Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

[EBUS-guided cryobiopsy in the diagnosis of mediastinal lesions - step by step]. / EBUS-gestützte Kryobiopsie mediastinaler Läsionen ­ Schritt für Schritt.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the gold standard in the diagnosis of mediastinal and hilar lesions. For certain purposes, such as the diagnosis and subtyping of lymphoproliferative disorders or molecular pathology, a larger amount of intact sample material is required. EBUS cryobiopsy is a new and efficient tool for this purpose. As it is a new approach, there is still no standardised workflow. In this review, we present the procedure step by step as it is performed at the Ruhrlandklinik in Essen.

Hodgkin lymphoma: hypodense lesions in mediastinal masses.

Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-18F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.

Schwannoma diagnosed by endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized biopsy forceps: A case report.

Schwannomas are classified as neurogenic tumors and are the most frequent nerve sheath tumors in the paravertebral mediastinum. Recently, the addition of endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB) using standard-sized biopsy forceps (SBFs) to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for metastatic lymph nodes in lung cancer patients reportedly improved the quality and quantity of the obtained specimens without significant complications. However, reports on the usefulness of this technique for benign diseases remain scarce. Here we report a case of schwannoma in the middle mediastinum, which was diagnosed by EBUS-IFB using SBFs, despite inadequate specimens obtained via EBUS-TBNA. An 80-year-old woman presented with dyspnea and a 5-cm sized middle mediastinal tumor. EBUS-TBNA and EBUS-IFB using SBFs were performed for histological diagnosis. No complications were associated with the bronchoscopy procedure, and schwannoma was solely diagnosed using the EBUS-IFB specimens. EBUS-IFB using SBFs is potentially useful for diagnosing benign diseases, including schwannomas, which are often difficult to diagnose with EBUS-TBNA.

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Large atypical lipomatous tumour of the neck with mediastinal extension managed by transcervical excision.

Tumours of adipose tissue origin are relatively rare in the head and neck. Here, we report a case of an unfamiliar lipomatous lesion that involved the neck and mediastinum. A nil-comorbid man in his 40s presented with a slowly progressive anterior neck swelling of 3 years, which was diagnosed as lipoma by histopathological sampling. Computed tomography demonstrated the lesion to be involving parapharyngeal and retropharyngeal spaces with mediastinal extension. The lesion was removed by the transcervical approach. The final histology of the excised specimen, with immunohistochemistry for mouse double minute 2 (MDM2) and p16, suggested an atypical lipomatous tumour (ALT). This report accentuates the occurrence of this rare neoplasm in the neck, which often mimics lipoma clinically. Although radiology can demonstrate suggestive features, histology with MDM2 and/or p16 positivity can confirm the diagnosis of ALT as against the lipoma. A successful transcervical excision, despite the deeper extension of the lesion between the critical structures of the neck and mediastinum, demonstrates the non-infiltrating nature of the tumour.

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Sarcoma of the Lung and Mediastinum.

Primary sarcoma of the lung and mediastinum is rare. The diagnosis requires careful exclusion of sarcomatoid carcinoma, sarcomatoid mesothelioma, and metastases from extra-thoracic sites. This review summarizes the key morphologic, immunohistochemical, and molecular characteristics of sarcomas that are encountered in the lung and mediastinum. The tumor types discussed are synovial sarcoma, well-differentiated/dedifferentiated liposarcoma, myxoid pleomorphic liposarcoma, intimal sarcoma of the pulmonary artery, inflammatory myofibroblastic tumor, epithelioid hemangioendothelioma, primary pulmonary myxoid sarcoma, malignant peripheral nerve sheath tumor, Ewing sarcoma, and CIC-rearranged sarcoma. Relevant differential diagnoses are also addressed.

A first-in-class inhibitor of HSP110 to potentiate XPO1-targeted therapy in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma.

BACKGROUND: Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) are distinct hematological malignancies of B-cell origin that share many biological, molecular, and clinical characteristics. In particular, the JAK/STAT signaling pathway is a driver of tumor development due to multiple recurrent mutations, particularly in STAT6. Furthermore, the XPO1 gene that encodes exportin 1 (XPO1) shows a frequent point mutation (E571K) resulting in an altered export of hundreds of cargo proteins, which may impact the success of future therapies in PMBL and cHL. Therefore, targeted therapies have been envisioned for these signaling pathways and mutations. METHODS: To identify novel molecular targets that could overcome the treatment resistance that occurs in PMBL and cHL patients, we have explored the efficacy of a first-in-class HSP110 inhibitor (iHSP110-33) alone and in combination with selinexor, a XPO1 specific inhibitor, both in vitro and in vivo. RESULTS: We show that iHSP110-33 decreased the survival of several PMBL and cHL cell lines and the size of tumor xenografts. We demonstrate that HSP110 is a cargo of XPO1wt as well as of XPO1E571K. Using immunoprecipitation, proximity ligation, thermophoresis and kinase assays, we showed that HSP110 directly interacts with STAT6 and favors its phosphorylation. The combination of iHSP110-33 and selinexor induces a synergistic reduction of STAT6 phosphorylation and of lymphoma cell growth in vitro and in vivo. In biopsies from PMBL patients, we show a correlation between HSP110 and STAT6 phosphorylation levels. CONCLUSIONS: These findings suggest that HSP110 could be proposed as a novel target in PMBL and cHL therapy.

[Imaging characteristics and diagnosis of primary middle mediastinal tumors].

Objectives: To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Methods: Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. Results: The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Conclusion: Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.

Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy versus Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Disorders: A Meta-Analysis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. METHODS: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. RESULTS: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p < 0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). CONCLUSION: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

A rare presentation of primary cardiac myxofibrosarcoma: Case report and literature review.

BACKGROUND: Primary cardiac myxofibrosarcoma is a rare and aggressive malignancy, with the majority of approaching strategies relying on case reports. This article provides insights into its diagnosis and treatment. CASE PRESENTATION: This paper presents the case of a 40-year-old man with sudden onset hemoptysis, leading to the diagnosis of primary cardiac myxofibrosarcoma. Treatment involved open-heart surgery to excise the left atrium tumor, followed by 6 cycles of adjuvant chemotherapy. Unfortunately, brain metastasis developed, leading to the patient's death 1 year after initial diagnosis. CONCLUSION: Primary cardiac myxofibrosarcoma remains a clinical challenge with an unfavorable prognosis. Early diagnosis through advanced imaging is crucial, and research is needed to explore innovative treatments. This case underscores the complexities of managing this rare cardiac malignancy and highlights the necessity for ongoing investigations to enhance patient outcomes.

[Malignant melanotic nerve sheath tumor of the posterior mediastinum]. / Tumor maligno melanocítico de la vaina neural en mediastino posterior.

Melanotic schwannoma (MS) is a rare and infrequent subtype of schwannoma characterized by cytoplasmic deposits of melanosomes (melanin). Unlike the other schwannomas, it could have malignant transformation. Due to distinctive characteristics and atypical behavior from classic schwannomas subtypes, MS were renamed and reclassified as "melanocytic malignant neural sheath tumor" in the 5th ed. of the World Health Organization's classification of central nervous system tumors in 2021. We present two cases of MS that underwent complete surgical resection.

El schwannoma melanótico (SM) es una variante rara e infrecuente caracterizada por el depósito citoplasmático de melanosomas (melanina). A diferencia de las otras variantes de schwannomas, tienen capacidad de malignización. Por poseer características y comportamiento distintos al resto de los schwannomas, fue reclasificado como "tumor maligno melanocítico de la vaina neural" en la 5ta edición de la clasificación de los tumores del sistema nervioso central de la Organización Mundial de la Salud en 2021. Presentamos dos casos de SM de ubicación mediastinal en los que se realizó una resección quirúrgica completa.

Posterior mediastinal leiomyosarcoma: Case report and literature review.

BACKGROUND: Posterior mediastinal leiomyosarcoma is an extremely rare malignant mesenchymal tumor with no special clinical symptoms, which is easily confused with some common tumors in the posterior mediastinum, affecting the accuracy of the first diagnosis by clinicians and delaying the treatment of patients. CASE SUMMARY: We report a 59-year-old woman with a space-occupying lesion in the posterior mediastinum. The patient was mistakenly diagnosed with lumbar muscle or vertebral body lesions due to chest and back pain and underwent conservative treatment, but her symptoms did not improve significantly and she gradually developed pain in both lower limbs. Chest computed tomography (CT) scan indicated the left lower lung paraspinal space and underwent standard single-aperture video-assisted thoracoscopic surgery (VATS), which was pathologically confirmed as posterior mediastinal leiomyosarcoma. CONCLUSION: Complete surgical resection of posterior mediastinal leiomyosarcoma can achieve good clinical results.

Spatiotemporal distribution of mediastinal neoplasms: A comprehensive multi-center study.

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.