Path - Thyroid

Question 1

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

Answer 1

Hashimoto thyroiditis

Question 2

in fin needle aspiration biopsy samples, the presence of Hurthle cells in conjunction with a heterogenous population of lymphocytes is characteristic of what?

Answer 2

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

Question 3

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

Answer 3

subacute lymphocytic (painless) thyroiditis

Question 4

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

Answer 4

granulomatous thyroiditis

Question 5

what is seen early in the active inflammatory phase of granulomatous thyroiditis?

Answer 5

scattered follicles may be disrupted and replaced by neutrophils forming microabscesses

Question 6

what is seen later in the inflammatory phase of granulomatous thyroiditis?

Answer 6

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

Question 7

what is seen in late stages of granulomatous thyroiditis?

Answer 7

chronic inflammatory infiltrate and fibrosis may replace the foci of injury

Question 8

what is the most common cause of hypothyroidism, in regions where dietary iodine levels are sufficient?

Answer 8

Hashimoto thyroiditis

Question 9

autoimmune thyroiditis characterized by progressive destruction of thyroid parenchyma, Hurthle cell change, and mononuclear (lymphoplasmacytic infiltrates, with germinal centers and with/without extensive fibrosis

Answer 9

Hashimoto thyroiditis

Question 10

often occurs after a pregnancy, is typically painless, and is characterized by lymphocytic inflammation in the thyroid

Answer 10

subacute lymphocytic thyroiditis (postpartum thyroiditis)

- is also a type of autoimmune thyroiditis

Question 11

self-limited disease, probably secondary to a viral infection, and is characterized by pain and the presence of a granulomatous inflammation of the thyroid

Answer 11

granulomatous (de Quervain) thyroiditis

Question 12

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

Answer 12

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

Question 13

what does administration of iodine cause in Graves disease?

Answer 13

involution of the epithelium and the accumulation of colloid by blocking thyroglobulin secretion

Question 14

what does treatment with the antithyroid drug propylthiouracil (PTU) cause?

Answer 14

it exaggerates epithelial hypertrophy and hyperplasia by stimulating TSH secretion

Question 15

what are the changes in extrathyroidal tissue listed?

Answer 15

• 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

Question 16

what is characterized by the triad of thyrotoxicosis, ophthalmopathy and dermopathy?

Answer 16

Graves disease

- most common cause of endogenous hyperthyoidism

Question 17

autoimmune disorder caused by activation of thyroid epithelial cells by autoantibodies to TSH receptor that mimic TSH action

Answer 17

Graves disease

Question 18

how is the thyroid characterized in Graves disease?

Answer 18

diffuse hypertrophy and hyperplasia of follicles and lymphoid infiltrates

Question 19

what causes ophthalmopathy and dermopathy in Graves disease?

Answer 19

glycosaminoglycan deposition and lymphoid infiltrates

Question 20

what are the levels of TSH and free T3/4 in Graves disease?

Answer 20

• free T3/4 are HIGH

- TSH is LOW

Question 21

what are the two phases of a diffuse nontoxic goiter?

Answer 21

1. hyperplastic phase

2. colloid involution

Question 22

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

Answer 22

the hyperplastic phase of a nontoxic goiter

Question 23

what happens dietary iodine subsequently increases or if the demand for thyroid hormone decreases during the hyperplastic phase of a nontoxic goiter?

Answer 23

the stimulated follicular epithelium involutes to form an enlarged, colloid-rich gland -> COLLOID GOITER

Question 24

what does a colloid goiter look like?

Answer 24

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

Question 25

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)

Answer 25

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

Question 26

what is it called when the goiter grows behind the sternum and clavicles?

Answer 26

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

Question 27

what is seen on microscopy of a multinodular goiter?

Answer 27

colloid-rich follicles lined by flattened, inactive epithelium and areas of follicular hyperplasia, accompanied by degenerative changes related to physical stress

Question 28

how do multinodular goiters differ from follicular neoplasms?

Answer 28

they lack a prominent capsule between the hyperplastic nodules and residual compressed thyroid parenchyma

Question 29

what features are important in making the distinction between a thyroid adenoma and multinodular goiter?

Answer 29

thyroid adenoma is a solitary, spherical, encapsulated lesion that is demarcated from the surrounding thyroid parenchyma by a well-defined, intact capsule

Question 30

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

Answer 30

follicular adenoma

Question 31

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

Answer 31

follicular adenoma

Question 32

what is the hallmark of all follicular adenomas?

Answer 32

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**

Question 33

what does extensive mitotic activity, necrosis, or high cellularity warrant?

Answer 33

close inspection to exclude follicular carcinoma and the follicular variant of papillary carcinoma

Question 34

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

Answer 34

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

Question 35

papillary carcinomas may contain branching papillae, which are what?

Answer 35

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

Question 36

what do the nuclei of papillary carcinoma cells contain?

Answer 36

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

Question 37

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

Answer 37

psammoma bodies

Question 38

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

Answer 38

follicular variant of papillary carcinoma

Question 39

which variant has a generally favorable prognosis?

Answer 39

encapsulated follicular variant

Question 40

which variants need to be treated more aggressively?

Answer 40

poorly circumscribed and infiltrative lesions

Question 41

what are the genetic alterations that differ in the follicular variant of papillary carcinomas?

Answer 41

- lower frequency of RET/PTC rearrangements - lower frequency and different spectrum of BRAF mutations - *significantly higher frequency of RAS mutations*

Question 42

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

Answer 42

tall-cell variant

Question 43

what are the genetic alterations that differ in the tall-cell variant of papillary carcinomas?

Answer 43

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

Question 44

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%

Answer 44

diffuse sclerosing variant carcinomas

Question 45

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

Answer 45

papillary microcarcinoma

Question 46

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

Answer 46

follicular carcinoma

Question 47

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

Answer 47

follicular carcinomas

Question 48

why is the diagnosis of widely invasive follicular carcinoma obvious?

Answer 48

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

Question 49

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

Answer 49

sporadic medullary thyroid carcinoma

Question 50

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

Answer 50

medullary thyroid carcinoma

Question 51

what is one of the characteristic features of familial medullary cancers?

Answer 51

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

Question 52

most thyroid neoplasms manifest as what?

Answer 52

solitary thyroid nodules | - only 1% of nodules are neoplastic

Question 53

what are the most common benign neoplasms?

Answer 53

follicular adenomas

Question 54

what are the most common malignancies?

Answer 54

papillary carcinoma

Question 55

what two tumors are both composed of well-differentiated follicular epithelial cells?

Answer 55

follicular adenomas and carcinomas | - carcinomas are distinguished by evidence of capsular and/or vascular invasion

Question 56

what tumors are recognized based on nuclear features (ground-glass nuclei, pseudoinclusions) even in the absence of papillae?

Answer 56

papillary carcinomas

Question 57

what are a characteristic feature of papillary carcinomas?

Answer 57

psammoma bodies | - these neoplasms often metastasize by way of lymphatics, but prognosis is excellent

Question 58

what tumors are thought to arise by dedifferentiation of more differentiated neoplasms?

Answer 58

anaplastic carcinomas

Question 59

what tumors are neoplasms arisiing from the parafolicular C-cells and can occur in either sporadic (70%) or familiar (30%) settings?

Answer 59

medullary cancers

Question 60

what are the features of familial medullary thyroid cancers?

Answer 60

multicentricity and C-cell hyperplasia

Question 61

what is a characteristic hostologic finding of medullary thyroid cancer?

Answer 61

amyloid deposits