NEOPLASMS OF THE THYROID PATHOLOGY OF PARATHYROID GLANDS BY: Shifaa’ Qa’qa’

Neoplasmas of the thyroid thyroid nodules Neoplastic ---- benign, malignant Non neoplastic

Solitary nodules ----- neoplastic Nodules in younger patients ----- neoplastic Nodules in males ---- neoplastic history of radiation treatment to the head and neck------ malignancy hot nodules ------ benign

Adenomas Follicular adenomas Solitary Nonfunctional---- M.C--- RAS, PAX8/PPARG fusion gene toxic adenomas---- TSHR, α-subunit of Gs (GNAS)---- autonomy---- thyrotoxicosis Carcinoma ??

well-defined, intact capsule Adenoma----- no invasion Carcinoma----- invasion Multinodular goiter---- no capsule Uniform follicles

Hürthle cell adenoma ??? endocrine atypia ??

cold nodules---10% of cold nodules eventually prove to be malignant. hot nodules---- malignancy is rare---- toxic adenoma ultrasonography fine needle aspiration biopsy (FNA) Because of the need for evaluating capsular integrity, the definitive diagnosis of thyroid adenoma can be made only after careful histologic examination of the resected specimen.

Carcinomas Papillary carcinoma (85% of cases) Follicular carcinoma (5% to 15% of cases) Anaplastic (undifferentiated) carcinoma (less than 5% of cases) Medullary carcinoma (5% of cases)

Papillary thyroid carcinomas: m.c ionizing radiation nonfunctional tumors - Activation of the MAP kinase pathway: Rearrangements of RET (RET/PTC) BRAF nuclear features ??? Papillae ???? lymphatic permeation, LN indolent lesions, with 10-year survival rates in excess of 95%.

Follicular thyroid carcinomas: older age than that typical for papillary carcinoma iodine deficiency Solitary cold thyroid nodules - mutations in the PI-3K/AKT signaling pathway: RAS and PIK3CA PTEN PAX8/PPARG fusion genes widely invasive minimally invasive hematogenous dissemination surgical excision, radioactive iodine

Anaplastic Carcinoma: - undifferentiated Mortality rate approaching 100% (mets, local effect) mean age of 65 years giant cells Spindle cells

Medullary Carcinoma: - parafollicular cells, or C cells----neuroendocrine neoplasms Sporadically familial cases (30%)---- MEN syndrome 2A, 2B, familial medullary thyroid carcinoma RET mutations Multicentricity???? multicentric C cell hyperplasia???? Mass peptide hormone

PARATHYROID GLANDS free (ionized) calcium

HYPERPARATHYROIDISM primary Secondary tertiary

Primary Hyperparathyroidism: - Adenoma—85% to 95% - Primary hyperplasia (diffuse or nodular)—5% to 10% Parathyroid carcinoma—1% Sporadic----- m.c---- Cyclin D1, MEN1 Familial ------ MEN1, MEN2A, Familial hypocalciuric hypercalcemia hypercalcemia

parathyroid adenomas: By definition, parathyroid adenomas are almost invariably confined to single glands 0.5 - 5 g. dipose tissue is inconspicuous within adenomas rim of compressed, non-neoplastic parathyroid tissue, generally separated by a fibrous capsule

Parathyroid hyperplasia: Multiglandular process weight of all glands rarely exceeds 1.0 g Parathyroid carcinomas: exceed 10 g in weight invasion of surrounding tissues and metastasis

Morphologic changes in other organs: osteitis fibrosa cystica brown tumors Nephrolithiasis Nephrocalcinosis Metastatic calcification

The most common manifestation of primary hyperparathyroidism is an increase in serum ionized calcium primary hyperparathyroidism is the most common cause of clinically silent hypercalcemia--- PTH is high, hypophosphatemia The most common cause of clinically apparent hypercalcemia in adults is paraneoplastic syndromes associated with malignancy and bone metastases

“painful bones (fractures), renal stones, abdominal groans, and psychic moans.” Gastrointestinal disturbances: constipation, nausea, peptic ulcers, pancreatitis, and gallstones Central nervous system alterations: depression, lethargy, and seizures Neuromuscular abnormalities: weakness and hypotonia Polyuria and secondary polydipsia

Secondary Hyperparathyroidism Renal failure is by far the most common cause of secondary hyperparathyroidism RF: hyperphosphatemia, hypocalcemia----- Serum calcium remains near normal The parathyroid glands in secondary hyperparathyroidism are hyperplastic tertiary hyperparathyroidism

HYPOPARATHYROIDISM Surgically induced hypoparathyroidism (hyroidectomy) Congenital absence ??? Autoimmune hypoparathyroidism Hypocalcemia: increased neuromuscular irritability (tingling, muscle spasms, facial grimacing, and sustained carpopedal spasm or tetany), Cardiac arrhythmias, increased intracranial pressures and seizures