Poorly differenciated thyroid carcinoma

anaplastic cancer of thyroid, medullary cancer of thyroid and lymphomas of the thyroid

1. ANAPLASTIC AND MEDULLARY THYROID CARCINOMA BY N.AISHWARYA FINAL YEAR MBBS

2. CLASSIFICATION OF THYROID NEOPLASMS BENIGN FOLLICULAR ADENOMA MALIGNANT PRIMARY FOLLICULAR EPITHELIUM-DIFFERENCIATED FOLLICULAR PAPILLARY FOLLICULAR EPITHELIUM-UNDIFFERENCIATED ANAPLASTIC PARAFOLLICULAR CELLS MEDULLARY LYMPHOID CELLS LYMPHOMA SECONDARY METASTATIC LOCAL INFILTRATION

3. RELATIVE INCIDENCE OF PRIMARY TUMOUR OF THYROID GLAND RELATIVE INCIDENCE PERCENTAGE PAPILLARY CARCINOMA 60 FOLLICULAR CARCINOMA 20 ANAPLASTIC CARCINOMA 10 MEDULLARY CARCINOMA 5 MALIGNANAT LYMPHOMA 5

4. ANAPLASTIC THYROID CARCINOMA ATC is the most aggressive and lethal form of thyroid cancer. 1-2% of all thyroid cancer ATC portends a dismal prognosis, with a median survival of 4 to 12 months from the time of diagnosis

5. Pathology Whether it arises de novo or from a preexisting WDTC is an area of controversy. WDTC can progress to ATC with the loss of the p53 tumor suppressor gene. WDTC and ATC co-exist with zones of transition. Grossly ATCs are unencapsulated, tan-white, fleshy tumors that infiltrate into the surrounding soft tissues of the neck

6. Microscopically Three histologic patterns : spindle, giant cell, and squamoid. There is no prognostic difference in these patterns . All three variants have- numerous mitotic figures, with large areas of necrosis , hemorrhage , and vascular invasion . tumors often display p53 mutations and do not stain for TG. Anaplastic cells typically do not have thyrotropin receptors, do not transport iodine, and do not produce TG.

7. Clinical Characteristics The peak incidence of ATC occurs in the 6th to 7th decade of life . Women comprise 55% to 77% of patients with ATC a rapidly growing , painful, low anterior neck mass that is often firm and fixed to underlying structures . local compressive symptoms including dysphagia, dysphonia, stridor, dyspnea, and neck pain and tenderness Direct tissue invasion and systemic metastasis to lung, bone and brain

8. anaplastic carcinoma of the thyroid with pleomorphic giant tumor cell nuclei Rapidly enlarging mass with tumor fungation seen at the tracheostomy site

9. Diagnosis The diagnosis of ATC is usually suspected on clinical examination and confirmed by FNAB or core biopsy . ATC has been confused with lymphoma and poorly differentiated medullary thyroid carcinoma Computed tomography scans and magnetic resonance imaging are useful in defining the local extent of disease and identifying distant metastases. PET scans are also useful in detecting distant disease since ATC is highly metabolic.

10. MANAGEMENT

11. MEDULLARY THYROID CARCINOMA Derived from the "light," or "C," or "parafollicular" cells. These are calcitonin (CT)-secreting cells, distinct from thyroid acinar cells, and are of ultimo-branchial origin . occur sporadically (about 70% of the total) or as part of the MENII syndromes or as familial medullary thyroid carcinoma

12. Pathology Activating point mutation in the RET proto-oncogene in familial and sporadic medullary carcinoma. In MEN II germ line mutation in RET proto-oncogene on chromosome 10q11.2 M orphology Sporadic-solitary nodule,FMTC-bilateral,multricentric Solid masses of cells with large vesicular nuclei , considerable associated fibrosis , and deposits of amyloid are a helpful diagnostic point. Electron microscopy reveals membrane bound electron-dense granules In FMTC foci of C-cell hyperplasia

13. Medullary (C-cell) carcinoma of the thyroid with amyloid stroma Immunohistochemical anti-calcitonin antibody stain of a medullary carcinoma showing strong red positivity

14. Clinical features Cases with MEN occur in younger patients even during first decade of life, in contrast sporadic and FMTC are lesion of adulthood with a peak at 40s-50s MEN-II (or IIA) includes patients with medullary thyroid cancers, pheochromocytomas , and parathyroid hyperplasia or adenomas . MEN-III (or MEN-IIB) includes medullary thyroid carcinoma, mucosal neuromas, marfanoid habitus, pheochromocytomas , which are usually bilateral and often malignant

15. Paraneoplastic syndrome occur with elaboration of ectopic hormones such as serotonin, ACTH, VIP Gastrointestinal symptoms including diarrhea, constipation, and rarely megacolon occur in these patients and may occur before the thyroid tumor is detected Diagnosis and management The calcitonin assay provides a screening procedure in families with this genetic trait . Family members at risk should firstly be screened for RET proto- oncogene mutation in their blood.

16. when recognized as a carrier of the mutation, should be screened by neck ultrasound and calcitonin Every member of one of these families with either a thyroid mass or elevated calcitonin levels should have a thyroidectomy Secretion of calcitonin by medullary cancer is remarkably increased by calcium or pentagastrin infusion . This procedure can be helpful in establishing a diagnosis. Treatment is total thyroidectomy and either prophylactic or therapeutic resection of central and bilateral cervical nodes