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Context.—: The rapid evolution of optical imaging modalities in recent years has opened the opportunity for ex vivo tissue imaging, which has significant implications for surgical pathology practice. These modalities have promising potential to be used as next-generation digital microscopy tools for examination of fresh tissue, with or without labeling with contrast agents., Objective.—: To review the literature regarding various types of ex vivo optical imaging platforms that can generate digital images for tissue recognition with potential for utilization in anatomic pathology clinical practices., Data Sources.—: Literature relevant to ex vivo tissue imaging obtained from the PubMed database., Conclusions.—: Ex vivo imaging of tissues can be performed by using various types of optical imaging techniques. These next-generation digital microscopy tools have a promising potential for utilization in surgical pathology practice.

There have been several updates recently on the classification of uterine tumors. Endometrial carcinomas have traditionally been divided into 2 types, but some are difficult to classify and do not fit readily into either of the currently recognized categories. The Cancer Genome Atlas Research Network has recently defined 4 new categories of endometrial cancer on the basis of mutational spectra, copy number alteration, and microsatellite instability, which might provide independent prognostic information beyond established risk factors. The Society of Gynecologic Oncology, moreover, now recommends systematic screening of every patient with endometrial cancer for Lynch syndrome. The new definition of high-grade endometrial stromal sarcoma disregards the number of mitotic figures as a primary diagnostic criterion and instead specifies moderate atypia still resembling stromal origin but lacking the pleomorphism of undifferentiated uterine sarcoma; these tumors also harbor a JAZF1-SUZ12 gene rearrangement. Mitotic count, atypia, and coagulative necrosis are the main histologic criteria that define leiomyosarcoma. Determining the type of necrosis can be very challenging in patients receiving various treatment modalities for symptomatic fibroids before myomectomy, since key histologic features of ischemic-type necrosis are often absent. Ancillary stains including p16, p53, MIB-1, trichrome, and reticulin may be helpful in tumors harboring necrosis that is difficult to classify. Minimally invasive gynecologic surgeries have introduced histologic artifacts that complicate the diagnosis. It is essential to recognize these as procedure-related artifacts to avoid upstaging tumors and triggering unnecessary adjuvant treatment.

Precision medicine is altering the traditional role of the surgical pathologist in caring for patients with lung cancer. Diagnosing specific cell type is now a foundation for selecting lung cancers for predictive-biomarker testing by molecular techniques. Using conventional techniques and familiar equipment, the surgical pathologist's role goes beyond this important step and will include screening for, and possibly diagnosis of, predictive biomarkers as we illustrate for one predictive biomarker. Pathologists should embrace the innovations described at the Houston Lung Symposium but must recognize that their traditional expertise will be an important component of precision medicine for the foreseeable future.

Context: Digital viewing of histologic images is moving from presentations and publications to incorporation into the daily work of practicing pathologists. Many technologic limitations have been overcome recently, which should make widespread adoption more practical. The task now is for pathologists to become actively involved in its development and implementation, to ensure that the technology is developed with the intent to optimize workflow and to maintain diagnostic accuracy. An understanding of the basic precepts of digital imaging is required to make informed decisions related to hardware and software implementation and to collaborate with vendors and professionals outside of pathology (eg, regulatory agencies) as the technology rapidly develops., Objective: To describe the state of digital microscopy as it applies to the field of pathology and to define specific issues related to adoption of whole slide imaging systems., Data Sources: The information is derived from the experience of the author and review of the literature., Conclusions: Digital microscopy is an important tool for surgical pathologists. It is currently an area of intense and rapid technologic development that will likely transform the workflow of many laboratories during the next several years.

Context: Renal cell carcinoma is a heterogeneous group of tumors with distinct histopathologic features, molecular characteristics, and clinical outcome. These tumors can be sporadic as well as familial or associated with syndromes. The genetic abnormalities underlying these syndromes have been identified and were subsequently found in corresponding sporadic renal tumors., Objective: To review the recent molecular and genetic advancements relating to sporadic and familial renal carcinomas as well as those related to Xp11.2 translocation-associated renal cell carcinoma and renal medullary carcinoma., Data Sources: Literature review, personal experience, and material from the University of Chicago., Conclusions: Molecular genetic diagnostic techniques will continue to introduce new biomarkers that will aid in the differential diagnosis of difficult cases. The identification of specific signaling pathways that are defective in certain renal tumors also makes possible the development of new therapies that selectively target the aberrant activity of the defective proteins.

Context: Digital photography is commonly used to document microscopic features of tissue samples, but it relies on the capture of arbitrarily selected representative areas. Current technologic advances permit the review of an entire sample, some even replicating the use of a microscope., Objective: To demonstrate the applicability of digital video to the documentation of histologic samples., Design: A Canon Elura MC40 digital camcorder was mounted on a microscope, glass slide-mounted tissue sections were filmed, and the unedited movies were transferred to a Apple Mac Pro computer. Movies were edited using the software iMovie HD, including placement of a time counter and a voice recording., Results: The finished movies can be viewed in computers, incorporated onto DVDs, or placed on a Web site after compression with Flash software. The final movies range, on average, between 2 and 8 minutes, depending on the size of the sample, and between 50 MB and 1.6 GB, depending on the intended means of distribution, with DVDs providing the best image quality., Conclusions: Digital video is a practical methodology for documentation of entire tissue samples. We propose an affordable method that uses easily available hardware and software and does not require significant computer knowledge. Pathology education can be enhanced by the implementation of digital video technology.

Context: The endomyocardial biopsy is the mainstay for monitoring acute allograft rejection in heart transplantation. Objective and accurate assessment of cellular and humoral types of rejection is important to optimize immunosuppressive therapy, avoid therapeutic complications, and improve patient outcome. The grading system for evaluation of heart transplant biopsies published in 1990 was revised in 2004 after more than a decade of implementation., Objective: In this review, we focus on a practical approach to the evaluation of human heart transplant biopsies as diagnostic surgical pathologic specimens. We discuss the revised International Society of Heart and Lung Transplantation working formulation., Data Sources: We reviewed pertinent literature, incorporating ideas and vast experience of participants in various work groups that led to the revision of the 1990 grading system., Conclusions: The grading system for cellular rejection is presented with detailed light microscopic morphology and comparison of the 1990 and 2004 International Society of Heart and Lung Transplantation working formulations. We show how the pathologic recognition of cellular rejection and antibody-mediated rejection has evolved. We emphasize the interpretation of immunostains for complement components C4d and C3d in the diagnosis of antibody-mediated rejection. Evidence of regulation of complement activation in human heart transplant biopsies is presented in this context. We also discuss the pitfalls, caveats, and artifacts in the interpretation of allograft endomyocardial biopsies. Lastly, we discuss the pathology of human cardiac allograft vasculopathy in practical detail.

During the past few years a new high-throughput molecular technology, array comparative genomic hybridization, has received a great deal of attention. As a DNA-based tool, this technique is presumably more reproducible than expression arrays. In this review, I discuss how array comparative genomic hybridization is remarkably similar with regard to genome analysis to fluorescent in situ hybridization, a technique that is generally regarded as one of the more accurate and reproducible molecular techniques in diagnostic surgical pathology. A thorough understanding of this technology will be useful for all surgical pathologists in the near future, as this technology will no doubt have some influence on our daily practice.

Objective: Several new immunohistochemical markers that can assist in the diagnosis of mesotheliomas have been recognized recently. This article reviews the current information available on these markers and also provides a practical approach to the immunohistochemical diagnosis of epithelioid mesotheliomas., Data Sources: Current literature concerning immunohistochemical markers for epithelioid mesotheliomas was collected and reviewed., Study Selection: Literature emphasizing immunohistochemical diagnosis of epithelioid mesotheliomas was selected., Data Extraction: Data deemed helpful to the general surgical pathologist for the diagnosis of epithelioid mesothelioma were included in this review., Data Synthesis: Markers identified as potentially useful in the diagnosis of epithelioid mesothelioma include positive markers (namely, calretinin, keratin 5/6, D2-40, podoplanin, mesothelin, and Wilms tumor 1 protein [WT1]) and negative markers (namely, carcinoembryonic antigen, MOC-31, B72.3, and Ber-EP4). Thyroid transcription factor 1 (TTF-1) can assist in determining the lung origin of a carcinoma, and renal cell carcinoma marker (RCC Ma) may help establish its renal origin., Conclusions: D2-40 and podoplanin are the 2 most recently recognized markers that have been found to be useful in the diagnosis of epithelioid mesotheliomas. Since D2-40 and podoplanin appear to be highly sensitive and specific for epithelioid mesotheliomas, either may be considered for inclusion in the battery of antibodies currently recommended for distinguishing epithelioid mesotheliomas from metastatic carcinomas. However, it should be kept in mind that their utility has not yet been fully determined in routine diagnostic work.

Objectives: To document the practice parameters and case characteristics associated with personal (expert) consultations. We also examine the value, level of participant (customer) satisfaction, turnaround time, and rate of personal consultations., Design: We asked participants in the College of American Pathologists' Q-Probes program to document cases sent for consultation during 4 months or up to 20 cases. They documented patient and specimen characteristics, the turnaround times, and the participants' levels of satisfaction with the consultation experience., Participants: One hundred eighty laboratories/surgical pathology practices. One hundred seventy-two (95.6%) were from the United States; the remainder were located in Canada and Australia., Main Outcome Measures: Rate and turnaround time of consultations and participant level of satisfaction., Results: A total of 2746 consultation cases were examined for an aggregate consultation rate of 0.5% (median, 0.7%). Institutions with a higher occupied bed size and a greater number of surgical pathology cases both had lower consultation rates (P < or =.05). The median turnaround time (defined as the interval from the date on which the case was sent to the date on which the diagnosis was received) was 6 days. Twenty-nine percent and 68% of cases had a turnaround time within 3 and 7 days, respectively. Fifty-two percent of cases were sent to nationally known experts, and 32% were sent to local experts. Skin (18.0%), hematolymphoid (11.6%), and breast (9.6%) specimens were most commonly sent for consultation. In 70.5% of cases, the consultant confirmed the referring pathologist's original diagnosis, but in 15.9% of cases, the consultant also added significant information. Satisfaction rates were higher with faster turnaround times and verbal reporting. Satisfaction rates were lower for cases in which the patient or the clinician requested the consultation and in which the consultant's diagnosis was ambiguous., Conclusions: This study establishes a multi-institutional consultation rate of 0.5%, defines the nature of surgical pathology consultations, and demonstrates that satisfaction with consultations is associated with a faster turnaround time and receipt of additional, clinically meaningful information.

As a quality assurance measure, the usefulness of transmission electron microscopy (EM) and immunohistochemistry (IHC) in our surgical pathology laboratory was compared. The surgical pathology reports from 150 consecutive neoplasms that were examined by both EM and IHC were reviewed. Based on the reported clinical histories, final diagnoses, light microscopy results, and the findings by EM or IHC, the contributions of EM and IHC were classified as "helpful" or "not helpful" for each specimen. Electron microscopy was helpful (92%) more often than was IHC (73%). Electron microscopy was most useful in further classifying poorly differentiated carcinomas, while IHC was particularly useful in classifying poorly differentiated neoplasms. Electron microscopy and IHC were of limited value in identifying the origin of metastatic carcinomas of an uncertain primary. All cases determined to be "not helpful" by either modality were further analyzed to establish a reason for the lack of information provided in each case. This analysis demonstrated a need for improved technical quality and ordering patterns of immunohistochemical stains in our laboratory.