Histological Definition Research Articles

Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC. Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing. Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.

Diagnosis and classification of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis: Current concepts and remaining challenges

The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining "non-alcoholic"; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.

Incidence of discordant temporal artery biopsy in the diagnosis of giant cell arteritis

ObjectiveWe investigated the rate of discordant biopsy results (i.e., 1 side negative, 1 side positive) in patients who underwent initial bilateral temporal artery biopsies for suspected giant cell arteritis (GCA). DesignA cohort study. ParticipantsConsecutive patients undergoing temporal artery biopsy were enrolled. Of the 259 patients enrolled, 250 underwent initial bilateral temporal artery biopsies. MethodsPositive biopsies were defined based on accepted histologic definitions. Healed arteritis was considered a positive result. Clinical information was collected for all patients using a questionnaire administered by an ophthalmologist. Pathology results, including biopsy length (as measured by the pathologist), and laboratory information (i.e., serum erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] levels) were collected from digital patient records for statistical analysis. The main outcome was the rate of discordant biopsy in consecutive patients who underwent initial bilateral temporal artery biopsy. ResultsGiant cell arteritis was confirmed in 62 (24.2%) of the 250 patients, including 3 patients with biopsies recorded as healed arteritis. The rate of discordant biopsy was 4.4% with 11 unilaterally positive biopsies. There was no statistical difference between the length of the left- and right-sided biopsies in either the unilaterally or bilaterally positive groups (p = 0.13 and p = 0.79, respectively). The average maximum ESR value for the bilateral group (58.7 mm/h) was significantly higher than the average maximum ESR value for the unilateral group (30.7 mm/h, p = 0.03). The average maximum CRP value for the bilateral group was 59.2 mg/L and 28.6 mg/L for the unilateral group (p = 0.30). Discordance between the localization of symptoms and the side of positive biopsy occurred in 3 patients (i.e., 3 patients had left-sided symptoms only, yet a right-sided positive biopsy). ConclusionsThe rate of discordant biopsies in patients who underwent initial bilateral temporal artery biopsies was considerable in our patient cohort. Given this reasonably high rate of discordance between sides, as well as the lack of correlation between side of positivity and laterality of presenting symptoms, we recommend initial bilateral temporal artery biopsies to enhance the diagnostic certainty of the disease.

Development of new criteria for cortical bone histomorphometry in femoral neck: intra- and inter-observer reproducibility

Histomorphometry is commonly applied to study bone remodeling. Histological definitions of cortical bone boundaries have not been consistent. In this study, new criteria for specific definition of the transitional zone between the cortical and cancellous bone in the femoral neck were developed. The intra- and inter-observer reproducibility of this method was determined by quantitative histomorphometry and areal overlapping analysis. The undecalcified histological sections of femoral neck specimens (n=6; from men aged 17-59years) were processed and scanned to acquire histological images of complete bone sections. Specific criteria were applied to define histological boundaries. "Absolute cortex area" consisted of pure cortical bone tissue only, and was defined mainly based on the size of composite canals and their distance to an additional "guide" boundary (so-called "preliminary cortex boundary," the clear demarcation line of density between compact cortex and sparse trabeculae). Endocortical bone area was defined by recognizing characteristic endocortical structures adjacent to the preliminary cortical boundary. The present results suggested moderate to high reproducibility for low-magnification parameters (e.g., cortical bone area). The coefficient of variation (CV %) ranged from 0.02 to 5.61 in the intra-observer study and from 0.09 to 16.41 in the inter-observer study. However, the intra-observer reproducibility of some high-magnification parameters (e.g., osteoid perimeter/endocortical perimeter) was lower (CV %, 0.33-87.9). The overlapping of three histological areas in repeated analyses revealed highest intra- and inter-observer reproducibility for the absolute cortex area. This study provides specific criteria for the definition of histological boundaries for femoral neck bone specimens, which may aid more precise cortical bone histomorphometry.

Gastritis and gastropathy

Alterations of the stomach mucosa in response to different adverse effects result in various morphological and clinical symptoms. Gastric mucosa alterations can be classified on the bases of diverse viewpoints. It makes this overview difficult, that identical toxic effects may cause different mucosal changes and different toxic agents may produce similar mucosal appearance. The more accurate understanding of the pathological processes which develop in the stomach mucosa needs reconsideration. The authors make an attempt to define gastritis and gastropathy in order to classify and present their features. Gastritis is a histological definition indicating mucosal inflammation. Acute gastritis is caused by infections. The two most important forms of chronic gastritis are metaplastic atrophic gastritis with an autoimmune origin and Helicobacter pylori inflammation. Gastropathy is the name of different structural alterations of the mucosa. Its most important feature is the paucity of inflammatory signs. Gastropathies can be divided into 4 categories based on the nature of the underlying pathological effect, on its morphological appearance and the way of the development. Differential diagnosis is an important pathological and clinical task because different treatment methods and prognosis.

A Finite Element Model for Recognizing Breast Cancer

Breast cancer recognition is an important issue in elastography diagnostic imaging. Breast tumor biopsy has been for many years the reference procedure to assess histological definition for breast diseases. But biopsy measurement is an invasive method besides it takes larger time. So, fast and improved methods are needed. Using elastography technology, a digital image correlation technique can be used to calculate the displacement of breast tissue after it has suffered a compression force. This displacement is related to tissue stiffness, and breast cancer can be classified into benign or malignant according to that displacement. The value of compression force affects the displacement of tissue, and then affects the results of the breast cancer recognition. Finite element method was being used to simulate a model for the breast cancer as a phantom to be used in measurements and study of breast cancer diagnosis. The breast cancer using this phantom can be recognized within a short time. The proposed work succeeded in recognizing breast tumor phantom by an average correct recognition ratio CRR of about 94.25% on a simulation environment. The strain ratio SR for benign and malignant models is also computed. The result of the simulated breast tumor model is compared with real data of 10 lesion cases (6 benign and 4 malignant). The coefficient of variation CV between the simulated SR and the SR using real data reaches to about 5% for benign lesions and 4.78% for malignant lesions. The results of CRR and CV in this proposed work assure that the proposed breast cancer model using finite element modeling is a robust technique for breast tumor simulation where the behavior of real data of breast cancer can be predicted.

Transplant Glomerulopathy: The Interaction of HLA Antibodies and Endothelium

Transplant glomerulopathy (TG) is a major cause of chronic graft dysfunction without effective therapy. Although the histological definition of TG is well characterized, the pathophysiological pathways leading to TG development are still poorly understood. Electron microscopy suggests an earlier appearance of TG and suggests that endothelial cell injury is the first sign of the disease. The pathogenic role of human leukocyte antigen (HLA) antibodies in endothelial cells has been described in acute vascular and humoral rejection. However the mechanisms and pathways of endothelial cell injury by HLA antibodies remain unclear. Despite the description of different causes of the morphological lesion of TG (hepatitis, thrombotic microangiopathy), the strong link between TG and chronic antibody mediated rejection suggests a major role for HLA antibodies in TG formation. In this review, we describe the effect of classes I or II HLA-antibodies in TG and especially the implication of donor specific antibodies (DSA). We update recent studies about endothelial cells and try to explain the different signals and intracellular pathways involved in the progression of TG.

Eyes wide shut: the illusory tale of 'occult' microscopic endometriosis

The visual appearance of endometriosis is important because every intellectual and therapeutic process begins with a surgeon identifying disease. Inaccurate identification of disease can introduce selection bias at a firstorder level and confound all conclusions, leading to inaccurate concepts of epidemiology, natural history, disease origin and treatment. David B. Redwine, M.D. (1990) In this issue of Human Reproduction, Khan et al. (2013) revive the debate on the existence and clinical relevance of invisible microscopic endometriosis (IME)—now renamed by them as occult microscopic endometriosis (OME). They report new evidence for immunoreactive microscopic endometriosis in visually normal peritoneum during laparoscopy, as well as an incidence of OME, which is higher than that reported in previous laparoscopic studies of visually normal peritoneum (Redwine, 1988a; Redwine and Yocom, 1990; Nezhat et al., 1991). It is important to outline the concepts central to any discussion on OME— namely, the definition of OME, the criteria and methodology employed to identify visually normal peritoneum, and the definition of endometriosis applied in judging the presence or absence of disease in the biopsied tissue. In defining OME an important distinction must be drawn between failure to recognize visually detectable areas of disease and the presence of microscopic disease that truly cannot be visually detected by the laparoscope. Recognition of the complete morphological repertoire of endometriosis, in all its protean presentations, and the utilization of welldefined criteria and methodology to detect all areas of visually abnormal peritoneum are paramount. Doing so ensures that contributions to the IME/OME literature are internally valid, reproducible and can be critically evaluated within the context of the existing body of research. Moreover, consensus is needed as to the histological definition of endometriosis. If different authors apply ever-broader definitions of disease, there is a risk of defining endometriosis into existence from any histologic appearance. The concept of OME is of importance not only in predicting the outcomes and clinical utility of the complete surgical excision of endometriosis but also has far-reaching implications regarding disease phenomenology, pathogenesis and prognosis as indicated in the historical quote introduced in this editorial (Redwine, 1990). How confused has the endometriosis literature become by virtue of incomplete identification of disease? Murphy et al. (1986) introduced the concept of OME in, reporting microscopic disease in visually normal peritoneum in 25% of a series of 20 patients undergoing laparotomy for endometriosis. This prevalence of OME remains to this day the highest rate ever reported. No formal criteria for normal peritoneum were used in that study, however, and the peritoneal surfaces were viewed at arm’s length and with the limited illumination attendant to laparotomy. Subsequent studies conducted via

Foreword to special issue on “Myocarditis”

William Osler, with a very actual sentence, stated, back in year 1892, in its Medicine textbook: ‘‘There are three phases to treatment: diagnosis, diagnosis and diagnosis’’ [1]. This sentence clearly highlights that the best clinical management is based upon the most accurate diagnosis. Historically myocarditis has being considered a rare and poorly understood condition, a conundrum with polymorphic clinical presentation and variable prognosis ranging from spontaneous resolution to progressive heart failure and death. The first comprehensive review with a modern approach to etiopathogenesis was published in 1980 by Woodroof JF, who highlighted the possible etiological role of Coxsackie viruses and of the immune system in the progression of cardiac damage, with possible evolution to a dilated cardiomyopathy [2]. A major advance in diagnosis was the refinement of the endomyocardial biopsy technique using the King’s bioptome by Richardson [3]. Another important step was the development of a consensus pathological classification and histological definition of myocarditis by endomyocardial biopsy, known as the Dallas criteria [4]. Meanwhile, the first experimental observations were made by several investigators, suggesting a possible involvement of autoimmune mechanisms to cardiac autoantigens; in particular, a mouse model for myosin-induced autoimmune myocarditis was described by the Neu et al. [5]. In addition, various groups in the late 80s and early 90s reported the presence of circulating anti-heart autoantibodies against myosin as well as other autoantigens in acute and chronic myocarditis or dilated cardiomyopathy, in keeping with the hypothesis of autoimmunity being involved in a subset of patients [6–14]. A retrospective multicenter registry from the USA coordinated by Cooper et al. [15] reported the efficacy of immunosuppressive therapy in a rare but lethal form of myocarditis, e.g., giant cell myocarditis. On these premises, the multicenter Myocarditis Treatment Trial was designed using the Dallas criteria to recruit myocarditis patients to 6 months immunosuppression; the therapy with azathioprine and prednisone or cyclosporine A and prednisone was well tolerated, and no significant effect on survival was observed, although the study was not powered to detect differences in survival [16]. The results of the trial had a profoundly negative effect in the next decade on the use of endomyocardial biopsy to detect and treat myocarditis. However, researchers developed new diagnostic tools to be added to standard histology, in particular immunohistochemistry, to increase sensitivity of endomyocardial biopsy particularly in focal and chronic myocarditis and characterize the number and type of infiltrating inflammatory cells, and molecular detection of genomic material of infectious agents mainly by polymerase chain reaction (PCR), to diagnose infectious, particularly viral myocarditis [17–24]. This work leads to another major step forward, e.g., the 1995 WHO classification of cardiomyopathies, with the acknowledgment that myocarditis is diagnosed on endomyocardial biopsy by established histological, immunological and immunohistochemical criteria; molecular techniques on EMB were recommended to identify viral etiology [25]. In the WHO classification, infectious, autoimmune and idiopathic forms of myocarditis are recognized that may lead to dilated cardiomyopathy [25]. Using serum cardiac autoantibody testing as well as histology, immunohistology and viral PCR on endomyocardial biopsy, it is nowadays possible to define distinct etiopathogenetic A. L. P. Caforio (&) Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, Centro ‘‘V. Gallucci’’, University of Padova-Policlinico, Via Giustiniani, 2, 35128 Padua, Italy e-mail: alida.caforio@unipd.it

A Basosquamous Cell Carcinoma of the Periorbital Region Arising From a Chronic Wound Created by Laser Ablation of a Basal Cell Carcinoma

Basosquamous cell carcinomas (BSCs) are very rare and behave aggressively, with features of both basal cell carcinoma and squamous cell carcinoma. The diagnosis of BSC includes a spectrum of histologic definitions, ranging from coexistence of basal cell carcinoma and squamous cell carcinoma with or without a transition zone, to any basal cell carcinoma with evidence of keratinization.A 63-year-old man presented with a BSC within a chronic periorbital wound, which was confirmed through a postoperative histologic examination. The wound was created from a previous laser ablation of a diagnosed basal cell carcinoma. The BSC was excised without causing any deformity, and coverage of the defect was obtained using a local perforator-based flap. No recurrence was observed during a 5-month follow-up.

Atherosclerotic Plaque Composition and Classification Identified by Coronary Computed Tomography

Background— Computed tomography (CT) is used routinely for coronary angiography, and higher-risk features of plaques can also be identified. However, the ability of CT to discriminate individual plaque components and classify plaques according to accepted histological definitions is unknown. Methods and Results— We first determined CT attenuation ranges for individual plaque components using combined in vivo CT coregistered with virtual histology intravascular ultrasound (VH-IVUS) in 108 plaques from 57 patients. Comparison with contrast attenuation created plaque/contrast attenuation ratios that were significantly different for each component. In a separate validation cohort of 47 patients, these Plaque Maps correlated significantly with VH-IVUS–determined plaque component volumes (necrotic core: r =0.41, P =0.002; fibrous plaque: r =0.54, P &lt;0.001; calcified plaque: r =0.59, P &lt;0.001; total plaque: r =0.62, P &lt;0.001). We also assessed VH-IVUS and CT Plaque Maps against coregistered histology in 72 (VH-IVUS) and 87 (CT) segments from 8 postmortem coronary arteries. The diagnostic accuracy of CT to detect calcified plaque (83% versus 92%), necrotic core (80% versus 65%), and fibroatheroma (80% versus 79%) was comparable with VH-IVUS. However, although VH-IVUS could identify thin-cap fibroatheromas (TCFA) with a diagnostic accuracy of between 74% and 82% (depending on the TCFA definition used), the spatial resolution of CT prevented direct identification of TCFA. Conclusions— CT-derived Plaque Maps based on contrast-adjusted attenuation ranges can define individual plaque components with a similar accuracy to VH-IVUS ex vivo. However, coronary CT Plaque Maps could not reliably classify plaques and identify TCFA, such that high-risk plaques may be misclassified or overlooked.

Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC.

Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. To determine whether tumour thickness in sBCC is a predictor of treatment failure. We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.

Interstitial lung disease in children

Children's interstitial lung disease (ILD) includes a wide range of rare respiratory disorders associated with high morbidity and mortality.Genetic factors, systemic disease processes, nonspecific inflammatory or fibrotic patterns of repair seen in a number of clinical settings are involved in the ILD pathogenesis.Specific disorders more prevalent in young children include diffuse developmental disorders, alveolar growth abnormalities, genetic surfactant disorders, pulmonary interstitial glycogenosis and neuroendocrine cell hyperplasia of infancy.It may be difficult to recognize these entities and this can lead to delayed treatment. The diagnostic approach is based on a combination of history/physical examinations, imaging studies, pulmonary function testing, genetic testing, bronchoalveolar lavage (BAL) and in most cases an open lung biopsy.Although some disease types overlap with those seen in adults, in this review emphasis is placed on entities unique to the pediatric population focusing on clinical characteristics, histologic definitions, radiologic–pathologic correlation and therapeutic strategies.

Dense Pattern of Embryonal Rhabdomyosarcoma, a Lesion Easily Confused With Alveolar Rhabdomyosarcoma

To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology. We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children's Oncology Group study D9803, comparing histopathology with fusion status. Our review of 255 original ARMS cases (compared with a control group of 38 embryonal rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS. To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.

Histologic definition of gastro-esophageal reflux disease

To review recent data supporting the development of new histology-based definitions of gastro-esophageal reflux disease (GERD). Three precisely definable columnar epithelial types--cardiac, oxyntocardiac and intestinal--may be interposed between esophageal squamous epithelium and gastric oxyntic (acid secreting) mucosa. This enables definition of a new histologic concept: the squamo-oxyntic gap. The squamo-oxyntic gap is zero or very small in autopsies performed on patients without evidence of GERD. The gap progressively increases in length with the severity of GERD, indicating that the squamo-oxyntic gap is a marker for chronic GERD. The distal part of the gap lines gastric-type rugal folds and, therefore, is distal to the present endoscopic definition of the gastro-esophageal junction. I contend that this distal gap segment (which has esophageal submucosal glands) is actually the dilated distal esophagus; this is the pathologic correlate of destruction of the abdominal segment of the lower esophageal sphincter. The dilated distal esophagus is mistaken for 'gastric cardia' by present endoscopic definitions. I believe that these data support the adoption of novel histologic definitions of GERD as follows: the presence of any squamo-oxyntic gap defines GERD; the length of the gap is a measure of severity of chronic GERD; and the presence of intestinal metaplasia in the gap defines Barrett esophagus and cancer risk.

MicroRNA Expression Profiling in the Histological Subtypes of Barrett's Metaplasia

OBJECTIVES:The histological definition of Barrett's esophagus (BE) is debated, particularly regarding the phenotype of its metaplastic columnar epithelium. Histologically proven intestinal metaplasia (IM) was the sine qua non condition for a diagnosis of BE but, more recently, non-intestinalized (i.e., cardiac gastric-type; GM) columnar metaplasia has been re-included in the spectrum of Barrett's histology. MicroRNAs modulate cell commitment, and are also reportedly dysregulated in Barrett's carcinogenesis. This study investigates miRNA expression in the histological spectrum of esophageal columnar metaplastic changes, specifically addressing the biological profile of GM vs. IM.METHODS:A study was performed to discover microRNA microarray in 30 matching mucosa samples obtained from 10 consecutive BE patients; for each patient, biopsy tissue samples were obtained from squamous, GM and intestinalized epithelium. Microarray findings were further validated by qRT-PCR analysis in another bioptic series of 75 mucosa samples.RESULTS:MicroRNA profiling consistently disclosed metaplasia-specific microRNA signatures. Six microRNAs were significantly dysregulated across the histological phenotypes considered; five of them (two overexpressed (hsa-miR-192; -miR-215) and three under-expressed (hsa-miR-18a* -miR-203, and -miR-205)) were progressively dysregulated in the phenotypic sequence from squamous to gastric-type, to intestinal-type mucosa samples.CONCLUSIONS:A consistent microRNA expression signature underlies both gastric- and intestinal-type esophageal metaplasia. The pattern of microRNA dysregulation suggests that GM may further progress to IM. The clinico-pathological implications of these molecular profiles prompt further study on the “personalized” cancer risk associated with each of these metaplastic transformations.

Dysplastic Nevi and Melanoma

Dysplastic nevi are described as being on a continuum between common acquired nevi and melanoma because they are morphologically and biologically intermediate between these 2 entities. Since initially being reported as histologic lesions observed in melanoma-prone families, there has been considerable debate about the definition of dysplastic nevi, the histologic and clinical criteria used to define them, and their biologic importance. Their role as precursor lesions for melanoma is not their primary role in their relationship to melanoma because of the rarity of transformation of any individual nevus to a melanoma. Although there is still no single, universally agreed upon histologic or clinical definition or even name for these nevi, dysplastic nevi should be considered important because of their association with an increased risk for melanoma.

Liver fibrosis recognition using multi-compression elastography technique

Liver fibrosis recognition is an important issue in diagnostic imaging. The accurate estimation of liver fibrosis stages is important to establish prognosis and to guide appropriate treatment decisions. Liver biopsy has been for many years the reference procedure to assess histological definition for liver diseases. But biopsy measurement is an invasive method besides it takes large time. So, fast and improved methods are needed. Using elastography technology, a correlation technique can be used to calculate the displacement of liver tissue after it has suffered a compression force. This displacement is related to tissue stiffness, and liver fibrosis can be classified into stages according to that displacement. The value of compression force affects the displacement of tissue and so affects the results of the liver fibrosis diagnosing. By using finite element method, liver fibrosis can be recognized directly within a short time. The proposed work succeeded in recognizing liver fibrosis by a percent reached in average to 86.67% on a simulation environment.

Cholestatic hepatitis C following liver transplantation: An outcome-based histological definition, clinical predictors, and prognosis

Cholestatic hepatitis C virus (HCV) is a rare form of recurrent HCV following liver transplantation (LT) without specific diagnostic criteria. An outcome-based method to improve its diagnosis and a description of its prognosis are needed. All 1-year post-LT protocol liver biopsy samples and biopsy samples initially reported to show cholestatic HCV from patients transplanted with HCV between February 2002 and December 2009 were reviewed for the inflammation grade, the fibrosis stage, and 4 cholestatic HCV features: ductular proliferation, canalicular cholestasis with or without intracellular cholestasis, hepatocyte swelling with or without lobular disarray, and sinusoidal/pericellular fibrosis. We used patient and graft survival to define histological criteria for cholestatic HCV, and compared the clinical features of these patients to those of patients with minimal or significant post-LT fibrosis. One hundred seventy-nine patients were analyzed, the median age was 56 years, and 73% were male. Patients with 3 or more of the 4 cholestatic HCV criteria had significantly worse survival (log-rank P < 0.001) regardless of the fibrosis stage, and this was used as our novel definition of cholestatic HCV. Using this definition, we found that 27 patients (15%) had cholestatic HCV, 53 (30%) had significant fibrosis (stage ≥ 2/4), and 99 (55%) had minimal fibrosis (stage < 2/4). The final model for clinical predictors of cholestatic HCV included donor age [odds ratio (OR) = 1.37 per decade, P = 0.04] and previous rejection (Banff grade ≥ 5; OR = 4.19, P = 0.002). Total bilirubin was the strongest laboratory predictor of cholestatic HCV (area under the curve = 0.93), whereas the HCV viral load was not a significant predictor. The final model of post-LT survival included the pathology group {cholestatic HCV [hazard ratio (HR) = 6.07, P < 0.001] and significant fibrosis (HR = 2.53, P = 0.02)}, donor age (HR = 1.49 per decade, P < 0.001), and cold ischemia time (HR = 1.11 per hour, P = 0.02). In conclusion, we propose diagnostic criteria for cholestatic HCV that include specific criteria (the presence of at least 3 of the 4 histopathological features on biopsy) and other supportive and exclusionary criteria. Older donor age and rejection increase the risk of cholestatic HCV, and an elevation in the total bilirubin level may help to identify these patients. These criteria must be validated prospectively.

Are Neuroendocrine Tumors Going Mainstream?

Are Neuroendocrine Tumors Going Mainstream?