Ming S. Tsao, MD, FRCPC, of the Princess Margaret Cancer Centre, Toronto, delivered a Plenary Presentation during the 2020 World Conference on Lung Cancer outlining key updates found in the 5th edition of the World Health Organization (WHO) Book on Classification of Thoracic Tumours. The new book has implemented many new formats and involve new authors and editors. New sections that will be especially useful for pathologists in their clinical practice include “Diagnostic Molecular Pathology” and “Essential or Desirable Diagnostic Criteria”.
Dr. Tsao said that as compared to the previous edition published in 2015, few new tumor types have been added to the 2020 classification; these are all low incidence tumors. He briefly described salient features of these new tumor entities.
Bronchiolar Adenoma (ciliated muconodular papillary tumor) is a benign tumor which typically shows the perforations of two layers of bland appearing cells along the bronchiolar epithelium. Interestingly, these tumors may harbor driver mutations found in lung cancer. “It is important to distinguish bronchiolar adenoma from lepidic adenocarcinoma or adenocarcinoma in situ based on the morphology of the two-layer epithelial cell perforation,” he said.
Thoracic SMARCA4-Deficient Undifferentiated Tumor is a highly malignant, undifferentiated lung tumor with or without pleural chest wall invasions. This type of lung cancer is characterized by the loss of expression of SMARCA-4, which can be detected by immunohistochemistry (IHC). SMARCA-4 gene is involved in chromatin remodeling, and the loss of expression is mostly due to mutation.
Mesothelioma in Situ is a pre-invasive, single-layer surface proliferation of neoplastic mesothelial cells. This entity is found in patients with non-resolving pleural effusion(s), and with history of heavy asbestos exposure, prior radiation, or with a family history of mesothelioma. The lesion can only be diagnosed by demonstration of the loss of expression of BAP1 and/or MTAP by IHC and/or CDKN2A homozygous deletion by fluorescence in situ hybridization (FISH). Importantly, this disease has high potential to progress into invasive epithelioid mesothelioma, a malignant version.
Dr. Tsao also highlights new important updates in the new classification book on some of the thoracic cancers.
Subtyping invasive non-mucinous adenocarcinoma based on the predominant histological pattern is now standard in lung adenocarcinoma classification and diagnosis. These subtypes have prognostic significance. Lepidic-predominant tumors have a better prognosis, papillary or acinar predominant tumors have an intermediate prognosis, and micropapillary/solid tumors have poor prognosis; the latter may predict survival benefit from adjuvant chemotherapy. However, there are additional tumor features that have traditionally been associated with prognosis including nuclear and cytology grade, mitosis, necrosis, and most recently, the spread through air spaces (STAS). In a study by the IASLC Pathology Committee, it was found that the presence of 20% or more of secondary high-grade patterns (micropapillary, solid and complex gland) on top of the primary pattern, can increase the risk of recurrence or death in a training cohort and independently validated in 2 additional patient cohorts. Based on these findings, the IASLC Differentiation Grading System for invasive non-mucinous pulmonary adenocarcinoma was proposed and included in the new WHO Classification book. This grading system appears to improve the stratification of the prognosis of early-stage non-mucinous adenocarcinoma patients compared to predominant pattern-based prognostication alone. Furthermore, the IASLC Grading System may possibly increase the percentage of patients (with grade 3 tumors) who might potentially benefit from adjuvant chemotherapy, although this requires additional supporting data.
The mesothelioma chapter in the 2021 WHO Classification Book provides a more detailed description of the disease including the various histological or cytological features and the new grading system for the tumor; some of these carry prognostic implications. The chapter also provides recommendations on what should be included in pathological reporting of biopsy or resection specimens for this tumor.
The 5th edition of the WHO Thoracic Classification of Thoracic Tumours will become available in spring of 2021. The new book will be available by online subscription, which includes access to whole slide images.
- Moreira AL. Ocampo PSS, Xia Y, et al. A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee. J Thorac Oncol. 2020;15(10):1599-1610.