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

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Background: Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population.Methods: We analysed data from the hospital-based KCH cancer registry, from June 2009 to September 2012, including data from a nested substudy on coinfections among cancer patients. Demographics and behavioural variables, including smoking and alcohol use, were collected through personal interviews with patients. We assessed HIV prevalence across cancer types. The distribution of cancer types was reported overall and by gender. Logistic regression was used to assess risk factors associated with common cancer types.Results: Data from 504 registered cancer patients were included—300 (59.5%) were female and 204 (40.5%) were male. Mean age was 49 years (standard deviation, SD = 16). There were 343 HIV-negative patients (71.2%), and 139 (28.8%) were HIV-positive. The commonest cancers were oesophageal (n = 172; 34.5%), cervical (n = 109; 21.9%), and Kaposi’s sarcoma (KS) (n = 52; 10.4%). Only 18% of cancer cases were histologically confirmed. Patients with oesophageal cancer were likely to be older than 50 years (odds ratio, OR = 2.22), male (OR = 1.47), and smokers (OR = 2.02). Kaposi’s sarcoma patients had the highest odds (OR = 54.4) of being HIV-positive and were also more likely to be male (OR = 6.02) and smokers. Cervical cancer patients were more likely to be HIV-positive (OR = 2.2) and less than 50 years of age.Conclusions: Age, smoking, and HIV are important risk factors for the 3 commonest cancer types (oesophageal, KS, and cervical) at this teaching hospital in Malawi. HIV is the single most important risk factor for Kaposi’s sarcoma and cervical cancer

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population

Extranodal natural killer/T-cell lymphoma in Malawi: a report of three cases

Abstract Background Extranodal NK/T-cell lymphoma (ENKTCL) reports from sub-Saharan Africa (SSA) are remarkably rare, despite early childhood acquisition and high prevalence of the causative infectious agent, Epstein-Barr virus (EBV), and frequent occurrence of other lymphoproliferative disorders causally associated with EBV. Case presentations At a national teaching hospital in Malawi, three patients of African descent were seen with ENKTCL between 2013 and 2014. Patients were aged between 29 and 60 years, two with craniofacial involvement and one with a primary abdominal tumor, and all were HIV-negative. All had systemic B symptoms, and two severely impaired performance status. On histologic review, morphology and immunophenotyping demonstrated classical ENKTCL features in all cases, including diffuse proliferations of intermediate-to-large atypical lymphocytes with high mitotic activity and extensive background necrosis, positivity for CD3 and CD56, and negativity for CD20. By in situ hybridization, all three tumors were positive for EBV-encoded RNA (EBER). Baseline plasma EBV DNA was also markedly elevated for all three patients. Due to radiotherapy and chemotherapy limitations, patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with rapid disease progression. All three patients died from progressive lymphoma within 3 months of initial diagnosis. Conclusions Our experience with these three patients in Malawi can highlight that ENKTCL does indeed occur in SSA, increase familiarity with ENKTCL among clinicians and pathologists throughout the region, and emphasize the need for better diagnosis and treatment for this neglected population

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

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