Lung Neoplasia II Resection specimens Pathobasic Lukas Bubendorf Pathology
Agenda Preneoplastic lesions Histological subtypes of lung cancer Histological patterns of AC
Cells of origin and characteristic alterations according to histological subtype P40 + TTF1 + Swanton & Govindan, NEJM 2016
Basal cell hyperplasia Squamous cell metaplasia Dysplasia (l - m s) CIS AAH (atypical adenomatous hyperplasia) DIPNECH? Squamous cell carcinoma Adenocarcinoma Carcinoid Small cell carcinoma 30-40% 50-60% -15%
Bronchial squamous dysplasia / CIS Expansion Basal zone/ crowding Expansion basal zone/ crowding vertical nuclei Mitoses vertical nuclei Chaos Mitoses Expansion basal zone/ crowding Vertical nuclei Mitoses mild dysplasia moderate dysplasia severe dysplasia Carcinoma In situ mod. Kerr KM J Clin Pathol 2001
p53
Angiogenic squamous dysplasia Micropapillomatosis 34% of heavy smokers 3p LOH in 53% High capillary density Keith RL et al, Clin Cancer Res 2000
Course of squamous preneoplasia mild/ moderate dysplasia max. 9% Progression CIS / inv.ca Severe dysplasia 40% persistance/ progression Spontanous regression dysplasia: >50% CIS: 13% Ishizumi T et al, Cancer Metastasis Rev 2010
Terminal Respiratory Unit (TRU) EGFR KRAS EML4-ALK HER2 ROS1 BRAF TTF-1+ adenocarcinoma (TRU-type) BADJ = bronchoalveolar duct junction Yasushi Yatabe, Cancer Metastasis Rev 2010
Atypical adenomatous hyperplasia (AAH) Definition Proliferation of mildly to moderately atypical type II alveolar cells Intercellular gaps; nuclear inclusions 5mm Prevalence NSCLC resection specimens: 10-20% (AC 34%, SCC -7%) Benign lung disease: 5-10%
Bronchiolar cylindric cell dysplasia Ullmann R et al, Virchows Arch 2003
Basal cell hyperplasia Squamous cell metaplasia AAH (atypical adenomatous hyperplasia) Dysplasia (l - m s) CIS DIPNECH? Squamous cell carcinoma Adenocarcinoma Carcinoid Small cell carcinoma 30-40% 50-60% -15%
Tumourlet ( 5mm)
DIPNECH (diffuse idiopathic pulmonary neuroendocrine cell hyperplasia) Neuroendocrine cell proliferation along the bronchioles 200 cases in the literature Associated with intra- and extraluminal fibrosis obstructive functional disorder Mainly women (>90%) Concurrent carcinoids (50%) Rare association with MEN1 Syndrome Wirtschafter E et al, Lung 2015
WHO Histological Classification 2015 HE, Mucin, IHC, Genetics & Radiology IHC makes a difference in resection specimens TTF1 solid Adenocarcinoma P40 non-keratinizing SCC Decreasing proportion of LCLC
2015 WHO Classification Book, Page 83
Large cell carcinoma Redefined by Immunohistochemistry and Genomics ADC 55 % SCC 26 % Null 19 % Sholl L. Curr Opin Pulm Med. 2014;20(4)
Adenocarcinoma 2004 WHO Mixed subtype Acinar Papillary BAC Solid Variants 2015 WHO Invasive ADC Lepidic Acinar, papillary Micropapillary, Solid (mucin or TTF1+) Variants (mucinous, colloid, fetal, enteric) Minimally invasive ADC (MIA) 3cm with 5mm invasion ( 3%) Preinvasive lesions AAH AIS ( 3cm) ( 0.2%)
Lepidic pattern (formerly: bronchoalveolar carcinoma) Warth A, J Clin Oncol 2012 >50% lepidic Anami; J Thorac Oncol TO 2009 The more, the better...
Invasive Adenocarcinoma Acinar predominant Papillary predominant Micropapillary predominant Solid predominant with mucin Semiquantitative assessment in 5-10% increments
Histologic patterns of lung adenocarcinoma Predominant pattern in mixed tumors
Grading of NSCLC Official grading not yet established Ongoing project Separate criteria for Squamous & Adeno
Multiple lung tumors Metastasis vs. Independent tumors pt1 pt2 pm1a pt2(m) Comprehensive histological assessment AC subtype, cytological & stromal features Molecular testing (IHC phenotype, mutations by NGS)
Spread Through Air Space (STAS) 40% of AC
Spread Through Air Space (STAS) Lobectomy group Recurrence Limited resection group Kadota K et al, J Thorac Oncol 2015
Pleomorphic, spindle cell, and giant cell carcinoma Pleomorphic CA: poorly diff. NSCLC (squamous or AC) or undiff. CA with at least 10% spindle and/or giant cells Spindle cell CA: almost pure population of epithelial spindle cells Giant cell CA: made almost entirely of tumor giant cells (incl. multinucleated)
Pleomorphic carcinoma (ex adenocarcinoma)
Combined LCNEC