Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case...
Transcript of Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case...
![Page 1: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/1.jpg)
1
Case –based applications – part III
Los Angeles Society Of Pathologists January 25, 2014
Sanja Dacic, MD, PhD University of Pittsburgh Medical Center
![Page 2: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/2.jpg)
2
CASE 1
A 44-year-old woman with multiple lung nodules.
![Page 3: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/3.jpg)
3
Tumor nodule 1
![Page 4: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/4.jpg)
4
Tumor nodule 1
![Page 5: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/5.jpg)
5
Tumor nodule 1
![Page 6: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/6.jpg)
6
Tumor nodule 1
![Page 7: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/7.jpg)
7
Tumor nodule 2
![Page 8: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/8.jpg)
8
Tumor nodule 2
![Page 9: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/9.jpg)
9
Tumor nodule 2
![Page 10: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/10.jpg)
CASE 1
TWO INDEPENDENT PRIMARY LUNG ADENOCARCINOMAS
TUMOR NODULE 1
Invasive adenocarcinoma, acinar pattern dominant
TUMOR NODULE 2
Invasive adenocarcinoma, lepidic pattern dominant
10
![Page 11: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/11.jpg)
11
OUTLINE
Clinical characteristics of multiple lung cancers
Morphologic and molecular approach to staging
and classification of multiple lung cancers
![Page 12: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/12.jpg)
12
SYNCHRONOUS LUNG TUMORS
0.5-2% reported incidence
Increased detection
HRCT
screening of smokers
closer follow up of patients after initial surgical
resection
![Page 13: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/13.jpg)
Clinical management of multiple lung tumor
nodules
Finley et at. JTO 2010; 5(2):197-205
![Page 14: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/14.jpg)
14 14
PATHOLOGISTS ROLE
Pathologist must identify tumors and describe them accurately (nodule number and size)
Gross and microscopic location of the various tumors in relationship to each other needs to be described
Histologic evaluation
Statement to determine whether the tumors represent synchronous primaries or intrapulmonary metastases
![Page 15: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/15.jpg)
PROBLEM 1
How to stage multiple synchronous lung carcinomas?
15
![Page 16: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/16.jpg)
16
MULTIPLE PRIMARY LUNG CANCERS
Different histology
Same histology
Anatomically separated Temporally separated (2-4 years, no systemic
metastases)
ADDITIONAL TUMOR NODULES (“SATELLITE NODULES”) Same histology Same lobe Grossly identified No systemic metastases
Modified from Martini N. et al. J Thorac Cardiovasc Surg. 1975Oct;70(4):606-12.
SYNCHRONOUS CARCINOMA STAGING
![Page 17: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/17.jpg)
17
7th AJCC TNM classification of
synchronous lung tumors
Tumor
Location
AJCC
6th Edition
AJCC
7th Edition
Same lobe T4 T3
Ipsilateral
Different lobe
M1 T4
Contralateral
lung
M1 M1a
![Page 18: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/18.jpg)
• When multiple tumors are of the same cell type, they should only be considered to be synchronous primary tumors if in the opinion of the pathologist, based on features such as associated carcinoma in situ or differences in morphology, immunohistochemistry, and or molecular studies, they represent differing subtypes of the same histopathological cell type, and…
18 AJCC 7th edition
SYNCHRONOUS CARCINOMA STAGING
![Page 19: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/19.jpg)
PROBLEM 2
Are there any molecular tests that can improve staging of synchronous lung carcinomas?
19
![Page 20: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/20.jpg)
20
Molecular approach to multiple lung
tumors
PCR clonality assays
DNA microsatellite analysis
X-chromosome inactivation analysis
DNA mutational analysis
Comprehensive aCGH, SNPs and gene
expression analysis
![Page 21: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/21.jpg)
21
DNA microsatellite analysis of synchronous
adenocarcinomas of the lung
HOMOGENOUS 70%
HETEROGENOUS 30%
Dacic S et al. AJSP 2005;29:897-902
1st tumor
2nd tumor
R=1.09
R=3.6
R=19
Normal
1st tumor
2nd tumor
![Page 22: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/22.jpg)
22
Clonality analysis and p53 mutations
Synchronous and
metachronous tumors
Adenocarcinomas
and squamous cell
carcinomas
~ 70% identical
molecular profile
Wang X et al.JNCI 2009; 101:560; Van Rens MT. et al. Cancer 2002;94:188; Shimizu S. CCR 2000:6:3994
![Page 23: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/23.jpg)
23
LIMITATIONS OF EARLY MOLECULAR STUDIES
Relatively small number of analyzed cases
Mixed analysis of synchronous and
metachronous tumors
Use of different methods and interpretation
criteria
Limited number of analyzed genes
![Page 24: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/24.jpg)
24
Genomic profiling of multiple NSCLC
Metastases
Independent primaries
Girard N. et al. Clin Cancer Res 2009; 15 (16):5184
![Page 25: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/25.jpg)
LIMITATIONS OF COMPREHENSIVE
MOLECULAR STUDIES
Relatively inadequate for clinical laboratories
Significant cost
Biostatistical support
DNA quality may affect the analysis
Performance status of different platforms may
vary between laboratories
25
![Page 26: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/26.jpg)
Can a routine molecular testing for oncogenic mutations be of any value in staging of synchronous lung carcinomas?
26
![Page 27: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/27.jpg)
CAP/AMP/IASLC guideline for molecular testing of lung adenocarcinoma
1.5 : Expert Consensus: In patients with multiple, apparently separate, primary lung adenocarcinomas, each tumor may be tested but testing of multiple different areas within a single tumor is not necessary.
27 Arch Pathol Lab Med; J Mol Diagn; J Thor Oncol ; 2013
![Page 28: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/28.jpg)
28
Tumor nodule 1 Mutant EGFR
Exon 21 Sequencing (TG transversion)
CASE 5 Molecular results
Tumor nodule 2 EGFR WILD TYPE
![Page 29: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/29.jpg)
PROBLEM 3
Is there any role of IASLC/ATS/ERS classification in the staging of synchronous lung adenocarcinoma?
29
![Page 30: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/30.jpg)
Two tumor nodules
30
TUMOR 1
TUMOR 2
![Page 31: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/31.jpg)
BACK TO HISTOLOGY
CASE 1
CASE 2
![Page 32: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/32.jpg)
Girardi N. AJSP 2009; 33: 1752.
![Page 33: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/33.jpg)
PROBLEM 4
How to stage multiple AIS, multiple MIA or AIS and MIA?
33
![Page 34: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/34.jpg)
Synchronous primary tumors are most commonly encountered when dealing with either BAC or adenocarcinoma of mixed subtype with a BAC component
34 AJCC 7th edition
![Page 35: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/35.jpg)
35
INTEGRATION OF CLINICAL, MOLECULAR
AND HISTOLOGIC DATA
Girard N. et al. AJSP 2009;33(12):1752
Martini- Melamed
Molecular assessment Histology
![Page 36: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/36.jpg)
SUMMARY
7th AJCC staging of multiple lung cancers is suboptimal and multidisciplinary approach should be adopted
Histologic assessment is important in staging of lung adenocarcinomas
Molecular approach should be further investigated in prospective studies
36
![Page 37: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/37.jpg)
37
CASE 2
69-year-old man with recurrent pleural effusions. Chest CT scan showed pleural thickening.
![Page 38: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/38.jpg)
38
![Page 39: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/39.jpg)
39
![Page 40: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/40.jpg)
40
![Page 41: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/41.jpg)
41
![Page 42: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/42.jpg)
42
![Page 43: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/43.jpg)
DIAGNOSIS
Desmoplastic mesothelioma (DM)
![Page 44: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/44.jpg)
OUTLINE
Histological criteria for diagnosis of sarcomatoid/desmoplastic mesothelioma
Ancillary studies in the diagnosis of sarcomatoid/desmoplastic mesothelioma
![Page 45: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/45.jpg)
GENERAL RULES FOR DESMOPLASTIC MESOTHELIOMA
Adequate tissue
large surgical specimens (core biopsies, pleural peel)
DM usually does not shed into the effusion fluid which may contain overlying reactive epithelioid mesothelial cells
Talk to surgeons
Review CT scans
Ignore clinical history of asbestos exposure
Do appropriate IHC
45
![Page 46: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/46.jpg)
Differential diagnosis
• Fibrous pleurisy
• Sarcoma
![Page 47: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/47.jpg)
NOT useful histologic criteria
Cellularity
Atypia (unless severe)
Mitoses (unless atypical)
![Page 48: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/48.jpg)
HISTOLOGIC CRITERIA Storiform pattern
Desmoplastic mesothelioma
Often prominent
![Page 49: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/49.jpg)
HISTOLOGIC CRITERIA Necrosis
Fibrous pleurisy Surface (if present)
Desmoplastic mesothelioma
Bland necrosis of collagenized tissue
![Page 50: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/50.jpg)
HISTOLOGIC CRITERIA Pleural thickness
Fibrous pleurisy Uniform
Desmoplastic mesothelioma Uneven, nodules
![Page 51: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/51.jpg)
HISTOLOGIC CRITERIA Zonation
Fibrous pleurisy Hypercellular at the surface
Desmoplastic mesothelioma Lack of zonation
![Page 52: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/52.jpg)
HISTOLOGIC CRITERIA Blood vessels
Fibrous pleurisy Perpendicularly oriented
Desmoplastic mesothelioma
Paucity of blood vessels, no orientation
![Page 53: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/53.jpg)
HISTOLOGIC CRITERIA Stromal invasion
Fibrous pleurisy Absent
Desmoplastic mesothelioma Present
![Page 54: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/54.jpg)
“FAKE FAT”
54 Husain et al. Arch Pathol Lab Med ; 2012 Guidelines
AE1/AE3
AE1/AE3 –fat invasion
![Page 55: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/55.jpg)
S100, laminin, collagen IV
55
FAKE FAT TRUE FAT
![Page 56: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/56.jpg)
Immunohistochemical panels in sarcomatoid mesotheliomas
Cytokeratins (AE1/3, Cam 5.2, CK7)
Focal, weak, variable
Calretinin
Usually focal in <10% of cells
D2-40
Other mesothelioma markers and adenocarcinoma
markers not helpful (WT-1, CK5/6, Ber-EP4, CEA,
MOC31)
![Page 57: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/57.jpg)
CYTOKERATIN IHC IN DM
![Page 58: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/58.jpg)
Potential IHC markers in separation between benign and malignant mesothelial proliferations
![Page 59: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/59.jpg)
59 59
Attanoos RL. et al. Histopathology. 2003;43(3):231-8
Malignant
Reactive
IMMUNOHISTOCHEMISTRY
Desmin EMA p53
10%
85% 20% 0%
80% 45%
% positive cases
![Page 60: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/60.jpg)
Diagnostic Difficulties in Interpretation of GLUT-1 IHC
Monaco et al. AJCP 2011; 135 (4):619-27.
GLUT-1
Reactive
Malignant
3%
67%
![Page 61: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/61.jpg)
IMP3 (insulin-like growth factor II messenger RNA-binding protein 3)
EMM SM
Reactive
0%
75% 100%
Shi M. et al. AJSP 2011; 33(6): 878
![Page 62: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/62.jpg)
Molecular markers in DM
62
![Page 63: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/63.jpg)
63
GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
Loss of p16 (9p21) is the most common genetic alteration in MM
Homozygous deletion, point mutation, methylation
![Page 64: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/64.jpg)
64 64
9p21 deletion and mesothelioma histology
0
20
40
60
80
100
Epithelioid Biphasic Sarcomatoid
%
![Page 65: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/65.jpg)
65 65
FISH FOR 9p21 (p16) DELETION
Ilei et al. Cancer Cytopath 2003; 99(1):; Chiosea et al. Mod Pathol 2008 Jun;21(6):742-7. Husain et al. Arch Pathol Lab Med ; 2012 Guidelines
Deleted
Deleted Not deleted
p16
CEP9
![Page 66: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/66.jpg)
SUMMARY
Diagnosis of mesothelioma requires correlation between morphology, imaging studies and intraoperative findings
Interpretation of IHC in DM is challenging
No IHC markers are reliable in separation between benign and malignant mesothelial proliferations
FISH for p16 deletion is a promising diagnostic assay
66
![Page 67: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/67.jpg)
MAML2 translocation and prognosis
Behboudi A, et al. Genes, Chromosomes and Cancer 2006; 45:470-81.
![Page 68: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/68.jpg)
SUMMARY
Diagnosis of lung tumors is mostly based on a routine H&E
Limited specificity and sensitivity of molecular changes in lung carcinomas precludes development of molecular assays for diagnostic purposes
Active research for markers for early detection of lung carcinomas, detection of lymph node metastases and molecular staging is in progress
![Page 69: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/69.jpg)
CASE 3
• 54-year-old male with a history of stage I pancreatic carcinoma, status post Whipple resection and a solitary lung nodule.
![Page 70: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/70.jpg)
![Page 71: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/71.jpg)
![Page 72: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/72.jpg)
![Page 73: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/73.jpg)
![Page 74: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/74.jpg)
![Page 75: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/75.jpg)
![Page 76: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/76.jpg)
Survival
![Page 77: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/77.jpg)
Immunohistochemical staining patterns in
tumors with mucinous features
Pancreatic
Metastases
(% positive)
Lung Primaries
(% positive)
P value
CK20 17/26 (65%) 5/18 (28%) .03
CDX2 17/27 (63%) 1/18 (6%) .0001
MUC2 4/24 (17%) 1/10 (10%) NS
TTF-1 1/26 (4%) 16/21 (76%) .0001
Napsin A 0/25 (0%) 3/9 (33%) .014
SMAD4 loss
(%loss)
10/27 (37%) 8/28 (28%) .NS
![Page 78: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/78.jpg)
KRAS MUTATIONS
TRANSVERSION MUTATIONS
-substituting a pyrimidine for a purine,
or purine for a pyrimidine
TRANSITION MUTATIONS
-substituting a purine for a purine, or a
pyrimidine for a pyrimidine
![Page 79: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/79.jpg)
KRAS mutation type and smoking history
MUTATIONS NUCLEOTIDE FORMER/CURRENT SMOKER
NEVER SMOKER
G12A GGT GCT 13 0
G12C GGT TGT 38 0
G12V GGT GTT 20 1
G13C GGC TGC 2 0
G13D GGC GAC 1 0
G12D GGT GAT 15 10
G12S GGT AGT 1 1
TOTAL - 90 12
Modified from
![Page 80: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/80.jpg)
KRAS mutations in pancreatic carcinoma
G12D
G12V
G12C
G12R
Other
![Page 81: Case based applications part IIIlasop.com/pgs/hdouts/2014-01-Dacic_Case presentations.pdf1 Case –based applications – part III Los Angeles Society Of Pathologists January 25, 2014](https://reader033.fdocuments.us/reader033/viewer/2022041813/5e5935397ce18c4f666b4181/html5/thumbnails/81.jpg)
PANCREATIC VS. LUNG ADC
Sensitivity Specificity PPV NPV
Mucious PDAC
Mets
KRAS mutation 80% 54% 53% 81%
CK20 + 65% 72% 77% 59%
CDX2 + 63% 94% 94% 63%
Mucinous Lung
Primaries
KRAS G12C 39% 95% 88% 62%
TTF-1 + 76% 96% 94% 83%
NapsinA + 33% 100% 100% 81%
KRAS Mutated
Lung Primaries
KRAS G12C 44% 96% 96% 41%
KRAS Mutated
PDAC
KRAS G12R 15% 99% 86% 74%