Pathology - Handorf II Flashcards

1
Q

Thyroid Nodules

A

-solitary nodules are more likely to be neoplastic than multiple nodules
-nodules in younger patients or males are more likely to be noeplastic
-History of radiation of head/neck is associated with increased thyroid malignancy
-Radionuclide imaging: hot almost always benign
cold nodules 10% malignant

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2
Q

Benign Thyroid Nodules

A
  • “colloid” nodules
  • Follicular adenomas
  • Cysts
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3
Q

Malignant Thyroid Nodules

A
  • Papillary Carcinoma (75-85%)
  • Follicular carcinoma (10-20%)
  • Medullary carcinoma (5%)
  • Anaplastic carcinoma (<5%)
  • Rare malignancies

Needle aspiration of these nodules with cytologic evaluation of the aspirated material is a rapid and cost effective diagnostic technique.

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4
Q

Distinguishing Follicular Adenoma and Follicular Carcinoma

A

-Cannot distinguish follicular adenoma from follicular carcinoma on fine needle aspirate—diagnosis will be “follicular lesion”
Cytologic characteristics including nuclear features, mitotic figures, etc are the same for both benign and malignant follicular lesions
Capsular and/or vascular invasion (or metastasis) must be demonstrated on surgically excised tissue to diagnose malignancy

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5
Q

Follicular Adenoma Pathology

A
  • solid, well circumscribed, encapsulated, and fairly homogeneous in appearance. These are all features of a benign lesion, but the lack of capsular and vascular invasion must be confirmed on microscopic evaluation to be certain that this is benign.
  • Solid, trabecular, or follicular patterns can be expressed in adenomas; all produce colloid to some extent. The major feature of an adenoma is lack of microscopic invasion.
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6
Q

Thyroid Carcinoma

A

Circa 1.0% of human malignancies
125/1324 well differentiated thyroid
carcinomas had head or neck
radiation in childhood; these were
more likely to be bilateral
1515/15,200 thyroid carcinomas in
surgical specimens [10.0%]
35.0% of 258 thyroid carcinomas
were poorly differentiated
Medullary and anaplastic tumors after age 40 years; papillary and follicular carcinomas before age 40 years
Large series: 1,074/1,578 papillary carcinomas [68%]; 504 follicular
Two small cell carcinomas in 110 medullary carcinomas, a series which included both familial and sporadic types

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7
Q

Prognosis in Thyroid Carcinoma

A
Type             5 years   10 years     
  -----------------------------------------
  Papillary          92%       87%
  Follicular         74%       66%
  -----------------------------------------
  Key factors: age and spread beyond
  capsule at diagnosis
-Medullary carcinoma prognosis is
  similar to papillary carcinoma
-The thyroid malignancy is the direct 
cause of death in half of papillary
carcinoma and two-thirds of the
follicular type
-Immediate post operative mortality is
about 1.0%
-Post treatment recurrence: 8.7%
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8
Q

Papillary Carcinoma

A
  • not to be as circumscribed as benign lesions
  • no papillary thyroid adenomas - all carcinoma
  • can produce lamellar calcified structures known as “psammoma” bodies
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9
Q

Follicular Carcinoma

A
  • tend not to be as well circumscribed as follicular adenomas
  • presence of capsular invasion (in carcinoma)
  • also vascular invasion
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10
Q

Medullary Carcinoma

A
  • Tumor of the parafollicular cells (“C cells”) which are responsible for producing calcitonin; patients present with hypocalcemia.
  • 80% are sporadic; others seen in MEN IIA (germline mutation in RET protooncogene), MEN IIB, and in non-MEN familial cases
  • May be solitary or multiple/bilateral and typically produce amyloid
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11
Q

Anaplastic Carcinoma

A
  • Rare, but terrible prognosis; typically invade locally and metastasize widely
  • Mean age of 65 years
  • Most have history of thyroid disease (goiter or differentiated carcinoma); 20-30% have concurrent differentiated carcinoma (often papillary)
  • Theorized that anaplastic ca develops in the context of other tumors with loss of p53 tumor suppressor gene
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12
Q

Anaplastic Giant Cell Carcinoma

A
  • one of the worst human cancers (10% 2 year survival)

- rapidly enlarging neck

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13
Q

Lymphoma

A

2% of all malignant thyroid tumors and is almost always of B-cell lineage. The main presenting symptom is a rapidly enlarging goiter and approximately half present with disease limited to the thyroid gland. Due to its rarity, there is limited information with regard to prognosis or management. Pre-existing chronic autoimmune (Hashimoto’s) thyroiditis is the only known risk factor.

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14
Q

Small Cell Carcinoma

neuroendocrine carcinoma

A

-most commonly seen in the lungs (also called “oat cell carcinoma”) and is associated with smoking. Primary small cell cancers are seen in almost every other organ, however; the thyroid is no exception. -small cell carcinoma originating in the thyroid is highly malignant. It is usually metastatic at time of initial diagnosis.

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15
Q

Malignant Struma Ovarii

A

-Very rarely, thyroid carcinoma will develop in struma ovarii. This may be follicular or papillary carcinoma or may be, as in the case shown above, be very poorly differentiated and difficult to classify

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16
Q

Parathyroid Anatomy and Development

A

The four parathyroid glands (2 superior and 2 inferior) develop from the third and fourth branchial pouches. The 2 inferior parathyroids develop from the third branchial pouch, which also gives rise to the thymus, whilst the 2 superior parathyroids develop from the fourth branchial pouch. Recent molecular genetic studies have identified some of the genes (eg. GATA3, Gcm2 and Hoxa3) involved in these developmental pathways of the branchial pouches and parathyroids. Normally, the four parathyroids are located posterior to the thyroid at the upper an lower poles; up to eight parathyroids have been described, however, and they may be seen intrathyroidally or even in the mediastinum.

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17
Q

Parathyroid Adenoma

A
  • A tumor of the parathyroid gland and the most common disorder of the gland.
  • gland increases in size and produces PTH in excess with resultant hypercalcemia.
  • patients normally unaware of the tumors, and they are found when a patient’s routine blood test results have elevated blood calcium and PTH levels.
  • In more serious cases, the bone density will diminish and kidney stones can form. Other non-specific symptoms include depression, muscle weakness, and fatigue.
  • Moans, bones, and stones*

Pathologically, adenomas distinguish themselves by being larger than normal parathyroid glands and by not having the usual complement of fat seen in normal parathyroids; also, there will often be a rim of normal parathyroid tissue “hugging” the adenoma.

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18
Q

Parathyroid Carcinoma

A

very rare

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19
Q

Parathyroid Hyperplasia

A

-is defined as an absolute increase in the mass of the parenchymal cells of the parathyroid gland, usually via hyperplasia of all of the glands. The vast majority of cases are secondary to a hyperplasia of the chief cells. Patients present with increased production of parathyroid hormone leading to an increase in serum calcium. The presenting symptoms are similar to patients with parathyroid adenomas. The most important bit of information is the status of the other parathyroid glands. If all or most of the glands are enlarged, a diagnosis of hyperplasia is likely. If only one gland is enlarged, a diagnosis of adenoma is favored

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20
Q

Anatomy of Adrenal Glands

A
  • paired glands
  • composed of 2 endocrine organs, retroperitoneal, superomedial to kidneys, each weighs 4-5grams
  • cortex, medula
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21
Q

The 3 layers of cortex?

A
  • mesodermal orgion
    1) Glomerulosa - mineralocorticoids “salt”
    2) Fasciculata - glucocorticoids “sugar”
    3) Reticularis - estrogens & androgens “sex”
22
Q

Medulla of Adrenals

A
  • neuroectodermal orgion

- epinephrine and norepinephrine

23
Q

What determines adrenal shape?

A
  • configuration of surrounding organs

- if kidney absent, its more spherical

24
Q

Shark

A

-cortex and medulla are completely separate

25
Q

Amphibia

A

-cortex and medulla are in close contact

26
Q

Birds

A

-cortex and medulla are completely intermingled

27
Q

Microanatomy of Adrenals

A

-shows capsule, glomerulosa, fasciculata, reticularis, medulla

28
Q

Cushing Syndrome

A
  • truncal obesity, skin streai, breast, small penis, ache, moon face
  • tied with effects of cortisol
29
Q

Cushing Disease

A
  • Dr. Cushing
  • “pituitary Cushing syndrome”
  • responsible for 65% of endogenous Cushing syndrome
30
Q

Hyperaldosteronism

A
  • small group of uncommon syndromes characterized by excess aldosterone production
  • Clinically: HTN and hypokalemia, high Na
  • commonly due to aldosterone secreting cortical adenoma (COnn Syndrome)
31
Q

Adrenal Adenoma

A

-often yellow

32
Q

Adrenogenital Syndrome

A
  • 21-Hydroxylase or 11-beta-hydroxylase deficiency impairs the synthesis of both cortisol & aldosterone
  • decrease feedback inhibition causes increased secretion of adrenocorticotropic hormone
  • ultimately results in adrenal hyperplasia and increased synthesis of testosterone
33
Q

Acute Adrenal Insufficiency

A

Prototype: Waterhouse-Friderichsen Syndrome
Other Causes:
-sudden withdrawal of exogenous corticosteroids
-patients w/chronic adrenal insufficiency with sudden stress

34
Q

Waterhouse-Friderichsen Syndrome

A
  • overwhelming sepsis in adults (N. meningitidis) leading to disseminated intravascular coagulopathy, hypotension, shock, acute adrenal insufficiency
  • other causal bacteria (staphlococcus, pneumococcus, Haemophilus)
  • Newborns: may be due to perinatal trauma/hypotension

“bag of blood”

35
Q

Waterhouse-Friderichsen Syndrome Symptoms

A
  • DIC
  • diffuse purpura
  • sepsis
36
Q

Chronic Adrenal Insufficiency Symptoms

A

“Addisonian” Addison’s Disease

  • weakness, nausea, weight loss, hypotensive
  • “emotional”
  • original cases were TB
  • autoimmune adrenalitis & hemachromatosis are frequent
  • secondary adrenal insufficiency as Addison disease: Hypothalamic pituitary disease, neoplasm, infection, sarcoidosis
  • Hypothalamic Pituitary supperssion: long term steroid, steroid producing neoplasms
37
Q

Skin in Primary hypoadrenocorticism

A
  • skin & buccal mucosa will usually be hyperpigmented (due to increased ACTH)
  • look at freckles, nipples, palmar creases, old scars
38
Q

Lab studies in Addison’s Disease

A
  • hyponatremia
  • hyperkalemia
  • metabolic acidosis
  • hypoglycemia
  • low serum cortisol
  • low urinary 17-OH-steroids
  • failure to respond to various “stimulation tests” by increasing cortisol output
39
Q

Prognosis of Addisons

A
  • patients can die suddenly and unexpectely before anyone thinks adrenal insufficiency
  • replacement therapy is life saving
40
Q

Post-menopausal women with addisonism get?

A

-osteoporosis because of loss of adrenal androgens

41
Q

Adrenal Cortical Adenoma

A
  • common neoplasm
  • “silent”
  • well circumscribed up to 2.5cm diameter
  • if functional, adjacent & opposite gland is atrophic
  • if non-functional, adjacent & opposite gland normal
  • yellow
42
Q

Micrograph Adrenal Cortical Adenoma

A
  • typical adrenal cortical tissue

- cells arranged in ribbons and cords

43
Q

Adrenal cortical Carcinoma

A
  • uncommon
  • children/adults
  • functioning >90%
  • > 5cm or 50g more likely malignant
  • may be histologicaly bland or aggressive
  • large, yellow, necrotic
44
Q

Adrenal cortical Carcinoma Micrograph

A

-bland, no mitosis, no anaplasia

45
Q

Neuroblastoma

A
  • most common extracranial solid tumor of childhood
  • 650 per year
  • may occur anywhere in sympathetic nervous system or brain, but adrenals and paraaotic ganglia are most common
46
Q

Pheochromacytoma

A
  • in medulla
  • 10% neoplasm, familial, extra-adrenal, bilateral, childhood,
  • surgically correctable cause
47
Q

Pheochromacytoma Gross Appearance

A
  • medulla of adrenal
  • red to tan mass
  • complete yellow cortisol ribbon surrounding the mass
48
Q

Pheochromacytoma Micrograph

A
  • fairly nondescript cells
  • bizarre nucleus in cells
  • cellular atypic does not suggest malignancy and lack of atypia does not suggest benignancy
49
Q

Paraganglion System

A
  • sites of paraganglion cell nests where neoplasms form
  • extra-adrenal portion of system is grouped into 3 families based on anatomic distribution, innervation, & macroscopic structure
    1) branchiometric
    2) intravagal
    3) aorticosympathetic
50
Q

Metastatic Adrenal Neoplasmas

A
  • most common site
    1) lung
    2) breast
  • every other
  • commonest malignant neoplasm in adrenals (by far)
  • multifocal &/or bilateral tumors are almost certainly metastatic
51
Q

Primary Adrenal Neoplasms: Cortex

A
  • adrenal cortical adenoma

- adrenal cortical carcinoma

52
Q

Primary Adrenal Neoplasmas: Medulla

A
  • neuroblastoma

- pheochromocytoma