ANAPLASTIC AND MEDULLARY THYROID CARCINOMA

BYN.AISHWARYA

FINAL YEAR MBBS

CLASSIFICATION OF THYROID NEOPLASMS

BENIGN FOLLICULAR ADENOMA

MALIGNANT PRIMARY FOLLICULAR EPITHELIUM-DIFFERENCIATED

FOLLICULARPAPILLARY

FOLLICULAR EPITHELIUM-UNDIFFERENCIATED

ANAPLASTIC

PARAFOLLICULAR CELLS

MEDULLARY

LYMPHOID CELLS LYMPHOMA

SECONDARY METASTATICLOCAL INFILTRATION

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

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

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

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.

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

anaplastic carcinoma of the thyroid with pleomorphic giant tumor cell nuclei

Rapidly enlarging mass with tumor fungation seen at the tracheostomy site

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.

MANAGEMENT

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

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

Morphology• 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

Medullary (C-cell) carcinoma of the thyroid with amyloid stroma

Immunohistochemical anti-calcitonin antibody stain of a medullary carcinoma showing strong red positivity

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

• 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.

• 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