We present two cases of tongue schwannoma in two young males. The unusual, exogenetic clinical manifestation might be a big challenge for most dentists in making a correct diagnosis. The two patients had no special genetic or environmental background. Both patients denied cigarette smoking or alcohol abuse. Physical examination of the cervical lymph nodes yielded negative results. Their astonishing medical histories revealed that both had self-injurious practices using sharp instruments. The diagnosis of tongue schwannoma was confirmed by histopathology, revealing typical Antoni type A and B areas, and reactivity with S-100 by immunohistochemistry. The lesions were excised transorally under local anesthesia with no signs of recurrence for more than two years.

Cluster of differentiation 47 (CD47) delivers an inhibitory signal that suppresses phagocytosis and prevents immune clearance of tumor cells by interacting with signal regulatory protein alpha (SIRPα) on myeloid cells. Although blockade of the CD47-SIRPα axis is a promising immunotherapeutic strategy, clinical development has been hindered by on-target toxicities (e.g., severe anemia) and insufficient potency. Herein we report a third generation CD47-SIRPα inhibitor HCB101, a rationally designed SIRPα-Fc fusion protein generated from a large-scale screening of a structure-guided SIRPα extracellular domain (ECD) mutant library and fused to a human IgG4 Fc. HCB101 demonstrates high-affinity binding to CD47, robustly promotes macrophage-mediated phagocytosis of tumor cells without affecting red blood cells and exhibits unique advantages over current CD47-targeting agents, including Hu5F9-G4, TTI-622, and ALX148. In multiple xenograft cancer models, HCB101 induced significant inhibition of tumor growth as a single agent and showed synergistic anti-tumor effects when combined with anti-HER2 or anti-EGFR monoclonal antibodies. Additionally, HCB101 treatment increased the M1/M2 macrophage ratio in the tumor microenvironment, suggesting repolarization of tumor-associated macrophages (TAMs) toward a pro-inflammatory phenotype. No dose-limiting toxicities or hematologic adverse effects were observed in murine or non-human primate studies.

Pituitary metastasis of malignant melanoma (MM) is rare. This study aimed to explore its diagnostic features using a multimodal approach and retrospectively analyzed previously reported cases to summarize its pathogenesis and diagnostic challenges.

We screened all published case reports and case series on pituitary metastatic MM using PubMed, focusing on cases with detailed clinical data, imaging features, pathological examination, and molecular test results. A total of 24 cases of MM with pituitary metastasis, including our case, were retrospectively analyzed. Additionally, the index patient underwent histopathological, immunohistochemical (S100, SOX10, Melan-A, HMB-45, BRAF V600E), and BRAF V600E PCR analyses.

This case involved a 65-year-old female patient whose pathological examination revealed tumor cells with epithelioid and spindle cell features. Immunohistochemical analysis showed diffuse positivity for S-100, vimentin, and BRAF V600E, with focal positivity for Melan-A and HMB-45. The Ki-67 proliferation index was approximately 15%. Molecular testing confirmed BRAF V600E mutation. The patient died 12 months postoperatively. Our literature review indicated that MM with pituitary metastasis demonstrates male predominance, a median onset age of 62 years, a frequent association with BRAF V600E mutation, and a median survival time of 12 months.

Diagnosing MM with pituitary metastasis requires integrating detailed clinical history, imaging features, pathological examination, and molecular testing. Our findings highlight the importance of a comprehensive diagnostic approach with multidisciplinary collaboration when managing atypical pituitary masses, along with detailed investigation of a patient's previous tumor history, to improve diagnostic accuracy and patient outcomes.

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder syndrome, that predominantly affects women of reproductive age. It is characterized by marked clinical heterogeneity involving multiple systems including reproductive, metabolic and immune systems, while existing diagnostic protocols remain inadequate for clinical needs. Moreover, the incomplete understanding of PCOS etiology has limited therapeutic strategies for symptomatic management rather than interventions targeting core pathological mechanisms, resulting in PCOS frequently persisting as a chronic condition with an increased risk of long-term complications such as type 2 diabetes, metabolic disorder-associated fatty liver disease and cardiovascular disease. This clinical reality underscores the urgent need to elucidate its pathogenic network at the molecular level. Emerging evidence suggests that the Hippo signaling pathway plays a central role in the pathological process of PCOS through dynamically regulating cell proliferation-apoptosis balance, differentiation programs and metabolic homeostasis. This review examines the molecular mechanisms governing Hippo signaling transduction and its physiological relevance, with a focused analysis of its diverse implications in PCOS pathophysiology, particularly in reproductive dysfunction, metabolic-endocrine disturbances, and immune dysregulation. These mechanistic insights not only advance our understanding of PCOS pathogenesis but also provide a theoretical foundation for developing signaling pathway-targeted precision therapies.

Adrenal angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that is frequently misdiagnosed preoperatively. This diagnostic challenge is compounded by its nonspecific clinical presentation and radiological features, which often overlap with more common adrenal neoplasms such as pheochromocytoma, adrenocortical carcinoma, and metastasis. This report describes a case of adrenal AFH that was successfully managed via retroperitoneal laparoscopic adrenalectomy.

An 18-year-old male presented with a two-week history of recurrent abdominal pain and vomiting. Preoperative computed tomography angiography and urography suggested a pheochromocytoma. Pheochromocytoma was initially suspected based on preoperative computed tomography angiography and urography findings; however, postoperative pathological analysis confirmed the diagnosis as adrenal angiomatoid fibrous histiocytoma. There was no recurrence of adrenal angiomatoid fibrous histiocytoma during the follow-up of 10 months.

Adrenal AFH is a rare tumor with a high propensity for misdiagnosis. It should be considered in the differential diagnosis of adrenal masses with imaging features suggestive of hemangioma. Surgical resection is the primary treatment, and the prognosis is generally favorable without the need for adjuvant radiotherapy or chemotherapy. Long-term surveillance is recommended due to its intermediate biological potential and documented risk of late recurrence.

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm with highly variable, multisystem manifestations that present significant diagnostic and therapeutic challenges. This retrospective multicenter case series included 11 adult patients diagnosed with biopsy-proven ECD across Canada between January 2015 and June 2024. The cohort comprised six females and five males with a median age of 55 years (range 41-74). PET-CT was used for disease staging and treatment monitoring in nine cases. The most commonly involved sites were bone (n=8), kidney (n=6), and lungs (n=5). BRAF V600E mutations were detected in seven patients. Treatments included vemurafenib, interferon, tocilizumab, cladribine, cobimetinib, and cytarabine. Treatment responses varied, with several patients achieving remission or stable disease, while others had progressive or end-stage disease. This study highlights the clinical heterogeneity of ECD and the value of integrating histopathology, molecular profiling, and imaging to guide management and improve outcomes.

Cancer of unknown primary (CUP) is characterized by metastatic cancer cells with no identifiable primary tumor despite extensive diagnostics. This study investigates the epidemiologic, histopathological, and prognostic factors in 352 CUP cases in Iran.

This retrospective study reviewed the clinical documents of CUP patients registered in MACSA, a charity-based referral center in central Iran, Isfahan, within 2016-2021. The patients' data were analyzed, and survival associations were assessed using Cox proportional hazards regression models.

Altogether 352 CUP patients were included in the study. The mean age at diagnosis was 65.9 ± 14.3 years, with 52.6% being male. Abdominal pain (32.1%) was the most common presentation. Metastatic adenocarcinoma (31.5%) was the most frequent histopathological type, with the liver (48.6%) as the most prevalent metastatic site. Single-site metastasis was seen in 55.4% of patients. Immunohistochemistry, conducted in 40.3% of patients, was inconclusive in identifying the primary site. The median overall survival was 5 months (95% confidence interval [CI]: 4.0-7.0). Multivariable Cox regression analysis showed older age increased risk of death (hazard ratio [HR]: 1.028, 95% CI: 1.019-1.037). Neuroendocrine tumors were linked to a lower risk (HR: 0.553, 95% CI: 0.313-0.978), while metastasis to the liver (HR: 1.382, 95% CI: 1.076-1.774) and pancreas (HR: 2.138, 95% CI: 1.094-4.176) increased mortality risk.

This study provides large-scale evaluation of CUP in an Iranian population, revealing its poor prognosis and the limited diagnostic utility of IHC. The findings align with global data and highlight the urgent need for improved diagnosis and treatment to enhance patient outcomes.

Skin-related adverse events (AEs) induced by apalutamide occur frequently in Japanese patients with prostate cancer. However, biomarkers for predicting these skin-related AEs have not yet been identified. Therefore, this study investigated whether the proportion of eosinophils could serve as a predictive biomarker for skin-related AEs in Japanese patients with prostate cancer treated with apalutamide.

A total of 109 patients were enrolled in this study. Among them, 79 patients with prostate cancer who received apalutamide were categorized into two groups: the skin AE group (n = 45) and the non-skin AE group (n = 34), based on whether they experienced skin-related AEs of any grade. The eosinophil proportions in baseline samples collected before treatment were then analyzed.

The baseline eosinophil proportion was significantly higher in the skin AE group compared with the non-skin AE group (P < 0.05). The optimal cut-off value of the eosinophil proportion for predicting skin-related AEs of any grade was 1.8% (area under the receiver operating characteristic curve [AUC] = 0.768). In multivariate analysis, an eosinophil proportion ≥1.8% was identified as an independent factor associated with skin-related AEs of any grade (odds ratio, 13.3; 95% confidence interval, 3.82-46.4; P < 0.05).

The baseline eosinophil proportion may serve as a predictive biomarker for skin-related AEs of any grade in Japanese patients with prostate cancer treated with apalutamide.

Malignant mesothelioma is an aggressive cancer that arises from the mesothelial cells lining the pleura, peritoneum, pericardium, or tunica vaginalis. While occupational exposure accounts for most cases, nonoccupational exposures (to ionizing radiation, carbon nanotubes, and different natural fibers) remain important and under-recognized. The rarity of nonoccupational pleural mesothelioma cases with prolonged survival substantiates a detailed analysis of the presented clinical case to increase awareness and review and contribute to the scientific literature.

We present a clinical case of a 64-year-old Caucasian male patient still alive after a diagnosis in 2017 of epithelial-type pleural mesothelioma and three episodes of pleuritis accompanied by dyspnea, fever, and chest pain. The patient lived near a contaminated area but no other exposure was reported. The diagnosis was established by thoracic computed tomography scan and thoracentesis. The patient subsequently underwent chemotherapy and pneumonectomy, followed by semiannual follow-up visits that showed no evidence of disease recurrence.

This case highlights the importance of considering nonoccupational risk factors in patients with pleural mesothelioma and suggests that long-term survival can be achieved with early diagnosis and multimodal treatment. This literature review supports the need for further studies to improve the understanding and management of nonoccupational pleural mesothelioma.

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. N6-methyladenosine (m⁶A) modification represents a pivotal layer of epitranscriptomic regulation in cancer. Fat mass and obesity-associated protein (FTO), an m⁶A demethylase, has been implicated in several malignancies. While FTO's involvement in OSCC is emerging, its regulation of glycolytic metabolism remains uncharacterized. This study aimed to investigate the biological function of FTO in OSCC and determine whether it modulates PKM2 expression through an m⁶A-dependent mechanism involving YTHDF2.

FTO expression was analyzed in OSCC tissues by immunohistochemistry and Western blotting. Functional assays were performed in SCC25 and CAL27 cells with stable FTO knockdown or overexpression to assess proliferation, migration, invasion, and glycolytic activity. Global m⁶A levels, RNA-protein associations, and mRNA stability were examined using dot blot, RIP-qPCR, and actinomycin D treatment. NF-κB pathway activation was evaluated by Western blotting. In vivo tumorigenicity was assessed using xenograft models.

FTO was markedly upregulated in OSCC tissues and correlated with aggressive clinical features. Silencing FTO attenuated malignant phenotypes and glycolytic flux. Mechanistically, FTO stabilized PKM2 mRNA by reducing YTHDF2-mediated degradation via m⁶A demethylation. FTO expression also coincided with enhanced NF-κB signaling activity.

These findings define an FTO/m⁶A/YTHDF2/PKM2 axis that promotes OSCC progression through glycolytic reprogramming and tumor growth, highlighting a potential metabolic vulnerability for therapeutic intervention.