Current diagnostic pathology最新文献

Gastrointestinal stromal tumours (GISTs) comprise the largest subset of mesenchymal tumours of the digestive tract. These tumours have been the subject of considerable debate in the literature regarding their histogenesis, criteria for diagnosis, prognostic features and biological behaviour.

The majority of GISTs express CD117 immunostaining and show various degrees of differentiation towards the phenotype of interstitial cell of Cajal.

Clinically and histologically, GISTs represent a spectrum that includes benign and malignant variants. The prediction of clinical behaviour is best achieved by evaluation of multiple parameters including clinical, morphological and cytogenetic features.

The recognition of the central role played by activating mutations of c-kit and platelet derived growth factor receptor alpha in the pathogenesis of GISTs and the introduction of STI-571, a receptor tyrosine kinase inhibitor that has proved extremely effective in the treatment of GISTs, have not only have focused attention on these tumours but also made it necessary to accurately define these tumours and separate them from other mesenchymal lesions. This review discusses the definition, histogenesis, epidemiology, clinical presentation, morphological and immunohistochemical features and the differential diagnosis of GISTs and addresses predictors of malignancy and management of GISTs.

In addition to the broad spectrum of epithelial, neuroectodermal and lymphoreticular neoplasms arising in the skin, a wide variety of mesenchymal tumours are characterised by a primary cutaneous presentation.

Benign and malignant mesenchymal tumours represent a heterogeneous and complex group of lesions that are currently classified on a histogenetic basis according to the mature tissues they might resemble. While histomorphological assessment remains the cornerstone of tumour classification, the continuing technical developments in the fields of immunohistochemistry and (cyto)genetics have become increasingly useful in aiding accurate histopathological classification of problematic cases.

It is our aim in this short review to discuss the spectrum of mesenchymal lesions commonly presenting in the skin with special emphasis on the diagnostic dilemmas that a subset of these tumours may present in daily practice.

High-grade central osteosarcoma (OS) is the most common histological variant of OS. Diagnosis requires histological and radiographical examinations. OS is characterized by the presence of osteoid–extracellular matrix. Tumours are treated with neo-adjuvant chemotherapy and limb salvage surgery. Targeted drugs are not yet available for these sarcomas. OS has a remarkably high level of chromosomal alterations. Genetic mutations have been identified for TP53, RB1, CDKN2A, CDK4, MDM2 and CHK2 and may, in some cases, be inherited through the germline. Telomere maintenance is obtained through two different mechanisms, the expression of telomerase enzyme (TERT) or by alternative lengthening of telomeres (ALT). Several genome-wide expression profiling studies are aiming to identify new prognostic markers and targets for therapy.

Fibroepithelial lesions of the breast are biphasic lesions with epithelial and stromal components, as exemplified by fibroadenoma and phyllodes tumour. Fibroadenomas are benign, but a subset of complex fibroadenoma is associated with slightly increased long-term cancer risk. Phyllodes tumour is characterised by a leaf-like pattern arising from stromal expansion. It shows a variable degree of malignancy, with a potential for recurrence or metastasis. Conventionally, histological parameters of stromal cellularity, nuclear pleomorphism, overgrowth, mitotic activity and margin configuration are used for grading, but no definitive criteria have been identified to predict the behaviour. Other markers that have been investigated so far include p53, hormonal receptors, proliferation markers, angiogenesis, c-kit (CD117) and CD10 (CALLA), all without clear-cut advantage over histological criteria. There is also emerging histological and molecular evidence that fibroadenoma and phyllodes tumour may be related and epithelial–stromal interaction may play a role in the pathogenesis of these fibroepithelial lesions.

One critical role played by the pathologist in contemporary breast cancer management is that of providing accurate tumour measurements for staging and prognosis. Numerous factors have the potential to affect the final pathologist-recorded tumour size including diligence in measurement, tumour histology and growth pattern, tissue fixation and processing, prior biopsy and prior therapy. The pathologist should strive to provide three-dimensional tumour measurements in 0.1 cm increments from the gross specimen and then confirm these measurements microscopically whenever possible. In the era of breast conservation and emerging ablative therapies, the pathologist should also be familiar with the size-determining capability of various breast imaging techniques and their correlation with pathology. In determining final dimension, the pathologist is in a favourable position to verify or modify the size of a breast tumour based on the sum of information from all pathology specimens and, if appropriate, to correlate size with the patient's imaging studies.

Conventional anti-cancer drugs usually act against dividing cells and work on the premise that cancer cells divide more quickly than normal cells in the body, so that repeated doses will put the cancer cells at a selective disadvantage. In many tumours, however, it is not the rate of proliferation that causes tumour growth but the lack of tumour cell death by apoptosis, so these drugs will not be effective against such tumours. These agents also cause many side-effects because of their effect on normal rapidly dividing cells in the body, such as the bone marrow and the epithelial lining of the gut, and it is these side-effects which often limit the dose. There are now a whole range of new anti-cancer agents that target cancer cells more specifically because they are directed against unique protein targets in these cells. These targets often include specific growth factor receptors that are overexpressed in particular types of cancer. These new agents are often monoclonal antibodies directed against these proteins or small molecule inhibitors of their enzymatic intracytoplasmic domains. Examples include cetuximab, trastuzumab, bevacizumab, imatinib mesylate and gefitinib. This article reviews the molecular pathology of these agents and describes the role of histopathology testing in selecting these therapies for individual patients.

The review article gives a personal account of being a trainee at one of the new senior house officer histopathology training schools in the UK, discussing the strengths and weaknesses of such training. The review compares traditional ad hoc ‘apprenticeship’ training with the new senior house officer school model of teaching a cohort of new trainees academically and practically in a ‘systems-based’ way. The academic content of the course is discussed. The structure of registrar training is described, highlighting new changes occurring in 2005 when a new continuous training schedule from senior house officer to consultant was initiated. The article discusses some issues arising from this, such as research opportunities and an accelerated schedule of examination attainment. The strengths of histopathology training in the UK are outlined, and generic aspects of this may be translatable to training in other environments.

In this second of two articles, we explore the range of common smaller specimens that present to the ophthalmic histopathology laboratory. Some of these specimens are quite small and difficult to handle, with a proven rate of loss during processing. This article contains techniques to overcome such difficulties. The full spectrum of biopsy material is covered, from full-thickness eyelid pentagonal resections, through to aspirations of intraocular tumours and handling tiny epiretinal membranes.

Dramatic curricular reforms in undergraduate medical education mean that many pathologists now find themselves involved in courses that are significantly different from those which they encountered as medical students. Department-led didactic courses in pathology have been replaced by centrally managed, problem-based integrated curricula in which pathology may at first be difficult to identify. This article discusses how curriculum reform has changed the ways in which medical students encounter pathologists and pathology, and the way in which pathology teaching is managed. The various teaching modalities that can be used to convey a knowledge of pathology are considered, with special reference to the autopsy. Finally, consideration is given to the necessity for those involved in undergraduate medical education to be proficient both in their own discipline and in teaching. Pathologists have a continuing role at all levels of the curriculum, from design and management through to delivery.