Case report: Multicentric Castleman disease as a manifestation of immune reconstitution inflammatory syndrome in Malawi

Introduction Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by systemic inflammation, lymphadenopathy, and cytopenias. MCD caused by Kaposi sarcoma herpesvirus (MCD-KSHV) frequently arises in the context of HIV. It can be associated with immune reconstitution inflammatory syndrome (IRIS), but MCD-IRIS is rarely reported in sub-Saharan Africa (SSA) where HIV and KSHV infection are common. Case description A 36-year-old woman in Malawi with HIV on antiretroviral therapy (ART) for nine years presented with fatigue, weight loss, and lymphadenopathy. Lymph node biopsy was consistent with HIV lymphadenitis without evident KSHV-MCD and HIV RNA was 4,244 copies/mL. She switched to second-line ART and returned four months later with worsening lymphadenopathy, fever, night sweats, weight loss, and anemia. A repeat lymph node biopsy demonstrated unequivocal KSHV-MCD features not present on the original biopsy. Her repeat HIV viral load was undetectable and she received chemotherapy with subsequent remission on continued ART for 24 months. Discussion This is among the first reported cases of MCD-IRIS from SSA, which has implications for a region where HIV and KSHV are highly prevalent. MCD-IRIS may contribute to early mortality after ART initiation in SSA, and increased awareness alongside improved diagnostic and treatment capacity are needed

Human papillomavirus in head and neck squamous cell carcinoma: A descriptive study of histologically confirmed cases at Kamuzu Central Hospital in Lilongwe, Malawi

Background: Head and neck squamous cell carcinoma (HNSCC) is common in sub-Saharan Africa, but the aetiologic contribution of human papillomavirus (HPV) is not well established.Methods: We assessed HNSCC cases for HPV using p16 immunohistochemistry (IHC) in Malawi. Associations between p16 IHC and tumour site, behavioural risk factors, demographic characteristics, and HIV status were examined.Results: From 2010 to 2014, 77 HNSCC cases were identified. Mean age was 52 years, 50 cases (65%) were male, and 48 (62%) were in the oropharynx (OP) or oral cavity (OC). HIV status was known for 35 patients (45%), with 5 (14%) HIV-infected. Substance use was known for 40 patients (52%), with 38% reporting any tobacco and 31% any alcohol. Forty-two cases (55%) had adequate tissue for p16 IHC, of which seven (17%) were positive, including 22% of OP/OC tumours.Conclusions: Despite high cervical cancer burden, HPV-associated HNSCC is not very common in Malaw

High pretreatment plasma Epstein-Barr virus (EBV) DNA level is a poor prognostic marker in HIV-associated, EBV-negative diffuse large B-cell lymphoma in Malawi

Plasma Epstein-Barr virus (EBV) DNA measurement has established prognostic utility in EBV-driven lymphomas, where it serves as a circulating tumor DNA marker. The value of plasma EBV measurement may be amplified in sub-Saharan Africa (SSA), where advanced imaging and molecular technologies for risk stratification are not typically available. However, its utility in diffuse large B-cell lymphoma (DLBCL) is less certain, given that only a subset of DLBCLs are EBV-positive. To explore this possibility, we measured plasma EBV DNA at diagnosis in a cohort of patients with DLBCL in Malawi. High plasma EBV DNA at diagnosis (≥3.0 log10 copies/mL) was associated with decreased overall survival (OS) (P =.048). When stratified by HIV status, the prognostic utility of baseline plasma EBV DNA level was restricted to HIV-positive patients. Unexpectedly, most HIV-positive patients with high plasma EBV DNA at diagnosis had EBV-negative lymphomas, as confirmed by multiple methods. Even in these HIV-positive patients with EBV-negative DLBCL, high plasma EBV DNA remained associated with shorter OS (P =.014). These results suggest that EBV reactivation in nontumor cells is a poor prognostic finding even in HIV-positive patients with convincingly EBV-negative DLBCL, extending the potential utility of EBV measurement as a valuable and implementable prognostic marker in SSA

CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV

Early Experience after Developing a Pathology Laboratory in Malawi, with Emphasis on Cancer Diagnoses

Abstract Background: Despite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses

Early Experience after Developing a Pathology Laboratory in Malawi, with Emphasis on Cancer Diagnoses

BackgroundDespite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses.Methods and FindingsWe performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99%) with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%). Among cancers, cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91, 11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75, 9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19–1.29) among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14–1.56) among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not.ConclusionsDespite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical information for pathologically confirmed cancers can allow these data to complement population-based registration

Outcomes for paediatric Burkitt lymphoma treated with anthracycline-based therapy in Malawi

Burkitt lymphoma (BL) is the most common paediatric cancer in sub-Saharan Africa (SSA). Anthracyline-based treatment is standard in resource-rich settings, but has not been described in SSA. Children ≤ 18 years of age with newly diagnosed BL were prospectively enrolled from June 2013 to May 2015 in Malawi. Staging and supportive care were standardized, as was treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for six cycles. Among 73 children with BL, median age was 9.2 years (interquartile range 7.7–11.8), 48 (66%) were male and two were positive for human immunodeficiency virus. Twelve (16%) had stage I/II disease, 36 (49%) stage III and 25 (34%) stage IV. Grade 3/4 neutropenia occurred in 17 (25%), and grade 3/4 anaemia in 29 (42%) of 69 evaluable children. Eighteen-month overall survival was 29% (95% confidence interval [CI] 18–41%) overall. Mortality was associated with age >9 years [hazard ratio [HR] 2.13, 95% CI 1.15–3.94], female gender (HR 2.12, 95% CI 1.12–4.03), stage (HR 1.52 per unit, 95% CI 1.07–2.17), lactate dehydrogenase (HR 1.03 per 100 iu/l, 95% CI 1.01–1.05), albumin (HR 0. 96 per g/l, 95% CI 0.93–0.99) and performance status (HR 0.78 per 10-point increase, 95% CI 0.69–0.89). CHOP did not improve outcomes in paediatric BL compared to less intensive regimens in Malawi

Plasmablastic lymphoma in Malawi

Abstract Plasmablastic lymphoma (PBL) clinical descriptions are scarce from sub-Saharan Africa (SSA) where both HIV and EBV are highly endemic. We identified 12 patients with pathologically confirmed PBL from a prospective cohort in Lilongwe, Malawi. Median age was 46 (range 26–71), seven (58%) were male, and six (50%) were HIV-positive. Eight patients were treated with CHOP and four with a modified EPOCH regimen. One-year overall survival was 56% (95% CI 24–79%), without clear differences based on HIV status. PBL occurs in Malawi in HIV-positive and HIV-negative individuals and can be treated successfully with curative intent, even in a low-resource setting in SSA

Update on pathology laboratory development and research in advancing regional cancer care in Malawi

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs

Human papillomavirus in head and neck squamous cell carcinoma: A descriptive study of histologically confirmed cases at Kamuzu Central Hospital in Lilongwe, Malawi

Head and neck squamous cell carcinoma (HNSCC) is common in sub-Saharan Africa, but the aetiologic contribution of human papillomavirus (HPV) is not well established