Follicular Derived Thyroid Tumors

Transcription

1 Follicular Derived Thyroid Tumors Jennifer L. Hunt, MD, MEd Aubrey J. Hough Jr, MD, Endowed Professor of Pathology Chair of Pathology and Laboratory Medicine University of Arkansas for Medical Sciences 1

2 Dissecting Indeterminate Benign vs. Malignant Follicular variant of PTC NIFT-P Follicular carcinoma In pursuit of the low grade malignancy 2

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4 Follicular Variant of Papillary Chen KTK, Rosai J. Follicular variant of thyroid papillary carcinoma: A clinicopathologic study of six cases. American Journal of Surgical Pathology, 1(2):123, Juan Rosai 4

5 Follicular Variant Histology: Definition Pure follicular architecture Papillary carcinoma nuclei Growth Pattern Invasive and infiltrative Encapsulated 5

6 Invasive follicular variant PTC

7 Encapsulated follicular variant PTC

8 Encapsulated Follicular Variant Low power clues Nuclear atypia at 4X Clustered nuclear atypia Nuclear features better under capsule Peri-follicular fibrosis Dense colloid 8

9 Follicular variant PTC

10 Follicular variant PTC

11 Encapsulated Follicular Variant High power clues: Nuclear atypia Flattened, pushed in, irregular nuclear contours Peripheral condensed chromatin Small peripheral nucleoli 11

12 Follicular variant PTC

13 Encapsulated Follicular Variant Borderline nuclear atypia: not perfect FVPTC Patchy nuclear atypia: Good nuclei, but very non-uniform distribution 13

14 Follicular variant PTC

15 Patchy features

16 Patchy features

17 The Problem Most of these tumors behave well.but Some have nodal metastases Rare cases have distant metastases In pursuit of the low grade malignancy 17

18 Attempts to Resolve Ancillary tests to refine diagnosis Special stains Molecular markers Changing terminology Changing practice patterns 18

19 Immunohistochemistry Stains might be useful, when. Nuclear features are incomplete Nuclear features are only patchy Stains are not diagnostic, they are only supportive 19

20 Immunohistochemical Stains 100% 90% 80% 70% 60% 50% 40% 30% CK19 HBME 1 Galectin 3 CD 56 20% 10% 0% Follicular adenoma Follicular carcinoma Hurthle cell carcinoma Papillary carcinoma Dunderovic, Diagnositc Pathology 10:196;

21 Immunohistochemical Stains 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Classic PTC FVPTC Follicular adenoma CK19 HBME1 Galectin 3 HBME/CK19 Scognamiglio T, AJCP, 126:700,

22 Incomplete and patchy nuclear features

23 CK19 HBME 23

24 Molecular Mutations in Thyroid Cancer Papillary carcinoma BRAF gene mutations RET/PTC translocations RAS mutations Follicular carcinomas RAS mutations PPARγ/PAX8 translocations 24

25 BRAF Mutations in Thyroid Lesions 25

26 RAS Gene Mutations 100% 80% 60% 40% 20% 0% FVPTC Conv PTC FA FCC 26

27 Reported Molecular Profiles Category Name RAS BRAF RET/ PTC PAX8/ PPAR Conventional Papillary Ca 10-20% 50-75% ~30% 0 Follicular carcinoma ~30-50% 0 0 ~30-35% Follicular Adenoma ~30% 0 0 ~5-10% Follicular Variant PTC ~25% ~5% ~5% ~35% 27

28 Commercial Assays Gene expression array testing Mutation panel approach 28

29 <1% risk 5-10% risk 20-30% risk 50-75% risk Thyroid Fine Needle Aspiration Benign Molecular Result Suspicious Molecular Result 7% risk 47% risk

30 The Real Question Will the results of the molecular test change treatment? Will some patients be spared unnecessary surgery? Will some patients be given more extensive (appropriate) surgery? Will there be overall cost savings? 30

31 Attempts to Resolve Improving diagnosis Special stains Molecular markers Changing terminology Changing practice patterns 31

32 Chernobyl Classification FVPTC Category Name Atypical Nuclei Invasion Follicular Adenoma X X Follicular carcinoma X Yes Well differentiated carcinoma, NOS Questionable Yes Well differentiated tumor of UMP Questionable X Follicular tumor of UMP X Questionable For consensus classification, not for diagnostic and clinical utility Williams ED, Int J Surg Pathol 2000;8:

33 New Proposed Terminology Non-invasive follicular thyroid neoplasm with papillary-like nuclear features 24 pathologists 109 thyroids Retrospective analysis with years followup NIkiforov, JAMA Oncology 2(8):1023,

34 NIFT-P Criteria Follicular growth pattern (<1% papillae) No psammoma bodies Encapsulation or clear demarcation Nuclear score 2-3 No vascular or capsular invasion No tumor necrosis <30% solid, trabecular, insular growth Low mitotic activity (<3 /10 HPF) 34

35 Abortive papillae

36 Implications of NIFT-P A very low risk of adverse outcome when the tumor is non-invasive 36

37 My 2 Cents I infrequently use NIFT-P, because Some lesions have papillae Some lesions have some invasion or are suspicious for invasion Some lesions have increased mitoses or nuclear atypia My most common use: lesions I used to call adenoma, after worrying about atypia 37

38 Dissecting Indeterminate Benign vs. Malignant Follicular variant of PTC NIFT-P Follicular carcinoma In pursuit of the low grade malignancy 38

39 39 Thin capsule Intermediate capsule Thick capsule

40 Follicular carcinoma, NOS Minimally Invasive Widely Invasive Minimally Invasive Encapsulated Angio-invasive

41 Follicular carcinoma Widely invasive Multifocal invasion throughout thyroid Invasion outside of the thyroid 41

42 Mortality in Follicular Tumors Capsular invasion Vascular invasion Widely invasive Measured Van Heerden (1992) D Avanzo (2004) 0% 28% N/A Disease specific mortality 2% 20% 62% 5-year mortality Van Heerden, Surgery 112:1130, 1992 D Avanzo, Cancer 100:1123,

43 Minimally Invasive Follicular carcinoma By definition: Capsular invasion Invasion through the capsule Usually with a mushroom type appearance 43

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45 Capsular Invasion

46 Capsular Invasion

47 Avoid FNA track areas

48 Angio-Invasive Follicular carcinoma By definition: Vascular invasion At or beyond level of tumor capsule Medium to large sized vessels Usually tumor is attached to vessel wall Tumor has reaction around it Endothelialization Fibrin deposition Capsular invasion may be present 48

49 Vascular Invasion Vascular Invasion

50 Vascular Invasion 50

51 Vascular Invasion

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53 Capsular Vessels make right angle turns

54 Vascular invasion

55 Vascular invasion

56 Vascular invasion

57 ATA Risk Stratification Low Risk Intermediate Risk High Risk Papillary carcinoma & FVPTC No metastases No vascular invasion No extrathyroidal extension No aggressive variants Papillary carcinoma N1 disease Vascular invasion Extrathyroidal spread Variants: tall, columnar, hobnail Multifocal microscopic Distant mets Large lymph node mets Grossly identified extrathyroidal extension Minimally invasive follicular and angioinvasive follicular carcinoma (with <4 foci vascular invasion Follicular carcinoma with >4 foci vascular invasion 57

58 Changing Practice Patterns Very Low Risk Low Risk Intermediate Risk Papillary carcinoma Unifocal microscopic papillary carcinoma Encapsulated FVPTC (NIFT-P) Papillary carcinoma No metastases No vascular invasion No extrathyroidal extension No aggressive variants Papillary carcinoma N1 disease Vascular invasion Extrathyroidal spread Variants: tall, columnar, hobnail Multifocal microscopic Minimally invasive follicular carcinoma (capsular invasion alone) Angio-invasive follicular carcinoma (with <4 foci vascular invasion 58

59 Summary Follicular variant Non-invasive follicular neoplasm with papillary like nuclear features (NIFT-P) Follicular carcinoma 59