The pathologist's role in minimal breast cancer.
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In this article, the pathologic findings of carcinoma of the prostate were reviewed. Criteria were discussed for the pathologic diagnosis of prostatic carcinoma (PC), premalignant lesions, lesions that simulate PC, immunopathologic findings, special types of PC, effects of therapy on the prostate, and recent efforts to improve diagnostic and prognostic capabilities. The possible role of the study of nucleolar organizing regions was reported. A new method for demonstrating chromosomes in formaldehyde-fixed paraffin-embedded tissue was mentioned. The need for research in all aspects of the pathology of prostatic cancer was emphasized.
A prospective audit of all large bowel cancer resections is being conducted in the adjacent Health Boards of Lothian and Borders. The results of surgery in 750 consecutive patients recruited during the first 2 years are presented. In this time, 249 (33.2 per cent) patients presented as an emergency, 490 (65.3 per cent) had resection of a colonic cancer, and 36 (4.8 per cent) patients died within 30 days. Abdominal resection was performed in 741 patients and intestinal continuity was restored in 646 (87.2 per cent). Of all anastomoses performed, 31 (4.8 per cent) leaked (15 of 467 (3.2 per cent) and 16 of 179 (8.9 per cent) after resection of colonic and rectal cancers, respectively). Of the patients presenting with a rectal cancer, 251 (96.5 per cent) underwent abdominal resection and intestinal continuity was restored in 179 (71.3 per cent). Five of 28 consultants were responsible for half of these patients. Patients treated by these five consultants were no more likely to undergo anastomosis, but when an anastomosis was performed it was less likely to leak (four of 95 (4.2 per cent) versus 12 of 84 (14.3 per cent) (chi 2 = 4.63, P < 0.05)). The overall outcome of surgery appears to be improved when compared to previous similar audits. Considerable intersurgeon variation remains in the results of resection of rectal cancer.
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Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.
The bone marrow aspirate and biopsy is an important medical procedure for the diagnosis of hematologic malignancies and other diseases, and for the follow-up evaluation of patients undergoing chemotherapy, bone marrow transplantation, and other forms of medical therapy. During the procedure, liquid bone marrow is aspirated from the posterior iliac crest or sternum with a special needle, smeared on glass microscope slides by one of several techniques, and stained by the Wright-Giemsa or other techniques for micro-scopic examination. The bone marrow core biopsy is obtained from the posterior iliac crest with a Jamshidi or similar needle and processed in the same manner as other surgical specimens. Flow cytometric examination, cytochemical stains, cytogenetic and molecular analysis, and other diagnostic procedures can be performed on bone marrow aspirate material, while sections prepared from the bone marrow biopsy can be stained by the immunoperoxidase or other techniques. The bone marrow procedure can be performed with a minimum of discomfort to the patient if adequate local anesthesia is utilized. Pain, bleeding, and infection are rare complications of the bone marrow procedure performed at the posterior iliac crest, while death from cardiac tamponade has rarely occurred from the sternal bone marrow aspiration. The recent development of bone marrow biopsy needles with specially sharpened cutting edges and core-securing devices has reduced the discomfort of the procedure and improved the quality of the specimens obtained.
The computer and the digital camera provide a unique means for improving hematology education, research, and patient service. High quality photographic images of gross specimens can be rapidly and conveniently acquired with a high-resolution digital camera, and specialized digital cameras have been developed for photomicroscopy. Digital cameras utilize charge-coupled devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) image sensors to measure light energy and additional circuitry to convert the measured information into a digital signal. Since digital cameras do not utilize photographic film, images are immediately available for incorporation into web sites or digital publications, printing, transfer to other individuals by email, or other applications. Several excellent digital still cameras are now available for less than 2,500 dollars that capture high quality images comprised of more than 6 megapixels. These images are essentially indistinguishable from conventional film images when viewed on a quality color monitor or printed on a quality color or black and white printer at sizes up to 11x14 inches. Several recent dedicated digital photomicroscopy cameras provide an ultrahigh quality image output of more than 12 megapixels and have low noise circuit designs permitting the direct capture of darkfield and fluorescence images. There are many applications of digital images of pathologic specimens. Since pathology is a visual science, the inclusion of quality digital images into lectures, teaching handouts, and electronic documents is essential. A few institutions have gone beyond the basic application of digital images to developing large electronic hematology atlases, animated, audio-enhanced learning experiences, multidisciplinary Internet conferences, and other innovative applications. Digital images of single microscopic fields (single frame images) are the most widely utilized in hematology education at this time, but single images of many adjacent microscopic fields can be stitched together to prepare "zoomable" panoramas that encompass a large part of a microscope slide and closely simulate observation through a real microscope. With further advances in computer speed and Internet streaming technology, the virtual microscope could easily replace the real microscope in pathology education. Later in this decade, interactive immersive computer experiences may completely revolutionize hematology education and make the conventional lecture and laboratory format obsolete. Patient care is enhanced by the transmission of digital images to other individuals for consultation and education, and by the inclusion of these images in patient care documents. In research laboratories, digital cameras are widely used to document experimental results and to obtain experimental data.
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The first well-documented case in which the juxtaoral organ was identified in a surgical specimen removed because of oral cancer is reported. Recognition of this normal structure, the histological picture of which considerably resembles that of a mucoepidermoid carcinoma was crucial in determining the precise extent of the malignant process. Misinterpreting the JOO as cancer may lead to false prognoses or to unnecessarily extensive surgery. The differential diagnostic importance of orofacial epithelial structures localised perineurally is discussed.
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Developments in telepathology robotic systems have evolved the concept of a 'virtual microscope' handling 'digital slides'. Slide digitization is a method of archiving salient histological features in numerical (digital) form. The value and potential of this have begun to be recognized by several international centres. Automated complete slide digitization has application at all levels of clinical practice and will benefit undergraduate, postgraduate, and continuing education. Unfortunately, as the volume of potential data on a histological slide represents a significant problem in terms of digitization, storage, and subsequent manipulation, the reality of virtual microscopy to date has comprised limited views at inadequate resolution. This paper outlines a system refined in the authors' laboratory, which employs a combination of enhanced hardware, image capture, and processing techniques designed for telepathology. The system is able to scan an entire slide at high magnification and create a library of such slides that may exist on an internet server or be distributed on removable media (such as CD-ROM or DVD). A digital slide allows image data manipulation at a level not possible with conventional light microscopy. Combinations of multiple users, multiple magnifications, annotations, and addition of ancillary textual and visual data are now possible. This demonstrates that with increased sophistication, the applications of telepathology technology need not be confined to second opinion, but can be extended on a wider front.
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