1. April 2014 Dr J King Dr K Syred

2.  90% mesotheliomas are linked to asbestos exposure  May be eligible for compensation  3 yr survival rate 8%  Subtype related to prognosis and different treatment options ◦ Epithelioid 1yr survival 52% ◦ Sarcomatoid 1 yr survival 13%

3.  Correlation of tissue diagnosis with clinical and radiology  IHC: ◦ Panel 1: TTF-1, CEA, calretinin, CK5, D240, WT-1, MOC31 ◦ Panel 2: MNF116, CD15, CK7, CK20 IhcReactiveMalignant EMA-/++ Strong membranous Desmin+- p53-+

4.  Identify practice within our department ◦ Typing ◦ Assess what ihc has been performed ◦ Determine any improvements in diagnosis ◦ Report quality

5.  Reviewed mesothelioma reports in the last 9 months (1/1/14 – 30/9/14)  Identify further work done  Possibly devise an improved panel of markers make diagnosis more efficient and cost saving

7.  ‘ 6.4 Pathological  Histological type should be stated (epithelioid, biphasic, sarcomatoid (desmoplastic variant if present). Given the need for ancillary investigations to make the diagnosis, the immunohistochemistry panel used should be documented, this being at least two ‘mesothelium-associated’ markers and two ‘epithelium-associated’ markers for epithelioid and biphasic tumours (discussed in section 5). For sarcomatoid variants, due to the wide differential diagnosis, the full repertoire of antibodies used should be listed.’

8.  ‘For pleural mesothelioma-like tumours with an epithelial component, it is recommended that immunolabelling for both calretinin and TTF-1 is routinely carried out.’

9.  ‘As with biopsies, cytological findings should be correlated with the clinical and imaging findings to establish whether the available cytological material is sufficient to render a specific diagnosis or a clinically relevant differential diagnosis. If a pleural cytology specimen is positive or suspicious for malignancy, and there is no other specimen, then material should undergo the same ancillary investigations as for biopsies in terms of the differential diagnosis, which ideally is via a cell pellet for histology as this allows preservation of residual material. Identification of an epithelial phenotype will allow a definitive diagnosis of metastatic carcinoma. Identification of a mesothelial phenotype will allow further management decisions in terms of a definitive diagnosis of mesothelioma or further sampling, dependent on the clinical scenario’

10. 1. All diagnoses of mesothelioma should be typed. 2. Where immunohistochemistry is performed, there should be a panel including 2 mesothelial and 2 epithelial markers. 3. If an epithelioid subtype, caltretinin and TTF-1 should be performed 4. Immunohistochemistry should be performed on tissue rather than pleural fluid when available.

11.  Search on i-lab ◦ M-90503 – mesothelioma, NOS ◦ M-90513 – fibrous mesothelioma, NOS ◦ M-90523 – epithelioid mesothelioma, NOS ◦ M-90533 – biphasic mesothelioma, NOS  1/1/14 – 30/9/14  From the list each report looked up on i-lab  Data in-putted into spread sheet

12.  Lab no  What procedure was done to obtain a diagnosis  Any previous relevant investigations  Any immunohistochemistry performed on the procedure and if so what was ordered (the SPLI function was used to identify the immunohistochemical stains performed as not all of them were mentioned in the report. Where mentioned in the report, the result (positive or negative) was recorded).  It was noted if there was pleural fluid taken at the same time as any biopsy.  If there was mention of a pleural fluid on the biopsy form

13.  Diagnosis of mesothelioma if pleural or peritoneal in during the time period stated above.  Previous results e.g. any previous pleural fluids sampled in previous years were also included in this audit.

14.  Outside cases for review at the MDT eg. from Truro.  Cases that are coded incorrectly.  LN biopsy for metastatic malignant mesothelioma  PM histology as not all of the PMs would have been picked

15.  Total 31 biopsies performed ◦ 3 excluded 1outside case 2 adenocarcinomas coded incorrectly  Remaining 28 ◦ 26 pleural bx - 20 had cytology at the same time ◦ 2 omental bx ◦ 27 had ihc  1 did not as it was being performed on the fluid ◦ 1 had ihc on both bx and fluid

16.  Accompanying cytology ◦ 8/20 (36%) malignant or suspicious of malignancy ◦ 12/20 no malignant cells seen ◦ 6 cytology forms mentioned bx taken  7 cases bx only taken ◦ 1 recurrent case with prev diagnosis 3 yrs ago ◦ 1 had 2 previous pleural fluids – blood only and nmcs ◦ 5 did not have any previous procedure  2 cases diagnosed on pleural fluid alone

17.  24/28 (86%) mesotheliomas diagnosed on tissue were subtyped. TypeNo Epithelioid malignancy2 Epithelioid malignant mesothelioma17 Epithelioid and sarcomatous malignant mesothelioma 1 Biphasic malignant mesothelioma3 Malignant mesothelioma3 Recurrent malignant mesothelioma1 Sarcomatoid malignant mesothelioma1

18.  13/29 cytology cases were suspicious/ malignant.  only 7 were classed as mesothelioma and only 2 were subtyped. 2/13 = 15% ReportNo Favour malignancy / malignancy strongly suspected4 Atypical epithelioid cells highly suspicious of malignancy 1 Malignant1 Favour / suggestive / suspicious of mesothelioma4 Mesothelioma1 Epithelioid meosthelioma2

19. biopsy27 Accompanying cytology2 Cytology alone2 Previous cytology4 Total35

20.  39 different immuno-stains were ordered  Total of 286 ihc orders  Average = 8 per case  Mucin stains = 10

23. Meso vs adeno panels IhcTotalPos bxPos cytolNeg bxNeg cytol Panel 1TTF-12400194 CEA1810143 MOC-312453123 Calretini n 3320730 CK52619510 D24073130 WT12618230 Panel 2CKMNF1 16 1210010 CD1500000 CK795120 CK2080051

24. Mesothelial markers% positive CK596% (27/28) Calretinin90% (29/32) WT-188% (22/25) Epithelial markers% positive CEA6% (1/18) BerEp429% (7/24) MOC3135% (8/23) TTF10% (0/23)

25.  30/35 (86%) had 2 epithelial and 2 meso markers  Remaining 5: ◦ One had reactive panel ◦ 4 had both an epithelial and mesothelial marker, some with 2 of one but not 2 of both

26.  23 of mesotheliomas typed as epithelioid  15/23 (65%) had both calretinin and TTF-1 performed  One had reactive panel  The remaining did not have TTF-1  2 were omental bx and may not need TTF-1

27.  Ihc performed on 27 of the biopsies  1 did not have ihc as it was requested on the cytology (commented on in the report)  Only 1 patient had ihc on both biopsy and cytology

28.  Standard 1: 86% tissue and 15% cytology subtyped  Standard 2: 86% had 2 mesothelial and 2 epithelial markers  Standard 3: 65% epithelioid mesotheliomas had calretinin and TTF-1  Standard 4: 1 had ihc on fluid rather than bx and 1 had ihc on both

29.  New mesothelioma IHC panel ◦ CK5CEA ◦ CalretininBerEp4 ◦ WT-1Moc31 TTF-1  Proforma to guide reporting biopsies and cytology ◦ Subtype ◦ List of ihc

30.  http://www.hscic.gov.uk/media/15038/Meso thelioma- audit/pdf/EMBARGOEDTO120914_NLCA_Mes o_Report_final.pdf http://www.hscic.gov.uk/media/15038/Meso thelioma- audit/pdf/EMBARGOEDTO120914_NLCA_Mes o_Report_final.pdf  Standards and datasets for reporting cancers. The dataset for the histological reporting of mesothelioma. RCPath guidelines