Current diagnostic pathology最新文献

Greater awareness and use of screening has led to an increase in the proportion of ‘early’ breast cancers. Conventional prognostic factors such as tumour size and nodal status are of limited use with these tumours, because most of them are node negative and small. There is a need for factors that are not only prognostic, but also predict response to therapy, in the selection of appropriate therapy for these low-risk patients, especially to avoid the administration of toxic therapies to patients who are unlikely to gain significant benefit. This has led to the emergence of newer molecular prognostic factors, gene-expression signatures being the latest. Although not many of these newer prognostic factors have proved clinical utility, recent studies report remarkable results with the use of gene-expression signatures as prognostic and predictive factors. These results, though promising, have been compared only with simple parameters such as tumour grade and with broad practice guidelines. Additional studies documenting superiority of gene signatures over existing prognostic algorithms such as the Nottingham prognostic index and Adjuvant! Online are necessary before their widespread routine use. Currently, gene signatures are best used as a part of randomized clinical trials such as MINDACT and TAILORx. In this review, we discuss the biological basis, scientific evidence and clinical application of conventional and molecular prognostic factors, including gene-expression signatures.

Most histopathology laboratories routinely handle diagnostic and excisional breast surgical specimens, and the range of specimens received is limited. However, the apparent simplicity of breast specimens is often deceptive, and the importance of thorough macroscopic assessment is often underestimated. Surgical techniques vary between institutions, and an understanding of the local surgical protocol is essential for optimal specimen handling. Adequate and appropriate sampling is essential for optimal reporting of the minimum data set information, particularly an accurate assessment of the size of the lesion and the excision margin status. This article offers some guidelines for the handling of benign and malignant surgical breast specimens, including more complex specimens such as excisions following neo-adjuvant therapy.

The last 15 years or so have seen many changes in the practice of breast pathology relating to changes in methods of detection of breast disease and the increased use of markers for selecting specific forms of therapy. There have also been developments in immunohistochemistry and a much wider range of antibodies are suitable for use with formalin-fixed paraffin-embedded tissue. Immunohistochemistry can now be used to aid diagnosis in several areas such as benign vs malignant lesions, non-invasive vs invasive, and lobular neoplasia vs ductal carcinoma in situ. This review discusses the background to the different myoepithelial and luminal epithelial markers, with a discussion of their advantages and disadvantages diagnostically. The need to combine interpretation with histological findings is emphasized, along with the need for use of more than one marker. Methods of assessment of oestrogen receptors, progesterone receptors and HER-2 are described, with the problems that can occur. Regular audits are recommended to ensure reproducibility over time and uniformity.

Sentinel lymph node biopsy is rapidly becoming the standard of care in staging the axilla for early-stage, clinically node-negative breast carcinoma. This paper discusses the rationale and methods of sentinel lymph node biopsy and critically analyses the data concerning its accuracy and usefulness. The impact of axillary surgery as a staging technique and as a therapeutic intervention on breast cancer prognosis is discussed. The pathological methods for handling and assessing sentinel lymph nodes are described and evaluated. Broad guidelines on how to dissect, process, stain, assess and report sentinel lymph nodes are provided.

The family of small round-cell tumours (SRCTs) represents a heterogeneous group of malignancies featuring a primitive, undifferentiated round-cell morphology. SRCTs mostly occur in children, adolescents and young adults, and tend to involve the skeletal system or soft tissue. They constitute approximately 20% of solid tumours in children and, because of their significant morphological overlap, have become a paradigm for an integrated approach to diagnosis. The combination of both immunophenotypic and genetic analysis with classic morphology has proved useful not only on diagnostic grounds, but also in the context of prognostication. This review will focus on SRCTs primarily involving soft tissues and includes the Ewing's family of tumours, also known as Ewing's sarcoma/primitive neuroectodermal tumour, alveolar rhabdomyosarcoma, desmoplastic SRCT, poorly differentiated round-cell synovial sarcoma and mesenchymal chondrosarcoma.

Predictive and prognostic testing for breast cancer is now an important part of cellular pathology. The UK National External Quality Assessment Scheme (NEQAS) for immunocytochemistry and fluorescent in situ hybridization plays a significant role in ensuring that the quality of testing meets the clinical standards required, by assessing the performance of each participant laboratory every 3 months. Besides receiving a confidential performance report, data on the methods used are collected, analysed against the scores and published in the UK NEQAS journal. This information is intended to help those who are not achieving the best scores to improve their performance.

Renal transplant pathology occupies an ever-changing spectrum, due to new techniques and drugs. Acute and chronic antibody-mediated rejection is diagnosed by a combination of light, immunofluorescence (C4d) and electron microscopic features, and these newly recognized diseases are now in the Banff schema. C4d deposition, with normal graft histology, is a sign of accommodation, most common in ABO-incompatible grafts. Chronic allograft nephropathy has been removed from the Banff system in an attempt to promote more specific diagnosis and treatment of the causes of late graft injury. A new aspect of polyomavirus is the formation of immune complexes along tubular basement membranes. Rapamycin causes lesions resembling myeloma cast nephropathy and exacerbates proteinuria, probably due to tubular and/or glomerular toxicity. Protocol biopsies, now part of routine care in many centers, detect the early stages of pathological processes, such as subclinical rejection, polyomavirus infection or transplant glomerulopathy, when they are potentially treatable.

Liver transplantation has been increasingly used over the past four decades as an effective treatment for end-stage liver disease. Although the demand exceeds the supply of cadaveric organs, the donor pool has expanded with the increasing use of split-liver grafts, non-heart-beating donor livers and living-related donors. Histopathologists play a role in the pre-transplant and post-transplant period; their input is crucial in both identifying and monitoring post-transplant complications. The degree of acute cellular rejection is best assessed histologically, and biopsy interpretation informs changes to the immunosuppressive regimen. Chronic rejection is characterised by progressive ductopenia; a number of lesions have been identified that predict the likelihood of progression to chronic rejection. Other post-transplant complications readily assessed on liver core biopsies include vascular and biliary complications, infectious, recurrent and de novo disease. De novo hepatitis with ‘autoimmune’ features is described as is idiopathic chronic hepatitis, but the relationship of these lesions to alloimmune pathways remains uncertain. Although liver transplantation is generally performed in specialist centres, an increasing number of histopathologists working in non-specialist units are being exposed to post-transplant biopsies and need to be aware of the spectrum of changes that can occur.

Cholangiocarcinoma, which is endemic in certain geographic regions, shows a strong association with liver fluke infection and hepatolithiasis, with recurrent inflammation and the high consumption of nitrates, nitrites, dimethylnitrosamines and N-nitropyrolidines as probable mutagenic cofactors. K-ras, p53 and bcl-2 have been implicated in cholangiocarcinogenesis and several immunohistological markers have been studied, although none is a reliable predictor of outcome. Three macroscopic types of cholangiocarcinoma have been characterized and implicated to be of prognostic relevance, but their behaviour might be a function of their anatomical location rather than a biological characteristic. Periductal-infiltrating tumours present at an advanced stage with infiltration of the portal pedicle. They arise closer to the hepatic hilum than mass-forming tumours, which tend to be peripherally located and show portal invasion and intrahepatic recurrence. The intraductal tumour shows the best prognosis, and long-term survival has been reported. Poor prognostic factors include large tumour size, multifocality, lymphovascular, perineural and serosal invasion, lymph node metastases and involvement of resection margins. Survival following surgical resection, the mainstay of treatment, is generally very poor.