thyroid neoplasms Flashcards
goiter
Enlargement of the thyroid, or goiter is caused by impaired synthesis of thyroid hormone, which is most often the result of dietary iodine deficiency
Diffuse Nontoxic (Simple) Goiter
enlargement of the entire gland without producing nodularity.
Endemic- where low iodine
- eating cabbage, cauliflower, Brussels sprouts, turnips, and cassava), has been documented to be goitrogenic
Sporadic goiter occurs less frequently than does endemic goiter. There is a striking female preponderance and a peak incidence at puberty or in young adult life.
Impairment of thyroid hormone synthesis leads to
a compensatory rise in the serum TSH level, which, in turn, causes hypertrophy and hyperplasia of thyroid follicular cells and, ultimately, gross enlargement of the thyroid gland.
Clinical Course of a simple goiter
most are clinically euthyroid
mass effects major issue (push on trachea, suppress SVC, etc)
serum T3 and T4 levels are normal, the serum TSH is usually elevated or at the upper range of normal, as is expected in marginally euthyroid individuals.
Multinodular Goiter
recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed multinodular goiter.
Multinodular goiters produce the most extreme thyroid enlargements and are more frequently mistaken for neoplasms than any other form of thyroid disease
Clinical course of a multinodular goiter.
mostly mass effects
. In addition to the obvious cosmetic effects, goiters may cause airway obstruction, dysphagia, and compression of large vessels in the neck and upper thorax (superior vena cava syndrome).
most patients are euthyroid
sometimes, an autonomous nodule may develop within a long-standing goiter and produce hyperthyroidism (toxic multinodular goiter). This condition, known as Plummer syndrome, is not accompanied by the infiltrative ophthalmopathy and dermopathy of Graves disease.
Dominant nodules in a multinodular goiter can present as
a “solitary thyroid nodule”, mimicking a thyroid neoplasm. A radioiodine scan demonstrates uneven iodine uptake (including the occasional “hot” autonomous nodule)
solitary thyroid nodule
is a palpably discrete swelling within an otherwise apparently normal thyroid gland
4x more in women
major concern: possible malignant neoplasm
most are localized, nonneoplastic lesions or benign neoplasms such as follicular adenoma.
benign neoplasms outnumber thyroid carcinomas by a ratio of nearly 10 : 1.
likelihood of a thyroid nodule to be neoplastic
More likely to be neoplastic:
- Solitary nodules
- younger patients
- males
- A history of radiation treatment to the head and neck region
- Cold nodules
(Functional nodules that take up radioactive iodine in imaging studies (hot nodules) are much more likely to be benign than malignant.)
Thyroid adenomas
typically discrete, solitary masses, derived from follicular epithelium, and hence they are also known as follicular adenomas.
a small subset produces thyroid hormones and causes clinically apparent thyrotoxicosis. Hormone production in functional adenomas (“toxic adenomas”) is independent of TSH stimulation.
thyroid adenoma morphology
solitary, spherical, encapsulated. (distinguishes from multinodular)
what does hurthle cell change mean?
lots of eosinophilic cytoplasm
metaplastic change in thyroid
unpredictable
follicular adenomas
tend to be cold nodules, unilateral painless masses
Careful evaluation of the integrity of the capsule is therefore critical in distinguishing follicular adenomas from follicular carcinomas
definitive dx can only be made after histologic exam of the resected specimen
major subtypes of thyroid carcinoma
Papillary carcinoma (>85% of cases) Follicular carcinoma (5% to 15% of cases) Anaplastic (undifferentiated) carcinoma (<5% of cases) Medullary carcinoma (5% of cases)
Pathogenesis of thyroid carcinoma
Genetic alterations in the three follicular cell–derived malignancies are in growth factor receptor signaling pathways
environmental factors in thyroid carcinomas
The major risk factor predisposing to thyroid cancer is exposure to ionizing radiation, particularly during the first 2 decades of life.
In keeping with this, there was a marked increase in the incidence of papillary carcinomas among children exposed to ionizing radiation after the Chernobyl nuclear disaster in 1986.
Deficiency of dietary iodine (and by extension, an association with goiter) is linked with a higher frequency of follicular carcinomas.
papillary carcinoma histology
eyeballs of orphan annie
“optically clear nuclei”
psammoma bodies
concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary
papillary carcinoma staining
RET immunostaining
Clinical course for papillary carcinoma
Most conventional papillary carcinomas present as asymptomatic thyroid nodules, but the first manifestation may be a mass in a cervical lymph node. Interestingly, the presence of isolated cervical nodal metastases does not have a significant influence on prognosis, which is generally good
Papillary carcinomas are cold masses on scintiscans
Excellent prognosis
youngest presentation
Follicular Carcinoma
more frequent in areas with dietary iodine deficiency
3:1 women
between 40-60 years of age
Clinical Course of follicular carcinoma
present as slowly enlarging painless nodules.
Most frequently they are cold nodules on scintigrams, although rare, better-differentiated lesions may be hyperfunctional, take up radioactive iodine and appear warm on scintiscan.
little propensity for invading llymphatics, but vascular dissemination is common with metastases to bone, lungs, liver, and elsewhere
prognosis depends on invasion and stage at presentation.
treatment of follicular carcinoma
total thyroidectomy followed by the administration of radioactive iodine, which can be used to identify metastases and to ablate such lesions.
In addition, because any residual follicular carcinoma may respond to TSH stimulation, patients are usually treated with thyroid hormone after surgery to suppress endogenous TSH levels. Serum thyroglobulin levels are used for monitoring tumor recurrence, because this thyroid protein should be barely detectable in a patient who is free of disease.
Molecular diagnosis - follicular carcinomas
associated with acquired mutations that activate RAS or the PI-3K/AKT arm of the receptor tyrosine kinase signaling pathway
Anaplastic (Undifferentiated) Carcinoma
undifferentiated tumors
mortality rate approaching 100%
older people- mean age 65 yrs
Approximately a quarter of patients with anaplastic thyroid carcinomas have a past history of a well-differentiated thyroid carcinoma
Clinical Course of anaplastic carcinoma
rapidly enlarging bulky neck mass
In most cases, the disease has already spread beyond the thyroid capsule into adjacent neck structures or has metastasized to the lungs at the time of presentation.
Symptoms related to compression and invasion, such as dyspnea, dysphagia, hoarseness, and cough, are common.
no effective therapies
usually death in less than a year
Medullary Carcinoma
neuroendocrine neoplasms derived from the parafollicular cells, or C cells.
secrete calcitonin, the measurement of which plays an important role in the diagnosis and postoperative follow-up of patients.
(classically find amyloid)
Clinical Course of medullary carcinoma- sporadic
Sporadic cases- most often a mass in the neck, sometimes associated with dysphagia or hoarseness.
In some instances, the initial manifestations are those of a paraneoplastic syndrome caused by the secretion of a peptide hormone (e.g., diarrhea due to the secretion of VIP, or Cushing syndrome due to ACTH).
Notably, hypocalcemia is not a prominent feature, despite the presence of raised calcitonin levels. In addition to circulating calcitonin, secretion of carcinoembryonic antigen by the neoplastic cells is a useful biomarker, especially for presurgical assessment of tumor load and in calcitonin-negative tumors.
Clinical Course of medullary carcinoma- familial
may come to attention because of symptoms localized to the thyroid or as a result of endocrine neoplasms in other organs (e.g., adrenal or parathyroid glands). Medullary carcinomas arising in the context of MEN-2B are generally more aggressive and metastasize more frequently than those occurring in patients with sporadic tumors, MEN-2A, or FMTC.
what do we do with asymptomatic MEN-2 patients carrying germline RET mutations?
they are offered prophylactic thyroidectomy as early as possible to prevent the otherwise inevitable development of medullary carcinomas
thyroid neoplasms- key concepts
most are solitary and non-neoplaastic
follicula adenoma- most common benign neoplasm
papillary carcinoma- most common malignancy
RAS/ Pl-3K gene- follicularcarcinoma
RET/ BRAF- in papillary
RET- in medullary
follicular adenomas and carcinomas- well-differentiated; latter has capsular and/or vascular invasion
papillary carcinomas– ground-glass nuclei, pseudoinclusions, etc. Psamoma bodies
anaplastic- dedifferentiation, highly aggressive, lethal
medullary- arise from parafollicular C cells. Sporadic or familial. amyloid deposits
plummer syndrome
sometimes, an autonomous nodule may develop within a long-standing goiter and produce hyperthyroidism (toxic multinodular goiter). This condition, known as Plummer syndrome, is not accompanied by the infiltrative ophthalmopathy and dermopathy of Graves disease.
