Search Results (556)

Background/Objectives: The inflammatory burden index (IBI), calculated as C-reactive protein (CRP) multiplied by the neutrophil-to-lymphocyte ratio (NLR), has demonstrated prognostic value across several solid tumors. Its role in breast cancer, however, has not been investigated. This study evaluated whether pretreatment or post-treatment IBI could predict pathological complete response (pCR) in patients with HER2-positive or triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy (NAC). Methods: This single-center retrospective study included 61 patients who completed NAC followed by surgery between 2019 and 2025. IBI was calculated before and after NAC, and the treatment-related change (ΔIBI) was assessed. Conventional inflammatory indices, including NLR, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), C-reactive protein-to-albumin ratio (CAR), and absolute lymphocyte count (ALC), were evaluated for comparison. Analyses included Mann–Whitney U tests, paired Wilcoxon signed-rank tests, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression. Results: Twenty-nine patients (47.5%) achieved pCR. No pretreatment or post-treatment inflammatory index was significantly associated with pCR. In paired within-patient analysis, IBI increased significantly during treatment only in patients achieving pCR (p = 0.036), while remaining unchanged in the non-pCR group (p = 0.627). CAR showed an identical pattern, increasing exclusively in the pCR group (p = 0.013). This selective rise was not observed for any index lacking a CRP component and was independent of molecular subtype, anti-HER2 therapy, and chemotherapy regimen. On ROC analysis, ΔCAR yielded the highest area under the curve (AUC) among all inflammatory indices (0.637; p = 0.067), followed by ΔIBI (0.606; p = 0.157); neither reached statistical significance. Ki-67 was the only independent predictor of pCR (AUC 0.724; p = 0.003; optimal cutoff ≥25%). Conclusions: This is the first study to evaluate IBI in HER2-positive and TNBC receiving NAC. Static IBI values did not predict pCR. The selective rise in IBI and CAR during treatment in patients achieving pCR—two independently formulated CRP-based indices showing an identical pattern—suggests that the CRP component carries the biologically relevant signal. This hypothesis-generating observation warrants prospective validation in larger cohorts. Full article

Background/Objectives: Primary thyroid lymphoma accounts for approximately 0.2–2% of thyroid malignancies. Plasmablastic lymphoma (PBL), an aggressive large B-cell neoplasm with plasma-cell differentiation and frequent loss of conventional B-cell markers, is a rare thyroid presentation. We report a thyroid PBL presenting as an acute surgical airway emergency in an immunocompetent patient and highlight the diagnostic and management pitfalls that distinguish this from anaplastic thyroid carcinoma. Case Presentation: A 75-year-old man without any significant past medical history presented with rapidly progressive right-sided neck swelling, dysphagia, inspiratory stridor, and respiratory failure. Imaging demonstrated a large, thyroid-centered mass with tracheal involvement, initially raising concern for anaplastic thyroid carcinoma. Histopathology revealed a diffuse infiltrate of large, atypical cells with immunoblastic and plasmablastic morphology. The neoplastic cells were CD20- and CD138-negative but strongly MUM1-positive, with lambda light-chain restriction, bright CD38 by flow cytometry, a Ki-67 proliferation index exceeding 95%, aberrant cytoplasmic CD3 expression, and a MYC::IGH rearrangement, supporting a diagnosis of PBL. Staging identified extranodal perinephric disease and mesenteric lymphadenopathy, consistent with disseminated extranodal Ann Arbor stage IV disease. The patient underwent systemic treatment and initially had an excellent response; however, one month after the last treatment cycle they presented to the hospital with a mass consistent with recurrence. Discussion: Rapid growth, fixation, and tracheal invasion strongly suggest anaplastic thyroid carcinoma in routine clinical practice. However, plasmablastic lymphomas can present similarly and require fundamentally different treatment. In this case, loss of conventional B-cell markers, CD138 negativity, and aberrant cytoplasmic CD3 expression created substantial diagnostic challenges. Light-chain restriction, plasma-cell-associated markers, flow cytometry, and MYC cytogenetics were vitally important. Conclusions: Thyroid-presenting PBL is exceptionally rare and may closely mimic anaplastic thyroid carcinoma, including presentation with life-threatening airway compromise and tracheal involvement. This case highlights several diagnostic pitfalls: CD138 negativity despite plasma-cell differentiation, and aberrant cytoplasmic CD3 expression. Prompt airway stabilization, adequate tissue acquisition, broad immunophenotyping, light-chain assessment, flow cytometry, EBV/HHV8/ALK testing, and MYC cytogenetics are essential for accurate diagnosis and lymphoma-directed treatment. Full article

Sinonasal papilloma is a rare benign neoplasm arising from the Schneiderian epithelium lining the nasal cavity and paranasal sinuses. It is classified into three histological subtypes: exophytic, inverted, and oncocytic, the latter being the least common. We report a case of a giant oncocytic sinonasal papilloma treated by endoscopic surgery, highlighting the diagnostic approach and comparing the findings with the existing literature. Histopathological examination confirmed the diagnosis. Immunohistochemical analysis demonstrated p53 positivity in both the cytoplasm and nucleus, and Ki-67 showed a low labeling index. The patient underwent complete excision via an endoscopic approach. Notably, the lesion was larger than those typically described in the literature. An 18-month follow-up revealed no complications or evidence of recurrence. It is important to bear in mind that a combined tomographic and histopathological evaluation is essential for accurate diagnosis and therapeutic approach. Full article

Background/Objectives: Adrenocortical carcinoma (ACC) is a rare tumor. Diagnosis relies on combined histopathological criteria that, in a multifactorial scoring system, may suggest malignancy. The recent ADIUVO trial, a multicenter trial randomizing ACC patients between mitotane treatment or surveillance only, demonstrated that patients with localized, low-grade ACC (Ki67 labeling index (LI) ≤ 10%) have a better prognosis than historically anticipated, questioning the routine use of adjuvant mitotane. This post hoc analysis aimed to investigate whether automated, centralized Ki67 LI assessment improves prognostic stratification beyond expert manual assessment in low-risk ACC patients enrolled in the original ADIUVO trial. Methods: Ki67 LI was centrally reassessed in 70 ADIUVO patients by digitizing slides and applying an automated algorithm to manually selected hotspots. Primary endpoints were correlation between methods and the impact of automated scoring on recurrence-free survival (RFS) and overall survival (OS). Results: Automated Ki67 LI assessment was feasible in 47 patients. Manual and automated Ki67 LI values showed good agreement (mean 5.6 ± 3.1% vs. 5.4 ± 5.3%). Automated scoring identified eight patients with KI67 LI > 10%. In this subgroup, RFS and OS did not differ significantly between patients treated with mitotane and those under surveillance. Patients with an automated Ki67 LI > 10% had larger tumors (median 16.0 cm vs. 7.0 cm, p = 0.003). Conclusions: Our findings support the original ADIUVO results and support continued use of manual expert Ki67 LI scoring. This traditional approach remains robust and pragmatic for most clinical settings, especially where automated systems are not readily accessible. Full article

Background/Objectives: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Conventional computed tomography (CT) is the preferred imaging modality for evaluating pulmonary nodules because of its high spatial resolution; however, it primarily provides morphological information, including lesion size, shape, and density. Dual-energy CT (DECT), a more recent imaging technique, uses two different energy levels to enable material decomposition and quantitative parameter assessment. These parameters may provide additional information regarding tumor perfusion, vascularization, and tissue composition. This rapid review aimed to evaluate the current evidence regarding the clinical utility of DECT in the detection, characterization, and staging of lung tumors. Methods: This rapid review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed in the PubMed and Cochrane Library databases for studies published between 2005 and 2026. Studies were included if they evaluated the detection, characterization, or staging of lung tumors using quantitative DECT parameters. Case reports, editorials, duplicate studies, and studies without quantitative DECT data were excluded. Descriptive data analysis was performed using Microsoft Excel. Results: A total of 24 studies were included, comprising 18 retrospective (75%) and 6 prospective studies (25%). Only one study evaluated the role of DECT in lung tumor detection, demonstrating improved detection of mixed ground-glass nodules and invasive adenocarcinoma. Significant correlations were found between iodine uptake and tumor perfusion, highlighting the potential of DECT to improve differentiation between benign and malignant lesions. Several studies also demonstrated associations between DECT parameters and tumor biomarkers, including Ki-67 Proliferation Index (Ki-67) expression, Epidermal Growth Factor Receptor (EGFR) mutation status, Programmed Death-Ligand 1 (PD-L1) expression, and treatment response in non-small cell lung cancer. In addition, DECT provided complementary metabolic information regarding tumor malignancy and showed correlations between iodine uptake and fluorodeoxyglucose (FDG) parameters. Associations between iodine volume and tumor differentiation grade were also reported. One study demonstrated the potential role of DECT in tumor staging by predicting mediastinal lymph node metastasis. Across all included studies, iodine-based parameters (50%), radiomics and material decomposition parameters (16.67% each), and spectral attenuation parameters (12.50%) were the most frequently investigated DECT metrics. Conclusions: DECT appears to be a promising complementary imaging technique that provides quantitative perfusion-related and compositional surrogate information beyond the morphological assessment offered by conventional CT. However, the current evidence remains heterogeneous and is largely based on retrospective studies with relatively small patient cohorts. Larger prospective studies with standardized imaging protocols are necessary to further establish the clinical utility of DECT in lung tumors. Full article

The diagnosis and clinical management of myelodysplastic neoplasms are increasingly challenged by the disease’s inherent heterogeneity, particularly with respect to the diagnosis of low-grade variants. While standardized flow cytometric protocols traditionally rely on static biomarkers for lineage assignment, these often fail to capture the dynamic biological behavior of the malignant clone. This review synthesizes studies on the integration of functional biomarkers, specifically the nuclear proliferation marker Ki-67 and the anti-apoptotic protein Bcl-2, into the diagnostic and prognostic workflow. By utilizing high-dimensional multiparameter flow cytometry (MFC) and software-based maturation continuum analysis, the survival and growth kinetics of the myeloid, erythroid, and monocytic lineages can be quantified. These findings redefine myelodysplastic syndromes (MDS) as characterized by a significant decrease in cell-cycle progression and an increase in anti-apoptotic activity during early stages of maturation. Recent studies demonstrate that integrating the erythroid Ki-67 proliferation index as a fifth parameter into the conventional Ogata score dramatically improves diagnostic sensitivity for detecting MDS from 66% to 90% while maintaining 100% specificity. In particular, the sensitivity for detecting low-grade MDS improved from 56% to 91%. Additionally, a reduced erythroid Ki-67 index (≤28%) is a powerful independent predictor of transfusion dependence within 1 year. Beyond diagnostics, the introduction of the Bcl-2:Ki-67 ratio provides a superior metric for biological aggressiveness and a potential predictive tool for precision medicine. A high ratio identifies a quiescent, apoptosis-resistant cell population that is likely refractory to standard chemotherapy but is an ideal candidate for targeted Bcl-2 inhibition with Venetoclax. The integration of functional biomarkers bridges the gap between complex mutational landscapes and clinical manifestations. While digital imaging and artificial intelligence (AI) are beginning to automate blast enumeration and maturation analysis, functional kinetics may provide a necessary biological readout for personalized therapy. Full article

Background/Objectives: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by multisystem infiltration of foamy histiocytes, leading to chronic inflammation, fibrosis, and organ dysfunction. Breast involvement in ECD is extremely uncommon, and the sonographic features of ECD involving the breast remain poorly described. Case Presentation: We report the case of a 59-year-old woman with chronic bone pain and multisystem disease who experienced an extended diagnostic course despite undergoing renal biopsy, biopsy of a right elbow lesion, bone marrow examination, and multidisciplinary evaluation. Breast ultrasound revealed bilateral infiltrative hypoechoic lesions involving the breasts and axillae. These were classified as BI-RADS 4C and were highly suspicious for breast malignancy. Subsequently, an ultrasound-guided core needle biopsy was performed on the breast and axillary lesions. Results: Histopathology showed fibroadipose tissue infiltrated by numerous foamy histiocytes, scattered epithelioid cells, and occasional Touton giant cells. Immunohistochemistry showed positivity for CD68, CD163, CD4, and Cyclin D1, partial positivity for OCT2 and CD30, and negativity for S100, CD1a, Langerin, ALK, CK (Pan), and GATA3. The Ki-67 index was approximately 3%. Molecular testing detected the BRAF V600E mutation, supporting the diagnosis of ECD. A review of reported cases showed that breast involvement in ECD lacks specific ultrasound findings and may closely mimic primary breast malignancy. Conclusions: Breast involvement in ECD is rare and may present as bilateral infiltrative hypoechoic lesions with axillary involvement on ultrasound. In patients with chronic bone pain, symmetric osteosclerosis, or multisystem disease, ECD should be considered in the differential diagnosis. Ultrasound-detected superficial lesions may provide accessible biopsy targets, helping to establish a timely diagnosis and reduce diagnostic delay. Full article

Background and Clinical Significance: Proliferative fasciitis (PF) is an infrequent benign fibroblastic/myofibroblastic proliferation that may closely resemble a soft tissue sarcoma, creating a diagnostic dilemma out of proportion to its biological behaviour. Because no single clinical, histological or immunohistochemical feature is diagnostic, accurate classification depends on the integration of complementary findings. We describe a challenging case of PF involving the lower leg and present a practical clinicopathological approach to its evaluation. Case Presentation: A 34-year-old man presented with a painless subcutaneous nodule on the lateral aspect of the left lower leg, discovered incidentally. Clinical examination suggested a benign superficial soft-tissue lesion, and because no features raised suspicion for malignancy, complete excision was performed without preoperative imaging. Gross examination revealed a 1.9 × 1.6 × 0.7 cm fascial-based lesion composed of spindle cells and scattered ganglion-like cells within a variably myxoid stroma. Focal nuclear pleomorphism, typical mitotic activity (2 mitoses/10 high-power fields), and limited extension into adjacent adipose tissue broadened the differential diagnosis. Immunohistochemistry demonstrated focal SMA positivity, weak focal desmin and S100 expression, absence of CD31 and CD34 staining, and a low Ki-67 proliferative index (approximately 2–3%). Negative surgical margins, together with integration of the clinical presentation, gross findings, histomorphology, and immunophenotype, supported the diagnosis of proliferative fasciitis. The patient remains free of local recurrence four months after surgery. Conclusions: PF should be considered in the differential diagnosis of superficial spindle-cell proliferations showing deceptively aggressive histological features. Careful clinicopathological correlation remains the cornerstone of diagnosis and helps distinguish this benign entity from its malignant mimics. The clinicopathological framework proposed in this report may assist pathologists in the systematic evaluation of similar diagnostically challenging lesions. Full article

Background/Objectives: Breast cancer is the most frequent malignant neoplasm in women and presents marked biological heterogeneity. The androgen receptor (AR) has emerged as a biomarker with important prognostic and therapeutic implications, its effect varying according to the molecular subtype. The objective of this study was to analyze AR expression in breast carcinoma samples and its relationship with the different molecular subtypes and clinicopathological variables. Methods: An observational, descriptive, cross-sectional, and prospective study was conducted based on the immunohistochemical analysis of 215 formalin-fixed, paraffin-embedded breast carcinoma samples. AR expression was digitally evaluated as the percentage of positive tumor cells after incubation with an anti-AR monoclonal antibody. Results: A high frequency of AR expression was demonstrated in the cohort, with a median of 53.3%. There were statistically significant differences between molecular subtypes (p < 0.001), detecting greater expression in luminal tumors and markedly low levels in triple-negative breast cancer (TNBC) (median 0.41%). A significant negative correlation was evidenced between AR expression and the Ki-67 proliferation index (ρ = −0.272; p < 0.001), both in the overall sample and in the TNBC subgroup. Conclusions: The androgen receptor is associated with specific molecular subtypes and lower tumor proliferation, suggesting a less aggressive phenotype and supporting its role as a biological biomarker and potential therapeutic target in the management of breast cancer. Full article

Background/Objectives: Paragangliomas (PGLs) are rare neuroendocrine tumors, and data describing them from a medical oncology perspective are limited. We characterized clinicopathological features, tumor localization, and treatment outcomes. Methods: We retrospectively analyzed 43 patients with PGL at a single medical oncology department. The primary endpoint was recurrence-free survival (RFS), defined as time to first recurrence or death from any cause; overall survival (OS), objective response rate (ORR), disease control rate (DCR), and prognostic associations were secondary. Results: Median age was 44 years, 60.5% were female, and tumors were sympathetic (extra-adrenal) in 55.8% and parasympathetic (head and neck) in 39.5%. After a median follow-up of 116.8 months, 40 patients (93.0%) underwent resection, among whom 14 RFS events occurred (13 recurrences, 1 unrelated death). Median RFS and OS were not reached (60-month RFS, 67.1%; 120-month OS, 83.3%). Among nine patients receiving first-line systemic therapy (eight response-evaluable), ORR was 12.5% and DCR 37.5%. In exploratory univariable analysis, a Ki-67 index ≥ 3% correlated with recurrence (time-averaged hazard ratio, 4.53; 95% CI, 1.55–13.19; p = 0.006), alongside an R1 resection margin (not significant after Bonferroni correction). Conclusions: These findings may support further evaluation of Ki-67 within risk-adapted surveillance but do not replace germline testing. Full article

Background: Pyogenic granuloma (PG) is an uncommon vascular proliferation that, when it arises intraorally, is predominantly gingival; buccal mucosal involvement is rare. Extragingival PG in elderly patients may mimic malignant vascular tumors. Methods: We report a 69-year-old woman with a 1.0 cm ulcerated mass of the left lower buccal mucosa that enlarged after biting trauma. The excised lesion was examined histopathologically and by immunohistochemistry for CD31, CD34, D2-40, S100, human herpesvirus 8 (HHV-8), Ki-67, and p53. Reports of buccal mucosal PG published up to December 2025 were reviewed. Results: The initial pathology report described an atypical vascular tumor with involved margins, requiring exclusion of hemangioendothelioma, angiosarcoma, and Kaposi sarcoma. Immunohistochemistry showed diffuse CD31 and CD34 positivity and preserved S100-positive perilesional nerve bundles, with absent HHV-8, a low Ki-67 index, and no aberrant p53 expression; the diagnosis was formally amended to PG. No recurrence occurred at 9 months despite involved margins. Among 11 previously reported cases, recurrence was documented in 6, none of which recurred. Conclusions: Buccal mucosal PG may mimic vascular malignancy in elderly patients, and immunohistochemistry can be decisive. Whether prognosis differs by site remains an open question requiring larger series. Full article

Middle ear neuroendocrine tumours (MeNETs) are rare epithelial neoplasms with neuroendocrine differentiation that pose significant diagnostic and therapeutic challenges. The clinical presentation of MeNETs is often nonspecific and can mimic other middle ear pathologies, such as chronic otitis media, cholesteatoma, or paraganglioma Common symptoms include conductive hearing loss, otalgia, intermittent or persistent tinnitus, ear fullness, and dizziness. We present five patients who underwent surgery in our University Otolaryngology Centre between 2019 and 2025, in whom histopathological examination confirmed the diagnosis of MeNET. Although MeNET is typically considered an indolent tumour, rare cases of locally aggressive behaviour and distant metastases have been reported in the literature. Metastatic potential appears to correlate with histopathological features such as increased mitotic activity, Ki-67 proliferation index > 5%. The treatment of choice for MeNET is surgical resection of the tumour, with the choice of surgical technique depending on the stage of the tumour, its relationship to surrounding anatomical structures, and the possibility of hearing preservation. In our study, we highlighted the importance of radical tumour excision to minimize the risk of recurrence. Given the risk of recurrence and the risk of potential metastases, long-term follow-up is necessary, particularly in patients with advanced-stage tumours. Full article

Background/Objectives: Primary renal NETs are exceptionally rare neoplasms that occur disproportionately in horseshoe kidneys. Their rarity and non-specific clinical and radiological features make preoperative diagnosis particularly challenging. Methods: Herein, we report the case of a 60-year-old woman presenting with a painful left lumbar mass associated with dysuria and pollakiuria. Results: Computed tomography revealed a large heterogeneous tumor arising from the left moiety of a horseshoe kidney. Histopathological examination of the resected specimen demonstrated a 14 cm well-differentiated NET (grade 1) with diffuse chromogranin A and synaptophysin expression, a mitotic count of 1 per 2 mm², and a Ki-67 proliferation index of <1%. The histopathological and immunohistochemical findings, together with the absence of an extrarenal primary site on staging investigations, supported the diagnosis of a primary renal NET. The postoperative course was uneventful, and the patient remained disease-free after two years of follow-up. Conclusions: This case highlights the diagnostic challenges posed by this rare entity and underscores the importance of including primary renal neuroendocrine tumors in the differential diagnosis of renal masses arising in horseshoe kidneys. Full article

Background: Primary intra-axial cerebral schwannomas are exceptionally rare benign tumors that arise within the brain parenchyma without any association with cranial nerves. Their nonspecific clinical and radiological features frequently mimic high-grade gliomas, making preoperative diagnosis challenging. Case Presentation: We report the case of a 17-year-old male who presented with recent-onset right-sided visual disturbance and bilateral early papilledema. Magnetic resonance imaging demonstrated a lobulated, contrast-enhancing left occipitoparietal intra-axial mass with restricted diffusion, hyperperfusion, extensive vasogenic edema, and adjacent calvarial remodeling, raising suspicion for glioblastoma, gliosarcoma, or pleomorphic xanthoastrocytoma. The patient underwent gross-total resection through a left occipital craniotomy. Histopathological examination revealed a well-circumscribed cellular spindle-cell neoplasm with alternating hypercellular and hypocellular areas, perivascular hyalinization, and an absence of mitotic activity or necrosis. Immunohistochemistry demonstrated diffuse positivity for S100 and SOX10, negative Olig2 staining, retained INI-1 expression, and a low Ki-67 proliferation index of approximately 5%, establishing the diagnosis of a WHO grade 1 cellular schwannoma. Conclusions: Intra-axial cerebral schwannoma should be considered in the differential diagnosis of enhancing supratentorial brain lesions in children and adolescents, particularly when imaging suggests a high-grade glioma. Definitive diagnosis relies on histopathological and immunohistochemical evaluation. Gross-total resection is associated with excellent outcomes and durable disease control, although continued radiological surveillance remains advisable given the rarity of the condition. Full article

Triple-negative breast cancer (TNBC) lacking androgen receptor (AR) expression defines quadruple-negative breast cancer (QNBC), which is characterized by younger age at diagnosis, high Ki-67 index, and high genomic instability, however a comprehensive description of the genomic characteristics remains poorly defined. A total of 54 TNBC cases were categorized as TNBC with 100% AR expression (TNBC AR-100%) or QNBC, TNBC with 0% AR expression (TNBC AR-0%). Clinical, molecular, and genomic parameters, specifically pathogenic/likely pathogenic (P/LP) variants in homologous recombination repair (HRR) and cancer-related pathways were measured and analyzed. The QNBC cohort exhibited a high homologous recombination deficiency (HRD) score and a greater overall incidence of copy number variants (CNVs). QNBC harbored a higher mutation rate in TP53 and MYC signaling pathway than TNBC AR-100% tumors. P/LP variants corresponding to the HRR, PI3K/AKT, and RTK/RAS pathways were exclusively identified in QNBC. These results suggest that, at both molecular and genomic levels, the two groups are distinct, holding QNBC tumors more aggressive characteristics, genomic instability, and particular impairments in HRR and cancer-related pathways. In terms of actionability, these differences could potentially be leveraged through different combinations of therapies. Full article