Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next-generation sequencing.

Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints (RB1, CDKN2A). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics. Expression of AXL messenger RNA is elevated in a variety of sarcoma types, with the highest levels reported in MFS, but the pathogenic significance of this finding remains unknown. To assess a role for AXL abnormalities in MFS, we undertook a search for AXL genomic alterations in a comprehensive genomic profiling database of 463,546 unique tumors (including 19,879 sarcomas, of which 315 were MFS) interrogated by targeted next-generation DNA and/or RNA sequencing. Notably, the only genomic alterations recurrent in a specific sarcoma subtype were AXL W451C (n = 8) and AXL W450C (n = 2) mutations. The tumors involved predominantly older adults (age: 44 to 81 [median: 72] y) and histologically showed epithelioid and spindle-shaped cells in a variably myxoid stroma, with 6 cases diagnosed as MFS, 3 as undifferentiated pleomorphic sarcoma (UPS), and 1 as low-grade sarcoma. The AXL W451C mutation was not identified in any non-sarcoma malignancy. A review of publicly available data sets revealed a single AXL W451C-mutant case of UPS that clustered with MFS/UPS by methylation profiling. Functional studies revealed a novel activation mechanism: the W451C mutation causes abnormal unregulated dimerization of the AXL receptor tyrosine kinase through disulfide bond formation between pairs of mutant proteins expressing ectopic cysteine residues. This dimerization triggers AXL autophosphorylation and activation of downstream ERK signaling. We further report sarcomas of diverse histologic subtypes with AXL gene amplifications, with the highest frequency of amplification identified in MFS cases without the W451C mutation. In summary, the activating AXL W451C mutation appears highly specific to MFS, with a novel mechanism to drive unregulated signaling. Moreover, AXL gene amplifications and messenger RNA overexpression are far more frequent in MFS than in other sarcoma subtypes. We conclude that these aberrations in AXL are distinct features of MFS and may aid diagnosis, as well as the selection of available targeted therapies.

The 2021 Chronic Kidney Disease Epidemiology Collaboration Race-Free Estimated Glomerular Filtration Rate Equations in Kidney Disease: Leading the Way in Ending Disparities.

Purpose: In 2020, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) convened a Task Force to recommend an evidence-based race-free approach to estimated glomerular filtration rate (eGFR). After the rigorous review of more than 20 approaches, the NKF/ASN Task Force published the final report that recommended the implementation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation for eGFR using creatine and expanded utilization of cystatin C testing. The purpose of this manuscript is to provide a comprehensive overview of the evolution of eGFR equations, and an overview of the Task Force deliberations and recommendations. For over two decades, the equation recommended to calculate eGFR included a race coefficient to adjust for data that suggested that American adults with African ancestry had consistently higher serum creatinine levels. Methods: We will provide a discussion illustrating why the 2021 CKD EPI equations are the most equitable solution to eGFR. We will also provide an overview of the current implementation status and best practices for the new equations. Lastly, we will discuss how deployment of the new equations is an important step toward eliminating significant disparities in CKD care which disproportionately affect communities of color. Results: Removing race from the algorithm used to assess kidney function is most equitable. Since race is a social construct, its use in clinical algorithms has facilitated health disparities in Black/African American people, Hispanic/Latino people, and other racial and ethnic minority groups-those who are already disproportionately impacted by diabetes, hypertension, and kidney disease. In turn, these same individuals experience significant inequities in kidney health care including reduced access to nephrology care, home dialysis, and kidney transplant. Conclusions: Adoption of the race-free 2021 CKD-EPI eGFR equations will have life changing implications for kidney health. It will aid in appropriate referral, identification, diagnosis, treatment, and management of kidney disease and transplantation services/options. The outcomes of widespread implementation of the new equations coupled with system change quality improvement interventions such as the kidney profile will lead to more equitable outcomes and begin to address the crippling disparities in early, appropriate testing for CKD.

Synovial Sarcoma of the Gastrointestinal Tract.

We report the clinicopathologic and immunohistochemical features of 18 cases of confirmed primary synovial sarcoma of the gastrointestinal tract. The neoplasms arose in 10 women and 8 men ranging in age from 23 to 81 years (mean: 50; median: 57.5 years). The tumors for which size was known ranged from 1.8 to 15.0 cm (mean: 5.2; median: 5.1 cm). Microscopically, 14 synovial sarcomas were of the monophasic type, 2 were biphasic, and 2 were poorly differentiated. Immunohistochemical analysis of 4 cases showed strong, diffuse staining for SS18::SSX (4/4 cases). Pancytokeratin and EMA immunohistochemistry were performed on 13 and 9 tumors, respectively, and each showed patchy-to-diffuse staining. By reverse-transcription PCR, 3 cases were positive for the SS18::SSX1, and 2 cases were positive for the SS18::SSX2 gene fusion. Six cases contained an SS18 gene rearrangement by fluorescence in situ hybridization, and next-generation sequencing identified an SS18::SSX2 gene fusion in one case. Clinical follow-up information was available for 9 patients (4 months to 4.6 years; mean, 2.8 y; median: 29 months), and one patient had a recent diagnosis. Three patients died of disease within 41 to 72 months (mean, 56 months) of their diagnosis. Five patients were alive without evidence of disease 4 to 52 months (mean, 17.6 months) after surgery; of whom 1 of the patients received additional chemotherapy treatment after surgery because of recurrence of the disease. A single patient was alive with intraabdominal recurrence 13 months after surgery. We conclude that synovial sarcoma of the gastrointestinal tract is an aggressive tumor, similar to its soft tissue counterpart, with adverse patient outcomes. It is important to distinguish it from morphologically similar gastrointestinal tract lesions that may have different treatment regimens and prognoses.

Patterns of Immunoreactivity with TTF-1 Antibodies 8G7G3/1 and SPT24 Suggest Distinct Immunoprofiles Between Most Pulmonary and Nonpulmonary Small Cell Carcinomas.

Introduction. Small cell carcinoma can arise from various sites. Herein, we analyze the ability of 2 thyroid transcription factor-1 (TTF-1) antibodies (SPT24 and 8G7G3/1) to separate pulmonary from nonpulmonary small cell carcinoma. Materials and Methods. We analyzed 26 pulmonary and 83 nonpulmonary small cell carcinomas, and 14 Merkel cell carcinomas. Each tumor was stained with SPT24 and 8G7G3/1. Extent of nuclear staining was scored as diffuse (>50%), focal (11%-50%), rare (1%-10%), or negative (<1%). Results. All pulmonary small cell carcinomas were positive for SPT24 and 8G7G3/1. Four Merkel cell carcinomas (29%) were positive for SPT24 (ranging from rare-to-diffuse), while 2 (14%) showed rare expression with 8G7G3/1. For nonpulmonary small cell carcinomas, 69 (83%) were positive for SPT24 and 40 (48%) were positive for 8G7G3/1. For SPT24 positive tumors, the extent of 8G7G3/1 expression was equal in 17 (25%) and less in 52 tumors (75%), including 29 (42%) that were negative for 8G7G3/1. No nonpulmonary small cell carcinoma had more staining with 8G7G3/1 compared to SPT24. The differences in staining between 8G7G3/1 and SPT24 in the nonpulmonary cohort were statistically significant (P < 0.0001) with no significant difference between primary and metastatic lesions for 8G7G3/1 (P = 0.66) or SPT24 (P = 0.77). Conclusion. Most pulmonary small cell carcinomas are diffusely positive for both SPT24 and 8G7G3/1, whereas most nonpulmonary small cell carcinomas exhibit focal-to-no staining with 8G7G3/1 and significantly less staining with 8G7G3/1 compared to SPT24. However, these trends are not absolute and should be interpreted in conjunction with clinical and radiological findings.

NIPBL::NACC1 Fusion Hepatic Carcinoma.

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.

Pregabalin produces similar effects as gabapentin for preanesthetic sedation in cats.

OBJECTIVE: To compare the effects of oral pregabalin versus gabapentin on sedation quality and anesthesia recovery times in cats in a typical perioperative setting. ANIMALS: 50 healthy cats with > 1 kg body weight presenting for elective surgery. METHODS: In this randomized, prospective clinical trial, cats presenting to the University of California-Davis Veterinary Medical Teaching Hospital were assigned to receive buprenorphine 0.02 mg/kg IM followed by 1 of 2 oral sedation treatments: pregabalin 4 mg/kg or gabapentin 10 mg/kg. Cats were then anesthetized using a standardized protocol. Physical examination parameters and behavioral scores were measured by 2 treatment-blinded veterinarians to compare sedation levels before and after drug administration. Inadequate sedation for handling or IV catheter placement was addressed by dexmedetomidine administration. After surgery was completed, anesthesia recovery times and quality were assessed by the same veterinarians. The effects of pregabalin versus gabapentin on body temperature, respiratory rate, and heart rate were analyzed using Student t tests; behavioral assessments were analyzed using Wilcoxon signed-rank tests; and drug treatment effects on dexmedetomidine sedation rescue and frequency of delirium during anesthetic recovery were analyzed using Fisher exact tests. A P < .05 indicated statistical significance. RESULTS: There was no significant difference in change of physiologic parameters or sedation scores before and after sedation between groups. The need for rescue sedation for IV catheter placement and the incidence of emergence delirium were infrequent and similar for both treatments. CLINICAL RELEVANCE: At the doses studied, oral pregabalin and gabapentin produced indistinguishable effects as adjunctive perioperative sedation agents in cats.

Endometriosis with colonic mucosal colonisation: a diagnostic confounder.

AIMS: Secondary mucosal colonisation by a carcinoma originating from a distant site is a pattern of metastasis to the intestines and hepatobiliary tract and a mimic of primary neoplasia. Although endometriosis is considered benign, its ability to spread widely underscores its quasi-neoplastic nature. After noting that endometriotic glands can colonise the colonic mucosa along the basement membrane, mimicking metastatic disease, we conducted an intradepartmental review of intestinal specimens showing endometriosis obtained from 2016 to 2023 to characterise and quantify the incidence of this phenomenon. METHODS: Material from 38 lower gastrointestinal specimens with a primary or ancillary diagnosis of endometriosis was identified from our surgical pathology database. Slides were reviewed, documenting the extent and micro-anatomic location affected by endometriosis, with a focus on identifying examples showing mucosal colonisation. RESULTS: The most common site of involvement was the distal colon (23 cases; 11 of rectum, 9 of sigmoid colon and 3 of rectosigmoid) followed by the appendix (N=10), cecum (N=2), small intestine (N=2) and 'colon not otherwise specified' (N=1). Mucosal involvement was identified in eight cases (21%), half of which demonstrated seamless colonisation of the epithelium by endometriotic glands. In two of these, the procedure was prompted by the presence of a rectal mass or stricture with concern for malignancy. CONCLUSION: Endometriosis occasionally (4/38; 10.5%) colonises colonic epithelium, potentially mimicking a metastasis or intraepithelial neoplasia/dysplasia. Although unusual, this phenomenon was observed in half of specimens from patients with mucosal involvement in whom a mass or stricture suggested malignancy, a potentially misleading pattern of endometriosis.

Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review.

Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.

Intraosseous hibernoma: clinicopathologic and imaging analysis of 18 cases.

AIMS: Intraosseous hibernomas are rarely reported tumours with brown adipocytic differentiation of unknown aetiology, with only 38 cases documented in the literature. We sought to further characterise the clinicopathologic, imaging and molecular features of these tumours. METHODS AND RESULT: Eighteen cases were identified occurring in eight females and 10 males (median age = 65 years, range = 7-75). Imaging indication was cancer surveillance/staging in 11 patients and clinical concern for a metastasis was raised in 13 patients. The innominate bone (7), sacrum (5), mobile spine (4), humerus (1) and femur (1) were involved. Median tumour size was 1.5 cm (range = 0.8-3.8). Tumours were sclerotic (11), mixed sclerotic and lytic (4) or occult (1). Microscopically, tumours were composed of large polygonal cells with distinct cell membranes, finely vacuolated cytoplasm, central or paracentral small bland nuclei with prominent scalloping. Growth around trabecular bone was observed. Tumour cells were immunoreactive for S100 protein (15/15) and adipophilin (5/5), while negative for keratin AE1/AE3(/PCK26) (0/14) and brachyury (0/2). Chromosomal microarray analysis, performed on four cases, did not show clinically significant copy number variation across the genome or on 11q, the site of AIP and MEN1. CONCLUSION: Analysis of 18 cases of intraosseous hibernoma, to our knowledge, the largest series to date, revealed that these tumours are most often detected in the spine and pelvis of older adults. Tumours were generally small, sclerotic and frequently found incidentally and can raise concern for metastasis. Whether or not these tumours are related to soft tissue hibernomas is uncertain.

Sinonasal Myxoma: A Distinct Entity or a Myxoid Variant of Desmoid Fibromatosis?

Sinonasal myxoma (SNM) is a rare benign mesenchymal tumor that arises in the sinonasal cavity or maxilla and almost exclusively affects young children. Currently, it is considered a specific entity, but its molecular characteristics have not been reported. Lesions diagnosed as SNM and odontogenic myxoma/fibromyxoma were identified from the participating institutions, and the clinicopathologic features were recorded. Immunohistochemistry for ß-catenin was performed in all cases with available tissue. Next-generation sequencing was performed in all cases with SNM. Five patients with SNM were identified, including 3 boys and 2 girls with an age range of 20-36 months (mean: 26 months). The tumors were well defined, centered in the maxillary sinus, surrounded by a rim of woven bone, and composed of a moderately cellular proliferation of spindle cells oriented in intersecting fascicles in a variably myxocollagenous stroma that contained extravasated erythrocytes. Histologically, the tumors resembled myxoid desmoid fibromatosis. Three tested cases showed nuclear expression of ß-catenin. In 3 tumors, next-generation sequencing revealed intragenic deletions of APC exons 5-6, 9 and 15, or 16, respectively, with concurrent loss of the other wild-type copy of APC predicted to result in biallelic inactivation. The deletions were identical to those that occur in desmoid fibromatosis, and copy number analysis raised the possibility that they were germline. In addition, 1 case showed the possible deletion of APC exons 12-14, and another case exhibited a CTNNB1 p. S33C mutation. Ten patients with odontogenic myxoma/fibromyxoma were identified, including 4 women and 6 men (mean age: 42 years). Seven tumors involved the mandible and 3 the maxilla. Histologically, the tumors differed from SNM, and all cases lacked nuclear expression of ß-catenin. These findings suggest that SNM represents a myxoid variant of desmoid fibromatosis that often arises in the maxilla. The APC alterations might be germline, and therefore, genetic testing of the affected patients should be considered.

The Morphologic Spectrum of Gastric Type 1 Enterochromaffin-Like Cell Neuroendocrine Tumors.

Although most well-differentiated gastric neuroendocrine tumors (gNETs) arise from enterochromaffin-like (ECL) cells in patients with autoimmune metaplastic atrophic gastritis (AMAG), the morphologic spectrum of these type 1 ECL-cell gNETs is not well defined. The extent of metaplastic progression in the background mucosa of AMAG patients with gNETs is likewise unclear. Here we report the histomorphology of 226 gNETs, including 214 type 1 gNETs (78 cases from 50 AMAG patients) pooled from a population with high AMAG prevalence. Most type 1 gNETs were ≤1.0 cm, of low grade, and multifocal, consistent with the results of previous reports. However, a high proportion (70/214, 33%) displayed unusual gNET morphologies not previously appreciated in AMAG patients. Unlike other type 1 gNETs with conventional neuroendocrine tumor morphologies, unconventional type 1 gNETs displayed cribriform networks of atrophic cells embedded within myxoid matrix (secretory-cribriform variant, 59%), sheets of deceptively bland discohesive cells resembling inflammatory infiltrates (lymphoplasmacytoid variant, 31%), or wreath-like arrangements of columnar cells wrapped around collagenous cores (pseudopapillary variant, 14%). Another unusual feature was that unconventional gNETs grew laterally within the mucosa (50/70, 71%) and were only rarely sampled from the submucosa (3/70, 4%). These features also differed from the conspicuous radial nodules (99/135, 73%) and frequent submucosal involvement (57/135, 42%) observed for conventional gNETs (P < .0001). Irrespective of morphology, type 1 gNETs were nearly always detected at first AMAG diagnosis (45/50, 90%) and tended to persist thereafter (34/43, 79%), despite similar clinical symptoms and laboratory values between AMAG patients with gNETs and those without. However, unlike AMAG patients without gNETs (n = 50), the background mucosa in patients with gNETs (n = 50) had already progressed to the morphologic equivalent of end-stage metaplasia (P < .0001). This included diffuse loss of parietal cells (92% vs 52%), complete intestinal metaplasia (82% vs 40%), and pancreatic metaplasia (56% vs 6%). Thus, type 1 ECL-cell gNETs are morphologically heterogeneous with a high prevalence of unconventional gNET morphologies. They tend to present silently at first AMAG diagnosis as multifocal lesions that persist within fields of mature metaplasia.

Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer.

We have shown that KRAS-TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS-TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell-dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF-TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell-neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC. SIGNIFICANCE: By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell-excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer. This article is highlighted in the In This Issue feature, p. 1275.

Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall.

Gastric mucosal biopsies and resections from patients treated with neoadjuvant radiation and/or chemotherapy are frequently encountered. These samples may show histologic features related to therapy including inflammation, ulceration, and epithelial atypia. In some cases, epithelial atypia may be marked, prompting the use of adjunct p53 immunohistochemistry. We examined p53 expression by immunohistochemistry in gastric mucosa following therapy.We evaluated the histology and p53 immunohistochemical expression in gastric mucosa from 57 resections and 3 mucosal biopsies, from 60 patients treated with radiation and/or chemotherapy for gastroesophageal carcinoma (n = 33) or pancreatic carcinoma (n = 27).We identified histomorphologic features of therapy-related epithelial changes in 50 of 60 cases (83%). Abnormal p53 expression was present at least focally in nearly half the cases (27 of 60 cases; 45%), all of which showed morphologic evidence of therapy-related epithelial changes. Neuroendocrine cell micronests were present in 37 of 60 cases (62%). Next-generation sequencing (NGS) of foci with therapy-related epithelial changes showing abnormal p53 expression and carcinoma from the same patient was attempted and yielded results in 1 patient. Interestingly, differing TP53 alterations in the patient's adenocarcinoma and in a histologically benign esophageal submucosal gland with therapy-related epithelial changes and abnormal p53 expression were identified.Our results demonstrate that abnormal p53 expression is relatively common in gastric mucosal samples following radiation and/or chemotherapy and suggest that p53 expression should be avoided when distinguishing therapy-related changes from dysplasia or carcinoma. Furthermore, our NGS results raise interesting biological questions, which may warrant further investigation.

Symblepharon in kittens: a retrospective study of 40 kittens and 54 eyes (2002-2022).

OBJECTIVES: The aim of this study was to retrospectively evaluate the signalment, treatment, surgical technique and outcomes for feline symblepharon. METHODS: A retrospective medical record review and standardized grading of clinical descriptions and photographs was undertaken. RESULTS: Forty kittens (54 eyes) aged 3-46 weeks had symblepharon of five types in various combinations: eyelid deformation (24 kittens; 32 eyes); ankyloblepharon (four kittens; four eyes); conjunctiva-to-conjunctiva (11 kittens; 12 eyes); third eyelid-to-conjunctiva (24 kittens; 29 eyes); and corneoconjunctival adhesions (14 kittens; 16 eyes). At initial presentation, 23 (43%) eyes were affected by one type of symblepharon, 25 (46%) eyes by two types and six (11%) eyes by three types; 11 (20%) corneas were ulcerated. Twenty-four (44%) eyes of 18 (45%) kittens were managed medically. Surgery was performed under general anesthesia/sedation (30 occasions) or topical anesthesia (21 occasions) on 30 (56%) eyes of 22 kittens; 12 eyes (40%) underwent multiple surgeries. Four techniques were commonly employed: separation of conjunctival-to-conjunctival adhesions ± eyelid margins (14 eyes); resection of third eyelid adhesions ± temporary tacking of the third eyelid (modified Arlt's pterygium technique; 18 eyes); en bloc resection of the third eyelid (two eyes); and separation of corneoconjunctival adhesions (14 eyes). Median duration of follow-up was 55 days (range 1-1051). Median symblepharon grade in kittens treated surgically improved for all types except corneoconjunctival symblepharon. Median symblepharon grade in kittens receiving medical management remained the same or improved. Corneoconjunctival symblepharon opacity decreased for eyes treated surgically but increased for eyes treated medically. Three eyes were enucleated due to complications of corneoconjunctival symblepharon. At final presentation, symblepharon persisted in 46 (85%) eyes; however, menace response was evident in 13/16 eyes and dazzle reflex in 23/23 eyes. CONCLUSIONS AND RELEVANCE: Symblepharon is a heterogeneous group of conditions with diverse anatomic involvement, clinical appearance and impact, optimal treatment and prognosis for vision.

Histologic Features of Syphilitic Gastritis: A Rare but Resurging Imitator of Common Diseases.

OBJECTIVES: The range of histopathologic features of gastric syphilis is not well described. Here we describe the clinicopathologic findings of eight patients with syphilitic gastritis. METHODS: A search of our Pathology Data System (2003-2022) and multiple other institutions identified eight patients with syphilitic gastritis. Clinical information, pathology reports, and available slides were reviewed. RESULTS: Lesions predominated in middle-aged adults (mean age, 47.2 years; range, 23-61 years) with a propensity for men (n = 7). Three patients had a documented history of human immunodeficiency virus. Clinical presentations included weight loss, abdominal pain, hematochezia, fever, dyspepsia, nausea and vomiting, hematemesis, anemia, and early satiety. Endoscopic findings included ulcerations, erosions, abnormal mucosa, and nodularity. All specimens shared an active chronic gastritis pattern with intense lymphohistiocytic infiltrates, variable plasma cells, and gland loss. Prominent lymphoid aggregates were seen in four specimens. The diagnosis was confirmed either by immunostain for Treponema pallidum (n = 7) or by direct immunofluorescence staining and real-time polymerase chain reaction (n = 1). All patients with available follow-up data showed resolution of symptoms after antibiotic therapy (n = 4). CONCLUSIONS: Recognition of the histologic pattern of syphilitic gastritis facilitates timely treatment, prevents further transmission, and avoids unnecessarily aggressive treatment.

Injury patterns and potential diagnostic pitfalls associated with radiation and radio-chemotherapy in the stomach and gastroesophageal junction.

Chemoradiation-associated injury may cause marked epithelial and stromal changes in gastric specimens. We characterized these histologic features in a retrospective series of cases. Nineteen cases of radiochemotherapy-associated gastropathy were identified, including 16 from our institution and 3 from consultation material. Patient charts and hematoxylin and eosin-stained slides were reviewed. Most patients were men (79%) with a median age of 66 years. All patients had a documented history of radiation and 15 patients also received chemotherapy. The median time from treatment to biopsy or resection was 2.3 months. Gross and endoscopic findings included erythematous, hemorrhagic, or ulcerated mucosa. Mucosal eosinophilia was seen in 16 cases (84%) while 10 cases (53%) featured acute inflammation including neutrophilic microabscesses. Epithelial changes included increased apoptosis (6 cases, 32%) and marked epithelial atypia (10 cases, 53%), potentially mimicking malignancy in some cases. However, the atypical cells featured voluminous eosinophilic cytoplasm with low nuclear-to-cytoplasmic ratio, a clue to their benign nature. Neuroendocrine cell nests were seen in 4 cases (21%) and loosely aggregated in 1 case, potentially mimicking a well-differentiated neuroendocrine tumor or enterochromaffin-like (ECL) cell hyperplasia in autoimmune gastritis. Eleven cases (58%) featured vascular changes that included vessel dilation, hobnailed endothelial cells, and fibrin thrombi. Stromal changes were seen in 11 cases (58%) and included lamina propria hyalinization, submucosal fibrosis, and myofibroblast atypia. Injury associated with radiochemotherapy is histologically varied and may affect epithelial, stromal, and vascular compartments. Familiarity with these features is important as a subset of these findings may provoke concern for neoplasia.

Examining Associations Between Mental Health, IPV Exposure, HIV Risk Behaviors, and PrEP Use in South African Women: An Analysis of Data from the Charisma Study.

Intimate partner violence (IPV) has been associated with poorer mental health outcomes and increased human immunodeficiency virus (HIV) risk behaviors. We examine the relations between IPV, mental health symptomology (defined as psychological distress and alcohol misuse), and engagement in HIV risk behaviors among a sample of South African women who participated in a randomized controlled trial of CHARISMA, an intervention to increase women's agency to use oral pre-exposure prophylaxis (PrEP) safely and consistently as well as mitigate relationship challenges. We also examined the impact of trial participation on women's mental health, as well as the impact of psychological distress on the effectiveness of the CHARISMA intervention. Mental health symptomology and IPV exposure were prevalent and associated with some HIV risk and protective behaviors. Trial participation reduced psychological distress. There was no evidence for mental health symptomology impacting the effectiveness of the CHARISMA intervention.

Exploring the spectrum of serrated epithelium encountered in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer. Currently, dysplasia is the best marker of CRC risk. Assessing dysplasia is a challenging task for pathologists as the longstanding inflammation causes marked reactive cytologic changes and architectural distortion. Recent descriptions of nonconventional types of dysplasia in IBD have added to the complexity. In this review, we focus on the clinical, endoscopic, histologic, and molecular findings in lesions with serrated epithelium. Serrated epithelial change (SEC), sessile serrated lesion (SSL)-like, serrated lesion-not otherwise specified (SL-NOS), and traditional serrated adenoma (TSA)-like lesions all typically occur in patients with longstanding IBD with mean ages in the fifth-sixth decade. SEC is often encountered in nontargeted biopsies while the others form visible polyps. While serrated lesions have significant histologic overlap, subtle differences can help pathologists separate them. SEC has markedly distorted architecture with crypts losing perpendicular orientation to the muscularis mucosae. The crypts are goblet cell-rich and have irregular serrations that involve the full length of the crypt. SSL-like lesions are goblet cell poor and have microvesicular cytoplasm. Like their sporadic counterpart in non-IBD patients, these lesions have lateral growth at the crypt bases. TSA-like lesions are characterized by their villous architecture, ectopic crypts, pink cytoplasm, and hyperchromatic elongated nuclei. We also explore molecular findings that help in distinguishing these lesions, current knowledge on the association of each of these lesions with dysplasia and CRC, and future research needed to better characterize these entities.