Search Results (115)

We report a diagnostically challenging case of a 79-year-old man who presented with mediastinal lymphadenopathy, hepatosplenomegaly, and renal enlargement, raising suspicion for clinical lymphoma. However, the histological evaluation of a submandibular gland excision revealed fibrosis, a dense IgG4-positive plasma cell infiltrate (>100/HPF), and an IgG4:IgG ratio > 40%, supportive of IgG4-related disease (IgG4-RD) in the appropriate clinicopathologic context. This case illustrates an important but well-recognised diagnostic pitfall in which IgG4-RD may clinically and radiologically mimic lymphoma. PET-CT demonstrated multiorgan involvement with diffuse FDG uptake, but definitive diagnosis required the integration of clinical, radiologic, serologic, and pathologic findings. The patient’s laboratory profile, including hypocomplementemia and elevated inflammatory markers, supported the proliferative phenotype of IgG4-RD—recently proposed in the literature as a clinically distinct subgroup with systemic involvement and steroid responsiveness. Rather than representing a novel presentation, this case reinforces the importance of integrated assessment in distinguishing IgG4-RD from haematolymphoid malignancy. PET-CT served as a useful adjunct for identifying multiorgan disease and guiding diagnostic evaluation, but tissue evaluation remained essential to avoid misdiagnosis and inappropriate treatment. Recognition of this entity is vital to avoid misdiagnosis and inappropriate treatment. Full article

Background and Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique widely used for mediastinal staging and diagnosis in patients with lung cancer and extrathoracic malignancies. This study aimed to evaluate patient and procedural factors associated with malignant histopathological outcomes in individuals undergoing EBUS-TBNA for intrathoracic lymphadenopathy across three malignancy groups: primary lung cancer, extrathoracic solid organ malignancy, and hematological malignancy. Materials and Methods: This retrospective descriptive study included patients who underwent EBUS-TBNA at Ankara Bilkent City Hospital between March 2019 and December 2023. Demographic characteristics, histopathological findings, procedural details, additional sampling techniques, and imaging parameters, including FDG SUVmax values from pre-procedural PET-CT, were recorded. Histopathological outcomes were categorized as malignant or non-malignant. Binary and multinomial logistic regression analyses were performed to identify independent predictors of malignancy and to differentiate between malignancy groups and lung cancer subtypes. Results: A total of 776 patients underwent EBUS-TBNA, and 667 were included after excluding non-diagnostic samples. Malignancy was detected in 274 patients, including primary lung cancer (n = 213, 77.7%), extrathoracic malignancy (n = 43, 15.7%), and hematological malignancy (n = 18, 6.6%). Of the included patients, 426 (63.9%) were male; the median age was 63 (IQR = 16) years. Older age (OR = 1.03, 95% CI = 1.02–1.05, p < 0.001), male sex (OR = 2.05, 95% CI = 1.43–2.93, p < 0.001), and larger lymph node size (OR = 1.09, 95% CI = 1.06–1.11, p < 0.001) were independently associated with malignant outcomes. Younger age, female sex, and smaller lymph node size were associated with extrathoracic malignancy compared to primary lung cancer, while younger age was the only predictor of hematological malignancy. Larger lymph node size was inversely associated with adenocarcinoma and squamous cell carcinoma compared with small cell lung cancer. Conclusions: Older age, male sex, and larger lymph node size independently predict malignant EBUS-TBNA outcomes. Younger age and female sex favor extrathoracic malignancy, whereas small cell lung cancer is associated with more extensive nodal involvement. Additional bronchoscopic techniques may enhance diagnostic accuracy in selected patients. Full article

Background: Extrinsic compression of the left atrium (LA) is a rare and underrecognized condition that may result in significant hemodynamic compromise and atrial arrhythmias. The available evidence has been largely limited to isolated case reports and small case series, and clinical awareness has remained low. Methods: We performed a structured review of published case reports and case series indexed in PubMed between 2016 and 2026 describing extracardiac LA compression. A predefined and reproducible literature search strategy with explicit eligibility criteria was applied. The structured review included 22 publications reporting 23 individual cases of LA compression; in addition, two institutional cases with distinct etiologies were presented separately. Demographic characteristics, presenting symptoms, diagnostic modalities, complications, management strategies, and outcomes were synthesized descriptively. Results: The structured review identified gastroesophageal disorders, particularly hiatal hernia, as the most frequent etiology, followed by vascular, mediastinal, malignant, and musculoskeletal causes. Dyspnea was the most common presenting symptom, while hemodynamic compromise, pulmonary edema, and atrial arrhythmia represented the most frequent complications. Transthoracic echocardiography was the initial diagnostic modality in all reported cases, with computed tomography required for definitive etiological diagnosis. The two institutional cases illustrated both a common cause, hiatal hernia mimicking intracardiac mass, and a rare, aggressive malignant cause with extensive mediastinal involvement. Conclusions: Extrinsic LA compression arises from diverse extracardiac pathologies and may be clinically severe. Transthoracic echocardiography can serve as a pivotal first-line tool for early recognition and differentiation from intracardiac masses, while cross-sectional imaging is essential for etiological clarification. By integrating institutional experience with a structured synthesis of published cases, this review can provide practical insights to support timely diagnosis and management of this potentially life-threatening condition. Full article

Pure mediastinal yolk sac tumor is an uncommon and aggressive malignant germ cell neoplasm that presents considerable diagnostic difficulties owing to its pronounced clinical and morphological variability. Mediastinal yolk sac tumors, in contrast to their gonadal equivalents, typically occur at later stages, are typically associated with mixed germ cell components, and have a diverse array of histologic patterns that may resemble both germ cell and somatic malignancies. Accurate identification of these types of cancer is essential since diagnostic misclassification may significantly impact treatment and prognosis. This review provides a comprehensive overview of the morphologic spectrum of mediastinal yolk sac tumor, with emphasis on both classic and variant histologic patterns, including reticular, solid, glandular, papillary, hepatoid, and other less common growth forms. The immunohistochemical correlations of these patterns and their role in resolving diagnostic dilemmas are discussed, along with key differential diagnoses encountered in small mediastinal biopsy specimens. Particular attention is given to the limitations of limited tissue sampling, the impact of post-chemotherapy morphologic changes, and the potential for misinterpretation in this challenging anatomic site. By integrating morphologic features with clinical, radiologic, and laboratory findings, this review aims to enhance diagnostic accuracy and improve recognition of mediastinal yolk sac tumor across its diverse presentations. Full article

Background and Clinical Significance: Mixed-phenotype acute leukemia (MPAL) is a rare hematologic malignancy characterized by the co-expression of myeloid and lymphoid markers and is associated with poor prognosis. Myeloid sarcoma (MS), particularly in the mediastinum, is an uncommon extramedullary manifestation and is rarely reported in association with MPAL. Case Presentation: We report a rare case of mediastinal MS with biphenotypic features and pericardial extension occurring concurrently with MPAL, highlighting diagnostic challenges, therapeutic strategies, and long-term outcomes. We describe the clinical course, diagnostic workup, treatment, and follow-up of a 21-year-old woman who presented with cardiac tamponade secondary to a mediastinal mass. Histopathology and immunophenotyping established the diagnosis of mediastinal MS associated with MPAL (B/myeloid, NOS). Management included surgical cytoreduction, intensive induction chemotherapy, and consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. Fertility preservation with oocyte retrieval, in vitro fertilization (IVF), and embryo cryopreservation was performed prior to conditioning. A focused literature review of MPAL cases with extramedullary involvement was conducted. The patient achieved complete remission following induction therapy and underwent allo-HSCT. Despite the historically poor prognosis of mediastinal MS and MPAL, she remains in sustained complete remission 13 years after diagnosis. A literature review identified only eight reported cases of MPAL with extramedullary disease, with mediastinal involvement described in a single case and allo-HSCT performed in only two patients. Conclusions: This case illustrates a rare presentation of MPAL with mediastinal myeloid sarcoma and cardiac tamponade, demonstrating that aggressive multimodal therapy including allo-HSCT may achieve durable remission even in high-risk presentations. Early multidisciplinary management and consideration of fertility preservation are essential in young patients. Full article

Background: Mediastinal ectopic pancreas (EP) is an exceptionally rare entity that can mimic malignancy. Diagnosis is typically established post-operatively; pre-operative confirmation is challenging. Case Presentation: We describe a 28-year-old man presenting with life-threatening airway obstruction due to a progressive mediastinal mass, requiring emergency tracheal stenting. Diagnostic workup revealed a critical discordance: while CT-guided core biopsy confirmed benign ectopic pancreatic tissue, concurrent flow cytometry identified a monoclonal B-cell population with a high Ki-67 index (~86%), raising concern for a high-grade lymphoid process. However, no morphological evidence of lymphoma was found, and PET-CT showed only moderate metabolic activity (SUVmax 4.6), making an untreated aggressive lymphoma less consistent. The patient declined surgical resection. Management proceeded with a conservative strategy of structured clinical surveillance based on the benign histology. At 6-month follow-up, the patient remained clinically stable without chemotherapy, supporting the diagnosis of benign ectopic pancreas and suggesting the flow cytometric findings represented reactive “pseudo-monoclonality” secondary to inflammation. Conclusions: This case highlights mediastinal EP as a rare airway emergency and illustrates a major diagnostic pitfall: flow cytometric clonality and high proliferative fractions can occur in inflammatory settings and must not override benign architectural histology. When discordance persists and definitive tissue cannot be obtained, management should emphasize multidisciplinary review, deliberate specimen triage, and structured surveillance with predefined triggers for repeat higher-yield biopsy or surgical sampling and airway-stent reassessment. Full article

Ectopic liver is a rare anomaly characterized by the presence of hepatic tissue outside its normal anatomical location without continuity with the main liver. Reports of this condition are sporadic in human medicine, and cases in veterinary species remain limited. This condition may arise as a congenital developmental defect or as a consequence of prior traumatic injury leading to fragmentation and displacement of hepatic tissue. This case study describes an incidental intrathoracic ectopic liver identified in a 6-year-old male cat that died of acute suppurative bacterial pneumonia. Necropsy revealed a well-demarcated, encapsulated, large mass within the middle of the caudal mediastinum, unattached to the diaphragm, lungs, or pericardium. Cytologic and histopathologic examinations confirmed the presence of hepatic tissue with preserved lobular architecture. No evidence of previous trauma or diaphragmatic defects was present, supporting the congenital origin. The accompanying severe bacterial pneumonia was unrelated to the mediastinal mass. This study highlights the diagnostic challenges associated with intrathoracic ectopic liver, which can mimic neoplastic or inflammatory masses. Awareness of this entity is essential for accurate diagnosis. Given the documented risk of malignant transformation in ectopic hepatic tissue, surgical excision and histopathological assessment should be considered whenever such lesions are detected. Full article

Background: Ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases that share immunological pathways but rarely coexist. The increasing use of biologic agents in inflammatory bowel disease (IBD) has raised concerns regarding paradoxical inflammatory manifestations, including sarcoidosis-like reactions. Case presentation: We report the case of a 63-year-old man with long-standing UC treated with vedolizumab who developed systemic sarcoidosis characterized by bilateral hilar lymphadenopathy, mediastinal and abdominal lymph node enlargement, pulmonary involvement, and erythema nodosum. Extensive diagnostic work-up, including imaging and histopathology, confirmed non-necrotizing granulomatous disease consistent with sarcoidosis, while alternative infectious, malignant, and drug-induced causes were excluded. Vedolizumab was temporarily discontinued, leading to UC relapse, and subsequently reintroduced with rapid clinical remission of UC. Discussion: Sarcoidosis remained clinically and radiologically stable despite vedolizumab re-initiation, suggesting a coincidental association rather than a direct causal relationship. This case highlights the diagnostic challenges and therapeutic dilemmas in patients with immune-mediated diseases receiving biologic therapy. Conclusion: The coexistence of UC and sarcoidosis during vedolizumab therapy is rare. Although causality cannot be established, our findings suggest that vedolizumab may be safely continued in selected patients under close multidisciplinary monitoring. Full article

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive non-Hodgkin lymphoma with significant molecular heterogeneity. This variability arises in part from its distinct molecular subtypes, including germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL), which differ markedly in their genetic profiles, signaling pathway activities, and clinical outcomes. Although rituximab-based R-CHOP regimens have significantly improved patient outcomes, around 40% of patients still experience relapsed or refractory disease. DLBCL cells sustain their rapid proliferation through the establishment of an intricate lipid metabolism regulatory network. The interplay between this network, cell death mechanisms (e.g., ferroptosis), and the tumor immune microenvironment (TIME) significantly impacts the malignant progression of the disease and its resistance to treatment. This review summarizes recent advances in understanding the molecular mechanisms and interplay among these processes in DLBCL and discusses the clinical relevance of associated prognostic biomarkers, thus providing new insights into the development of precision therapies. Full article

Background: Computed tomography (CT)-guided lung biopsy plays a pivotal role in diagnosing thoracic lesions. However, its diagnostic yield may be compromised in large, necrotic, or heterogeneous tumours due to inadvertent sampling of non-viable tissue. Dual-energy CT (DECT) iodine mapping provides functional imaging by identifying iodine-avid, perfused areas, thereby offering the potential to improve biopsy targeting. Methods: This single-centre retrospective study evaluated the clinical feasibility and diagnostic performance of DECT-guided biopsy. Adult patients with suspected necrotic lung or mediastinal lesions who underwent DECT iodine mapping prior to CT-guided biopsy between April 2021 and December 2022 were evaluated. DECT iodine maps were generated using dual-source CT and used to identify viable tumour regions for targeted biopsy. The primary outcome was diagnostic yield, defined as obtaining a definitive histopathological diagnosis. Secondary outcomes included safety and adequacy of samples for molecular testing. Results: Twenty patients were included. A definitive diagnosis was obtained in 18/20 biopsies (90%). Diagnostic yield was 9/11 (81.8%) for pulmonary lesions and 9/9 (100%) for mediastinal/pleural lesions. Diagnoses included non-small-cell lung cancer (n = 8), Hodgkin lymphoma (n = 4), thymoma (n = 3), and other malignancies (n = 3). Biopsy material was sufficient for additional molecular testing in 13/20 cases (65%). Complications were minor (one pneumothorax not requiring drainage and two self-limited bleeding events). Conclusions: DECT iodine map-guided targeting was feasible in this retrospective cohort and was associated with high diagnostic yield, low complication rates, and frequent acquisition of tissue suitable for molecular analyses. Prospective controlled studies are needed to quantify benefit over conventional CT guidance. Full article

Immune checkpoint proteins including PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT regulate T-cell functions, which are essential for anti-tumor immunity. Over-expression of these immune checkpoint proteins leads to T-cell exhaustion and a significant impairment of anti-tumor immunity. Rejuvenation of effector T-cell function with immune checkpoint inhibitors (ICI) restores anti-tumor immunity, which translates into clinical efficacy in the frontline and salvage treatment of various hematological malignancies. Efficacy of ICIs is highest in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and NK/T-cell lymphomas, and modest in immune-privileged-site lymphomas and cutaneous T-cell lymphoma. However, in myeloid malignancies and multiple myeloma, the efficacy of ICIs remains doubtful. In addition to being used as single agents, ICIs have also been combined with other ICIs; as well as chemotherapy, antibody drug conjugates, and epigenetic agents (histone deacetylase inhibitors and hypomethylating agents). More innovative strategies include the use of ICIs in the context of allogeneic haematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. This review synthesizes current evidence for the use of ICI in different haematological malignancies, and highlights future directions toward biomarker-driven, rationally designed therapeutic combinations. Full article

Background and Clinical Significance: Breast cancer is the most frequent malignancy in women. Metastatic breast cancer is considered a treatable but incurable condition, with a median overall survival of only 2–3 years. Among its subtypes, triple-negative breast cancer (TNBC) accounts for a high proportion of breast cancer-related deaths. It is characterized by an aggressive clinical course, early recurrence, and a strong propensity for visceral and brain metastases. Case Presentation: We report the case of a Caucasian woman who developed systemic disease recurrence with lung and mediastinal lymph node metastases, occurring two years after her primary diagnosis and treatment for TNBC. The patient received three months of chemotherapy combined with an adjuvant integrative protocol consisting of melatonin, cannabidiol, and oxygen–ozone therapy. This combined approach led to the complete disappearance of the lung nodules. Subsequently, stereotactic radiotherapy was performed and, in association with the ongoing integrative treatment, resulted in a significant reduction in mediastinal adenopathy. Introduction of immunotherapy, supported continuously by the same adjuvant strategy, achieved a complete and durable remission. Strikingly, the patient remained disease-free five years after the diagnosis of lung and mediastinal metastases. Conclusions: This clinical case highlights the potential benefit of using melatonin, cannabidiol, and oxygen–ozone therapy as part of an integrative approach in patients with aggressive metastatic TNBC. While it is not possible to establish causality from a single case, the sustained remission observed suggests that such unconventional adjuvant strategies could play a supportive role in enhancing the efficacy of standard oncologic therapies. Full article

Background and Clinical Significance: Isolated mediastinal lymphadenopathy is an exceptionally rare and diagnostically challenging initial manifestation of microscopic polyangiitis (MPA), often mimicking malignancy or infection. This case highlights the pivotal role of an innovative minimally invasive technique in achieving a definitive diagnosis. To the best of our knowledge, this is the first reported case of MPA diagnosed via EBUS-TMC. Case Presentation: A 55-year-old male livestock farmer from a rural area with a history of recurrent pneumonia presented with four weeks of persistent fever, significant weight loss (7 kg), myalgia, and asthenia. Physical examination revealed fever and cachexia. Notable findings included leukocytosis (17,000/μL), normocytic anemia, thrombocytosis (672,000/μL), highly elevated inflammatory markers (CRP 145 mg/L, ESR 120 mm/h), and strongly positive MPO-ANCA (>134 U/mL). Serological testing was significant for IgG antibodies against Coxiella burnetii (Phase I 1:64, Phase II 1:256). PET-CT imaging demonstrated hypermetabolic bilateral hilar and mediastinal lymphadenopathy. Diagnostic challenges included overlapping serological findings suggestive of past Coxiella burnetii exposure. Endobronchial ultrasound–guided transbronchial mediastinal cryobiopsy (EBUS-TMC) of a subcarinal lymph node was performed, providing a high-quality sample that revealed neutrophilic small-vessel vasculitis with fibrinoid necrosis, definitive for MPA. Immunosuppressive therapy with high-dose corticosteroids and rituximab (1000 mg on days 1 and 15) was initiated, leading to the complete resolution of all constitutional symptoms. Conclusions: This case illustrates that EBUS-TMC is a safe and highly effective diagnostic tool for obtaining critical histological evidence in systemic vasculitides with atypical presentations. This technique should be considered in the diagnostic algorithm for unexplained mediastinal lymphadenopathy to avoid more invasive surgical procedures. Full article

Background and Clinical Significance: Histiocytic sarcoma (HS) is a rare and aggressive form of malignant histiocytosis, often associated with poor prognosis. The diagnosis and management of HS are challenging due to the complexity of its pathogenesis, molecular profile, and the unclear cellular origin of histiocytic neoplasms, compounded by the limited literature on treatment strategies. Case Presentation: We report the case of a young patient with HS localized to the lymph nodes, spleen, and liver, who also presented with hemophagocytic lymphohistiocytosis (HLH) documented on bone marrow biopsy. Initial treatment with CHOEP-21 and ICE-21 chemotherapy resulted in only a partial metabolic response, as evidenced by a Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)/CT scan. Given the aggressive nature of the disease and the presence of HLH, an allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was performed as consolidation therapy, leading to a progressive complete response without significant toxicity. A suspected relapse at 18 months post-transplant was excluded following a mediastinal lymph node biopsy, which revealed a benign intravascular papillary endothelial hyperplasia (IPEH). Over five years post-diagnosis and more than four years after transplantation, the patient remains in complete remission with full functional recovery. Conclusions: This case highlights the diagnostic and molecular challenges of HS and demonstrates the curative potential of early allogeneic HSCT, even when only partial remission is initially achieved. Full article

Mediastinal radiotherapy plays a central role in the treatment of several malignancies, particularly Hodgkin lymphoma and breast cancer. However, exposure to thoracic radiation is associated with long-term cardiovascular complications, among which valvular heart disease (VHD) is increasingly recognized. Radiation-induced VHD typically presents after a latency period of 10–20 years and is characterized by progressive valve fibrosis, thickening, and calcification, most commonly affecting the left-sided valves. Management of radiation-induced VHD generally follows standard guidelines but remains challenging due to extensive calcification and coexisting radiation-related cardiac or pulmonary injury. A history of thoracic radiotherapy is associated with increased perioperative risk and may negatively impact surgical outcomes, which often alters the risk–benefit balance and favors less invasive therapeutic approaches. Advances in the transcatheter approach have expanded treatment options for this high-risk population; however, data on long-term outcomes remain limited. Evolving dose-reduction techniques, such as deep-inspiration breath-hold, intensity-modulated radiotherapy, and proton therapy, together with predictive dosimetric models, aim to minimize future cardiac toxicity. Given the delayed onset and progressive nature of radiation-associated VHD, structured long-term surveillance is essential to enable early detection and timely intervention in cancer survivors at risk. Full article