This Correspondence relates to the article by Li et al (Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the ...Association for Molecular Pathology, American Society of Clinical Oncology, and the College of American Pathologists. J Mol Diagn 2017, 19:4–23).
Aggressive non‐Hodgkin lymphoma (NHL) is among the most common cancers in sub‐Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly ...diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16‐63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9‐460), and nine (82%) had suppressed HIV RNA < 400 copies/mL. Patients received a median of six cycles (range 2‐8) and median follow‐up was 14 months (range 2‐34) among patients still alive. Grade 3/4 neutropenia was observed in 26% of cycles and in 65% of patients. Sixteen (94%) responded to EPOCH and 10 (59%) achieved a complete response. One‐year overall survival (OS) was 62% (95% confidence interval CI, 42%‐91%). Five patients (29%) died from progressive NHL and three (18%) from treatment‐related complications. These data suggest EPOCH with setting‐appropriate modifications may be a practical, safe, and effective option for improving high‐risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.
We evaluated the safety and efficacy of EPOCH, with modifications as required for local administration, for patients with high‐risk NHL in Malawi. We treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Our experience suggests that EPOCH with setting‐appropriate modifications may be a practical, safe, and effective option for improving high‐risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.
Diagnostic complexities of eosinophilia Montgomery, Nathan D; Dunphy, Cherie H; Mooberry, Micah ...
Archives of pathology & laboratory medicine (1976)
137, Številka:
2
Journal Article
Recenzirano
The advent of molecular tools capable of subclassifying eosinophilia has changed the diagnostic and clinical approach to what was classically called hypereosinophilic syndrome.
To review the ...etiologies of eosinophilia and to describe the current diagnostic approach to this abnormality.
Literature review.
Eosinophilia is a common, hematologic abnormality with diverse etiologies. The underlying causes can be broadly divided into reactive, clonal, and idiopathic. Classically, many cases of eosinophilia were grouped together into the umbrella category of hypereosinophilic syndrome, a clinical diagnosis of exclusion. In recent years, an improved mechanistic understanding of many eosinophilias has revolutionized the way these disorders are understood, diagnosed, and treated. As a result, specific diagnoses can now be assigned in many cases that were previously defined as hypereosinophilic syndrome. Most notably, chromosomal rearrangements, such as FIP1L1-PDGFRA fusions caused by internal deletions in chromosome 4, are now known to be associated with many chronic eosinophilic leukemias. When present, these specific molecular abnormalities predict response to directed therapies. Although an improved molecular understanding is revolutionizing the treatment of patients with rare causes of eosinophilia, it has also complicated the approach to evaluating and treating eosinophilia. Here, we review causes of eosinophilia and present a framework by which the practicing pathologist may approach this diagnostic dilemma. Finally, we consider recent cases as clinical examples of eosinophilia from a single institution, demonstrating the diversity of etiologies that must be considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
A subgroup of patients with atopic dermatitis (AD) suffers from recurrent, disseminated herpes simplex virus skin infection, termed eczema herpeticum. To determine the transcriptional mechanisms of ...the skin and immune system pathobiology that underlie development of AD with eczema herpeticum (ADEH), we performed RNA-sequencing analysis of nonlesional skin (epidermis, dermis) from AD patients with and without a history of ADEH (ADEH+, n = 15; ADEH−, n = 13) along with healthy controls (n = 15). We also performed RNA sequencing on participants’ plasmacytoid dendritic cells infected in vitro with herpes simplex virus 1. ADEH+ patients exhibited dysregulated gene expression, limited in the dermis (14 differentially expressed genes) and more widespread in the epidermis (129 differentially expressed genes). ADEH+-upregulated epidermal differentially expressed genes were enriched in type 2 cytokine (IL4R, CCL22, CRLF2, IL7R), interferon (CXCL10, ICAM1, IFI44, IRF7), and IL-36γ (IL36G) inflammatory gene pathways. All ADEH+ participants exhibited type 2 cytokine and inteferon endotypes, and 87% were IL36G-high. In contrast, these endotypes were more variably expressed among ADEH− participants. ADEH+ skin also had dysregulated epidermal differentiation complex gene expression of the late-cornified envelope, S100A, and small proline-rich gene families, which are involved in skin barrier function and antimicrobial activities. Plasmacytoid dendritic cell transcriptional responses to herpes simplex virus 1 infection were unaltered by ADEH status. The study concluded that the pathobiology underlying ADEH+ risk is associated with a unique, multifaceted epidermal inflammation that accompanies dysregulation of epidermal differentiation complex genes. These findings will help direct future studies that define how these inflammatory patterns may drive risk of eczema herpeticum in AD.
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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.
The patient responded to his first chemotherapy dose, but on review in our weekly telepathology conference we felt the lymph node biopsy sample might have been reactive to infection, possibly to his ...HIV, and after extensive discussion we stopped chemotherapy. 2 months later he developed worsening hepatosplenomegaly, lymphadenopathy, fatigue, and oedema. A pathology review of lymph nodes from Uganda showed LANA positivity in two of 64 reactive nodes, suggesting multicentric Castleman's disease.3 A pathology review from South Africa reported many HIV-associated B-cell lymphoproliferations, although neither multicentric Castleman's disease nor LANA staining were described.4 Our case highlights the need to increase familiarity with multicentric Castleman's disease among clinicians and pathologists in KSHV-endemic regions, and to develop high-quality diagnostic pathology services throughout sub-Saharan Africa.5 Without such investments, the diversity of KSHV-associated diseases will remain underappreciated.
The care of patients with lymphoma relies heavily on accurate tissue diagnosis and classification. In sub-Saharan Africa, where lymphoma burden is increasing because of population growth, aging, and ...continued epidemic levels of human immunodeficiency virus infection, diagnostic pathology services are limited. This article summarizes lymphoma epidemiology, current diagnostic capacity, and obstacles and opportunities for improving practice in the region.
Air pollution particulate matter <2.5 μm (PM
) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM
-induced lung pathobiology are poorly understood but likely involve ...cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM
samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM
extracts. We found that PM
organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through
,
, and
. This OE exposure also robustly activated a mucus secretory expression program (>100 genes), which included transcriptional drivers of mucus metaplasia (
and
). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the
/
gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g.,
and
). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC
secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM
exposure.
Plasmablastic lymphoma in Malawi Zuze, Takondwa; Painschab, Matthew S; Seguin, Ryan ...
Infectious agents and cancer,
06/2018, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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.
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