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Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P 10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Data regarding the lower diagnostic threshold for gastric graft-versus-host disease is lacking. The aim of this study was to review a cohort of gastric biopsies taken to evaluate for graft-versus-host disease, and to correlate histologic findings with clinical and endoscopic evidence of graft-versus-host disease as well as biopsy findings from other locations to define a lower diagnostic threshold for gastric graft-versus-host disease. Gastric biopsies were evaluated for the maximum number of apoptotic bodies per 10 contiguous gastric pits, presence of ≥1 apoptotic body per biopsy (NIH criteria), and presence of gastric pit dropout and/or ulceration. To evaluate histologic specificity, sixty gastric biopsies from non-stem cell transplant patients were selected as a control group. Clinical information was collected from chart review. The study group consisted of 65 gastric biopsies from 52 stem cell transplant patients. The mean apoptotic count per 10 contiguous gastric pits for stem cell transplant biopsies was 1.8 (range 0–8) and for control cases 1.0 (range 0–5). Nineteen stem cell transplant biopsies (29%) had ≥1 apoptotic body per biopsy and only a single case had >6 apoptotic bodies per 10 contiguous gastric pits. When the NIH guidelines were combined with presence of at least two apoptotic bodies per 10 contiguous gastric pits, this cutoff point was significantly associated with treatment for graft-versus-host disease (OR = 9.4, 95% CI = 1.7–176.7, p = 0.04) and evidence of extraintestinal graft-versus-host disease (OR = 3.2, 95% CI = 1.1–10.7, p = 0.04). The diagnostic specificity for our proposed cutoff value is 94%. We present criteria for the lower diagnostic threshold of gastric graft-versus-host disease, which uses a lower apoptotic cutoff value than has been utilized in colonic biopsies. Although sensitivity remains a challenge for gastric graft-versus-host disease biopsies, this newly proposed cutoff provides higher specificity than NIH guidelines alone and better correlates with clinical evidence of graft-versus-host disease.

Context.— Fatty liver disease is now one of the most commonly encountered entities in the practice of liver pathology. Distinguishing simple steatosis from steatohepatitis is critical because the latter requires follow-up because of long-term risks that include cirrhosis and hepatocellular carcinoma. An organized approach for evaluating liver biopsies with steatosis is recommended to capture all of the relevant features: (1) degree of steatosis, (2) presence or absence of ballooning degeneration, (3) lobular inflammation, and (4) fibrosis. Herein, we provide a stepwise approach that readers can use to evaluate liver biopsies with steatosis, including examples, pitfalls, differential diagnostic considerations, and suggested diagnostic phrasing. Objective.— To provide a stepwise approach for the evaluation of liver biopsies showing significant steatosis (involving ≥5% of liver parenchyma). Data Sources.— Biopsies demonstrating fatty liver disease encountered in our daily practice were examined as well as recent literature. Conclusions.— Effective evaluation of liver biopsies with steatosis requires careful histologic examination and correlation with clinical history, particularly regarding medications, nutrition status, and alcohol use. Examples of uniform reporting, including appropriate use of the nonalcoholic steatohepatitis Clinical Research Network Activity Score, are provided.

Background Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Microalbuminuria is the most popular method for detecting the early signs of DN. However, pathological changes occur before the onset of microalbuminuria. So, there is a need for another biomarkers that might provide a sensitive and fast means for identification of the progression of DN. Pentraxin 3 (PTX3) is an acute-phase glycoprotein and a soluble receptor acting as an opsonin. PTX3 protein is expressed in vascular endothelial cells and macrophages. Thereby, its levels may reflect more directly the inflammatory status of the vasculature. Aim Evaluation of the levels of serum and urinary PTX3 in type 2 diabetes mellitus (T2DM) patients and its relation to DN. Patients and methods Group A: 20 healthy volunteers (control group). Group B: 20 patients with normoalbuminuric T2DM. Group C: 20 patients with microalbuminuric T2DM. Group D: 20 patients with macroalbuminuric T2DM. Also all the participants divided into two subgroups: Group 1: 40 participants with no nephropathy (controls and normoalbuminuric patients). Group 2: 40 patients with nephropathy (microalbuminuric and macroalbuminuric patients). Results There was no significant difference among all studied groups with respect to age, sex, lipid profile, urinary PTX3, C-reactive protein, and liver function test. Whereas BMI, hemoglobin level, HBA1C, fasting blood sugar, postprandial blood sugar, serum creatinine, estimated glomerular filtration rate, and 24 h urinary albumin excretion; showed high significant difference among all studied groups. Serum albumin and total protein levels were highly significantly decreased in macroalbumiuric group as a result of proteinuria compared to the other three groups Serum PTX3 showed high significant difference between nephropathic (micro and macroalbuminuric) group and non nephropathic group (control and normoalbuminuric). There were highly significant positive correlations between serum PTX3 and (fasting blood sugar, postprandial blood sugar, HBA1C, and 24 h urinary albumin) significant positive correlation with serum creatinine, whereas there were highly significant negative correlations between serum PTX3 and serum total protein and serum albumin. Conclusion Serum PTX3 increased progressively with DN and may be a serum biomarker for early diagnosis of DN. Whereas urinary PTX3 has no relation to DN.

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ± 0.5 and 2.4 ± 0.4 respectively (P .001), and 3.4 ± 0.4 for metastases (P .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ± 3.0 for adverse group, 5.7 ± 2.7 for controls, and 4.1 ± 1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ

Alveolar soft part sarcoma (ASPS) is a rare soft tissue neoplasm generally affecting adolescents and young adults. Its unique histologic and ultrastructural features have been well-described; however, the cytopathological features of ASPS are less well-characterized, and recognition of this entity's features on cytologic preparations can ensure that the specimen adequacy and appropriate/rapid tissue allocation for additional testing. Herein we report a FNA case of ASPS with emphasis on cytomorphologic characteristics.

Stensen’s duct carcinoma (StDC) is an extremely rare neoplasm, with fewer than 40 cases reported in the literature. We report a unique case of primary StDC with papillary features and intestinal differentiation of a 74-year-old male. We discuss the radiologic and pathologic correlation along with the differential diagnosis of this rare entity.

Objectives We assess the diagnostic yield of repeat testing for C. difficile using molecular methods within 7 days of a negative test and identify specific factors associated with conversion from negative to positive test result within a 7-day period to aid in selective test utilization. Methods A retrospective chart review of 20,866 laboratory test orders for C. difficile PCR was conducted. The test result, clinicopathologic patient features, and previous test results were recorded. Univariate and multivariate analysis was conducted to compare patients with initial and repeat negative results (n = 248) to a group of patients with conversion from negative to positive results within 7 days. Results Univariate analysis demonstrated a history of C. difficile infection, receipt of antibiotics within 14 days, and duration of hospital stay as factors significantly different between patients with repeat negative and conversion to positive C. difficile test result. Only history of C. difficile infection was significantly different upon multivariate analysis. Conclusions Identification of prior C. difficile infection as the only factor significantly correlated with conversion from negative to positive C. difficile test result within 7 days aids in selective test utilization and reduces the costs associated with unnecessary laboratory testing.

Introduction: Angiosarcoma of the gastrointestinal tract is a rare, aggressive malignant neoplasm of vascular origin. Commonly, this tumor occurs due to metastases from other sites like the head and neck region and the soft tissue. When occurring as a primary tumor of the intestines, this entity poses a diagnostic dilemma due to its non-specific clinical presentation, coupled to its infiltrative features that may occur without an obvious lesion amenable to routine gastrointestinal interventions. The findings from an autopsy and surgical case with a brief review of its diagnostic features and relevant literature are discussed.Methods: We present a 73-year-old male with a history of a recent onset of gastrointestinal bleeding who was referred to our facility for persisting bleeding. He underwent endoscopy without an identifiable source of bleeding and subsequently received a colectomy at our facility, with repeated blood transfusions for persisting gastrointestinal bleeding. He was eventually transitioned to hospice and died shortly after presentation. A complete autopsy was performed.Results: There was anasarca with hemoperitoneum and intestinal intraluminal blood. Present in the small intestinal mucosa were three hemorrhagic nodules. Histologically, the nodules demonstrated medium to large epithelioid vasoformative neoplastic cells infiltrating through the wall of the small intestine and extending to the omentum. The findings from the gross and histology examination, as well as the immunohistochemical stains were consistent with an epithelioid angiosarcoma.Conclusion: Primary epithelioid angiosarcoma of the intestine is an uncommon aggressive tumor that poses a diagnostic challenge. Although rare, this diagnosis needs to be considered in patients with intractable gastrointestinal bleeding. Due to its morphologic overlap with other benign and malignant neoplasms, the use of ancillary testing during histologic examination is key in arriving at an accurate diagnosis.

ObjectivesTo investigate concussion injury rates, the likelihood of sustaining concussion relative to the number of rugby union matches and the risk of subsequent injury following concussion.MethodsA four-season (2012/2013–2015/2016) prospective cohort study of injuries in professional level (club and international) rugby union. Incidence (injuries/1000 player-match-hours), severity (days lost per injury) and number of professional matches conferring a large risk of concussion were determined. The risk of injury following concussion was assessed using a survival model.ResultsConcussion incidence increased from 7.9 (95% CI 5.1 to 11.7) to 21.5 injuries/1000 player-match-hours (95% CI 16.4 to 27.6) over the four seasons for combined club and international rugby union. Concussion severity was unchanged over time (median: 9 days). Players were at a greater risk of sustaining a concussion than not after an exposure of 25 matches (95% CI 19 to 32). Injury risk (any injury) was 38% greater (HR 1.38; 95% CI 1.21 to 1.56) following concussion than after a non-concussive injury. Injuries to the head and neck (HR 1.34; 95% CI 1.06 to 1.70), upper limb (HR 1.59; 95% CI 1.19 to 2.12), pelvic region (HR 2.07; 95% CI 1.18 to 3.65) and the lower limb (HR 1.60; 95% CI 1.21 to 2.10) were more likely following concussion than after a non-concussive injury.ConclusionConcussion incidence increased, while severity remained unchanged, during the 4 years of this study. Playing more than 25 matches in the 2015/2016 season meant that sustaining concussion was more likely than not sustaining concussion. The 38% greater injury risk after concussive injury (compared with non-concussive injury) suggests return to play protocols warrant investigation.

Objective To assess the possibility of using cytological examination and DNA image-analysis of testicular fine-needle aspirates instead of open surgical biopsy in the investigation of infertile men, as testicular biopsy has long been used for investigating infertility but the interpretation of histological slides is usually subjective. Patients and methods Thirty-three men (aged 22–36 years) were evaluated for infertility and underwent both open biopsy and fine-needle aspiration of their testes. Subsequently, the needle aspirates were assessed histopathologically and cytologically, and by DNA image cytometry. The percentages of haploid, diploid and tetraploid cells were determined for each patient. Results The cases were divided into four categories: (1) Complete spermatogenesis, with a DNA pattern of 1n > 2n > 4n; (2) Maturation arrest, with a DNA pattern of 2n > 4n with no haploid cells; (3) Sertoli cell-only syndrome, with a DNA pattern of only 2n, with no haploid or tetraploid cells; (4) Hypospermatogenesis, with a variable DNA pattern, i.e. mild with 1n > 2n, moderate with 2n > 1n > 4n, and marked where the DNA pattern was 2n > 4n > 1n. From the cytological and DNA image-analysis of the aspirate a diagnosis was possible that had a strong correlation with the histological diagnosis of the same case. From image analysis we could exclude interstitial cells, Sertoli cells and sperms on the static image, and differentiate between spermatozoa and spermatids based on morphological characteristics in the cytological smear. This technique can therefore be used to quantitatively determine the percentages of various cell types within the seminiferous tubules. By coupling image ploidy analysis and cytological examination of a cytological smear, spermatogenesis can be assessed accurately. Conclusion Image cytometry could be used to exclude interstitial cells, Sertoli cells and sperms on the static image and so produce an accurate assessment of spermatogenesis. A combination of ploidy and cell morphology characteristics in cytological smears provides an accurate, reproducible and easily used alternative to open testicular biopsy.

Objectives: PD-L1/PD-1 expression has been identified in a subset of colorectal cancers, but evaluation in precursor colorectal polyps has not been performed. Our goal was to evaluate the expression of PD-1/PD-L1 in colon polyps to better understand the role in colorectal carcinogenesis. Methods: A tissue microarray consisting of 16 tubulovillous adenomas (TVAs), 10 traditional serrated adenomas (TSAs), and 27 tubulovillous adenomas with …

As the most common and most important cancer of the pancreas, with rapid mortality and now also as the third leading cause of cancer-related deaths in the United States, pancreatic ductal adenocarcinoma (PDAC) has become synonymous with "pancreas cancer". PDAC is also the prototype of the "pancreatobiliary-type" adenocarcinomas, along the biliary tract, ampullary and gallbladder cancers with the similar morphology and behavior. Recent molecular profiling studies have identified distinct subsets of PDAC, potentially with different behaviors and targetability. Moreover, while PDAC is by far the most common cancer of the pancreas, there are various other types that occur in this organ and are erroneously classified together with PDAC. Many of these have different molecular and biologic characteristics that warrant their management separately although they are also technically "pancreatic cancers". While some are closely related to PDAC and have as aggressive behavior (such as adenosquamous carcinomas which are recently recognized under "basal" like category in profiling studies, which are actually even worse prognostically than PDACs), in the meantime, others such as colloid carcinoma has a much better behavior than PDAC, and as a carcinoma with intestinal lineage (MUC2/CDX2) colloid carcinoma may require an entirely different treatment approach as well. Similarly, medullary carcinomas also appear to have different biology. Additionally, non-ductal cancers such as acinar, neuroendocrine, solid-pseudopapillary neoplasms and pancreatoblastoma have their respective clinicopathologic and molecular associations and warrant careful elimination in the management and study protocols. Another very problematic aspect in the classification of "pancreas cancer" is its delineation from the cancers of neighboring organs, in particular, ampullary/duodenal and common bile duct (CBD) cancers, for which recently more refined criteria have been provided. Additionally, the possibility of metastasis from another site and lymphomas also need to be considered. In summary, there is a whole host of cancers that occur in the pancreas that ought to be considered carefully before a case is classified as an ordinary "pancreas cancer" (PDAC).

Four types of impotence were diagnosed in 75 consecutive impotent diabetic patients: chronic persistent organic type due to vascular and/or neurologic factors (44%), temporary organic types due to medical illness other than diabetes (10.6%) or uncontrolled metabolic state (6.6%), and psychogenic impotence (38.6%). Despite higher incidence of organic etiology (61.3%) the incidence of psychogenic impotence was significant. None of the methods used to diagnose the type of impotence in the present study proved 100 per cent accurate, and we advise a combination of history-taking including the wife's history, physical examination including vascular and neurologic tests, nocturnal penile tumescence studies, and therapeutic trials with sex therapy to differentiate between true organic, temporary organic, and psychogenic types of impotence in diabetic patients. This differentiation is mandatory since the latter two types may have a better prognosis.