Lung Neoplasia II Resection specimens Pathobasic. Lukas Bubendorf Pathology

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1 Lung Neoplasia II Resection specimens Pathobasic Lukas Bubendorf Pathology

2 Agenda Preneoplastic lesions Histological subtypes of lung cancer Histological patterns of AC

3 Cells of origin and characteristic alterations according to histological subtype P40 + TTF1 + Swanton & Govindan, NEJM 2016

4 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%

5 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

6

7 p53

8 Angiogenic squamous dysplasia Micropapillomatosis 34% of heavy smokers 3p LOH in 53% High capillary density Keith RL et al, Clin Cancer Res 2000

9 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

10 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

11 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%

12

13

14 Bronchiolar cylindric cell dysplasia Ullmann R et al, Virchows Arch 2003

15 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%

16

17 Tumourlet ( 5mm)

18

19 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

20 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

21

22 2015 WHO Classification Book, Page 83

23 Large cell carcinoma Redefined by Immunohistochemistry and Genomics ADC 55 % SCC 26 % Null 19 % Sholl L. Curr Opin Pulm Med. 2014;20(4)

24 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%)

25 Lepidic pattern (formerly: bronchoalveolar carcinoma) Warth A, J Clin Oncol 2012 >50% lepidic Anami; J Thorac Oncol TO 2009 The more, the better...

26 Invasive Adenocarcinoma Acinar predominant Papillary predominant Micropapillary predominant Solid predominant with mucin Semiquantitative assessment in 5-10% increments

27 Histologic patterns of lung adenocarcinoma Predominant pattern in mixed tumors

28 Grading of NSCLC Official grading not yet established Ongoing project Separate criteria for Squamous & Adeno

29 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)

30 Spread Through Air Space (STAS) 40% of AC

31 Spread Through Air Space (STAS) Lobectomy group Recurrence Limited resection group Kadota K et al, J Thorac Oncol 2015

32 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)

33 Pleomorphic carcinoma (ex adenocarcinoma)

34 Combined LCNEC

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