THYROID PATHOLOGY ELLEN GREENEBAUM, MD MPH ASSOCIATE PROFESSOR OF CLINICAL PATHOLOGY P&S 77 Phone:

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1 THYROID PATHOLOGY ELLEN GREENEBAUM, MD MPH ASSOCIATE PROFESSOR OF CLINICAL PATHOLOGY P&S 77 Phone:

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9 DEFINIT TIONS GOITER: enlarged thyroid EUTHYROID: normal thyroid function NONTOXIC: thyroid not hyperfunctional TOXIC: hyperfunctio onal thyroid

10 GRAVES DISEASE DIFFUSE TOXIC GOITER MOST COMMON CAUSE OF GROSS: HYPERTHY YROIDISM DIFFUSELY ENLARGED UP TO 3-4X NORMAL (normal 10-35gm) SURGERY RARE

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13 GRAVES DISEASE MICROSCOPIC: Hyperplasia of follicular lining cells New follicles formed; tall, columnar cells Scalloping of colloid Lymphoid cell infilt tratest?source of abnormal autoantibodies

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15 HASHIMOTO S S THYROIDITIS May be found incidentally visible neck mass compressing trachea or esophagus GROSS: Usually enlarged up to 2-3X Usually symmetrical, diffuse & firm if nodular, suspect neo oplasm Light tan or gray L-thyroxine therapy may shrink gland

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17 HASHIMOTO SS THYROIDITIS Lymphocytic thyroiditis with oxyphilia MICROSCOPIC: LYMPHOCYTES & HURTHLE CELLS = Oxyphilic cells Abundant pink cytoplasm pink = acidophilic = Electron Microscopy numerous mitochondria plasma cells eosinophilic

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19 NONTOXIC NOD DULAR GOITER Common: NTNG 4-7% adults in US have palpable nodular goiter usually asymptomatic but most are MULTINODULAR may have only one palpable nodule clinical concern to ru le out neoplasm do ultrasound to detect other nodules do needle aspirate or may cause compression core bx to diagnose NTNG

20 NONTOXIC NOD DULAR GOITER NTNG GROSS: >1 round, well demarcated, tan glistening i nodu ules of variable sizes within nor rmal red-brown bo thyroid tissue.

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23 NONTOXIC NOD DULAR GOITER MICROSCOPIC: Follicles F l NTNG VARYING SIZE ES, usually large filled with COLLOID lined by cuboidal cells Zones of FIBROS SIS & HEMORRHAGE

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26 THYROID N EOPLASMS BENIGN: ADENOMA GROSS: Nodule well encapsulated solid deep-ta an

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30 THYROID N EOPLASMS How to distinguis ish Follicular l ADENOMA from CARCINOMA? Search for invasion of capsule or blood vessels Examine entire nodule, especially capsule

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32 THYROID CA ARCINOMA PAPILLARY: 70-80% 2. FOLLICULAR: 10-20% 3. MEDULLARY: 5% 4. ANAPLASTIC: 1-3% % % Papillary Follicular Medullary 1 Undiff. 0

33 PAPILLARY CARCINOMA 70-80% of thyroid carcinomas GROSS: most often solitary BUT... MICRO: mostoftenoften multifocal if opposite lobe is serially sectioned, another focus will be found in 50-75% of cases

34 PAPILLARY CARCINOMA GROSS: GRANULAR or FI RM WHITE LESION IRREGULAR BORDERS

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36 MICRO: PAPILLA ARY CA PAPILLARY FRON NDS CUBOIDAL LINING CELLS MOST LESIONS ALSO HAVE FOLLICULAR AREAS SAME BIOLOGIC BEHAVIOR REGARDLESS OF % PAP VS. FOLL

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40 PAPILLA ARY CA NUCLEAR FEATURES: GROUND GLASS OPTICALLY CLEAR ORPHAN ANNIE-EYEY YE PSAMMOMA BODIES= SMALL CONCENT TRIC CONCRETIONS

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43 PAPILLA ARY CA RELIABLY DIAGNOSED BY: 1. FINE NEEDLE ASPIRATION (FNA) 2. CORE NEEDLEE BIOPSY 3. FROZEN SECTION DIAGNOSIS

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45 PAPILLA ARY CA METASTATIC SPREAD: LYMPHATIC TO PA ARATHYROIDAL LNs MULTICENTR RIC FOCI IN THYROID? MULTIPLE PRIMARIES? MET FOCI VIA LYMPHATIC SPREAD CLINICAL OR SUB BCLINICAL

46 PAPILLA ARY CA SPREAD: RARELY DIE OF PAPILLARY CA IF DIE, USUALLY PULMONARY OR CEREBRAL METS INVASION OF JUG GULAR, CAROTID OR AIRWAY ANAPLASTIC DIFFERENTIATION

47 FOLLICU ULAR CA 10-20% OF THYROID CARCINOMAS USUALLY SOLITARY COLD LOW RAI UPTAKE

48 GROSS: SOLITARY FOLLICU ULAR CA MAY HAVE CAPSULE INVASION DISTINGUISH HES CA FROM ADENOMA MAY INVADE ADJACENT THYROID OUTSIDE THYROID & CAUSE ADHESIONS TO ADJACENT STRUCTURES

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50 FOLLICU ULAR CA MICRO: SOLITARY IN ONE LOBE METASTATIC SPREAD: INVADES AND METS VIA VEINS COMMON SITES OF METS: LUNGS AND BONES

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53 CHORNOBYL PROJECT I 131 Radioisotope scan of 24 year old man with thyroid cancer and lung metastases

54 FOLLICU ULAR CA Treatment: t Total thyroidect t tomy (1 or 2 stages) If metastatic to lung or bone, treat with hi dose 131 Itoablate 10 year survival l: 50-70%

55 THYROID N EOPLASMS How to distinguish Follicular ADENOMA from CARCINOMA? Search for in vasion of capsule or blood vessels Examine entire nodule, especially ca apsule

56 FOLLICU ULAR CA VERY DIFFICULT VERY DIFFICULT TO DIAGNOSE BY FROZEN SECTION Bland tumor cells Subtle invasion EASY TO DIAGNOSE ANY CA WITH GROSS INVASION &/OR ANAPLASIA AND MITOSES

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58 MEDULL LARY CA 5% OF THYROID CAR RCINOMAS ARISE from PARAFOLLICULAR CELLS ( C CELLS) ARISE FROM NEUR RAL CREST 75% SPORADIC 25% FAMILIAL (+MEN 2) ASSOC D WITH RET PROTO-ONCOGENE

59 MEDULL LARY CA C CELLS PRODUCE MA AINLY CALCITONIN & OTHER PP HORMONES ie SERATONIN, ACTH PRE-OP SERUM CALCITONIN FOR DIAGNOSIS POST-OP SERUM CALCITONIN TO DETECT RESIDUAL OR RECURRENT TUMOR TOTAL THYROIDECTOMYY LN DISSECTION IF ENLARGED OR SUSPICIOUS NODES

60 MEDULL LARY CA GROSS: YELLOW-TAN ILL-DEFINED BORDERS INFILTRATES ADJACENT TISSUES

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62 MEDULL LARY CA MICROSCOPIC: SOLID NESTS ROUND TO SPINDLY CELLS AMYLOID-LIKE STROMA CONGO RED, POLARIZED: APPLE GREEN BIREFRINGENCE

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67 MEDULL LARY CA SPREAD: LYMPHATIC VENOUS METS TO LUN NG AND BONES MULTIFOCALL

68 Autosomal Dominant Inheri tance 50% affected, 50% unaffected

69 Multiple Endocrine Neoplasia 2 Medullary thyroid carcinoma (99%)-usual and possibly only presentation Pheochromocytoma h (50 0%) Hyperparathyroidism (15-30%) MEN2B has associated features of marfanoid body habitus, hypotonia, mucosal neuromas, and ganglioneuromatos g sis of the gut, earlier onset tumors Familial MTC-isolated finding

70 Patient history Patient history/fhx Early age of onset Unusual tumors Multiple synchronous or hyperplasia Associated medical conditions Family history Should include three generations metachronous tumors or Cause and age of death of all first and if possible second degree relatives Goiter, sudden death, hy pertension, renal stones Resolution of ambiguous medical histories

71 Clinical Manag gement of MEN2 It is standard of care by ASCO for ALL cases of medullary thyroid cancer to undergo genetic testing for RET proto-oncogene Mutation ti positive indiv viduals should undergo prophylactic total thyroidectomy Screen for pheochromocytoma prior to thyroid surgery (or any surger ry) Screen biochemically annually for pheochromocytoma and hyperparathyroidism p y

72 ANAPLA ASTIC CA 1-3% OF THYROID CARCINOMAS VERY POOR PROGNOSIS (<5% SURVIVE 5 YEARS) LESS FREQUENT than 40 years ago

73 CLINICAL: ANAPLA ASTIC CA Patients >50 years Old nodule begins old to grow rapidly? arose in pre-existing nodule? Lower incidence due to more resected nodules

74 ANAPLA ASTIC CA CLINICAL: Rapid growth Invasion of adjacent structures Tracheostomy frequently necessary Usually unresectable Chemo / Radiation not useful in most

75 MICRO: ANAPLA ASTIC CA HIGHLY UNDIFFER RENTIATED!!!!! small cells giant cells spindle cells May need immunostains to distinguish from lymphoma & sarcoma

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78 MALIGNANT LYMPHOMA OF THY YROID USUALLY ARIS ES IN HASHIMOTO S S THYROIDITIS RARELY PRIMARY IN THYROID

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80 THYROGLOSSA AL DUCT CYST PERSISTENT THYROID ALONG EMBRYONAL MIGRATION PATH IN MIDLINE NECK, ANTERIOR TO LARYNX & HYOID BO ONE RESECTED WHEN RESIDUAL TRACT / CYST PERSISTS OR RECURS MICRO: LINED BY CILIATED RESPIRATORY EPITHELIUM, SQUAMO OUS, OR BOTH

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