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Metastasis is the major cause of death in patients with cancer and thus attempts have been made for more than a century to experimentally dissect its component parts. Multiple arbitrary divisions have been offered that often begin with immortalized and transformed cells demonstrating altered cell proliferation, cell cycle and apoptotic pathways initiating their journey of dissemination by detaching from the primary tumor mass, initiating angiogenesis, degrading and penetrating the basement membranes and the surrounding connective tissue boundaries, intravasating, circulating and extravasating through the blood or lymphatic circulation and after evading the immune system eventually reaching one or more distant metastatic sites where they must undergo a similar process in reverse order. Tumor cell invasion is one of the key steps in this complex process. As the metastatic potential of tumor cells is largely dependent on their ability to degrade and migrate through extracellular matrix (ECM) barriers, inhibition of its subroutines (proteolysis, ECM degradation, chemotaxis, haptotaxis etc.) become logical targets for experimental cancer therapy. To explore potential approaches to inhibit tumor invasion, various in vitro invasion assays have been devised and become widely-accepted surrogate endpoints to mimic the in vivo condition. Most invasion assay systems are based on measuring the ability of cells to invade across purified ECM components such as collagen or complex artificial or reconstituted ECMs. Each has certain strengths, quantitative abilities, ease of manipulation of treatments etc. and like the tumor cells themselves, each is counterbalanced by inherent weaknesses. These are reviewed in this chapter. [ABSTRACT FROM AUTHOR]

Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of pancreatic malignancy and other biological phenomena. This chapter reviews current methods for obtaining anatomically specific signals from molecules isolated from tissues, a basic requirement for productive linking of phenotype and genotype. The quality of samples isolated from tissue and used for molecular analysis is often glossed-over or omitted from publications, making interpretation and replication of data difficult or impossible. Fortunately, recently developed techniques allow life scientists to better document and control the quality of samples used for a given assay, creating a foundation for improvement in this area. Tissue processing for molecular studies usually involves some or all of the following steps: tissue collection, gross dissection/identification, fixation, processing/embedding, storage/archiving, sectioning, staining, microdissection/annotation, and pure analyte labeling/identification. High-quality tissue microdissection does not necessarily mean high-quality samples to analyze. The quality of biomaterials obtained for analysis is highly dependent on steps upstream and downstream from tissue microdissection. We provide protocols for each of these steps, and encourage you to improve upon these. It is worth the effort of every laboratory to optimize and document its technique at each stage of the process, and we provide a starting point for those willing to spend the time to optimize. In our view, poor documentation of tissue and cell type of origin and the use of nonoptimized protocols is a source of inefficiency in current life science research. Even incremental improvement in this area will increase productivity significantly. [ABSTRACT FROM AUTHOR]

The objectives of this review are: (1)review WHO/ISUP Consensus Classification with comments on particular lesions to follow; (2)review of flat lesions of the urinary bladder; (3)review of invasive neoplasms with an emphasis on the potential diagnostic pitfalls and problems. [ABSTRACT FROM AUTHOR]

Digital imaging systems are rapidly becoming a valued asset in the field of pathology education and practice as more emphasis is being placed upon digital technology and improved efficiency in medicine. Pathology is an image-intensive discipline which relies upon the diagnostic clarity and accuracy of pathological specimens, and technological advances in image acquisition and delivery have spurred the emergence of pathology as an increasingly "digital" discipline. Well-implemented digital imaging systems can maximize efficiency, reduce costs, and allow for the rapid repurposing of resources in addition to facilitating collaborations among educators and practitioners. Pathology collections that previously were underutilized or lie dormant in storage may now be resurrected from the notorious "image graveyard" through digitization efforts. However, acquisition of digital images can easily lead to the development of "digital image graveyards" if appropriate measure are not taken to ensure that these images are easily retrievable and accessible for use in teaching or in practice. As such, an understanding of image acquisition in addition to editing, processing, storage, management, and delivery of digital images is crucial in revitalizing pathology collections and reaping the benefits that digital imagery provides in terms of efficiency, collaboration, and repurposing. [ABSTRACT FROM AUTHOR]

Despite predictions in the mid-twentieth century that bacterial and viral diseases would be wiped out by the year 2000, microbial infections in the early years of twenty-first century have remained major causes of morbidity and mortality. The emergence and spread of antimicrobial-resistant bacteria in the hospital environment, and more recently in community settings, augmented by frequent reports in the lay press, has heightened the awareness of primary care physicians as well as specialists in the importance of surveillance for antimicrobial-resistant bacteria, and that the administration of antimicrobial chemotherapy should be guided by in vitro susceptibility data whenever possible. The increased attention focused on microbiology data by clinicians has a secondary effect in that it mandates involvement of the clinical pathologist as a leader in how laboratory information is obtained and communicated to physicians in the most accurate, timely, and effective manner. Keeping abreast of the epidemiologic trends in antimicrobial resistance locally and nationally, maintaining awareness of current guidelines and recommendations for susceptibility testing, communication of data in an understandable format, and regular interactions with clinicians require considerable time allotment by the pathologist in order to ensure optimum patient management and fiscal responsibility to the hospital or laboratory that generates the data. [ABSTRACT FROM AUTHOR]

The process of tooth formation (odontogenesis) encompasses complex processes, which combine two principal phenomenons: cellular morphodifferentiation and histodifferentiation. Epithelial odontogenic tumors, in essence, recapitulate odontogenesis at various stages of development and are histologically related to remnants of odontogenic epithelium, left behind near the crown and root portions, following the cessation of this complex and detailed process. Theoretically, odontogenic tumors may develop from these rests or any of the cells that contributed to the process of odontogenesis. [ABSTRACT FROM AUTHOR]

Grading of gliomas of the central nervous system remains a controversial subject among neuropathologists. Different grading systems have proliferated, likely due to the inability of one system to completely classify all tumors. Most of the systems used today are based on the 1929 system of Bailey and Cushing. As expected, all of the systems have their advantages and proponents, as well as their drawbacks. Dissension among various institutions regarding grading systems and the propagation of different grading systems via publications in medical journals also serve to confuse the clinicians responsible for the care of patients with brain tumors, largely neurologists, neuro-oncologists, and neurosurgeons. [ABSTRACT FROM AUTHOR]

The aggressive B-cell lymphomas are surprisingly heterogeneous in morphologic and architectural features, despite their common cell lineage. There are, in addition, a variety of differences among these entities that have no morphologic correlates. These disorders were spotlighted in the XI Workshop of the European Association of Hematopathology in May 2002 in Siena, Italy, and reviewed in the symposium of the American Society for Hematopathology in March 2003 at the Annual Meeting of the US-Canadian Academy of Pathology.1-3 Like the symposium, this presentation is derived from material presented at the XI European Workshop.Our intention is to provide a practical,illustrated update on the aggressive B-cell lymphomas for general pathologists in practice. [ABSTRACT FROM AUTHOR]

The patient was a 59-year-old male with 1.5 months of diarrhea, cramping, and 5-lb weight loss. On physical examination he was found to have a mobile 4 x 6 cm RUQ mass. He underwent a colonoscopy and biopsy. Later, a right colectomy with attached segment of small bowel was done. On opening the specimen a circumferential mass was seen in the small bowel extending into the proximal cecum. The mass itself occupied approximately 20 cm segment of the bowel and on sectioning it displayed a homogenous solid, white-tan, fleshy appearance. Few peri-colonic lymph nodes were found (0.8-2.0 cm). [ABSTRACT FROM AUTHOR]

At some point in their training,pathologists learn that the diagnosis of bone lesions should not be undertaken without first reviewing the clinical radiographs. If a pathologist strictly adheres to this philosophy, the orthopedic surgeon will eventually provide the patient's x-rays (better to share x-rays than get no diagnosis). When this happens, a pathologist who knows little about x-ray interpretation may begin to feel like a dog running and barking at passing cars (if the car ever stopped and the dog jumped inside, what would the dog do with it?). This is because pathologists are seldom taught in their residencies how radiographic data are actually incorporated into the formulation of histological diagnosis. [ABSTRACT FROM AUTHOR]

Currently, pancreatic cancer is the fourth leading cause of cancer-associated deaths in the United States and ranks ninth in its incidence. Increased mortality from this tumor results from multiple factors including detection at advanced stages, aggressive biology, and relative resistance to available therapy. It is reported that resection of early (size<3.0cm) organ-confined tumors provide significantly improved patient survival in comparison to large tumors.1 It is, therefore, important to detect these tumors early. Imaging studies (percutaneous ultrasound and CT scan) have provided a valuable support in detection of these tumors for a long time. Endoscopic ultrasound (EUS) is a relatively new imaging modality and is reported to be superior to both CT scans and MRI in detecting pancreatic lesions, especially when lesions are smaller than 3.0 cm.2 [ABSTRACT FROM AUTHOR]

In this chapter,we are going to discuss the morphology and differential diagnosis of neuroendocrine tumor, bronchioalveolar carcinoma, non-small-cell lung carcinoma, metastatic tumors to the lung, and spindle cell neoplasm. [ABSTRACT FROM AUTHOR]

Accumulation of an excess amount of fluid, or effusion, in the pleural or pericardial cavities is always pathological. About 20% of effusions are caused by malignancy. Metastatic diseases are more common than primary malignancy. Among the former, the majority are adenocarcinomas. The primary indication of cytologic examination of exfoliated cells in fluid is to rule out a malignancy. [ABSTRACT FROM AUTHOR]

Mediastinum refers to the space in the thoracic cavity that is bound by the pleura, sternum, vertebral column, thoracic inlet, and diaphragm. It contains major anatomic structures and can be involved by diverse pathologic processes. It is customarily to divide the mediastinum into several compartments: superior, anterior, middle, and posterior because the lists of differential diagnoses vary according to the location. (see Table 1) In addition, the patient's age may also be helpful. For example, thymoma and carcinoid are less common in children. [ABSTRACT FROM AUTHOR]

What are we actually speaking of when we use the term "marker"? Practicing pathologists and oncologists have applied the concept for many years without necessarily giving deep thought to what they were doing. Markers are features (of tumors, in the context we are using) that predict future behavior. In fact, the whole exercise of histopathology could arguably be thought of as interpretation of "markers." Traditionally, the features that proved most useful were tumor stage and grade. As useful as these have been there was always an element of stock market disclaimer to them: "Past performance does not necessarily predict future results." The effort to identify important features of tumors has moved inexorably to attempts to identify molecular features of tumors or biomarkers. Ideally, biomarkers would impact oncology in five main areas: cancer screening, diagnosis, tumor classification, prognosis, and predicting therapeutic response. [ABSTRACT FROM AUTHOR]

Diverticular disease is very common in Western countries, with the prevalence increasing with age to involve over 50%of the population by age 85. The pathogenesis is thought to be due to a lack of fiber in the Western diet with resultant low stool volumes. In fiber-rich diets, stools are bulky, which serves to keep the colon distended during muscular activity. On the other hand, with fiber-poor small-volume stools, muscular contraction closes off small areas or segments of the colon, and these segments develop high intraluminal pressure with further muscular contraction. In response to this pressure, portions of mucosa then herniate out along perforating arteries. [ABSTRACT FROM AUTHOR]

This chapter will be devoted to infrequently encountered lesions of the female reproductive tract. Some of these will be lesions that are rarely seen, while others will be lesions that you may anticipate seeing from time to time, although certainly not everyday. [ABSTRACT FROM AUTHOR]

The parathyroid glands arise as paired structures from the third and fourth branchial pouches. The superior glands arise from pouch IV and assume their usual (approximately 80%) location at the cricothyroid junction or at the junction of the recurrent laryngeal nerve and inferior thyroid artery (see Figure 1a). The lower glands arising from pouch III have a more variable distribution. Usually the inferior glands are found at the lower pole of the thyroid lobe, but may be found at the level of the hyoid, within the mediastinum, and even within the pericardium (see Figure 1b). Most individuals (>90%)have the expected four parathyroid glands, but supernumery glands may be present with up to 12 glands reported in rare cases. These supernumery glands likely arise from embryologic rests of the developing glands, and most are found within the thymus, which arises from pouch III along with the inferior glands. [ABSTRACT FROM AUTHOR]

Overexpression of erbB-2 is important in the pathogenesis of a variety of human neoplasms. Overexpression of the erbB-2 gene product has been associated with poor clinical prognosis with respect to malignancies originating in the ovary, breast, gastrointestinal tract, salivary gland, and lung (1-4) and has led to the development of several therapeutic strategies to target tumor cells exhibiting increased surface levels of erbB-2. Monoclonal antibodies that exhibit high-affinity binding to the extracellular domains of the erbB-2 protein have been developed (5,6). Several studies have demonstrated that a subset of these antibodies can elicit growth inhibition of erbB-2 overexpressing cells both in vitro and in vivo (5,6). Antitumor therapies directed at erbB-2 have also been developed utilizing targeted immunotoxins (7). Gene-therapy strategies such as antisense technology has been widely used in these areas of research to achieve selected knockout of genes both at transcriptional or posttranscriptional levels (8-10). Recombinant fusion proteins consisting of various bacterial toxins selectively targeted to the tumor by virtue of single-chain anti-erbB-2 antibody (sFv) moieties has also been utilized in this context (7). [ABSTRACT FROM AUTHOR]