Pathology of thyroid 3 Dr: Salah Ahmed

Follicular adenoma - are benign neoplasms derived from follicular epithelium - are usually solitary - the majority of adenomas are nonfunctional, a small proportion produces thyroid hormones ("toxic adenomas") and causes thyrotoxicosis. Pathogenesis: - Mutations in TSH receptor signaling pathway plays an important role in the pathogenesis of toxic adenomas, cause chronic overproduction of cAMP, generating cells growth and excess hormone secretion within adenoma - About 20% of follicular adenomas have point mutations in the RAS oncogenes, which have also been identified in approximately half of follicular carcinomas. This finding has raised the possibility that some adenomas may progress to carcinomas.

Morphology: - typical adenoma is solitary, spherical in shape - compresses the adjacent normal thyroid - possesses a capsule (unlike dominant nodule in multinodular goiter which not compresses the adjacent thyroid parenchyma, and lack a well-formed capsule) - Microscopically: -uniform follicles that contain colloid lined by uniform cells with well-defined cell borders - Occasionally the cells acquire brightly eosinophilic granular cytoplasm ( Hürthle cell adenoma) - The hallmark of all follicular adenomas is the presence of an intact well-formed capsule encircling the tumor (to differentiate adenomas from follicular carcinomas)

Follicular adenoma (solitary spherical nodule)

Follicles lined by well-defined uniform cells and containing colloid

Hurthe cell adenoma

Clinical Features: - painless nodules, often discovered during a routine physical examination - Larger masses may produce local symptoms such as difficulty in swallowing - persons with toxic adenomas can present with features of thyrotoxicosis - Investigations: 1- TFT 2- most adenomas take up iodine less than does normal thyroid parenchyma "cold" nodules. Toxic adenomas appear as "hot" nodules in the scan. 3 - fine-needle aspiration biopsy 4- Because of the need for evaluating capsular integrity, the definitive diagnosis of thyroid adenoma can only be made after careful histologic examination of the resected specimen. - Treatment: surgical removal - Thyroid adenomas have an excellent prognosis and do not recur or metastasize

Carcinoma - includes: 1- Papillary carcinoma (75% to 85% of cases) from follicular cells 2- Follicular carcinoma (10% to 20% of cases) from follicular cells 3- Medullary carcinoma (5% of cases) from parafollicular cells 4- Anaplastic carcinomas (<5% of cases) from follicular cells 1- Papillary carcinoma: - is the most common form of thyroid cancer - may occur at any age Pathogenesis: - both genetic and environmental factors are involved 1- incidence increases with previous neck exposure to radiation 2- Rearrangement of RET tyrosine kinase receptors (chromosome 10) and mutation in BRAF genes

Morphology: - solitary or multifocal lesion with infiltration of adjacent parenchyma - microscopically :- papillary projections -the cells have empty-appearing nuclei (ground glass appearance) - Psammoma bodies (areas of calcification ) - different histological variants (follicular, tall cell variants) - the diagnosis of papillary carcinoma is based on nuclear features even in the absence of a papillary architecture - metastases to regional lymph nodes (cervical). In a minority of patients, hematogenous metastases are present most commonly to the lung Clinical manifestation: - are nonfunctional tumors, they present most often as a painless mass in the neck, either within the thyroid or as metastasis in a cervical lymph node - Has a better prognosis than other thyroid cancers

2- Follicular carcinoma: - Is the second most common thyroid cancer - usually present at older age than do papillary carcinomas, with a peak incidence in the middle adult years Pathogenesis: - both genetic and environmental factors are involved: 1- incidence increases in areas of dietary iodine deficiency 2 - mutation in RAS oncogene Morphology: - grossly: solitary or infiltrative lesions - microscopically: composed of uniform cells forming small follicles some of them contain colloid or may composed of nests or sheets of neoplastic cells with no follicles - capsular invasion

Uniform cells forming small follicles some of them contain colloid

The capsular invasion in carcinoma in compression with adenoma

- tend to metastasize through the bloodstream to the lungs, bone, and liver. Regional nodal metastases are uncommon in contrast to papillary carcinomas. Clinical manifestation: - present most frequently as solitary "cold" thyroid nodules - In rare cases, they may be hyperfunctional - Follicular carcinomas are treated with surgical excision 3- Medullary carcinoma: - are neuroendocrine neoplasms derived from the parafollicular cells, or C cells - secrete calcitonin (like C cells), the measurement of which plays an important role in the diagnosis and postoperative follow-up (serotonin, VIP) - Medullary carcinomas arise sporadically in about 80% of cases - The remaining 20% are familial cases occurring in the setting of MEN syndromes or familial medullary thyroid carcinoma (FMTC) without an associated MEN syndrome

- both familial and sporadic medullary forms show mutations RET oncogene - Sporadic as well as FMTC, occur in adults, with a peak incidence in the fifth to sixth decades. Cases associated with MEN occur in younger patients and may even arise in children. Morphology: - solitary or multifocal lesions - solid tumor with no capsule - composed of polygonal to spindle cells arranged in nests or follicles - amyloid deposits (from calcitonin) present in stroma 4- Anaplastic carcinoma: - Are undifferentiated tumor of follicular cells - Are aggressive tumors - Uncommon, most common in elderly individuals particularly in areas of endemic goiter

Solid tumor, do not have a capsule

- Mutation of P53 gene plays a role in pathogenesis Morphology: - composed of highly anaplastic cells, which have three patterns : 1- large pleomorphic giant cells 2- spindle cells with sarcoma appearance 3- small anaplastic cells - Very poor prognosis

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