Capsule of thyroid nodule

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1 of thyroid nodule of Follicular Cell Tumors, its Significance and Morphology RYOHEI KATOH, TADAO NAKAZAWA, AND TETSUO KONDO DEPARTMENT OF HUMAN PATHOLOGY UNIVERSITY OF YAMANASHI, JAPAN NODULAR GOITER FOLLICULAR ADENOMA FOLLICULAR CARCINOMA PAPILLARY CARCINOMA POORLY DIFFERENTIATED CARCINOMA MEDULLARY CARCINOMA OTHERS CAPSULE OF THYROID NODULE CAPSULE IN PAPILLARY THYROID CARCINOMA Nodular goiter NON-ENCAPSULATED TYPE ENCAPSULATED TYPE CYSTIC TYPE Follicular adenoma/carcinoma MACROSCOPIC TYPES OF PAPILLARY THYROID CARCINOMAS DIAGNOSIS OF FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA Encapsulated type 6% CLASSICAL TYPE Partly encapsulated type Non-encapsulated type Cystic type 11% 75% 7% (150 PTCs with classical histology) PAPILLARY THYROID CARCINOMA Liu J, et al. Cancer 2006;107: FOLLICULAR VARIANT NON-ENCAPSULATED TYPE ENCAPSULATED TYPE PROBLEMATIC ISSUE

2 ENCAPSULATE FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA s with a small number of PTC nuclei and/or questinable PTC nuclei often diagnosed High as observer Encapsulated variation follicular variant of PTC WITH EFV-PTC FTC MALIGNANT WITHOUT WDT-IMP WELL-DIFFERENTIATED TUMOUR OF INDETERMINATED MALIGNANT POTENTIAL Williams ED Int J Surg Pathol 2000, 8: This tumor should be treated as BENIGN. FOLLICULAR ADENOMA/CARCINOMA FOLLICULAR ADENOMA/CARCINOMA ADENOMA CARCINOMA A BENIGN ENCAPSULATED TUMOUR OF THE THYROID SHOWING EVIDENCE OF FOLLICULAR CELL DIFFERENTIATION A MALIGNANT EPITHELIAL TUMOUR SHOWING EVIDENCE OF FOLLICULAR CELL DIFFERENTIATION AND LACKING THE DIAGNOSTIC NUCLEAR FEATURE OF PAPILLARY CARCINOMA. Diagnostic algorithm of follicle forming thyroid nodule PERHAPS THE MOST DIFFICULT PROBLEM IN THYROID PATHOLOGY IS THE DISTINCTION OF FOLLICULAR CARCINOMA FROM FOLLICULAR ADENOMA AND FROM THE FOLLICULAR VARIANT OF PAPILLARY CARCINOMA. Evans HL. Cancer 54: , 1984 thyroid nodule Poorly diff. carcinoma Follicular carcinoma Papillary carcinoma cell nuclei + Papillary carcinoma Hyalinizing trabecular tumour Nodular goiter Follicular a./c. Poorly diff. carcinoma Solid, trabecular, insular pattern, necrosis, mitosis Follicular c. Poorly diff. c. Invasion + - Follicular a. Nodular goiter

3 I My PROCEDURE S Cover glass 24mm Capsular invasion Vascular invasion Longitudinal sections Nodule <= 2cm Most of sections should include the tumour capsule and adjacent throid tissue, if present Entire nodule Nodule > 2cm 10 sections + Additional sections nodulectomy, lobectomy, subtotal/total thyroidectomy Patterns of Capsular Invasion (CI) 1. CAPSULAR (CI) True CI Insufficient CI True CI True CI Insufficient CI Capsular invasion is defined by tumour penetration through the tumour capsule unassociaqted with the site of a previous fine needle aspiration biopsy. (WHO 2004) Patterns of Capsular Invasion (CI) penetration through the tumour capsule Patterns of Capsular Pseudoinvasion (CPI)

WHAFFT Worrisome histologic alterations following FNA of the thyroid. LiVolsi VA, Merino MJ. Lab Invest 62, 1990 2.

4 WHAFFT Worrisome histologic alterations following FNA of the thyroid. LiVolsi VA, Merino MJ. Lab Invest 62, VASCULAR (VI) Hemorrhage and hemosiderin Focal and geographic pattern of lesion Patterns of Vascular Invasion (VI) Patterns of Vascular Invasion (VI) Artifactuallydislodged tumour cell (or tissue) Pseudo VI Capsular invasion is defined by the presence of intravascular tumourcells either covered by endothelium or associated with thrombus. (WHO 2004) Capsular invasion is defined by the presence of intravascular tumourcells either covered by endothelium or associated with thrombus. (WHO 2004) Patterns of Pseudovascular Invasion (VI) DIAGNOSIS OF FOLLICULAR CARCINOMA Pseudo VI Follicular tumours Artifactually dislodged tumour cells (or tissue) showing definite invasion showing questionable invasion PTC nuclei (-) Follicular tumors of uncertain malignant potential (FT-UMP) PTC nuclei (questionable) Well differentiated tumour of uncertain malignant potential (WDT-UMP) Williams ED Int J Surg Pathol 2000, 8:

IMMUNOHISTOCHEMICAL DEMONSTRATION OF LYMPHATIC AND BLOOD VESSELS IMMUNOHISTOCHEMISTRY Vascular Markers Factor VIII Laminin CD31 or CD34 Type IV collagen Ulex europaeus lectin Elastic tissue stains :

D2-40 Lymphaic and blood vessel density in the follicular patterned lesions of thyroid DISTRIBUTION OF LYMPHATIC VESSELS IN ENCAPSULATED FOLLICULAR TUMORS Intratumoral region Follicular variant Of

5 IMMUNOHISTOCHEMICAL DEMONSTRATION OF LYMPHATIC AND BLOOD VESSELS IMMUNOHISTOCHEMISTRY Vascular Markers Factor VIII Laminin CD31 or CD34 Type IV collagen Ulex europaeus lectin Elastic tissue stains : only limited use in identifying intracapsular vessels CD34 CD34 FLT4 IMMUNOHISTOCHEMISTRY Lymphatic Markers Live-1 D2-40 DISTRIBUTION OF LYMPHATIC AND BLOOD VESSELS IN THE FOLLICULAR THYROID TUMOURS D2-40 Lymphaic and blood vessel density in the follicular patterned lesions of thyroid DISTRIBUTION OF LYMPHATIC VESSELS IN ENCAPSULATED FOLLICULAR TUMORS Intratumoral region Follicular variant Of PTC Follicular adenoma Intratumoral lymphatic vessel density D2-40 staining Lymphatic vessels Peritumoral region Intratumoral lymphatic vessel density was significantly higher in the follicular variant of PTC than in either follicular adenoma or follicular carcinoma. Giogrgadeze TA, et al. Mod Pathol (2005) 18: Normal Intracapsular lymphatic vessels: scant or none

6 DISTRIBUTION OF BLOOD VESSELS IN ENCAPSULATED FOLLICULAR TUMORS DISTRIBUTION OF LYMPHATIC AND BLOOD VESSELS CD34 staining Blood vessels CD34 staining for blood vessels ( ) + D2-40 staining for lymphatic vessels ( ) Capillaries Minimally invasive follicular carcinoma (Encapsulated follicular carcinoma) with vascular and capsular invasions Intratumoral vessels Intrapsular vessels Peritumoral vessels s tend to give rise to hematogenous spread and do not usually show lymphatic spread possibly due to lymphatic and blood vessel distributions. THICKNESS OF TUMOR CAPSULE CAPSULE THICKNESS Follicular adenomas (20 s) Minimally invasive follicular thyroid carcinomas (48 s) thickness The capsule of follicular carcinoma tends to be thicker and more irregular than that of adenoma. Evans, H.L. Cancer 54: , 1984 Yamashina M. Am J Surg Pathol 1992, 16: Follicular adenoma thickness (µm) mean 174 SD The follicular carcinoma tends to be surrounded by a wide thick capsule. SUBTYPES OF FTC AND RECURRENCE AND/OR METASTASIS NO. OF VASCULAR IN SUBTYPES OF FTC Without recurrence and/or distant With recurrence and/or distant No. vascular invasion More than 4 25% % 0 31% No. vascular invasion More than 4 79% Widely invasive FTC Inc. poorly Widely invasive FTC (INC. POORLY) s with recurrence and/or distant vascular invasion Widely invasive FTC (23%) 11 (79%) Widely invasive FTC : capsular invasion alone

7 NO. OF VASCULAR AND RECURRENCE AND/OR METASTASIS IN MINIMALLY INVASIVE FTC SIGNIFICANCE OF vascular invasion (VI) VI< 4 VI>= 4 64% With recurrence and/or Without 19% Encapsulated Widely invasive With capsular invasion only With limited (<4) vascular invasion With extensive (>=4) vascular invasion Rosai J. Surgical Pathology, 9 th ed vascular invasion 0 1 2, Without With There is a prognostic difference depending on the number of vessels involved. STI PATTERN IN MINIMALLY INVASIVE FTC DISTANT METASTASIS IN MINIMALLY INVASIVE FTC size Gender Not significant for thickness The capsule of MI-FTC is thicker than that of adenoma STI Absent Present Solid Trabecular Insular 18% 33% STI pattern With Absent 33 6 (18%) With Capsular invasion Not significant for Vascular invasion Number of VI could be important With extensive (>=4) vascular invasion Solid, Trabecular, and Insular patterns Possible significant marker Present 15 5 (33%)