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We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that Cluster of differentiation (CD) 3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

Hemophagocytic lymphohistiocytosis (HLH) constitutes a life-threatening inflammatory syndrome. Postmortem histological findings of bone marrow (BM) from COVID-19 patients showed histiocytosis and hemophagocytosis and supported the hypothesis that secondary HLH (sHLH) may be triggered by SARS-CoV-2 infection. However, there are a limited number of sHLH cases in which trephine has been performed in living post-COVID-19 patients. Here we present a recent case and a mini-review of sHLH diagnosed by trephine biopsy in living patients after COVID-19. An 81-year-old man with a past medical history of hypertension, diabetes, ischemic stroke, was referred to the hospital to evaluate leukocytosis, pyuria, and elevation of inflammatory markers four weeks after recovering from COVID-19. Computed tomography of the abdomen did not reveal focal signs of infection or hepatosplenomegaly. The patient received intravenous meropenem and two packed red blood cell units. Leukocytes and C-reactive protein were gradually decreased. A BM biopsy was performed and the patient was discharged on cefixime. BM smear revealed severe anemia, lymphopenia, and dysplastic morphologic findings of erythroblasts, neutrophils, and megakaryocytes. Trephine biopsy revealed hypercellular marrow dyserythropoiesis, plasmacytosis, lymphocytosis, histiocytosis, hemophagocytosis, and the absence of granulomas or carcinoma. Immunohistochemistry documented a mixed population of T lymphocytes (CD3+) and B lymphocytes (CD20+). Strong positivity for CD68 confirmed histiocytosis. CD138 κ, λ staining proved polyclonal plasmacytosis. Perl's staining showed excess hemosiderin deposits. Based on our findings, we document sHLH in trephine BM biopsy of a living post-COVID-19 patient and persistent leukocytosis, underscoring the diagnostic value of trephine biopsy in preventing life-threatening conditions such as COVID-19.

To explore the clinical value of ultrasound shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) in transrectal prostate biopsy.A total of 54 patients (average age: 67.79±12.01 years) in the experimental group underwent transrectal prostate biopsy under the guidance of SWE, while 46 patients (average age: 69.22±11.54 years) in the control group underwent transrectal prostate biopsy guided by CEUS.There were a total of 451 needles, with an average of 8.35±1.67 needles per patient in the experimental group, and a total of 462 needles, with an average of 10.04±1.33 needles per patient in the control group. The difference in puncture times between the two groups was statistically significant (P0.05). There was no significant difference in the positive detection rate, sensitivity or specificity between the two groups (P0.05), but there was a significant difference in the diagnostic accuracy between the two groups (P0.05). The EIn summary, both SWE- and CEUS-guided transrectal prostate biopsy can help find the focus and guide the puncture, and improve the positive detection rate.

BACKGROUND Active surveillance (AS) is a validated option for the treatment of small renal masses (SMRs), especially in older patients. This study investigates the oncologic outcomes and competitive mortality of older patients prospectively assigned to AS. METHODS We conducted a monocentric study on patients ≥75 years treated between 2011 and 2016 for a SMR. Treatment modalities, biopsy data, survivals (overall, specific, cancer progression) and delayed interventions (DI) were analyzed. RESULTS Overall, 106 patients (median age 80.5 years) were included, of which 41 were managed by AS during a follow-up of 3.4 years [0-7.1]. Seven patients (17%) had a primary biopsy with 3 confirmed renal cell carcinomas. Fourteen patients (34.1%) presented with progression (29.2% local; 4.9% metastatic), 8 (19.5%) requiring DI (75% ablative therapy and 25% radical nephrectomy). Overall survival (OS) was 68.3% and cancer specific survival (CSS) was 95.1% during the study period. Competitive mortality was higher (84.6%) than cancer specific mortality (15.4%), p=0.001. CONCLUSION The growth rate of progression including 4.9% metastatic progression underlines the value of AS compared to simple watchful surveillance in the treatment of SMRs in older patients. Of note, the higher competitive mortality confirm that AS should be preferred to active intervention at the beginning of the management. MICROABSTRACT Management of small renal tumors in older patients is challenging. This study shows that older patients managed by active surveillance (AS) will mostly die from other causes than renal cancer, confirming the safety of AS. However, the significant progression rate under AS confirms the need of a careful and vigilant radiological follow-up rather than a simple watchful waiting surveillance.

Background & Aims Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice. Methods To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published. We used 178 FFPE-archived HCC samples, including 109 surgical samples for the training set and 69 paired pre-operative biopsies for the validation set. In 14 cases of the training set, a paired biopsy was available and was also analyzed. Results We identified a 6-gene signature (ROS1, UGT2B7, FAS, ANGPTL7, GMNN, MKI67) strongly associated with MVI in the training set of FFPE surgical HCC samples, with 82% accuracy (sensitivity 82%, specificity 81%, AUC 0.82). The NanoString gene expression was highly correlated in 14 paired surgical/biopsy HCC samples (mean R: 0.97). In the validation set of 69 FFPE HCC biopsies, the 6-gene NanoString signature predicted MVI with 74% accuracy (sensitivity 73%, specificity 76%, AUC 0.74). Moreover, on multivariate analysis, the MVI signature was associated with overall survival in both sets (hazard ratio 2.29; 95% CI 1.03-5.07; p = 0.041). Conclusion We defined a 6-gene signature that can accurately predict MVI in FFPE HCC biopsy samples, which is also associated with overall survival, although its survival impact must be confirmed by extensive study with further clinical data. Lay summary Microvascular invasion, a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma, is only detectable by microscopic examination of a surgical specimen. In this study, we defined a relevant surrogate signature of microvascular invasion in hepatocellular carcinoma that may be applied in clinical practice with routine tumor biopsy and integrated into the therapeutic strategy.

Objectives: To measure the diagnostic accuracy of intraoperative frozen section examination of sentinel lymph nodes (SLN) in vulvar cancer and to describe associated patient outcomes. Methods: This retrospective cohort study included patients with invasive squamous cell carcinoma of the vulva who underwent SLN biopsy with intraoperative frozen section at one cancer centre from Jan 2008 - Feb 2020. Exclusion criteria were tumor size >4cm, multifocal tumor, palpable groin lymph nodes and neoadjuvant therapy. The SLN procedure was performed by injection of the primary vulvar tumor or scar with technetium-99m, ICG and/or blue dye. We compared the intraoperative SLN frozen section diagnosis and the paraffin section report for concordance. Recurrence location was described and recurrence free survival (RFS) was compared using the Kaplan-Meier method. Results: A total of 173 patients (258 groins) met inclusion and exclusion criteria. On frozen section, there were 36/258 positive groins on frozen section and 222 negative groins. On final pathology, there were 39/258 positive groin nodes: 30 macro-metastases, 7 micro-metastases, 2 isolated tumor cells (ITCs). There were 219 negative groins. The sensitivity and specificity for frozen section detecting any metastatic disease compared to final pathology, was 89.7% and 99.5%, respectively. The positive-predictive value (PPV) was 97.2% and the negative-predictive-value (NPV) was 98.2%. There were 4 cases of false negative frozen section where final pathology revealed two cases of ITCs, 1 micro-metastasis and 1 macro-metastasis. A total of 30 patients (17.3%) underwent a full inguinal femoral lymphadenectomy during the same operation due to the frozen section results and avoided a second operation. A total of 2 patients (1.2%) required a second operation for lymphadenectomy due to false negative results on frozen section. Median (range) follow up was 38.0 (1-137.8) months. Median RFS was 14.9 (3.6 to 98.2) months. There were 46 recurrences in the study population, of which 29 were confined to the vulva, 9 groin recurrences and 8 distant recurrences. Among patients with a negative SLN biopsy on both frozen section and final pathology, there were 10 (3.9 %) groin and/or distant recurrences. A total of 6 nodal recurrences were ipsilateral, 1 was contralateral, 2 were bilateral and 1 recurrence was distant. After exclusion of patients with local recurrence only, the RFS at 3 years was 91.6% (95% CI 86.2-97.4%) for patients with negative SLN on frozen section and 64.6% (95% CI 46.5-89.7%) for positive SLN on frozen section. On final pathology, patients with negative SLN had a 3-year RFS of 91.7% (95% CI 86.3-97.4%), macro-metastases 58.4% (95% CI 38.5-87.7%), and micro-metastases/ITCs was 100%. Conclusions: Intraoperative frozen section of SLNs in vulvar cancer is an accurate intraoperative guide to determine if complete inguinal femoral lymphadenectomy should be performed. SLN biopsy reduced the need for a second surgical procedure and does not appear to compromise patient outcomes.

Purpose The purpose of this study was to identify which combination of imaging modalities should be used to obtain the best diagnostic performance for the non-invasive diagnosis of giant cell arteritis (GCA). Materials and methods This IRB-approved prospective single-center study enrolled participants presenting with a suspected diagnosis of GCA from December 2014 to October 2017. Participants underwent high-resolution 3T magnetic resonance imaging (MRI), temporal and extra-cranial arteries ultrasound and retinal angiography (RA), prior to temporal artery biopsy (TAB). Diagnostic accuracy of each imaging modality alone, then a combination of several imaging modalities, was evaluated. Several algorithms were constructed to test optimal combinations using McNemar test. Results Forty-five participants (24 women, 21 men) with mean age of 75.4 ± 16 (SD) years (range: 59–94 years) were enrolled; of these 43/45 (96%) had ophthalmological symptoms. Diagnosis of GCA was confirmed in 25/45 (56%) patients. Sensitivity and specificity of MRI, ultrasound and RA alone were 100% (25/25; 95% CI: 86–100) and 86% (19/22; 95% CI: 65–97), 88% (22/25; 95% CI: 69–97) and 84% (16/19; 95% CI: 60–97), 94% (15/16; 95% CI: 70–100) and 74% (14/19; 95% CI: 49–91), respectively. Sensitivity, specificity, positive predictive and negative predictive values ranged from 95 to 100% (95% CI: 77–100), 67 to 100% (95% CI: 38–100), 81 to 100% (95% CI: 61–100) and 91 to 100% (95% CI: 59–100) when combining several imaging tests, respectively. The diagnostic algorithm with the overall best diagnostic performance was the one starting with MRI, followed either by ultrasound or RA, yielding 100% sensitivity (22/22; 95% CI: 85–100%) 100% (15/15; 95% CI: 78–100) and 100% accuracy (37/37; 95% CI: 91–100). Conclusion The use of MRI as the first imaging examination followed by either ultrasound or RA reaches high degrees of performance for the diagnosis of GCA and is recommended in daily practice.

Introduction: Cytological examination of exfoliated epithelial cells of the uterine cervix, oral cavity, or rectum has been successfully used in the diagnostics of pathological conditions of these organs for many years. In these cases, the test material is collected from the available regions. Aim: The aim of the study consisted in the analysis of cytological smears of laryngeal epithelial cells from patients hospitalized at the Department of Otolaryngology, Head and Neck Surgery of the 4th Military Teaching Hospital and Polyclinic in Wrocław in years 2019–2020. The analysis was aimed at demonstrating whether representative laryngeal epithelial material could be obtained from brush biopsies. Material and methods: The study was carried out in 92 subjects aged between 26 and 85 years, including 34 women (37.0%), from whom material for cytological examination had been collected from the larynx in the course of microsurgical procedures carried out using the Kleinsasser laryngeal instrument set in 2019–2020. Results: Analysis was performed on 90 out of 92 cell smears (97.8%). Two smears were not qualified for analysis due to ille-gibility. The smears were assessed using a proprietary scale consisting in a modification of the Bethesda system. Abnormal results of cytological examinations were obtained in a majority of cases. HSILs with invasive features were the most common abnormal results of cytological examinations. Conclusions: Laryngeal epithelial cells can be successfully evaluated by means of cytological examination. Abnormal presen-tation of cytological smear is frequently hypercellular, with inflammatory cells being observed less frequently. No statistically significant relationship was observed between the results of the cytological examination and the overall quality of the smear, number of cells, number of erythrocytes, or the severity of inflammation.

Purpose This study aimed to develop a model for predicting pathologic extracapsular extension (ECE) and seminal vesicle invasion (SVI) while integrating magnetic resonance imaging-based T-staging (cTMRI, cT1c-cT3b).Materials and Methods A total of 1,915 who underwent radical prostatectomy between 2006-2016 met the inclusion/exclusion criteria. We performed a multivariate logistic regression analysis as well as Bayesian network (BN) modeling based on possible confounding factors. The BN model was internally validated using 5-fold validation.Results According to the multivariate logistic regression analysis, initial prostate-specific antigen (iPSA) (β=0.050, p < 0.001), percentage of positive biopsy cores (PPC) (β=0.033, p < 0.001), both lobe involvement on biopsy (β=0.359, p=0.009), Gleason score (β=0.358, p < 0.001), and cTMRI (β=0.259, p < 0.001) were significant factors for ECE. For SVI, iPSA (β=0.037, p < 0.001), PPC (β=0.024, p < 0.001), Gleason score (β=0.753, p < 0.001), and cTMRI (β=0.507, p < 0.001) showed statistical significance. BN models to predict ECE and SVI were also successfully established. The overall area under the receiver operating characteristic curve (AUC)/accuracy of the BN models were 0.76/73.0% and 0.88/89.6% for ECE and SVI, respectively. According to internal comparison between the BN model and Roach formula, BN model had improved AUC values for predicting ECE (0.76 vs. 0.74, p=0.060) and SVI (0.88 vs. 0.84, p < 0.001).Conclusion Two models to predict pathologic ECE and SVI integrating cTMRI were established and installed on a separate website for public access to guide radiation oncologists.

Background Hemorrhage is one of the most common complications of bronchoscopy. Although several hemorrhage risk factors have been proposed, it remains unclear whether blood pressure affects the onset of biopsy-induced endobronchial hemorrhage. Methods We conducted a retrospective cohort study of 643 consecutive adults with lung cancer over an approximately 4-year period (from January 2014 to February 2018) at a large tertiary care hospital. Patients were divided into the hemorrhage group and the non-hemorrhage group based on endobronchial biopsy (EBB) findings. The association between systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), pulse pressure (PP), PP to DP ratio (PP/DP) and the risk of EBB-induced hemorrhage was evaluated using multivariate regression analysis and smooth curve fitting adjusted for potential confounding factors. Results The EBB-induced bleeding incidence was 37.8% (243/643) in our cohort. An independent association was found between PP/PD and the EBB-induced hemorrhage risk (per 1 SD, adjusted odds ratio, 0.788; 95% confidence interval, 0.653-0.951). The multivariate regression analysis performed using quartiles of PP/DP revealed that lower level of PP/DP ratio was related to a higher risk of EBB-induced hemorrhage (P for trend Conclusions Low PP/DP was the independent risk factor for biopsy-induced endobronchial hemorrhage during bronchoscopy in patients with lung cancer.

OBJECTIVE The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors’ a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23–88 years). The median follow-up was 8.5 months (range 0.1–231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Purpose Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. Materials and methods This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. Results A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. Conclusions Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.

International audience; Objectives: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL).Methods: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models.Results: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS.Conclusions: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Objectives: Radiologist input in peer review of head and neck radiotherapy has been introduced as a routine departmental approach. The aim was to evaluate this practice and to quantitatively analyse the changes made. Methods: Patients treated with radical-dose radiotherapy between August and November 2020 were reviewed. The incidence of major and minor changes, as defined by The Royal College of Radiologists guidance, was prospectively recorded. The amended radiotherapy volumes were compared with the original volumes using Jaccard Index (JI) to assess conformity; Geographical Miss Index (GMI) for undercontouring; and Hausdorff Distance (HD) between the volumes. Results: In total, 73 out of 87 (84%) patients were discussed. Changes were recommended in 38 (52%) patients: 30 had ≥1 major change, eight had minor changes only. There were 99 amended volumes: The overall median JI, GMI and HD was 0.91 (interquartile range [IQR]=0.80–0.97), 0.06 (IQR = 0.02–0.18) and 0.42 cm (IQR = 0.20–1.17 cm), respectively. The nodal gross-tumour-volume (GTVn) and therapeutic high-dose nodal clinical-target-volume (CTVn) had the biggest magnitude of changes: The median JI, GMI and HD of GTVn was 0.89 (IQR = 0.44–0.95), 0.11 (IQR = 0.05–0.51), 3.71 cm (IQR = 0.31–6.93 cm); high-dose CTVn was 0.78 (IQR = 0.59–0.90), 0.20 (IQR = 0.07–0.31) and 3.28 cm (IQR = 1.22–6.18 cm), respectively. There was no observed difference in the quantitative indices of the 85 ‘major’ and 14 ‘minor’ volumes (p = 0.5). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and can help avoid gross error in contouring. Advances in knowledge: The major and minor classifications may benefit from differentiation with quantitative indices but requires correlation from clinical outcomes.

To establish the epidemiological, clinical, pathological and genetic characteristics of epidermolysis bullosa (EB) in New Zealand (NZ).Participants were recruited through the Dystrophic Epidermolysis Bullosa Research Association of New Zealand (DEBRA NZ). Dedicated EB nurse medical records, Genetic Health Service NZ (GHSNZ) records and, where available, public hospital records were manually reviewed for relevant clinical data.Ninety-two participants took part in the study (56% participation rate). Forty-nine (53%) participants had EB simplex (EBS), 40 (43%) had dystrophic EB (DEB), and 3 (3%) had junctional EB (JEB). Point prevalence for EB of all types was 19.5 per million, and 10.4, 8.6 and 0.9 per million for EBS, DEB and JEB, respectively. Thirty-four participants had intermediate or severe EB. There were 29 paediatric cases and almost even numbers of males and females. Compared to NZ European and Māori, prevalence rates were lower for Pacific and Asian people and higher in the Middle Eastern/Latin American/African population. Eight out of 14 skin biopsy results were informative, and 14 of 15 genetic test results were informative.New Zealand has similar prevalence rates of EB compared with other national cohorts. This is likely to be an underestimate due to methodological limitations. Recent advancements in genomic testing have resulted in an improved diagnostic rate in our population. Further research into ethnic differences in prevalence, and exploring the characteristics of lethal forms of EB, is warranted. A dynamic registry may be helpful for the EB community in NZ.

Background Stroke mimics are noncerebrovascular conditions that present with classical stroke symptoms. They account for up to 30% of stroke presentations in the emergency department (ED). Emergency physicians are faced with a diagnostic dilemma—rapid treatment of stroke, a leading cause or mortality and morbidity in the United States, or ruling out the ever-growing list of conditions that mimic strokes. Case Report An 87-year-old man with a 60-year smoking history, chronic obstructive pulmonary disease, and extensive cardiovascular disease history presented to the ED with a chief symptom of new onset right-arm weakness. Computed tomography (CT) excluded hemorrhage and lesions, and additional CT angiography imaging revealed a large mass compressing the right subclavian artery. Given the initial workup, mass effect on the right brachial plexus better explained the patient's symptoms. Two weeks later, a CT scan of the chest, abdomen, and pelvis revealed masses on the pubic ramus, iliac bone, and several vertebral bodies. Biopsy of the rib mass revealed squamous cell carcinoma. The patient was diagnosed with bone metastasis of unknown origin and started on radiation therapy. Why Should an Emergency Physician Be Aware of This? Even in fast-paced settings, clinicians must maintain a high level of suspicion for stroke mimics. This case illustrates the vital importance of neuroimaging in the diagnosis of stroke mimics and discusses clinical characteristics and patient risk factors that increase the likelihood of a stroke mimic diagnosis, serving as a tool for physicians facing this diagnostic dilemma.

Background Minimally invasive breast biopsy (MIBB) is the standard of care for the diagnosis of breast cancer, with consensus guidelines suggesting MIBB goals of 90% of total biopsies. In a previous study of patients in the rural state of Vermont, USA (population size of 640,000), rural breast cancer patients had open biopsies 42% of the time compared to 29% of urban breast cancer patients. The aim of this study was to assess overall population‐based biopsy trends in Vermont. Methods The Vermont Breast Cancer Surveillance System (VBCSS) was used to identify women receiving MIBB and excisional breast biopsies in Vermont. Patient zip code at the time of initial biopsy was used to determine the patient residence rurality by rural–urban commuting area codes (RUCA 2.0™). Results There were 9122 diagnostic episodes from 1999 to 2018. MIBB was the initial biopsy method in 7524 (82.5%) cases, while surgical excision was the initial biopsy method in 1598 (17.5%) cases. A linear trend fit estimated an increase of 1.3% per year (p, Minimally invasive needle biopsy has been the standard of care for breast cancer diagnosis since the early 2000’s. However, a number of studies through 2010, including our prior report from Vermont, showed persistently high rates of open surgical biopsies in rural populations. In this manuscript, we report updated results from a state‐wide retrospective study of breast biopsies, stratified by rurality of patient residence; we evaluated the trend of minimally invasive breast biopsies from 1999 to 2018 and show for the first time that the state as a whole has reached the standard of care of over 90% breast biopsies performed as minimally invasive.

Background The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand‐1 (PD‐L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. Methods From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD‐L1 status and age, sex, stage, histological type, and prognosis were investigated. Results PD‐L1‐positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD‐L1‐positive PSC cases, two showed high PD‐L1 expression in the vimentin‐positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD‐L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD‐L1 staining in the sarcomatoid survived, whereas the other with negative PD‐L1 staining did not. Conclusion The present study showed that sarcomatoid carcinoma had a higher PD‐L1 expression compared to non‐small‐cell lung cancer and that both PSC and MPM tended to exhibit PD‐L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results., In malignant pleural mesothelioma (MPM) and pulmonary sarcomatoid carcinoma (PSC), which are thoracic mesenchymal malignant tumors, programed cell death ligand‐1 (PD‐L1) was positive in the vimentin‐positive part or the sarcomatoid area, found to be clinicopathologically significant. In MPM, the effectiveness of immune checkpoint inhibitors (ICIs) has been shown, especially in nonepithelioid type. Our results support the possibility that ICIs will work as well as MPM if PSC is also positive for PD‐L1 and has mesenchymal features such as vimentin‐positive or sarcomatoid compartments.

Introduction: It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). Methods: This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. Results: The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios Conclusions: Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.

BACKGROUND: In 2014, technetium-99m tilmanocept (TcTM) replaced technetium-99m sulfur colloid (TcSC) as the standard lymphoscintigraphy (LS) mapping agent in melanoma patients undergoing sentinel lymph node biopsy (SLNB). The aim of this study was to examine differences in mapping time, intra-operative identification of sentinel lymph node (SLN), and false negative rate (FNR) between patients who underwent SLNB with TcTM compared to TcSC. METHODS: Patients who underwent SLNB between 2010 and 2018 were retrospectively identified. Patient demographic, tumor, and imaging data was stratified by receipt of TcSC (n = 258) or TcTM (n = 133). Student's t test and χ(2) test were used to compare characteristics and outcomes. RESULTS: Both cohorts were similar in demographic, primary tumor characteristics, and total number of SLN identified (TcTM 3.56 vs. TcSC 3.28, p = 0.244). TcTM was associated with significantly shorter LS mapping times (51.8 vs. 195.1 min, p < 0.01). There was no significant difference in the number of patients with positive SLN (TcTM 11.3 vs. TcSC 17.4%, p = 0.109) and the FNR was similar between both groups (TcTM 25% vs. TcSC 22%). CONCLUSION: TcTM was associated with significantly shorter LS mapping time while identifying similar numbers of SLN. Our results support further study to ensure similar FNR and oncologic outcomes between agents.

OBJECTIVES AND METHODS Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically in newly diagnosed AML patients receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non‐small‐cell lung cancer (NSCLC). Next‐generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real‐world clinical data using the Oncomine Dx Target Test Multi‐CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%‐83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P = .005). Multivariate analysis revealed a significant difference for surgical resection alone (P = .006, 95% CI 1.36‐6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings., The mutation identification success rate for all four genes was 80.1%. Surgical resection was associated with the highest success rate. Multivariate analysis showed a significant difference for surgical resection alone.

Background COVID‐19 is associated with several cutaneous manifestations, including chilbain‐like lesions, urticaria, erythema multiforme, and maculopapular lesions. Dermatoses may be directly linked to the viral infection or also represent a consequence of systemic therapies administrated for COVID‐19. A potential role of SARS‐CoV‐2 in triggering the reactivation of other viruses, such as HHV‐6, HHV‐7 and Epstein‐Barr virus has been hypothesized. Objective To better understand and hypothesize possible pathogenetic correlations of COVID‐19 with other dermatological conditions. Methods We report the case of an 83‐year‐old woman hospitalized in a nursing home for several years. On November 2020, the patient had been diagnosed with SARS‐CoV‐2 infection, with repeated positive swabs until January 2021. After a month, new‐onset asymptomatic cutaneous purplish macular lesions and violaceous patches occurred bilaterally on the feet. Results An incisional cutaneous biopsy and the histological examination of the plantar lesion revealed the diagnosis of Kaposi Sarcoma. Conclusion We report a unique case of new‐onset bilateral Kaposi's sarcoma following COVID‐19, speculating on a possible role of SARS‐CoV‐2 in the reactivation of human herpes virus‐8 (HHV‐8) infection.

Background Resection of pure intraorbital tumors is challenging owing to the nearness of the optic apparatus. The objective of this article was to report our experience with different intraorbital tumors and discuss classic approaches and obstacles. Methods A retrospective case series of patients who underwent surgery for intraorbital tumors at a tertiary neurosurgical center between June 2007 and January 2020 was performed. Results The study included 34 patients (median age 58 years; range, 18–87 years; 55.9% [19/34] female, 44.1% [15/34] male). Preoperative proptosis was observed in 67.6% (23/34); visual impairment, in 52.9% (18/34); diplopia, in 41.2% (14/34); and ptosis, in 38.3% (13/34). Intraconal tumors were found in 58.8% (20/34). The most common lesions were cavernous hemangiomas in 26.5% (9/34) and metastases in 14.7% (5/34). Gross total resection rate was 73.5% (25/34). Planned biopsy was performed in 14.7% (5/34). Median follow-up time was 15.5 months (interquartile range: 0–113 months). Surgical approaches included supraorbital approach (23.5% [8/34]), pterional approach (52.9% [18/34]), lateral orbitotomy (14.7% [5/34]), transnasal approach (5.9% [2/34]), and combined transnasal approach/lateral orbitotomy (2.9% [1/34]). Excluding planned biopsies, gross total resection was achieved in 80.0% (12/15) with pterional approach, 100% (7/7) with supraorbital approach, 80.0% (4/5) with lateral orbitotomy, and 100% (1/1) with transnasal approach/lateral orbitotomy. Complication rate requiring surgical intervention was 11.8% (4/34). Conclusions Considering the low operative morbidity and satisfactory functional outcome, gross total resection of intraorbital lesions is feasible. We support use of classic transcranial and transorbital approaches. More invasive and complicated approaches were not needed in our series.

Background Surgeons sometimes have difficulty determining which result to favor when preoperative results (MRI + preoperative endometrial biopsy [pre-op EB]) differ from intraoperative frozen section histology (FS) results. Investigation of how FS can complement ordinary preoperative examinations like MRI and pre-op EB in identification of patients at high risk of lymph node metastasis (high-risk patients) could provide clarity on this issue. Therefore, the aim of this study is to assess the utility of pre-op EB, MRI and FS results and determine how to combine these results in identification of high-risk patients. Methods The subjects were 172 patients with endometrial cancer. Patients with a histological high-grade tumor (HGT), namely, grade 3 endometrioid cancer, clear cell carcinoma or serous cell carcinoma, or with any type of cancer invading at least half of the uterine myometrium were considered high-risk. Tumors invading at least half of the uterine myometrium were classified as high-stage tumors (HST). We compared (a) detection of HGT using pre-op EB versus FS, (b) detection of HST using MRI versus FS, and (c) identification of high-risk patients using MRI + pre-op EB versus FS. Lastly, we determined to what degree addition of FS results improves identification of high-risk patients by routine MRI + pre-op EB. Results (a) Sensitivity, specificity, and accuracy for detecting HGT were 59.6, 98.4 and 87.8% for pre-op EB versus 55.3, 99.2 and 87.2% for FS (P = 0.44). (b) These figures for detecting HST were 74.4, 83.0 and 80.8% for MRI versus 46.5, 99.2 and 86.0% for FS (P < 0.001). (c) These figures for identifying high-risk patients were 78.3, 85.4 and 82.6% for MRI + pre-op EB versus 55.1, 99.0 and 81.2% for FS (P < 0.001). The high specificity of FS improved the sensitivity of MRI + pre-op EB from 78.3 to 81.2%, but this difference was not statistically significant (P < 0.16). Conclusion Frozen section enables identification of high-risk patients with nearly 100% specificity. This advantage can be used to improve sensitivity for identification of high-risk patients by routine MRI + pre-op EB, although this improvement is not statistically significant.

Introduction Although the diagnostic utility of lymph node fine-needle aspiration (FNA) is well established in the evaluation of metastatic malignancy, its value in the diagnosis of lymphoma is more controversial; yet, there is a growing trend among practitioners towards less-invasive procedures such as FNA and core needle biopsy (CNB). The guidelines recently published by the American Society for Clinical Pathology/College of American Pathology (CAP) regarding the workup of lymphoma include recommendations on the value and limitations of FNA. Materials and methods We reviewed 1237 image-guided lymph node aspirates from 695 procedures (410 nodes from 360 ultrasound [US]-guided cases, 799 from 309 endobronchial ultrasound [EBUS], 25 from 23 endoscopic ultrasound [EUS], and 3 from 3 computed tomography [CT]). Results The majority (40 of 46, 87%) of lymph nodes suspected of lymphomatous involvement were aspirated under ultrasound. Core needle biopsy [CNB] was obtained for 41 (89%) lymph nodes, including all 40 US specimens. Flow cytometry (FC) was performed on 37 (80%) aspirates; aspirates without FC were from patients who had a history of Hodgkin lymphoma, or showed granulomata or non-hematologic malignancy onsite. Thirty-one (67%) lymph nodes were sent for review by hematopathology. Forty-two (91%) lymph node FNA/CNB yielded actionable diagnoses. Seventeen of 241(7%) cases aspirated for other indications (14 US, 3 EBUS) were involved by a lymphoproliferative process. All were reviewed by hematopathology. All 14 US cases had FC and CNB. Conclusion Our institutional approach towards lymph node cytopathology for lymphoma workup appears to be in accordance with the new CAP guidelines, and demonstrates a potential triage and workflow model for lymph node FNA specimens that allows for accurate diagnosis in cases where lymphoma is a consideration.

Background The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death –ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. Methods A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors’ (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. Results The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. Conclusion Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Background Metastatic cancer in nonagenarians and those older is rare and understudied. Here we explored whether these patients appear to benefit from antineoplastic therapy and whether outcomes differ based on whether or not untreated patients had a histologic/cytologic confirmation of cancer. Methods In this single-institution, multi-site study, we reviewed 10 years of consecutive medical records of patients 90+ years of age with a histologic/cytologic cancer diagnosis and metastatic cancer or, alternatively, a presumed metastatic cancer diagnosis. Results Sixty-eight patients are the focus with a median age of 93 years (range: 90, 103 years). Patients fell into 3 groups: 1) no tissue/cytologic cancer diagnosis and no treatment (=23); 2) tissue/cytologic diagnosis but no treatment (n = 21); and 3) cancer treatment rendered (n = 24). The median survival in groups 1,2, and 3 was 5 weeks (95% confidence interval (CI): 2, 11 weeks), 9 weeks (95% CI: 3, 23 weeks), and 60 weeks (95% CI: 38 weeks, not yet reached), respectively. For those patients in group 3 who received cancer therapy, chemotherapy, radiation, and surgery were administered in 11 (16%), 6 (9%), and 4 (6%), respectively. Fourteen received other cancer therapy: hormonal therapy (n = 6), targeted therapy (n = 6), and immunotherapy (n = 2). Only one patient experienced an adverse event that required hospitalization. Conclusions Although these older patients likely received cancer treatment on a selective basis, such treatment was associated with improved survival and was well-tolerated. However, based on survival outcomes, one might question whether to put patients through a biopsy, if they have limited therapeutic options.

The surgical management of cutaneous malignancies has evolved over recent years with the introduction of novel medical therapies and an increasing emphasis upon early adjuvant systemic therapy. As such, completion lymph node dissection (cLND) is now no longer recommended following a positive sentinel lymph node biopsy (SLNB) in melanoma. We evaluated our ten-year practice at a regional tertiary centre, assessing the change in lymph node dissection (LND) caseload volume, anatomical distribution, and indication for the procedure. A retrospective search was carried out of all LNDs performed by the Plastic Surgery department at Cambridge University Hospitals NHS Trust, UK from 1 January 2010 to 31 December 2019. Case notes were retrospectively analysed for each procedure, with the site and pathology recorded. A total of 491 LNDs were performed over the 10-year period. Surgical volume peaked in 2015 with 67 cases, followed by a decline to 41 cases in 2019. The number of neck dissections increased over the decade, as well as the proportion of cases due to macroscopic nodal disease. We sub-analysed the number of LNDs in three contiguous 18-month intervals, corresponding to changes in practice due to evidence from the DeCOG and MSLT-II Trials. We found a 41.67% reduction in LNDs caseload between July 2018-Dec 2019, compared to a similar period prior to trial evidence (July 2015-Dec 2016) (p=0.0.14). In summary, the surgical volume of LNDs has decreased significantly since 2018, reflecting emerging evidence and changes to national guidelines. This will require ongoing monitoring for workforce planning and surgical training.

BACKGROUND Patients with bilateral lacrimal gland disease are a unique subset of patients where there is a paucity of literature. This presentation often represents systemic disease or malignancy and can cause diagnostic difficulties. We aim to describe the diagnoses and features of bilateral lacrimal gland disease. METHOD Retrospective multi-centre case series involving 115 patients with bilateral lacrimal gland disease from 1995 to 2020. RESULTS 115 patients were included. Their ages ranged from 9 to 85 (mean 47.3 years) with a female predominance (73, 63.5%). The most common category of diagnosis was inflammatory (69, 60%) followed by lymphoproliferative (23, 20%), structural (17, 14.8%) and other conditions (6, 5.2%). The five most common specific diagnoses were IgG4 related disease (20, 17.4%) and idiopathic orbital inflammatory disease (20, 17.4%), lymphoma (16, 13.9%), lacrimal gland prolapse (13, 11.3%), and sarcoidosis (11, 9.6%). Corticosteroid treatment was used most commonly (29, 25.2%) followed by observation (25, 21.7%). At last follow up, the majority of patients had complete resolution, significant improvement with mild residual disease or stable disease without further progression (104, 90.4%). CONCLUSION Bilateral lacrimal disease may be due to a range of aetiologies, most of which are systemic. The most common are inflammatory and lymphoproliferative conditions. Due to the wide range of aetiologies of bilateral lacrimal gland disease, it is extremely difficult to accurately determine a cause based on clinical findings alone, highlighting the vital role of lacrimal gland biopsy in patients presenting with bilateral lacrimal gland disease.

An 80-year-old woman was admitted to our hospital due to appetite loss and vomiting. A blood examination showed liver disorder with disseminated intravascular coagulation. All tumor markers and hepatitis virus markers were negative. Contrast-enhanced computed tomography did not show tumor lesions, bone lesions, lymphadenopathies, or thrombosis. A bone marrow biopsy revealed large, atypical cells with brown pigmentation and positive immunostaining for HMB-45, S100 proteins, and CD79a without myeloid or lymphoid markers. We experienced a case of disseminated carcinomatosis of the bone marrow due to malignant melanoma of unknown primary origin.

Abstract Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) have been linked to mutations in many of the proteins that are involved in alternative complement pathway activation. Age and etiology confounded, the prevalence of such mutations has been reported to be over 30 to 50% in these diseases. However, the cohorts studied included many children or individuals with a familial history of complement-related disorders and genetic tests were usually limited to exome sequencing of known causative or risk-associated genes. In this study, a retrospective adult cohort of 35 patients with biopsy-proven thrombotic microangiopathy (the largest in Canada) and 10 patients with C3 glomerulopathy was tested through an extended exome panel to identify causative defects in associated or candidate genes including those of the alternative and terminal complement pathways. A variant of unknown significance was also analyzed for pathogenicity through in vitro studies. To our surprise, the prevalence of known causative or risk-associated variants in either of these cohorts was found to be less than ~ 15% overall. However, the panel used and analyses carried out allowed to identify novel variants of potential clinical significance and a number of candidate genes. The prevalence of known genetic defects in adult-onset aHUS and C3G is thus probably much lower than 30 to 50%. Our results also point towards the importance of investigating diseases of the alternative complement pathway through extended exome panels and in vitro analyses. Key messages The alternative complement pathway plays a major role in the pathogenesis of hemolytic uremic syndrome and C3 glomerulopathy. Based on previous studies, both disorders have been commonly linked to variants in the various intermediates that sustain or regulate this pathway. The prevalence of such mutations in the adult-onset and sporadic forms of these diseases is probably much lower than expected based on larger series. The sporadic forms of complementopathies are likely to involve additional genes that are yet to be uncovered.

Background Inverse psoriasis represents a less commonly described form of psoriasis in intertriginous areas. The pathologic findings of inverse psoriasis are typically grouped in with those of plaque psoriasis, as the histopathological features specific to inverse psoriasis have not received significant investigation. Methods A single institution, retrospective cohort study was performed to review biopsy slides for psoriasis occurring in typical intertriginous areas. Patient's charts were reviewed and only those where the clinical diagnosis of inverse psoriasis was also favored were included. Results 12 patients met inclusion criteria - 58% male and 42% female, 18-86 years of age. Classic features of psoriasis such as hypogranulosis, confluent parakeratosis, and thinning of the suprapapillary plate were seen in 100%. Regular psoriasiform acanthosis and dilated tortuous dermal vessels were seen in 92%. Neutrophils were present in the scale in 83% and in the dermis in 100%. Features considered atypical for psoriasis included spongiosis in 83%, eosinophils in 67%, and focal serum in the scale in 42%. Conclusions While inverse psoriasis commonly exhibits features considered to be classic for psoriasis, it is not unusual for inverse psoriasis to show features considered atypical for plaque psoriasis such as dermal eosinophils, epidermal spongiosis, and focal serum in the scale. This article is protected by copyright. All rights reserved.

BACKGROUND Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real-world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders. MATERIALS AND METHODS A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure. RESULTS Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with

Background Black men in the United States have markedly higher rates of prostate cancer than the general population. National guidelines for prostate-specific antigen (PSA) screening do not provide clear guidance for this high-risk population. The purpose of this study is to estimate the benefit and harm of intensified PSA screening in Black men. Methods Two microsimulation models of prostate cancer calibrated to incidence from the Surveillance, Epidemiology, and End Results program among Black men project the impact of different screening strategies (varying screening intervals, starting and stopping ages, and biopsy utilization following an abnormal PSA) on disease-specific mortality and overdiagnosis. Each strategy induces a mean lead time (MLT) for detected cases. A longer MLT reduces mortality according to estimates combining the US and European prostate cancer screening trials but increases overdiagnosis. Results Under historical population screening, Black men had similar MLT to men of all races and similar mortality reduction (range between models = 21%-24% vs 20%-24%) but a higher frequency of overdiagnosis (75-86 vs 58-60 per 1000 men). Screening Black men aged 40-84 years annually would increase both mortality reduction (29%-31%) and overdiagnosis (112-129 per 1000). Restricting screening to ages 45-69 years would still achieve substantial mortality reduction (26%-29%) with lower overdiagnosis (51-61 per 1000). Increasing biopsy utilization to 100% of abnormal tests would further reduce mortality but substantially increase overdiagnosis. Conclusions Annual screening in Black men is expected to reduce mortality more than that estimated under historical screening. Limiting screening to men younger than 70 years is expected to help reduce overdiagnosis.

The purpose of this study was to evaluate which radiological depth of invasion (r-DOI) measurement is the most concordant to clinical DOI (c-DOI) derived from correction for the shrinkage rate of the histopathological specimens.We retrospectively reviewed 128 patients with tongue carcinoma who had undergone glossectomy between 2006 and 2019. At first, the width shrinkage rate during formalin fixation and preparation process of histopathological specimens was evaluated. From the shrinking rates, a formula to calculate c-DOI from pathological DOI (p-DOI) was developed. The correlation between c-DOI and r-DOI was evaluated.The specimen shrinkage rate during the histopathological specimen preparation process was 10.3%. Based on that, we yielded the correct formula for c-DOI based on p-DOI and preparation shrinkage rate: c-DOI = p-DOI × 100/89.7. The regression equations for the association of c-DOI with r-DOI measured by ultrasound (n = 128), MRI before biopsy (n = 18), and MRI after biopsy (n = 110) were y = 1.12 * x + 0.21, y = 0.89 * x − 0.26, and y = 0.52 * x + 2.63, respectively, while the coefficients of determination were 0.664, 0.891, and 0.422, respectively. In conclusion, r-DOI using MRI before biopsy most strongly correlated with c-DOI.

To determine the impact of definitive presurgical diagnosis on surgical margins in breast-conserving surgery (BCS) for primary carcinomas; clinicopathological features were also analyzed.This retrospective study included women who underwent BCS for primary carcinomas in 2016 and 2017. Definitive presurgical diagnosis was defined as having a presurgical core needle biopsy (CNB) and not being upstaged between biopsy and surgery. Biopsy data and imaging findings including breast density were retrieved. Inadequate surgical margins (IM) were defined per latest ASCO and ASTRO guidelines. Univariable and multivariable analyses were performed.360 women (median age, 66) met inclusion criteria with 1 having 2 cancers. 82.5% (298/361) were invasive cancers while 17.5% (63/361) were ductal carcinoma in situ (DCIS). Most biopsies were US-guided (284/346, 82.0%), followed by mammographic (60/346, 17.3%), and MRI-guided (2/346, 0.6%). US and mammographic CNB yielded median samples of 2 and 4, respectively, with a 14G needle. 15 patients (4.2%) lacked presurgical CNB. The IM rate was 30.0%. In multivariable analysis, large invasive cancers (20 mm), dense breasts, and DCIS were associated with IM (p = 0.029, p = 0.010, and p = 0.013, respectively). Most importantly, lack of definitive presurgical diagnosis was a risk factor for IM (OR, 2.35; 95% CI: 1.23-4.51, p = 0.010). In contrast, neither patient age (50) nor aggressive features (e.g., LVI) were associated with IM.Lack of a definitive presurgical diagnosis was associated with a two-fold increase of IM in BCS; other risk factors were dense breasts, large invasive cancers, and DCIS.

Background By comparing the detection rate and type of targeted gene mutations in non-small cell lung cancer (NSCLC) between amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS), the characteristics and application advantages of non-small cell lung cancer detection are explained, providing a basis for clinicians to effectively select the corresponding detection methods. Methods and materials The cases of targeted genes for lung cancer were selected from the First Affiliated Hospital of Chongqing Medical University from January 2016 to October 2020. A sample of 4467 cases was selected, and they were diagnosed with NSCLC by Pathological biopsy. Sample sources include surgical resection, bronchoscope biopsy, metastatic biopsy, blood, sputum, cytology of pleural effusion. Among them, 3665 cases were detected by ARMS-PCR technique, and 802 cases were detected by NGS technology. The detection rate and type of ARMS-PCR and NGS techniques for EGFR gene mutations (including exon 18, exon 19, exon 20, exon 21 and so on) in different NSCLC samples were compared, respectively. Results The total mutation rate of EGFR gene detected by ARMS-PCR was 47.6% while 42.4% detected by NGS which indicated that there was a significant difference between the two methods in detecting total mutation of EGFR gene (P Conclusion It showed that NGS could direct the drug use for the resistant patients. However, some rare loci could be detected by NGS but the importance and directed meaning are still unknown and the number of rare mutations is rare too. Further research on new biomarkers and technique is still needed for early diagnosis, directing drug use and assessing the therapy prognosis.

MRI-targeted prostate biopsy improves detection of clinically significant prostate cancer (PCa). However, up to 70% of PCa lesions display intralesional tumor heterogeneity. Current target sampling strategies do not yet adequately account for this finding. This prospective study included 118 patients who underwent transperineal robotic assisted biopsy of the prostate. We identified a total of 58 PCa-positive PI-RADS lesions. We compared diagnostic accuracy of a target-saturation biopsy strategy to accuracy of single, two, or three randomly selected targeted biopsy cores and analysed potential clinical implications. Intralesional detection of clinically significant cancer (ISUP ≥ 2) was 78.3% for target-saturation biopsy and 39.1%, 52.2%, and 67.4% for one, two, and three targeted cores, respectively. Target-saturation biopsies led to a more accurate characterization of PCa in terms of Gleason score and reduced rates of significant cancer missed. Compared to one, two, and three targeted biopsy cores, target-saturation biopsies led to intensified staging procedures in 21.7%, 10.9, and 8.7% of patients, and ultimately to a potential change in therapy in 39.1%, 26.1%, and 10.9% of patients. This work presents the concept of robotic-assisted target saturation biopsy. This technique has the potential to improve diagnostic accuracy and thus individual staging procedures and treatment decisions.

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.

Purpose To assess differences in referral and pathologic outcomes for uro-oncology cases prior to and during the COVID pandemic, comparing clinical and pathological data of cancer surgeries performed at an academic referral center between 2019 and 2020. Methods We collected data of 880 prostate biopsies, 393 robot-assisted radical prostatectomies (RARP) for prostate cancer (PCa), 767 trans-urethral resections of bladder tumor (TURB) and 134 radical cystectomies (RC) for bladder cancer (BCa), 29 radical nephro-ureterectomies (RNU) for upper tract urothelial carcinoma, 130 partial nephrectomies (PN) and 12 radical nephrectomies (RN) for renal cancer, and 41 orchifunicolectomies for testicular cancer. Data of patients treated in 2019 (before COVID-19 pandemic) were compared to patients treated in 2020 (during pandemic). Results No significant decline in uro-oncological surgical activity was seen between 2019 and 2020. No significant increase in time between diagnosis and surgery was observed for all considered cancers. No differences in terms of main pathologic features were observed in patients undergoing RARP, TURB, RNU, RN/PN, or orchifunicolectomy. A higher proportion of ISUP grade 3 and 4 PCa were diagnosed in 2020 at biopsy (p = 0.001), but this did not translate into worse pathological grade/stage at RARP. In 2020, more advanced disease features were seen after RC, including lymph node involvement (p = 0.01) and non-organ confined disease (p = 0.02). Conclusion Neither decline in uro-oncologic activity nor delay between diagnosis and treatment was observed at our institution during the first year of COVID-19 pandemic. No significant worsening of cancer disease features was found in 2020 except for muscle-invasive BCa. Supplementary Information The online version contains supplementary material available at 10.1007/s00345-021-03842-y.

AIMS To examine our hypothesis that a higher number of touching tumour-infiltrating lymphocytes (TILs) in low-risk ductal carcinoma in situ (DCIS) detected in a setting such as an active surveillance clinical trial correlates with upgrading to high-grade DCIS (HG-DCIS) in the subsequent excisional biopsy. METHODS AND RESULTS The clinical inclusion criteria of the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) trial were applied to women who were mammographically screened between 2007 and 2017. In the core needle biopsy, touching TILs were assessed by counting the number of TILs touching the ductal basement membrane or away from it by one lymphocyte thickness. The highest number of TILs around a single involved duct and the average number among involved ducts were recorded. DCIS was graded as low or intermediate. Twenty-six of 129 (20.2%) cases had upgrading [14 (10.9%) to pure HG-DCIS, and 12 (9.3%) to invasive carcinoma, two of them with concurrent HG-DCIS]. An increased average number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 11 of 16 (68.8%) cases, and a decreased average number of touching TILs and low-grade DCIS correlated with no upgrading in 89 of 113 (78.8%) cases [accuracy of 0.775; area under the curve (AUC) of 0.746]. An increased highest number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 12 of 16 (75%) cases, and a decreased highest number of touching TILs and low-grade DCIS correlated with no upgrading in 82 of 113 (72.6%) cases (accuracy of 0.7287; AUC of 0.734). A highest number of touching TILs of ≥10 correlated with upgrading to invasive carcinoma and/or HG-DCIS (P = 0.018). CONCLUSIONS Intermediate-grade and touching TILs may be good variables to examine in the COMET trial and to correlate with the risk of upgrading.

Background Advanced hepatocellular carcinoma (HCC) is commonly diagnosed using non-invasive radiological criteria (NIRC) defined by the European Association for the Study of the Liver or the American Association for the Study of Liver Diseases. In 2017, The National Institute for Clinical Excellence mandated histological confirmation of disease to authorise the use of sorafenib in the UK. Methods This was a prospective multicentre audit in which patients suitable for sorafenib were identified at multidisciplinary meetings. The primary analysis cohort (PAC) was defined by the presence of Child-Pugh class A liver disease and performance status 0–2. Clinical, radiological and histological data were reported locally and collected on a standardised case report form. Results Eleven centres reported 418 cases, of which 361 comprised the PAC. Overall, 76% had chronic liver disease and 66% were cirrhotic. The diagnostic imaging was computed tomography in 71%, magnetic resonance imaging in 27% and 2% had both. Pre-existing histology was available in 45 patients and 270 underwent a new biopsy, which confirmed HCC in 93.4%. Alternative histological diagnoses included cholangiocarcinoma (CC) and combined HCC-CC. In cirrhotic patients, NIRC criteria had a sensitivity of 65.4% and a positive predictive value of 91.4% to detect HCC. Two patients (0.7%) experienced mild post-biopsy bleeding. Conclusion The diagnostic biopsy is safe and feasible for most patients eligible for systemic therapy

BACKGROUND Early and accurate diagnosis of subungual melanoma (SUM) through histopathologic examination is critical, but lack of clinical suspicion leads to delays in diagnosis. Hutchinson sign (HS) can be one of the important clinical indicators for diagnosing SUM. OBJECTIVE To evaluate the diagnostic value of small biopsies of HS for detecting SUM in situ. METHODS We retrospectively evaluated 12 patients who were diagnosed as SUM in situ and underwent punch biopsy at HS areas. Clinical features, dermoscopic findings, and histopathologic findings in HS regions were analyzed. RESULTS In most cases, HS was seen in hyponychium (11/12, 91.7%) with 1 case found in proximal nail fold, and 1 case in both the hyponychium and proximal nail fold. Dermoscopic features of HS showed irregular diffuse pigmentation (12/12, 100%) and parallel ridge pattern (7/12, 58.3%). Histopathologically, all cases showed irregularly scattered atypical melanocytes with hyperchromatic nuclei. Two cases showed subtle changes in melanocytes with little nuclear atypia, but additional section specimen showed more definitive findings of SUM in situ. CONCLUSION We present a supplementary biopsy technique for diagnosing SUM. Biopsy of HS may help in the diagnosis of SUM.

BACKGROUND The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P

Sprue-like enteropathy associated with olmesartan is characterized by villous atrophy in the duodenum. We report the case of an 81-year-old woman diagnosed with olmesartan-associated sprue-like enteropathy with no villous atrophy in the duodenum. The patient had been taking olmesartan for 10 years and complained of diarrhea and weight loss. Despite undergoing general treatment for 2 months, her symptoms showed no improvement. Gastrointestinal endoscopy and pathological findings showed no villous atrophy in the duodenum. However, villous atrophy was observed in the small intestine by capsule endoscopy. Pathological biopsy with double balloon endoscopy provided a definitive diagnosis. Diarrhea improved with the discontinuation of olmesartan and weight increased within a week of withdrawal. After the improvement of clinical symptoms, both endoscopic and pathological findings of villous atrophy in small intestine showed improvement.

The purpose of this study was to retrospectively compare two puncture routes (transpleural vs. transpulmonary) for computed tomography (CT) fluoroscopy-guided cutting needle biopsy of lung nodules with pleural contact.A total of 102 patients (72 men; mean age, 71.1±9.5 [SD] years) were included and 102 biopsies of 102 lung nodules (mean size, 16.7±5.9 [SD] mm; range, 6.0-29.4mm; mean length of pleural contact, 10.1±4.2 [SD] mm; range, 2.8-19.6mm) were analyzed. All procedures were classified as biopsies via the direct transpleural route or the transpulmonary route. The patient-, lesion-, and biopsy-related variables, diagnostic yields, and incidence of complications were compared between the two routes.Biopsy was performed via the direct transpleural route (n=59; 57.8%) and transpulmonary route (n=43; 42.2%). In the transpulmonary route group, the mean distance of the intrapulmonary pathway was 17.7±9.4 [SD] mm (range: 4.1-47.6mm; P0.001) and the introducer needle trajectory angle of45° was significantly observed (8.5% [5/59] vs. 60.5% [26/43]; P0.001). There was no significant difference in diagnostic accuracy between the direct transpleural and transpulmonary routes (93.2% [55/59] vs. 90.7% [39/43]; P=0.718). The frequencies of all complications (64.4% [38/59] vs. 97.7% [42/43]; P0.001), pneumothorax (33.9% [20/59] vs. 65.1% [28/43]; P=0.003), pneumothorax with chest tube placement (3.4% [2/59] vs. 18.6% [8/43]; P=0.016), and pulmonary hemorrhage (47.5% [28/59] vs. 76.7% [33/43]; P=0.004) were significantly lower in the direct transpleural group.Direct transpleural route is recommended for CT fluoroscopy-guided biopsy of lung nodules with pleural contact because it is safer and yields similar diagnostic accuracy than transpulmonary route.

To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy.Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed.11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P0.001). There was no difference in infectious complications between augmented and provider-discretion pathways.The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.

Early Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline., Specific transcriptional changes in microglia associated with Alzheimer’s disease have been reported. Here, the authors show that transcriptional analysis of human hydrocephalus biopsies identifies changes in immune response genes associated with early AD pathology, including cognitive decline.