Path - Thyroid Flashcards
the thyroid is often diffusely enlarged, although more localized enlargement may be seen in some cases
- the capsule is intact, and the gland is well demarcated from adjacent structures
- the cut surface is pale yellow-tan, firm, and somewhat nodular
- extensive infiltration of the parenchyma by a mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells, and well-developed germinal centers
- follicles are atrophic and are lined in many areas by epithelial cells distinguished by the presence of abundant eosinophilic, granular cytoplasm termed Hurthle cells
Hashimoto thyroiditis
in fin needle aspiration biopsy samples, the presence of Hurthle cells in conjunction with a heterogenous population of lymphocytes is characteristic of what?
Hashimoto thyroiditis
- in “classic” Hashimoto thyroiditis, interstitial connective tissue is increased and may be abundant
- unlike Reidel thyroiditis, the fibrosis does NOT extend beyond the capsule of the gland
except for possible mild symmetric enlargement, the thyroid appears grossly normal
- microscopic examination reveals lymphocytic infiltration with large germinal centers within the thyroid parenchyma and patchy disruption and collapse of thyroid follicle
- unlike Hashimoto’s, fibrosis and Hurthle cell metaplasia are NOT present
subacute lymphocytic (painless) thyroiditis
the gland may be unilaterally or bilaterally enlarged and firm, with an intact capsule that may adhere to surrounding structures
- on cut section, the involved areas are firm and yellow-white and stand out from the more rubbery, normal brown thyroid substance
- histologic changes are patchy and depend on the stage of the disease
granulomatous thyroiditis
what is seen early in the active inflammatory phase of granulomatous thyroiditis?
scattered follicles may be disrupted and replaced by neutrophils forming microabscesses
what is seen later in the inflammatory phase of granulomatous thyroiditis?
more characteristic features appear in the form of aggregates of lymphocytes, activated macrophages, and plasma cells associated with collapsed and damaged thyroid follicles
- multinucleate giant cells enclose naked pools of fragments of colloid
what is seen in late stages of granulomatous thyroiditis?
chronic inflammatory infiltrate and fibrosis may replace the foci of injury
what is the most common cause of hypothyroidism, in regions where dietary iodine levels are sufficient?
Hashimoto thyroiditis
autoimmune thyroiditis characterized by progressive destruction of thyroid parenchyma, Hurthle cell change, and mononuclear (lymphoplasmacytic infiltrates, with germinal centers and with/without extensive fibrosis
Hashimoto thyroiditis
often occurs after a pregnancy, is typically painless, and is characterized by lymphocytic inflammation in the thyroid
subacute lymphocytic thyroiditis (postpartum thyroiditis)
- is also a type of autoimmune thyroiditis
self-limited disease, probably secondary to a viral infection, and is characterized by pain and the presence of a granulomatous inflammation of the thyroid
granulomatous (de Quervain) thyroiditis
the thyroid is usually symmetrically enlarged due to diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells
- increases in weight over 80gm are common
- on cut section, the parenchyma has a soft, meaty appearance resembling muscle
- histologically, the follicular epithelial cells in untreated cases are tall and more crowded than usually -> resulting in formation of small papillae, which project into the follicular lumen and encroach on the colloid, sometimes filling the follicles
Graves disease
- the papillae lack fibrovascular cores
- colloid within the lumen is pale, with scalloped margins
- lymphoid infiltrates (mostly T cells) along with scattered B cells and mature plasma cells, are present throughout the interstitium
- germinal centers are common
what does administration of iodine cause in Graves disease?
involution of the epithelium and the accumulation of colloid by blocking thyroglobulin secretion
what does treatment with the antithyroid drug propylthiouracil (PTU) cause?
it exaggerates epithelial hypertrophy and hyperplasia by stimulating TSH secretion
what are the changes in extrathyroidal tissue listed?
- lymphoid hyperplasia (especially the thymus is younger patients)
- heart may be hypertrophied (also ischemic changes)
- pts with ophthalmopathy, the tissue of the orbit are edematous d/t presence of hydrophillic mucopolysaccharides (also lymphocytic infiltration and fibrosis)
- orbital muscles are initially edematous but may undergo fibrosis late in the course of the disease
- thickening of the dermis d/t deposition of glycosaminoglycans and lymphocyte infiltration
what is characterized by the triad of thyrotoxicosis, ophthalmopathy and dermopathy?
Graves disease
- most common cause of endogenous hyperthyoidism
autoimmune disorder caused by activation of thyroid epithelial cells by autoantibodies to TSH receptor that mimic TSH action
Graves disease
how is the thyroid characterized in Graves disease?
diffuse hypertrophy and hyperplasia of follicles and lymphoid infiltrates
what causes ophthalmopathy and dermopathy in Graves disease?
glycosaminoglycan deposition and lymphoid infiltrates
what are the levels of TSH and free T3/4 in Graves disease?
- free T3/4 are HIGH
- TSH is LOW
what are the two phases of a diffuse nontoxic goiter?
- hyperplastic phase
2. colloid involution
thyroid is diffusely and symmetrically enlarged, although the increase is usually modest, and the gland rarely exceeds 100-150gms
- the follicles are lined by crowded columnar cells, which may pile up and form projections similar to those seen in Graves disease
- the accumulation is not uniform throughout the gland and some follicles are hugely distended, whereas others remain small
the hyperplastic phase of a nontoxic goiter
what happens dietary iodine subsequently increases or if the demand for thyroid hormone decreases during the hyperplastic phase of a nontoxic goiter?
the stimulated follicular epithelium involutes to form an enlarged, colloid-rich gland -> COLLOID GOITER
what does a colloid goiter look like?
the cut surface is usually brown, somewhat glassy, and translucent
- histologically, the follicular epithelium is flattened and cuboidal, and colloid is abundant during periods of involution
multilobulated, asymmetrically enlarged glands that can reach weights of more than 2k grams
- pattern of enlargement is unpredictable and may involve one lobe far more than the other, producing lateral pressure on midline structures (trachea, esophagus)
multinodular goiter
- on cut section, irregular nodules containing variable amounts of brown, gelatinous colloid are present
- older lesions have areas of hemorrhage, fibrosis, calcification, and cystic change
what is it called when the goiter grows behind the sternum and clavicles?
intrathoracic or plunging goiter
- occasionally, most of it is hidden behind the trachea and esophagus
- sometimes one nodule may stand out, imparting the clinical appearance of a solitary nodule
what is seen on microscopy of a multinodular goiter?
colloid-rich follicles lined by flattened, inactive epithelium and areas of follicular hyperplasia, accompanied by degenerative changes related to physical stress
how do multinodular goiters differ from follicular neoplasms?
they lack a prominent capsule between the hyperplastic nodules and residual compressed thyroid parenchyma
what features are important in making the distinction between a thyroid adenoma and multinodular goiter?
thyroid adenoma is a solitary, spherical, encapsulated lesion that is demarcated from the surrounding thyroid parenchyma by a well-defined, intact capsule
in freshly resected specimens, the tumor bulges from the cut surface and compresses the adjacent thyroid
- color ranges from gray-white to red-brown, depending the the cellularity and its colloid content
- areas of hemorrhage, fibrosis, calcification, and cystic change, similar to those encountered in multinodular goiters are common
follicular adenoma
microscopically, the constituent cells often form uniform appearing follicles that contain colloid
- follicular growth pattern is usually quite distinct from the adjacent nonneoplastic thyroid
- the neoplastic cells show little variation in cell size, shape, or nuclear morphology
- mitotic figures are rare
follicular adenoma
what is the hallmark of all follicular adenomas?
the presence of an intact, well-formed capsule encircling the tumor
- careful evaluation of the integrity of the capsule is therefore critical in distinguishing follicular adenomas from follicular carcinomas
what does extensive mitotic activity, necrosis, or high cellularity warrant?
close inspection to exclude follicular carcinoma and the follicular variant of papillary carcinoma
these tumors may be solitary or multifocal
- some are well-circumscribed and even encapsulated, others infiltrate the adjacent parenchyma and have ill-defined margins
- tumors may contain areas of fibrosis and calcification, are often cystic
- the cut surface sometimes reveals papillary foci that point to the diagnosis
papillary carcinomas
- foci of lymphatic invasion by the tumor are often present, but involvement of blood vessels is relatively uncommon, especially in smaller lesions
- metastases to adjacent cervical lymph nodes occur in up to 50% of cases
papillary carcinomas may contain branching papillae, which are what?
a fibrovascular stalk covered by single or multiple layers cuboidal epithelial cells
- in most neoplasms, the epithelium covering the papillae consist of well-differentiated, uniform, orderly cuboidal cells
- can also have failrly anaplastic epithelium showing considerable variation in cell and nuclear morphology
- when present, the papillae differ from those seen in areas of hyperplasia in being more complex and having dense fibrovascular cores
what do the nuclei of papillary carcinoma cells contain?
finely dispersed chromatic, which imparts an optically clear or empty appearance, giving rise to the designation of ground glass or ORPHAN ANNIE EYE NUCLEI
- invaginations of the cytoplasm may give the appearance of intranuclear inclusions (pseudo-inclusions) or intranuclear grooves
these concentrically calcified structures are often present in papillary carcinomas, usually within the cores of papillae
- these structures are almost never found in follicular and medullary carcinomas, and so when present in fine needle aspiration material, they are a strong indication that the lesion is a papillary carcinoma
psammoma bodies
what is the most common variant of papillary carcinoma?
- has characteristic features of papillary carcinomas and an almost entirely follicular architecture
- can be either encapsulated or poorly circumscribed and infiltrative
follicular variant of papillary carcinoma
which variant has a generally favorable prognosis?
encapsulated follicular variant
which variants need to be treated more aggressively?
poorly circumscribed and infiltrative lesions
what are the genetic alterations that differ in the follicular variant of papillary carcinomas?
- lower frequency of RET/PTC rearrangements
- lower frequency and different spectrum of BRAF mutations
- significantly higher frequency of RAS mutations
this variant has tall columnar cells with intensely eosinophilic cytoplasm lining the papillary structures
- these tumors tend to occur in older individuals and have higher frequencies of vascular invasion, extrathyroidal extension, and cervical and distant metastases than conventional papillary thyroid carcinoma
tall-cell variant
what are the genetic alterations that differ in the tall-cell variant of papillary carcinomas?
BRAF mutations and RET/PTC translocations
- the occurrence of these two together may synergistically enhance MAPK signaling, contributing to the aggressive behavior of this variant
this variant occurs in younger individuals, including kids
- tumor has a prominent papillary growth pattern intermixed with solid areas containing nests of squamous metaplasia
- there is extensive, diffuse fibrosis throughout the thyroid gland, often associated with a prominent lymphocytic infiltrate, stimulating Hashimoto thyroiditis
- lymph node metastases are present in almost all cases
- they lack BRAF mutations, but RET/PTC translocations are found in approx 50%
diffuse sclerosing variant carcinomas
this variant is defined as an otherwise conventional papillary carcinoma, less than 1cm
- lesions most commonly come to attention as an incidental finding in patients undergoing surgery, and may be precursors of typical papillary carcinomas
papillary microcarcinoma
single nodules that may be well circumscribed or widely infiltrative
- sharply demarcated lesions may be exceedingly difficult to distinguish from follicular adenomas by gross exam
- larger lesions may penetrate the capsule and infiltrate well beyond the thyroid capsule into the adjacent neck
- they are gray to tan to pink on cut section and may be somewhat translucent d/t presence of large, colloid-filled follicles
- can have degenerative changes, such as central fibrosis
follicular carcinoma
microscopically, most of these carcinomas are composed of fairly uniform cells forming small follicles containing colloid
- occasional tumors are dominated by cells with abundant granular, eosinophilic cytoplasm (Hurthle cells)
- the nuclei lack the features of typical papillary carcinoma, and do NOT have psammoma bodies
follicular carcinomas
why is the diagnosis of widely invasive follicular carcinoma obvious?
they infiltrate the thyroid parenchyma and extrathyroidal soft tissues
- histologically, these cancers tend to have a greater proportion of solid or trabecular growth pattern less evidence of follicular differentiation, and increased mitotic activity
these tumors present as a solitary nodule
- larger lesions contain areas of necrosis and hemorrhage and may extend through the capsule of the thyroid
- the tumor tissue is firm, pale gray to tan, and infiltrative
- there may be foci of hemorrhage and necrosis in larger lesions
sporadic medullary thyroid carcinoma
microscopically, these tumors are composed of polygonal to spindle-shaped cells, which may form nests, trabeculae, and even follicles
- small, anaplastic cells are present and may be the predominant cell type
- acellular AMYLOID DEPOSITS derived from calcitonin polypeptides are present in the stroma in many cases
- calcitonin is readily demonstrable within the cytoplasm as well as in the stromal amyloid -> STAINING
medullary thyroid carcinoma
what is one of the characteristic features of familial medullary cancers?
the presence of multicentric C-CELL HYPERPLASIA
- is believed to be a precursor lesion in familial cases
- presence of multiple prominent clusters of C-cells scattered throughout the parenchyma should raise the specter of an inherited predisposition, even if there is no family history
most thyroid neoplasms manifest as what?
solitary thyroid nodules
- only 1% of nodules are neoplastic
what are the most common benign neoplasms?
follicular adenomas
what are the most common malignancies?
papillary carcinoma
what two tumors are both composed of well-differentiated follicular epithelial cells?
follicular adenomas and carcinomas
- carcinomas are distinguished by evidence of capsular and/or vascular invasion
what tumors are recognized based on nuclear features (ground-glass nuclei, pseudoinclusions) even in the absence of papillae?
papillary carcinomas
what are a characteristic feature of papillary carcinomas?
psammoma bodies
- these neoplasms often metastasize by way of lymphatics, but prognosis is excellent
what tumors are thought to arise by dedifferentiation of more differentiated neoplasms?
anaplastic carcinomas
what tumors are neoplasms arisiing from the parafolicular C-cells and can occur in either sporadic (70%) or familiar (30%) settings?
medullary cancers
what are the features of familial medullary thyroid cancers?
multicentricity and C-cell hyperplasia
what is a characteristic hostologic finding of medullary thyroid cancer?
amyloid deposits
