Primary mediastinal large B-cell lymphoma.

Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a distinct molecular signature that overlaps with nodular sclerosis classic Hodgkin lymphoma (cHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using ribonucleic acid derived from paraffin-embedded tissue and are integral to future studies. However, given that ∼5% of DLBCL can have a molecular PMBCL phenotype in the absence of mediastinal involvement, clinical information remains critical for diagnosis. Studies during the past 10 to 20 years have elucidated the biologic hallmarks of PMBCL that are reminiscent of cHL, including the importance of the JAK-STAT and NF-κB signaling pathways, as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era; however, whether there is a single standard treatment for all patients and when to integrate radiotherapy remains controversial. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting the high efficacy of PD1 inhibitors in PMBCL, studies are underway that integrate them into the up-front setting.

Neurogenic tumours of the posterior mediastinum and differential diagnosis considerations.

The mediastinal compartment harbours vital organs and structures, including the heart, great vessels, major airways, and thymus. These structures are embedded in and associated with soft-tissue elements consisting of adipose and fibro-collagenous tissue in which soft-tissue tumours may develop. A detailed inventory of soft-tissue tumours that may be encountered in the mediastinum based on the WHO 2013 classification was published in 2015. In addition, several comprehensive reviews on mediastinal soft-tissue pathology are available, including reviews focusing specifically on a single tumour type. This review will focus on primary neurogenic and spindle cell tumours of the somatic soft tissue of the posterior mediastinum and provide a discussion of the pertinent differential diagnoses.

Benign lesions of the mediastinum.

Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of some of these tumours in characteristic mediastinal compartments, an anatomical subdivision of the mediastinum in the prevascular (anterior), visceral (middle), and paravertebral (posterior) is helpful for the differential diagnosis. Benign anterior mediastinal tumours linked to an enlargement of the thymic gland mainly consist of thymic cysts and several types of thymic hyperplasia: true thymic hyperplasia, rebound hyperplasia, lymphofollicular hyperplasia, and so-called thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features. Mature teratomas, ectopic (para)thyroid tissue, and benign thymic tumours such as thymolipoma or thymofibrolipoma represent further typical tumours of the anterior mediastinum. Pericardial, bronchogenic, or oesophageal duplication cysts predominate in the middle mediastinum, whereas neurogenic tumours and myelolipomas are characteristic findings in the posterior compartment. Vascular tumours, lipomas, adenomatoid tumours, Castleman disease, or mediastinitis are further examples of less frequent tumours or tumorous lesions affecting the mediastinum. This review focuses on benign mediastinal lesions with an emphasis on benign tumours of the thymus. Besides histology, characteristic epidemiological and clinical aspects prerequisite for the correct diagnosis and patient management are discussed.

Primary germ cell tumours of the mediastinum: A review with emphasis on diagnostic challenges.

This article will review current aspects of the histopathological, immunohistochemical and molecular analysis of primary mediastinal germ cell tumours (PMGCTs) as well as their aetiological, epidemiological, clinical and therapeutic features. PMGCTs represent an important differential diagnosis in the spectrum of mediastinal tumours, and their diagnosis is usually made on small tissue samples from core needle biopsies in combination with diagnostic imaging and serum tumour markers. As in lymphomas, a small biopsy is often the only viable tumour sample available from these patients, as they receive chemotherapy prior to eventual surgical resection. Pathologists therefore need to apply an efficient combination of immunohistochemical markers to confirm the diagnosis of a PMGCT and to exclude morphological mimics.

Mediastinal Germ-cell Tumors Relapse in a Male With Klinefelter Syndrome. Is Longer Surveillance Needed?

Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT. There are no recommendations for screening for KS in patients with mediastinal GCT and there are no specific guidelines for surveillance of GCT in KS patients. Our experience suggests that KS should be suspected in patients with mediastinal GCT, and a longer follow-up plan should be implemented when GCT occurs in patients with KS.

Successful endoscopic approach for peripheral neuroblastic tumors in children.

BACKGROUND: Recently, reports of endoscopic approaches for neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (peripheral neuroblastic tumor; PNTs) have been increasing. This study aimed to clarify the indications for endoscopic surgery for PNTs. METHODS: Pediatric patients who underwent endoscopic surgery for PNTs at our institution were included in this study. Image-defined risk factors (IDRFs) were analyzed using preoperative computed tomography (CT). RESULTS: Twenty-four patients underwent endoscopic surgery for PNTs. The diagnoses included neuroblastoma (n = 11), ganglioneuroma (n = 10), and ganglioneuroblastoma (n = 3). Regarding the tumor site, there were 18 cases of adrenal tumors, five cases of mediastinal tumors, and one case of retroperitoneal tumors. Image-defined risk factors were positive in eight cases (contacted with a renal vessel, n = 6; compression of principal bronchi, n = 2). Complete resection was accomplished in 21 cases (14 of 16 IDRF-negative cases and seven of eight IDRF-positive cases). All patients survived without recurrence during the follow-up period. CONCLUSIONS: The CT findings of contact with renal vessels and compression of principal bronchi do not seem to be indicators of incomplete resection. An endoscopic approach to PNTs in pediatric patients is feasible with a good prognosis if patients are selected strictly.

Is mediastinal fine needle aspiration cytology required or redundant? A single institution-based correlation study with core needle biopsy.

INTRODUCTION: Fine Needle Aspiration cytology (FNAC) and core needle biopsy (CNB) are rapid, minimally invasive and useful techniques to evaluate mediastinal lesions. OBJECTIVES: To compare cytopathology with histopathology of mediastinal lesions and analyse reasons for discordance. MATERIAL & METHODS: Retrospective analysis was done in a tertiary care centre in North West India over a period of seven and half years from 1stJuly 2016 to 31st December 2023. Only those patients who had undergone FNAC and trucut biopsy of mediastinal masses were included. The cytopathology and histopathology slides were studied to analyse causes of discordance. Sensitivity, specificity, positive and negative predictive values of FNAC were calculated keeping histopathology as gold standard. RESULTS: Out of 57 cases analysed, eight cases were non diagnostic on cytology. Cytology could effectively classify a lesion as non neoplastic (7) or neoplastic (42). For further subtyping, histopathology and Immunohistochemistry (IHC) were required. Out of 27 cases of cytological - histopathological discordance, 8 cases had sampling error, 15 cases had limited concordance where FNAC could predict possibility of tumor and 4 cases were discordant where subtyping of malignancy varied on CNB. Sensitivity of FNAC to predict definite diagnosis was 90.2 %, specificity was 50 %, positive predictive value of FNAC to give a definite diagnosis was 93.9 %, negative predictive value was 37.5 %. CONCLUSION: Evaluation of mediastinal masses requires combination of cytology, histopathology and ancillary techniques like IHC. FNAC and CNB are complementary modalities and both are essential for rapid, accurate and comprehensive diagnosis.

[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.

[Surgery for mediastinal teratoma containing pancreatic tissue]. / Khirurgiya teratomy sredosteniya, soderzhashchei tkan' podzheludochnoi zhelezy.

Surgery for mediastinal tumors is still one of the most difficult in modern medicine. This is due to vital organs and various nature of tumors in this area. Teratomas are relatively rare among mediastinal tumors. However, they have certain features that is important for treatment strategy and management of possible complications. This can complicate diagnostic algorithm, exclude transthoracic biopsy and contribute to active surgical approach even for benign process. Oncogenesis of teratoma has its own characteristics. Tissues of different organs are always present in this tumor. Among these, pancreatic tissue inclusions are rare. A few data in the world literature on the treatment of such patients do not allow to develop a universally accepted algorithm of diagnosis and treatment. The authors present two patients with mediastinal teratoma. The second patient had teratoma with pancreatic tissue. The authors discuss the diagnostic algorithm for similar cases. A special attention is paid to description of possible complications throughout long-term follow-up period. Surgical aspects including the choice of access and local spread of process (adhesions in the area of surgical interest) are considered. The report on the treatment of two patients with rare mediastinal tumors containing pancreatic tissue will be useful for primary care physicians, thoracic surgeons, oncologists and morphologists.

[Thoracoscopic resection of recurrent atypically located parathyroid adenoma of anterior mediastinum in a patient with hyperparathyroidism undergoing renal replacement therapy]. / Torakoskopicheskoe udalenie retsidivnoi atipichno raspolozhennoi adenomy okoloshchitovidnoi zhelezy perednego sredosteniya u patsientki s giperparatireozom, nakhodyashcheisya na zamestitel'noi pochechnoi terapii.

We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline, parathyroidectomy via cervical access was performed for parathyroid adenomas. After 6 years, clinical and laboratory relapse of disease required thoracoscopic resection of atypically located anterior mediastinal adenoma. This case demonstrates that this disease is one of the most difficult in modern medicine requiring a special approach in diagnosis and treatment. Patients with CKD and hyperparathyroidism need for follow-up, control of total and ionized serum calcium, inorganic phosphorus and parathormone, osteodensitometry, ultrasound and scintigraphy of thyroid and parathyroid glands, and, if necessary, CT or MRI of the neck and chest organs.

A Case Report of Mediastinal Teratoma in a Pediatric Patient With Nephrotic Syndrome: Paraneoplastic Syndrome or Incidental Finding?

A 12-year-old female presented with weight gain, edema, and shortness of breath. Laboratory and urine studies confirmed nephrotic syndrome and presence of a mediastinal mass, identified as a mature teratoma after resection. Nephrotic syndrome persisted despite resection and renal biopsy confirmed minimal change disease, which ultimately responded to steroid treatment. She had two relapses of nephrotic syndrome after vaccination administration, both of which occurred within eight months of tumor resection and were responsive to steroids. Autoimmune and infectious workup for other causes of nephrotic syndrome was negative. This is the first reported case of nephrotic syndrome associated with mediastinal teratoma.

Primary mediastinal germ cell tumors.

Mediastinal germ cell tumors share similar histopathological, immunohistochemical, and molecular features with their counterparts in the gonads. Therefore, proper clinical and radiological evaluation of patients with an anterior mediastinal mass becomes essential in the final interpretation of these tumors. The gold standard for the diagnosis of these tumors remains histopathological evaluation. However, immunohistochemical stains and molecular studies also provide an aid in cases in which the histology is not typical. It is also important to keep in mind that a small mediastinoscopic biopsy may not be representative of the entire neoplasm. In this review, we will provide our perspective regarding histopathological diagnosis, staging, immunohistochemical and molecular profile, and briefly family of tumors address pertinent epidemiological, clinical and treatment options. However, the main emphasis is to review the process of pathological assessment in pre and post-treated tumors. Knowledge of the different growth patterns and histological associations is important, mainly when confronted with mediastinoscopic biopsies, which ultimately will determine treatment options.

Timely diagnostics and safe procedures in children with anterior mediastinal masses (AMMs): a qualitative review of the AMM protocol at BC Children's Hospital in Vancouver BC.

The presence of an anterior mediastinal mass should prompt rapid triage, workup and treatment to effectively manage and prevent emergent complications. Implementation of an AMM protocol can ensure the response is standardized and coordinated. Importantly, such a protocol can encourage prompt multi-disciplinary communication to mitigate risks associated with procedures required for timely diagnosis. The aim of this review is to evaluate the BC Children's Hospital's Pediatric New/Suspected Anterior Mediastinal Mass (AMM) Protocol. Retrospective chart review was conducted for 18 patients admitted from February 2016 to May 2020 with AMM for whom the protocol was enacted. Primary parameters assessed presence of high-risk feature at time of presentation, time from admission and/or protocol activation to specific time points, including imaging, first diagnostic procedure, and diagnosis. Data regarding perioperative management, including anesthetic considerations and peri-operative complications, was also collected. Mean time from protocol activation to first diagnostic procedure and diagnosis were 1.88 days (range 0-7) and 2.24 days (range 0-7), respectively. The majority of procedures were conducted under sedation (n = 77, 64%), followed by general anesthetic (GA; n = 34, 28%) and local anesthetic (n = 10, 8%). Despite 15 cases having more than one high risk feature, pre-operative steroids were only administered for four of the total 158 procedures (3%) and extracorporeal life support (ECLS) and otolaryngology (ENT) were only required for immediate availability for seven procedures (4%). Furthermore, only 10 procedures (8%) had associated complications and none of these complications resulted in patient death. Our data demonstrate that implementation of a streamlined multi-disciplinary protocol can expedite time to diagnosis without impacting patient safety.

[Solitary mediastinal fibrous tumor complicated by hypoglycemic crises (Doege-Potter syndrome)]. / Solitarnaya fibroznaya opukhol' sredosteniya, oslozhnennaya gipoglikemicheskimi krizami (sindrom Doge­Pottera).

Diagnostic and treatment algorithms for large mediastinal tumors are clear. However, long-term results are not always good. They largely depend on early diagnosis and morphological structure of tumor. Neoplasms may be asymptomatic for a long time, especially in case of slow growth. These tumors are usually diagnosed as soon as complications occur (for example, compression syndrome). Routine X-ray screening is rarer situation. Paraneoplastic syndromes are rare, and some ones are casuistic and unknown to surgical community. We describe the diagnosis and treatment of a patient with giant solitary mediastinal tumor complicated by hypoglycemic crises (Doege-Potter syndrome). This complication was life-threatening and required a multidisciplinary approach. Aggressive surgical approach cured the patient and returned her to normal lifestyle. The proposed algorithm for perioperative drug therapy was effective and deserves attention. This report will be useful for surgeons, oncologists, anesthesiologists, intensive care specialists and endocrinologists.

Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach.

AIMS: Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. The aim of this study was to develop a diagnostic algorithm using immunohistochemical staining, with a focus on novel markers, and molecular analysis of isochromosome 12p [i(12p)]. METHODS AND RESULTS: Paraffin-embedded tissues of 32 mediastinal tumours were analysed with immunohistochemical staining for sal-like transcription factor 4 (SALL4), Lin-28 homologue A (LIN28), octamer-binding transcription factor 3/4 (OCT3/4), D2-40, cluster of differentiation 117 (CD117), sex-determining region Y-box 17, sex-determining region Y-box 2 (SOX2), cluster of differentiation 30, the ß-subunit of human chorionic gonadotropin (ß-hCG), GATA-binding protein 3 (GATA3), forkhead box protein A2 (FOXA2), glypican-3 (GPC3), α-fetoprotein (AFP), terminal deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and pan-cytokeratin. Quantitative real-time polymerase chain reaction was performed to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each entity had different immunohistochemical staining patterns, which helped to distinguish them: OCT3/4, D2-40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and ß-hCG and GATA3 for choriocarcinoma. Mature teratomas stained positively for pan-cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2-40, and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 24 of 27 PMGCTs (89%). CONCLUSION: A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary, in addition to morphological features. The i(12p) status serves as an additional option to indicate a germ cell origin in selected cases.

Approach to Mediastinal Fine Needle Aspiration Cytology.

Mediastinal fine needle aspirations are routinely encountered in cytopathology practice. Mediastinal lesions may pose diagnostic challenges owing to their rarity and locations associated with the complexity of the mediastinal anatomic structures in the thoracic cavity. Diagnosing mediastinal lesions and guiding patient management usually require correlating with clinical and radiologic findings, being familiar with cytomorphologic features and appropriately triaging the diagnostic material for ancillary testing. This review proposes a practical approach to interpret mediastinal fine needle aspirations and emphasizes potential diagnostic pitfalls for mediastinal lesions including benign cysts, thymic neoplasms, lymphoproliferative disorders, germ cell tumors, mesenchymal tumors, and metastatic tumors.

End of treatment FDG-PET in primary mediastinal B-cell lymphoma treated with R-chemotherapy: Prognostic indicator and implications for consolidation radiotherapy.

The ideal therapeutic regimen in primary mediastinal B-cell lymphoma (PMBCL) is controversial and may include consolidation radiotherapy (RT). An adequate strategy is essential in a population where long-term effects of RT are significant. We evaluated the prognostic value of end-of-treatment (EOT) FDG-PET in 50 patients receiving rituximab and anthracycline-containing chemotherapy and its implications for consolidative RT. Thirty patients (60%) obtained complete metabolic response (CMR), five received consolidation RT. The remaining patients had partial response (14) and progression (6). Of these, 12 received mediastinal RT, six salvage chemotherapy, and two no further treatment. Five-year progression free survival was 100% and 48% (95% CI 30%-77%) in patients with negative and positive EOT FDG-PET, respectively (P < .001). Five-year overall survival for negative and positive EOT FDG-PET was 100% and 67% (95% CI 48%-93%) respectively (P = .001). Within positive EOT FDG-PET cases, an association was found between Deauville score and survival. The negative predictive value (NPV) of EOT FDG-PET for disease relapse/progression was 100% (95% CI 0.88-1.00); the positive predictive value was 47% (95% CI 0.24-0.71). This study demonstrates the importance of metabolic assessment in PMBCL and is relevant for its high NPV. Our data favor the use of EOT FDG-PET for decisions concerning RT.

Mediastinal neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: Pathology review and diagnostic approach.

Neuroblastic tumors are a group of tumors of the sympathetic ganglia and adrenal medulla that derive from primordial neural crest cells. These tumors include neuroblastoma, intermixed ganglioneuroblastoma, nodular ganglioneuroblastoma, and ganglioneuroma. Neuroblastomas are the most common extracranial solid tumor arising in childhood and may occur in different anatomic sites. Neuroblastic tumors are common mesenchymal tumors of the mediastinum. Herein, we describe advances in our understanding of neuroblastic tumor biology. Pathologists should be aware of diagnostic challenges associated with these tumors to ensure correct histologic diagnosis and appropriate clinical management. We describe updated mediastinal neuroblastic tumor pathology, focusing on morphological, immunohistochemical, and molecular features and differential diagnoses.

Spindle cell tumors of the mediastinum.

Spindle cell tumors originating in the mediastinum are extremely rare. Due to the profusion of structures and organs located in the mediastinum, a wide variety of spindle cell neoplastic processes can develop in this location. These include various different tumor types including epithelial, vascular, lipomatous, fibroblastic and neural tumors among others. Many of these different tumor types are associated with specific immunohistochemical and molecular genetic profiles that help differentiate them from each other. Although spindle cell morphology has traditionally been associated with mesenchymal neoplasms, in the mediastinum the most common spindle cell tumor is spindle cell thymoma, an epithelial rather than mesenchymal neoplasm. Except for neurogenic tumors originating in the posterior mediastinum, mesenchymal neoplasms are quite rare in mediastinal locations and require clinical correlation to rule out the possibility of a metastasis from an extra-mediastinal soft tissue or somatic sarcoma. Herein we will review the most common types of spindle cell neoplasms that occur in the mediastinum, with particular emphasis in their differential diagnosis and the role of ancillary techniques for diagnosis.

Successful resolution of ectopic Cushing syndrome by minimally invasive thoracoscopic resection of the neuroendocrine tumor of the thymus: a rare case report.

BACKGROUND: Ectopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach. CASE PRESENTATION: A 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient's chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing's syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively. CONCLUSION: Thoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus.