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Programmed cell death ligand-1 (PD-L1), expressed on both tumor cells (TC) and tumor-associated immune cells (IC), has been shown to be a useful biomarker and predictive of response to anti-PD-L1 agents in certain tumor types. In recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), there is a growing interest in the role of PD-L1 expression on ICs, as well as TCs, for predicting response to immune checkpoint inhibitors. Using pooled data from the phase II HAWK and CONDOR studies, we investigated the association of baseline PD-L1 expression with durvalumab efficacy in patients with R/M HNSCC. To determine an optimal PD-L1 cut-off point for predicting survival, we assessed PD-L1 expression levels at different TC and IC cut-off points in patients treated with durvalumab. Longer survival was associated with higher TC membrane PD-L1 expression and IC staining. When the combined TC/IC algorithm was applied, a cut-off point for PD-L1 expression of ≥50% on TCs or ≥25% on ICs (TC ≥ 50%/IC ≥ 25%) showed a higher objective response rate (17.2% vs. 8.8%), longer median progression-free survival (2.8 vs. 1.9 months), and longer median overall survival (8.4 vs. 5.4 months) in the PD-L1–high versus PD-L1–low/negative patient populations, respectively. A scoring algorithm combining PD-L1 expression on TCs and ICs using the cut-off point TC ≥ 50%/IC ≥ 25% was optimal for identifying patients with HNSCC most likely to benefit from durvalumab treatment. The new algorithm is robust and can be reproducibly scored by trained pathologists. Significance: A novel algorithm for PD-L1 expression using the cut-off point TC ≥ 50%/IC ≥ 25% is robust for identifying patients with HNSCC most likely to benefit from durvalumab treatment and can be reproducibly scored by trained pathologists.

The COVID-19 pandemic presented numerous challenges to the continuity of programmed cell death ligand 1 (PD-L1) assay training events conducted by our organization. Under typical conditions, these training events are face-to-face affairs, where participants are trained to assay algorithms on glass slides during multi-headed scope sessions. Social distancing measures undertaken to slow pandemic spread necessitated the adaptation of our training methods to facilitate assay training and subsequent continuation of clinical trials. The present report details the creation and use of the Roche pathology training portal (PTP) that allowed for remote training to diagnostic assay algorithms. The PTP is a web-based system comprised of a learning management system (LMS) coupled to an image management system (IMS). Whole slide images (WSIs) were produced using a DP200 instrument (Roche, Pleasanton, CA) and these scan files were then uploaded to an IMS. Courses were created on the LMS using annotated WSIs that were shared with enrolled pathologists worldwide during assay training events. These courses culminated in assay certification examinations, where pathologists evaluated test-case WSIs and evaluated these cases within the LMS. Trainee submissions were analyzed for pass/fail status by comparing user data entries with consensus scores on these test-case WSIs. To date, 47 pathologist trainings have occurred and of these, 44 have successfully passed the associated assay certification exam on the first attempt (93% 1st-try pass rate). The PTP allowed roche to continue training sites during the COVID-19 pandemic, and these early results demonstrate the capability of this digital solution regarding PD-L1 diagnostic assay training events.

Background Recent studies reported abnormal alpha-synuclein deposition in biopsy-accessible sites of the peripheral nervous system in Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if deposition occurs early, it may enable tissue diagnosis of prodromal PD. Objective The aim of this study was to develop and test an automated bright-field immunohistochemical assay of cutaneous pathological alpha-synuclein deposition in patients with idiopathic rapid eye movement sleep behavior disorder, PD, and atypical parkinsonism and in control subjects. Methods For assay development, postmortem skin biopsies were taken from 28 patients with autopsy-confirmed Lewy body disease and 23 control subjects. Biopsies were stained for pathological alpha-synuclein in automated stainers using a novel dual-immunohistochemical assay for serine 129-phosphorylated alpha-synuclein and pan-neuronal marker protein gene product 9.5. After validation, single 3-mm punch skin biopsies were taken from the cervical 8 paravertebral area from 79 subjects (28 idiopathic rapid eye movement sleep behavior disorder, 20 PD, 10 atypical parkinsonism, and 21 control subjects). Raters blinded to clinical diagnosis assessed the biopsies. Results The immunohistochemistry assay differentiated alpha-synuclein pathology from nonpathological-appearing alpha-synuclein using combined phosphatase and protease treatments. Among autopsy samples, 26 of 28 Lewy body samples and none of the 23 controls were positive. Among living subjects, punch biopsies were positive in 23 (82%) subjects with idiopathic rapid eye movement sleep behavior disorder, 14 (70%) subjects with PD, 2 (20%) subjects with atypical parkinsonism, and none (0%) of the control subjects. After a 3-year follow-up, eight idiopathic rapid eye movement sleep behavior disorder subjects phenoconverted to defined neurodegenerative syndromes, in accordance with baseline biopsy results. Conclusion Even with a single 3-mm punch biopsy, there is considerable promise for using pathological alpha-synuclein deposition in skin to diagnose both clinical and prodromal PD. © 2020 International Parkinson and Movement Disorder Society.

Tumor suppressor p53 maintains genome stability by differentially activating target genes that control diverse cellular responses, such as the antioxidant response, cell cycle arrest and apoptosis. Despite the fact that many p53 downstream genes have been well characterized, novel p53 target genes are continuously being identified. Here, we report that Tpt1 is a direct target gene of p53. We found that p53 upregulates the transcription of Tpt1 and identified a p53-responsive element in the promoter of the mouse Tpt1 gene. Furthermore, p53-dependent induction of Tpt1 was able to reduce oxidative stress, minimize apoptosis, and promote cell survival in response to H 2O2 challenge. In addition, a positive correlation between the expression of p53 and Tpt1 only existed in normal lung tissues, not in lung tumors. Such positive correlation was also found in lung cell lines that contain wild-type p53, but not mutated p53. Based on the important role of Tpt1 in cancer development, chemoresistance, and cancer reversion, identification of Tpt1 as a direct target gene of p53 not only adds to the complexity of the p53 network, but may also open up a new avenue for cancer prevention and intervention.

Telepathology, the distant service component of digital pathology, is a growth industry. The word "telepathology" was introduced into the English Language in 1986. Initially, two different, competing imaging modalities were used for telepathology. These were dynamic (real time) robotic telepathology and static image (store-and-forward) telepathology. In 1989, a hybrid dynamic robotic/static image telepathology system was developed in Norway. This hybrid imaging system bundled these two primary pathology imaging modalities into a single multi-modality pathology imaging system. Similar hybrid systems were subsequently developed and marketed in other countries as well. It is noteworthy that hybrid dynamic robotic/static image telepathology systems provided the infrastructure for the first truly sustainable telepathology services. Since then, impressive progress has been made in developing another telepathology technology, so-called "virtual microscopy" telepathology (also called "whole slide image" telepathology or "WSI" telepathology). Over the past decade, WSI has appeared to be emerging as the preferred digital telepathology digital imaging modality. However, recently, there has been a re-emergence of interest in dynamic-robotic telepathology driven, in part, by concerns over the lack of a means for up-and-down focusing (i.e., Z-axis focusing) using early WSI processors. In 2010, the initial two U.S. patents for robotic telepathology (issued in 1993 and 1994) expired enabling many digital pathology equipment companies to incorporate dynamic-robotic telepathology modules into their WSI products for the first time. The dynamic-robotic telepathology module provided a solution to the up-and-down focusing issue. WSI and dynamic robotic telepathology are now, rapidly, being bundled into a new class of telepathology/digital pathology imaging system, the "WSI-enhanced dynamic robotic telepathology system". To date, six major WSI processor equipment companies have embraced the approach and developed WSI-enhanced dynamic-robotic digital telepathology systems, marketed under a variety of labels. Successful commercialization of such systems could help overcome the current resistance of some pathologists to incorporate digital pathology, and telepathology, into their routine and esoteric laboratory services. Also, WSI-enhanced dynamic robotic telepathology could be useful for providing general pathology and subspecialty pathology services to many of the world's underserved populations in the decades ahead. This could become an important enabler for the delivery of patient-centered healthcare in the future.

PRESENTATION A 62-year-old woman’s dermatologic difficulties were compounded when light treatment for psoriasis spurred pemphigus foliaceus; an occurrence very rarely noted in the medical literature. She presented with an erythematous, crusted eruption involving her entire head and neck and most of her trunk. The lesions developed several months after consecutive exposures to narrowband ultraviolet B (UVB) phototherapy for chronic plaque psoriasis (Figure 1).

An innovative telemedicine-enabled rapid breast care service is described that bundles telemammography, telepathology, and teleoncology services into a single day process. The service is called the UltraClinics Process. Because the core services are at 4 different physical locations, a challenge has been to obtain stat second opinion readouts on newly diagnosed breast cancer cases. To provide same day quality assurance rereview of breast surgical pathology cases, a DMetrix DX-40 ultrarapid virtual slide scanner (DMetrix Inc, Tucson, AZ) was installed at the participating laboratory. Glass slides of breast cancer and breast hyperplasia cases were scanned the same day the slides were produced by the University Physicians Healthcare Hospital histology laboratory. Virtual slide telepathology was used for stat quality assurance readouts at University Medical Center, 6 miles away. There was complete concurrence with the primary diagnosis in 139 (90.3%) of cases. There were 4 (2.3%) major discrepancies, which would have resulted in a different therapy and 3 (1.9%) minor discrepancies. Three cases (1.9%) were deferred for immunohistochemistry. In 2 cases (1.3%), the case was deferred for examination of the glass slides by the reviewing pathologists at University Medical Center. We conclude that the virtual slide telepathology quality assurance program found a small number of significant diagnostic discrepancies. The virtual slide telepathology program service increased the job satisfaction of subspecialty pathologists without special training in breast pathology, assigned to cover the general surgical pathology service at a small satellite university hospital.

Virtual slide telepathology is an important potential tool for providing re-review of surgical pathology cases as part of a quality assurance program. The University of Arizona pathology faculty has implemented a quality assurance program between 2 university hospitals located 6 miles apart. The flagship hospital, University Medical Center (UMC), in Tucson, AZ, handles approximately 20 000 surgical pathology specimens per year. University Physicians Healthcare Hospital (UPHH) at Kino Campus has one tenth the volume of surgical pathology cases. Whereas UMC is staffed by 10 surgical pathologists, UPHH is staffed daily by a single part-time pathologist on a rotating basis. To provide same-day quality assurance re-reviews of cases, a DMetrix DX-40 ultrarapid virtual slide scanner (DMetrix, Inc, Tucson, AZ) was installed at the UPHH in 2005. Since then, glass slides of new cases of cancer and other difficult cases have been scanned the same day the slides are produced by the UPHH histology laboratory. The pathologist at UPHH generates a provisional written report based on light microscopic examination of the glass slides. At 2:00 pm each day, completed cases from UPHH are re-reviewed by staff pathologists, pathology residents, and medical students at the UMC using the DMetrix Iris virtual slide viewer. The virtual slides are viewed on a 50-in plasma monitor. Results are communicated with the UPHH laboratory by fax. We have analyzed the results of the first 329 consecutive quality assurance cases. There was complete concordance with the original UPHH diagnosis in 302 (91.8%) cases. There were 5 (1.5%) major discrepancies, which would have resulted in different therapy and/or management, and 10 (3.0%) minor discrepancies. In 6 cases (1.8%), the diagnosis was deferred for examination of the glass slides by the reviewing pathologists at UMC, and the diagnosis of another 6 (1.8%) cases were deferred pending additional testing, usually immunohistochemistry. Thus, the quality assurance program found a small number of significant diagnostic discrepancies. We also found that implementation of a virtual slide telepathology quality assurance service improved the job satisfaction of academic subspecialty pathologists assigned to cover on-site surgical pathology services at a small, affiliated university hospital on a rotating part-time basis. These findings should be applicable to some community hospital group practices as well.

This small exploratory study was designed to test the hypothesis that thin melanoma lesions contain nuclei of two similar phenotypes, in different proportions. In lesions likely to progress to metastatic disease, one of these phenotypes predominates. Histopathological sections from 18 cases of thin melanomas which did not progress to metastasis, and from 10 cases which did progress were imaged and digitized at high resolution, with a total of 2084 and 1148 nuclei, respectively, recorded. Five karyometric features were used to discriminate between nuclei from indolent and from potentially metastatic lesions. For each case, the percentage of nuclei classified by the discriminant function as having come from a potentially metastatic lesion was determined and termed as case classification criterion. Standard histopathological criteria, such as ulceration and high mitotic index, indicated in this material the need for intensive therapy for only one of the 10 participants, as compared with 7/10 identified correctly by the karyometric measure. Using a case classification criterion threshold of 40%, the overall accuracy was 86% in the test set. The proportion of nuclei of an aggressive phenotype may lend itself as an effective prognostic clue for thin melanoma lesions. The algorithm developed in this training set appears to identify those patients at high risk for metastatic disease, and demonstrates a basis for a further study to assess the utility of prognostic clues for thin melanomas.

We report a case of a renal metanephric adenoma in a 10-year-old boy, in which cytogenetic analysis showed a balanced translocation, t(9;15)(p24;q24) and a balanced paracentric inversion of chromosome 12, inv(12)(q13q15). Immunohistochemically, the tumor showed diffuse reactivity for cytokeratin AE1/AE3, CAM5.2, CD57, and WT1; patchy reactivity for CD56; and focal reactivity for cytokeratin 7, epithelial membrane antigen, and CD10. Tumor cells were entirely nonreactive for α-methyl acyl coenzyme A racemase. Published cytogenetic data for metanephric adenomas are limited, and this is the first report of these cytogenetic abnormalities. The involvement of the chromosome region 9p24 is particularly interesting because of the recent identification of a tumor suppressor gene, KANK (kidney ankyrin repeat-containing protein), at this locus.

Sodium/hydrogen exchanger (NHE) 8 is expressed at the apical membrane of the epithelial cells and plays important roles in neutral sodium absorption in the gastrointestinal tract and the kidney. It also has an important role in epithelial mucosal protection in the gastric gland and the intestine. Although NHE8 has broad tissue distribution, the precise location and the physiological role of NHE8 in the eye remain unknown. In the present study, we successfully detected the expression of NHE8 in the ocular surface by PCR and Western blot in human and mouse eyes. Immunohistochemistry staining located NHE8 protein at the plasma membrane of the epithelial cells in the conjunctiva, the cornea, and the lacrimal gland both in human and mouse. We also detected the expression of downregulated-in-adenoma (DRA, a Cl−/HCO3−transporter) in the ocular surface epithelial cells. Using NHE8−/− mouse model, we found that loss of NHE8 function resulted in reduced tear production and increased corneal staining. These NHE8−/− mice also showed increased expression of TNF-α and matrix metalloproteinase 9 (MMP9) genes. The expression of epithelial keratinization marker genes, small proline-rich protein 2h (Sprr2h) and transglutaminase 1 (Tgm1), were also increased in NHE8−/− eyes. Furthermore, DRA expression in NHE8−/− mice was reduced in the conjunctiva, the cornea, and the lacrimal glands in association with a reduction in conjunctival mucosal pH. Altered ocular surface function and reduced epithelial DRA expression in NHE8−/− mice suggest that the role of NHE8 in ocular surface tissue involve in tear production and ocular epithelial protection. This study reveals a potential novel mechanism of dry eye condition involving abnormal NHE8 function.

Cutaneous metastasis is an uncommon but well recognized phenomenon occurring as a result of internal malignancy. Cancers most often associated with cutaneous metastasis are melanoma and primary malignancies of the breast and head and neck. Cutaneous metastatic prostate cancer is rare, representing only 1% of cases. Herein we report a case of advanced prostate cancer with multiple cutaneous metastases and briefly review the literature highlighting the clinical and histopathological features as well as a management approach to the patient with metastatic prostate cancer involving the skin.

A monoclonal IgG isolated from a patient with multiple myeloma has been shown to bind to exosite II of thrombin, prolong both the thrombin time and the activated partial thromboplastin time (aPTT) when added to normal plasma, and alter the kinetics of hydrolysis of synthetic peptide substrates. Although the IgG does not affect cleavage of fibrinogen by thrombin, it increases the rate of inhibition of thrombin by purified antithrombin approximately 3-fold. Experiments with plasma immunodepleted of antithrombin or heparin cofactor II confirm that prolongation of the thrombin time requires antithrombin. By contrast, prolongation of the aPTT requires neither antithrombin nor heparin cofactor II. The IgG delays clotting of plasma initiated by purified factor IXa but has much less of an effect on clotting initiated by factor Xa. In a purified system, the IgG decreases the rate of activation of factor VIII by thrombin. These studies indicate that binding of a monoclonal IgG to exosite II prolongs the thrombin time indirectly by accelerating the thrombin-antithrombin reaction and may prolong the aPTT by interfering with activation of factor VIII, thereby diminishing the catalytic activity of the factor IXa/VIIIa complex.

Cutaneous metastasis is an uncommon but well recognized phenomenon occurring as a result of internal malignancy. Cancers most often associated with cutaneous metastasis are melanoma and primary malignancies of the breast and head and neck. Cutaneous metastatic prostate cancer is rare, representing only 1% of cases. Herein we report a case of advanced prostate cancer with multiple cutaneous metastases and briefly review the literature highlighting the clinical and histopathological features as well as a management approach to the patient with metastatic prostate cancer involving the skin.

Metastatic Crohn's disease (CD) is a rare cutaneous manifestation of CD that was first described nearly 50 years ago. Many subsequent reports have defined its most common clinical and histopathologic features. The pathogenesis underlying metastatic CD is unknown but various hypotheses exist. An established standard therapy is lacking. Owing to its rarity and nonspecific clinical presentation along with the diversity of inflammatory skin disorders that often complicate CD, the diagnosis of metastatic CD may be overlooked. This report highlights the salient features of this disorder to facilitate recognition and management of this rare dermatosis.

Currently, the sole treatment option for patients with heart failure is transplantation. The battle of prolonging graft survival and modulating innate and adaptive immune responses is still being waged in the clinic and in research labs. The transcription factor Nrf2 controls major cell survival pathways and is central to moderating inflammation and immune responses. In this study the effect of Nrf2 levels in host recipient C57BL/6 mice on Balb/c allogeneic graft survival was examined. Importantly, Nrf2−/−recipient mice could not support the graft for longer than 7.5 days on average, whereas activation of Nrf2 by sulforaphane in Nrf2+/+hosts prolonged graft survival to 13 days. Several immune cells in the spleen of recipient mice were unchanged; however, CD11b+macrophages were significantly increased in Nrf2−/−mice. In addition, IL-17 mRNA levels were elevated in grafts transplanted into Nrf2−/−mice. Although Nrf2 appears to play a crucial role in graft survival, the exact mechanism is yet to be fully understood.

Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure.

The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. Oncogenes c-Src, c-myc, and eIF4E are regulated by hnRNP K. We have shown an increased cytoplasmic hnRNP K in pancreatic cancer. In the present study, we investigated the altered expression of hnRNP K protein and its correlation with p-ERK in melanoma using human melanoma cell lines and tissue microarray.The protein levels of hnRNP K and p-ERK in 8 human melanoma cell lines and a melanoma progression tissue microarray containing 80 melanoma, 23 dysplastic nevi, and 14 benign nevi specimens were analyzed using Western blot and immunohistochemistry analysis. hnRNP K was knocked down by siRNA, and its effect on melanoma cells was assessed.We showed a higher hnRNP K protein level in both melanoma cell lines and melanoma tissue specimens, which correlated with a higher c-myc expression. An increase in the cytoplasmic hnRNP K and eIF4E protein levels in melanoma cells is also seen. p-ERK level was also higher in dysplastic nevi and melanoma tissues, but did not correlate with hnRNP K protein level. We then demonstrated that knocking down of hnRNP K by siRNA inhibited melanoma cell growth and colony formation, as well as c-myc expression.hnRNP K expression correlated with melanoma and may play a role in melanoma tumorigenesis.

A needle-free system that delivers lidocaine to the dermis using pressurized gas is often used as an alternative anesthetic for venipuncture and intravenous catheterization in children. This case report illustrates the potential histologic artifacts that may arise when using a needleless device for a cutaneous punch biopsy. We suggest against using a needleless system for pediatric skin biopsies.

Lung cancer is the leading cause of cancer-related deaths in the world, with increasing incidence in many developed countries. Epidemiological data suggest that consumption of soy products may be associated with a decreased risk of cancer. Despite the association of nutrition and cancer, the molecular mechanisms by which the active metabolite in the soy diet, genistein, exerts its biological response have not been studied. We previously showed that genistein can inhibit the growth of H460 non-small-cell lung cancer (NSCLC) cells in vitro. To explore the molecular mechanisms by which genistein inhibits the growth of NSCLC cells, we investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 cells, which harbor wild-type p53, and H322 cells, which possess mutated p53. Genistein was found to inhibit H460 and H322 cell growth in a dose-dependent manner. Staining with 4,6-diamidino-2-phenylindole, poly(ADP-ribose) polymerase cleavage, and flow cytometric apoptosis analysis were used to investigate apoptotic cell death, and the results show that 30 microM genistein causes cell death via a typical apoptotic pathway. Western blot analysis demonstrated upregulations of p21WAF1 and Bax by genistein in wild-type and mutant p53 cell lines. Furthermore, cells treated with genistein showed an increased expression of endogenous wild-type p53, while the level of the mutant p53 protein remained unchanged. From these results, we conclude that genistein induces apoptosis in NSCLC cells through a p53-independent pathway and, thus, may act as an anticancer agent.

Lung cancer is the leading cause of cancer-related death in the world, with increasing incidence in many developed countries. Epidemiological data suggest that consumption of soy products (the isoflavone genistein) may be associated with a decreased risk of breast and prostate cancer; however, such studies are not available for lung cancer. We investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 non-small lung cancer cells. Genistein inhibited H460 cell growth in a dose-dependent manner. Flow-cytometric analysis showed that 30 microM genistein arrested cell cycle progression at the G2-M phase. 4,6-Diamidino-2-phenylindole staining, flow-cytometric analysis, and DNA laddering were used to investigate apoptotic cell death, and the results show that 30 microM genistein can cause typical DNA laddering, a hallmark for apoptosis. In addition, flow cytometry and 4,6-diamidino-2-phenylindole staining showed induction of apoptosis by genistein. Our investigation also demonstrated the modulation of p21WAF1 by Western blot analysis of cell lysates obtained from cultured cells treated with 30 and 50 microM genistein for 24, 48, and 72 hours. Simultaneously, immunocytochemical staining was conducted for the expression of p21WAF1 protein. Our results showed that genistein can upregulate p21WAF1 expression in genistein-treated cells. From these results, we conclude that genistein may act as an anticancer agent, and further studies may prove its efficacy in non-small lung cancer cells. Thus the biological effects of genistein may, indeed, be due to the modulation of cell growth, cell death, and cell cycle regulatory molecules.

Background: The case triage practice workflow model was used to manage incoming cases on a telepathology-enabled surgical pathology quality assurance (QA) service. Maximizing efficiency of workflow and the use of pathologist time requires detailed information on factors that influence telepathologists’ decision-making on a surgical pathology QA service, which was gathered and analyzed in this study. Materials and Methods: Surgical pathology report reviews and telepathology service logs were audited, for 1862 consecutive telepathology QA cases accrued from a single Arizona rural hospital over a 51 month period. Ten university faculty telepathologists served as the case readers. Each telepathologist had an area of subspecialty surgical pathology expertise (i.e. gastrointestinal pathology, dermatopathology, etc.) but functioned largely as a general surgical pathologist while on this telepathology-enabled QA service. They handled all incoming cases during their individual 1-h telepathology sessions, regardless of the nature of the organ systems represented in the real-time incoming stream of outside surgical pathology cases. Results: The 10 participating telepathologists’ postAmerican Board of pathology examination experience ranged from 3 to 36 years. This is a surrogate for age. About 91% of incoming cases were immediately signed out regardless of the subspecialty surgical pathologists’ area of surgical pathology expertise. One hundred and seventy cases (9.13%) were deferred. Case concurrence rates with the provisional surgical pathology diagnosis of the referring pathologist, for incoming cases, averaged 94.3%, but ranged from 88.46% to 100% for individual telepathologists. Telepathology case deferral rates, for second opinions or immunohistochemistry, ranged from 4.79% to 21.26%. Differences in concordance rates and deferral rates among telepathologists, for incoming cases, were significant but did not correlate with years of experience as a practicing pathologist. Coincidental overlaps of the area of subspecialty surgical pathology expertise with organ-related incoming cases did not influence decisions by the telepathologists to either defer those cases or to agree or disagree with the referring pathologist's provisional diagnoses. Conclusions: Subspecialty surgical pathologists effectively served as general surgical pathologists on a telepathology-based surgical pathology QA service. Concurrence rates with incoming surgical pathology report diagnoses, and case deferral rates, varied significantly among the 10 on-service telepathologists. We found no evidence that the higher deferral rates correlated with improving the accuracy or quality of the surgical pathology reports.