Proposal for a standardized methodology for performing endobronchial ultrasound-guided mediastinal cryobiopsy: a four-step approach.

Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the mediastinum. Although EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is the first choice in the diagnosis of mediastinal pathology, mediastinal cryobiopsy offers a larger and higher quality biopsy with minimal artifacts and no crushing when compared to conventional cytological samples obtained through EBUS-TBNA. It is particularly valuable in pathologies where EBUS-TBNA has diagnostic limitations, such as lymphoproliferative diseases, benign granulomatous conditions like sarcoidosis and silicosis, some rare infectious processes, metastases from rare non-pulmonary tumors, and in advanced stages of non-small cell lung cancer (NSCLC) where immunohistochemistry and molecular analysis are essential for personalized treatment. Therefore, mediastinal cryobiopsy seems to play a crucial role in these challenging scenarios. However, there is ongoing debate in the field of interventional pulmonology regarding the best approach for obtaining a mediastinal cryobiopsy. Some interventional pulmonologists use a high-frequency needle knife to create an incision in the tracheobronchial wall adjacent to the mediastinal lesion before inserting the cryoprobe, while others use a needle to create a pathway to the target area. There are also variations in the use of endoscopic or ultrasound imaging for guidance. In this article, we aim to review the current literature on different methods of performing mediastinal cryobiopsy and share our own clinical experience and methodology in a systematic way for its implementation in a safe, fast, and effective way.

Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: safety, feasibility and diagnostic yield - experience in 50 cases.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the technique of choice in the study of mediastinal and hilar lesions; however, it can be affected by the insufficiency of intact biopsy samples, which might decrease its diagnostic yield for certain conditions, thus requiring re-biopsies or additional diagnostic procedures such as mediastinoscopy when the probability of malignancy remains high. Our objectives were to 1) attempt to reproduce this technique in the same conditions that we performed EBUS-TBNA, i.e. in the bronchoscopy suite and under moderate sedation; 2) describe the method used for its execution; 3) determine its feasibility by accessing different lymph node stations applying our method; and 4) analyse the diagnostic yield and its complications. Methods: This was a prospective study of 50 patients who underwent EBUS-TBNA and EBUS-guided transbronchial mediastinal cryobiopsy (TMC) in a single procedure using a 22-G TBNA needle and a 1.1-mm cryoprobe subsequently between January and August 2022. Patients with mediastinal lesions >1 cm were recruited, and EBUS-TBNA and TMC were performed in the same lymph node station. Results: The diagnostic yield was 82% and 96% for TBNA and TMC, respectively. Diagnostic yields were similar for sarcoidosis, while cryobiopsy was more sensitive than TBNA in lymphomas and metastatic lymph nodes. As for complications, there was no pneumothorax and in no case was there significant bleeding. There were no complications during the procedure or in the follow-up of these patients. Conclusions: TMC following our method is a minimally invasive, rapid and safe technique that can be performed in a bronchoscopy suite under moderate sedation, with a higher diagnostic yield than EBUS-TBNA, especially in cases of lymphoproliferative disorders and metastatic lymph nodes or when more biopsy sample is needed for molecular determinations.

Pleural metastasis from pulmonary primary signet-ring squamous cell carcinoma. Case report and literature review.

Signet-ring cells are morphologically defined by the presence of a large intracytoplasmic vacuole that compresses and displaces the nucleus to the periphery. In most cases, these cells are associated with adenocarcinomas of various locations, and with non-epithelial neoplasms. To date, less than 20 cases of squamous cell carcinoma with signet-ring morphology have been described, mainly located on the skin. We present the case of a 73-year-old male with pleural effusion and a left lower lobe mass. The cytological study of the pleural effusion allowed the diagnosis of metastasis of squamous cell carcinoma, signet-ring cell variant. The treatment of lung cancer in advanced stages requires a precise diagnosis that allows the best therapy to be offered to the patient, depending on the clinical stage and the positivity of the biomarkers, among others. Our patient died 18 months after the initial diagnosis.

Routine flow cytometry approach for the evaluation of solid tumor neoplasms and immune cells in minimally invasive samples.

BACKGROUND: Multidimensional flow cytometry (MFC) is routinely used for the diagnosis and follow-up of hematolymphoid neoplasms but its contribution to the identification of non-hematolymphoid malignant tumors is limited. METHODS: The presence of non-hematolymphoid cells in clinical samples obtained via minimally invasive methods was ascertained by using a panel of monoclonal antibodies previously developed in our laboratory comprising a mixture of antibodies: CD9-PacB/CD45-OC515/CD57-FITC/CD56-PE/CD3-PerCP-Cy5.5/CD117-PE-Cy7/CD326-APC/CD81-APC-C750. Histopathological studies were performed using standard techniques. RESULTS: 164 specimens of different origins were included. Malignancy was finally confirmed in 142 (86.5%), while 22 non neoplastic samples were identified. The most frequent diagnosis was small cell lung carcinoma (SCLC) (50%). High sensitivity (S = 98.6%) was reached combining MFC and conventional pathology. Individual markers differed according to the cellular origin of the neoplasm, with neuroendocrine tumors showing a unique immunophenotypic profile (CD56+ CD326+ CD117-/+ and variable tetraspanins expression). Principal component analysis efficiently distinguished SCLC from other tumor samples. In immune cell populations, differences between reactive and malignant biopsies were found in different cell compartments, especially in B cells and Plasma cells. Differences also emerged in the percentage of CD4+ CD8- T cells, CD4-CD8+ T cells and NK cells and these were dependent on the origin of the tumor cells. CONCLUSIONS: These results support the use of MFC as a rapid and valuable technique to detect non-hematolymphoid tumoral cells in clinical specimens, providing an initial orientation to complement hystopathological studies and allow a more precise diagnosis, especially in neuroendocrine neoplasms. The impact of different immune cell patterns warrants further research.

Spontaneous regression of metastatic squamous cell lung cancer.

Spontaneous regression (SR) of cancer is a rare but confirmed spectacular phenomenon, and it is even rarer in the context of advanced NSCLC. It is essential to understand this phenomenon in order to elucidate the nature of neoplastic disease and develop new treatment methods.

Transbronchial cryobiopsy in interstitial lung disease: experience in 106 cases - how to do it.

Transbronchial biopsy using forceps (TBB) is the first diagnostic technique performed on patients with interstitial lung disease (ILD). However, the small size of the samples and the presence of artefacts in the tissue obtained make the yield variable. Our objectives were 1) to attempt to reproduce transbronchial cryobiopsy under the same conditions with which we performed conventional TBB, that is, in the bronchoscopy unit without intubating the patient and without fluoroscopy or general anaesthesia; 2) to describe the method used for its execution; and 3) to analyse the diagnostic yield and its complications. We carried out a prospective study that included 106 patients with clinical and radiological features suggestive of ILD who underwent cryo-transbronchial lung biopsy (cryo-TBB) under moderate sedation without endotracheal intubation, general anaesthesia or use of fluoroscopy. We performed the procedure using two flexible bronchoscopes connected to two video processors, which we alternated until obtaining the number of desired samples. A definitive diagnosis was obtained in 91 patients (86%). As for complications, there were five pneumothoraces (4.7%) and in no case was there severe haemorrhage or exacerbation of the underlying interstitial disease. Cryo-TBB following our method is a minimally invasive, rapid, safe and economic technique that can be performed in a bronchoscopy suite under moderate sedation without the need for intubating the patient or using fluoroscopy and without requiring general anaesthesia.

Successful Healing of Tracheal Radionecrosis: Role of Hyperbaric Oxygen Therapy.

Hyperbaric oxygen therapy, the administration of 100% oxygen at pressures > 1 atm, is believed to promote wound healing by increasing angiogenesis and collagen synthesis. To our knowledge, this treatment modality has never been described in patients with tracheal radionecrosis. Here, we report the case of a 55-year-old man diagnosed with stage IIIB lung adenocarcinoma who was treated with chemotherapy and concomitant external intensity-modulated radiotherapy involving the left lung and mediastinum. Nine months later, he presented with neck pain, cough with mucopurulent sputum, and fever. A PET-CT scan revealed a fissure in the posterior wall of the left upper trachea. Flexible bronchoscopy showed a tracheal ulceration with a small left posterior wall fissure that extended into the mediastinum. To our knowledge, this is the first report in the literature that suggests that treatment with hyperbaric oxygen therapy, local debridement, and antibiotics is a feasible and successful management option for patients with complicated tracheal radionecrosis.

Community-Acquired Moraxella catarrhalis Bacteremic Pneumonia: Two Case Reports and Review of the Literature.

Moraxella (formerly Branhamella) catarrhalis was discovered at the end of the nineteenth century, and for many decades it was considered to be a harmless commensal of the upper respiratory tract. It is a Gram-negative, aerobic diplococcus considered to be the third most common pathogen isolated in childhood sinusitis and otitis media and in adult chronic lower respiratory disease, as well as an etiological agent of pneumonia in immunosuppressed patients or those with chronic obstructive pulmonary disease. Moraxella catarrhalis pneumonia is rarely associated with bacteremia. Here, we present two cases of community-acquired Moraxella catarrhalis bacteremic pneumonia.

Poncet's disease mimicking rheumatoid arthritis in a patient with suspected Crohn's disease.

Poncet's disease is a rarely reported entity with an unknown pathogenesis. However, because it has a very favorable prognosis with antituberculosis drugs, we believe it should be considered as a differential diagnosis for patients with fever and polyarthritis of unknown cause, particularly if active tuberculosis is suspected.