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Catatonia in children and adolescents is not rare and, as in adults, has a favorable outcome, provided it is recognized and treated promptly. Nevertheless, in clinical practice we encounter several obstacles in terms of diagnosis and treatment in this population of patients. We describe a 14-year-old boy with an intellectually disability and autism spectrum disorder (ASD) in which clinicians did not diagnose catatonia until 1 year after the development of symptoms. Moreover, hesitations surrounding the correct treatment led to its delayed initiation. With this case report we aim to contribute to reduced reluctance and increased alertness in the treatment of catatonia in adolescents with developmental disorders.

Adenocarcinoma, not otherwise specified (NOS) is a heterogenous group of salivary gland tumors that likely contains distinct tumors that have not yet been characterized. Indeed, in recent years, cases previously diagnosed as adenocarcinoma, NOS have been recategorized into novel tumor designations such as secretory carcinoma, microsecretory adenocarcinoma, and sclerosing microcystic adenocarcinoma. We sought to describe a distinctive, hitherto-undescribed salivary gland tumor encountered in the authors' practices. Cases were pulled from the surgical pathology archives of the authors' institutions. Histologic, immunohistochemical, and clinical findings were tabulated, and targeted next-generation sequencing was performed on all cases. Nine cases were identified, arising in 8 women and 1 man ranging from 45 to 74 years (mean, 56.7 y). Seven tumors (78%) arose in the sublingual gland, while 2 (22%) arose in the submandibular gland. The cases shared a distinctive morphologic appearance. They were biphasic, with ducts scattered among a predominant polygonal cell with round nuclei, prominent nucleoli, and pale eosinophilic cytoplasm. These cells were arranged as trabeculae and palisaded as pseudorosettes around hyalinized stroma and vessels, resembling a neuroendocrine tumor. Four of the cases were well-circumscribed, while the remaining 5 showed infiltrative growth including perineural invasion in 2 (22%) and lymphovascular invasion in 1 (11%). Mitotic rates were low (mean, 2.2/10 HPFs); necrosis was absent. By immunohistochemistry, the predominant cell type was strongly positive for CD56 (9 of 9) and variably positive for pan-cytokeratin (AE1/AE3) (7 of 9) with patchy S100 (4 of 9), but negative for synaptophysin (0 of 9) and chromogranin (0 of 9), while the ducts were strongly positive for pan-cytokeratin (AE1/AE3) (9 of 9) and CK5/6 (7 of 7). Next-generation sequencing did not reveal any fusions or obvious driver mutations. All cases were resected surgically, with external beam radiation also done in 1 case. Follow-up was available in 8 cases; there were no metastases or recurrences after 4 to 160 months (mean, 53.1 mo). A dual population of scattered ducts with a predominance of CD56-positive neuroendocrine-like cells characterizes a unique salivary gland tumor which is often encountered in the sublingual glands of women, for which we propose the term "palisading adenocarcinoma." Although the tumor was biphasic and had a neuroendocrine-like appearance, it lacked convincing immunohistochemical evidence of myoepithelial or neuroendocrine differentiation. Although a subset showed unequivocally invasive growth, this tumor appears to behave in an indolent manner. Moving forward, recognition of palisading adenocarcinoma and its separation from other salivary adenocarcinomas, NOS will facilitate a better understanding of the characteristics of this previously unrecognized tumor., Competing Interests: Conflicts of Interest and Source of Funding: Supported by Jane B. and Edwin P. Jenevein M.D Endowment for Pathology at UT Southwestern Medical Center. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: The optimal stereotactic ablative radiotherapy (SABR) doses for adrenal tumors are unknown. Some trials have specified that organ at risk (OAR) dose constraints should take priority over target coverage. We performed a retrospective review of the outcomes of MR-guided adrenal SABR (MRgRT) delivered with OAR sparing., Materials and Methods: Patients who underwent adrenal MRgRT between 2016 and 2023 were identified from our Ethics-approved institutional database. Dose ranged between 8 and 24 Gy per fraction, delivered in 1-5 fractions. A 3 mm margin was added to the breath-hold gross tumor volume (GTV) to derive a PTV. Plan were delivered to an 'optimized' PTV that was generated by excluding any overlap with OARs., Results: Adrenal SABR was performed in 107 patients (114 metastases). The commonest scheme used 5 fractions of 10 Gy (53.5 %); 82 % of plans delivered a BED 10 ≧ 80 Gy. Systemic therapy was administered within 3 months preceding or following SABR in 53.5 % of patients. Grade 3 acute toxicity (CTCAE v5.0) occurred in 0.9 % of patients, and 4.4 % reported late toxicity, consisting of adrenal insufficiency and a vertebral collapse. Median follow-up was 13.8 months (range, 0.0-73.4 months). Local progression occurred in 7.4 % of evaluable patients. PTV underdosage was frequent, with a coverage compromise index (D99/prescription dose) of < 0.90 in 52 % of all plans. Recurrences were independent of the prescription doses., Conclusion: MRgRT for adrenal metastases is well tolerated with high local control rates despite prioritizing OAR sparing over PTV coverage. Studies using deformable dose accumulation may lead to a better understanding of dose-response relationship with adaptive SABR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

A 76-year-old gentleman presented with persistent lower urinary tract symptoms. Multiple biopsies, radiological correlation and ancillary studies were required to achieve a diagnosis. The main differential diagnoses lies between urothelial carcinoma and anaplastic large cell lymphoma (ALCL), both of which are known to be positive for p63 and GATA3. An accurate diagnosis is crucial as the management is significantly different. To avoid misdiagnosis a comprehensive immunohistochemistry panel is necessary. Primary bladder lymphomas are rare. Our case represents the first case of primary ALK-negative TP63-rearranged ALCL. We reviewed the literature and discussed the potential pitfalls for misdiagnosis.

Background: We performed a retrospective analysis to determine the incidence of neurotrophic tropomyosin-receptor kinase ( NTRK) fusion in non-small cell lung cancer (NSCLC)., Methods: Archival NSCLC tissues between 2018-2020 were screened by immunohistochemistry (IHC) with IHC-positive cases undergoing confirmatory molecular analysis. Correlative clinicopathologic parameters were collected., Results: Of 289 samples analyzed, 10 (3.5%) cases had NTRK expression on IHC. The median age of patients with NTRK-positivity on IHC was 74.9 (range, 44-88) years and 70% had a smoking history. The cohort included seven adenocarcinomas and one each squamous cell carcinoma, large-cell neuroendocrine and not otherwise specified histologies. PDL1 expression was ≤50% in five cases. Concurrent EGFR mutations were detected in three cases, with two cases also showing a PIK3CA E542K mutation and MET amplification, respectively. Due to insufficient tumor material, RNA-sequencing was undertaken in only one IHC-positive case, with the other nine cases analyzed by Fluorescent in-situ Hybridisation. A NTRK fusion, EML4-NTRK3 gene fusion was detected in one patient, a frequency of 0.35%., Conclusions: NTRK fusions in NSCLC are rare. This study highlights real world diagnostic challenges regarding NTRK testing, such as requirements of adequate tumor tissue and appropriate testing methodologies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-113/coif). SP served on the advisory board of Astra Zeneca, received speaking honoraria from Astra Zeneca, Roche and MSD, and received research funding from Roche outside the submitted work. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Children and youth with an intellectual disability and psychiatric problems are a complex group. By identifying clients who require highly specialized mental health care at an early stage, it is expected that the provided care can be utilized more effectively, there will be less non-response and clients will more efficiently receive the most appropriate care., Aim: To develop a decision tool which can identify clients who need highly specialized care at an early stage., Method: A review of the literature and qualitative research methods were used, including a Delphi study to get consensus on criteria that could be used as indicators for highly specialized care. These criteria were included in a decision tool, followed by validation of these criteria by testing them on the population of the Banjaard, a mental health care setting for young people with intellectual disability and psychiatric problems., Results: Ten criteria emerged from the Delphi method that were seen to be predictive of the need for highly specialized care. After applying these criteria to the Banjaard population, it appeared that three or more criteria reliably identified clients needing highly specialized care (sensitivity 76.5% and specificity 75.6%)., Conclusion: The decision tool developed in the current study is a reasonable instrument for identifying clients who could benefit from highly specialized mental health care.

Background: The effectiveness of mental health care is currently monitored through routine quantitative symptom-driven measurements in most clinical settings. These measurements seem inadequate, especially for target groups with complex, multi-faceted problems. There is as yet no alternative method., Aim: 1. To describe why quantitative symptom-driven measurements are inadequate for measuring healthcare effectiveness; and 2. to introduce a new data platform that adjusts for socioeconomic and environmental factors to monitor the effectiveness of healthcare., Method: Overview of developments based on literature and introduction of a unique data platform., Results: In the case of complex, multi-faced problems, such as in children with mild intellectual disability and comorbid psychopathology, mental health problems cannot be quantified, isolated, and individualized, i.e., decontextualized. To evaluate care for external benchmarking and scientific research, a shift is advised from measuring clinical symptoms within the treatment period to measuring longer-term group-level social functioning across multiple life domains, with a focus on socio-demographic differences. The Extramuraal LUMC Academisch Netwerk Gezond & Gelukkig Den Haag (ELAN-GGDH ; in English: Extramural LUMC Academic Network Healthy & Happy The Hague) data platform accomplishes this by combining mental health data with Statistics Netherlands microdata., Conclusion: The data platform could add value to external benchmarking and scientific research at group level.

Introduction: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy., Methods: PM cases (n = 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n = 234)., Results: BAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio = 2.49, p < 0.001, and 1.48, p = 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p < 0.001) and Australian cohorts (19.6 versus 11.1 mo, p < 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p < 0.01)., Conclusions: BAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification., (Copyright © 2022 International Association for the Study of Lung Cancer. All rights reserved.)

We studied treatment patterns for adrenal metastases using surgery or SABR at a single institution during a 10-year period. The number of patients undergoing SABR doubled since 2016, without a change in numbers undergoing surgery. Both treatments resulted in low rates of acute toxicity and similar survivals., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized., Methods: All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples., Results: The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples., Conclusions: Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ., (© 2022 American Cancer Society.)

When pain persists beyond healing time and becomes a "false alarm" of bodily threat, protective strategies, such as avoidance, are no longer adaptive. More specifically, generalization of avoidance based on conceptual knowledge may contribute to chronic pain disability. Using an operant robotic-arm avoidance paradigm, healthy participants (N = 50), could perform more effortful movements in the threat context (eg, pictures of outdoor scenes) to avoid painful stimuli, whereas no pain occured in the safe context (eg, pictures of indoor scenes). Next, we investigated avoidance generalization to conceptually related contexts (ie, novel outdoor/indoor scenes). As expected, participants avoided more when presented with novel contexts conceptually related to the threat context than in novel exemplars of the safe context. Yet, exemplars belonging to one category (outdoor/indoor scenes) were not interchangeable; there was a generalization decrement. Posthoc analyses revealed that contingency-aware participants (n = 27), but not non-aware participants (n = 23), showed the avoidance generalization effect and also generalized their differential pain-expectancy and pain-related fear more to novel background scenes conceptually related to the original threat context. In contrast, the fear-potentiated startle response was not modulated by context. PERSPECTIVE: This article provides evidence for contextual modulation of avoidance behavior and its generalization to novel exemplars of the learned categories based on conceptual relatedness. Our findings suggest that category-based generalization is a plausible mechanism explaining why patients display avoidance behavior in novel situations that were never directly associated with pain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology., Methods: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis., Results: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus., Conclusions: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy., (© 2021 John Wiley & Sons Ltd.)

Abstract: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated repressor of retinoic acid signaling which is expressed in melanoma and has emerged as a potential biomarker for malignant behavior in melanocytic neoplasms. Although ancillary molecular techniques such as fluorescence in situ hybridization (FISH) are established techniques in the diagnosis of problematic cutaneous melanocytic proliferations, they are expensive, time-consuming, and require appropriate infrastructure, which places them out of reach of some laboratories. The advent of readily available commercial antibodies to PRAME has the potential to provide a more accessible alternative. The aim of this study was to determine whether immunohistochemistry for PRAME could serve as a surrogate for FISH analysis in a subgroup of challenging superficial melanocytic proliferations. Cases which had previously been submitted for FISH analysis were stained for PRAME and interpreted by a panel of at least 3 dermatopathologists is a blinded fashion. Of a study set of 55 cases, 42 (76%) showed a pattern of PRAME immunostaining which was concordant with the cytogenetic interpretation, with an unweighted kappa of 0.42 (representing mild-to-moderate agreement). Thus, although there was a correlation between positive immunohistochemistry for PRAME and abnormal findings on FISH analysis, in our view, the concordance was not sufficient to enable PRAME immunohistochemistry to act as a surrogate for FISH testing. Our findings reiterate the principle that interpretation of problematic superficial melanocytic proliferations requires a synthesis of all the available data, including clinical scenario, morphological features, immunohistochemistry, and ancillary molecular investigations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The distinction between nevoid melanoma and a mitotically active nevus can be challenging at the microscopic level. In this study, we performed cytogenetic testing on a cohort of 25 mitotically active melanocytic proliferations resembling common melanocytic nevus from 25 patients. Based on cytogenetic findings, the lesions were classified as "nevoid melanoma" (n = 13) or "mitotically active nevus" (n = 12). Subsequently, we compared the clinicopathological features between these 2 groups. Nevoid melanomas occurred in older patients (P = 0.007); however, there were no significant differences in gender, size, or anatomical distribution between the 2 groups. Histologically, deep/marginal mitoses (P = 0.006), lack of maturation with depth (P = 0.036), and pseudo-maturation (P = 0.006) were significantly more common in nevoid melanomas. Immunohistochemically, complete loss of p16 was an important divisive feature (P = 0.0004), seen in 70% of nevoid melanomas, and highly correlated with loss of CDKN2A gene (chromosome 9p21). Our findings suggest that such reproducible immunomorphological differences can be of value in distinguishing nevoid melanoma from mitotically active nevus. Nevoid melanomas demonstrated a spectrum of chromosomal aberrations similar to those seen in common subtypes of melanoma, which can serve as a powerful adjunct diagnostic tool in morphologically challenging lesions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Contingency learning, i.e. learning that a cue predicts the presence (or absence) of an event, is central to the formation of beliefs regarding painfulness of body postures. Such beliefs may spread to safe cues due to compromised learning (e.g., excessive generalization, impaired safety learning), prompting avoidance and leading to disability. Despite its importance, compromised learning about low back pain is underinvestigated. We propose a low back pain scenario contingency learning task for the investigation of back pain-related learning., Methods: Sixty healthy participants viewed pictures of an avatar in various back postures, and for each posture gave pain-expectancy judgments and viewed the verbal outcome (pain/no pain) for a fictive back pain patient. During acquisition, one posture was followed by pain (conditioned stimulus; CS+), whereas another was not (CS-). During generalization, unreinforced novel intermediate back postures (generalization stimuli; GSs) were tested. During extinction, only the CSs were presented, not followed by pain. During generalization of extinction, only the GSs were presented, not followed by pain., Results: Participants expected pain more for the CS + than the CS- (differential acquisition) and generalized their pain-expectancy to the GS most similar to the CS+ (generalization). During extinction, pain-expectancy for the CS + decreased and generalized to the GS most similar to the CS+ (generalization of extinction)., Limitations: Future research should investigate generalizability of findings to clinical samples and consider the role of pre-existing pain threat beliefs., Conclusions: This task is an easily applicable, non-invasive way to investigate the formation of back pain-related threat beliefs., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BRCA1-associated protein-1 (BAP1)-deficient cutaneous tumors are common in patients with BAP1 tumor predisposition syndrome, frequently presenting before other associated neoplasms, and can serve as an early marker to identify individuals with this disease. The typical lesions are dermal based and composed of a combination of larger epithelioid melanocytes with abundant glassy cytoplasm and smaller cells resembling those of a conventional nevus. There is often a component of interspersed lymphocytes. However, BAP1-deficient melanocytic tumors can show a spectrum of histologic appearances, ranging from lesions with pure epithelioid, pure conventional nevus, or rhabdoid cells and tumors with an intraepidermal component. To demonstrate such morphologic variation, we present a case of a 50-year-old woman with multiple histologically diverse BAP1-deficient melanocytic tumors and germline BAP1 mutation, identified after a diagnosis of pleural mesothelioma. We also discuss the pathogenesis and potential histopathological and clinical indications of germline versus sporadic etiology in the assessment of BAP1-deficient melanocytic tumors.

A group of melanomas characterised by predominant growth as large nests within the epidermis has been described. These cases present a diagnostic challenge, as many traditional architectural criteria for the recognition of melanoma are absent. We report the clinical, histological, immunohistochemical, morphometric and cytogenetic features of a series of 12 cases of large nested melanoma. In this series, large nested melanoma accounted for 0.2% of cases of melanoma. The majority occurred on the trunk of middle aged patients with absent or minimal solar elastosis and 42% were associated with a component of benign intradermal melanocytic naevus, speaking to classification of these melanomas as falling within the spectrum of lesions developing in skin with low cumulative sun damage. In 67% of cases invasive melanoma was present. Criteria such as asymmetry, variation in nest size and intraepidermal nests with an underlying rim of junctional keratinocytes appear to be highly specific, and are strongly predictive of typical cytogenetic abnormalities of melanoma, which were identified in 92% of cases. Conversely, in addition to features which are definitionally absent or limited, features such as solar elastosis and cytological atypia do not appear to be particularly helpful in recognition of this variant., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

T- and NK-cell lymphoproliferative disorders of the gastrointestinal (GI) tract are uncommon, but are important to recognise as there may be morphological and immunophenotypic overlap between lymphoid lesions with vastly different clinical outcomes. Recent data have led to the reclassification of some lymphomas and inclusion of new entities in the 2016 revision of World Health Organization (WHO) classification of lymphoid neoplasms. It has become clear that enteropathy associated T-cell lymphoma (EATL), formerly thought to be composed of two subtypes known as type I and type II, are distinct entities. Type I EATL is now simply classified as EATL; it is strongly associated with coeliac disease and occurs mainly in Western populations. Type II EATL has been renamed monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); it shows no definite association with coeliac disease and occurs worldwide with a predominance in Asian populations. There is also a group of aggressive intestinal T-cell lymphomas which do not meet criteria for EATL, MEITL, extranodal NK/T-cell lymphoma of nasal type or anaplastic large cell lymphoma. These neoplasms are now designated intestinal T-cell lymphoma, not otherwise specified. Indolent T-cell lymphoproliferative disorder of the GI tract has been included as a provisional entity in the most recent WHO classification. It is a clonal T-cell lymphoproliferative disorder (CD4+ or CD8+) with an indolent clinical course. Finally, benign NK-cell proliferations of the GI tract, variably designated 'NK-cell enteropathy' and 'lymphomatoid gastropathy' have also been recognised in the last two decades but have not been included in the WHO classification as their neoplastic nature is not established. This review covers the aforementioned lymphoid proliferations, emphasising their salient clinicopathological features and genetic abnormalities. It also provides practical insights into resolving difficult differential diagnoses in daily surgical pathology practice., (Copyright © 2019. Published by Elsevier B.V.)

Pancreatoduodenectomy (PD) is increasingly performed in high-volume centers, which may compromise waiting times. The aim of this study was to evaluate patient flow and outcome of PD within a regional oncology network of two high-volume centers. A post hoc analysis of a partially retrospective and prospective database was performed of all patients who underwent PD for pancreatic or periampullary neoplasms in both centers of the Gastrointestinal Oncology Center Amsterdam, a collaboration between an academic center and affiliated general teaching hospital, from 2010 to 2014. Outcomes included waiting time to surgery and postoperative morbidity and mortality. A total of 525 PDs were performed, 329 in the academic center (annual volume 66) and 196 in the teaching hospital (annual volume 39). Neoadjuvant treatment was more often used in the academic center, other baseline characteristics were similar. Overall time to surgery was 26 days, which was significantly less in the teaching hospital. The major postoperative morbidity rate was 38.3% (n = 201), and the 30- and 90-day mortality was 2.3% and 3.6%. A regional oncology network between an academic center and a general teaching hospital for PD can be an attractive option to safeguard waiting times in selected patients, without compromising outcome.

In advanced-stage diffuse large B-cell lymphoma (DLBCL), the presence of an activated B-cell phenotype or a non-germinal center (GCB) phenotype, coexpression of MYC and BCL2 by immunohistochemistry, and the cooccurrence of MYC and BCL2 or BCL6 rearrangements are associated with inferior outcomes. It is unclear whether these variables remain prognostic in stage I/II patients. In this retrospective study, we evaluated the prognostic impact of cell of origin (COO), as well as dual-expressor (DE) status and molecular double-hit (DH) status, in stage I/II DLBCL by positron emission tomography with computed tomography (PET-CT). A total of 211 patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens, with or without radiotherapy, was included. The median follow-up in the entire cohort was 4 years (range, 0.4-9.4), with estimated 4-year progression-free survival (PFS) and overall survival (OS) rates of 85% (95% confidence interval [CI], 79-89) and 88% (95% CI, 83-92), respectively. By univariable analysis, DE (PFS: hazard ratio [HR], 1.27; 95% CI, 0.58-2.81, P = .55 and OS: HR, 1.40; 95% CI, 0.60-3.30; P = .44), DH (PFS: HR, 1.21; 95% CI, 0.27-5.31; P = .80 and OS: HR, 0.61; 95% CI, 0.08-4.73; P = .64), and non-GCB status (PFS: HR, 1.59; 95% CI, 0.83-3.03; P = .16 and OS: HR, 1.80; 95% CI, 0.89-3.67; P = .10) were associated with poorer outcomes. In patients with PET-CT-defined stage I/II DLBCL treated with R-CHOP-like therapy, with or without radiation, COO and DE and DH status were not significantly associated with inferior PFS or OS., (© 2019 by The American Society of Hematology.)

In chronic pain, pain-related fear seems to overgeneralize to safe stimuli, thus contributing to excessive fear and avoidance behavior. Evidence shows that pain-related fear can be acquired and generalized based on conceptual knowledge. Using a fear conditioning paradigm, we investigated whether this concept-based pain-related fear could also be extinguished. During acquisition, exemplars of 1 action category (conditioned stimuli [CSs]; eg, opening boxes) were followed by pain (CS+), whereas exemplars of another action category were not (CS-; eg, closing boxes). Participants reported more pain-related fear and expectancy toward exemplars of the CS+ category compared with those of the CS- category. During generalization, fear and expectancy spread to novel exemplars (generalization stimuli [GSs]) of the CS+ category (GS+), but not to those of the CS- category (GS-). During extinction, exemplars of both categories were presented in the absence of pain. At the end of extinction, participants no longer reported elevated fear or expectancy toward CS+ exemplars compared to CS- exemplars. These findings were not replicated in either the eye-blink startle or skin conductance measures. This is the first study to demonstrate extinction of concept-based pain-related fear, thus providing evidence for the potential of extinction-based techniques in the treatment of conceptual pain-related fear. PERSPECTIVE: This study demonstrates the acquisition, generalization, and extinction of concept-based pain-related fear in healthy participants. These are the first results to show that concept-based pain-related fear can be extinguished, suggesting that conceptual relationships between fear-inducing stimuli may also be important to consider in clinical practice., (Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Visual expertise induces changes in neural processing for many different domains of expertise. However, it is unclear how expertise effects for different domains of expertise are related. In the present fMRI study, we combine large-scale univariate and multi-voxel analyses to contrast the expertise-related neural changes associated with two different domains of expertise, bird expertise (ornithology) and mineral expertise (mineralogy). Results indicated distributed expertise-related neural changes, with effects for both domains of expertise in high-level visual cortex and effects for bird expertise even extending to low-level visual regions and the frontal lobe. Importantly, a multivariate generalization analysis showed that effects in high-level visual cortex were specific to the domain of expertise. In contrast, the neural changes in the frontal lobe relating to expertise showed significant generalization, signaling the presence of domain-independent expertise effects. In conclusion, expertise is related to a combination of domain-specific and domain-general changes in neural processing., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Granular cell tumour is a rare soft tissue tumour that can occur in any part of the body, but seldom in ocular adnexa. It usually behaves in a benign fashion. We report a case of a 54-year-old man with a well-demarcated, solitary, slow-growing orbital tumour which lead to significant ocular symptoms. The case was a diagnostic and therapeutic challenge due to its location and difficulty in obtaining tissue for a histological diagnosis. Surgical biopsy attempts were made but they all failed to uncover the true identity of the lesion. A definitive diagnosis was revealed with complete surgical excision of the tumour, which was challenging due to its size and close association with rectus muscle. This case has highlighted that orbital granular cell tumour may result in significant ocular symptoms. Adequate exposure to the anatomical site is the key to obtaining diagnosis and complete excision of a lesion.