Giant cell tumor of the bone (GCTB) is a locally aggressive benign neoplasm with a significant propensity for local recurrence following intralesional surgery. Isolated involvement of the lateral condyle of the distal femur is uncommon. Extended intralesional curettage with chemical adjuvants and polymethylmethacrylate bone cementing is the accepted limb-salvage treatment. Management of recurrent disease, particularly with repeat joint-preserving surgery, and long-term outcomes beyond 10 years following revision procedures remain underreported in the literature. A 40-year-old male presented with a six-month history of right knee pain and difficulty walking. Radiography demonstrated a well-defined eccentric expansile lytic lesion with a soap-bubble appearance involving the lateral condyle of the right distal femur. Computed tomography confirmed cortical erosion and soft-tissue involvement. Fine-needle aspiration cytology yielded hemorrhagic fluid. Histopathology confirmed giant cell tumor. The patient underwent extended curettage, phenolization, and gentamicin-infused cementing in August 2012. Two years later, local recurrence was detected radiologically; repeat extended curettage and re-cementing were performed in September 2014. The patient remained disease-free at a 13-year follow-up (February 2026) with full knee range of motion, bilateral weight-bearing ambulation, and a structurally intact cement mantle on serial radiographic surveillance. This case proves that repeated curettage with phenolization and cementation is a viable option for limb salvage in cases of recurrent GCTB involving the distal femoral lateral condyle without radiographic spread. Thirteen years of tumor-free survival, functional integrity, and persistence of cement mantle after repeated procedures indicate the efficacy of the procedure, making it a preferable option to wide excision.

Gastric neuroendocrine tumors (gNETs) are uncommon neoplasms arising from enterochromaffin-like (ECL) cells of the gastric mucosa and account for less than 2% of all gastric malignancies.Their clinical presentation varies widely, ranging from incidental indolent polyps to aggressive, disseminated disease. Presentation with portal hypertensive ascites closely mimicking decompensated chronic liver disease (CLD) is exceptionally rare. A 63-year-old postmenopausal woman presented with six months of progressive abdominal distension and was initially evaluated as having decompensated CLD based on a high serum-ascites albumin gradient (SAAG) in ascites. Upper gastrointestinal endoscopy demonstrated a proliferative polypoidal lesion along the lesser curvature of the stomach with high-grade oesophageal varices. Triphasic computed tomography (TPCT) revealed multiple arterially hyperenhancing gastric lesions, retroperitoneal lymphadenopathy, hepatic and splenic deposits, and spleno-portal axis thrombosis, highly suggestive of a gastric neuroendocrine tumor, subsequently confirmed on image-guided biopsy. The patient received therapeutic paracentesis, portal hypertension-directed therapy, nutritional rehabilitation, and geriatric-focused multidisciplinary care. Surgery was deferred in view of comorbidities and functional status; endoscopic surveillance was selected as the preferred management strategy. This case highlights the diagnostic challenge posed by gNETs masquerading as decompensated CLD and underscores the need to consider occult malignancy in elderly patients with unexplained high-SAAG ascites lacking established liver disease risk factors.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare, autosomal dominant tumor predisposition syndrome. It is characterized by the early onset of cutaneous and uterine leiomyomas as well as aggressive renal cell carcinomas (RCC).

This review focuses on the characterization of HLRCC syndrome, its clinical manifestations, and histopathological and molecular diagnostics to optimize the identification of affected patients and families.

The review was conducted based on the current WHO classifications of female genital tumours, urinary and male genital tumours, and genetic tumor syndromes, as well as the current German S3 guideline for renal cell carcinoma, supplemented by a selective literature review focusing on the key clinical and morphological features.

The syndrome is caused by germline mutations in the fumarate hydratase (FH) gene. FH-deficient tumours are highly characteristic but not entirely specific for HLRCC. While uterine leiomyomas occur in up to 80% of affected women and often require early surgical treatment, at least 15% of patients develop aggressive renal cell carcinoma. The diagnosis is based on characteristic morphology, immunohistochemistry (including FH deficiency), and detection of the germline mutation.

Given the potentially aggressive renal manifestation, early pathological identification of FH-deficient tumours plays a central role, as it enables the initiation of genetic testing and structured screening for affected patients and families.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly aggressive hematologic malignancy characterized by frequent cutaneous involvement, rapid systemic dissemination, and poor clinical outcomes. Although initially misclassified due to overlapping morphologic and immunophenotypic features with other acute leukemias, lymphomas, and NK-cell neoplasms, BPDCN is now recognized as a distinct hematologic malignancy. Advances in immunophenotyping, transcriptional profiling, and genomic analysis have clarified the cellular origin of BPDCN and revealed that the disease commonly arises from hematopoietic stem or progenitor cells harboring clonal hematopoiesis (CH)-associated mutations. Subsequent transcriptionally regulated lineage commitment to the pDC program and acquisition of cooperating genetic and epigenetic lesions drive malignant transformation. Recurrent alterations affecting epigenetic regulators, RNA splicing factors, transcriptional networks, and chromatin organization disrupt interferon signaling, promote immune evasion, and stabilize malignant identity. A defining clinical and biological feature of BPDCN is its marked skin tropism, mediated by aberrant expression of adhesion molecules and chemokine receptors and shaped by ultraviolet light-associated mutational selection within the cutaneous microenvironment. This review integrates the current knowledge of BPDCN ontogeny, morphologic and immunophenotypic features, genetic and epigenetic architecture, immune dysregulation, and mechanisms of skin tropism into a proposed unified model of leukemogenesis with implications for diagnosis, prognostication, and biology-driven therapeutic strategies.

Ameloblastoma is a benign yet locally aggressive odontogenic neoplasm characterized by local invasion and a substantial risk of recurrence. Effective management balances resection for cure and functional preservation.

The purpose of this study was to estimate recurrence-free survival (RFS) following treatment of ameloblastoma, to evaluate the association between extraction of teeth involved within the lesion and RFS, and to identify factors associated with time to recurrence.

A retrospective cohort study was conducted at Careggi University Hospital (Florence, Italy) between 2014 and 2024. Eligible patients were screened and subjects with histologically confirmed ameloblastoma and complete clinical and radiologic follow up were included.

The primary predictor variable was treatment modality categorized as resection or nonresection surgery.

The primary outcome variable was time to recurrence, defined as the interval between primary surgical treatment and clinical, radiologic, or histologic evidence of recurrence.

Covariates included age, sex, smoking status, anatomic site, radiographic appearance, and extraction of teeth involved within the lesion.

RFS was estimated using Kaplan-Meier methods and compared using the log-rank test. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. Statistical significance was set at P value < .05.

The final sample included 33 subject with a mean age of 52.6 years (SD 18.5); 72.7% (n = 24) were male. During a median follow up of 124 months (interquartile range 82 to 171), recurrence occurred in 6 subjects (18.2%). Five-year and 10-year RFS rates were 87.5 and 82.6%, respectively. Treatment modality was not associated with RFS in the unadjusted Cox model (HR = 1.14; 95% CI, 0.21 to 6.29; P = .900). In the secondary analysis of subjects with recorded tooth extraction status, absence of extraction of teeth involved within the lesion was associated with an increased hazard of recurrence. (HR = 11.93; 95% CI, 1.08 to 132.18; P = .043; log-rank P = .010).

Within the limitations of this retrospective study, treatment modality was not associated with RFS in this cohort, whereas extraction of teeth involved within the lesion was associated with improved RFS.

Epitranscriptomic regulation has emerged as a critical mechanism in cancer biology, particularly in the development of chemoresistance. RNA modifications including N6-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), N1-methyladenosine (m¹A), 7-methylguanosine (m⁷G), pseudouridine (Ψ), and A-to-I editing dynamically control mRNA stability, splicing, translation, and degradation. RNA-modifying proteins called 'writers,' 'erasers,' and 'readers' regulate post-transcriptional networks to enable tumor adaptation and chemoresistance. In platinum-resistant tumors, epitranscriptomic changes modulate DNA damage response, apoptosis, drug efflux, and detoxification pathways. Preclinical studies demonstrate that pharmacological inhibition of key regulators, such as METTL3 inhibitors (STC-15, STM2457, UZH2) or FTO inhibitors, can sensitize tumors to platinum drugs and stimulate anti-tumor immunity. However, clinical translation remains limited by off-target effects, toxicity, and highly context-specific responses. Epitranscriptomic profiling may help identify novel biomarkers and guiding precision strategies to overcome chemoresistance.

Follicular-patterned thyroid lesions are common and are composed of a wide spectrum of thyroid lesions, including non-neoplastic, benign/low-risk neoplastic, to malignant lesions. The pathologic classifications of these lesions are based predominantly on three features: 1) the invasion status, 2) the nuclear features of papillary thyroid carcinoma (PTC), and 3) the presence of >75% oncocytic cells. This review summarizes the diagnostic criteria, subtyping, pathologic features, differential diagnosis, clinical characteristics, and molecular findings of follicular-patterned thyroid lesions, including follicular nodular disease, follicular adenoma, follicular carcinoma, oncocytic adenoma, oncocytic carcinoma, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid tumor of uncertain malignant potential, papillary thyroid carcinoma infiltrative follicular subtype, and invasive encapsulated follicular variant of papillary thyroid carcinoma.

Robotic Surgery (RS) adoption in public healthcare is limited by high costs. The authors evaluated clinical outcomes and micro-costs of RS for Gastrointestinal (GI) cancers at a Brazilian reference center.

A prospective, randomized trial (NCT02292914) compared RS (da Vinci Si) to a mixed comparator arm (laparoscopic/open) for esophagectomy, gastrectomy, and rectal resection. Primary outcomes were Length of Stay (LOS) and per-patient operative costs. Micro-costing followed national guidelines, including deterministic and probabilistic sensitivity analyses. Analyses followed the intention-to-treat principle.

The authors analyzed 135 patients (65 RS, 70 control). RS significantly reduced LOS in esophagectomy (14.7 ± 8.2 vs. 20.3 ± 7.4 days, p < 0.001) and rectal resection (8.9 ± 2.1 vs. 10.0 ± 2.5 days, p < 0.05); gastrectomy LOS was similar (11.3 ± 3.8 vs. 11.5 ± 4.1). Estimated blood loss decreased by > 50% across all RS procedures (p < 0.05). Oncologic adequacy (R0 rates and lymph node yield) was comparable between groups. No significant differences in major complications occurred. RS increased per-patient incremental costs: esophagectomy +US$ 3,018; gastrectomy +US$ 2,816; and rectal resection +US$ 1,470, with a pooled GI incremental cost of +US$ 2,326 (95% CrI: 1,718-2,944). Proprietary instruments were the primary cost drivers.

Robotic GI surgery reduces LOS and blood loss with oncologic outcomes comparable to conventional approaches. However, it carries a significant cost premium (approx. US$ 2,326/case). Whether these clinical gains justify the investment within the public system requires further multicenter studies incorporating long-term quality-of-life data.

Intramucosal carcinoma (IMC) of the colorectum is a rare and diagnostically challenging neoplasm frequently recognized in patients with Lynch syndrome (LS) recently. This study aimed to compare the clinicopathologic features and immunophenotypes of LS-associated mismatch repair-deficient (MMR-D) colorectal IMCs with mismatch repair-proficient (MMR-P) IMCs and sporadic MMR-D IMCs, as well as to examine APC pathway alterations in LS-associated MMR-D IMCs.

Pathology archives from 2004 to 2024 were reviewed for colorectal IMC cases. Clinical, endoscopic, morphologic, immunohistochemical, and next-generation sequencing data were analyzed.

A total of 31 IMC cases were identified, including 9 LS-associated MMR-D, 5 sporadic MMR-D, and 17 MMR-P. Patients with LS who had MMR-D IMCs were significantly younger (P = .013), had more prior malignancies (P = .003), and had shorter colonoscopy intervals (P = .011) compared with patients with MMR-P and sporadic MMR-D. The LS-associated MMR-D IMCs were larger, more often infiltrated normal mucosa, and exhibited medullary and mucinous features more frequently than other IMCs. While expressing CDX2 and SATB2, LS-related MMR-D tumors showed less CK20 positivity than sporadic MMR-D and MMR-P IMCs (P = .003). Among LS-associated MMR-D IMCs, 37.5% exhibited nuclear β-catenin immunoreactivity, regardless of the specific MMR gene affected.

These findings suggest that LS-associated MMR-D IMCs have distinct clinicopathologic and immunophenotypic profiles compared with MMR-P and sporadic MMR-D IMCs, emphasizing the need for unique diagnostic and management strategies for these patients.

Despite widespread storage of frozen whole blood (FWB) in biobanks worldwide, its suitability for extracellular vesicle (EV) research remains largely unassessed. Here, we developed a robust and practical workflow for EV-based cancer biomarker analysis from FWB by comparing differential ultracentrifugation (dUC), size-exclusion chromatography, and their combination. All methods successfully recovered vesicles within the expected 50-150 nm range, enriched for canonical EV markers, while reducing blood-derived EV contaminants, and displayed vesicle-like morphology. Among tested methods, dUC emerged as the most cost-effective and labor-efficient approach. Applying this pipeline to biobanked FWB samples from patients with small intestinal neuroendocrine neoplasms yielded an average of ∼1,000 proteins detected per sample using mass spectrometry-based proteomics, including known neuroendocrine markers and enrichment in synapse organization signaling pathways. These findings demonstrate the feasibility of EV isolation from FWB and biomarker-relevant downstream analysis, highlighting the untapped potential of EV-based biomarker discovery across diseases from existing biobanks.