Johann W. Schneider

Polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma: a review and comparison of immunohistochemical markers

Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (ACC) have several overlapping histological patterns, including cribriform, tubular and solid patterns. The overlapping clinicopathological features of PLGA and ACC may result in a diagnostic pitfall. ACC has a much worse prognosis than PLGA, making differentiation important for therapeutic and prognostic purposes. Histopathological features remain the most reliable criteria to distinguish between these two tumours. Although PLGA and ACC have many features in common, PLGA is uncommon in the major salivary glands. Histopathological distinction is therefore mainly a problem in tumours of minor salivary gland origin where small biopsies often contribute to diagnostic difficulties. This paper reviews studies which have utilised several immunohistochemical markers in attempts to distinguish between PLGA and ACC, and also studies which have focussed on the two tumours individually. The potential discriminating value of immunohistochemistry between cases of PLGA and ACC still remains controversial.

The 2000 Burkitt lymphoma trial in Malawi.

We previously reported 57% 12‐month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity.

The immunoexpression of bcl‐2 and p53 in Kaposi’s sarcoma

The aim of this study was to examine the immunohistochemical expression of p53 and bcl‐2 in Kaposi’s sarcoma and relate this with proliferation index (as measured by MIB‐1 staining) and clinicopathological subtypes. Twenty formalin‐fixed, paraffin‐embedded cases of Kaposi’s sarcoma were stained with commercially available antibodies to p53, bcl‐2 and MIB‐1, after pressure cooking antigen retrieval. All cases were strongly positive for bcl‐2 with the majority containing more than 75% positive cells. In comparison, p53 expression was less striking. Eleven cases contained less than 24% (+1) of cells staining positively. Only two cases showed greater than 75% of positive cells, and both of these latter two lesions had metastasized. The MIB‐1 staining in all cases of Kaposi’s sarcoma was strongly positive, irrespective of clinicopathological type, in keeping with the highly proliferative nature of this lesion. Thus, we have demonstrated uniformly increased expression of bcl‐2 protein in Kaposi’s sarcoma irrespective of clinicopathological subtype and MIB‐1 staining, while p53 expression is relatively less common, except in those cases which have metastasized. This may help identify those cases that will behave in a more aggressive manner. However, more cases need to be evaluated to verify this.

Detection and subtyping of human herpesvirus-8 in renal transplant patients before and after remission of Kaposi's sarcoma

BACKGROUND Kaposis sarcoma (KS) is a complication of renal transplantation. If the human herpesvirus-8 (HHV-8) causes KS, the virus should be present in all KS lesions and be drastically reduced or cleared from involved tissue on remission of the KS. METHODS Fourteen renal transplant patients with cutaneous KS, including autopsy material from two cases, were investigated for the presence of HHV-8. A second skin biopsy was taken from 11 survivors, after remission of KS, from normal skin in the same anatomical region as the first biopsy. Remission was induced by reduction or cessation of immunosuppression. A peripheral blood sample was collected simultaneously with the repeat biopsy. A nested polymerase chain reaction assay was used to detect HHV-8 DNA in the biopsy tissue and peripheral blood mononuclear cells followed by direct sequencing of polymerase chain reaction product to detect any nucleotide changes. RESULTS HHV-8 DNA was detected in all the cutaneous KS and all the visceral KS samples, as well as a number of KS-free organs including the thyroid, salivary gland, and myocardium that have not been described before. Mutations in the viral DNA could be demonstrated in all patients. The mutations found were related more to that seen in AIDS-KS cases than that found in African endemic KS cases. HHV-8 sequences could be detected in follow-up frozen skin biopsies of five patients but were negative in the equivalent formalin-fixed specimens. Viral DNA was also detected in 2 of 11 peripheral blood mononuclear cell samples collected at the time of the follow-up skin biopsies. CONCLUSION Reduction or withdrawal of immunosuppression allows the immune system to recover sufficiently to reduce viral replication with subsequent viral persistence and low grade viral replication that coincides with clinical remission of the KS lesions. This provides further evidence for the important etiological role played by HHV-8 in the pathogenesis of posttransplant KS.

Dynamic active telepathology over National Health Laboratory service network, South Africa: feasibility study using Nikon Coolscope.

Telepathology recently entered a new era with the introduction of digital microscopes combined with Internet technology. The microscope allows viewing real time of whole slide (macro) as well as different chosen fields in four different magnifications. Three Nikon Coolscope were installed in NHLS laboratories in Mthatha, East London and Port Elizabeth. All these microscopes are connected to NHLS server allowing real time viewing of the full slide at any time of the day using Internet browser. Viewing is possible from any PC connected to NHLS Intranet. The challenge was to be able to view slides from other than NHLS computers due to NHLS IT Department network security measures. This was solved by installing NHLS Virtual Private Network server. About 60 cases were viewed by pathologists in Cape Town (Stellenbosh University) and Pretoria (MEDUNSA). All users assessed the system as a helpful tool allowing easy access to cases needing consultation or second opinion. The quality of images was very good. Our experience with Nikon Coolscope is positive. It is an excellent tool for remote small histopathology departments lacking specialists in such areas as dermatopathology, oncology, and haematopathology. Further studies are needed especially in the scope of full utilization of the microscopes installed and impact on laboratory services.

TAL-1 protein expression in vascular lesions.

The distribution of TAL‐1 protein, an important vascular promoter in mice, has been examined immunohistochemically in a range of human vascular lesions and normal tissues. Formalin‐fixed, paraffin‐embedded vascular lesions including granulation tissue, haemangiomas, Kaposis sarcomas, spindle cell haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal antibody to recombinant TAL‐1. Endothelial cells in all lesions gave positive immunostaining of variable intensity. Granulation tissue and spindle cell areas of the vascular tumours gave the strongest staining (nuclear and cytoplasmic). The better‐differentiated endothelial cells within the tumours and resident well‐formed vessels were less positive and some cells were in fact negative. The malignant endothelial cells in angiosarcomas showed less intense positive staining than KS cells. This study has shown TAL‐1 protein expression in a range of reactive, benign, and malignant vascular lesions. Protein expression appears to be stronger in the spindle cell areas, perhaps reflecting greater expression in less‐differentiated endothelial cells.

The role of histopathology in establishing the diagnosis of tuberculous pericardial effusions in the presence of HIV

Aims : To establish the influence of human immunodeficiency virus (HIV) infection on the histopathological features of patients presenting with tuberculous pericarditis.

Detection of human herpes virus 8 DNA and sequence polymorphism in classical, epidemic, and iatrogenic Kaposi's sarcoma in South Africa

The aetiology and detection of human herpes virus type 8 (HHV‐8) DNA sequences in Kaposis sarcoma (KS) is a matter of intense investigation. We report on the detection of HHV‐8 DNA and sequence polymorphism in different clinicopathological subtypes of cutaneous KS samples from South Africa. The diagnosis was confirmed by histological examination in all cases. Six patients had classic KS (CKS), 3 epidemic KS (EKS), and 3 iatrogenic KS (IKS). A nested polymerase chain reaction (PCR) assay was used to detect HHV‐8 DNA in cell lysates, prepared from formalin fixed, paraffin embedded sections. We investigated polymorphism in the HHV‐8 DNA using single‐stranded conformational polymorphism (SSCP) analysis on the PCR products, followed by direct sequencing. HHV‐8 DNA was detected in all the patients with KS, irrespective of the clinicopathological subtype. Direct sequencing was performed on 5 selected cases and showed single base pair substitutions in all. The spectrum of mutations was similar to those described previously. No correlation was found between the different types of KS and sequence variation. The results support the hypothesis that HHV‐8 is strongly associated with different clinicopathological subtypes of KS and confirm the occurrence of HHV‐8 in patients with CKS, EKS, and IKS in South Africa. J. Med. Virol. 52:168–172, 1997.

The spectrum of rare morphological variants of cutaneous epithelioid angiosarcoma.

Unusual cytoplasmic alterations have recently been reported in poorly differentiated cutaneous angiosarcoma, making an accurate diagnosis challenging. As these tumours remain poorly documented, we aimed to study their clinicopathological characteristics more comprehensively.

Axillary lymph node involvement in stage III breast cancer: treatment implications.

The introduction of multimodal therapy has improved the prognosis in stage III breast cancer. A knowledge of the likely axillary lymph node status at presentation is important, both to plan surgical therapy to the axilla and to establish the effect of induction therapy on the axillary nodes.