Imaging and pathological discordance amongst the plethora of breast lesions in breast biopsies.

INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.

Enhancing Interrogation of Skeletal Muscle Samples for Informative Quantitative Data.

Careful quantitative analysis of histological preparations of muscle samples is crucial to accurate investigation of myopathies in man and of interpretation of data from animals subjected to experimental or potentially therapeutic treatments. Protocols for measuring cell numbers are subject to problems arising from biases associated with preparative and analytical techniques. Prominent among these is the effect of polarized structure of skeletal muscle on sampling bias. It is also common in this tissue to collect data as ratios to convenient reference dominators, the fundamental bases of which are ill-defined, or unrecognized or not accurately assessable. Use of such 'floating' denominators raises a barrier to estimation of the absolute values that assume practical importance in medical research, where accurate comparison between different scenarios in different species is essential to the aim of translating preclinical research findings in animal models to clinical utility in Homo sapiens.This review identifies some of the underappreciated problems with current morphometric practice, some of which are exacerbated in skeletal muscle, and evaluates the extent of their intrusiveness into the of building an objective, accurate, picture of the structure of the muscle sample. It also contains recommendations for eliminating or at least minimizing these problems. Principal among these, would be the use of stereological procedures to avoid the substantial counting biases arising from inter-procedure differences in object size and section thickness.Attention is also drawn to the distortions of interpretation arising from use of undefined or inappropriate denominators.

Effectiveness Regarding Hantavirus Detection in Rodent Tissue Samples and Urine.

The natural hosts of Orthohantaviruses are rodents, soricomorphs and bats, and it is well known that they may cause serious or even fatal diseases among humans worldwide. The virus is persistent among animals and it is shed via urine, saliva and feces throughout the entirety of their lives. We aim to identify the effectiveness of hantavirus detection in rodent tissue samples and urine originating from naturally infected rodents. Initially, animals were trapped at five distinct locations throughout the Transdanubian region in Hungary. Lung, liver, kidney and urine samples were obtained from 163 deceased animals. All organs and urine were tested using nested reverse transcription polymerase chain reaction (nRT-PCR). Furthermore, sera were examined for IgG antibodies against Dobrava-Belgrade virus (DOBV) and Puumala virus (PUUV) by Western blot assay. IgG antibodies against hantaviruses and/or nucleic acid were detected in 25 (15.3%) cases. Among Apodemus, Myodes, and Microtus rodent species, DOBV, PUUV and Tula virus (TULV) were clearly identified. Amid the PCR-positive samples, the nucleic acid of the viruses was detected most effectively in the kidney (100%), while only 55% of screened lung tissues were positive. Interestingly, only three out of 20 rodent urine samples were positive when tested using nRT-PCR. Moreover, five rodents were seropositive without detectable virus nucleic acid in any of the tested organs.

International Histopathology Consensus for Unilateral Primary Aldosteronism.

OBJECTIVE: Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). CONTEXT: Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. PATIENTS AND METHODS: Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. RESULTS: Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. CONCLUSION: The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

Examination of total hip and knee arthroplasty tissues.

BACKGROUND: Many practices require tissues from hip and knee arthroplasty procedures to be sent for pathologic examination. These examinations rarely provide information beyond the clinical or radiologic diagnosis and rarely alter clinical management. We aimed to determine the rate at which histologic diagnoses based on gross assessment alone or gross plus microscopic assessment correspond with reported clinical diagnoses in patients undergoing total joint arthroplasties and whether the histologic diagnoses alter patient management. METHODS: We retrospectively reviewed arthroplasty cases performed at a high-volume teaching hospital in Manitoba, Canada. The clinical diagnosis was compared with the final pathology report based on gross examination, with or without histologic assessment. The results of the comparison were classified into 3 categories: concordant (same diagnosis), discrepant (different diagnoses without alterations in management) and discordant (different diagnoses resulting in management change). The overall provincial cost for pathologic examination was determined by multiplying the total examination cost by the estimated number of arthroplasty cases. RESULTS: There were 773 patients in our study sample. The concordant rate was 98.3% (95% confidence interval [CI] 97.1%-99.1%), the discrepant rate was 1.7% (95% CI 0.9%-2.9%) and the discordant rate was 0.0% (95% CI 0%-0.5%) for 773 cases. The pathology diagnosis did not alter patient management in any case. A total of 91.5% of specimens did not require full histologic review and received gross descriptions only. The discrepancy rate was higher in cases that included microscopic examination than in those that received only gross descriptions (15.2% v. 0.4%, p < 0.001). The overall provincial cost for pathologic examination was estimated at Can$304 556. CONCLUSION: Submitting routine tissue from arthroplasty procedures to pathology does not affect patient management and therefore provides no value for the health care resources expended in doing so.

CONTEXTE: Beaucoup d'établissements exigent que des tissus soient envoyés pour un examen anatomopathologique après une arthroplastie de la hanche et du genou. Ces examens n'apportent généralement pas d'information nouvelle quant au diagnostic clinique ou radiologique et modifient rarement la prise en charge. Notre objectif était de déterminer le pourcentage de correspondance entre les diagnostics histologiques fondés sur l'inspection grossière uniquement ou sur l'inspection grossière et l'examen au microscope, et les diagnostics cliniques des patients qui subissent des arthroplasties totales. Nous cherchions également à savoir si les diagnostics histologiques modifient la prise en charge. MÉTHODES: Nous avons procédé à une analyse rétrospective d'arthroplasties effectuées dans un grand hôpital universitaire du Manitoba, au Canada. Le diagnostic clinique était comparé au rapport final de pathologie fondé sur une inspection grossière, avec ou sans examen histologique. Les résultats de cette comparaison étaient classés en 3 catégories : concordance (même diagnostic), divergence (diagnostics différents, sans modification de la prise en charge) et discordance (diagnostics différents entraînant une modification de la prise en charge). Le coût global pour la province associé aux examens pathologiques a été établi en multipliant le coût total d'un examen par le nombre estimé de cas d'arthroplastie. RÉSULTATS: Notre échantillon comprenait 773 patients. Le taux de concordance était de 98,3 % (intervalle de confiance [IC] de 95 % 97,1 %­99,1 %), le taux de divergence était de 1,7 % (IC de 95 % 0,9 %­2,9 %) et le taux de discordance de 0,0 % (IC de 95 % 0 %­0,5 %). Dans tous les cas, le diagnostic pathologique n'a pas modifié la prise en charge. Au total, 91,5 % des spécimens ne nécessitaient pas d'examen histologique complet et n'ont fait l'objet que d'une inspection grossière. Le pourcentage d'anomalie était plus élevé pour les spécimens analysés au microscope que pour ceux ayant uniquement subi une inspection grossière (15,2 % c. 0,4 %, p < 0,001). Le coût total des examens pathologiques pour la province a été estimé à 304 556 $ CA. CONCLUSION: L'analyse pathologique systématique de tissus prélevés lors d'arthroplasties n'entraîne pas une modification de la prise en charge du patient; il n'y a donc pas de valeur associée aux ressources de santé utilisées pour ces examens.

Evaluating the optimum number of biopsies to assess histological inflammation in ulcerative colitis: a retrospective cohort study.

BACKGROUND: The optimal ulcerative colitis biopsy protocol is unclear. AIM: To evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitis METHODS: Biopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4-biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item-level ratings from four biopsies, was compared to 1-, 2- and 3-biopsy estimates. Agreement was determined using bivariate errors-in-variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed. RESULTS: Forty-six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2-biopsy (tolerance interval: -7.66, 4.79) and 3-biopsy (tolerance interval: -4.86, 3.46) RHI scores demonstrated acceptable agreement with 4-biopsy scores. One-biopsy scores demonstrated unacceptable agreement (tolerance interval: -13.99, 7.78). Mean RHI scores using the 2-, 3- and 4-biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1-biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2-, 3- and 4-biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1). CONCLUSIONS: A minimum of two - conservatively, three - biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.

On the cortical connectivity in the macaque brain: A comparison of diffusion tractography and histological tracing data.

Diffusion-weighted magnetic resonance imaging (DW-MRI) tractography is a non-invasive tool to probe neural connections and the structure of the white matter. It has been applied successfully in studies of neurological disorders and normal connectivity. Recent work has revealed that tractography produces a high incidence of false-positive connections, often from "bottleneck" white matter configurations. The rich literature in histological connectivity analysis studies in the macaque monkey enables quantitative evaluation of the performance of tractography algorithms. In this study, we use the intricate connections of frontal, cingulate, and parietal areas, well established by the anatomical literature, to derive a symmetrical histological connectivity matrix composed of 59 cortical areas. We evaluate the performance of fifteen diffusion tractography algorithms, including global, deterministic, and probabilistic state-of-the-art methods for the connectivity predictions of 1711 distinct pairs of areas, among which 680 are reported connected by the literature. The diffusion connectivity analysis was performed on a different ex-vivo macaque brain, acquired using multi-shell DW-MRI protocol, at high spatial and angular resolutions. Across all tested algorithms, the true-positive and true-negative connections were dominant over false-positive and false-negative connections, respectively. Moreover, three-quarters of streamlines had endpoints location in agreement with histological data, on average. Furthermore, probabilistic streamline tractography algorithms show the best performances in predicting which areas are connected. Altogether, we propose a method for quantitative evaluation of tractography algorithms, which aims at improving the sensitivity and the specificity of diffusion-based connectivity analysis. Overall, those results confirm the usefulness of tractography in predicting connectivity, although errors are produced. Many of the errors result from bottleneck white matter configurations near the cortical grey matter and should be the target of future implementation of methods.

Histological scoring system for subchondral bone changes in murine models of joint aging and osteoarthritis.

To establish a histopathological scoring system for changes in subchondral bone in murine models of knee osteoarthritis (OA), three key parameters, subchondral bone plate (Subcho.BP) consisting of the combination of Subcho.BP.thickness (Subcho.BP.Th) and angiogenesis, bone volume (BV/TV) and osteophytes, were selected. The new grading system was tested in two mouse OA models, (1) senescence accelerated mouse (SAM)-prone 8 (SAMP8) as spontaneous OA model with SAM-resistant 1 (SAMR1) as control; (2) destabilization of the medial meniscus in C57BL/6 mice as surgical OA model. Results of the spontaneous OA model showed that Subcho.BP.Th was significantly wider, angiogenesis was greater, and BV/TV was higher in SAMP8 than SAMR1. Notably, subchondral bone score was dramatically higher in SAMP8 at 6 weeks than SAMR1, while OARSI cartilage scores became higher only at 14 weeks. In the surgical OA model, the results were similar to the spontaneous OA model, but osteophytes appeared earlier. There were strong correlations both in Subcho.BP.Th and BV/TV between this scoring system and µCT (r = 0.89, 0.84, respectively). Inter-rater reliabilities for each parameter using this system were more than 0.943. We conclude that this new histopathological scoring system is readily applicable for evaluating the early changes in aging and OA-affected murine subchondral bone.

ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology.

Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.

Coronavirus disinfection in histopathology.

The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.

Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission.

BACKGROUND: Clinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established. AIM: To quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission. METHODS: This study included patients with UC from a prospective registry who were in complete endoscopic remission. Histologic activity was quantified by a senior gastrointestinal pathologist. Histologic activity was defined as lack of normalisation (Geboes score > 0) as well as histologically active disease (Geboes score ≥2.1 and ≥3.1). The primary outcome was clinical relapse within 2 years. Multivariable regression adjusting for potential confounders examined the independent predictive value of histologic changes. RESULTS: The study included 83 patients (51% women) (median age 44 years; median disease duration 11 years). Forty-one (49%) had complete histologic normalisation. Within two years, 26 (31%) experienced clinical relapse. Patients with complete histologic normalisation were less likely to experience relapse (5/41, 12%) compared to those without normalisation (21/42, 50%, P < 0.001) (multivariable OR 7.22, 95% confidence interval (CI) 2.48-24.70) by the Geboes score. The individual components of the Geboes score predictive of relapse were architectural changes (P = 0.03) and increased chronic inflammatory infiltrate (P < 0.001). CONCLUSIONS: Complete histologic healing using the Geboes score was associated with reduced rates of clinical relapse among patients with UC in endoscopic remission.

Comparison of line-field confocal optical coherence tomography images with histological sections: Validation of a new method for in vivo and non-invasive quantification of superficial dermis thickness.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is an imaging technique providing "optical biopsies" of the skin in real time and non-invasively. At a center optical wavelength of 1.3 µm, this innovative technology can be applied to dermo-cosmetic product development due to both high image resolution (~2 µm) and sufficient penetration (~0.5 mm). Nevertheless, the precise dermal area analyzed with LC-OCT has never been identified. In this study, the objective was to compare LC-OCT images with histological sections of the same area, in order to validate a new method for in vivo and non-invasive quantification of superficial dermis thickness. Once validated, this standardized and quantitative method was used to assess age-related changes of the superficial dermis. MATERIALS AND METHODS: Ex vivo LC-OCT acquisitions and hematoxylin-eosin-safran staining were performed on a panel of four healthy Caucasian female volunteers. In vivo LC-OCT study of skin aging was performed on a panel of 37 healthy Caucasian female divided into five different age-groups. RESULTS: Comparison with histological sections revealed that LC-OCT images allow the visualization and the quantification of the superficial portion of papillary dermis. Applied to different age-group of volunteers, LC-OCT images show a constant decrease in this superficial dermis thickness with age. CONCLUSIONS: In conclusion, we have introduced LC-OCT as a novel technique for in vivo and non-invasive evaluation of superficial dermis thickness. This approach could be used in the future to demonstrate visually and quantitatively the capacity of a dermo-cosmetic active ingredient to renormalize the structural properties of the dermis.

Comparison of histologic methods for the detection of Desmozoon lepeophtherii spores in the gills of Atlantic salmon.

Desmozoon lepeophtherii is a microsporidian associated with gill disease in farmed Atlantic salmon (Salmo salar). Detection of the parasite in histologic tissue sections is challenging using common histochemical stains given that the small, widely distributed parasite spores typically occur individually or in small clusters. We compared the ability of 4 histologic methods to detect D. lepeophtherii spores in serial sections of Atlantic salmon gill tissue: hematoxylin and eosin (H&E), Gram-Twort (GT), calcofluor white (CW), and immunohistochemistry (IHC). Using CW as a benchmark to calculate a relative ratio, IHC consistently detected more spores than CW (median: 1.3), followed by GT (median: 0.2) and H&E (median: 0.1). IHC detected significantly more spores than GT (p < 0.05) and H&E (p < 0.05), and GT more than H&E (p < 0.05). We found significant underestimation of numbers of microsporidia spores in gill disease in Atlantic salmon using conventional histochemical stains and recommend the use of CW or IHC to detect the parasite in tissue sections.

Utilizing supervised machine learning to identify microglia and astrocytes in situ: implications for large-scale image analysis and quantification.

BACKGROUND: The evaluation of histological tissue samples plays a crucial role in deciphering preclinical disease and injury mechanisms. High-resolution images can be obtained quickly however data acquisition are often bottlenecked by manual analysis methodologies. NEW METHOD: We describe and validate a pipeline for a novel machine learning-based analytical method, using the Opera High-Content Screening system and Harmony software, allowing for detailed image analysis of cellular markers in histological samples. RESULTS: To validate the machine learning pipeline, analyses of single proteins in mouse brain sections were utilized. To demonstrate adaptability of the pipeline for multiple cell types and epitopes, the percent brain coverage of microglial cells, identified by ionized calcium binding adaptors molecule 1 (Iba1), and of astrocytes, by glial fibrillary acidic protein (GFAP) demonstrated no significant differences between automated and manual analyses protocols. Further to examine the robustness of this protocol for multiple proteins simultaneously labeling of rat brain sections were utilized; co-localization of astrocytic endfeet on blood vessels, using aquaporin-4 and tomato lectin respectively, were efficiently identified and quantified by the novel pipeline and were not significantly different between the two analyses protocols. Comparison with Existing Methods: The automated platform maintained the sensitivity and accuracy of manual analysis, while accomplishing the analyses in 1/200th of the time. CONCLUSIONS: We demonstrate the benefits and potential of adapting an automated high-throughput machine-learning analytical approach for the analysis ofin situ tissue samples, show effectiveness across different animal models, while reducing analysis time and increasing productivity.

Systematized protocol for interventional pathology reports. Pathology report paradigm for pathologist-performed Ultrasound Guided Fine Needle Aspiration (USFNA) and Ultrasound Guided Core Needle Biopsy (USCNB) / Protocolo sistematizado para informes de patología intervencionista. Informe de anatomía patológica para punción-aspiración con aguja fina con ecografía (EcoPAAF) y biopsia con aguja gruesa con ecografía (EcoBAG)

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[Method and experience of lymph node examination after gastrectomy with D2 lymphadenectomy for gastric cancer].

The insufficiency of the examined number of lymph nodes after surgery for gastric cancer may undermine the stage of lymph node metastasis, which would have a significant impact on prognostic evaluation and strategy formulation of adjuvant therapy. Under the premise of standard D2 lymphadenectomy, the number of harvested lymph nodes is mainly dependent on the procedures of lymph node examination. Since 2013, our center has set up a special lymph node examination team. In the same year, the average number of harvested lymph nodes in each sample was 46, which was significantly higher than before (average 18 nodes/case in 2004-2012). After continuous quality improvement and regular quality control in 2014, average number of retrieved lymph nodes was 64 per specimen. Therefore, this paper summarizes the methods and experience of lymph node examination in gastric cancer specimens of general surgery in Southern Hospital. The overall construction of the lymph node examination team of gastric cancer in our center mainly includes three parts: establishment of a specialized lymph node examination team, effective standard operating procedures (SOP), and long-term and sustained quality control. The specialized lymph node examination team consists of postgraduate students who are not involved in surgery but have been trained by surgeons. Standard procedures include theoretical reserve of gastric anatomy, surgical observation to correspond to specimens in vitro and in vivo, and standardized specimen processing procedures. Long-term and sustained quality control requires periodic report of lymph node examination data and continuous feedback optimization of the process. Intraoperative lymph node tracing navigation and specimen lymph node intensification are carried out with nanocarbon and indocyanine green dye staining, and then lymph nodes are harvested based on the traditional methods, which can improve the examination rate of lymph nodes, especially for small lymph nodes. Research on lymph node tracing methods, requires multidisciplinary cooperation in particular, will become a hot topic.

Troubleshooting in the histology laboratory.

Humans and machines both have an inherent error rate. As long as this is true, sub-optimal events will occur in the histology laboratory. The best approach to troubleshooting and remedying these events is to (1) understand the various theories of action behind histology procedures and stains then (2) apply a problem-solving mentality to develop a corrective action. These theories and problem solving strategies are presented in this review article.

Stacked in-plane histology for quantitative validation of non-invasive imaging biomarkers: Application to an infiltrative brain tumour model.

BACKGROUND: While it is generally agreed that histopathology is the gold standard for assessing non-invasive imaging biomarkers, most validation has been by qualitative visual comparison. To date, the difficulties involved in accurately co-registering histology sections with imaging slices have prevented a voxel-by-voxel assessment of imaging modalities. By contrast with previous studies, which focus on improving the registration algorithms, we have taken the approach of improving the quality of the histological processing and analysis. NEW METHOD: To account for imaging slice orientation and thickness, multiple histology sections were cut in the MR imaging plane and averaged to produce stacked in-plane histology (SIH) maps. When combined with intensity sensitive staining this approach gives histopathology maps, which can be used as the gold standard to validate imaging biomarkers. RESULTS: We applied this pipeline to a patient-derived mouse model of glioblastoma multiforme (GBM). Increasing the number of stacked histology sections significantly increased SIH measured tumour volume. The SIH technique proposed here resulted in reduced variability of volume measurements and this allowed significant improvements in the quantitative volumetric assessment of multiple MRI modalities. Further, high quality registration enabled a voxel-wise comparison between MRI and histopathology maps. Previous approaches to the validation of imaging biomarkers with histology, have been either qualitative or of limited accuracy. Here we propose a pipeline that allows for a more accurate validation via co-registration with SIH maps, potentially allowing validation in a voxel-wise mode. CONCLUSION: This work demonstrates that methodically produced SIH maps facilitate the quantitative histopathologic assessment of imaging biomarkers.

Three case reports of collagenous gastritis in children: Lessons for an endoscopic and histologic approach to mucosal nodularity of the stomach.

RATIONALE: Collagenous gastritis (CG) is a rare form of chronic gastritis defined histologically by a thickened subepithelial collageneous band in the lamina propria. However, the clinical features and endoscopic findings of CG have not been clearly established in the pediatric population. PRESENTING CONCERNS: We report the cases of 3 children who presented with intractable anemia and minimal or no gastrointestinal (GI) symptoms and were followed up without definitive diagnosis determination even through diagnostic endoscopic evaluations. DIAGNOSES: On repeated endoscopic examination, we determined thickened subepithelial collagen band, confirmed by Masson trichrome staining using targeted biopsies of the intervening mucosa between the prominent nodular lesions. INTERVENTIONS: Under the diagnosis of CG, a course of steroid was administrated in 1 patient, while all patients continued oral iron replacement therapy. OUTCOMES: All 3 patients remained asymptomatic and their anemia was alleviated with continued administration of oral iron. MAIN LESSONS: We recommend early endoscopic evaluation for patients with unexplained anemia, emphasizing a high index of suspicion for CG, despite the absence of definitive GI symptoms. Targeted gastric biopsies should be performed in the depressed mucosa surrounding the nodules, as well as the nodules themselves, to confirm CG, when presented with nodular gastric mucosa in endoscopy.