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12 pages, 15695 KB  
Case Report
Torsion of the Vermiform Appendix in an 18-Day-Old Neonate: A Case Report from Romania and Review of the Literature
by Paul Tchouala Tchakoute, Alin Iuhas, Vlad-Ionuț Nechita, Andrei Vasile Pașcalău and Ion Cosmin Puia
Reports 2026, 9(2), 182; https://doi.org/10.3390/reports9020182 - 10 Jun 2026
Viewed by 274
Abstract
Background and Clinical Significance: Torsion of the vermiform appendix is a rare condition with a clinical presentation closely resembling acute appendicitis, while preoperative investigations are of limited value in distinguishing between the two entities. In most cases, the definitive diagnosis is made incidentally [...] Read more.
Background and Clinical Significance: Torsion of the vermiform appendix is a rare condition with a clinical presentation closely resembling acute appendicitis, while preoperative investigations are of limited value in distinguishing between the two entities. In most cases, the definitive diagnosis is made incidentally during surgery. Case Presentation: The authors present the case of an 18-day-old female neonate who presented with marked abdominal distension, diffuse spontaneous and palpation-induced abdominal pain, guarding, and signs of peritoneal irritation. The clinical manifestations and paraclinical findings mimicked a neonatal intestinal obstruction; however, intraoperative exploration revealed a gangrenous vermiform appendix twisted 240° anticlockwise, associated with a fibrinous pseudomembrane and multiple enlarged mesenteric lymph nodes. Although the initial therapeutic strategy was to perform a laparoscopy, severe abdominal distension caused by marked aerocolia necessitated conversion to a supra- and infraumbilical midline laparotomy. We thus describe, to the best of our knowledge, one of the youngest neonatal cases of appendiceal torsion reported in the literature. Conclusions: Although rare, appendiceal torsion should be considered in the differential diagnosis of neonatal acute abdomen, and timely surgical exploration is key to achieving a favorable outcome. Full article
(This article belongs to the Section Surgery)
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19 pages, 17979 KB  
Review
Preoperative and Intraoperative Localization of Small Pulmonary Nodules for Sublobar Resection: Practical Insights into Percutaneous, Bronchoscopic/Robotic, RFID (SuReFInD), and Hybrid-OR CT Workflows
by Kanji Tanaka, Masaru Takenaka, Daikichi Meguro, Nobuyuki Take, Teppei Hashimoto, Yasuhiro Fujita, Takehiko Manabe, Katsuma Yoshimatsu, Hiroki Matsumiya, Masataka Mori, Asahi Nagata and Hidetaka Uramoto
Diseases 2026, 14(6), 195; https://doi.org/10.3390/diseases14060195 - 30 May 2026
Cited by 1 | Viewed by 405
Abstract
Thin-slice high-resolution computed tomography (CT) has improved the detection of small pulmonary nodules, increasing the demand for minimally invasive diagnostic and therapeutic resection. While lobectomy with lymph node dissection remains the standard surgical approach for many patients with resectable non-small cell lung cancer, [...] Read more.
Thin-slice high-resolution computed tomography (CT) has improved the detection of small pulmonary nodules, increasing the demand for minimally invasive diagnostic and therapeutic resection. While lobectomy with lymph node dissection remains the standard surgical approach for many patients with resectable non-small cell lung cancer, accumulating evidence supports sublobar resection for selected small, peripheral, and ground-glass-dominant lesions when sufficient margins are achievable. In thoracoscopic and robotic surgery, localization of nodules ≤10 mm or lesions located >5 mm from the pleural surface can be challenging, and failure to identify the target may lead to conversion, larger resection than intended, or prolonged operative time. Several localization strategies have been developed, including CT-guided percutaneous wire/coil/dye marking, bronchoscopic dye mapping, and virtual-assisted lung mapping (VAL-MAP), robotic-assisted bronchoscopic dye or fiducial localization, radiofrequency identification microtag systems (Surgical Real-Time FInger Navigation and Detection) that provide real-time depth information, and single-stage intraoperative CT-guided marking and resection in hybrid operating rooms. This review synthesizes representative evidence and published outcome ranges, and compares workflows, marker-to-lesion precision metrics, complication profiles, operational burden, and cost structures. We emphasize the practical contrast between two-stage and single-stage workflows, the access-route differences between transthoracic and transbronchial techniques, and the need to report localization-to-incision “time at risk”. We also present an expert-consensus decision algorithm aimed at facilitating tailored selection of localization strategies for modern minimally invasive thoracic surgery. Full article
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16 pages, 1879 KB  
Case Report
Asphyxial Mechanisms in Sand Burial, Findings and Diagnostic Challenges—A Case Report and a Literature Review
by Donato Morena, Anna Claudia Caruso, Martina Padovano, Matteo Scopetti and Vittorio Fineschi
Diagnostics 2026, 16(11), 1691; https://doi.org/10.3390/diagnostics16111691 - 30 May 2026
Viewed by 262
Abstract
Background: Fatal sand burial is a rare and diagnostically challenging entity in forensic practice. In such cases, death may result from thoracic or thoracoabdominal compression, airway obstruction by particulate material, massive inhalation of sand or soil, or a combination of these mechanisms. External [...] Read more.
Background: Fatal sand burial is a rare and diagnostically challenging entity in forensic practice. In such cases, death may result from thoracic or thoracoabdominal compression, airway obstruction by particulate material, massive inhalation of sand or soil, or a combination of these mechanisms. External signs may be subtle or absent, making postmortem interpretation highly dependent on a comprehensive, multilevel assessment. Case Presentation and Methods: We report the case of a 17-year-old male who died following accidental sand burial caused by the collapse of a self-excavated beach tunnel. External examination, autopsy, histological and toxicological analyses were performed. A review of the literature was also conducted to identify published forensic cases of fatal sand or soil burial and to compare circumstantial, macroscopic, microscopic, and ancillary findings. Results: Autopsy revealed marked pulmonary edema and congestion, multivisceral congestion, scattered sand granules within the larynx, and epicardial petechiae. Histological examination demonstrated acute pulmonary emphysema, edema, vascular congestion, and hemorrhagic laterocervical lymph nodes. Overall, the findings were considered most consistent with mechanical asphyxia due to thoracic compression. The literature review identified six eligible studies describing eight fatal cases. Despite the limited sample size and marked heterogeneity, two main diagnostic patterns emerged: compression-related deaths, usually associated with tunnel or beach-hole collapse and minimal or absent particulate material within the airways, and aspiration-/obstruction-related deaths, characterized by abundant or compact sand or soil material within the airways. In cases without massive aspiration, mixed mechanisms may coexist. Pulmonary edema and congestion were the most frequently reported autopsy findings. When available, histological examination appeared useful in distinguishing antemortem from postmortem burial. Conclusions: Fatal sand burial should not be regarded as a uniform forensic entity. External examination alone is often insufficient, and accurate diagnosis requires a comprehensive, multidisciplinary approach integrating scene reconstruction, autopsy data, histopathological findings, and ancillary analyses. Hemorrhagic involvement of the laterocervical lymph nodes may represent a potentially relevant but currently underexplored finding, whose diagnostic significance warrants further investigation in analogous cases. Full article
(This article belongs to the Special Issue Advances in Pathology for Forensic Diagnosis)
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12 pages, 2140 KB  
Article
Histologic Heterogeneity of Metastases in Clear Cell Renal Cell Carcinoma with Sarcomatoid Differentiation
by Kaitlin Berry, William Paul Skelton, Madison Karabinus, Steven Monda, Raina Tandon, Henry Frierson and Allison M. May
J. Clin. Med. 2026, 15(10), 3959; https://doi.org/10.3390/jcm15103959 - 21 May 2026
Viewed by 545
Abstract
Background/Objectives: Sarcomatoid or rhabdoid renal cell carcinoma (sRCC) represents an aggressive dedifferentiated phenotype of RCC associated with high metastatic potential. The histologic composition of metastatic lesions arising from clear cell RCC with sarcomatoid/rhabdoid differentiation (ccRCC/sRCC) and its relationship to the primary tumor [...] Read more.
Background/Objectives: Sarcomatoid or rhabdoid renal cell carcinoma (sRCC) represents an aggressive dedifferentiated phenotype of RCC associated with high metastatic potential. The histologic composition of metastatic lesions arising from clear cell RCC with sarcomatoid/rhabdoid differentiation (ccRCC/sRCC) and its relationship to the primary tumor remain incompletely characterized. Methods: We retrospectively reviewed patients undergoing nephrectomy for ccRCC/sRCC who had at least one resected metastatic lesion between 2013 and 2025 at a single institution. Primary and metastatic lesions were characterized by the percentage of clear cell versus sarcomatoid/rhabdoid histology. Associations between sarcomatoid/rhabdoid percentage in the primary tumor, metastatic histology, metastatic location, and overall survival were examined. Results: Twenty-six patients with 63 metastases were included. Metastatic histology demonstrated substantial heterogeneity, with 27 lesions (43%) showing pure clear cell histology, 21 (33%) mixed, and 15 (24%) pure sarcomatoid/rhabdoid. Some patients had multiple metastases with differing histology. Increasing sarcomatoid/rhabdoid percentage in the primary was associated with a higher likelihood of sarcomatoid/rhabdoid in metastases (p < 0.001). ROC analysis demonstrated primary tumor sarcomatoid/rhabdoid percentage predicted sarcomatoid/rhabdoid differentiation in metastases (AUC 0.84, 95% CI 0.73–0.95). An optimal cutoff of 10% sarcomatoid/rhabdoid differentiation predicted sarcomatoid/rhabdoid features in metastases. Metastatic histology varied by site, with lymph node metastases more frequently demonstrating clear cell morphology and visceral metastases more commonly exhibiting sarcomatoid/rhabdoid features. Conclusions: Metastases arising from ccRCC with sarcomatoid/rhabdoid differentiation exhibit marked histologic heterogeneity. These findings highlight the complex biology of ccRCC/sRCC metastasis and underscore the need for studies examining molecular drivers of metastatic heterogeneity, as well as the relationship between metastatic histology and therapeutic response. Full article
(This article belongs to the Special Issue Kidney Cancer: From Diagnostic to Therapy)
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11 pages, 6730 KB  
Case Report
Histiocytic Sarcoma Presenting as a Submandibular Mass in a 93-Year-Old Patient: A Case Report
by Evangelos Kostares, Athina Chatzigavriil, Georgia Kostare, Domna Efthymiou, Charikleia Kouvidou, Ourania Schoinohoriti, Christos Perisanidis and Stavroula Diamantopoulou
Reports 2026, 9(2), 161; https://doi.org/10.3390/reports9020161 - 20 May 2026
Viewed by 667
Abstract
Background and Clinical Significance: Histiocytic sarcoma is a rare and aggressive hematopoietic malignancy, which is particularly uncommon in the head and neck region and exceedingly rare within lymph nodes associated with salivary glands. The present study aims to describe the clinical, radiologic, [...] Read more.
Background and Clinical Significance: Histiocytic sarcoma is a rare and aggressive hematopoietic malignancy, which is particularly uncommon in the head and neck region and exceedingly rare within lymph nodes associated with salivary glands. The present study aims to describe the clinical, radiologic, histopathologic, and immunophenotypic features of a primary histiocytic sarcoma, arising in a lymph node within the submandibular gland, and to highlight the diagnostic challenges and management considerations through a correlation with the existing literature. Case presentation: This case report was conducted according to the CARE guidelines. A 93-year-old male presented with a progressively enlarging mass at the right submandibular region. Clinical examination, magnetic resonance imaging, and fine-needle aspiration cytology were performed, raising suspicion for a malignancy. The patient underwent surgical excision of the right submandibular gland with limited level Ib lymph node dissection. Histopathological evaluation combined with an extensive immunohistochemical panel established the diagnosis of histiocytic sarcoma. The tumor was composed of pleomorphic epithelioid and spindle-shaped cells with marked cytologic atypia and high mitotic activity. Immunohistochemistry demonstrated strong positivity for histiocytic markers (CD163, CD68, CD14) and negativity for epithelial, lymphoid, and dendritic cell markers, allowing for the exclusion of major differential diagnoses. The proliferative index (Ki-67) was approximately 90%, indicating aggressive biological potential. FDG PET-CT performed two months after surgery showed no evidence of residual, regional, or distant disease. Considering the localized presentation and the patient’s advanced age, no adjuvant therapy was administered. During follow-up, no evidence of recurrence or disease progression was observed. Conclusions: Primary histiocytic sarcoma involving a lymph node within the submandibular gland is extremely rare and may clinically and cytologically mimic other malignancies. Accurate diagnosis relies on comprehensive immunohistochemical evaluation and exclusion of phenotypic mimickers. A review of previously reported cases of cervical lymph node histiocytic sarcoma demonstrated an age range from 35 to 80 years, with a male predominance and a higher incidence in Asian countries. Most cases presented with localized cervical lymph node disease. Surgical excision was the most commonly applied treatment, and was frequently associated with favorable outcomes, with several patients remaining disease-free during follow-up periods ranging from 24 to 48 months. The accumulation of additional well-documented cases is essential to improve diagnostic accuracy and guide evidence-based treatment strategies for this uncommon entity. Full article
(This article belongs to the Special Issue Case Reports in Oral Diseases)
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19 pages, 12167 KB  
Article
Immune Correlates of Denileukin Diftitox Treatment in TFH-Type Lymphoma
by Tatsuro Jo, Takahiro Sakai, Kazuhiro Noguchi, Kaori Yamaguchi, Kaho Umemoto, Masatoshi Matsuo, Yasushi Sawayama, Jun Taguchi, Ritsuko Kubota-Koketsu, Kuniko Abe and Kazuto Shigematsu
Cancers 2026, 18(10), 1529; https://doi.org/10.3390/cancers18101529 - 9 May 2026
Viewed by 426
Abstract
Background/Objectives: Follicular helper T-cell (TFH)-type lymphomas, including angioimmunoblastic T-cell lymphoma (AITL) and TFH lymphoma, not otherwise specified (TFH-NOS), are characterized by marked immune dysregulation in the tumor microenvironment. We investigated whether TFH-type lymphomas are enriched in immunosuppressive cells and explored immunologic changes associated [...] Read more.
Background/Objectives: Follicular helper T-cell (TFH)-type lymphomas, including angioimmunoblastic T-cell lymphoma (AITL) and TFH lymphoma, not otherwise specified (TFH-NOS), are characterized by marked immune dysregulation in the tumor microenvironment. We investigated whether TFH-type lymphomas are enriched in immunosuppressive cells and explored immunologic changes associated with denileukin diftitox (DD) treatment. Methods: FOXP3-positive mononuclear cells were quantified by immunohistochemistry in lymph node specimens from 10 patients with TFH-type lymphoma and six with non-TFH-type T-cell lymphoma. Paired skin biopsy specimens obtained before and after DD treatment from two patients with AITL were evaluated for CD4, CD8, CD68, CD163, and FOXP3 expression. Longitudinal flow cytometric T-cell receptor Vβ repertoire analysis of CD8-positive T-cell subsets was performed in three patients with AITL treated with DD. Clinical responses were retrospectively assessed in seven patients with relapsed or refractory TFH-type lymphoma treated with DD. Results: TFH-type lymphomas showed significantly higher intra-tumoral FOXP3-positive cell densities than non-TFH-type lymphomas (p = 0.0024). In paired skin biopsies, DD treatment was associated with reductions in CD68- and CD163-positive macrophage-rich infiltrates and a suggested decrease in FOXP3-positive cells. Among seven patients treated with DD, the overall response rate was 86%, including one complete response and five partial responses. Responders showed selective Vβ over-representation patterns in effector and/or memory CD8-positive T-cell subsets, whereas such findings were not convincing in the non-responder. Conclusions: TFH-type lymphomas were associated with higher FOXP3-positive cell density than selected non-TFH-type comparators. DD treatment may be associated with changes in tissue immune infiltrates and peripheral CD8/TCR Vβ skewing in responding cases, although these findings remain exploratory and do not establish causality. Full article
(This article belongs to the Special Issue The Development of Immunotherapies to Treat Lymphoma)
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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 407
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)
18 pages, 659 KB  
Review
Tumor Budding in Gastric Carcinoma: Beyond Counting Cells at the Invasive Front—A Review of Current Evidence and Biological Perspectives
by Catalin-Bogdan Satala, Gabriela Gurau, Alina-Mihaela Gurau, Gabriela Patrichi and Daniela Mihalache
Int. J. Mol. Sci. 2026, 27(9), 3787; https://doi.org/10.3390/ijms27093787 - 24 Apr 2026
Cited by 1 | Viewed by 444
Abstract
Tumor budding is increasingly recognized as a histopathologic feature associated with invasive behavior in gastrointestinal malignancies. While its prognostic value is well established in colorectal carcinoma, its significance in gastric adenocarcinoma remains less clearly defined because of marked morphologic heterogeneity, variable growth patterns, [...] Read more.
Tumor budding is increasingly recognized as a histopathologic feature associated with invasive behavior in gastrointestinal malignancies. While its prognostic value is well established in colorectal carcinoma, its significance in gastric adenocarcinoma remains less clearly defined because of marked morphologic heterogeneity, variable growth patterns, and the absence of gastric-specific assessment criteria. Multiple studies have associated high budding density with adverse clinicopathologic features, including lymph node metastasis, lymphovascular invasion, advanced tumor stage, and poorer survival, particularly in intestinal-type tumors. However, these associations are more difficult to interpret in diffuse-type and mixed carcinomas, where intrinsic discohesion and architectural variability complicate the distinction between true budding and baseline growth patterns. Beyond prognostic assessment, tumor budding has been linked to localized alterations in cell adhesion, cytoskeletal organization, tumor–stroma interaction, and partial epithelial–mesenchymal transition. Emerging evidence also suggests that its biological significance may differ across molecular subtypes of gastric cancer. This review examines the current evidence on the definition, morphologic spectrum, methodological limitations, and biologic context of tumor budding in gastric adenocarcinoma. We propose that, in gastric cancer, tumor budding is best interpreted not as a uniformly applicable scoring parameter, but as a context-dependent morphologic indicator of invasive tumor remodeling whose meaning varies according to tumor architecture, stromal interface, and molecular subtype. Full article
(This article belongs to the Section Molecular Oncology)
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8 pages, 2530 KB  
Case Report
Merkel Cell Carcinoma of the Thigh Presenting as a Hemorrhagic Mass: A Rare Case Report and Literature Review
by Hüseyin Emre Tepedelenlioğlu, Özlem Orhan, Şefik Murat Arıkan and Güldal Esendağlı
Curr. Oncol. 2026, 33(4), 204; https://doi.org/10.3390/curroncol33040204 - 1 Apr 2026
Viewed by 694
Abstract
Background: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma with a marked propensity for early regional lymph node metastasis. Although MCC most often arises on sun-exposed head and neck skin in older adults, tumors of the lower extremity are [...] Read more.
Background: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma with a marked propensity for early regional lymph node metastasis. Although MCC most often arises on sun-exposed head and neck skin in older adults, tumors of the lower extremity are uncommon and may be mistaken for benign hemorrhagic lesions. Case presentation: A 54-year-old woman developed a rapidly enlarging, hemorrhagic mass in the left suprapatellar thigh. Magnetic resonance imaging demonstrated an extracompartmental subcutaneous soft-tissue mass without quadriceps muscle invasion. Wide local excision including the quadriceps fascia was performed. Histopathologic examination showed a dermal/subcutaneous small blue round cell neoplasm with brisk mitotic activity. Immunohistochemistry demonstrated diffuse cytoplasmic synaptophysin positivity, paranuclear dot-like CK20 reactivity, chromogranin A positivity, and negative MCPyV staining; TTF-1, S100, melan-A, HMB-45, and hematolymphoid markers were negative. Staging positron emission tomography/computed tomography identified ipsilateral inguinal nodal involvement. Therapeutic inguinal lymph node dissection revealed metastatic MCC in one of four lymph nodes without extranodal extension. The final stage was pT3 pN1b cM0 (AJCC 8th edition), corresponding to stage IIIB disease. Adjuvant radiotherapy (57 Gy in 20 fractions) was delivered to the primary bed and ipsilateral inguinal basin. The patient remains disease-free at 5-year follow-up. Conclusions: Lower-extremity MCC can mimic hemorrhagic or post-traumatic lesions, contributing to diagnostic delay. Persistent or rapidly enlarging “hematoma-like” lesions warrant early biopsy, and timely pathologic nodal staging is essential. Multimodal management can achieve durable control even in node-positive disease Full article
(This article belongs to the Section Dermato-Oncology)
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16 pages, 2899 KB  
Article
A New Pearl in Chronic Venous Disease Pathophysiology—The Duplex Ultrasound and the Elastographic Features of Lymph Nodes Varicose Veins in the Groin
by Ioana-Teofana Dulgheriu, Carolina Solomon, Stefan Timofte, Anca-Ileana Ciurea and Sorin Marian Dudea
Diagnostics 2026, 16(6), 905; https://doi.org/10.3390/diagnostics16060905 - 18 Mar 2026
Viewed by 556
Abstract
Background/Objectives: Chronic venous disease (CVD) is a prevalent condition marked by valve dysfunction and increased pressure in lower limb veins. The trans-nodal veins in the inguinal region and Scarpa triangle, which connect the superficial and deep venous systems, provide new insight into [...] Read more.
Background/Objectives: Chronic venous disease (CVD) is a prevalent condition marked by valve dysfunction and increased pressure in lower limb veins. The trans-nodal veins in the inguinal region and Scarpa triangle, which connect the superficial and deep venous systems, provide new insight into venous insufficiency pathways. While they function normally in healthy individuals, they can become dilated in chronic venous disease or following surgery. The purpose of this study was to provide an ultrasonographic anatomical description of intranodal varicose veins and to assess possible changes in the stiffness of varicose, dilated inguinal lymph nodes. Methods: The study comprised 92 participants, including 69 women and 23 men, who underwent Doppler ultrasound examinations of the lower-limb venous system, focusing on the groin from both a descriptive morphological and an elastographic perspective. The diagnosis of lymph node varices was made according to established criteria, its severity was assessed using an original classification system, and shear-wave elastography (SWE) values were recorded. Results: More than 83% of patients with operated CVD had lymph node varicose veins. Patients with lymph node varicose veins had larger groin lymph node diameters than patients with CVD without lymph node varicose pathology. The mean shear wave elastography values were significantly lower in the group with lymph node varices compared to the group without (12.2 ± 1.1 kPa vs. 20.1 ± 2.3 kPa; p < 0.05). Elastographic values correlate with lymph node diameter (p = 0.039) and with varicose vein grade (p < 0.001). Conclusions: Intranodal varices may indicate disease progression. These vascular abnormalities impact SWE measurements by altering tissue mechanics. It is imperative to consider the interactions between the lymphatic and venous systems in the management of CVD to improve patient outcomes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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9 pages, 2841 KB  
Case Report
Paraneoplastic Hepatitis Associated with Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma
by Jasmin Nelissen, Sandra Coenen, King Lam, Michael Doukas, Harry L. A. Janssen and Yasmina Serroukh
Hematol. Rep. 2026, 18(2), 18; https://doi.org/10.3390/hematolrep18020018 - 28 Feb 2026
Viewed by 823
Abstract
Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an indolent B-cell lymphoma with long-term survival and a tendency for late relapse. Hepatic manifestations of varying etiologies have been described in lymphoproliferative disorders. However, paraneoplastic hepatitis is rare, and reports typically describe acute presentations. [...] Read more.
Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an indolent B-cell lymphoma with long-term survival and a tendency for late relapse. Hepatic manifestations of varying etiologies have been described in lymphoproliferative disorders. However, paraneoplastic hepatitis is rare, and reports typically describe acute presentations. We describe an unusual case of paraneoplastic hepatitis with an indolent and progressive clinical course occurring in the setting of relapsed NLPHL. Case Presentation: A 32-year-old man with a history of NLPHL was found to have marked transaminase elevation with preserved liver function during routine follow-up. Extensive evaluation excluded viral, autoimmune, and metabolic causes of liver disease. Liver biopsy demonstrated confluent and bridging necrosis with lymphoplasmacytic infiltrates, without evidence of direct lymphoma involvement. Excisional biopsy of a cervical lymph node revealed relapse of NLPHL without histologic transformation. Treatment with corticosteroids resulted in partial biochemical improvement, and subsequent rituximab monotherapy achieved lymphoma remission. Despite this, low-grade transaminase elevation persisted, and follow-up imaging and liver biopsy demonstrated progression to fibrosis, suggesting a tendency towards chronicity. Conclusions: Paraneoplastic hepatitis should be considered in patients with NLPHL who present with unexplained liver abnormalities. This report illustrates a fibrosing form of paraneoplastic hepatitis associated with NLPHL and broadens the clinical spectrum of paraneoplastic hepatic injury. Early recognition, histological confirmation, and tailored immunosuppressive management are critical to optimizing hepatic and lymphoma-related outcomes. Full article
(This article belongs to the Special Issue Treatment and Prognosis of Hematological Malignancies)
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12 pages, 4684 KB  
Case Report
A Perplexing Plexopathy After Pembrolizumab Therapy in Early-Stage Triple-Negative Breast Cancer
by Toluwalogo Baiyewun, Brian McNamara, Emily Aherne, Alex James Bryan, Julie Twomey, Sorcha NiLoingsigh, Bolanle Ofi, Derek Power and Seamus O’Reilly
Curr. Oncol. 2026, 33(2), 125; https://doi.org/10.3390/curroncol33020125 - 20 Feb 2026
Cited by 1 | Viewed by 1162
Abstract
Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing [...] Read more.
Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognizing toxicity from recurrence and optimizing response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of the left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05 Gy/15 fr to the breast and nodes, followed by a 13.35 Gy/5 fr boost to the tumour bed (breast). Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs. clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusions: Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalized treatment strategies are urgently needed to balance cure with long-term functional outcomes. Full article
(This article belongs to the Section Breast Cancer)
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19 pages, 4199 KB  
Article
Gene Expression Profiling and Prognostic Significance of Nuclear and Membrane Progesterone Receptors in Head and Neck Squamous Cell Carcinoma
by Josipa Jelačić, Nina Milutin, Ilijana Stojković, Ozren Vugrinec, Ana Kvolik Pavić, Sanja Vušković, Ivan Mumlek, Vedran Zubčić, Dinko Leović, Mario Bilić and Petar Ozretić
Int. J. Mol. Sci. 2026, 27(4), 1853; https://doi.org/10.3390/ijms27041853 - 14 Feb 2026
Viewed by 863
Abstract
The risk of developing some types of head and neck squamous cell carcinoma (HNSCC) is seven times higher in males, and such disparities may not be associated only with tobacco and alcohol consumption or HPV infection. Therefore, the endocrine microenvironment is considered another [...] Read more.
The risk of developing some types of head and neck squamous cell carcinoma (HNSCC) is seven times higher in males, and such disparities may not be associated only with tobacco and alcohol consumption or HPV infection. Therefore, the endocrine microenvironment is considered another risk factor, as epidemiologic studies have unequivocally shown the protective effect of estrogen in women. This research was focused on progesterone receptors (PRs), the least-studied sex hormone receptors in HNSCC. Our study included fresh tissue samples from 95 primary tumors, 25 metastatic lymph nodes and 40 healthy oral mucosa. Gene expression of nuclear (PGR) and seven membrane PRs (PAQR5, PAQR6, PAQR7, PAQR8, PAQR9, PGRMC1 and PGRMC2) was analyzed by qRT-PCR and associated with clinicopathological characteristics. The results showed that, compared to control tissue, PGR was increased in metastatic lymph nodes, while PAQR5, PAQR7, PAQR8 and PAQR9 were decreased in primary tumors (all p < 0.05). The expression of almost all PRs was greater in older patients and showed moderate to strong positive mutual correlations in both tumors and controls. PARQ8 and PAQR9 were increased in females and pT4 tumors (all p < 0.05). Survival analysis showed that higher PAQR5 (hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.19–6.57, p = 0.019) and PAQR7 (HR 2.0, 95% CI 1.01–3.81, p = 0.048) were associated with worse overall survival, but their independence was not proven in multivariate analysis. Although most PRs were reduced in primary tumors, an increased PAQR5 expression, also associated with tumor invasion markers, could likely mark a specific aggressive, advanced stage of primary tumors and potentially serve as a negative prognostic biomarker for HNSCC. Full article
(This article belongs to the Section Molecular Oncology)
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14 pages, 396 KB  
Review
Endoscopic Tattooing Using Indocyanine Green (ICG) Fluorescence for Intraoperative Guidance in Colorectal Surgery: Review of the Literature
by Fotios Seretis, Antonia Panagaki, Georgios Tziatzios, Paraskevas Gkolfakis, Evdokia Romanou, Vasilis Papastergiou, Andreas Theodorou, Andreas Kapiris, Dimitrios Theodorou, Tania Triantafyllou, Stylianos Kapiris and Konstantina Paraskeva
Cancers 2026, 18(1), 22; https://doi.org/10.3390/cancers18010022 - 20 Dec 2025
Cited by 1 | Viewed by 995
Abstract
Background and Objectives: Accurate endoscopic lesion localization is crucial for planning and performing curative-intent surgery in colorectal cancer management. The use of indocyanine green (ICG) has been described as a novel alternative for colorectal lesion marking. Materials and Methods: We have performed a [...] Read more.
Background and Objectives: Accurate endoscopic lesion localization is crucial for planning and performing curative-intent surgery in colorectal cancer management. The use of indocyanine green (ICG) has been described as a novel alternative for colorectal lesion marking. Materials and Methods: We have performed a systematic review of the literature on the use of ICG-based tattooing for patients with colorectal cancer undergoing surgery. Results: A total of 19 studies were identified. Seven studies reposted the rates of successful intraoperative localization following ICG tattooing. Additionally, six studies provided detailed descriptions of the administration protocols, including both timing and dosage. A total of twelve studies described the utility of ICG-based tattooing for subsequent lymphadenectomy and its oncologic implications. Lymphadenectomy under fluorescent guidance was associated with increased lymph node yields as well as a change to the surgical lymphadenectomy plan in a significant proportion of patients. Conclusions: ICG-based endoscopic tattooing has demonstrated significant value in facilitating precise lesion localization during curative-intent colorectal surgery. Moreover, its use has been extended to guiding lymphadenectomy, with reports indicating improved lymph node yields. Nevertheless, further research is required to standardize protocols and address existing limitations. Full article
(This article belongs to the Special Issue Novel Concepts in Gastrointestinal Surgical Oncology)
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14 pages, 3153 KB  
Case Report
Indocyanine Green-Guided Lymphatic Sparing Surgery for Lipedema: A Case Series
by Michael Mazarei, Shayan Mohammad Sarrami, Darya Fadavi, Meeti Mehta, Anna Bazell and Carolyn De La Cruz
Lymphatics 2025, 3(4), 42; https://doi.org/10.3390/lymphatics3040042 - 2 Dec 2025
Viewed by 1568
Abstract
Background: Lipedema is a progressive adipofascial disorder marked by painful nodular fat deposition that is often mistaken for obesity. While tumescent liposuction reduces limb volume with relative lymphatic safety, persistent large, painful lobules frequently remain, and excisional strategies risk iatrogenic lymphatic injury. We [...] Read more.
Background: Lipedema is a progressive adipofascial disorder marked by painful nodular fat deposition that is often mistaken for obesity. While tumescent liposuction reduces limb volume with relative lymphatic safety, persistent large, painful lobules frequently remain, and excisional strategies risk iatrogenic lymphatic injury. We evaluated the application of intraoperative indocyanine green (ICG) lymphography to identify and preserve lymphatic channels during debulking surgery for symptomatic lipedema. Methods: We conducted a single-center case series (University of Pittsburgh Medical Center, July 2023–December 2024) of adults with lipedema refractory to conservative therapy who underwent a selective dermato-lipectomy (lobule/skin excision) with or without tumescent liposuction. Patients with clinical lymphedema or dermal backflow in ICG were excluded. Near-infrared ICG (SPY-PHI) was used for pre-incision mapping and real-time intraoperative guidance; lymphatic trajectories were marked and spared during lobule excision. Primary measures included dermal backflow patterns and lymph node transit time; secondary outcomes were complications and symptom burden (Lymphedema Life Impact Scale, LLIS) through ≥24 months. Results: Eight patients (five female/three male; mean age 49.5 ± 14.4 years; median BMI 52.65 kg/m2) underwent ICG-guided surgery. Preoperatively, linear lymphatic patterns were visualized up to the knee in all patients, but dermal backflow patterns could not be visualized in 83% from the level of the knee to the groin. Still, 67% demonstrated inguinal nodal uptake (mean transit 24 min), suggesting preserved lymphatic transport. All cases achieved intraoperative confirmation of intact lymphatic flow after debulking. The mean liposuction aspirate was 925 ± 250 mL per lower extremity; the mean excision mass was 2209 ± 757 g per lower extremity. Complications included two superficial cellulitis events (25%) and one wound dehiscence (12.5%); no hematomas or skin necrosis occurred. No patient developed clinical or imaging evidence of iatrogenic lymphedema during follow-up. Conclusions: Intraoperative ICG lymphography is a practical adjunct for lymphatic-sparing debulking of symptomatic lipedema, enabling real-time identification and preservation of superficial collectors while addressing focal lobules. This hybrid approach—targeted tumescent liposuction followed by ICG-guided superficial dermato-lipectomy—was associated with meaningful symptom improvement and a low morbidity in this early series. Full article
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