (HIV) positive. The majority of the patients (68.6%) presented with Jackson's stages III and IV. Squamous cell carcinoma was the most common histopathological type (99.2%). Lymph node metastasis was recorded in 65.3% of cases, and it was significantly associated with the tumor size, histopathological subtype, histopathological grade, lympho-vascular invasion, positive resection margins, and urethral involvement (P < 0.001). Distant metastasis accounted for 4.2% of cases. The majority of patients (63.1%) underwent partial penectomy. Chemotherapy and radiotherapy were given in 14 (5.9%) and 12 (5.1%) patients, respectively. Complication and mortality rates were 22.0% and 4.2%, respectively. HIV positivity, histopathological stage and grade of the tumor, and presence of metastases at the time of diagnosis were the main predictors of death (P < 0.001). The median length of hospitalization was 14 days. Local recurrence was reported in 12 (5.3%) patients. Data on long-term survivals were not available as the majority of patients were lost to follow-up., Conclusions: Penile cancer is not rare in our environment. The majority of patients present late with advanced stage of the disease. Early detection of primary cancer at an early stage may improve the prognosis.

Background: Testicular cancers constitute major therapeutic challenges in resource-limited countries and still carry poor outcomes. There is a paucity of published data regarding testicular cancer in Tanzania, and Bugando Medical Centre in particular. This study describes the clinicopathological pattern, treatment outcome and challenges in the management of testicular cancer in our local setting., Methods: This was a retrospective study including all patients who had had histopathologically confirmed testicular cancer at Bugando Medical Centre between February 2004 and January 2014., Results: A total of 56 testicular cancer patients were enrolled in the study, representing 0.9% of all malignancies. The median age of patients at presentation was 28 years, with a peak incidence in the 21-to-30-year age group. A family history of testicular cancer was reported in four (5.4%) patients. A history of cryptorchidism was reported in six (10.7%) patients. Most patients (57.1%) presented late with an advanced stage of cancer. Testicular swelling was the main complaint in 48 (85.7%) patients. The right testis was involved in 67.9% of cases. Lymph node and distant metastases were documented in 10 (17.9%) and 12 (21.4%) patients, respectively. Histologically, 80.4% of patients had germ cell cancers, with seminoma accounting for 62.2% of cases. The most common surgical procedure was inguinal orchidectomy (77.4%). Adjuvant chemotherapy and radiotherapy were used in six (11.1%) and four (7.4%) patients, respectively. Eight (14.3%) patients died. The main predictors of mortality (P<0.001) were patient's age (>65 years), late presentation (>6 months), stage of disease, and presence of metastasis at time of diagnosis. The mean follow-up period was 22 months. At the end of five years, only 18 (37.5%) patients were available for follow-up and the overall 5-year survival rate was 22.2%. The main predictors of 5-year survival rate (P<0.001) were patients' age, stage of disease, and presence of lymph node and distant metastases., Conclusions: Testicular cancers, though rare in our setting, still carries a poor prognosis. Late presentation, poverty, paucity of resources and the high cost of newer imaging and treatment modalities are major challenges to management. Better health funding and education regarding testicular self-examination is essential.

Background: Pediatric neck masses are one of the common surgical conditions presenting to the pediatric surgical wards and clinics in many centers worldwide. There is paucity of published information regarding pediatric neck masses in Tanzania and the study area in particular. This study determines the etiology, clinico-histopathological patterns and treatment outcome of pediatric neck masses and to identify predictors of outcome in our local setting., Methods: This was a prospective cross-sectional hospital based study done in children aged ten years and below with neck masses for a five months period. Statistical data analysis was done using SPSS version 17.0., Results: A total of 148 patients were studied. Their ages ranged from 2 months to 10 years (median 3 years). The male to female ratio was 2.5:1. Inflammatory lesions were the most frequent cause of neck masses accounting for 43.9% of cases. The median duration of illness was 2 years. Except for the neck mass, 72 (48.6%) of the children had clinically stable health condition on presentation. The posterior triangle was commonly involved in 118 (79.7%) patients. eight (5.4%) were HIV positive. The majority of patients (95.9%) were treated surgically. Postoperative complication rate was 30.4% and surgical site infection was the most frequent complication in 37.5% of cases. The median length of hospital stay was 10 days and was significantly longer in patients with malignant masses and those with surgical site infection (p <0.001). The overall mortality rate in this study was 8.1% and it was significantly associated with malignant masses, associated pre-existing illness, late presentation, HIV positivity, low CD 4 count, high ASA class and presence of surgical site infections (p <0.001). The outcome of patients on discharge was excellent as more than 90% of patients were successfully treated and discharged well., Conclusion: Pediatric neck masses are among the most common causes of paediatric surgical admissions and pose a diagnostic and therapeutic challenge in our setting. We advocate early surgical consultation and thorough and timely histopathological examination of neck masses in children.

Background: Hepatocellular carcinoma is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding hepatocellular carcinoma in Tanzania, and the study area in particular. This study describes the clinicopathological profile of hepatocellular carcinoma in our local setting and highlights the challenging problems in the management of this disease., Methods: This was a retrospective study of histopathologically confirmed cases of hepatocellular carcinoma seen at Bugando Medical Center between March 2009 and February 2013., Results: A total of 142 patients (M: F = 2.2: 1) were studied representing 4.6% of all malignancies. The median age of patients was 45 years. Hepatitis B virus infection (66.2%) and heavy alcohol consumption (60.6%) were the most frequently identified risk factors for hepatocellular carcinoma. The majority of patients (88.0%) presented late with advanced stages. HBsAg was positive in 66.2% of the patients and Hepatitis C Virus antibody in 16.9%. Thirteen (9.2%) patients tested positive for HIV infection. Most patients (52.8%) had both right and left lobe involvement. The trabecular pattern (47.9%) was the most frequent histopathological type. None of patients had curative therapy because of the advanced nature of the disease. Coagulopathy (45.7%) was the most common complications. The overall mortality rate was 46.5% and it was significantly associated with comorbidity, HIV positivity, CD4+ count <200 cells/μl, high histological grade, advanced stage of the tumor, presence of distant metastases at the time of diagnosis, and associated complications (P < 0.001). The overall median duration of hospital stay was 14 days. The majority of patients (71.1%) were lost to follow-up at the end of the follow-up period., Conclusions: Hepatocellular carcinoma patients in this region are relatively young at diagnosis and the majority of them present late with an advanced stage and high rate of distant metastasis. Lack of awareness of the disease, poor accessibility to healthcare facilities, and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment, and proper follow-up to improve treatment outcome.

Background: Hirschsprung's disease (HD) is the commonest cause of functional intestinal obstruction in children and poses challenges to pediatricians and pediatric surgeons practicing in resource-limited countries. This study describes the clinical characteristics and outcome of management of this disease in our setting and highlights challenges associated with the care of these patients and proffer solutions for improved outcome., Methods: This was a descriptive prospective study of children aged ≤ 10 years who were histologically diagnosed and treated for HD at our centre between July 2008 and June 2013., Results: A total of 110 patients (M: F ratio= 3.6:1) with a median age of 24 months were studied. Six (5.5%) patients were in the neonatal period. Sixty-four (58.2%) patients had complete intestinal obstruction whereas 42 (38.2%) and 4 (3.6%) patients had chronic intestinal obstruction and intestinal perforation respectively. No patient had enterocolitis. Constipation (94.5%) was the most common complaints. 109 (99.1%) patients had colostomy prior to the definitive pull-through. The median duration of colostomy before definitive pull-through was 4 months. The majority of patients (67.3%) had short segment of aganglionosis localized to the recto-sigmoid region. The definitive pull-through was performed in 94 (85.5%) patients (Swenson's pull-through 76 (80.9%), Duhamel's pull-through (12.8%) and Soave's pull-through 4 (4.3%) patients). Postoperative complication rate was 47.3%. The median length of hospital stay was 26 days. Patients who developed complications stayed longer in the hospital and this was statistically significant (p <0.001). Mortality rate was 21.8%. The age < 4 weeks, delayed presentation and surgical site infection were the main predictors of mortality (p < 0.001). During the follow-up period, the results of Swenson's and Duhamel's pull through procedures were generally good in 87.8% and 42.9% of patients respectively. The result of Soave's procedures was generally poor in this study., Conclusion: HD remains the commonest cause of functional intestinal obstruction in children and contributes significantly to high morbidity and mortality in our setting. The majority of patients present late when the disease becomes complicated. Early diagnosis and timely definitive pull through procedure are essential in order to decrease the morbidity and mortality associated with this disease.

Introduction: Cancer of the cervix rank the second most common cause of cancer related deaths among women in Sub-Saharan Africa. It is estimated that 529, 409 new cases are diagnosed annually with a mortality rate approaching 274,883 per year. Cervical Intraepithelial Neoplasia (CIN) precedes almost all cervical cancers. The incidence rate of CIN among HIV infected women is five times higher as compared to the rate in HIV negative women. The screening for cervical dysplasia and an appropriate management in women with CIN are effective methods for preventing cervical cancer. This study was done to determine the prevalence and predictors of CIN among a HIV infected women attending Care and Treatment centre (CTC) at Bugando Medical Centre (BMC)., Methods: A cross sectional survey was undertaken among HIV infected women aged 18 years and above attending at BMC CTC clinic between February and March 2013. Visual Inspection with Acetic acid (VIA) was used as the screening method for detection of CIN. Socio-demographic, reproductive and clinical information was obtained from participants and the blood was collected for CD4 lymphocyte count. Cervical punch biopsy for histological examination was performed for those who had VIA positive test. Data were entered and analyzed using STATA Version 12.0 soft ware., Results: A total number of 95 (26.8%) participants had positive VIA test among three hundred and fifty-five (355) HIV infected women. Histology results showed; 4(4.2%) were normal, 26 (27.4%) had an inflammatory lesion, 58(61.1%) had CIN and 7(7.3%) had invasive cervical cancer. CIN was found to be associated with a history of multiple sexual partners (P<0.001), a history of genital warts (P<0.001), and a history of STI (P = 0.010)., Conclusion: The Cervical Intraepithelial Neoplasia is a problem among HIV infected women. A history of multiple sexual partners, a history of genital warts, a history STI and a low baseline CD4 T lymphocyte were significant predictors for CIN. Screening for Cervical Intraepithelial Neoplasia is recommended for all women with HIV.

Background: Esophageal cancer is one of the most serious gastrointestinal cancer worldwide, owing to its rapid development and fatal prognoses in most cases. There is a paucity of published data regarding esophageal cancer in Tanzania and the study area in particular. This study was conducted to describe the endoscopic and clinicopathological patterns of esophageal cancer in this part of the world. The study provides baseline local data for future comparison., Methods: This was a retrospective study of histologically confirmed cases of esophageal cancer seen at Bugando Medical Center and Muhimbili National Hospital between March 2008 and February 2013. Data were retrieved from medical record computer database and analyzed using SPSS computer software version 17.0., Results: A total of 328 esophageal cancer patients were enrolled in the study, representing 25.3% of all malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The median age of patients at presentation was 47 years. The majority of patients (86.6%) were peasants coming from the rural areas. Smoking and alcohol consumption were documented in 74.7% and 61.6% of patients respectively. Family history of esophageal cancer was reported in 4.6% of cases. The majority of patients (81.7%) presented late with advanced stage of cancer. Progressive dysphagia and weight loss were the most common presenting symptoms occurring in all patients. The middle third esophagus (58.5%) was the most frequent anatomical site for esophageal cancer followed by lower third (27.4%) and upper third esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%) patients were diagnosed with advanced esophageal cancer (Stages III and IV). According to tumor grading, most of tumors were moderately differentiated accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of patients., Conclusion: Esophageal cancer is not uncommon in this region and shows a trend towards a relative young age at presentation and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations and detecting esophageal cancer at an early stage in order to improve chances for successful treatment and survival.

Despite recent advances both in preoperative diagnosis and postoperative care, obstructive jaundice still contributes significantly to high morbidity and mortality. A prospective study was undertaken to identify predictors of outcome among patients with obstructive jaundice at Bugando Medical Centre in north-western Tanzania. A total of 138 patients were studied. The male to female ratio was 1:1.6. The median age of patients was 58 years. Patients with malignant obstructive jaundice were older than those of benign type (P < 0.001). Ca head of pancreas (65.1%) was the commonest malignant cause of jaundice where as choledocholithiasis (51.9%) was the commonest benign cause. Twelve (9.7%) patients were HIV positive with a median CD 4+ count of 342 cells/μl. A total of 130 (94.2%) patients underwent surgical treatment and the remaining 8 (5.8%) patients were unfit for surgery. The complication rate was 30.4% mainly due to surgical site infections and it was significantly influenced by malignant causes, WBC count > 10 X 109/l and HIV infection with low CD4 (200 cells/μl) (p < 0.0001). The median hospital stay and mortality rate were 18 days and 20.3%, respectively. A low haematocrit and presence of postoperative complications were the main predictors of the hospital stay (P < 0.001), whereas age > 60 years, prolonged duration of jaundice, malignant causes, high bilirubin levels, HIV infection with low CD4+ count (200 cells/ μl) and presence of postoperative complications significantly predicted mortality (P < 0.001). In conclusion, our study highlighted the important factors that predict the outcome of patients presenting with obstructive jaundice at BMC; therefore attention should be focused to these factors so as to improve the outcome of these patients.

Primary leiomyoma of the ovary is rarely described in literature. It accounts for 0.5-1% of all benign ovarian tumours. Bilateral ovarian leiomyoma are rare and only few cases have been described. In this report, we describe a case of 29-year-old nulliparous, Tanzanian lady presented with one-year history of abdominal swelling and secondary amenorrhea. Examination revealed a palpable, suprapubic mass, and a pelvic ultrasound showed features of ovarian tumour. An explorative laparotomy was performed to confirm the diagnosis. A bilateral salpingo-oophrectomy and hysterectomy was performed for huge bilateral ovarian tumours. Histopathological examination confirmed ovarian leiomyoma. Challenges remain in the management of bilateral primary ovarian tumours, especially for young and nulliparous women. Pre-laparotomy diagnostic measures are important so as to know the type of the tumour you are dealing with and plan the appropriate management.

Background: Gastric outlet obstruction poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. There is a paucity of published data on this subject in our setting. This study was undertaken to highlight the etiological spectrum and treatment outcome of gastric outlet obstruction in our setting and to identify prognostic factors for morbidity and mortality., Methods: This was a descriptive prospective study which was conducted at Bugando Medical Centre between March 2009 and February 2013. All patients with a clinical diagnosis of gastric outlet obstruction were, after informed consent for the study, consecutively enrolled into the study. Statistical data analysis was done using SPSS computer software version 17.0., Results: A total of 184 patients were studied. More than two-third of patients were males. Patients with malignant gastric outlet obstruction were older than those of benign type. This difference was statistically significant (p < 0.001). Gastric cancer was the commonest malignant cause of gastric outlet obstruction where as peptic ulcer disease was the commonest benign cause. In children, the commonest cause of gastric outlet obstruction was congenital pyloric stenosis (13.0%). Non-bilious vomiting (100%) and weight loss (93.5%) were the most frequent symptoms. Eighteen (9.8%) patients were HIV positive with the median CD 4+ count of 282 cells/μl. A total of 168 (91.3%) patients underwent surgery. Of these, gastro-jejunostomy (61.9%) was the most common surgical procedure performed. The complication rate was 32.1 % mainly surgical site infections (38.2%). The median hospital stay and mortality rate were 14 days and 18.5% respectively. The presence of postoperative complication was the main predictor of hospital stay (p = 0.002), whereas the age > 60 years, co-existing medical illness, malignant cause, HIV positivity, low CD 4 count (<200 cells/μl), high ASA class and presence of surgical site infection significantly predicted mortality ( p< 0.001). The follow up of patients was generally poor as more than 60% of patients were lost to follow up., Conclusion: Gastric outlet obstruction in our setting is more prevalent in males and the cause is mostly malignant. The majority of patients present late with poor general condition. Early recognition of the diagnosis, aggressive resuscitation and early institution of surgical management is of paramount importance if morbidity and mortality associated with gastric outlet obstruction are to be avoided.

Background: Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome., Methods: This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics., Results: A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision., Conclusion: Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis.

Background: Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature., Methods: A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0., Results: Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge., Conclusion: Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival.

Introduction: Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region., Methods: This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables., Results: A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006)., Conclusion: The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer.

Background: Colorectal cancer is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries, probably due to the acquisition of a western lifestyle. However, information regarding colorectal cancer in Tanzania and the study area in particular is limited. This study was conducted in our local setting to describe the clinicopathological pattern of colorectal cancer and highlight the challenging problem in the management of this disease., Methods: This was a retrospective study of histologically confirmed cases of colorectal cancer seen at Bugando Medical Center between July 2006 and June 2011. Data were retrieved from patients' files and analyzed using SPSS computer software version 17.0., Results: A total of 332 colorectal cancer patients were enrolled in the study, representing 4.7% of all malignancies. Males outnumbered females by a ratio of 1.6:1. The median age of patients at presentation was 46 years. The majority of patients (96.7%) presented late with advanced stages. Lymph node and distant metastasis at the time of diagnosis was recorded in 30.4% and 24.7% of cases, respectively. The rectosigmoid region was the most frequent anatomical site (54.8%) involved and adenocarcinoma (98.8%) was the most common histopathological type. The majority of adenocarcinomas (56.4%) were moderately differentiated. Mucinous and signet ring carcinomas accounted for 38 (11.6%)and 15 (4.6%) patients, respectively. Three hundred and twenty-six (98.2%) patients underwent surgical procedures for colorectal cancer. Only 54 out of 321 (16.8%) patients received adjuvant treatment. Postoperative complication and mortality rates were 26.2% and 10.5%, respectively. The overall median duration of hospital stay was 12 days. Only nine out of 297 survivors (3.0%) were available for follow-up at the end of 5 years. Cancer recurrence was reported in 56 of 297 survivors (18.9%). Data on long-term survival were not available as the majority of patients were lost to follow-up., Conclusions: Colorectal cancer is not uncommon in our environment and shows a trend towards a relative young age at diagnosis and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations, early diagnosis and effective cost-effective treatment and follow-up to improve outcome of these patients.

Background: Despite marked decreases in its incidence, particularly in developed countries, gastric cancer is still the second most common tumor worldwide. There is a paucity of information regarding gastric cancer in northwestern Tanzania. This study was undertaken to describe our experience, in our local setting, on the management of gastric cancer, outlining the clinicopathological and treatment outcome of these patients and suggesting ways to improve the treatment outcome., Methods: This was a retrospective study of histologically confirmed cases of gastric cancer seen at Bugando Medical Centre between January 2007 and December 2011. Data were retrieved from patients' files and analyzed using SPSS computer software version 17.0., Results: A total of 232 gastric cancer patients were enrolled in the study, representing 4.5% of all malignancies. The male to female ratio was 2.9:1. The median age of patients was 52 years. The majority of the patients (92.1%) presented late with advanced gastric cancer (Stages III and IV). Lymph node and distant metastasis at the time of diagnosis was recorded in 31.9% and 29.3% of cases, respectively. The antrum was the most frequent anatomical site (56.5%) involved and gastric adenocarcinoma (95.1%) was the most common histopathological type. Out of 232 patients, 223 (96.1%) patients underwent surgical procedures for gastric cancer of which gastro-jejunostomy was the most frequent performed surgical procedure, accounting for 53.8% of cases. The use of chemotherapy and radiotherapy was documented in 56 (24.1%) and 12 (5.1%) patients, respectively. Postoperative complication and mortality rates were 37.1% and 18.1%, respectively. According to multivariate logistic regression analysis, preoperative co-morbidity, histological grade and stage of the tumor, presence of metastases at the time of diagnosis was the main predictors of death (P <0.001). At the end of five years, only 76 (32.8%) patients were available for follow-up and the overall five-year survival rate was 6.9%. Evidence of cancer recurrence was reported in 45 (19.4%) patients. Positive resection margins, stage of the tumor and presence of metastasis at the time of diagnosis were the main predictors of local recurrence (P <0.001)., Conclusions: Gastric cancer in this region shows a trend towards relative young age at diagnosis and the majority of patients present late with an advanced stage. Lack of awareness of the disease, poor accessibility to health care facilities and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment and proper follow-up to improve treatment outcome.

Background: Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania., Methods: This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15., Findings: There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3., Conclusion: Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis.

Practicing pathology in a resource-poor setting presents many challenges that are unfamiliar to pathologists in developed countries. Typically, the number of pathologists in a resource-poor country is small, even as a percentage of the total medical workforce. Although pathology should play a central role in the delivery of appropriate health care to the patient, this role is often hidden and not well recognized by patients, clinical colleagues, or other stakeholders, such as administrators and politicians. The public tends to think of the pathologist as the "Doctor of the Dead." The financial rewards are also small. Consequently, it is difficult to recruit physicians into pathology. The lack of human and material resources allocated to pathology leads inevitably to a large gap in health care for many patients, with an unmeasured negative effect, at both the individual and societal levels. Correct management of the patient, even when available, is not administered because of the lack of pathologic information. Surgery may be performed without the benefit of preoperative or postoperative pathologic confirmation of the diagnosis, let alone identification of important prognostic information. The pathologist plays a key role as an educator in developing countries to medical students, allied health professionals, and medical colleagues and is, therefore, called upon to provide many hours of teaching. The pathologist is uniquely qualified to provide knowledge and understanding regarding the diseases in the region where he or she practices. Although many of these challenges are universal, they are perhaps nowhere more acute than in resource-poor settings.

Schistosomiasis is a communicable disease which commonly involves urinary bladder causing hematuria, or large bowel causing bloody stool. The common species encountered in this lake region surrounding Lake Victoria in Tanzania are Schistosoma haematobium and Schistosoma mansoni. Complications can lead to portal hypertension due portal fibrosis in liver, and fibrosis in lung can lead to pulmonary hypertension; this commonly seen with S. mansoni. Major complications of S. maeametobium are chronic cystitis with squamous metaplasia with subsequent development of squamous cell carcinoma. Involvement of spinal cord causing paraplegia has been observed in S. haematobium. Other unusual pathology of schistosomiasis has been described, such as involvement of the appendix, ovary, prostate, and cervix. Here, we present a case of schistosomiasis in a 9-year-old boy who presented with left scrotal pain for one year which was accompanied by scrotal swelling; surgical exploration was done, and the finding was hydrocele and atrophic testes with nodules on the surface. Histological examination reveals atrophic testis and heavy active granulomatous inflammation with schistosoma eggs consistent with Schistosoma haematobium in the tunica vaginalis.

Background: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular pathogenesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and reduced survival in patients., Objective: This was a retrospective laboratory based study carried out in the Department of Pathology Makerere University, Kampala, Uganda. The aim of the study was to evaluate the expression of p53 protein in colorectal carcinoma in Ugandan patients, specifically its association with histological types, degree of differentiation, sites of the tumor and demographic characteristics of the patients., Methods: Immunohistochemistry was carried out on 109 patient's paraffin embedded tissue blocks of colorectal carcinoma diagnosed in the Pathology Department, Faculty of Medicine Makerere University Kampala during the period 1995 to 2005. The indirect immunoperoxidase method using monoclonal antibody p53 DO-7 and Envision (+) Dual link system-HRP to detect p53 expression was used. Haematoxylin and eosin stain was used for evaluation of histological types and degree of differentiation of the tumors. Topography of the tumors and demographic data were obtained from accompanying histological request forms., Results: Out of 109 patient's tissue blocks that were studied, 61 cases (56%) expressed p53 protein in the nucleus of malignant cells. Right sided colonic tumors were commoner (53.2%) than left sided colonic tumors (46.8%). p53 protein was expressed more in left sided colonic tumors with a significant difference (p<0.05), it was also expressed more in well differentiated tumors and non mucinous adenocarcinomas but with no significant difference (p>0.05). p53 expression was not affected by age or sex., Conclusion: Frequency of p53 protein expression in Ugandan patients did not differ from that reported in the other parts of the world. It was expressed more in the left sided colonic tumors and this could support the hypothesis that right and left colonic tumors could have different pathogenesis and probably also responsible for difference in prognosis in these two topographic sites.