Immunohistochemical classification of lung carcinomas and mesotheliomas Prof. Mogens Vyberg NordiQC Institute of Pathology Aalborg, Denmark
Endobronchial ultrasound guided transbronchial needle biopsy
Transthoracic Needle Biopsy
Lung carcinomas vs. epithelioid malignant mesothelioma TTF-1 NapA p40 CK5 Calr Pod WT1 Vim Ep- CAM Cld4 Lung adenocarcinoma Lung squamous cell carcinoma Epithelioid mal. mesothelioma 80 * 80? 0 ** 5? 10 f 10 f 20? 30 95 100 15* w 10 f 95 95 50? 10 0 10? 95 95 0 0 0 80 90 90 90 90 10 f 0 Panou V, Vyberg M, et al. Cancer Treat Rev. 2015 Jun;41(6):486-95. ~ % positivity *Clone SPT24 ** p63: 5% f: focal, w: weak?: insuff. data
Lung markers TTF-1 Napsin p63/p40 (CK5) Squamous cell carcinoma: Risk of hemorrhage due to bevacizumab (Avastin)
Thyroid transcription factor-1 Thyroid gland: regulating thyroglobulin, thyroperoxidase and thyrotropin receptor Lung: regulating surfactant proteins and Clara cell secretory protein Thyroid follicles and C-cells Histiocytes Lung pneumocytes II and Clara cells Brain Pituitary Parathyroid Normal lung
TTF-1 Run 39/2013: 227 labs Optimal: 51% Insufficient: 29%
SPT24 8G7G3/1 1:100 Lung adenocarcinoma
Matoso et al, AIMM 2010,18:142-149 Thyroid transcription factor-1 % pos.: Lung adenocarcinoma 80 70 SPT24 8G7G3/1 - large cell carcinoma 50 40 - small cell carcinoma 90 90 - carcinoid 60 20 - squamous cell carcinoma 15 0 Non-lung small cell carcinoma 20-40? Thyroid carc. (non-anaplastic) 100 100 Non-lung carcinomas 0-5 0-5 Non-lung carcinoids ~ 0 ~ 0
TTF-1 pos. neoplasms outside lung Neuroendocrine neoplasms Small cell carcinoma ~40% GI tract,prostate, bladder, liver, uterine cervix, breast Large cell neuroendocrine carcinoma prostate, uterine cervix Neuroendocrine tumor/ carcinoid: GI tract Merkel cell carcinoma of skin Non-neuroendocrine adenocarcinomas Gastric, Colorectal, Breast, Primar peritoneal, Endocervical, Endometrial, Ovarian, Nasopharyngeal papillary Others Synovial sarcoma Melanoma Brain tumors
TTF-1 Run 39/2013: 227 labs Optimal: 51% Insufficient: 29%
Lung squamous cell carcinoma SPT24, SP141 Lung adenocarcinomas 8G7G3/1, MX011
Lung adenocarcinoma / TTF1-intermediate expressor SPT24 SP141 EP1584Y MX011 (8G7G3/1)
Lung squamous cell carcinoma SPT24 SP141 EP1584Y CK5 MX011 (8G7G3/1) p40
Lung squamous cell carcinoma / TTF-1 pos! SPT24 SP141 EP1584Y MX011 (8G7G3/1)
Napsin A Aspartic proteinase Type II pneumocytes Proximal and convoluted renal tubules (Pancreatic acini and ducts)
Napsin A Aspartic proteinase Type II pneumocytes Proximal and convoluted renal tubules (Pancreatic acini and ducts)
Napsin A: lung adenocarcinoma ~ 80%
Napsin A: Lung squamous carcinoma 0 30%
Napsin A: Renal cell carcinoma 0 70%
Napsin Run 39/2013: 104 labs 30% optimal 42% insufficient
49 Liver adenocarcinoma of unknown primary CK20
49 Liver adenocarcinoma of unknown primary: Lung TTF Napsin A
p63 / p40 Nuclear proteins - transcription factors Belongs to the p53 gene family Plays a critical role in the growth and development of many epithelia Confined to squamous epithelia urothelium basal cells/myoepithelial cells - lung, breast, sweat glands, salivary glands, and prostate
Adenocarc. Squamous cell carc.
?
Lung cancer panel Adenocarcinoma TTF1 +/- -(+) Napsin +/- -(+) Squamous cell carcinoma CK5 -(+) +(-) p63/p40 -(+) / - +(-) PAS/AB +/- -(+)
p63 TTF1 Adeno CK5/6 AB/PAS
P63/p40 TTF1 Squamous CK5 (5/6) AB/PAS
Tonsil p63/p40 p40 p40 p63 p63
Squamous cell carcinoma Diffuse large B-cell lymphoma p40 p40 p63 p63
p40 Run 44/2015: 124 labs Optimal prostate squamous cell carc. Insufficient
ALK expression in lung adenocarcinoma 3-6% of lung adenocarcinoma reveal a driver mutation, a chromosome 2 inversion (inv(2) (p21p23)) causing an ALK-EML4 gene fusion, which gives rise to the oncogen ALK-EML4 fusion protein. A kinase inhibitor, crizotinib (Xalkori, Pfizer), is approved for treatment of ALK mutated cases. ALK can be demonstrated with IHC, FISH and PCR
ALK (lu) Run 45/2015: 177 labs Optimal ALCL Lung adenocarc. Insufficient
ALK (lu) Run 45/2015: 177 labs
Malignant mesothelioma
Asbestos consumption in Denmark 1930-84 Metric tons År 42
Mesothelioma incidens i North Jutland: 5/100.000 13-fold incrase in 4 decades (1970-2013) and increasing MM tilfælde År Panou V, Meristoudis C, Røe OD. 26 th European Pathology Congress, London 2014 43
Mesothelial markers Calretinin Podoplanin WT1 Vimentin CA125 CK5
Calretinin Calcium-binding protein related to S-100 proteins Neurons Mesothelial cells Steroid producing cells adrenal cortical cells testicular Leydig and Sertoli cells ovarian theca interna cells and surface epithelium Neuroendocrine cells Breast glands...
Calretinin Mesothelium Appendix
Calretinin Ep. malignant mesotheliomas + (>50% nuclear) Steroid producing tumours +/- adrenal cortical tumour testicular Leydig and Sertoli cell tumour ovarian thecal tumours Adenocarcinomas -(+)...
Malignant mesothelioma Malignant mesothelioma Calretinin in neoplasms
Adrenal gland Granulosa cell tumour Calretinin
Calretinin Run 33/2011: 180 labs Optimal adrenal gland mesothelioma Insufficient
Calretinin Adenocarcinoma Optimal False positive
Podoplanin Lymphatic endothelium Fibroblasts, osteocytes Smooth and striated muscle cells Myoepithelial cells, Cajal cells Basal squamous epithelial cells Gastric crypt c., prostatic basal c. Immature Sertoli c. and gonocytes Renal glomerular podocytes Mesothelium (reactive) Follicular dendritic cells (controls) Some lymphocytes Glial/Schwann cells
Podoplanin Lymphatic endothelium Fibroblasts, osteocytes Smooth and striated muscle cells Myoepithelial cells, Cajal cells Basal squamous epithelial cells Gastric crypt c., prostatic basal c. Immature Sertoli c. and gonocytes Renal glomerular podocytes Mesothelium (reactive) Follicular dendritic cells (controls) Some lymphocytes Glial/Schwann cells
Podoplanin Mesothelioma Many other tumours but rarely adenocarcinomas
Podoplanin Run 36/2012: 102 labs Optimal tonsil mesothelioma Insufficient
Pleural biopsy malignant mesothelioma
Pleural biopsy malignant mesothelioma Cytokeratin 7 + Cytokeratin 5 Calretinin Podoplanin Normal mesothelium
Immunohistochemical classification of lung carcinomas and mesotheliomas Prof. Mogens Vyberg NordiQC Institute of Pathology Aalborg, Denmark