Thyroid MDS Dr Dass

M.D.S. on Thyroid : Role of Fine Needle Aspiration (FNA) Cytology in Diagnosis of Thyroid Cancer Dilip K. Das, MBBS, MD, PhD, DSc, FRCPath. Department of Pathology, Faculty of Medicine, Kuwait University. Fine Needle Aspiration (FNA) Cytology of Thyroid Nodules • FNA of thyroid is a simple, safe, inexpensive, and minimally invasive procedure without appreciable complications for the diagnosis of thyroid lesions. It is readily accepted by patients including children and can be repeated when necessary. It is an efficient tool for the diagnosis of thyroid nodules, both neoplastic and non-neoplastic. FAN cytology has the highest sensitivity, specificity, and diagnostic accuracy of all preoperative diagnostic evaluation methods. FNA cytology helps in planning of treatment, medical or surgical. • • • • Main Indications for FNA of Thyroid 1. 2. 3. 4. The diagnosis of the solitary or dominant thyroid nodule. The diagnosis of diffuse non-toxic goiters (Colloid goiters). Confirmation of a clinically obvious thyroid malignancy. To obtain material for ancillary investigations to to confirm the cytodiagnosis or define prognostic parameters: Immunocytochemistry, DNA ploidy, cell block preparation, electron microscopy, nuclear morphometry, and molecular biology. FNA Cytodiagnosis of Thyroid Lesions: Experience at Mubarak Al-Kabeer Hospital, Kuwait (1998-2002) FNA cytodiagnosis Colloid goiter Hyperplastic nodule Neoplastic goiter Inflammatory goiter Benign thyroid cells Miscellaneous lesions Inadequate Total No of cases 2066 179 185 688 152 32 229 3531 Percentage 58.5 5.1 5.2 19.5 4.3 0.9 6.5 Frequency of Major Thyroid Lesions: Diagnosis by FNA at Mubarak Al-Kabeer Hospital, Kuwait (1998-2002) FNA cytodiagnosis Colloid goiter 1998 61.7% 1999 61.6% 2000 58.7% 2001 2002 Total 57.5% 53.1% 58.5% Hyperplastic nodule Inflammatory goiter 3.9% 18.5% 5.5% 18.0% 4.3% 21.6% 5.3% 6.2% 5.1% 18.7% 20.7% 19.5% Nepolastic goiter 3.8% Total No of cases 713 5.1% 744 6.1% 675 5.4% 670 5.9% 729 5.2% 3531 FNA Cytologic Features of Nodular Colloid Goiter • Abundant colloid, thick and thin. • A small to moderate number of follicular epithelial cells in cohesive monolayered sheets and poorly cohesive groups, many bare nuclei. • Coexistence of involutional and hyperplastic cells. • Foamy and phagocytosing cells (cyst cells). • Old blood, cell debris, and cholesterol crystals. Nodular Colloid Goiter Common Thyroid Neoplasms and Frequency of Thyroid Cancers Benign: Adenomas (Follicular adenoma). Malignant: Carcinomas: 1. Papillary carcinoma (75% to 85% cases) 2. Follicular carcinoma (10% to 20% cases) 3. Medullary carcinoma (5% cases) 4. Anaplastic carcinoma(< 5% cases) Lymphomas Common Neoplasms of Thyroid Diagnosed by FNA Cytology • • • • • Papillary thyroid carcinoma (PTC). Follicular thyroid neoplasm (FTC). Medullary Thyroid carcinoma (MTC). Anaplastic carcinoma. Lymphoma. Classification of Thyroid Neoplasms Diagnosed by Fine Needle Aspiration FNA cytodiagnosis Mubarak Al-Kabeer Hospital, Kuwait (1998-02) No of case Follicular neoplasm Papillary carcinoma Hurthle cell neoplasm 39 119 14 % 21.1 64.3 7.6 Medullary carcinoma Misc. malignancies Total 10 3 185 5.4 1.6 Papillary Thyroid Carcinoma: FNA Cytologic Features 1. 2. 3. 4. Papillary (finger-like) tissue fragments with or without a fibrovascular core. Irregular shaped or tubular neoplastic follicles. Monolayer sheets: flat sheets of cells with a distinct ‘anatomical border’. Enlarged, ovoid, pale nuclei, finely granular, powdery chromatin, and multiple distinct nucleoli. Intranuclear cytoplasmic inclusions. Nuclear grooves Dense cytoplasm with distinct cell borders. Scanty, viscous, stringy colloid (‘chewing gum colloid’ ). Psammoma bodies: calcification in the form of concentric lamellation. Pale and dark cerebriform nuclei. 5. 6. 7. 8. 9. 10. Papillary Thyroid Carcinoma: FNA Cytology and Histology FNA Cytology of Papillary Thyroid Carcinoma Problems in Diagnosis of Papillary Thyroid Carcinoma 1. Cystic change. 2. Lymphocytic infiltration. 3. Mixed pattern of growth: follicular and papillary. 4. Oxyphilic change. Survival in Papillary Thyroid Carcinoma Patients Survival in Percentage 5-year 10-year 88.0 94.4 91.4 15-year 20-year 30-year 83.0 88.7 82.0 100.0 87.9 84.0 78.0 Esic et al (1996) Pelizzo et al (1997) Zidan et al (2003) Chow et al (2003) Gyory et al (2004) Investigators Follicular Neoplasm: FNA Cytologic Features: 1. Cellular, often bloody smears. Many equal-sized epithelial clusters or syncytial cell aggregates, scattered throughout the smear. Micro-follicles and rosettes. Nuclear crowding and overlapping. Scanty or no colloid. 2. 3. 4. 5. Problems in Diagnosis of Follicular Neoplasm by Cytology 1. Follicular adenoma vs. follicular carcinoma: The cytological appearances of follicular adenoma and follicular carcinoma are similar. Therefore the term follicular neoplasm is used for both the lesions. The proportion of carcinoma in lesions designated as follicular neoplasm ranges from 14% to 40%. Nodular goiter (Hyperplastic nodules). Papillary carcinoma (Follicular variant). Parathyroid adenoma. Vascularity and cystic changes. 2. 3. 4. 5. Follicular Adenoma: Cytology and Histology Follicular Carcinoma: Cytology and Histology Hyperplastic Nodule: FNA Cytologic Features Papillary Thyroid Carcinoma: Follicular Variant Follicular Variant (FV) of Papillary Thyroid Carcinoma (PTC) • Predominance of follicular architecture but optically clear nuclei of PTC with nuclear grooves and intranuclear inclusions. • Unencapsulated and infiltrative. • Easily confused with follicular adenoma and carcinoma but has prognosis similar to that of a typical papillary carcinoma (Galera-Davidson and Gonzalez- Campora, 1997). Before recognition of this entity, it was classified among true follicular carcinoma, which is clinically and biologically different. Hurthle Cell Neoplasm: FNA Cytologic Features • Highly cellular smears with little or no colloid. • Monomorphic population of Hurthle cells. • Little cohesiveness: dispersed or loose monolayered sheets. • Intracytoplasmic lumina. • Prominent vascularity. Hurthle cells: • Polygonal, large, and more or less uniform cells. • Large eccentric nuclei, either single or double, and some times pleomorphic. • Granular eosinophilic cytoplasm. • Well-defined cytoplasmic margin. • Prominent nucleoli in Pap stained smears. Hurthle Cell Neoplasm: Cytologic Features Medullary Thyroid Carcinoma: FNA Cytologic Features 1. 2. 3. 4. 5. 6. Cellular smears, mainly dispersed cells, some syncytial aggregates. Plasmacytoid, small round to oval or spindle cells. A few large, bi- and multinucleated forms. (rare INCI). A variable number of cells with cytoplasmic granularity (MGG), cytoplasmic dendritic processes and intracytoplasmic lumina. Fragments of amorphous pink/violet background material (amyloid). Positive staining for calcitonin and chromogranin. Medullary Thyroid Carcinoma: Cytologic and Immunocytologic Features CT Chr. Gr. Medullary Thyroid Carcinoma: Cytologic and Immunocytologic Features CT Chr. Gr Ck Anaplastic Carcinoma of Thyroid: FNA Cytologic Features 1. 2. 3. Bizarre, large malignant cells either epithelial or spindle (sarcomatoid) type, or rarely small cell type. Marked nuclear pleomorphism, multinucleation, mitotic figures. Necrotic fragments, cell debris and sometimes acute inflammatory background. Anaplastic Large Cell Carcinoma of Thyroid Number of Thyroid Neoplasms: Diagnosed by FNAC at Mubarak Al-Kabeer Hospital, Kuwait (1998-2002) FNA cytodiagnosis Follicular neoplasm No of cases 39 1998 9 1999 8 2000 11 2001 6 2002 5 Papillary carcinoma 119 14 2 2 0 27 23 4 2 1 38 22 4 2 2 41 25 2 3 0 36 35 2 1 0 43 Hurthle cell neoplasm 14 Medullary carcinoma Misc. malignancies Total 10 3 185 Impact of FNA Cytology on Thyroid Surgery and Yield of Cancer Author (Year) Patient undergoing thyroid surgery (%) Prior to FNAB Miller et al. (1981) Hamberger et al. (1982) Yield of thyroid cancer (%) Prior to FNAB 12 14 After FNAB 24 43 Decre ased by 24 24 After FNAB 14 29 Increas ed by 2 15 48 67 Ng et al. (1990) Caplan et al. (1991) 95 61 60 33 35 (p<.001) 18.4 18 26.2 39 7.8 21 28 Garcia Mayer et al. (1997) 67.8 46.3 21.5 24.4 32.9 8.5 (p< .05) Efficacy of FNA Cytology in the Diagnosis of Thyroid Nodules • Average value of sensitivity, specificity and diagnostic accuracy based on review of large number of studies: 85.2%, 95.6%, and 94.4% respectively (Bisi et al, 1992); 80.1%, 89.0%, and 88.4% respectively (Das et al, 2001). • Review: Impact of FNA cytology on surgery: Due to FNA cytology reduction of surgery ranged from 21.5% to 33% (average 26.3%) and yield of cancer increased by 2% to 33% (average 16.3%). FNA Cytologic Features of Autoimmune (Hashimoto’s) Thyroiditis • Oxyphilic epithelial (Askanazy) cells. • Hyperplastic follicular cells. • Moderate to abundant lymphoid cells including immunoblasts and plasma cells, and lymphohistiocytic aggregates. • Small multinucleate giant cells, epithelioid histiocytes. • Scanty or no colloid. FNA Cytologic Features of Hashimoto’s Thyroiditis Problems in FNA Cytodiagnosis of Hashimoto’s Thyroiditis • Distinguishing bare nuclei from lymphocytes. • Lymphocytic infiltration in other lesions, e.g. Papillary thyroid carcinoma. • Hashitoxicosis. • Lymphoma. • Oxyphilic cells. NHL Thyroid: Cytology and Histology Thank You RET/PTC Oncogene Rearrangement in Papillary Thyroid Carcinoma Author (Year) Grieco et al (1990)* Namba et al (1991) Viglietto et al (1995) No of cases 20 22 26** RET over all 5 (25.0%) 0 (0.0%) 11 (42.3%) RET/ PTC1 - RET/ PTC2 - RET/ PTC3 - Learoyd et al (1998) Mayr et al (1999) Fenton et al (2000) 50 99 33 4 (8.0%) 8 (8.1%) 15 (45.5%) 4 7 8+3 2+3 1 2 Kjellman et al (2001) Cheung et al (2001) Basolo et al (2001) 61 33 (FNA) 127 29 (47.5%) 17 (51.5%) 82 (64.6%) 1 - - 2 - Lam et al (2002) * Detected a 20 17 (85.0%) - - 17 novel activated oncogene by transfection analysis and designated it transforming gene PTC (papillary thyroid carcinoma). ** Occult PTC Role of Ionizing Radiation in RET Proto-oncogene Rearrangement in Papillary Thyroid Cancer Authors (Year) Exposure to radiation No of cases RET/ PTC No exposure to radiation No of cases RET/ PTC Thomas et al (1999) Rabes et al (2000) Takahashi et al (2003) Bounacer et al (1997) Smida et al (1999) 67 191 50 19 16 A+ 51 Ch 55.2% 62.3% 92.0% 84.2% 69% A+ 49% Ch 20 16 15.0% 19.0% Collins et al (2002) 30 86.7% 34 52.9% BRAF (V599E) Mutation in Papillary Thyroid Carcinoma Authors (Year) Percentage of thyroid lesions positive for BRAF PTC FTC MTC PD Ca Ana Ca FA Col Gtr Kimura et al (2003) 35.8 0.0 - - - - - Cohen et al (2003) Xu et al (2003) Nikiforova et al (2003) Soares et el (2003) Trovisco et al (2004) 69.0 38.0 38.0 46.0 36.0 0.0 0.0 - 0.0 - 13.0 - 10.0 - 0.0 0.0 - 0.0 0.0 - Xing et al (2004) Puxeddu et al (2004) 45.0 40.0 0.0 0.0 0.0 - - 20.0 0.0 0.0 0.0 0.0 - RET Rearrangement, BRAF Mutation , and RAS Mutation in Papillary Thyroid Carcinoma Authors (Year) Fukushima et al (2003) Soares et al (2003) Puxeddu et al (2004) BRAF 53.0% 46.0% 40.0% RET 15.0% RAS 6.0% 7.0% - Frattini et al (2004) 32.0% 33.0% 0.0% Epidemiology of Thyroid Cancer in Kuwait • Benign (hyperplastic) thyroid disease (OR= 6.4; 95% CI: 3.4-12.0 ) and habitual high consumption of various processed sea foods (OR= 2.2; 95% CI: 1.6-3.0) may be relevant to the etiology of thyroid cancer. Family history of benign thyroid disease (mother, sister, and aunt) is associated with increased risk of thyroid cancer (OR 2.1-2.6). Family history of thyroid cancer is also associated with increased risk (OR=3.0; 95% CI:0.8-11.1). Women having last pregnancy at age ≥30 years (OR= 2.1; 95% C.I: 1.2-3.8) and history of post partum thyroiditis (OR= 10.2; CI: 2.3-44.8) had a significantly high risk for thyroid cancer. Memon et al Br J Cancer 2002; 86: 1745-1750, Eur J Cancer 2004; 40: 754-760, Int J Cancer 2002; 97: 82-89. • • • • THANK YOU