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
Follicular adenomas Solitary Adenomas 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