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.
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
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
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
