Runjan Chetty

Cyclin E in human cancers

Regulators of the cell cycle such as cyclin E play an important part in neoplasia. The cyclin E protein forms a partnership with a specific protein kinase. This complex phosphorylates key substrates to initiate DNA synthesis. Cyclin‐dependent kinase inhibitors (CKIs) are able to suppress the activity of cyclin E. Various substances (including proteins produced by oncogenic viruses) affect cyclin E directly or indirectly through an interaction with CKIs. These interactions are important in elucidating the mechanisms of neoplasia. They may also provide prognostic information in a wide range of common cancers. Cyclin E may even be a target for treatment of cancers in the future.—Donnellan, R., Chetty, R. Cyclin E in human cancers. FASEB J. 13, 773–780 (1999)

Large artery vasculopathy in HIV-positive patients: Another vasculitic enigma

Human immunodeficiency virus (HIV) infection has impacted on all the systems of the body, and the cardiovascular system is no exception, with small to medium-sized vessel vasculitis being most frequently described. We present 16 HIV-positive patients with large vessel disease consisting of either aneurysms (often multiple) or occlusive disease. Nine men and 7 women ranging in age from 18 to 38 years presented with rupture of aneurysm, transient ischemic attacks, hypertension, ischemia to the lower extremity, or a mass at the site of the aneurysm. Eight patients had 1 aneurysm, 2 had 2 lesions, and the remaining 6 cases had from 3 to 7 aneurysms. Arteries affected included the common carotid, abdominal aorta, common iliac, femoral, and popliteal. Three patients had intercurrent infections, but none had any obvious infective vascular lesion. Only 1 patient had a positive TPHA test for syphilis. Microbiologic culture of both blood and thrombus contents was positive for Staphylococcus aureus in 1 case; no other organisms were cultured. The key histological features were within the adventitia: leukocytoclastic vasculitis of the vasa vasora and periadventitial vessels, proliferation of slit-like vascular channels, chronic inflammation, and fibrosis. There was associated medial fibrosis with loss and fragmentation of muscle and elastic tissue. Intimal changes consisted of duplication and fragmentation of the internal elastic lamina with calcification. Atheroma and marked intimal thickening were not evident We believe that the occurrence of this large vessel vasculopathy (mainly aneurysmal) often with multiple lesions in young HIV-positive patients, is characteristic of possible infective or immune complex origin, with leukocytoclastic vasculitis of vasa vasora and periadventitial vessels being pivotal in many cases.

Plasmablastic lymphoma in HIV+ patients: an expanding spectrum

Aim:u2002 To describe an unusual human immunodeficiency virus (HIV)‐associated lymphoma in uncommon sites. Plasmablastic lymphoma is a distinctive HIV‐associated tumour that was first described in the jaws and oral cavity. Only two cases (stomach and lung) have been documented in extra‐oral sites.

Arterial aneurysms in patients infected with human immunodeficiency virus: A distinct clinicopathology entity?

Arterial aneurysms have only recently been associated with the human immunodeficiency virus (HIV). The clinical and pathological features of 10 HIV-positive patients with arterial aneurysms were retrospectively evaluated. These aneurysms were unusual in that they affected young black patients, occurred in atypical sites, and tended toward multiplicity. Surgery was performed in eight patients. Acute and chronic inflammatory changes were revealed by means of histologic examination of the aneurysm walls, with occlusion of the vasa vasora by inflammatory infiltrate or edema being a prominent feature. Culture of the aneurysm wall or thrombus yielded positive results in two patients. The association between HIV and aneurysms may be coincidental, caused by direct viral action or by bacterial infection resulting from immunosuppression. Implications for therapy are discussed, and the need for further study is highlighted.

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.

Large cell neuroendocrine carcinoma of the thymus

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.

Intercalated duct hyperplasia: possible relationship to epithelial-myoepithelial carcinoma and hybrid tumours of salivary gland

Aims

Lung carcinomas composed of rhabdoid cells

Rhabdoid tumours form a distinctive morphological entity that is associated with aggressive biological behaviour. They have been described in several sites and tumour types. This paper presents three new cases of rhabdoid lung cancers. Lung cancers were analysed for the presence of cells with the rhabdoid phenotype: eccentric vesicular nuclei and abundant eosinophilic cytoplasm. Cells displaying this morphology were then subjected to immunohistochemistry and electron microscopy. The relevant clinical data on these cases were then accessed. Three cases conforming to the morphological, immunophenotypic and ultrastructural characteristics of rhabdoid cells were identified. Two of the cases were associated with foci of adenocarcinoma and the remaining case was a large cell neuroendocrine carcinoma. Two of the cases showed rapid clinical courses with the patients dying of disease within 6 months. Lung tumours with a rhabdoid phenotype are uncommon but are noteworthy because of their aggressive behaviour and, hence, poor prognosis.

Inflammatory pseudotumor of the breast

Summary Inflammatory pseudotumors (IP) have come to the forefront in recent times with this characteristic lesion being described in several sites.1–5 The multiplicity of sites of occurrence is matched by the plethora of names given to this condition. It has been rejoiced under the rubric of plasma cell granuloma, xanthomatous pseudotumor, xanthogranuloma, inflammatory myofibroblastic tumor/lesion and inflammatory fibromyxoid tumor, to name but some. This paper presents three cases of IP occurring in the breast and highlights the histological features in this unusual site.Abbreviations: IP, inflammatory pseudotumors.

Spindle epithelial tumour with thymus‐like element (SETTLE): the predominantly monophasic variant

To describe two cases of spindle epithelial tumour with thymus‐like element (SETTLE) which are composed predominantly of spindle cells. In addition, to highlight some unusual histological features in SETTLE and discuss its separation from histological mimics.