搜索结果：Cytopathology

TCF7L2 (OMIM:602228; HGNC:11641) is a transcription factor and critical effector of the Wnt/β-Catenin pathway. In 2021, 11 pediatric patients with mono-allelic predicted loss-of-function (pLOF) TCF7L2 variants and syndromic features were observed. Characterization of patients with pLOF TCF7L2 variants and neurodevelopmental features - herein referred to as TCF7L2-related neurodevelopmental disorder (TRND) - is urgently needed. We leveraged multiple methods (GeneMatcher, DECIPHER, literature review, public/private repositories) to identify an international cohort of 76 patients with pLOF TCF7L2 variants and neurodevelopmental features and phenotypically characterized them. We also retrospectively searched for an independent cohort of adults with pLOF TCF7L2 variants (n = 11) from 60,000+ PennMedicine BioBank (PMBB) patients. Among 76 patients with pLOF TCF7L2 variants, speech delay (95.3%), craniofacial dysmorphisms (73.3%), ophthalmologic conditions (65.5%), autism (62.1%), and orthopedic abnormalities (52.6%) were most commonly observed. Phenotypic differences did not cluster by variant type or genomic locus. Among PMBB patients, an association of nominal significance with type 2 diabetes with renal manifestations (OR = 5.8; p-value = 0.03) was detected, warranting further investigation. This represents the most comprehensive characterization to date of TRND, a novel neurodevelopmental disorder, defining its genotypic and phenotypic spectrum. We opened a Simons Searchlight natural history study (https://www.simonssearchlight.org/research/what-we-study/tcf7l2/) to enhance understanding of this condition.

Olmesartan-induced enteropathy is an uncommon but important cause of severe chronic diarrhea and weight loss that can mimic celiac disease and infiltrative gastrointestinal disorders. We report a 71-year-old man on long-term olmesartan who presented with months of diarrhea, nausea/vomiting, profound weakness, and ∼100 pounds of unintentional weight loss. Esophagogastroduodenoscopy demonstrated duodenal villous blunting with lamina propria lymphoplasmacytic inflammation and rare periodic acid-Schiff-positive macrophages. An empiric 3-week gluten-free diet trial was ineffective. Celiac serologies, infectious stool studies, and HIV testing were negative. Laboratory evaluation revealed anemia, elevated creatinine, hypercalcemia, and a gamma gap; serum and urine protein electrophoresis showed an M-protein, and bone marrow biopsy confirmed multiple myeloma. Repeat duodenal biopsies again showed villous blunting, while Congo red staining was negative, arguing against gastrointestinal amyloidosis. Olmesartan-induced enteropathy was favored; olmesartan was discontinued and budesonide was started. Within 1 month, gastrointestinal symptoms resolved and the patient gained 20 pounds. Recognition of this drug effect is critical, particularly when concurrent hematologic disease raises concern for infiltrative etiologies.

Hyperplastic dental follicle (HDF) is a rare odontogenic hamartomatous lesion typically associated with unerupted teeth in children and adolescents and is often found incidentally on radiographic imaging. HDF usually presents as a pericoronal radiolucency of 2-3 mm in diameter and is commonly difficult to distinguish from dentigerous cysts on radiographs. We report an unusual case of HDF in an 11-year-old male who was referred for evaluation of delayed eruption of the left maxillary canine. Panoramic radiography and cone-beam computed tomography (CBCT) revealed a remarkably large radiolucent area, with a maximum dimension of 25.3 mm. The initial clinical diagnosis was a dentigerous cyst; however, incisional biopsy revealed solid tissue characteristics, and histopathological examination confirmed HDF, with no evidence of cystic lining, neoplastic transformation, or inflammation. Following the patient's and parents' preference for complete removal, resection of the lesion together with extraction of the impacted canine was performed under general anesthesia. At the 6-month follow-up, no recurrence was observed and bone regeneration was confirmed on radiographic examination. This case underscores the diagnostic challenge posed by atypical radiographic findings and highlights the necessity of histopathological confirmation. Given the exceptional size and potential for recurrence, long-term follow-up is warranted.

Low back pain (LBP) is a leading global cause of disability, with lumbar paraspinal muscle degeneration playing a key pathophysiological role. Lumbar multifidus muscle (LMM) atrophy, detectable on magnetic resonance imaging (MRI) as fatty infiltration, is closely associated with degenerative lumbar pathology. However, the relationship between LMM fat infiltration and co-existing degenerative changes - disc herniation, intervertebral disc degeneration (IVDD) and facet joint degeneration (FJD) - requires further characterisation. This hospital-based cross-sectional study was conducted from March 2023 to February 2024. Eighty-six patients (38 males, 48 females; age 20-60 years) with clinically diagnosed LBP of &#x2265; three month-duration underwent 1.5 Tesla MRI lumbar spine in Assam Medical College and Hospital (AMCH), Dibrugarh, India. Lumbar multifidus muscle fat infiltration at the L4/L5 mid-disc level was graded using Goutallier's classification (Grades 0-4). Intervertebral disc degeneration was graded using Pfirrmann's system and facet joint changes by Pathria's grading. Statistical analysis was performed using Fisher's exact test. The majority of patients had Grade 2 LMM fat infiltration (45.34%), followed by Grade 3 (23.26%), Grade 1 (18.61%), Grade 4 (8.14%) and Grade 0 (4.66%). Disc herniation was present in 67.44% of patients, with Grade 3 being the most frequently seen (36.04%). A progressive increase in disc herniation grade was observed with increasing LMM atrophy grade. Pfirrmann Grade 3 IVDD was most prevalent (27.90%). Grade 1 facet joint degeneration predominated (50.0%). Higher grades of LMM fat infiltration correlated significantly with higher grades of IVDD and FJD (p < 0.05). MRI-based qualitative assessment of LMM fat infiltration using Goutallier's grading is a reliable, clinically practical method that should be incorporated into routine lumbar spine reporting. Increasing LMM atrophy correlates significantly with progressive degenerative changes including disc herniation, IVDD and FJD. Targeted lumbar muscle rehabilitation should be considered as an integral component of LBP management.

Mucormycosis is an opportunistic infection caused by fungi of the order Mucorales and Candida is a yeast which is the most common cause of fungal infections in humans. The most commonly known risk factor for these fungal infections is uncontrolled diabetes mellitus (DM), followed by other causes of immunosuppression like neutropenia and corticosteroid therapy. In atypical clinical presentations, all differential diagnosis should be considered, and followed by histopathological and microbiological examination for diagnosis of fungal infections like mucormycosis and candidiasis in uncommon locations. Early diagnosis and combined medical and surgical treatment, along with resolution of the associated risk factors can lead to effective results and good prognosis.

暂无摘要（点击查看详情）

Hairy cell leukemia (HCL), a rare B-cell lymphoproliferative disorder, originates from the splenic marginal zone B cell. However, diagnosis can be particularly challenging in resource-limited settings where advanced tests are not readily available. Misclassification may result in non-selective chemotherapy exposure and increased toxicity. Reporting such cases is important to highlight diagnostic challenges in resource-limited countries. A 51-year-old male presented with abdominal discomfort, weight loss, and fatigue. Examination revealed splenomegaly. Initial evaluation suggested lymphoplasmacytic lymphoma, and the patient received multi-agent chemotherapy (R-CHOP), which was complicated by severe cytopenias. Splenectomy was performed, yielding a spleen weighing 2216&#xa0;g. Histopathology and immunophenotyping confirmed hairy cell leukemia. Molecular testing for BRAF V600E (the gold standard for diagnosis) was unavailable due to financial and infrastructural restrictions. Treatment was switched to single-agent cladribine, resulting in marked clinical improvement and a significant reduction in chemotherapy adverse effects. Follow-up imaging and blood work revealed that the patient was in complete remission. In our case, we emphasize the diagnostic challenges of HCL in low-resource environments and clarify how the empirical administration of R-CHOP chemotherapy led to unnecessary toxicity and suboptimal outcomes. Splenectomy played a crucial diagnostic role when bone marrow tests were directional but not conclusive. We provide an extensive review of differential diagnoses, immunophenotypic hallmarks, what lies beyond the BRAF V600E mutation, and therapeutic approaches. Early recognition of HCL is crucial to avoid delayed optimal therapy and to enhance patient outcomes. This case emphasizes the critical role of morphology and immunophenotyping in confirming HCL, especially in resource-limited countries.

Fibrosing cholestatic hepatitis (FCH) is a devastating complication that can occur when hepatitis C virus (HCV) recurs following liver transplantation. When it occurs, FCH typically develops between 1 and 6 months following transplant and is associated with markedly elevated HCV levels. With the advent of direct-acting antiviral therapy, FCH C is now a rare occurrence. Here, we describe a rare case of early-onset FCH that occurred when an HCV nucleic acid test (NAT) positive liver graft was transplanted into a hepatitis C na&#xef;ve recipient. This case highlights the importance of initiation of antiviral therapy as soon as possible following transplantation of an HCV NAT-positive liver graft as recommended by current guidelines.

Lower gastrointestinal bleeding (LGIB) in older adults is most commonly caused by diverticular disease. Concomitant pathology may be encountered during evaluation, particularly in patients with multiple comorbidities. A 78-year-old man presented with painless hematochezia and hypovolemic shock while receiving clopidogrel. After stabilization, colonoscopy identified a sigmoid diverticulum with an adherent clot, which was treated with injection and clipping. During the same examination, an ulcerated ileocecal valve was noted. Retrograde single-balloon enteroscopy was subsequently performed, demonstrating terminal ileal ulceration consistent with Crohn's disease and an incidental Meckel's diverticulum. Hemorrhage control was achieved endoscopically and attributed to diverticular bleeding. Further evaluation was undertaken based on the ileocecal finding, allowing direct assessment of the terminal ileum. In this case, targeted evaluation, prompted by a focal ileocecal abnormality, identified silent Crohn's disease and an incidental Meckel's diverticulum; while unrelated to the bleeding source, their recognition informed subsequent management and surveillance.

Anaplastic thyroid cancer (ATC) is a rare malignancy with a poor prognosis. A substantial subset harbors the BRAF V600E mutation, enabling targeted therapy with dabrafenib and trametinib. We present the case of a 56-year-old woman with BRAF V600E-mutated ATC who developed acute airway obstruction and asphyxia-induced cardiac arrest. Due to critical tracheal stenosis, surgery was performed in combination with targeted therapy using dabrafenib plus trametinib. Total thyroidectomy successfully relieved tracheal compression and enabled continued treatment. Follow-up with a computed tomography examination demonstrated complete regression of nodal metastases, and subsequent lymph node dissection was performed, confirming the absence of residual disease. After about 1 year of follow-up, the patient remains disease-free postoperatively, illustrating the importance of molecular testing, multidisciplinary management, and a multimodal treatment strategy for ATC. Approximately one-third of cases of ATC may have the BRAF V600E mutation and thus be sensitive to treatment with dabrafenib plus trametinib. This is a paradigm shift in the treatment of ATC, where surgery should be adapted to the mutational status of the tumor, even if the cancer is metastatic and locally advanced. In selected patients, combining surgery with BRAF/MEK inhibition may transform ATC from an invariably fatal disease into a potentially curable condition.

To prospectively evaluate the influence of multiparametric magnetic resonance imaging (mpMRI) quality, as assessed by the Prostate Imaging Quality (PI-QUAL) score, on diagnostic accuracy in men undergoing prostate biopsy after external mpMRI at a tertiary referral center. From June 2024 to July 2025, a total of 246 consecutive patients referred for prostate biopsy after external mpMRI were prospectively enrolled. All patients underwent systematic biopsy with targeted biopsy when indicated. External mpMRI scans were centrally reviewed by expert uro-radiologists blinded to clinical and pathological data. Image quality and lesion grading were reassessed using PI-QUAL v2 and Prostate Imaging Reporting and Data System (PI-RADS) v2.1. Accuracy for clinically significant prostate cancer (csPCa; International Society of Urological Pathology [ISUP] grade &#x2265;2) was assessed using receiver operating characteristic-derived area under the curve AUC before and after review, stratified by PI-QUAL (1-2 vs 3). Median age and prostate-specific antigen (PSA) were 66.5&#x2009;years (interquartile range [IQR] 61-73) and 6.6&#x2009;ng/mL (IQR 4.8-9.7), respectively, and csPCa was detected in 128 patients (52%). After review, 49 (20%), 113 (46%), and 84 (34%) mpMRI scans were classified as PI-QUAL 1, 2, and 3, respectively. The proportion of indeterminate PI-RADS 3 findings was 27% for PI-QUAL 1, 15% for PI-QUAL 2, and 8% for PI-QUAL 3. PI-QUAL 3 scans demonstrated greater diagnostic accuracy than PI-QUAL 1-2 (AUC 0.79 vs 0.66, P&#x2009;=&#x2009;0.01). Central review improved csPCa detection in both PI-QUAL 1-2 (AUC 0.63 vs 0.78, P&#x2009;<&#x2009;0.01) and PI-QUAL 3 (AUC 0.77 vs 0.89, P&#x2009;<&#x2009;0.01) scans. High-quality mpMRI achieved approximately 15% higher diagnostic accuracy for csPCa and were associated with a lower prevalence of indeterminate findings than were low-quality MRI scans; centralized expert review reclassified nearly half of PI-RADS assessments. These findings support upfront high-quality mpMRI acquisition and PI-QUAL-based quality control to optimize diagnosis and reduce unnecessary procedures.

The INHAND Project is a joint initiative of the societies of toxicologic pathology from Europe, the United Kingdom, Japan, and North America to standardize diagnostic nomenclature and criteria used in toxicologic studies. The INHAND initiative includes recommended nomenclature for evaluating histologic specimens from nonclinical studies involving laboratory animals including rodents, non-human primates, dogs, minipigs, rabbits, and fish. Specific terminology and criteria are derived from the consensus opinions of senior toxicologic pathologists and subject matter experts who have expertise in the different species of interest. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included government databases, including the Registry of Tumors in Lower Animals (RTLA), academia, and industrial laboratories throughout the world. This introduction provides context for 14 chapters, arranged by organ system, that define the INHAND nomenclature and diagnostic criteria for fish used in nonclinical studies. Additionally, the current introductory chapter describes both general features of INHAND methodology as well as elements characteristic of toxicologic fish studies. The latter includes fish study design and conduct; euthanasia, sampling, the histologic processing of fish tissues, and a general approach to evaluating fish studies.

Burr cell hemolytic anemia is diagnosed through the identification of burr cells and thrombocytopenia on a peripheral blood smear, in conjunction with an increased reticulocyte count and elevated serum bilirubin levels. Burr cells, referred to as echinocytes, are a type of red blood cell that features short, evenly spaced spicules and a preserved central pallor. This condition is commonly associated with liver disorders or advanced kidney disease. Although the occurrence of burr cell hemolytic anemia in conjunction with varicose veins is rare, it may be indirectly related to liver damage. In this case report, we discuss a patient with congenital varicose veins who experienced tubal abortion and burr cell hemolytic anemia.

Microplastics (MPs) are emerging contaminants of increasing concern, yet their in vivo fate and mechanisms of intestinal toxicity remain poorly defined. Here, we demonstrate that polystyrene nanoplastics (PS-NPs) undergo a previously overlooked enterohepatic recirculation pathway that markedly enhances their intestinal retention. Using oral exposure and a Zombie mouse model with intravenous PS-NPs delivery, we show that systemically absorbed PS-NPs are efficiently captured by the liver, concentrated in the gallbladder, and subsequently reintroduced into the intestine via bile. Chronic PS-NPs exposure caused pronounced epithelial injury, including goblet cell loss, tight-junction disruption, and robust cytokine-mediated inflammation. Multiomics analyses revealed gut microbial dysbiosis, extensive shifts in metabolite profiles, and enrichment of neuroactive signaling pathways, suggesting microbiome-metabolite contributions to toxicity. We further identified significant enteric neurotoxicity characterized by reduced expression of vasoactive intestinal peptide, increased expression of tyrosine hydroxylase, and downregulation of the mechanosensitive PIEZO1 channel. Together, these findings establish hepatobiliary recycling as a key driver of intestinal PS-NPs accumulation and demonstrate that epithelial damage, microbiome-metabolite imbalance, and enteric nervous system dysfunction collectively mediate PS-NPs-induced gut pathology. This work provides mechanistic insights essential for evaluating the health risks of environmental PS-NPs exposure.

Human tumors likely differ in their mitotic ages, reflecting how many divisions elapse between the final tumor progenitor cell and surgical removal. We used a rapidly fluctuating CpG (fCpG) methylation clock to infer relative endometrial adenocarcinomas (EAC) mitotic ages. Experimentally, young tumors initiated from single cells show low-diversity, high-variance fCpG distributions with trimodal peaks near 0%, 50%, and 100%, reflecting inherited progenitor methylation states. fCpG methylation becomes polymorphic with divisions, and older tumors exhibit higher diversity, lower variance, and unimodal distributions centered around 50%. Mitotic ages varied across EAC samples. Synchronous hyperplasia and invasive regions generally shared similar ages, and primary-metastatic EAC pairs showed both synchronous and stepwise progression. The Cancer Genome Atlas (TCGA) EACs also showed variable mitotic ages: younger tumors were enriched for proliferation pathways, whereas older tumors showed more immune infiltration, immune-pathway activation, and evidence of T-cell exhaustion. These results show that human tumors can be ranked by mitotic age and suggest that the growth of older cancers is restrained by immune surveillance. &#xa9; 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Nail squamous cell carcinomas (SCCs) in skin of color (SoC) patients are exceedingly rare, with only 29 cases previously reported. We describe the case of a female Fitzpatrick skin-type V patient who presented with a 3-year history of a hyperpigmented plaque involving the proximal nail fold of her right thumbnail. The patient reported a positive Pap smear for human papillomavirus (HPV) 16 and 18 seventeen years ago and had not received the HPV vaccine. Biopsy showed SCC positive for high-risk HPV, and the patient underwent Mohs surgery. This case adds to only five prior reports of female SoC patients with nail SCC and emphasizes the importance of considering nail SCC in the differential diagnosis of a hyperpigmented nail fold, especially with a history of HPV.

Juvenile gigantomastia is a rare benign breast pathology that predominantly affects adolescents and women younger than 18&#xa0;years of age. It is characterized by excessive, diffuse enlargement of the breast tissue (more than 1.5-2.5 kg per breast or constituting over 3% of total body weight), involving both glandular and stromal components. The histological picture consists of a juvenile fibroadenoma (JFA), which represents a distinct subtype of fibroepithelial breast tumor. The condition can cause severe physical discomfort, pain, posture abnormalities, recurrent skin infections, difficulties with mobility and personal hygiene, low self-esteem, and social stigma. A 15-year-old female presented with a 1-year history of progressive bilateral breast enlargement without nipple discharge, systemic symptoms, or trauma. On local examination, the breasts were grossly enlarged, soft, and non-tender on palpation, with the skin overstretched and visible ulcerations. Modified Goldilocks reduction mammoplasty was performed after excluding other pathologies through a breast ultrasound and hormonology report. Histology reported JFA. JFA is a rare form of benign breast tumor, which manifests during puberty and leads to excessive breast development (gigantomastia) and its related discomfort. It is hypothesized that the causes are due to hypersensitivity of breast tissue to normal circulating estrogens, and hormonal therapy has been reported as a possible treatment, but surgery is considered the definitive treatment. Counseling on follow-up plans should be done to detect complications and recurrence. JFA patients seek care for physical disability and psychological distress. Surgical intervention is the definitive treatment, and histology confirms the diagnosis.

Envenomation by Daboia siamensis venom (RVV) can cause acute kidney injury (AKI), but its mechanisms remain unclear. Renal cell death via necrosis and apoptosis is central to AKI progression. Bax and Bcl-2 are key pro- and anti-apoptotic regulators and common markers of apoptosis; however, their roles in RVV-induced renal injury are poorly defined. Therefore, we investigated Bax and Bcl-2 gene expression and their ratio in AKI following the administration of RVV and its venom fractions. Kidney tissue samples from intact rabbits (in vivo) and the isolated perfused kidney (IPK) model treated with RVV and its venom fractions (PLA&#x2082;, MP, LAAO, and PDE) were analyzed for Bcl-2 family expression at both mRNA and protein levels, together with histopathological evaluation. Bcl-2 and Bax mRNA expression was quantified by RT-qPCR using the &#x394;&#x394;Ct method, and protein expression was assessed by immunohistochemical analysis. Following the administration of RVV and its venom fractions, histopathological analysis revealed extensive tubulonephrosis across all renal tubular segments in both intact kidneys and the IPK model. In contrast, renal tubular necrosis involving all tubular segments occurred in the IPK model after exposure to the RVV, PLA&#x2082; and MP fractions. Immunohistochemical analysis revealed a trend toward increased Bax protein expression and decreased Bcl-2 expression in multiple tubular segments compared to controls in both models. RT-qPCR analysis demonstrated a 1.5-fold upregulation of Bcl-2 and significant reductions in Bax expression and the Bax/Bcl-2 ratio (p < 0.05) in the IPK model relative to controls. Envenomation with RVV and its venom fractions induced nephrotoxic acute kidney injury by modulating Bax- and Bcl-2-mediated apoptosis in renal tubular epithelial cells, with greater susceptibility observed in intact kidneys and a reduced apoptotic response in the IPK model. These findings suggest that prolonged venom exposure may be partially reversible or may shift cell-death signaling from apoptosis toward necrosis.

Atypical eating disorder presentations challenge traditional diagnostic frameworks, leading to underdiagnosis and diagnostic delay, as each patient had prior clinical contacts in which eating disorder pathology went unrecognized. This study examines four cases highlighting unique risk factors, including high-performance athletics, trauma history, substance use, gender dysphoria, and environmental stressors. These patients were not identified as having eating disorders at initial clinical contact, as presenting complaints, including anxiety, alcohol use disorder, attention-deficit/hyperactivity disorder, and environmental stressors, obscured the underlying eating pathology.&#xa0; Athletes, particularly those in weight-class sports, may engage in restrictive eating while maintaining higher body weight, as seen in Case 1. Trauma history increases vulnerability, yet routine screening remains inadequate. Case 2 demonstrates the interplay between alcohol use disorder and binge-purge cycles, where substance use masked eating pathology. Gender dysphoria in Case 3 contributed to restrictive behaviors as a means of body modification, underscoring the importance of integrating gender-affirming care. Case 4 illustrates how environmental instability can drive disordered eating independent of body image concerns. These cases emphasize the necessity of broadening screening criteria and provider education to recognize atypical presentations. Addressing coexisting psychiatric conditions and social determinants of health is critical for early intervention and improved outcomes in patients with eating disorders.