Potential application of cryobiopsy for histo-molecular characterization of mediastinal lymph nodes in patients with thoracic malignancies: a case presentation series and implications for future developments

Background The management of non-small cell lung cancer (NSCLC) has become increasingly complex due to the evolution of personalized medicine approaches. Such approaches are characterized by the necessity of adequate tumor samples; hence, improved biopsy techniques are needed. Transbronchial lung cryobiopsy is a novel endoscopic procedure designed to collect peripheral pulmonary tissue, and it is currently employed in interstitial lung diseases. The use of this technique in oncology might result in improved mediastinum staging and molecular characterizations; however, available data involving the use of a cryoprobe on mediastinal lymph nodes are still limited. Case presentation Here we present a series of five consecutive patients who underwent endoscopic assessment of mediastinal lymph nodes for oncologic reasons. All patients were subjected both to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) and cryobiopsy of mediastinal lymph nodes during the same procedure, and no complications were observed. In three of the reported cases, both cryobiopsy and cell block from EBUS TBNA were positive, while in one case cryobiopsy was not diagnostic and EBUS TBNA was negative; moreover, one case showed discordance between the procedures, as cryobiopsy was negative and cell block obtained from multiple stations was diagnostic for small cell lung cancer. In one case involving a patient treated for lymphoma, cryobiopsy provided more complete histologic characterization, and in another case involving a patient affected by NSCLC cryobiopsy provided more material for molecular analyses. Conclusion This case presentation series suggests that cryobiopsy, which has been generally used on peripheral lung lesions so far, is a feasible and safe approach for diagnosis and staging of mediastinal lymph nodal involvement, especially when station 7 is involved. Compared to EBUS TBNA, cryobiopsy might provide more adequate histological samples, with a possible impact on molecular characterizations and, therefore, therapeutic decisions. However, the learning curve of the procedure has not to be understated and optimal protocols for implementing this technique are needed. In our opinion, further studies designed to integrate the routine use of cryobiopsy in current practice for solid and eventually hematologic tumors with mediastinal lymph node involvement are warranted.

The Diagnostic Yield of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Technique in Assessment of Mediastinal Lymph Nodes

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) technique provides a complementary assessment of the areas of mediastinal lymph node involvement, and allows sampling of suspected lymph nodes. But, the usefulness of EBUS-TBNA in assessing all areas of mediastinal lymph nodes is little known and it seems that such assess is dependent to various factors related to the patient's condition and especially the characteristics of local lymph nodes. We aimed to evaluate the utility of EBUS-TBNA in assessing mediastinal lymph nodes and the factors associated with this utility.Methods: This cross-sectional study was performed on 40 patients suspected to mediastinal lymphadenopathy scheduled for assessment by EBUS-TBNA and mediastinoscopy. The diagnostic yield of EBUS-TBNA to mediastinal lymph nodes was evaluated and non diagnostic cases evaluated by mediastinoscopy .Results: In evaluation with EBUS-TBNA, the diagnostic yield of EBUS in assess to mediastinal lymph nodes including 34 out of 40 cases was equal to 85%. The size of lymph node (lower than 10mm), the area of sample (left and right upper paratracheal), and the nature of the lymph node sample (benign type) were associated with lower diagnostic yield for EBUS-TBNA.Conclusion: The diagnostic yield of EBUS in assessing mediastinal lymph nodes for sampling and diagnosis is 85%. This benefit is expected in the case of lesions larger than 10 mm, lesions of a malignant nature, as well as lesions in the inferior paratracheal and subcarinal stations.

Sir William Osler's fatal trip to Scotland: “Mrs M” and the University Grants Committee

On 23 September 1919, Sir William Osler, after a telephone call from his friend Dyson Perrins, went to Glasgow where he saw a 40-year-old woman, Bethia Fulton Martin, in consultation with three local physicians. Osler called it “one of those remarkable Erythema cases (all sorts of skin lesions and three months on and off consolidation of both lower lobes).” Mrs Martin died 114 days later; her death certificate listed “angioneurotic oedema with chronic nephritis” and “tuberculous enlargement of the mediastinal lymph nodes.” Osler died 18 days before Mrs Martin of complications from a respiratory infection acquired on his way home from Scotland. We discuss factors that possibly prompted Osler to go to Scotland, including his role with the newly formed University Grants Committee, and the differential diagnosis of the case, which is mainly between systemic lupus erythematosus and Henoch-Schönlein purpura.

LOBE-SPECIFIC METASTASIS IN NON-SMALL CELL LUNG CANCER

Aim: to identify the pathways of lymph node metastases in non-small cell lung cancer (NSCLC).Material and Methods. The frequency of mediastinal lymph node metastases and treatment outcomes were analyzed in 327 patients with stage I–III non-small cell lung carcinoma (NSCLC), who underwent lung resection with systematic lymph node dissection (SLND) between 2007 and 2011.Results. In cases with tumor location in any lobe of the right lung, metastasis occurred in the superior and inferior mediastinal lymph nodes. In left-side tumors, the main pathways of lymphatic spread of tumors were superior and inferior mediastinal nodes as well as aortic lymph nodes. Left lower lobe tumors metastasized most often to inferior mediastinal lymph nodes. Skip metastases were observed at any location of the tumor. Routine examination of all ipsilateral mediastinal lymph nodes overstaged NSCLC in 19.5 % of cases. The overall 5-and 10-year survival rates in patients with stage I–III NSCLC with SND were 61.5 % and 49.2 %, respectively. The median survival time was 103 months.Conclusion. Despite typical metastatic patterns of mediastinal lymph nodes in patients with NSCLC, non-specific metastasis was observed at any location of the tumor, which required mandatory systematic nodal dissection.

Puncture biopsy of bifurcation lymph nodes in the diagnosis of lung cancer

Clinical, radiological and pathological data of a number of authors testify to the frequent defeat of the lymph nodes of the mediastinum with cancer metastases (MN Goryunova, 1951; Ya. G. Dillon, 1947; BK Osipov, 1959, etc.). Anatomical works of Ruvier (1932), DA Zhdanov (1947) and others testify to broad afferent connections of bifurcation lymph nodes in normal conditions with the organs of the chest cavity. These factors create the possibility of lymphogenous metastasis of cancer of the lung and esophagus in the mediastinal lymph nodes, in particular, in the bifurcation.