Reports (MDPI)最新文献

Background and Clinical Significance: Paroxysmal extreme pain disorder (PEPD) is an extremely rare autosomal dominant sodium channelopathy caused by SCN9A gain-of-function variants. It is characterized by infantile-onset excruciating paroxysmal pain, typically in rectal, ocular, or mandibular regions, triggered by innocuous stimuli and accompanied by autonomic flares. Carbamazepine is dramatically effective in most reported cases. To date, only two genetically confirmed cases have been documented in Chinese patients, and fewer than 20 disease-causing variants are reported worldwide. We report the third Chinese case harboring a novel likely pathogenic SCN9A variant (p.Leu1623Gln), notable for its unusually severe, progressive, and carbamazepine-refractory phenotype, as well as life-threatening psychiatric sequelae, highlighting phenotypic heterogeneity and the devastating impact when standard therapy fails. Case Presentation: A Chinese male proband with positive family history presented with lifelong trigger-induced catastrophic burning and tearing pain in the perineum and lower limbs, associated with erythema, swelling, and occasional non-epileptic seizures. Attacks worsened with age despite escalating polypharmacy, including high-dose opioids, benzodiazepines, topical lidocaine and carbamazepine. Both the proband and his father developed profound psychosocial sequelae including severe depression and suicidal attempts. Next-generation sequencing in the proband revealed a novel heterozygous likely pathogenic variant NM_001365536.1 (SCN9A): c.4868T>A p.(Leu1623Gln). Conclusions: This third reported ethnic Chinese PEPD case expands the genotypic and phenotypic spectrum of SCN9A-related channelopathies, demonstrating that some variants can produce carbamazepine-refractory, progressive, and profoundly disabling disease with high suicidality risk. Early genetic diagnosis is critical in family planning and cascade testing, and has the potential in guiding targeted therapy that is under active research.

Background and Clinical Significance: Synchronous gastrointestinal tumors are exceptionally rare, particularly when combining histologically distinct benign and malignant components. Schwannomas represent uncommon mesenchymal tumors of the gastrointestinal tract, most frequently arising in the stomach, while rectal localization is exceedingly unusual. Papillary adenocarcinoma of the gallbladder is an aggressive malignant entity derived from intracholecystic papillary-tubular neoplasms (ICPNs). The coexistence of these two unrelated neoplasms has not been previously reported, making this case of dual tumor pathogenesis clinically and academically significant. Case Presentation: A 68-year-old female was admitted for surgical management of grade IV uterovaginal prolapse. Preoperative imaging incidentally revealed a well-circumscribed rectal wall mass and gallstones. A combined abdominopelvic operation was performed, including total hysterectomy with bilateral adnexectomy (Wiart procedure), rectosigmoid resection with colorectal anastomosis, and bipolar cholecystectomy. Intraoperatively, a firm intramural rectal lesion and a friable papillary mass in the gallbladder fundus were identified. Histopathologic examination confirmed a benign rectal schwannoma (S-100 positive, CD117/DOG-1 negative) and a papillary adenocarcinoma of the gallbladder, pT3N0M0, with clear resection margins and no lymphovascular or perineural invasion. The postoperative course was uneventful, and the patient remained disease-free at six-month follow-up. Conclusions: This case represents an exceedingly rare benign-malignant synchronous tumor association. The simultaneous occurrence of rectal schwannoma and gallbladder papillary adenocarcinoma underscores the importance of thorough intraoperative exploration and histopathologic evaluation. Complete resection with negative margins and multidisciplinary follow-up remains crucial for optimal outcomes and contributes to understanding dual tumor pathogenesis within the gastrointestinal tract.

Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that systematic assessment for autoimmunity should be a standard component of the IHPM work-up. Case presentation: A 77-year-old woman presented with recurrent vertigo, imbalance, and headaches. Brain MRI showed diffuse pachymeningeal thickening with mild heterogeneous enhancement, radiologically stable over >2 years. Extensive evaluation excluded infectious, neoplastic (including paraneoplastic), cerebrospinal fluid hypotension and systemic autoimmune causes; findings did not support IgG4-related disease. Thyroid work-up revealed hypothyroidism with multinodular goiter; total thyroidectomy was performed, and there was no indication for adjuvant radioiodine therapy. Despite oncologic control, anti-Tg antibodies remained markedly elevated, while anti-thyroid peroxidase antibodies (anti-TPO) declined. Symptoms repeatedly improved with oral methylprednisolone and recurred on taper; adverse effects were mild and manageable. The patient remains under clinical and oncologic surveillance with symptom-guided steroid re-challenge. Conclusions: IHPM may exhibit a dissociation between clinical response and radiologic course. Persistently elevated anti-Tg after thyroidectomy can coexist with IHPM and may signal ongoing autoimmunity rather than active cancer.

Beyond their traditional role as short-lived antimicrobial cells, neutrophils are increasingly recognized as key regulators of adaptive immunity and tumor progression. This AI-assisted integrative review investigated the neutrophil-T-cell axis, particularly the role of Galectin-9 (Gal-9), across adult T-cell leukemia/lymphoma (ATL), Sézary syndrome (SS), coronavirus disease 2019 (COVID-19), and psoriasis. Leveraging AI tools (GPT-5 and Adobe Acrobat AI Assistant) for literature synthesis (2000-2025) and expert validation, we aimed to identify common immunological mechanisms. Across all conditions, neutrophils displayed persistent activation, elevated Gal-9 expression, and modulated T-cell interactions. In ATL and SS, neutrophilia correlated with poor survival and TCR signaling dysregulation, suggesting Gal-9-mediated immune modulation. In COVID-19 and psoriasis, neutrophil-derived Gal-9-linked innate hyperactivation to T-cell exhaustion and IL-17-driven inflammation. These findings define a recurring neutrophil-Gal-9 regulatory module connecting innate and adaptive immune responses. This study underscores the feasibility of combining AI-driven literature synthesis with expert review to identify unifying immunological mechanisms and therapeutic targets across malignancy and inflammation.

Background and Clinical Significance: Kidney transplant recipients have a 2-4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. Case Presentation: A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. Conclusions: Vigilant post-transplant cancer surveillance-including native-kidney RCC-tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis.

Background and Clinical Significance: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders that may present as paraneoplastic syndromes. Although most frequently associated with solid-organ malignancies, hematological neoplasia, particularly lymphomas, is also likely linked. Case Presentation: We describe a sexagenarian female with progressive proximal muscle weakness, myalgias, and lymphadenopathy. Laboratory evaluation revealed markedly elevated creatine phosphokinase and myositis-specific antibodies: anti-Mi-2α and anti-EJ. Magnetic resonance imaging of the thighs confirmed active myositis. Lymph node biopsy reported follicular lymphoma. The patient was initiated on methotrexate and rituximab, with which she reported significant symptomatic relief. Conclusions: Inflammatory myopathy is an exceedingly rare presentation of follicular lymphoma. This case emphasizes that lymphomas can closely mimic other disease processes and present significant diagnostic challenges, and they should be included in the differential diagnosis of myopathies. Improved awareness and early diagnosis of lymphoproliferative neoplasia often yield better overall clinical outcomes.

Background and Clinical Significance: Lymphoepithelial cysts are uncommon benign lesions of the head and neck, rarely encountered within the oral cavity and exceedingly infrequent in the palatine tonsils. Their nonspecific clinical presentation and ability to mimic more common benign entities often render diagnosis challenging. Case Presentation: We report the case of a 68-year-old woman with a four-year history of persistent foreign-body sensation in the oropharynx despite multiple normal otolaryngologic examinations. Flexible nasoendoscopy was non-diagnostic, as the lesion was deeply concealed within the superior tonsillar pole between the palatine pillars. Targeted tonsillar manipulation ultimately revealed a small pedunculated mass and contrast-enhanced computed tomography demonstrated a well-circumscribed, non-enhancing cystic lesion confined to the tonsillar parenchyma. Surgical excision under general anesthesia confirmed an oral lymphoepithelial cyst on histopathologic analysis. The patient remained asymptomatic with no recurrence at four months. Conclusions: This case underscores the rarity of tonsillar lymphoepithelial cysts, highlights the diagnostic limitations of endoscopic evaluation for cryptic superior-pole lesions and emphasizes the importance of meticulous dynamic oropharyngeal examination. Complete surgical excision is both definitive and curative, with an excellent prognosis.

Background and Clinical Significance: Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with a poor prognosis, where median survival typically ranges from 4 to 10 months. Advances in genetic profiling, particularly the identification of BRAF mutations, offer new opportunities for targeted therapy. Case Presentation: This case report details the journey of a woman in her late 50s diagnosed with symptomatic ATC. Initial immunohistochemistry (IHC) testing for BRAF mutations returned negative results, leaving the patient with limited treatment options and prompting her to pursue medical assistance in dying (MAiD). However, next-generation sequencing (NGS) confirmed a ^V600EBRAF mutation, and a basis for targeted therapy. The patient began treatment with dabrafenib-trametinib, followed by pembrolizumab as second-line therapy, ultimately extending her life by nearly seven months. Conclusions: This case underscores the importance of rapid and comprehensive diagnostic approaches, particularly the higher sensitivity of NGS over IHC for detecting BRAF mutations. The complexities of accessing newer therapies in Canada's single-payer healthcare system are also emphasized. The utilization of newer rapid diagnostic technologies can have a direct impact on directing treatment for ATC and other aggressive malignancies.

Backgroundand Clinical Significance: Statins are widely prescribed for cardiovascular risk reduction and generally demonstrate a favorable safety profile. While myalgia and elevations in liver enzymes are well-recognized adverse effects, headaches are less commonly reported and often underrecognized in clinical practice. This may result in unnecessary diagnostic evaluations, increased healthcare costs, and delayed identification of the underlying cause. Case Presentation: We describe an adult patient who developed intractable headaches that emerged after many years of statin therapy. The headaches persisted despite conventional analgesic treatment and resolved completely following discontinuation of the statin. Secondary causes were excluded, and comorbid conditions were systematically ruled out. Statin-associated headache is uncommon but clinically relevant. Proposed mechanisms include nitric-oxide-mediated vasodilation, central effects of lipophilic statins, and mitochondrial involvement. In this case, the patient was taking metoprolol succinate, lisinopril, simvastatin, clopidogrel, and tamsulosin. Except for lisinopril, none of the other comedications are strongly linked to new-onset headaches. Holding it did not resolve his headache, making simvastatin the most plausible contributor. This was confirmed by resolution of headache through its discontinuation. Because such headaches may be overlooked, clinicians should consider a statin-related cause when symptoms begin after initiation and may manage this by switching to a hydrophilic statin or using alternative lipid-lowering therapy. Conclusions: Clinicians should remain vigilant about the possibility of statin-induced headache, even in long-term users. Early recognition can prevent unnecessary diagnostic investigations, expedite symptom resolution, and support optimal management of both cardiovascular risk and treatment-related adverse effects.

Background and Clinical Significance: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is increasingly prescribed for autoimmune and inflammatory diseases. Although its therapeutic safety profile is well established, fatal intoxications have not been reported to date. Case Presentation: We describe the first fatal case of upadacitinib overdose in a 13-year-old girl. Following ingestion of approximately 600 mg (40 × 15 mg tablets Rinvoq^®), the patient presented with deep coma, profound bradycardia (~40 bpm) with third-degree atrioventricular block, conduction delay, hypotension, hypothermia, and metabolic acidosis. Laboratory tests showed hyperglycemia (17.8 mmol/L) and only minimal elevations in cardiac biomarkers (CK 57.03 U/L, CK-MB 30.64 U/L, troponin 0.003 ng/mL). Despite advanced resuscitation, the patient succumbed within a few hours. Forensic toxicology revealed extremely high concentrations of upadacitinib, 1.84 µg/mL (~1840 ng/mL) in blood and 70.3 µg/mL in gastric contents, far exceeding reported therapeutic plasma levels (Cmax 36.0 ± 8.8 ng/mL). This case establishes the first reported value for a lethal upadacitinib concentration in humans. The combination of conduction abnormalities, refractory shock, and minimal biomarker changes is consistent with an acute electrophysiological and hemodynamic collapse rather than myocardial infarction. Conclusions: The toxicity of upadacitinib in this case is characterized by profound central nervous system depression, severe cardiovascular (electrophysiological and hemodynamic) disturbances, and metabolic abnormalities (acidosis and hyperglycemia). These findings provide essential reference data for clinical and forensic toxicology, highlight the fatal potential of upadacitinib in overdose, and underscore the importance of secure medication storage and pharmacovigilance in households with adolescents.