Lobe-Specific Lymph Node Dissection for Clinical Early-Stage (cIA) Peripheral Non-small Cell Lung Cancer Patients: What and How?

OBJECTIVE: We investigated the possible lobe-specific lymph node (LN) metastasis pattern of early-stage peripheral non-small cell lung cancers (NSCLC) and define the extent of lobe-specific LN dissection for them. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy for clinical T1N0M0 peripheral NSCLC from January 2015 to December 2018. The LN metastasis pattern was analyzed by tumor lobe location. RESULTS: A total of 590 patients were included for analysis. The mean number of total dissected LNs was 12.3 ± 5.8 and 8.2 ± 4.1 for total dissected mediastinal LNs. The rate of mediastinal LN metastasis was 9.5%. For cases of upper lobe tumor and lower lobe tumor, 8.8% and 6.0% of them respectively metastasized to the upper LN zone (P = 0.274). However, upper lobe tumors hardly metastasized to the subcarinal (0.3%) and lower (0.3%) LN zones while for lower lobe tumors, the rate of LN metastasis was 10.2% and 5.4% respectively (both P < 0.001). However, all cases (100%) metastasizing from lower lobes to the upper LN zone had a tumor size of 2-3 cm, whereas cases with a tumor size ≤ 2 cm had no metastasis (0%). None of the tumors in the right middle lobe metastasized to the lower LN zone (0%). CONCLUSIONS: A lobe-specific LN metastasis pattern was observed in clinical stage IA peripheral NSCLC. For tumors in upper lobes (≤ 3 cm), there may be no need to dissect lower mediastinal LNs and for tumors in lower lobes (≤ 2 cm), dissecting upper mediastinal LNs may not be required.

The association of mediastinal mass in the formation of thrombi in pediatric patients with non-lymphoblastic lymphomas.

BACKGROUND: Children diagnosed with cancer are at a significantly higher risk of developing a thrombotic event (TE) compared with the general population. The rarity of these events makes it difficult to discern the specific risk factors; however, age, sex, presence of central venous lines, inherited thrombophilia, and mediastinal mass may play a role. The primary aim of this study is to identify prognostic characteristics of children diagnosed with non-lymphoblastic lymphomas associated with a greater risk of developing a TE early on in their disease, with an increased focus on mediastinal mass characteristics. METHODS: Retrospective chart review of pediatric patients diagnosed with non-lymphoblastic lymphoma between 2004 and 2014 at St. Jude Children's Research Hospital. RESULTS: TE occurred in 8.5% (n = 28/330) of individuals at a median of 21 days from the diagnosis of a non-lymphoblastic lymphoma, with 60% of TEs occurring within 30 days of diagnosis. Of the variables evaluated, only presence of a peripherally inserted central catheter (odds ratio [OR]: 3.14 [95% CI: 1.24-7.98; P = 0.02]) and degree of superior vena cava (SVC) compression of > 25% increased the odds of developing a TE (OR: 2.2 [95% CI: 1.01-4.93; P = 0.048]). CONCLUSION: Pediatric patients with non-lymphoblastic lymphoma are at increased risk of developing TEs. In contrast to previous studies, the presence of a mediastinal mass alone was not associated with a higher risk of TE, but individuals with a mediastinal mass with 25% or greater degree of SVC compression were more likely to develop a TE. This finding highlights a high-risk group of children who may benefit from prophylactic anticoagulation.

Primary Mediastinal Large B-Cell Lymphoma in a Child Presenting With Superior Mediastinal Syndrome and Chylous Pleural and Pericardial Effusion.

Primary mediastinal (thymic) large B-cell lymphoma is an aggressive B-cell lymphoma. It comprises <3% of all pediatric non-Hodgkin lymphomas (NHLs). Primary mediastinal (thymic) large B-cell lymphoma usually presents with serous pleural effusion, but presentation with chylous pleural and pericardial effusions is rare. We present a child who presented with features of a superior mediastinal syndrome. Biopsy of the mediastinal mass confirmed the diagnosis of large B-cell lymphoma. In view of nonimprovement of respiratory distress with chemotherapy and persistence of features of superior mediastinal syndrome, the child was evaluated and found to have massive pleural and pericardial effusion on imaging. Therapeutic thoracentesis and pericardiocentesis revealed chylous nature of the fluid.

Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B-cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion. The tumour microenvironment is manipulated by PMBCL tumours to avoid T-cell mediated destruction via strategies that include loss of tumour cell antigenicity, T-cell exhaustion and activation of suppressive T-regulatory cells. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and DA-EPOCH-R (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) are the most common first-line immunochemotherapy regimens. End of treatment positron emission tomography scans are the recommended imaging modality and are being evaluated to stratify patients for radiotherapy. Relapsed/refractory disease has a relatively poor outcome despite salvage immunochemotherapy and subsequent autologous stem cell transplantation. Novel therapies are therefore being developed for treatment-resistant disease, targeting aberrant cellular signalling and immune evasion.

Spontaneous mediastinal myeloid sarcoma in a common marmoset (Callithrix jacchus) and review of the veterinary literature.

BACKGROUND: Myeloid sarcoma is a rare manifestation of myeloproliferative disorder defined as an extramedullary mass composed of myeloid precursor cells. A 9-month old, female, common marmoset (Callithrix jacchus) had increased respiratory effort. METHODS: A complete necropsy with histology and immunohistochemistry was performed. RESULTS: The thymus was replaced by a firm, gray-tan mass with a faint green tint, filling over 50% of the thoracic cavity. Sheets of granulocytes, lymphoid cells, nucleated erythrocytes, megakaryocytes, and hematopoietic precursors of indeterminate cell lineage replaced the thymus, perithymic connective tissue, mediastinal adipose tissues, epicardium, and much of the myocardium. The cells demonstrated diffuse strong cytoplasmic immunoreactivity for lysozyme, and strong, multifocal membranous immunoreactivity for CD117. CONCLUSION: We report the first case of a myeloid sarcoma in a common marmoset (C. jacchus), similar to reported human cases of mediastinal myeloid sarcoma, and present a review of myeloproliferative diseases from the veterinary literature.

Surgical treatment for mediastinal abscess induced by endobronchial ultrasound-guided transbronchial needle aspiration: a case report and literature review.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful and less invasive procedure for the definitive diagnosis of mediastinal and hilar lymph nodes. However, infectious complications can occur after EBUS-TBNA, although they are extremely rare. CASE PRESENTATION: A 66-year-old man with necrotic and swollen lower paratracheal lymph nodes underwent EBUS-TBNA. A mediastinal abscess developed 9 days post-procedure. Surgical drainage and debridement of the abscess were performed along with lymph node biopsy followed by daily washing of the thoracic cavity. Surgical treatment was effective, leading to remission of the abscess. Biopsy revealed that the tumor was squamous cell carcinoma with no radiologically detected cancer elsewhere in the body. Mediastinal lung cancer was thus confirmed. Subsequent chemoradiotherapy led to the remission of the tumor. CONCLUSIONS: Mediastinitis after EBUS-TBNA is rare but should be considered, particularly if the target lymph nodes are necrotic. Mediastinitis can lead to serious and rapid deterioration of the patient's condition, for which surgical intervention is the treatment of choice.

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

BACKGROUND: Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. CASE PRESENTATION: In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. CONCLUSIONS: Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

A case of uncontrolled severe asthma patient with coexisting carcinoid tumor presenting as pneumomediastinum.

INTRODUCTION: Patients with inadequately controlled or uncontrolled asthma are at a greater risk of attacks for asthma requiring emergency room visits or hospital admissions. There is a significant correlation between the severity of the disease and the severity of exacerbations. Patients with poorly controlled asthma are at a higher risk for complications. CASE STUDY: We present a 24-year-old aspirin-intolerant, uncontrolled asthma patient with the complication of pneumomediastinum. RESULTS: Severe symptoms persisted after the resolution of the pneumomediastinum despite intense anti-inflammatory and anti-obstructive therapy. A bronchoscopy revealed an endobronchial lesion and she was diagnosed with a carcinoid tumor. CONCLUSION: This case is an example of the importance of re-evaluating asthma patients who do not respond to standard medical treatment. Clinicians should be aware of the complications associated with asthma attacks such as pneumomediastinum and the possibility of a differential diagnosis that worsen asthma symptoms such as a carcinoid tumor.

[PRIMARY MEDIASTINAL GERM CELL TUMOR ARISING IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1].

Neurofibromatosis type 1 (NF1) is a distinct genetic disorder due to the NF1 gene mutation which induces the aberrant activation of the RAS-signaling. Because RAS-related proteins function as oncogenic factors, NF1 patients frequently develop malignant tumors, especially of neural crest origin, such as peripheral nerve sheath. In addition, malignant tumors of the pancreas, colorectum, and lung have been reported to frequently arise in NF1 patients. However, the association between germ cell tumor and NF1 has not been clarified yet. A 29-year-old male with dyspnea was referred to our hospital because of the large mass in the anterior mediastinum and cervical lymph node swelling. The diagnosis was extragonadal germ cell tumor with cervical lymph node metastasis, and complete remission was obtained by multidisciplinary treatment consisted of combination chemotherapy and surgical resection. To our acknowledgement, this is the first case of extragonadal germ cell tumor in NF1 patients. We discuss the relevance between activation of the RAS-signaling and the development of germ cell tumor.

A patient with progressive dyspnoea and a new heart murmur.

A 74-year-old man was referred to the outpatient clinic of the cardiology department with progressive dyspnoea and a new heart murmur. Physical examination of the chest wall showed a hard immobile and painless sternal swelling at the level of the angulus of Ludovici. There was an increase of the velocities across the pulmonary valve (continuous Doppler) on echocardiography as a result of the RVOT and pulmonary trunk stenosis. Computed tomography (CT) of the chest revealed a mass in the anterior mediastinum which had grown through the sternum into the skin, as well as an external compression of the ascending aorta, the truncus pulmonalis and the pericardium. Anatomo-pathological examination revealed a non-small-cell lung carcinoma. PET CT showed another nodule with FDG uptake in the right kidney, suspected for metastasis, and an uptake in a right paratracheal lymph node. The tumour was staged as a cT4cN2M1b. Palliative radiochemotherapy was started. The patient had a good clinical and radiographic response, but relapsed a few months later.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.

Mediastinal seminoma occurring in Down syndrome.

The increased incidence of testicular tumor occurrence, especially seminoma, in Down syndrome has been well documented. However, primary mediastinal seminoma occurring in Down syndrome has not been reported. Incidental discovery of an anterior mediastinal tumor was made in a 28-year-old Japanese man with Down syndrome, who had been scheduled for bone marrow transplantation to treat aplastic anemia. Histopathological findings of the resected tumor were typical of seminoma. This case indicates that seminoma can occur in the mediastinum in addition to testis in Down syndrome.

A mass in the posterior mediastinum; extramedullary haemopoietic tissue.

Extramedullary haematopoiesis is a very rare cause of a posterior mediastinal tumour and may be clinically confused with many other mediastinal tumours; benign or malignant. Extramedullary haematopoiesis is a really rare cause of haemothorax and usually it is diagnosed incidentally. Extramedullary masses complicating thalassemias, apart from the known complications, may also bleed and produce acute manifestations like dyspnoea and fatigue. Pathologically, the masses are soft, deep red, and resemble spleen tissue on the cut surface. Histologically, they are formed of hematopoietic tissue mixed with adipose elements. The mass is extremely vascular and contains some fibrous tissue. This particular structure renders the mass prone to haemorrhage. We report a case of posterior mediastinal extramedullary haematopoietic mass in a 56-year-old man who presented with non-specific symptomatology and a paravertebral mass on chest X-ray and in the chest computed tomography. A percutaneous biopsy approach could be technically difficult due to the special location of the mass. Video assisted thoracic surgery (VATS), is a minimal invasive and alternative way of diagnosis, biopsy and treatment of these cases. Diagnosis was achieved in our patient by mini thoracotomy and open biopsy in order to prevent bleeding or neurological damage.

Mediastinal Hodgkin lymphoma arising from cystic lymphangioma: case report in a child.

Mediastinal disease is a frequent clinical presentation in children with Hodgkin lymphoma. It is usually due to mediastinal lymphadenopathy or involvement of the thymus gland. Cystic lymphangiomas are benign tumors of the lymphatic system, and less than 1% present as a solitary mediastinal mass. To our knowledge, there has been no report in the literature describing Hodgkin lymphoma arising from cystic lymphangioma. In this report, we describe a patient with mediastinal cystic lymphangioma, from which Hodgkin lymphoma was determined to have arisen.

[Differential diagnosis of thymic hyperplasia and mediastinal tumor in patients with lymphogranulomatosis after chemotherapy].

AIM: To make differential diagnosis of thymic hyperplasia and mediastinal tumor after chemotherapy (CT) in patients with Hodgkin's disease (HD). MATERIAL AND METHODS: The examination of 182 HD patients aged 16-71 years (median 28 years) included chest x-ray computed tomography (XCT) at baseline, during treatment, each 3 months, ultrasound investigation of the chest and abdominal cavity. All the patients received 6-8 courses of the treatment according to the program BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not followed in 45patients. RESULTS: Soft tissue tumor in the anterior mediastinum was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median 24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of the data of ultrasound investigation and tomography identified a mediastinal lesion as thymic hyperplasia. The patients are now in remission with follow-up median 21 months (13-36 months). No recurrence was registered. CONCLUSION: Young HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases within one year after chemotherapy. In view of this, detection of the lesion in the anterior mediastinum after CT demands complex examination for differential diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted intensification of the treatment.

Persistent Hypercalcemia Crisis and Recurrent Acute Pancreatitis Due to Multiple Ectopic Parathyroid Carcinomas: Case Report and Literature Review of Mediastinal Parathyroid Carcinoma.

Mediastinal parathyroid carcinoma (PC) is a rare entity in primary hyperparathyroidism. The aim of this report is to demonstrate a case of mediastinal PC, and to provide a systemic literature review of this rare condition. A 34-year-old woman who had already undergone two cervical operations for hyperparathyroidism suffered from another recurrence, presenting with recurrent acute pancreatitis and persistent hypercalcemic crisis. Technetium-99 methoxyisobutylisonitrile imaging (MIBI) and computed tomography scanning (CT) identified three possible parathyroid tumors, one of which was the recurrence of residual tumor locating in the thyroid region, while the other two were ectopic tumors locating in the suprasternal fossa and thymus region, respectively. Pathological examination confirmed the diagnosis of PC. We conducted a systemic literature review by searching the PubMed MEDLINE from 1951 to 2019 for studies of all types in the English language only, using terms "mediastinal, mediastinum, parathyroid, carcinoma." Including our reported case, a total of 21 cases with ectopic mediastinal PCs were assessed for demographic data, tumor location and size, biochemical findings, and symptomatology, etc. Two thirds of the patients were men, with a mean age of 44 years old, a mean serum calcium of 14.2 mg/dl, and a mean serum intact parathyroid hormone of 1,216 pg/ml. We identified 89.5% of carcinomas in the anterosuperior mediastinum, and 10.5% in the middle mediastinum, with a mean diameter of 54 mm, and a mean weight of 216 g. MIBI and CT were the most commonly used methods to localize these mediastinal tumors, with 69.2 and 100% sensitivity, respectively. Half of the patients underwent more than one operation. Diagnosis and treatment of mediastinal PCs represent a challenge. Early suspicion, appropriate preoperative localization studies, and the cooperation of endocrinologists and surgeons are crucial in the effective management.

[Abdominal cystic tumor revealing lymphangioleiomyomatosis]. / Tumeurs kystiques rétropéritonéales compliquées révélatrices d'une lymphangioléiomyomatose.

We report the case of a 39 year-old woman with many years of intermittent abdominal pain who was found to have cystic masses evocative of cystic lymphangioma involving the posterior mediastinal and retroperitoneum. Worsening abdominal pain led to a recommendation for laparoscopic unroofing and decompression of the cysts. During the postoperative period, hemorrhagic shock required reintervention with excision of the tumoral mass. Pathologic examination revealed lymphangioleiomyomatosis (LAM). On the 15th postoperative day, the patient developed a chylopneumothorax which required prolonged chest tube drainage. The presence of multiple polycystic lesions in the pulmonary parenchyma supported the diagnosis of diffuse LAM with primary extrapulmonary presentation. This diagnosis should be considered preoperatively since it modifies the treatment: a complete excision of the cystic lesions seems to be necessary in order to prevent bleeding and lymphatic extravasation.

[Langerhans cell sarcoma with pulmonary manifestation, mediastinum involvement and bronchoesophageal fistula. A rare location and difficulties in histopathological diagnosis]. / Miesak z komórek Langerhansa przebiegajacy z zajeciem miazszu pluca, naciekaniem sródpiersia i przetoka oskrzelowo-przelykowa. Rzadka lokalizacja i trudnosci w rozpoznaniu histopatologicznym.

Langerhans cell sarcoma, a neoplastic proliferation of Langerhans cells with malignant cytologic features, is a very rare disease. Only a few cases have been documented in the English-language literature. Special methods, like immunohistochemistry and/or ultrastructural examination, are indispensable for appropriate diagnosis. Correct diagnosis is difficult. In fact, the disease is often misdiagnosed. We present the case of a 47 year-old man with a large mass in the middle lobe of the lung, infiltrating anterior mediastinum, with multiple pulmonary round lesions and enlargement of local lymph nodes, and with bronchoesophageal fistula. Clinical examination indicated the possibility of advanced primary lung cancer. However, the first histological diagnosis was Langerhans cell histiocytosis. In spite of treatment, the progression of pulmonary lesions was observed. Therefore, upper- and middle-lobectomy was performed. The diagnosis of Langerhans histiocytosis was confirmed microscopically again. Nevertheless, the patient's condition deteriorated progressively and he was admitted to the National Tuberculosis and Lung Diseases Research Institute in order to establish a final diagnosis. Revision of earlier resected specimens, as well as an immunohistochemical and ultrastructural examination of samples, taken once again from a bronchial tumor, led to the establishment of a diagnosis of a unique form of Langerhans cell sarcoma with rare pulmonary manifestation.