July 2020

By M.Angeles Montero, BTOG Steering Committee Member

From 2011 and updated in 2015, the identification of therapeutic targets for the treatment of lung cancer has resulted in the new WHO classification system for non-resection specimens, small biopsies and cytologies. From that moment, tissue samples have no longer been managed for diagnosis alone, but also for molecular testing. Taking into consideration that approximately 70% of lung cancer is inoperable, with a presentation at an advanced stage, retrieval of tissue using minimally invasive procedures for diagnosis, tumour subtyping and molecular tests is the main approach to guide the medical management of these patients, and dealing judiciously with small specimens has turned into the new-normal way of working for thoracic pathologists.

In 2018, the Royal College of Pathologists wrote the dataset for histopathological reporting of lung cancer, which included a brief description about handling and reporting non-resection specimens. Its recommendations are addressed exclusively for histopathologists, and spanned from the handling of biopsies during the pre-examination to the post-diagnosis phase, with a particular emphasis in the fixation, preservation of tissue and multidisciplinary team discussion. Additionally, for the handling of cytology specimens it advised the processing of material to cellblock for immunohistochemistry and molecular tests.

Recently the College of American Pathologists in collaboration with the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytology, Society of International Radiology and Society of Thoracic Radiology have published the guidelines for collection and handling of thoracic small biopsy and cytology specimens for ancillary studies. In this report after a systematic review of the literature is performed, 16 guideline statements have been issued to assist clinicians and pathologists in collecting and processing thoracic small biopsies and cytologies.

As a starting point, the expert panel considered four critical questions as the methodological variables to optimise outcomes, the most effective protocols for sample collection, the best effective methods for handling and processing (the selection of the media, the priority of the disease and the optimal ischaemic time) along with the possibility of a support algorithm for the adequate management of the specimens. What is important to highlight is that the target of audience for this guideline is all the healthcare professionals involved in the collection and handling of this type of specimens conversely to the guidelines established by the Royal College of Pathologists.

The guideline statements accrue evidence-based recommendations for the appropriate collection and handling of small specimens, which had been divided into four groups depending on the type of procedure: endobronchial ultrasound-guided, transbronchial, bronchoscopy, and pleural effusions.

Recommendations
There are three strong recommendations: the use of endobronchial ultrasound-guided transbronchial biopsy (EBUS TBNA) for the initial evaluation (diagnosis, staging, identification of recurrence/metastasis) of mediastinal and hilar nodes as well as centrally located parenchymal lesions visible during the procedure, the use of rapid on-site evaluation (ROSE) when performing transthoracic needle procedures for adequacy assessment, which can be implemented with touch preparations and the use of cytology specimens (smears, cellblocks and liquid- based cytology) that may be used for ancillary studies if supported by adequate validation studies. The rest of the statements are recommendations with variable degree of quality evidence.

Summary
As a summary, the recommendations for EBUS TBNA procedure are: for the size of the needle 21 or 22-gauge may be used, the number of passes will vary from 3-5 without ROSE or as many as clinically necessary if ROSE is available. Despite the strong recommendation of ROSE, it is not recommended for all the cases. The bronchoscopist experience, the lack of adequate personnel, the inadequate pathologists’ reimbursement and the loss of material for ancillary and molecular testing are several reasons given in the studies reviewed.

Attending the transthoracic procedures the recommended gauze is 25 for fine needle aspiration (FNA) and 24 for the core biopsy. Multiple passes are necessary if FNA is performed, as a cellblock should be necessary for ancillary testing including molecular. It is also recommended a minimum of 3 core biopsies when performing transthoracic core needle biopsies.

As for the bronchoscopy procedures image-guidance adjuncts are recommended, as well as ROSE if available. When collecting pleural fluid for a suspected malignancy diagnosis, as much fluid as possible should be sent. Core needle biopsies should be fixed in 10% neutral buffered formalin. Additionally, two recommendations for the management of infectious diseases are also included.

Several key questions could not reach the level of recommendation, the collection media, the type of fixative and specific stains, the optimal ischaemic time and an adequate sequence algorithm.

This guideline emphasises the need to minimise the diagnostic workup and to perform all the studies clinically relevant in a timely manner to ensure the best customised treatment for every patient.