Jon van der Walt

Kaposi's-sarcoma-associated herpesvirus in HIV-negative Kaposi's sarcoma

events involving, to various degrees, microorganisms such as herpesviruses, hepatitis B virus, HIV, and Mycoplasma penetrans.H Chang and colleagues5 have identified herpesvirus-like DNA sequence in biopsy samples from patients with AIDS-associated KS. This DNA sequence was found exclusively in KS biopsy specimens but not in several other tested tissues. We report our results of screening DNA samples from isolated peripheral blood mononuclear cells (PBMCs). DNA was directly purified from uncultured PBMCs that

Guideline for investigation and management of adults and children presenting with a thrombocytosis.

Guy’s and St Thomas’ NHS Foundation Trust, London, Russells Hall Hospital, Dudley, West Midlands, Arrowe Park Hospital Arrowe Park Road Upton Wirral, Wellcome Trust Sanger Institute, Hinxton, Cambridge, St. James Hospital, James Street, Dublin, Gartnavel General Hospital 21 Shelley Road Glasgow, Addenbrooke’s Hospital, Cambridge, Salisbury Healthcare NHS Trust, Salisbury, Wiltshire, Cambridge Institute for Medical Research, Hills Road, Cambridge, John Radcliffe Hospital, Headley Way, Headington, Oxford, Royal Infirmary, Little France Crescent, Edinburgh, Sandwell and West Birmingham Hospitals, Dudley Road, Birmingham, Royal Hallamshire Hospital, Glossop Road, Sheffield, and Belfast City Hospital, Lisburn Road Belfast, UK

An immunohistochemical analysis of human aortic fatty streaks.

Recent studies have shown both macrophages and lymphocytes in very early intimal lesions of experimental aortic atherosclerosis. The authors obtained fresh samples of human aortic wall, which had been removed in the course of aortocoronary bypass graft surgery. Intimal fatty streaks were identified macroscopically and six were studied immunohistochemically. The fatty streaks contained foam cells that were virtually all labeled by antibodies directed against members of the mononuclear phagocyte series (RFD-2 and RFD-7). Macrophages demonstrated acid phosphatase activity and marked expression of HLA-DR, suggesting activation. Other monoclonal antibodies (UCHT-1, OKT-4, and RFT-8) identified T lymphocytes, of both helper and suppressor phenotypes, within the fatty streaks. T lymphocytes of suppressor phenotype appeared to predominate over helper cells. B lymphocytes were not detected. The presence of activated macrophages and T lymphocytes in the fatty streaks indicates that components of a cell-mediated immune response are present. Such an immune process may be important in the pathogenesis of human atherosclerosis.

European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis.

Background The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. Design and Methods To assess the reproducibility of the classification, six hematopathologists from five European countries re-classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. Results Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. Conclusions World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone.

Gastrointestinal malignancies in HIV-infected or immunosuppressed patients: pathologic features and review of the literature.

The gastrointestinal (GI) tract is a common internal organ to be involved by human immunodeficiency virus (HIV)-related malignancies. It is the second most common site for Kaposi sarcoma after skin, and the commonest visceral site, for Kaposi sarcoma in AIDS patients. GI lymphomas have been documented in approximately 25% of AIDS patients with systemic lymphomas. Moreover, GI involvement of AIDS-lymphoma has been associated with poor prognosis and short survival. Several other malignancies that occur in the GI tract are also closely related to HIV-infected or immunosuppressed individuals; these include posttransplant lymphoproliferative disorder, Epstein-Barr virus-associated smooth muscle tumors, anal precancerous lesions, and squamous cell carcinoma. As a result of active antiretroviral therapy, patients infected with HIV are living longer and are consequently at increased risk for development of cancer. Therefore, it is possible that the number of AIDS-associated malignancies will rise and the pattern of tumors may change in the future. In this paper, the clinicopathologic features of GI malignancies associated with AIDS patients are reviewed and the differential diagnosis with other mimic lesions is discussed.

Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene

Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)(-) FL displayed a mutational profile similar to t(14;18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)(-) FL in adults indicate that these are two different disorders.

Running an unknown risk: a marathon death associated with the use of 1,3-dimethylamylamine (DMAA).

Keywords: 1,3 dimethylamylamine (DMAA); sports supplement; Marathon; fatality; 4-methylhexane-2-amine; recreational drug

Identifying HIV infection in diagnostic histopathology tissue samples – the role of HIV‐1 p24 immunohistochemistry in identifying clinically unsuspected HIV infection: a 3‐year analysis

Moonim M T, Alarcon L, Freeman J, Mahadeva U, van der Walt J D & Lucas S B
(2010) Histopathology56, 530–541

Renal Failure with Granulomatous Interstitial Nephritis and Diffuse Leukemic Renal Infiltration in Chronic Lymphocytic Leukemia

Renal dysfunction is uncommon in patients with leukemic infiltration of the kidney due to Chronic Lymphocytic Leukanemia (CLL). Granulomatous interstitial nephritis (GIN) is also rare, but a characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. GIN has been associated with medications, infections, inflammation, Wegeners granulomatosis, and jejuno-ileal bypass. GIN combined with leukemic infiltration by CLL is very uncommon. We present a 72-year-old male with Binet stage A CLL who developed progressive renal failure over a period of four years requiring maintenance dialysis. During the course of his illness, he underwent renal biopsies at different time intervals, revealing varying degrees of involvement by GIN together with leukemic infiltration.

Plasmacytoid dendritic cell proliferations and neoplasms involving the bone marrow : Summary of the workshop cases submitted to the 18th Meeting of the European Association for Haematopathology (EAHP) organized by the European Bone Marrow Working Group, Basel 2016

Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1–5% and 35 PDC/HPF). A shared PTPN11 mutation between a mature PDC proliferation and an accompanying MDS provides evidence of clonal relationship in such instances and shows that PDC are a part of the malignant clone. CD123 and CD303 should be considered backbone markers to histopathologically establish the diagnosis of BPDCN, since they are detectable in almost all cases and properly well on biopsies subjected to different fixations. Expression of some T-cell markers (e.g., CD2 and CD7 but not CD3), B-cell markers (e.g., CD79a but not CD19 and CD20), and myeloid markers (e.g., CD33 and CD117 but not myeloperoxidase) can be observed in BPDCN. Genetical data of the summarized cases corroborate the important role of chromosomal losses in BPDCN. Together with five previously reported instances, one additional workshop case with MYC rearrangement proposes that translocations of MYC may be recurrent. The frequent nature of deleterious mutations of IKZF3 and deletions of IKZF1 suggests a role for the Ikaros family proteins in BPDCN.