Histopathology

Breast cancer is a heterogeneous disease that encompasses several distinct entities with remarkably different biological characteristics and clinical behaviour. Currently, breast cancer patients are managed according to algorithms based on a constellation of clinical and histopathological parameters in conjunction with assessment of hormone receptor (oestrogen and progesterone receptor) status and HER2 overexpression/gene amplification. Although effective tailored therapies have been developed for patients with hormone receptor‐positive or HER2+ disease, chemotherapy is the only modality of systemic therapy for patients with breast cancers lacking the expression of these markers (triple‐negative cancers). Recent microarray expression profiling analyses have demonstrated that breast cancers can be systematically characterized into biologically and clinically meaningful groups. These studies have led to the re‐discovery of basal‐like breast cancers, which preferentially show a triple‐negative phenotype. Both triple‐negative and basal‐like cancers preferentially affect young and African‐American women, are of high histological grade and have more aggressive clinical behaviour. Furthermore, a significant overlap between the biological and clinical characteristics of sporadic triple‐negative and basal‐like cancers and breast carcinomas arising in BRCA1 mutation carriers has been repeatedly demonstrated. In this review, we critically address the characteristics of basal‐like and triple‐negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer. In addition, the possible mechanisms are discussed leading to BRCA1 pathway dysfunction in sporadic triple‐negative and basal‐like cancers and animal models for these tumour types.

During repair of 12 atherosclerotic abdominal aortic aneurysms, fresh samples of aneurysm wall were obtained. Histology confirmed the presence of advanced atherosclerosis associated with medial thinning and a variable aortic adventitial chronic inflammatory cell infiltrate. Monoclonal antibodies were used to identify the inflammatory cells throughout the aortic wall. The majority of lymphocytes in the aortic adventitia were B‐cells. B‐cells were not present in atheromatous plaques. T‐cells, predominantly T‐helper cells, were found in atheromatous plaques and in aortic adventitia. The majority of lymphocytes and macrophages in aortic adventitia and most vascular endothelial cells were HLA‐DR positive. Ki‐67 staining was found in B‐cells and T‐helper cells, indicating that these cells were proliferating. Occasional lymphocytes were BerH2 positive, indicating that some lymphocytes were activated. These findings suggest that chronic periaortitis is an active, immunoiogically mediated, local complication of advanced human atherosclerosis.

Aims: Extra‐adrenal paragliomas are neoplasms which have been the subject of much debate regarding parameters to establish their biological behaviour. This study describes the clinicopathological and immunohistochemical features of 30 cases of spinal paragliomas. Methods and results: There were 15 male and 15 female patients. The median age at diagnosis was 46 years (range 20–74 years). Fourteen patients presented with back pain, two with numbness of the lower extremities, one with difficulty in walking and one with spinal cord compression. Nineteen tumours were located in the lumbar region, six in the cauda equina, two in the filum terminale, two in the thoracic region and one in the cervical region. All patients underwent gross total excision. The size of the tumours ranged from 10 to 50 mm. Histologically, 18 neoplasms showed alveolar (Zellballen) pattern, seven a spindle component, two eosinophilic granular cells suggestive of oncocytic metaplasia, two melanin pigment and one ganglion cells. Positive immunohistochemical results include: neuron‐specific enolase 23/23 (100%), synaptophysin 21/23 (91%), S100 protein 22/23 (95%, sustentacular cells), leu‐enkephalin 11/23 (47%), somatostatin 8/23 (34%), focal glial fibrillary acidic protein 7/23 (30%), focal keratin 5/23 (21%), neurofilament proteins 3/23 (13%) and adrenocorticotrophic hormine (ACTH) 1/23 (4%). Follow‐up information obtained in 20 patients show 17 patients alive over a period of 6–216 months. One patient had bone metastases. Two patients died of unrelated causes, including one of congestive heart failure and one of myocardial infarction. Conclusions: In our experience, spinal paragangliomas behave as slow‐growing tumours susceptible to potential cure by total excision. We agree with the current World Health Organization (WHO) classification as grade I tumours. Less than 1% may be locally aggressive. Spinal paragangliomas immunoreact not only for conventional neuroendocrine markers but also for peptides including somatostatin and ACTH and focally for the epithelial marker keratin.

An oncocytic neuroendocrine tumour (‘oncocytic paraganglioma’) of the cauda equina is reported. The tumour was predominantly intradural, with extension into and destruction of surrounding vertebral bone. The tumour had an organoid pattern, and the tumour cells had abundant non‐argyrophilic eosinophilic cytoplasm. Immunocytochemical stains for neurone‐specific enolase, S‐100 protein, keratin and carcinoembyronic antigen were positive, but stains for glial fibrillary acidic protein were negative. On ultrastructural examination, there were numerous mitochondria and scattered 200 nm dense‐core membrane‐bound granules, that rarely clustered in small aggregates. Intermediate filaments were focally arranged in long compact bundles. The histogenesis of tumours reported as cauda equina paragangliomas is discussed.

Recently, there has been intense interest in the study of gastrointestinal stromal tumour (GIST); one might call it a virtual GIST revolution. This is due largely to the realization that most GISTs express KIT and harbour activating c‐KIT (KIT) or platelet‐derived growth factor receptor‐alpha (PDGFRA) receptor tyrosine kinase mutations that can be targeted by small molecule pharmacological inhibitors. Pathologists have benefited greatly from this revolution, mainly in the form of an improved ability to classify GISTs and, even more recently, in understanding the molecular underpinnings that underlie many fascinating clinical and pathological correlations. It is the purpose of this review to summarize recent developments in GIST classification and the molecular pathogenesis of GIST.

We have reviewed the histological features and clinical outcome in 32 women with phyllodes tumours of the breast diagnosed in Nottingham between 1975 and 1990. We assessed 23 tumours as histologically benign, four as borderline and five as malignant. After clinical follow up for periods ranging from 36 months to 221 months (median 135 months), six of 23 benign tumours have recurred locally; in all these cases the original tumours had been incompletely excised. There were no recurrences amongst 10 benign tumours in which excision had been complete. Benign tumours which recurred showed a tendency to greater stromal cellularity and more pronounced stromal overgrowth than incompletely excised lesions which did not recur, but these differences were not statistically significant. The recurrent tumours resembled the respective original lesions histologically, except in one case in which two local recurrences were histologically malignant. The recurrent tumours were controlled by further excision or mastectomy in all cases and none have metastasized. All four borderline tumours were completely excised at initial surgery and none have recurred or metastasized. One of the five malignant tumours recurred within two months of incomplete excision, with widespread infiltration of the chest wall, although the patient died of unrelated causes. The other four malignant tumours have not recurred. We conclude that presence of tumour at the margins of the excised specimen is the major determinant of local recurrence in phyllodes tumours and that the histological features are of secondary importance. These findings are discussed in relation to other published series in the literature.