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5 pages, 2981 KB  
Interesting Images
An Extreme Clinical Diagnosis: Primary Metastatic Breast Cancer with Complete Bilateral Breast Contour Elimination and Ulceration
by Menelaos Zafrakas, Theodoros Argyriou, Panayiota Papasozomenou and Christos Emmanouilides
Diagnostics 2026, 16(11), 1744; https://doi.org/10.3390/diagnostics16111744 - 5 Jun 2026
Viewed by 272
Abstract
A 51-year-old woman was admitted with a malodorous ulceration covering the whole area of both breasts, without visible breast contour or remnants of breast tissue. After excision of a skin nodule an invasive ductal carcinoma was diagnosed; grade-2, hormone receptor (HR)-positive, HER2-negative, Ki-67 [...] Read more.
A 51-year-old woman was admitted with a malodorous ulceration covering the whole area of both breasts, without visible breast contour or remnants of breast tissue. After excision of a skin nodule an invasive ductal carcinoma was diagnosed; grade-2, hormone receptor (HR)-positive, HER2-negative, Ki-67 at 25%. Computed tomography of the thorax and abdomen showed pulmonary and osseous metastases. Six cycles of systemic chemotherapy with epirubicin and cyclophosphamide at three-week intervals were administered, followed by endocrine therapy with letrozole. Almost four years later, palbociclib became available and it was added to the patient’s treatment. Loco-regional and distant disease control was achieved attaining maximum response at 11 months after initial diagnosis and since then the patient remains progression-free with good quality of life for more than eight years. This is to the best of our knowledge an extreme case of primary metastatic ulcerative breast cancer with complete local tissue destruction and markedly prolonged progression-free survival. As this is a single-case clinical observation, any conclusions have limited generalizability. Given the rarity of primary metastatic ulcerative breast cancer there are no specific evidence-based treatment guidelines available and published studies have high heterogeneity and low level of evidence, necessitating multidisciplinary approach on a case-by-case basis. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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18 pages, 6438 KB  
Case Report
Recurrent Distant Metastatic Endometrial Cancer Treated with Immunotherapy with Pembrolizumab: A Case Report and Literature Review
by Oi-Yin Leung, Chiu-Hsuan Cheng and Dah-Ching Ding
Diagnostics 2026, 16(11), 1703; https://doi.org/10.3390/diagnostics16111703 - 1 Jun 2026
Viewed by 450
Abstract
Background and Clinical Significance: Advanced-stage and recurrent metastatic endometrial cancer (EC) is a complex and challenging disease with a poor prognosis. Immunotherapy is a promising treatment for advanced and recurrent mismatch repair deficiency (MMRd) EC. Case Presentation: A 57-year-old female patient with stage [...] Read more.
Background and Clinical Significance: Advanced-stage and recurrent metastatic endometrial cancer (EC) is a complex and challenging disease with a poor prognosis. Immunotherapy is a promising treatment for advanced and recurrent mismatch repair deficiency (MMRd) EC. Case Presentation: A 57-year-old female patient with stage 2 dedifferentiated EC with MMRd (immunohistochemistry revealed PMS2 loss) and stage 1 renal clear cell carcinoma received neoadjuvant chemotherapy, underwent radical hysterectomy, received adjuvant chemotherapy and radiotherapy, and underwent partial nephrectomy. Disease progression with recurrent metastases to the third rib and T12 + L1 vertebrae was observed by positron emission tomography–computed tomography (PET-CT) in April 2024. She also had concurrent papillary thyroid carcinoma. Genetic testing confirmed sensitivity to dostarlimab-gxly and pembrolizumab, leading to the initiation of pembrolizumab (200 mg Q3W) and lenvatinib (20 mg QD) in June 2024 after spine surgery. Treatment-related skin toxicities prompted a dose reduction to pembrolizumab 100 mg and lenvatinib 10 mg, but persistent discomfort led to lenvatinib discontinuation in December 2024, with symptom improvement. PET-CT in October 2024 revealed significant improvement in metastatic disease, with probable residual malignancy in the left third rib and posterior pleura, whereas recent follow-up PET-CTs in April and November 2025 showed significantly decreased 18F-fluorodeoxyglucose avidity in the spine and ribs compared with prior studies. She was admitted for her 30th Keytruda cycle in February 2026, with stable vital signs, normal tumor markers, and no post-infusion adverse reactions. Conclusions: We present a 57-year-old female patient initially diagnosed with FIGO Stage 2 EC, who subsequently developed distant metastases and was restaged as FIGO Stage 4B recurrent disease. The management of this patient illustrates the multimodal treatment approach and the critical role of molecular subtyping in guiding immunotherapeutic strategies for recurrent advanced EC. Full article
(This article belongs to the Special Issue Biomarker-Guided Advances in Diagnostic Medicine)
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18 pages, 563 KB  
Review
The Role of Laser Modalities in Melanoma Management: Critical Analysis of Local Control and Palliative Applications
by Francesco Russano, Luigi Dall’Olmo, Francesco Callegarin, Davide Brugnolo, Paolo Del Fiore, Giuseppe Sciacca, Rocco Caminiti, Marco Rastrelli and Simone Mocellin
Cancers 2026, 18(10), 1672; https://doi.org/10.3390/cancers18101672 - 21 May 2026
Viewed by 468
Abstract
Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive [...] Read more.
Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive histopathological diagnosis, Breslow thickness measurement, and surgical margin assessment, which are essential for accurate staging. This narrative review analyzed preclinical and clinical studies evaluating various laser modalities, including Nd:YAG, CO2, pulsed dye, photodynamic therapy (PDT) and photothermal therapy (PTT), for efficacy, recurrence rates, and limitations in cutaneous melanoma management. Nd:YAG laser (1064 nm) showed potential for local control in thin stage I melanomas, reporting a low local recurrence rate of 0–0.7% and favorable 5-year survival in small, non-randomized cohorts. CO2 laser (10,600 nm) provides effective palliation and local control for in-transit or unresectable metastases, but local recurrence is highly variable, reaching up to 46.7%. Photodynamic therapy showed variable efficacy, although Chlorin e6 achieved complete local regression in a small series of metastases. A critical limitation of laser therapy is the irreversible destruction of tissue, which precludes these vital assessments. Therefore, laser treatment should be cautiously reserved for cases where standard surgery is not feasible, acknowledging that it may interfere with the evaluation of curative outcomes and accurate staging. Laser therapy is a valuable minimally invasive adjunct for local control in selected patients who are poor surgical candidates or require palliative care. Routine use is restricted by the lack of randomized controlled trials. Future studies should prioritize combination strategies with systemic or immunotherapeutic approaches to enhance overall outcomes. Full article
(This article belongs to the Section Methods and Technologies Development)
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9 pages, 296 KB  
Article
Metastatic Patterns and Adverse Histopathologic Features in Advanced Renal Cell Carcinoma: A Five-Year Single-Center Retrospective Pathology Study
by Adelina Vidac, Alis Dema, Robert Barna, Aura Jurescu, Bianca Natarâș, Ioana Hurmuz, Diana Nicolcea and Vlad Dema
Medicina 2026, 62(5), 905; https://doi.org/10.3390/medicina62050905 - 7 May 2026
Viewed by 415
Abstract
Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution [...] Read more.
Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, “Pius Brînzeu” Emergency County Hospital, Timișoara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO/ISUP grade, tumor necrosis, sarcomatoid and/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies. Full article
(This article belongs to the Section Urology & Nephrology)
15 pages, 1934 KB  
Systematic Review
Regional Lymph Node Metastasis in Sebaceous Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis
by Talia A. Wenger, Margaret Nurimba, Marta Kulich and Mark S. Swanson
Cancers 2026, 18(9), 1424; https://doi.org/10.3390/cancers18091424 - 29 Apr 2026
Viewed by 556
Abstract
Background/Objectives: Sebaceous carcinoma (SC) is a rare and aggressive malignancy most often arising in the head and neck. The reported rate of lymph node metastasis is variable and current clinical guidelines surrounding pre-treatment imaging and management of lymph nodes are not well [...] Read more.
Background/Objectives: Sebaceous carcinoma (SC) is a rare and aggressive malignancy most often arising in the head and neck. The reported rate of lymph node metastasis is variable and current clinical guidelines surrounding pre-treatment imaging and management of lymph nodes are not well defined. The aim of our systematic review and meta-analysis was to determine a pooled rate of clinically apparent and occult lymph node metastases for SC of the head and neck to inform clinical guidelines. Methods: Per PRISMA guidelines, systematic search of the Pubmed/MEDLINE and EMBASE databases identified studies published before October 2023 reporting regional lymph node status in adults with SC of the head and neck. Meta analysis using the random-effects model was applied to calculate the pooled proportion of subjects with lymph node metastasis. Clinical characteristics of subjects were further analyzed using chi square tests and univariate logistic regression. Results: Thirty-eight studies met inclusion criteria with a total of 2371 patients. The pooled prevalence of regional lymph node involvement, including clinically apparent and occult disease, was 16% (95% CI 13–18%, I2 65%), with increased risk with increasing T stage. The pooled rate of occult lymph node metastases was 7% (95% CI 4–9%, I2 68%). Conclusions: There is a high rate of lymph node involvement in SC of the head and neck, much of which goes undetected during initial workup and treatment. Initial workup should reflect this risk and include appropriate physical exam, imaging, consideration for sentinel lymph node biopsy, and involvement of a multi-disciplinary team. Full article
(This article belongs to the Special Issue Precision Oncology for Rare Skin Cancers)
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8 pages, 1801 KB  
Case Report
An Unusual Case of Upper Digestive Bleeding—Metastatic Amelanotic Melanoma: Case Report and Literature Review
by Mihaela Dranga, Cristina Cijevschi Prelipcean, Otilia Nedelciuc, Alina-Ecaterina Jucan, Georgiana-Elena Sârbu, Atodiresei Carmen, Iolanda Valentina Popa, Roxana Nemțeanu, Irina Ciortescu, Victor Ianole and Catalina Mihai
Life 2026, 16(3), 469; https://doi.org/10.3390/life16030469 - 13 Mar 2026
Viewed by 744
Abstract
Metastatic melanoma is one of the most common malignancies associated with the spread of the primary tumor. The primary site is usually the skin or the eyes. The most frequent site of metastases is the gastrointestinal tract, accounting for 60% of cases at [...] Read more.
Metastatic melanoma is one of the most common malignancies associated with the spread of the primary tumor. The primary site is usually the skin or the eyes. The most frequent site of metastases is the gastrointestinal tract, accounting for 60% of cases at autopsy. In 2% of patients, metastases occur without a detectable primary tumor. We present a rare case of upper digestive bleeding caused by multiple gastrointestinal tract metastases from an amelanotic melanoma. This case report describes a 65-year-old male who arrived at the emergency department after experiencing an episode of upper gastrointestinal bleeding (melena). One week prior to admission, he had been treated with nonsteroidal anti-inflammatory drugs for lower back pain due to L4–L5 disc herniation. Upper digestive endoscopy revealed multiple polypoid masses in the stomach and duodenum, and capsule endoscopy showed additional lesions in the small bowel. Histopathological examination confirmed the diagnosis: metastases from an amelanotic malignant melanoma. Abdominal and cranial computed tomography scans revealed multiple secondary lesions in the brain, gallbladder, retroperitoneal area, gastrointestinal tract, and peritoneum. Localized radiotherapy was applied to the cerebral metastasis, and systemic chemotherapy with dacarbazine was initiated, resulting in a partial clinical response. Unfortunately, the disease progressed, and the patient died one month after diagnosis. Metastatic melanoma of the gastrointestinal tract is an exceedingly rare cause of upper digestive bleeding. Full article
(This article belongs to the Section Medical Research)
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55 pages, 4985 KB  
Systematic Review
Clinical, Dermatoscopic, Histological and Molecular Prognostic and Predictive Factors of Metastatic Melanoma Response to Immunotherapy: A Systematic Review and Drug Class Meta-Analysis
by Michail C. Papazoglou, Chrysostomos Avgeros, Eleni Sogka, Anestis Chrysostomidis, Georgios Karakinaris, Anastasios Boutis, Aimilios Lallas and Athanassios Kyrgidis
J. Clin. Med. 2026, 15(6), 2145; https://doi.org/10.3390/jcm15062145 - 11 Mar 2026
Viewed by 811
Abstract
Introduction: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic melanoma; however, predictive markers of therapeutic response remain poorly defined. This study systematically assesses clinical, histological, and molecular predictors associated with survival outcomes in melanoma patients treated with ICIs. Methods: Following the [...] Read more.
Introduction: Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic melanoma; however, predictive markers of therapeutic response remain poorly defined. This study systematically assesses clinical, histological, and molecular predictors associated with survival outcomes in melanoma patients treated with ICIs. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, a systematic search was conducted in MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published between January 2018 and October 2025. Eligible studies reported associations between predictive factors and overall survival (OS) or progression-free survival (PFS) in adult melanoma patients receiving ICIs. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) from univariate (UVA) and multivariate analyses (MVA) were synthesized using random-effects meta-analyses. Results: Sex was not a consistent predictor (contradictory effects; PFS heterogeneity I2 ≈ 90%), whereas older age predicted worse OS (MVA continuous: HR 1.05, 95% CI 1.02–1.08; UVA ≥ 65 vs. <65: HR 1.70, 95% CI 1.36–2.12). Poor performance status, assessed using the Eastern Cooperative Oncology Group (ECOG) scale, strongly predicted inferior outcomes (ECOG ≥ 1 vs. 0: MVA OS HR 2.01, 95% CI 1.61–2.51; MVA PFS HR 1.49, 95% CI 1.18–1.88; ECOG ≥ 2 vs. <2: MVA OS HR 2.24, 95% CI 1.79–2.81). Elevated lactate dehydrogenase (LDH) was consistently associated with poorer survival (MVA OS HR 1.71, 95% CI 1.53–1.91; MVA PFS HR 1.61, 95% CI 1.41–1.85), whereas body mass index (BMI) > 25 kg/m2 was associated with improved OS (HR 0.82, 95% CI 0.68–0.98). Higher disease burden predicted worse prognosis (Stage IV vs. III: MVA OS HR 1.57, 95% CI 1.16–2.13; >2 metastatic sites vs. ≤2: MVA OS HR 2.38, 95% CI 1.40–4.07; brain metastases: MVA OS HR 1.69, 95% CI 1.30–2.20; MVA PFS HR 1.52, 95% CI 1.00–2.33). Histologic and molecular factors showed prognostic value: ulceration worsened OS (UVA HR 2.08, 95% CI 1.25–3.44) and PFS (UVA HR 2.97, 95% CI 1.39–6.32); acral subtype had poorer OS than cutaneous melanoma (MVA HR 2.99, 95% CI 1.63–5.48); high tumor mutational burden (TMB) improved PFS (UVA HR 0.47, 95% CI 0.33–0.70); and cutaneous immune-related adverse events (irAEs) were associated with favorable outcomes (skin disorders: UVA OS HR 0.26, 95% CI 0.14–0.47; UVA PFS HR 0.50, 95% CI 0.34–0.74). In contrast, detectable circulating tumor DNA (ctDNA) predicted markedly worse PFS (MVA HR 4.72, 95% CI 2.31–9.65) and a non-significant trend toward worse OS (MVA HR 3.34, 95% CI 0.96–11.67). Liver metastases and programmed death-ligand 1 (PD-L1) expression were not significantly associated with survival. Discussion: This meta-analysis synthesizes evidence on clinicopathologic, laboratory, and histopathologic predictors of immunotherapy outcomes in metastatic melanoma. Performance status, age, LDH, BMI, and metastatic burden consistently correlated with prognosis, while ulceration, disease stage, and TMB emerged as key histologic determinants. Conversely, PD-L1 and gender showed no consistent predictive value, whereas cutaneous immune-related adverse events and ctDNA reflected favorable and poor outcomes, respectively. These findings highlight the multifactorial nature of immunotherapy response and support the further development of integrated prognostic models to refine patient stratification and optimize treatment outcomes. Full article
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16 pages, 1704 KB  
Article
Heterogeneity of Hormone Receptors and HER2 in Breast Cancer Cutaneous Metastases: An Institutional Experience
by Roberta Iozzo, Eugenia Belcastro, Giuseppe Nicolò Fanelli, Paola Cinacchi, Paola Ferrari, Andrea Nicolini and Cristian Scatena
Int. J. Mol. Sci. 2026, 27(5), 2377; https://doi.org/10.3390/ijms27052377 - 4 Mar 2026
Viewed by 726
Abstract
Cutaneous metastases are an uncommon but clinically relevant manifestation of breast cancer (BC), often indicating advanced disease and biological progression. Temporal heterogeneity between primary tumors and metastatic lesions, particularly involving hormone receptors (HRs) and HER2 status, may influence prognosis and treatment decisions. We [...] Read more.
Cutaneous metastases are an uncommon but clinically relevant manifestation of breast cancer (BC), often indicating advanced disease and biological progression. Temporal heterogeneity between primary tumors and metastatic lesions, particularly involving hormone receptors (HRs) and HER2 status, may influence prognosis and treatment decisions. We retrospectively analyzed BC patients with cutaneous metastases diagnosed at a tertiary care center between 2015 and 2024. Clinical data, histopathological features, and immunohistochemical profiles of estrogen receptor (ER), progesterone receptor (PgR), and HER2 were evaluated in paired primary tumors and cutaneous metastatic lesions under uniform pre-analytic and analytic conditions. Receptor discordance and survival outcomes were assessed. Among 660 patients with metastatic BC, 28 (4.2%) developed cutaneous metastases. Median age at diagnosis was 63 years, with chest wall as the most frequent site of skin involvement. HR-positive/HER2-negative tumors were predominant, while triple-negative breast cancer accounted for 19.4% of cases and was associated with a shorter disease course and earlier cutaneous metastatic spread. Receptor discordance occurred in 18.2% for ER, 36.4% for PgR and 41.4% for HER2, mainly involving transitions to or from HER2-low status. After skin involvement, prognosis remained poor. Cutaneous BC metastases show marked receptor heterogeneity, reflecting dynamic tumor evolution. These findings support re-biopsy and biomarker reassessment to guide personalized treatment in metastatic BC. Full article
(This article belongs to the Special Issue Molecular Research and Cellular Biology of Breast Cancer)
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11 pages, 903 KB  
Review
Dermoscopy of Cutaneous Melanoma Metastases: A Comprehensive Literature Review
by Martina D’Onghia, Serena Agueci, Biagio Scotti, Francesca Falcinelli, Sofia Lo Conte, Alessandra Cartocci, Christian Dorado Cortez, Emi Dika, Linda Tognetti, Pietro Rubegni, JeanLuc Perrot and Elisa Cinotti
Diagnostics 2026, 16(5), 738; https://doi.org/10.3390/diagnostics16050738 - 2 Mar 2026
Cited by 2 | Viewed by 619
Abstract
Background: Cutaneous melanoma metastases (CMM) represent a clinically relevant manifestation of advanced melanoma and may constitute the first sign of disseminated disease. Their diagnosis is challenging because CMM shows highly variable clinical and dermoscopic presentations and frequently mimic other benign or malignant [...] Read more.
Background: Cutaneous melanoma metastases (CMM) represent a clinically relevant manifestation of advanced melanoma and may constitute the first sign of disseminated disease. Their diagnosis is challenging because CMM shows highly variable clinical and dermoscopic presentations and frequently mimic other benign or malignant skin lesions. Although dermoscopy is routinely used to improve skin lesion assessment, dermoscopic criteria specific to CMM remain poorly defined and still non-standardized. Methods: We performed a narrative review of the literature to summarize dermoscopic features reported in CMM. MedLine (via PubMed) and Web of Science were searched up to 3 December 2025 using the keywords “dermoscopy” and “melanoma metastasis,” complemented by manual reference screening. Eligible studies were English-language full-text articles in peer-reviewed journals providing a complete dermoscopic description. Extracted data included patient demographics and major dermoscopic criteria, categorized as global patterns and focal dermoscopic and vascular structures. Due to heterogeneity, results were synthesized descriptively. Results: Twenty studies were included, comprising 774 patients. Dermoscopic findings were markedly heterogeneous. Globally, lesions frequently showed homogeneous pigmentation with variable colors and included amelanotic presentations. Commonly evaluated focal features included irregular dots and globules, crystalline structures, peripheral gray dots, and lacuna-like areas. Vascular patterns were prominent, particularly serpentine and corkscrew-like vessels. Conclusions: CMM dermoscopy is characterized by substantial heterogeneity and a lack of standardized criteria. Systematic classification of recurring dermoscopic features may improve diagnostic consistency and provide an interpretable framework for future artificial intelligence-based approaches supporting non-invasive recognition of melanoma metastases. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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13 pages, 4311 KB  
Case Report
Inflammatory Mammary Carcinoma in a Captive Bengal Tiger (Panthera tigris tigris) with Lymph Node and Pulmonary Metastases
by Ju-Won Kang, Jaewoo Choi, Hajin Jeong, Hyeon Jeong Moon, Gun Lee, Chung-Do Lee, Ho-Jin Lee, Min-Seop Song, Ji-Hyeon Kim, Yeong-Hun Ko, Hyunwoo Kim, Changmin Sung, Jun-Gyu Park, Yeong-Bin Baek and Sang-Ik Park
Animals 2026, 16(5), 757; https://doi.org/10.3390/ani16050757 - 1 Mar 2026
Viewed by 893
Abstract
Inflammatory mammary carcinoma (IMC) is an aggressive mammary carcinoma phenotype characterized by tumor emboli within superficial dermal lymphatic vessels and early metastasis. A captive Bengal tiger (Panthera tigris tigris) presented with large abdominal mammary masses and regional lymphadenopathy; contrast-enhanced computed tomography [...] Read more.
Inflammatory mammary carcinoma (IMC) is an aggressive mammary carcinoma phenotype characterized by tumor emboli within superficial dermal lymphatic vessels and early metastasis. A captive Bengal tiger (Panthera tigris tigris) presented with large abdominal mammary masses and regional lymphadenopathy; contrast-enhanced computed tomography also revealed a pulmonary nodule. Postmortem examination and histopathology confirmed mammary carcinoma with dermal lymphatic tumor emboli and metastases to regional lymph nodes and the lung. Tumor emboli were cytokeratin positive, supporting epithelial origin and an IMC diagnosis, and neoplastic cells were immunopositive for cytokeratin with concurrent vimentin immunoreactivity. This case highlights the clinicopathologic basis of IMC and the diagnostic importance of including full-thickness skin and adjacent subcutis in the sampling plan. Full article
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16 pages, 1057 KB  
Article
Linking Cancer Pain Features and Biosignals for Automatic Pain Assessment
by Marco Cascella, Francesco Perri, Alessandro Ottaiano, Mariachiara Santorsola, Maria Luisa Marciano, Fabiana Raffaella Rampetta, Monica Pontone, Anna Crispo, Francesco Sabbatino, Gianluigi Franci, Walter Esposito, Gennaro Cisale, Maria Romano, Francesco Amato, Amalia Scuotto, Vittorio Santoriello and Alfonso Maria Ponsiglione
Cancers 2026, 18(4), 646; https://doi.org/10.3390/cancers18040646 - 16 Feb 2026
Cited by 2 | Viewed by 883
Abstract
Background: Pain remains one of the most debilitating and prevalent symptoms in cancer patients. However, assessment based solely on subjective self-report tools is limited by cognitive impairment and the heterogeneous nature of cancer pain. Since evidence on the ability of physiological biosignals to [...] Read more.
Background: Pain remains one of the most debilitating and prevalent symptoms in cancer patients. However, assessment based solely on subjective self-report tools is limited by cognitive impairment and the heterogeneous nature of cancer pain. Since evidence on the ability of physiological biosignals to discriminate cancer pain intensity and pain phenotypes in real clinical settings remains limited, this study explored the potential of biosignals to discriminate between pain intensity and pain type. Methods: Electrodermal activity (EDA) and electrocardiogram (ECG) signals were recorded in cancer patients using the BITalino (r)evolution board (sampling frequency 1000 Hz). EDA was processed to extract skin conductance responses (SCRs) using continuous decomposition analysis (CDA) and trough-to-peak (TTP) methods. Heart rate variability (HRV) features were extracted in both time and frequency domains, including low frequency (LF), high frequency (HF), and the LF/HF ratio. Non-parametric Kruskal–Wallis tests were performed to compare biosignal parameters across pain intensity (Numeric Rating Scale, NRS: low 1–3; medium 4–6; and high 7–10) and pain types (nociceptive, neuropathic, mixed, and breakthrough cancer pain—BTCP). Results: Data from 61 patients were analyzed. For EDA, the maximum skin conductance response amplitude (MaxCDA) significantly differed across intensity groups (p = 0.037). Post hoc analysis showed a significant difference between the low- and high-intensity groups (p = 0.015), with the low-intensity group exhibiting a higher mean MaxCDA (0.063 µS) than the high-intensity group (0.024 µS). Several EDA parameters were significantly associated with pain type. The number of SCRs (TTP) (p = 0.015) and maximum SCR amplitude (TTP) (p = 0.040) were significantly lower in the mixed pain group compared with the nociceptive and neuropathic groups. No HRV parameters showed significant associations with pain intensity or pain type. BTCP did not significantly affect any biosignal parameters. Subgroup analyses showed that EDA features discriminating mixed pain were preserved in patients without bone metastases, BTCP, or high opioid burden, whereas no clinical variable modified the association between biosignals and pain intensity and type. Conclusions: In this investigation, selected EDA parameters were associated with cancer pain intensity and pain type, whereas heart rate variability measures did not show significant discrimination under the present methodological conditions. These findings suggest that EDA may provide complementary information on pain-related autonomic alterations in oncology patients. However, biosignals should not be considered standalone indicators of pain, and their interpretation requires integration with clinical variables and pharmacological context. Further studies adopting multimodal and longitudinal approaches are needed to clarify their role in automatic pain assessment in cancer care. Full article
(This article belongs to the Special Issue Palliative Care and Pain Management in Cancer)
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23 pages, 12933 KB  
Article
Mechanisms of the Antiproliferative Effects of SIRT6 Inhibition in Melanoma: A Multi-Omics Analysis
by Karla B. Anaya Aldrete, Durdana Muntaqua, Liz M. Garcia-Peterson, Mary A. Ndiaye, Jeong Ha Nam and Nihal Ahmad
Cancers 2026, 18(4), 590; https://doi.org/10.3390/cancers18040590 - 11 Feb 2026
Viewed by 1106
Abstract
Background/Objectives: Melanoma is one of the deadliest types of skin cancer due to its ability to metastasize if not treated early. While targeted- and immune- therapies have significantly improved melanoma treatment outcomes, acquired drug resistance even with combined therapeutics remain prevalent. SIRT6 is [...] Read more.
Background/Objectives: Melanoma is one of the deadliest types of skin cancer due to its ability to metastasize if not treated early. While targeted- and immune- therapies have significantly improved melanoma treatment outcomes, acquired drug resistance even with combined therapeutics remain prevalent. SIRT6 is a nuclear histone deacetylase that regulates DNA repair, metabolism, and chromatin remodeling. It is overexpressed in melanoma and its inhibition in melanoma is known to have anti-proliferative response, and alterations in pathways related to cell cycle, senescence, and metastasis. Methods: To deepen our understanding of the role of SIRT6 in melanoma, in this study we utilized RNA sequencing, proteomics, and Ingenuity Pathway Analysis on genetically modified human melanoma cells to determine the downstream mechanism of SIRT6 in melanoma. Results: SIRT6 knock down (KD) in A375 and G361 melanoma cells, with CRISPR/Cas9 or shRNA techniques, resulted in a significant decrease in proliferation and clonogenic survival of the cells. SIRT6 KD caused an altered expression of multiple genes associated with cell proliferation, mitotic regulation, invasion, cell death/senescence, and immunomodulation, including AURKB, ANLN, MYC, FOXM1, RABL6, E2F2, TP53, RBL1, OSM, TNF, IL1B, IL6, and IFNG. Comparative analysis at both transcription and translation levels revealed coordinated downregulation of proliferation, invasion, and migration and upregulation of targets related to cell death, apoptosis, and necrosis. Multi-omics analysis also predicted downregulation of signaling networks associated with MAP3K20, MYC, MKNK, and HMGCR. Conclusions: Given its involvement in tumorigenesis, this study underlines the importance of SIRT6 in melanoma and provides support to its potential as a novel therapeutic target for melanoma. Full article
(This article belongs to the Special Issue Insights from the Editorial Board Member)
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20 pages, 2612 KB  
Case Report
Multimodality Imaging in Cardiac Metastasis of Cutaneous Melanoma: Case Report and Systematic Review
by Karina L. Lara-Sampayo, Juan Carlos Ibarrola-Peña, Miranda de la Pena-Tamez, Jose A. Salinas-Casanova, Rafael Garcia, Carlos Jerjes-Sanchez, Jose Gildardo Paredes-Vazquez and Erasmo de la Pena-Almaguer
J. Cardiovasc. Dev. Dis. 2026, 13(2), 84; https://doi.org/10.3390/jcdd13020084 - 9 Feb 2026
Viewed by 922
Abstract
Background: Cardiac metastases from cutaneous melanoma are uncommon and often underdiagnosed due to their variable and frequently asymptomatic presentation. To better describe their clinical features, diagnostic strategies, and outcomes, we performed a systematic review of published case reports and present an illustrative clinical [...] Read more.
Background: Cardiac metastases from cutaneous melanoma are uncommon and often underdiagnosed due to their variable and frequently asymptomatic presentation. To better describe their clinical features, diagnostic strategies, and outcomes, we performed a systematic review of published case reports and present an illustrative clinical case. Case presentation: We report the case of a 67-year-old man with a history of stage IIA cutaneous melanoma who presented with progressive fatigue and dyspnea. Disease recurrence was confirmed by skin biopsy. Multimodal imaging, including echocardiography, FDG PET-CT, and cardiac magnetic resonance (CMR), demonstrated extensive myocardial infiltration consistent with cardiac metastases. Despite treatment with immunotherapy, the patient experienced progressive clinical deterioration and died six months after diagnosis. Discussion: The systematic review encompassed 23 published articles reporting 27 individual cases, with a mean age at diagnosis of 55.9 years and a clear male predominance. Cardiac involvement exhibited marked heterogeneity in both clinical presentation and anatomical distribution, most frequently affecting the left ventricular free wall and the interventricular septum. Echocardiography consistently served as the initial diagnostic modality, while cardiac magnetic resonance and CT/FDG PET-CT were used to refine lesion characterization and assess extracardiac disease. Notably, a complete multimodal imaging strategy was reported in fewer than one-third of cases, reflecting variability in diagnostic approaches. Survival outcomes were highly heterogeneous, with substantial mortality, underscoring the need for earlier detection and more accurate diagnostic strategies for cardiac involvement in melanoma. Conclusions: Cardiac metastases from melanoma represent advanced disease and remain associated with poor and heterogeneous outcomes. An integrated multimodal imaging approach supports detailed diagnostic characterization and may aid clinical evaluation and management in selected cases. Full article
(This article belongs to the Special Issue Multimodal Cardiac Imaging: New and Controversial Insights)
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17 pages, 1566 KB  
Systematic Review
A Systematic Review of Cutaneous Involvement in Metastatic Bone Sarcomas: Insights from 102 Reported Cases
by Nikolaos Sideris, Efstratios Vakirlis and Elena Sotiriou
Cancers 2026, 18(3), 437; https://doi.org/10.3390/cancers18030437 - 29 Jan 2026
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Abstract
Background/Objectives: Cutaneous metastases from primary bone sarcomas are exceedingly rare and poorly characterized, often posing diagnostic challenges due to their atypical presentation. This systematic review aimed to describe the clinical patterns, temporal relationships, and prognostic implications of cutaneous metastases across major bone sarcoma [...] Read more.
Background/Objectives: Cutaneous metastases from primary bone sarcomas are exceedingly rare and poorly characterized, often posing diagnostic challenges due to their atypical presentation. This systematic review aimed to describe the clinical patterns, temporal relationships, and prognostic implications of cutaneous metastases across major bone sarcoma histologies. Methods: A comprehensive literature search was conducted to identify all reported cases of cutaneous metastases from osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Data on patient demographics, primary tumor site, cutaneous lesion characteristics, latency periods, synchronous metastases, morphology, and clinical outcome were extracted and analyzed descriptively. Results: 102 cases were identified, with chordoma representing the most frequent histology. Cutaneous metastases showed histology-specific patterns: osteosarcoma and Ewing sarcoma typically presented with multiple lesions in the context of widespread systemic disease and poor prognosis, whereas chordoma more often exhibited solitary or skin-dominant metastases with longer latency and occasional favorable outcomes, including complete responses after local treatment. Conclusions: Cutaneous metastases in bone sarcomas display heterogeneous behavior, with chordoma demonstrating a more indolent and potentially manageable pattern compared to other histologies. Increased clinical awareness is essential to avoid diagnostic delays and optimize management. Full article
(This article belongs to the Special Issue Cutaneous Metastases: State-of-the-Art Research and Management)
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12 pages, 1412 KB  
Article
Radiofrequency Ablation for Recurrent Pleural Mesothelioma
by Hiroshi Kodama, Kozo Kuribayashi, Haruyuki Takaki, Kosuke Matsuda, Takashi Shinkai, Reona Wada, Atsushi Ogasawara, Masaki Hashimoto, Daichi Fujimoto, Toshiyuki Minami, Soichiro Funaki, Takashi Kijima and Koichiro Yamakado
Cancers 2026, 18(3), 381; https://doi.org/10.3390/cancers18030381 - 26 Jan 2026
Viewed by 744
Abstract
Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. [...] Read more.
Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. The cohort comprised 13 men and 1 woman, with a median age of 69 (range, 54–77) years. All patients had previously received systemic therapy, and 12 had undergone surgery. Seven patients (50%) presented with multiple lesions, and 25 tumors (median diameter 1.8 cm; range, 0.5–7.0 cm) were treated in 23 sessions. Outcomes assessed were local tumor control, complications, and survival. Local progression and overall survival were estimated using Kaplan–Meier analysis. Adverse events were classified according to the Society of Interventional Radiology guidelines. Results: Technical success was achieved in all sessions. Two tumors showed local recurrence, corresponding to 1- and 2-year local progression rates of 10.6%. Seven patients showed distant metastases, most of whom subsequently received systemic therapy. Three patients died, two from disease progression and one from treatment-related gastrointestinal perforation during therapy for an unrelated cancer. The overall survival rates were 100%, 100%, and 60% at 1, 3, and 5 years, respectively. Major and minor complications occurred in one case each (4.3%): a refractory skin ulcer and retroperitoneal hematoma, respectively. Conclusions: RFA was technically feasible and generally well tolerated and helped achieve encouraging local control and survival in patients with recurrent PM, warranting further evaluation of RFA as a complementary approach in multimodal treatment strategies. Full article
(This article belongs to the Special Issue Mesothelioma—from Diagnosis to Treatment)
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