THYROID TUMORS

OUTLINE Introduction Epidemiology Aetiology Classification Clinical features Investigations Treatment Prognosis

Epidemiology US: 40 per 1,000,000 per year <1% of all malignancies 6 deaths per million deaths p.a

Aetiology Irradiation of the thyroid.atomic bomb expo Heredity: RET oncogene (xsome 10) plays a significant role in the devt of papillary thyroid cancer. More common in childhood thyroid cancer. Others are C-myc, C-fos, C-ras, C-erb B2/neu. Mutated ras gene, implicated in follicular tumors. Point mutations in p53 gene (a tumor suppressor gene), common in most anaplastic thyroid cancers. Sustained TSH stimulation Nearness to volcanoes

Classification Benign Follicular adenoma Malignant Primary Differentiated tumors of follicular origin - Papillary ca - Follicular ca Differentiated of parafollicular origin - Medullary Undifferentiated / Anaplastic Secondary Metastatic

FOLLICULAR ADENOMA Typically, discrete, solitary masses derived from follicular epithelium Clinically, it may be difficult to distinguish from follicular hyperplasia or carcinoma. They are usually not premalignant xcept in rare cases. Usually non-functional tho some may produce hormones independent of TSH stimulation I.e toxic adenomas.

Pathology Mutation in TSH receptor leading to clonal expansion of follicular epith Macro: A solitary, spherical encapsulated lesion well demarcated from surrounding thyroid parenchyma. Micro: Uniform-appearing follicles containing colloid The integrity of the capsule is important in distinguishing it from a follicular Ca.

Features A unilateral painless mass Large masses = pressure symptoms. Toxic adenomas = symp of hyperthyroidism Appear as cold nodules on radionuclide scanning Ultrasonography Incisonal biopsy Thyroidectomy to rule out malignancy. PROGNOSIS is excellent, do not recur or metastasize.

Rare benign tumors Dermoid cyst Lipoma Hemangioma

PAPILLARY CARCINOMA Most common thyroid malignancy, approx 80% in Europe but abt 20% in Nigeria The predominant thyroid ca in children, 75% and people previously exposed to radiation in the neck (85 – 90%). Commoner in women, 2:1 male to female Mean age at presentation is 20 to 40yrs.

Pathology Usually hard and whitish and remain flat on sectioning with a blade, rather than bulging. Hisologically, they exhibit papillary projections or mixed pattern. Has chacteristic cellular features- pale abundant cyto, crowded nuclei (Orphan Annie cells). Psammoma bodies may be present Higher propensity for lymphatic spread and direct spread to contiguous structures. Haematogenous metastases is a late feature.

Clinical features Most patients are euthyroid. A slow-growing painless mass in the neck. Local invasion – dysphagia, dyspnea, hoarseness. Enlarged ipsilateral cervical glands, infact may be more apparent than the pry lesion –the lateral aberrant thyroid. Distant metastases in 1-15%

Diagnosis FNAC Radioiodine thyroid scans: Failure to take up radioiodine is xteristic (cold masses) Thyroid antibody test CT Sscan MRI

TNM Staging TUMOR NODES METASTASES TX Primary cannot be assessed T0 No evidence of primary T1 Limited to thyroid < 1cm T2 Limited to thyroid, >1cm but <4cm T3 Limited to thyroid >4cm T4 Extension to capsule, any size NODES NX Cannot be assessed NO No regional node metastases N1 Regional node metastases METASTASES MX Cannot be assessed M0 No metastases M1 Distant metastases

Management Unilateral lobectomy and isthmectomy Total or near-total thyroidectomy for bilateral dx or high risk patient Thyroxine 0.1-0.2mg daily to suppress endogenous TSH production Radioiodine to tx metastases if detected by scanning Thyroglobulin measurement to detect metastases post-op

Prognosis AGES Scale- Age, Grade, Extent of disease, Size of tumor. Low risk = young, well diff tumor, no metastases, small pry lesion. High risk =older, poorly diffd, local invasion, distant metastases, large pry lesion MACIS Scale- distant Metastasis, Age at presentation, Completeness of original surgical resection, extrathyroidal Invasion, Size of lesion. AMES- Age, Metastases, Extent, Size DNA Ploidy

FOLLICULAR CARCINOMA Accounts for about 20% of thyroid malignancies in Europe but abt 60% in Nigeria. Iodine-deficiency – hyperplasia -- neoplasia Female to male ratio is 3:1 Age at presentation is 40 - 50yrs. Hurthle cell tumors are a variant of FC in which oxyphil cells predominate. Assd with poorer prognosis.

Pathology Usually solitary and encapsulated in 90%. Haematogenous spread occurs more commonly. Lymphatic spread is a late fx, (<10%). Histologically, numerous follicles are seen which may be devoid of colloid.

Clinical features A solitary thyroid nodule with hx of rapid increase in size or hx of long standing goitre. Usu painless but can become painful if haemorrhage into the nodule occurs. Cervical lymphadenopathy is uncommon. Distant metastases. Rarely, features of thyrotoxicosis (<1%).

Management Definite pre-operative diagnosis is difficult bcos FNAC is unable to differentiate a benign follicular adenoma from a carcinoma. Px diagnosed by FNAC as having a follicular lesion should undergo thyroid lobectomy. Frozen section examination is done and diagnosed carcinomas shld have total thyroidectomy + radioactive iodine + Thyroxine

MEDULLARY CARCINOMA Accounts for about 5% of thyroid carcinomas. Arise from parafollicular or C cells derived from neural crest, found majorly in the lateral parts of superior poles. C cells secrete calcitonin wc has opposing action to PTH and lowers serum Ca levels. Also secretes serotonin, PGs, histamine, ACTH, somatostatin, bombesin, VIP. C cell hyperplasia is a premalignant precursor.

Associations May be familial (30%) or sporadic(70%). Familial dx occurs as part of other endocrinopathies. NON-MEN MTC MEN IIA or Sipple’s syndrome - MTC + Hyperparathyroidism + Phaechromocytoma MEN IIB – MTC + Phaechromocytoma + Ganglioneuromatosis + Marfan’s syndrome

Pathology Located in middle to upper thyroid poles Unilateral in about 75% of sporadic cases but with familial cases, 90% are bilateral. Has chacteristic amyloid stroma Immunohistochemistry for calcitonin is a diagnostic tumor marker. Also stain for carcinoembryonic antigen (CEA), histaminase and calcitonin gene-related peptide.. lymphatic spread occur initially before distant haematogenous occurs

Clinical fx A painful neck mass Palpable cervical lymphadenopathy in 15-20% Local invasion: Diarrhea (VIP) Cushing,s syndrome from ectopic ACTH production Kidney stones Hypertension

Management Genetic screening for familial cases + estimation of serum calcitonin. Prophylactic thyroidectomy are offered. Treatment = Total thyroidectomy and resection of involved lymph nodes. In all cases b4 surgery, phaeochromocytoma must be excluded by measurement of urinary catecholamines.

ANAPLASTIC CARCINOMA One of the most aggressive malignancies with few patients surviving 6mths beyond diagnosis. Incidence is abt 1% in US, but 5% in Nigeria. Endemic goiter is a precursor. Common in elderly women, 7th – 8th decade.

PATHOLOGY: Growth is extremely rapid, local infiltration an early feature. Spreads by lymphatics and blood stream. Microscopically, sheets of undifferentiated small or giant cells are seen.

CLINICAL FEATURES elderly women with hx of lump in the neck which suddenly enlarged rapidly and became painful. Associated dysphonia, dysphagia and dyspnea. Tumor is hard and may be fixed to surrounding structures, may be ulcerated. Palpable lymph nodes usually. Evidence of metastases.

Mgt Diagnosis is by FNAC- reveals giant and multinucleated cells. Incisional biopsy may be used to confirm the diagnosis. TREATMENT Radiotherapy Debulking thyroidectomy Chemotherapy wt Doxorubicin PROGNOSIS: Poor. Mortality =100%. Survival rarely exceeds 6months even wt treatment

LYMPHOMAS Approx 1% of thyroid maligs. Most are non-Hodgkin’s B-cell type. Usually develop in patients with chronic lymphocytic thyroiditis (Hashimoto’s). Px presents with features of anaplastic tumors, altho the rapidly enlarging mass is painless. Diagnosis is suggested by FNAC, needle or open biopsy is necessary for definitive diag. Lymph nodde biopsy helps clarify.

Response to chemo is good Response to chemo is good. CHOP- Cyclophosphamide, doxorubicin, vincristine and prednisolone. Combined radiotherapy and chemo is recommended. Thyroidectomy is used to alleviate tracheal compression. Prognosis is good if cervical nodes are not involved.

METASTATIC CA The thyroid gland is a rare site for metastases. Most common metastatic tumor is a hypernephroma. Others include breast, lung, melanoma

Rare neoplasms Fibrosarcoma Teratoma Sq. cell carcinoma mucoepidermoid