The histogenesis of Kaposi's sarcoma (KS) tumor spindle cells (SC) remains controversial but several immunohistochemical studies favor a lymphatic origin. Twenty KS surgical biopsies were analyzed for the coexpression of LANA, CD34, LYVE-1, D2-40, VEGFR-2, VEGFR3 by using double or triple immunostaining. Most of the SC in both early and late KS expressed the lymphatic markers LYVE-1, D2-40 and VEGFR-3 and the blood vascular endothelial/endothelial precursor cell markers CD34 and endothelial stem cell marker VEGFR-2. All the LANA1 SC in early and late KS were LYVE-11, but only 75% of these LANA1 cells were CD341. The CD341/LANA1 cells increased from early-(68.8%) to late-stage KS (82.2%). However, approximately 18% of the LANA1 SC in early KS were CD342 but were LYVE-11, suggesting that resident lymphatic endothelial cells (LEC) are targeted for primary infection by human herpesvirus-8. This LANA1/LYVE-11/CD342 (resident LEC) cell population clearly decreased during the development of KS from early (18.7%) to late KS (2.9%). Thus, in late stages of KS, most SC were LANA1/CD341/LYVE-11. However, in both early-and late-stage KS, approximately 18% of the SC were CD341/ LANA-/LYVE-12 and could represent newly recruited endothelial precursor cells, which become infected in the lesion and eventually undergo a phenotype switch expressing LEC markers. Our study apparently indicates that KS represents a unique variant of tumor growth with continues recruitment of tumor precursor cells as well as proliferation and decreased apoptosis of SC. ' 2006 Wiley-Liss, Inc.Key words: Kaposi's sarcoma; HHV-8; KSHV; LANA; lymphangiogenesis; lymphatic; vascular endothelium; immunohistochemistry Kaposi's sarcoma (KS) presents as a highly vascularized tumorlike lesion affecting primarily the skin but which during development also disseminates to lymphnodes and viscera. 1 The lesions develop from early stages of patch/plaque to late nodular tumor lesions, 2 with characteristic early infiltration of mononuclear inflammatory cells, formation of atypical small blood vessels and vascular slits (angiogenesis), extravasations of erythrocytes and increased appearance of so-called spindle cells (SC) regarded as the tumor cells. 3 Unlike metastatic cancers, KS may also develop as multicentric tumor lesions, each arising from a focal reactive lesion and appearance of endothelial SC. 4 In 1994, a new herpesvirus was identified, namely, KS-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8), 5 which subsequently also was found in the other clinicoepidemiological forms of KS, 6-8 i.e., classic KS, iatrogenic KS, endemic KS (EKS) as well as in some rare, often AIDS-associated lymphoid disorders as primary effusion lymphoma 9 and multicentric Castleman's disease. 10 The HHV-8 latency-associated nuclear antigen type 1 (LANA-1) is consistently expressed in infected cells and considered necessary for the maintenance of HHV-8 infection. 11 The histogenesis of KS remains controversial but several immunohistochemical studies favor an endothelial origin...

Summary Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B‐cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases – Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki‐67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B‐cell lymphomas from Europe and from sub‐Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not‐BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.

Tanzania requires more health professionals equipped to tackle its serious health challenges. When it became an independent university in 2007, Muhimbili University of Health and Allied Sciences (MUHAS) decided to transform its educational offerings to ensure its students practice competently and contribute to improving population health. In 2008, in collaboration with the University of California San Francisco (UCSF), all MUHAS's schools (dentistry, medicine, nursing, pharmacy, and public health and social sciences) and institutes (traditional medicine and allied health sciences) began a university-wide process to revise curricula. Adopting university-wide committee structures, procedures, and a common schedule, MUHAS faculty set out to: (i) identify specific competencies for students to achieve by graduation (in eight domains, six that are inter-professional, hence consistent across schools); (ii) engage stakeholders to understand adequacies and inadequacies of current curricula; and (iii) restructure and revise curricula introducing competencies. The Tanzania Commission for Universities accredited the curricula in September 2011, and faculty started implementation with first-year students in October 2011. We learned that curricular revision of this magnitude requires: a compelling directive for change, designated leadership, resource mobilization inclusion of all stakeholders, clear guiding principles, an iterative plan linking flexible timetables to phases for curriculum development, engagement in skills training for the cultivation of future leaders, and extensive communication.

BackgroundBreast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH).MethodsA cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January–December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS).ResultsA total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18–75 years and mean age was 48.36 years. Majority (64.3%) were in the 36–55 years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% (n = 53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% (n = 46/70) cases were immunostained for HER-2 and 15.2% (n = 7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive.ConclusionsHormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is higher than in a previous Tanzanian report and majority are luminal. HER2 over-expression is relatively common. It is strongly recommended that receptor status assessment be made routine for breast cancer patients at MNH.

corresponding to approximately 10% of KS registered during 1990-2005, were diagnosed (ELISA) as HIV-infected (OAKS) (74/78) and endemic KS (4/78). Females were 69.2% (54/78) with median age 31 and males 30.8% (24/78) with median age 38. More males (50%) had systemic KS than females (37%) and 4-times more multicentric OKS. All tested (34) oral KS patients sera had HHV-8 antibodies. Available (31/78) blood showed very low CD4 + T-lymphocyte counts. Most OKS (61.5%) had nodular histology. Immunostaining showed adult male nodular OAKS to have a significantly higher frequency of viral LANA + , endothelial CD34 + tumour spindle-cells (SC) and more Ki-67 + (median =24.1%) proliferating cells compared to females (17.2%). Juvenile nodular OAKS had more LANA + and Ki-67 + cells than corresponding adult cases. Significantly more LANA + and Ki-67 + cells were found in nodular OAKS compared to cutaneous HIV/AIDS Kaposi's sarcoma (CAKS). A positive correlation (60%) was found between the proliferation index (Ki-67 + cell frequency) and LANA + /CD34 + SC. OKS in Tanzania is since 1990, mostly seen in females, associated with HIV/AIDS and advanced (nodular) histopathology. Males have more systemic tumour burden while more females develop primary OAKS. HHV-8 + cells were more frequent in nodular male than female and in juvenile than adult nodular OAKS than cAKS. Higher tumoral HHV-8 content appeared to be correlated to proliferation index.

Kaposi's sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera, which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells (SC). These SC are infected with the Kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8). KS is promoted during HIV infection by various angiogenic and pro-inflammatory factors including HIV-Tat. The latency associated nuclear antigen type 1 (LANA-1) protein is well expressed in SC, highly immunogenic and considered important in the generation and maintenance of HHV-8 associated malignancies. Various studies favour an endothelial origin of the KS SC, expressing "mixed" lymphatic and vascular endothelial cell markers, possibly representing hybrid phenotypes of endothelial cells (EC). A significant number of SC during KS development are apparently not HHV8 infected, which heterogeneity in viral permissiveness may indicate that non-infected SC may continuously be recruited in to the lesion from progenitor cells and locally triggered to develop permissiveness to HHV8 infection. In the present study various aspects of KS pathogenesis are discussed, focusing on the histopathological as well as cytogenetic and molecular genetic changes in KS.

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BackgroundHIV infection is reported to be associated with some malignant lymphomas (ML) so called AIDS-related lymphomas (ARL), with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies.MethodsSections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH)/Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania from 1996–2001 were stained for hematoxylin and eosin and selected (70) cases for expression of pan-leucocytic (CD45), B-cell (CD20), T-cell (CD3), Hodgkin/RS cell (CD30), histiocyte (CD68) and proliferation (Ki-67) antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA) for HIV antibodies.ResultsThe proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200) comprising 77.84% non-Hodgkin (NHL) including 19.32% Burkitt's (BL) and 22.16% Hodgkin's disease (HD). The ML tumors frequency increased from 0.42% (1997) to 0.70% (2001) and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3–91 and peak age was 1–20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL) and primary central nervous system lymphoma (PCNSL) were diagnosed.ConclusionMalignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore, routine HIV screening of all malignant lymphoma patients at MNH is necessary to enable comprehensive ARL diagnosis and formulation of preventive and therapeutic protocols.