Search Results (4,493)

Background: Vulvar cancer is a rare gynecologic malignancy comprising 1–3% of all cases. No established standard exists for advanced disease, and treatment is often extrapolated from cervical cancer. Although HER2 overexpression is well defined in breast cancer and recognized across multiple solid tumors, its prevalence and significance in vulvar cancer remain unclear. Recent activity of HER2-directed antibody–drug conjugate Trastuzumab deruxtecan in solid tumors with an objective response rate (ORR) of around 37% highlights the need to better characterize HER2 expression in vulvar cancer. Methods: We performed a systematic search of Medline, Embase, and the Cochrane Library up to May 2025. Eligible studies included ≥10 vulvar cancer cases, predominantly vulvar squamous cell carcinoma (VSCC), excluding vulvar Paget’s disease, with available HER2 assessment by immunohistochemistry and/or in situ hybridization. Two reviewers independently screened the studies. A random-effects model was used to estimate pooled HER2 positivity. Heterogeneity was assessed using Cochrane’s Q and Higgins’s I². Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n = 752) met inclusion criteria. A total of 50 HER2-positive cases were observed. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Molecular profiling was limited. Among three studies with known TP53 status (n = 206), 59% of the tumors expressed TP53 (n = 122), and among two studies with known human papilloma virus (HPV) status (n = 128), 21% (n = 27) were HPV-positive. Six studies used American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines in breast cancer. Pooled HER2-positive expression across ASCO/CAP-based studies was 2% (95% CI: 1%, 3%) and for non-ASCO/CAP-based studies was 21% (95% CI: 2%, 52%). Exploratory pooled estimated proportion of HER2-positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies, I² value of 91.1% [95% CI: 85.4%; 94.6%], and no significant publication bias was observed (Egger’s test p = 0.364). This study could not assess prognostic value of HER2 overexpression in VSCC. Conclusions: HER2 positivity in VSCC appears uncommon but it remains to be fully explored. Standardized assessment using contemporary ASCO/CAP breast, endometrial-specific and/or gastric criteria are needed to clarify the prevalence of HER2-positive versus HER2-low/ultralow disease to inform potential use of HER2-targeted therapy. Full article

Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited therapeutic options in advanced and recurrent diseases. Advanced PSCC is typically managed with multimodal therapy, including neoadjuvant chemotherapy or chemoradiation followed by surgery; however, durable responses remain uncommon, and outcomes after recurrence are poor. Cancer vaccines represent a promising immunotherapeutic strategy, as these treatments induce tumor-specific immunity and heightened immune surveillance against penile cancer cells. While therapeutic cancer vaccines have not yet demonstrated consistent clinical efficacy as monotherapy in PSCC, their integration with complementary immune-modulating approaches, particularly immune checkpoint blockade, represents a rational strategy to enhance antitumor immunity. This review summarizes the rationale for vaccine development in PSCC, with emphasis on HPV-derived antigens, neoantigens, and emerging tumor-associated targets. We examine major vaccine platforms, including viral-vector, peptide-based, nucleic acid, and dendritic cell-based approaches. We also discuss how spatial transcriptomics, single-cell RNA sequencing, artificial intelligence-assisted antigen prediction, and nanotechnology-enhanced delivery systems may support future personalized vaccine development. Overall, therapeutic vaccines remain investigational in PSCC but may become relevant within biomarker-driven, combination-based immunotherapy strategies. Full article

Objectives: Pediatric nasopharyngeal carcinoma (NPC) is rare and often presents at an advanced stage. Although multimodal treatment can achieve favorable survival, long-term survivors may experience substantial treatment-related morbidity. We aimed to evaluate survival outcomes according to stage and metastatic status and to characterize late toxicity in a 20-year single-center pediatric NPC series. Methods. We retrospectively reviewed 24 pediatric patients diagnosed with NPC between 2003 and 2023. Histology was classified according to WHO criteria, and tumors were staged using the AJCC TNM system. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan–Meier method. Survival distributions were compared using the log-rank test. Late treatment-related toxicities documented during follow-up were recorded descriptively. Results: Twenty-four patients with WHO type III NPC were included. Fourteen patients had stage III disease and 10 had stage IV disease; three had distant metastasis at diagnosis. The median follow-up duration was 50.5 months. At last follow-up, 19 patients were alive and five had died. The estimated 5- and 10-year OS rates were both 72.7%, and the corresponding EFS rates were both 63.7%. Stage IV disease and metastatic presentation were associated with inferior OS. Dysphagia, malnutrition, xerostomia, fibrosis, hypothyroidism, and deafness were the most frequently recorded adverse health effects. Conclusions: This 20-year single-center experience shows that AJCC stage and metastatic status remain key determinants of survival in pediatric NPC. The high burden of late treatment-related complications highlights the importance of integrating long-term multidisciplinary survivorship surveillance into the care of pediatric NPC survivors. Full article

Background/Objectives: Sinonasal osteomas are benign, slow-growing tumors that are typically asymptomatic and incidentally detected. However, in rare cases, they may present with atypical and potentially serious complications involving other sinonasal, orbital, or intracranial structures. This review aims to synthesize these unusual manifestations and to highlight the underlying mechanisms, diagnostic challenges, and management implications. Methods: A narrative review of the literature was conducted, focusing on reported cases of sinonasal osteomas with rare or complicated presentations. Studies were analyzed with emphasis on clinical features, imaging findings, pathophysiological mechanisms, and treatment strategies. Results: Unusual presentations of sinonasal osteomas are primarily driven by sinus obstruction, progressive expansion, and skull-base erosion. These processes may result in complications such as pneumocephalus, intracranial mucoceles, cerebrospinal fluid leaks, orbital compression, and secondary infections. Clinical manifestations are often nonspecific, including headache, seizures, visual disturbances, or focal neurological deficits, which may delay diagnosis. High-resolution computed tomography is essential for identifying the osseous lesion and associated bone changes, while magnetic resonance imaging is critical for assessing soft-tissue involvement and intracranial extension. Management is individualized, with surgical resection indicated in most symptomatic or complicated cases, using endoscopic, open, or combined approaches. Conclusions: Although rare, atypical manifestations of sinonasal osteomas can result in significant morbidity. A mechanism-based understanding, supported by appropriate imaging, is essential for accurate diagnosis and timely management. Increased clinical awareness is crucial to improving outcomes in these uncommon but clinically significant cases. Full article

Background: MEIS1::NCOA1/2 fusion sarcomas are a recently described molecular entity arising predominantly in the genitourinary and gynecologic tracts. Their clinical presentation is often misleading, and no standardized treatment guidelines currently exist. Methods: A literature review was conducted using PubMed to identify all reported cases of molecularly confirmed MEIS1::NCOA1/2 fusion sarcomas. Clinicopathological, molecular, treatment, and outcome data were extracted for comparative analysis. Case: We report the case of a 38-year-old nulliparous woman who presented with a right vulvar induration clinically consistent with a Bartholin gland cyst. Surgical excision revealed a spindle cell mesenchymal tumor harboring a MEIS1::NCOA2 fusion transcript and a CTNNB1 exon 3 mutation, with probable incomplete resection margins. A local recurrence was documented by MRI and PET–CT at eight months. Surgical re-excision revealed diffuse involvement and complete excision was considered uncertain. Adjuvant external beam radiotherapy followed by an MR-Linac boost was administered. Discussion: This case highlights the diagnostic challenge of Bartholin gland masses. We provide a review of the literature on MEIS1::NCOA1/2 fusion sarcomas and examine the potential aggressiveness of tumors that additionally harbor a CTNNB1 mutation. Given the nonspecific immunophenotype of this entity, this case underscores the indispensable role of RNA-based molecular sequencing in the diagnosis of low-grade spindle cell tumors when immunohistochemistry proves inconclusive. We further discuss the surgical challenges inherent to this anatomical region and explore intention-to-treat radiotherapy as a potential therapeutic option. Conclusions: We report a rare case of a MEIS1::NCOA2 fusion-positive sarcoma arising in the Bartholin gland region, and, to our knowledge, the first case in which radiotherapy with curative intent has been explored for this entity. This observation expands the limited literature on this emerging clinicopathological entity. Full article

Background: The Ketogenic Diet (KD) has been proposed as an adjunct to standard therapy for gliomas by targeting tumor glycolysis. We systematically reviewed evidence on KD interventions in patients with glioma across multiple outcomes. Methods: Following Cochrane guidelines, we searched MEDLINE, Embase, and Cochrane Library (until 1 February 2025) for studies on humans with glioma treated with any KD versus usual care or other diets. Outcomes included overall survival (OS) and progression-free survival (PFS), quality of life (QoL), biochemical markers (glucose, ketones, glucose–ketone index GKI), anthropometric measures, safety, and tolerability. All study designs were eligible. The quality of the studies was assessed with JBI tools. Data were narratively synthesized due to heterogeneity. The PROSPERO registration is CRD42024547388. Results: Twenty-three studies (306 patients) were included: two RCTs, 11 quasi-experimental studies, six case series, and four case reports. Dietary interventions included classic KD, modified KD, medium-chain triglyceride KD, and Modified Atkins Diet, sometimes combined with fasting. The overall dropout was 20.3%, mainly due to dietary restrictiveness, disease progression, adverse effects, or QoL concerns. Survival results were inconsistent: RCTs showed no significant OS/PFS differences versus controls, although exploratory analyses suggested better outcomes with lower glucose levels. Ketosis was commonly achieved; glucose reductions were variable, and GKI was rarely reported, with target values seldom reached outside fasting periods. Weight/BMI generally decreased modestly or remained stable; adverse events were mostly mild and tolerability was acceptable. Conclusions: Evidence for KDs in glioma patients is heterogeneous and limited. Although ketosis and safety are achievable, survival or QoL benefits remain unproven. Given the methodological challenges, the clinical complexity, and the promising potential of the Ketogenic Diet, further well-designed studies are needed to clarify its clinical utility in glioma treatment. Full article

Background/Objectives: Medullary thyroid carcinoma (MTC) is a rare and aggressive endocrine malignancy frequently associated with RET alterations and dysregulation of RET-associated signaling pathways. In previous studies, first-generation nitro-substituted thieno[3,2-c]quinolines 1 showed promising antiproliferative activity in TT(RET^C634R) cells, while subsequent imidazole-based optimization generated second-generation derivatives 2 with broad-spectrum antiproliferative activity in the NCI-60 human tumor cell line panel. Since thyroid cancer models are not included in the NCI-60 platform, the present study aimed to evaluate the antiproliferative potential of these optimized derivatives in clinically relevant MTC cellular models. Methods: Imidazole-functionalized thieno[3,2-c]quinoline derivatives (2a–j) were evaluated against TT(RET^C634R) and MZ-CRC-1(RET^M918T) cells. The most active compounds were further characterized through induced fit docking (IFD), MM-GBSA calculations, and molecular dynamics (MD) simulations on representative molecular targets. In silico ADME/Toxicity profiling was also performed to assess their developability. Results: Several derivatives exhibited potent activity in both MTC cell models, with multiple compounds achieving submicromolar potency. Compounds 2b and 2g emerged as the most active derivatives in TT(RET^C634R) cells, whereas compounds 2d and 2i displayed the most favorable profile in the aggressive MZ-CRC-1(RET^M918T) model, thereby extending the biological applicability of the scaffold to an additional clinically relevant RET-mutant context. Computational studies supported RET as the most plausible molecular target for all selected lead compounds, while favorable PI3Kα interaction profiles were predicted for selected derivatives, suggesting distinct target engagement profiles within the series. The most promising derivatives also exhibited an overall favorable predicted ADME/Toxicity profile. Conclusions: The present findings support the success of imidazole-based optimization of the thieno[3,2-c]quinoline scaffold and identify thieno[3,2-c]quinolines 2 as promising lead structures for the future development of novel anti-MTC agents. Further biological and mechanistic investigations will be necessary to better clarify the molecular mechanisms underlying their antiproliferative activity and to guide future lead optimization studies. Full article

Background and Clinical Significance: Odontogenic myxoma (OM) is a rare benign neoplasm of the jawbones characterized by spindle-shaped cells embedded in a myxoid stroma. Despite its benign histological nature, it demonstrates locally aggressive behavior, significant invasiveness, and a high risk of recurrence. OM ranks as the third most common odontogenic tumor after odontoma and ameloblastoma. It affects both sexes and occurs more frequently in the mandible than in the maxilla, typically during the second to fourth decades of life. Macroscopically, OM is non-encapsulated, whitish-gray, and gelatinous. Radiographically, it usually presents as a radiolucent lesion with fine bony trabeculae, producing a characteristic “tennis racket” appearance. Case Presentation: We report a case of a 27-year-old male diagnosed with maxillary odontogenic myxoma measuring 2.3 × 1.7 cm. Clinical, radiographic, and histopathological findings were evaluated, and the lesion was treated conservatively by surgical enucleation and curettage. Results: The surgical procedure was completed without complications. Histopathological analysis confirmed the diagnosis of odontogenic myxoma. The patient showed satisfactory postoperative healing, and no evidence of recurrence was observed during a 10-month follow-up period. Conclusions: Although odontogenic myxoma is benign, its locally aggressive nature and recurrence potential require accurate diagnosis and appropriate management. Conservative treatment by enucleation and curettage may be effective for small, well-defined lesions, provided that careful long-term follow-up is maintained to monitor for recurrence. Full article

Background: Paraneoplastic neurological syndromes (PNSs) are rare immune-mediated disorders associated with malignancies and may precede the diagnosis of the underlying tumor. Ovarian cancers, including both epithelial tumors and teratomas, have been associated with a spectrum of antibody-mediated neurological syndromes, although their clinical implications remain poorly defined. Objective: To describe three cases of PNS associated with ovarian malignancies and to provide a narrative review of the literature focusing on their diagnostic and clinical implications. Methods: We report three patients managed at our institution who developed paraneoplastic neurological syndromes in association with ovarian cancer. In parallel, a narrative review of the literature was conducted through PubMed and Google Scholar to identify studies published between 2020 and 2025 reporting PNS in ovarian malignancies. Relevant studies were selected and analyzed qualitatively, with emphasis on timing of onset, clinical presentation, antibody profiles, treatment strategies, and outcomes. Results: Eighteen studies were included, the majority of which were case reports. In most cases, neurological symptoms preceded the diagnosis of ovarian cancer, highlighting their potential role as an early clinical indicator of malignancy. Cerebellar degeneration was the most frequent presentation, often associated with anti-Yo antibodies, while encephalitis was more commonly linked to anti-NMDAR antibodies. Our clinical cases illustrate the heterogeneity of presentation and the complexity of diagnosis and management, requiring a multidisciplinary approach. Across studies, outcomes were variable, with partial improvement or stabilization observed in most cases following oncologic and immunomodulatory treatment. Conclusions: Paraneoplastic neurological syndromes may represent an early clinical clue to ovarian malignancy. Increased awareness among clinicians is essential to prompt appropriate diagnostic evaluation and timely oncologic management. Further research is needed to clarify the role of onconeural antibodies in early detection and disease monitoring. Full article

Reliable osteosarcoma tissue characterization combines radiographic evidence of bone-level structural change with histopathological assessment of cellular morphology. In rare cancers, however, patient-matched multimodal datasets are rarely available because radiology and pathology follow separate clinical workflows and cohort sizes are small. This study examines whether decision-level fusion can integrate radiographs and histopathology images originating from independent, unpaired patient cohorts, and reports the results as a methodological proof of concept rather than as a clinically validated diagnostic system. Two EfficientNet-B0 encoders were trained separately using osteosarcoma-positive radiographs from the Kaggle Bone Tumor Classification dataset (180 images) and H&E-stained histopathology tiles from the TCIA Osteosarcoma Tumor Assessment collection (1144 tiles from four patients). Histopathology tiles carry three labels: non-tumor, viable tumor, and necrotic tumor. Because radiographs do not provide tissue-viability labels and cannot directly distinguish viable from necrotic tumor, the radiographic branch was used as a weak radiograph-derived probability prior mapped into the shared three-class decision space during fusion. Fusion operates only on modality-specific probability vectors; no case-level or patient-level pairing is assumed or required. The adaptive gating network estimates a per-sample radiograph-prior weight, α, from the concatenated vector, [Pr, Ph], where Pr denotes the radiograph-derived probability prior, Ph denotes the histopathology probability vector, and 1 − α denotes the histopathology weight. To limit leakage in the small histopathology cohort, the four patients were assigned to fixed training (P001 and P002), calibration (P003), and test (P004) partitions with strict patient-level separation. On the single held-out test patient (171 tiles), adaptive gating fusion classified 166 of 171 tiles correctly (97.08% accuracy, macro-F1 of 0.97, and macro-AUC of 0.99), compared with 161 of 171 tiles (94.15%) for fixed-α fusion at α = 0.25. McNemar’s test for this comparison gave χ² = 3.20, p = 0.074, so the improvement was numerically higher but not statistically significant at the 0.05 level. Simpler classifiers on the same three-dimensional fused vector reached comparable accuracy (95.91–96.49%), and none differed significantly from adaptive gating. These results indicate that confidence-aware decision-level fusion is feasible under unpaired, data-constrained conditions, and that its present value lies in interpretable per-sample modality weighting rather than in a demonstrated accuracy advantage. The single-patient histopathology test set precludes any claim of clinical generalizability; validation on larger, multi-institutional, patient-level cohorts remains necessary. Full article

Background: Peripheral nerve sheath tumors of the oral cavity are rare and encompass both benign and malignant entities. Differentiating between these lesions remains challenging due to overlapping clinical and histopathological characteristics. Case presentation: We present two cases illustrating the biological spectrum of peripheral nerve sheath tumors in the oral cavity. The first case involves a 76-year-old male with a recurrent lower lip lesion initially diagnosed as benign, which progressed to a high-grade malignant peripheral nerve sheath tumor (MPNST). The second case describes a 20-year-old male presenting with a nodular lesion of the tongue, initially suspected to be reactive following trauma, but histologically confirmed as a benign schwannoma. Both patients underwent surgical treatment with favorable immediate postoperative outcomes. Conclusions: These cases highlight the diagnostic complexity and heterogeneous behavior of peripheral nerve sheath tumors. Histopathological and immunohistochemical evaluations are essential for definitive diagnosis. Clinicians should maintain a high index of suspicion and consider possible association with NF1 or schwannomatosis, particularly in recurrent or atypical lesions. Full article

Acromegaly is a rare chronic endocrine disorder characterized by delayed diagnosis, multisystem comorbidity, and heterogeneous therapeutic response. We aimed to describe the clinical characteristics, tumor profile, treatment patterns, biochemical control, pituitary insufficiencies, and comorbidity burden in an endocrinology tertiary center in northeastern Romania. This observational retrospective study included 87 adult patients admitted for general inpatient evaluation between December 2023 and November 2024, with retrospective data collected from diagnosis and follow-up assessed through the last available hospital visit at St. Spiridon Clinical Emergency Hospital. Clinical, hormonal, imaging, and therapeutic data were analyzed using descriptive statistics and inferential statistical tests. Most patients were diagnosed in middle adulthood, with a female predominance. Macroadenomas and extrasellar extension were common, consistent with advanced tumor stage at presentation. Treatment was predominantly multimodal, with surgery as the main therapeutic intervention and somatostatin receptor ligands as the main medical treatment backbone. Biochemical improvement was observed over time, although complete remission was achieved only in a subset of patients. These findings describe the clinical and therapeutic complexity of acromegaly in a single tertiary-center inpatient cohort and support the need for individualized long-term monitoring. Full article

Inflammatory fibroid polyp (IFP) or Vanek’s tumor is a rare benign submucosal lesion of the gastrointestinal tract that may radiologically mimic mesenchymal gastric tumors, particularly gastrointestinal stromal tumors. We present the case of a 65-year-old patient with a contrast-enhancing gastric submucosal mass detected on computed tomography, initially interpreted as a suspected mesenchymal neoplasm. CT imaging demonstrated a well-defined enhancing lesion arising from the gastric wall without evidence of metastatic disease. Surgical resection was performed because imaging findings were considered highly suggestive of GIST. Gross intraoperative appearance and pathological examination, however, established the final diagnosis of gastric inflammatory fibroid polyp (Vanek’s tumor). Histopathological analysis demonstrated characteristic spindle-cell proliferation with inflammatory eosinophil-rich infiltrates, while immunohistochemistry excluded GIST. This case highlights the diagnostic challenge in differentiating IFP from other gastric submucosal neoplasms based solely on imaging findings and emphasizes the importance of histopathological confirmation for definitive diagnosis. Full article

A 54-year-old female patient presented with a gradually enlarging mass on the ulnar side of the left wrist. Magnetic resonance imaging demonstrated a fat-containing lesion deep within the flexor carpi ulnaris that showed heterogeneous signal intensity, as well as weak internal and peripheral enhancement, which are not typical for atypical spindle cell/pleomorphic lipomatous tumors (ASPLTs). The imaging appearance overlapped with spindle cell lipoma (SCL), atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), and hibernoma, which made preoperative diagnosis challenging. The mass was excised en bloc. Histologically, the tumor consisted of mature adipocytes with substantial size variation, mild atypical spindle cells within a myxoid stroma, and scattered lipoblasts. Immunohistochemistry showed CD34 positivity and loss of RB1, while MDM2 amplification was absent on fluorescence in situ hybridization analysis, supporting a diagnosis of ASPLT. ASPLT is known for its broad range of morphological and radiological presentations, and this case further highlights the difficulty inherent in distinguishing it from SCL and ALT/WDL based on imaging alone. Recognition of its diverse features and the use of molecular testing are essential for accurately diagnosing ASPLT. Surgical excision remains the standard treatment. Although recurrence has been reported, metastasis of ASPLT is exceedingly rare. Full article

Background and Clinical Significance: Tumors of the lacrimal drainage system are rare but clinically important diagnostic pitfalls because they may mimic benign lacrimal drainage obstruction, chronic dacryocystitis, or sinonasal disease. Pleomorphic adenoma (PA) in this region is exceptionally rare, and delayed recognition may allow progressive extension into adjacent structures. Case Presentation: A 51-year-old woman presented with left nasal obstruction 16 years after external dacryocystorhinostomy for presumed lacrimal drainage obstruction. Examination showed a firm left lacrimal sac mass, proptosis, mild ocular motility limitation, and an intranasal mass. Computed tomography and magnetic resonance imaging showed a large lesion centered in the lacrimal sac region and extending into the nasolacrimal duct, nasal cavity, and maxillary sinus, with orbital displacement. Preoperative biopsy showed epithelial neoplastic tissue without definitive malignant features, but low-grade epithelial malignancy could not be excluded. Complete en bloc excision and medial/inferior orbital wall reconstruction with an autologous calvarial outer table bone graft were performed. The tumor measured 55 × 35 × 25 mm. Final histopathology confirmed PA without malignant transformation. At 2 years postoperatively, there was no recurrence, and proptosis and ocular motility limitation had improved. Conclusions: This case illustrates two diagnostic pitfalls: an underlying tumor may masquerade as lacrimal drainage obstruction, whereas a large benign PA may clinically and radiologically mimic malignancy. Long-standing or atypical unilateral lacrimal symptoms should prompt consideration of tumors and selected use of imaging and tissue diagnosis before lacrimal drainage surgery. Full article