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Endo/Repro > Midterm > Flashcards

Midterm Flashcards

1
Q

What is the name for the anterior vs posterior pituitary

A

Anterior: adenohypophysis
Posterior: neurohypophysis

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2
Q

How do chromophobe cells stain

A

Poorly

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3
Q

What are the cell types of the anterior pituitary

A
  • somatotrophs: GH
  • mamosomatotrophs: GH and prolactin
  • lactotrophs: prolactin
  • corticotrophs: ACTH, POMC, MSH (melanocytes-stimulating hormone)
  • thyrotrophs: TSH
  • Gonadotrophs: FSH and LH
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4
Q

What are somatotrophs, mamma somatotrophs and lacctotrophs derived from

A

Stem cells that express pituitary transcription factor (PIT-1)

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5
Q

What is required for gonadotroph differentiation

A

Steroidogenic factor 1 (SF-1) and GATA-2

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6
Q

What are causes of hyperpituitarism

A

Pituitary adenoma, secretion of hormones by nonpituitary tumors, hypothalamic disorder

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7
Q

What are causes of hypopituitarism

A

Ischemic injury, surgery, radiation, inflammatory reactions, non functional pituitary adenomas

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8
Q

What are the mass lesion effects on the sella turcica

A

Stellar expansion, bony erosion, disruption of diaphragm sella

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9
Q

Is pituitary apoplexy an emergency

A

Yes; can cause sudden death

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10
Q

What is the most common cause of hyperpituitarism

A

Adenoma in anterior lobe

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11
Q

What is the most common combination in adenomas that secrete 2 hormones

A

GH and prolactin

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12
Q

Who are pituitary adenomas most commonly found in

A

Adults 35-60

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13
Q

How are adenomas classified

A
  • microadenomas: < 1 cm
  • macroadenomas: > 1 cm *non functional more likely to be macro
  • most are clinically silent (pituitary incidentaloma)
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14
Q

What syndromes do lactotrophs cause

A

Galactorrhea and amenorrhea, sexual dysfunction and infertility

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15
Q

What syndromes do somatotrophs produce

A

Gigantism and acromegaly

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16
Q

What syndrome do mammosomatotrophs produce

A

Combined features of GH and prolactin excess

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17
Q

What syndrome do corticotrophs produce

A

Cushing and Nelson syndrome

-subtypes: densely granulated, sparsely granulated, silent

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18
Q

What syndrome do thyrotrophs produce

A

Hyperthyroidism

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19
Q

What syndrome do gonadotrophs produce

A

Hypogonadism, mass effect, hypopituitarism

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20
Q

What are “null cell”

A

Silent gonadotroph adenomas

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21
Q

What is the most common mutation alterations seen in pituitary adenomas

A

G protein mutations; GNAS encodes Gsalpha - in basal state is inactive *seen in somatotroph cell adenomas - aberrant GTPase activity leading to constant activation; also in som corticotrophs adenomas *ABSENT in thyrotroph, lactotrophs, and gonadotrophs b/c do not act via cAMP dependent pathways

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22
Q

Are most pituitary adenomas genetic or sporadic

A

Sporadic

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23
Q

What genes are involved in genetic pituitary adenomas

A

MEN1, CDKN1B, PRKAR1A, AIP

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24
Q

What mutation is seen in pituitary carcinomas

A

HRAS

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25
Q

What does PRRKAR1A encode for

A

Negative regulator of PKA -> LOF leads to inappropriate cAMP activity; present in AD carney complex; associated with GH and prolactin adenomas

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26
Q

What pituitary tumors are associated with LOF in MEN

A

(Tumor suppressor) GH, prolactin and ACTH adenomas

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27
Q

What is a LOF in CDKN1B associated with

A

ACTH adenomas

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28
Q

What is a LOF mutation in Aryl hydrocarbon receptor interacting protein (AIP) associated with

A

GH adenomas *especially if <35

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29
Q

What is the morophology of a typical pituitary adenoma

A

Soft and well circumscribed; large lesions can extend superiority through diaphragm to suprasellar region; can invade sinuses (invasive adenomas); sparse mitosis * cellular monomorphism and absence of reticulum distinguishes pituitary adenomas from nonneoplastic ant pituitary parenchyma

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30
Q

What are atypical adenomas

A

Has elevated mitotic activity and nuclear p53 expression (TP53 mutations); aggressive behavior

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31
Q

What is the most common type of hyperfunctioning pituitary adenoma

A

Prolactin secreting lactotrophs

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32
Q

What is the morphology of lactotroph adenomas

A

Chromophobic cells with localization of PIT-1 - known as sparesely granulated lactotroph adenomas; rarer: acidophilic denely granulated lactotroph adenomas with diffuse PIT-1 expression; have a propensity to undergo calcification - psammoma bodies or pituitary stone formation; serum prolactin correlates to size of adenoma

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33
Q

What can a mass in the suprasellar compartment do

A

Disrupt normal inhibitory influence of hypothalamus on prolactin secretion

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34
Q

How are lactotroph adenomas treated

A

Surgery or bromocriptine (dopamine receptor agonist)

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35
Q

What is the morphology of somatotroph adenomas

A

Densely granulated: acidophilic cells

Sparesley granulated: chromophobe cells with pleomorphic mood and weak staining for GH

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36
Q

What does persistently elevated levels of GH stimulate

A

Hepatic secretion of insulin like GF-1

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37
Q

What are the features of acromegaly

A

Growth seen in skin, soft tissues, viscera (thyroid, heart, liver, adrenals), bones of face hands and feet; bone density can increase (hyperostosis) in spine and hips; prognathism (protruding jaw)

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38
Q

What can GH excess be associated with

A

Gonadal dysfunction, DM, generalized m weakness, HTN, arthritis, CHF and increased risk for GI cancer

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39
Q

How do you dx a somatotroph adenoma

A

Elevated levels of GH and IGF-1; failure to suppress GH with oral glucose (sensitive for acromegaly)

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40
Q

What is the morphology of corticotroph adenomas

A

Usually microadenomas; most often basophilic (Densely granulated) and occasionally chromobphobic (sparse); both stain with periodic acid Schiff (contain POMC)

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41
Q

What is Cushing disease

A

When excess ACTH is produced by the pituitary

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42
Q

What is Nelson syndrome

A

When corticotroph adenomas form after removal of adrenals for treatment of Cushing syndrome; hypercorticolism doe not develop b/c dont have adrenals; mass effect and hyperpigmentation

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43
Q

What are the features of gonadotroph adenomas

A

Produce LH and FSH; most frequent in mild aged omen and men when they become large; pituitary deficiencies can be seen - most commonly impaired secretion of LH; stain for Beta-LH and FSH; FSH usually predominantly secreted; express steroidogenic factor 1 and GATA-2

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44
Q

What do pituitary carcinomas most commonly secrete

A

Prolactin and ACTH; Mets occur late following multiple local recurrences

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45
Q

What is Sheehan syndrome

A

Postpartum necrosis of the anterior pituitary; during pregnancy, ant pituitary grows but blood supply remains the same so relative hypoxia

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46
Q

What are rathke cleft cysts lined by

A

Ciliated cuboidal epithelium

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47
Q

What is empty sella syndrome

A

Any condition or treatment that destroys part or all of the pituitary gland can results in this syndrome;

  • primary: defect in diaphragm allows CSF to herniate and compress pituitary ; occurs in obese women with hx of multiple pregnancies; visual ducts and hyperprolatinemia presentation
  • secondary: mass enlarges sella and is either removed or undergoes infarction leading to loss of pituitary function
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48
Q

What are craniopharyngiomas

A

Benign hypothalamic tumor

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49
Q

What are most malignant tumors in the hypothalamus

A

Met from breast and lung

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50
Q

What are congenital causes of hypopituitarism

A

Mutation in PIT-1; deficient in GH, prolactin and TSH

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51
Q

What does hypopituitarism lead to

A
  • dwarfism
  • amenorrhea, infertility, decreased libido, impotence, loss o pubic and axillary hair
  • TSH and ACTH def lead to hypothyroidism and hypoadrenalism
  • failure of postpartum lactation
  • pallor due to loss of MSH
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52
Q

What are the most common hypothalamic suprasellar tumors

A

Gliomas and craniopharyngiomas (arises from remnants of rathke’s pouch)

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53
Q

What are the features of craniopharyngiomas

A

Bimodal age distribution: 5-15 and 65; sx: headaches and visual disturbances or growth retardation; abnormalities of WNT pathway has Ben reported; can bulge into floor of 3rd ventricle

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54
Q

What is the morphology of craniopharyngiomas

A 
2 histo variants: adamantinomatous (children; most commonly has calcifications); nests of strat squamous embedded in spongy reticulum; palisading; lamellar keratin is diagnostic feature; cholesterol rich cysts (machine oil)
and papillary (adults); squamous; lack keratin, calcification and cysts 
Good prognosis
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55
Q

What is the function of thyroid follicular epithelial cells

A

Converts thyroglobulin into thyroxine (T4) and triiodothyronine (T3)

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56
Q

What are T3 and T4 bound to in circulation

A

Thyroid binding globulin and transthyretin

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57
Q

What kind of receptor does T3 have

A

Nuclear -> results in assembly of multiprotein hormone-receptor complex on thyroid hormone response elements (TREs) in target genes; stimulates carb and lipid catabolism and protein synthesis; brain development in neonate

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58
Q

What can inhibit the thyroid

A

Goitrogens; propylthiouracil inhibits oxidation of iodide and blocks production of T3 and 4; iodide blocks release of thyroid hormones by inhibiting proteolysis of thyroglobulin

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59
Q

What does calcitonin do

A

Promotes absorption of calcium by bones and prevents resorption of bone by osteoclasts

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60
Q

What is thyrotoxicosis

A

Hypermetabolic state caused by elevated circulating levels of free T3 and 4; hyperthyroidism is one cause

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61
Q

What are the most common causes of thyrotoxicosis

A

Diffuse hyperplasia of the thyroid associated with graves dz, hyperfunctional multinodular goiter, hyperfunctional thyroid adenoma

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62
Q

What hormones do the hypothalamus release

A

TRH, CRH, GHRH, GnRH, somatostatin, dopamine

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63
Q

What does the skin of thyrotoxicosis patients look like

A

Soft warm, and flushed (increased blood flow and peripheral vasodilation), increase heat loss, heat intolerance

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64
Q

What is thyrotoxic (hyperthyroid) cardiomyopathy

A

Left ventricular dysfunction and low output heart failure caused by hyperthyroidism

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65
Q

What is thyroid myopathy

A

Proximal m weakness and decreased m mass caused by hyperthyroidism

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66
Q

What are the ocular changes associated with hyperthyroidism

A

Wide staring gaze and lid lag (overstimulation of tarsal m - Muller’s m) proptosis only in grave’s dz

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67
Q

How is the skeletal system affected by hyperthyroidism

A

Stimulate bone resorption, increasing porosity of cortical bone and reducing volume of trabecular bone; atrophy of skeletal m with fatty infiltration and focal interstitial lymphocytic infiltrates; lymphoid hyperplasia nad LAD in graves dz

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68
Q

What causes thyroid storm

A

Graves dz; excess of catecholamines in asso with infection, surgery, cessation of antithyroid meds, any form of stress; patients fertile and tachycardia out of proportion to fever *medical emergency

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69
Q

What is apathetic hyperthyroidism

A

Thyrotoiosis in older adults in whom advanced age blunts features of thyroid hormone excess

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70
Q

What are the primary diseases associated with hyperthyroidism

A

Diffuse hyperplasia (graves), hyperfunctioning multinodular goiter, hyperfuncioning adenoma, iodine induced hyperthyroidism, neonatal thyrotoxicosis assoc with maternal graves

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71
Q

What are the secondary causes of hyperthyroidism

A

TSH-secreting pituitary adenoma

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72
Q

What are the diseases not associated with hyperthyroidism

A

Granulomatous thyroditis (painful), subacute lymphocytic thyroidtis (painless), strums ovarii (ovarian teratoma with ectopic thyroid), fictitious thyrotoxicosis (exogenous thyroxine intake)

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73
Q

What is the most useful test for dx of hyperthyroidism m

A

TSH levels (decreased); confirm with measurement of T4

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74
Q

How do you confirm a dx of secondary hyperthyroidism

A

Inject TRH; if normal rise in TSH - exclude secondary hyperthyroidism

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75
Q

After confirming dx of hyperthyroidism, how do you determine the etiology

A

Radioactive iodine uptake measurement (if diffuse uptake - graves, if uptake in solitary nodule - toxic adenoma, if decreased uptake - thyroiditis)

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76
Q

How do you treat hyperthyroidism

A

Beta blocker, thionamide to block new hormone synthesis, iodine solution to block release of thyroid hormone, and agents that inhibit peripheral conversion of T4 to T3; or radioiodine

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77
Q

What is the most common cause of congenital hypothyroidism

A

Endemic iodine deficiency in diet

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78
Q

What are other causes of congenital hypothyroidism

A

Inborn errors of thyroid metabolism (dyshormogenetic goiter), thyroid agenesis, thyroid hypoplasia

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79
Q

What mutations can cause defects in thyroid development

A

PAX8, FOXE1, TSH receptor

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80
Q

What mutation causes thyroid hormone resistance syndrome

A

THRB

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81
Q

What drugs can cause hypothyroidism

A

Lithium, iodides, p-aminosalicylic acid

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82
Q

What is the most common cause of hypothyroidism in iodine sufficient areas

A

Autoimmune

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83
Q

What abs are seen in hashimotos

A

Anti microsomal, antithyroid peroxidase and antithyroglobulin

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84
Q

What can autoimmune hypothyroidism occur in conjunction with (but not always)

A

Autoimmune polyendocrie syndromes (APS) types 1 and 2

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85
Q

What is cretinism

A

Hypothyroidism that develops in infancy or early childhood; impaired development of skeletal system and CNS, severe mental retardation, short stature, coarse facial features, protruding tongue, umbilical hernia; depends on iodine intake by mother

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86
Q

What is myxedema

A

Hypothyroidism developing in older children or adults; slowing of physical and mental activity - initially generalized fatigue, apathy, and mental sluggishness; speech and intellectual functions slowed; cold intolerance, overweight, constipation, decreased sweating, skin cool and pale, SOB, reduced exercise capacity; decreased transcription of calcium ATPases and beta adrenergic receptor -> low CO, increase in LDL, nonpitting edema, broadening and coarsening of facial features, enlargement of tongue and deepening of voice due to accumulation of matrix substances

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87
Q

What is the most sensitive test for dx of hypothyroidism

A

TSH - increased in primary

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88
Q

What is strums lymphomatosa

A

Lymphocytic infiltration of thyroid - seen in hashimotos

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89
Q

What is the profile for people affected typically by hashimotos

A

45-65 women

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90
Q

What is the pathogenesis of hashimoto thyroiditis

A

Breakdown in self tolerance to thyroid autoantigen; genetic mutations: CTLA4, PTPN22 (protein tyrosine phosphatase 22)

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91
Q

What contributes to thyroid cell death in hashimoto

A

CD8 mediated cell death, cytokine mediated cell death (activation of CD4 cells), binding of antithyroid abs followed by ab-dependent cell mediated cytotoxicity

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92
Q

What is the morphology of hashimoto

A

Infiltration of mononuclear cells containing small lymphocytes, plasma cells, well-developed germinal centers; hurthle cells; no invasive fibrosis beyond the capsule

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93
Q

What is the clinical presentation of hashimoto

A

Painless enlargement of gland; hypothyroidism develops gradually

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94
Q

What is hashitoxicosis

A

When hypothyroidism is preceded by transient thyrotoxicosis caused by disruption of thyroid follicles; T3 and 4 elevated, TSH decreased, radioactive iodine uptake decreased

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95
Q

What are people with hashimotos at increased risk for

A

Autoimmune diseases and extranodal marginal zone B cell lymphomas within the thyroid

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96
Q

What is subacute lymphocytic thyroiditis

A

Painless thyroiditis; comes to attention because of mild hyperthyroidism, goitous enlargement of the gland or both; more common in middle aged women *subset: postpartum thyroiditis - circulating antithyroid peroxidase abs or family hx of autoimmune dz; can turn into hashimotos

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97
Q

What is the morphology of subacute lymphocytic thyroiditis

A

Lymphocyte infiltration; but o fibrosis or hurthle cell metaplasia

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98
Q

What is the pathogenesis of granulomatous thyroiditis

A

Aka dequervain; thought to be triggered by virus; seasonal incidence (peak in summer)

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99
Q

What is the morphology of granulomatous thyroiditis

A

Gland is uni or b/l enlarged and firm; intact capsule that can adhere to surrounding structures; multinucleated giant cells; fibrosis later on

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100
Q

What is the clinical course of granulomatous thyroiditis

A

Pain (most common cause); enlargement; transient hyperthyroidism (diminishes over weeks even if not treated); radioactive uptake is diminished

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101
Q

What is riedel thyroiditis

A

Extensive fibrosis of thyroid and adjacent structures; associated with fibrosis of other sites (retroperitoneum) *IgG4 related disease

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102
Q

What is the triad found in Graves’ disease

A

Hyperthyroidism, infiltrative opthalmopathy, and localized infiltrative dermopathy (pretibial myxedema)

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103
Q

What population is graves seen in

A

Women 20-40

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104
Q

What abs are found in Graves’ disease

A

Anti TSH receptor ; TSI (thyroid stimulating immunoglobulin) - mimics TSH -> stimulates adenyly Cyclase and releasing hormones

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105
Q

What genetics are involved in graves

A

Mutations in CTLA4 and PTPN22; and HLA-DR3

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106
Q

What is the morphology of graves

A

Thyroid symmetrically enlarged due to diffuse hypertophy and hyperplasia of thyroid follicular epithelial cells; tall cells that are crowded and form papillae that lack fibrovascular cores; colloid has scalloped margins germinal centers

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107
Q

What extrathyroidal changes can occur to tissue in graves dz

A

Lymphoid hyperplasia, especially enlargement off thymus; hypertrophied heart, ischemic changes, orbital edema

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108
Q

What features of thyrotoxicosis are unique to graves

A

Diffuse hyperplasia of the thyroid, opthalmopathy and dermopathy

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109
Q

What happens to the blood flow to the thyroid in graves

A

Can increase and cause a bruit

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110
Q

What happens to radioiodine uptake in graves

A

Increases

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111
Q

What causes goiter

A

Impaired synthesis of thyroid hormone; leads to increase in TSH which causes hypertrophy and hyperplasia of thyroid -> euthyroid

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112
Q

What is diffuse nontoxic goiter

A

Enlargement of thyroid w/o nodularity; aka colloid goiter

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113
Q

What are the 2 types of diffuse nontoxic goiter

A
  • endemic: geographic areas with low level o iodine; also can be caused by goitrogens (broccoli,cabbage, Brussels sprouts, cassava)
  • sporadic: less frequent; more in females in puberty; can be an inherited condition (AR)
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114
Q

What is the clinical course of diffuse nontoxic goiter

A

Euthyroid; mass effect; in kids, dyshormonogenetic goiter can cause cretinism

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115
Q

What are multinodular goiters

A

Recurrent episodes of hyperplasia of thyroid; produce most extreme thyroid enlargements and are mistake for neoplasms; derive from simple goiter; can lead to rupture of follicles or vessels leading to hemorrhage, calcification and scarring

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116
Q

What is an intrathoracic goiter

A

Aka plunging goiter; multinodular goiter that grows behind sternum and clavicle

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117
Q

What is the clinical course of multinodular goiter

A

Mass effects - airway obstruction, dysphagia, compression of large vessels (SVC syndrome) most are euthyroid

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118
Q

What is toxic multinodular goiter

A

If it has an autonomous nodule that produces hyperhtoidism; known as Plummer syndrome - not accompanied by exopthlamos or dermopathy

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119
Q

What does a radioiodine scan show in multinodular goiters

A

Uneven take up with hot spots; FNA is helpful

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120
Q

What distinguishes multinodular goiter from follicular neoplasms

A

Multinodular goiter lacks a capsule

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121
Q

What kind of thyroid nodules are most likely to be neoplastic

A

Single, younger patients, males

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122
Q

Are follicular adenomas functional

A

Not usually

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123
Q

What mutations are seen in toxic adenomas and toxic multinodular goiters

A

TSH receptor signaling pathway (GNAS and TSHR)

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124
Q

What mutations are seen in non functional follicular adenomas

A

PAX8-PPARG fusion gene

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125
Q

What is the morphology of a follicular adenoma

A

Capsule *does not invade past capsule

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126
Q

How do follicular adenomas present

A

Painless mass; non functioning take up less iodine

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127
Q

Who does thyroid carcinoma occur in

A

Females; but in kids equal in males and females

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128
Q

What are most thyroid carcinomas derived from

A

Follicular epithelium; except medullary

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129
Q

What mutations are even in papillary carcinomas of the thyroid

A

GOF in RET (fusion with PTC)- seen in cancers arising from radiation
or NTRK1
or BRAF- correlates with extrathyroidal extension

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130
Q

What mutations are seen in follicular carcinomas

A

RAS or PI-3K/AKT; PAX8-PPARG

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131
Q

What mutation is seen in anaplastic carcinoma of the thyroid

A

P53

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132
Q

What do familial medullary thyroid carcinomas occur in

A

MEN2; assoc with RET mutation

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133
Q

What is the major risk factor for thyroid cancer

A

Radiation exposure

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134
Q

What is the most common thyroid cancer

A

Papillary carcinoma

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135
Q

What is the morphology of papillary carcinoma of the thyroid

A

Branching papillae with dense fibrovascular cores*, optically clear or empty appearance of nuclei (orphan Annie eye nucleus) - can make dx based on this, psammoma bodies; blood invasion not common; met to cervical LN

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136
Q

What is the follicular variant of papillary carcinoma of the thyroid

A

Features of papillary carcinoma but with follicular architecture; can be encapsulated (favorable prognosis) or poorly circumscribed (more aggressive); higher propensity to angioinvade and lower LN Mets

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137
Q

What is the tall-cell variant of papillary carcinoma

A

Tall columnar cells; tend to occur in older individuals and have higher frequencies of vascular invasion, extrathyroidal extension and cervical and distant mts

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138
Q

Who does the diffuse sclerosing variant of papilary carcinoma occur in

A

Younger individuals; contains nests of squamous metaplasia; extensive diffuse fibrosis;; LN met almost always

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139
Q

What is papillary microcarcinoma

A

< 1 cm

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140
Q

Where does papillary carcinoma most likely met

A

Lung

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141
Q

How do papillary carcinomas show up on radionuclide scanning

A

Cold

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142
Q

What is the prognosis of papillary thyroid cancer

A

Excellent

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143
Q

What does the prognosis of someone with papillary thyroid cancer depend on

A

Age, presence of extrathyroidal extension, and presence of distant Mets

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144
Q

How do follicular carcinomas present

A

Slowly enlarging painless nodules; most are cold nodules; dont usually involve lymphatics; vascular spread common - Mets to bone, liver, lung; prognosis based on extent of invasion

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145
Q

How are follicular carcinomas treated

A

Thyroidectomy with administration of radioactive iodine

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146
Q

What is the morphology of anaplastic carcinoma

A

Contain giant cells, spindle cells, and mixed; positive for cytokeratin but negative for thyroglobulin

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147
Q

What is medullary carcinoma of the thyroid

A

Neuroendocrine neoplasms derived from parafollicular cells; secrete calcitonin; can sometimes elaborate serotonin, ACTH or VIP; either sporadic or with MEN2A or 2B or familial medullary thyroid carcinoma

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148
Q

What is the morphology of medullary carcinoma

A

If b/l more likely to be familial; *amyloid deposits; in familial lesions - C cell hyperplasia seen

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149
Q

Is hypocalcemia a feature of medullary thyroid carcinoma

A

No

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150
Q

What is a useful bio marker for medullary carcinoma

A

Carcinoembryonic antigen

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151
Q

What is true of medullary carcinoma associated with MEN2B

A

It is more aggressive and met more frequently (offered prophylactic thyroidectomy)

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152
Q

What are the parathyroid glands composed of

A

Chief and oxphil cells

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153
Q

What are the actions of PTH

A

Increases Neal tubular reabsorption of calcium, increases conversion of vit D to active form, increases urinary phosphate excretion, augments GI calcium absorption

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154
Q

What is tertiary hyperparathyroidism

A

Persistent hypersecretion of PTH even after the cause of prolonged hypocalcemia is corrected (ie after renal tx)

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155
Q

Who is primary hyperparathyroidism common in

A

Women adults; most common cause is adenoma

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156
Q

What genetic defects cause sporadic parathyroid adenomas

A

Cyclin D1 gene inversions

MEN1 mutations

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157
Q

How can you preoperatively distinguish parathyroid adenomas from hyperplasia

A

Technetium sestamibi radionuclide scan

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158
Q

What genetic syndromes are associated with familial parathyroid adenomas

A

MEN 1 and 2 (MEN and RET mutations, respectively), familial hypocalciuric hypercalcemia (AD caused by LOF in CASR)

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159
Q

What is the morphology of parathyroid adenomas

A

Almost always solitary; composed of chief cells; uncommonly composed entirely of oxphil cells (oxphil adenomas); loss of adipose tissue

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160
Q

What is the morphology of primary parathyroid hyperplasia

A

Mostly of chief cells; loss of fat

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161
Q

What is the only reliable criteria for diagnosis of parathyroid carcinomas

A

Invasion of surrounding tissue

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162
Q

What are the skeletal manifestations of primary hyperparathyroidism

A

Osteoporosis (affects cortical bone more than medullary bone) - in medullary bone creates appearance of railroad tracks -> dissecting osteitis; can lead to fractures and hemorrhage high create a mass of reactive tissue known as a brown tumor (generalized osteitis fibrosis cystica)

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163
Q

What is the effect of primary hyperparathyroidism on the urinary tract

A

Nephrolithiasis an calcification of renal interstitium and tubules (nephrocalcinosis)

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164
Q

Is primary hyperparathyroidism usually symptomatic

A

No; usually caught before sx

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165
Q

What are the GI sx of hyperparathyroidism

A

Constipation, nausea, peptic ulcer, pancreatitis, gallstones

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166
Q

What are the CNS sx of primary hyperparathyroidism

A

Depression, lethargy, seizures

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167
Q

What are the neuromuscular features of primary hyperparathyroidism

A

Weakness and fatigue

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168
Q

What are the cardiac manifestations of primary hyperparathyroidism

A

Aortic or mitral valve calcifications

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169
Q

What are causes of hypercalcemia with decreased PTH

A

Malignancy, vit D toxicity, immobilization, thiazides, granulomatous dz (sarcoidosis)

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170
Q

What are causes of secondary hyperparathyroidism

A

Renal dz, vit d deficiency, steatorrhea

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171
Q

How does chronic renal failure lead to hyperPTH

A

Decreased phosphate excretion -> binds to calcium -> sensed as low -> increases PTH; also renal failure means cannot synth vit D and cannot absorb calcium

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172
Q

What is renal osteodystrophy

A

Skeletal abnormalities seen as a result of renal failure from hyperparathyroidism

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173
Q

What effect can secondary hyperparathyroidism have on the skin

A

Can cause calcification and lead o ischemia - calciphylaxis

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174
Q

How do you treat secondary hyperparathyroidism

A

Dietary vit d supplementation, phosphate binders

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175
Q

What is autoimmune hypoparathyroidism associated with

A

Chronic mucuocutanous candidiasis and primary adrenal insufficiency known as autoimmune polyendocrine syndrome type 1 (APS1) caused by mutation in AIRE; presents in childhood

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176
Q

What is AD hypoparathyroidism

A

Caused by GOF in CASR; senses low calcium as sufficient and suppresses PTH resulting in hypocalcemia and hypocalcuria

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177
Q

What is familial isolated hypoparathyroidism (FIH)

A

Rare; either AD (caused by mutation in PTH precursor peptide) or AR (LOF of glial cells missing-2 GCM2)

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178
Q

What can congenital absence of the parathyroid occur in

A

Digeorge (chrom 22)

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179
Q

What are the sx of hypoparathyroidism

A

Numbness, paresthesias, carpopedal spasm, laryngospasm, seizures, mental status change, calcifications of basal ganglia, parkinsonian-like movement, increased ICP, ocular disease (calcification of lens and cataract formation), prolongation of QT, dental hypoplasia, defective enamel

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180
Q

What is pseudohypoparathyroidism

A

Occurs because of end organ distance to actions of PTH; PTH normal or elevated; defect in G proteins; presents as hypocalcemia, hyperphosphatemia, and PTH

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181
Q

What does somatostatin do to insulin and glucagon

A

Inhibits their release

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182
Q

What does pancreatic polypeptide do

A

Stimulation of secretion of gastric acid and intestinal enzymes and inhibition of intestinal motility

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183
Q

What do D1 cells secrete

A

VIP. - induces glycogenolysis and hyperglycemia; stimulates I fluid secretion and causes secretory diarrhea

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184
Q

What do the enterochromaffin cells synthesize

A

Serotonin; source of pancreatic tumors that cause carcinoid syndrome

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185
Q

What is normal blood glucose

A

70-120

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186
Q

What is the diagnostic criteria for diabetes

A

Fasting plasma glucose >126, random plasma glucose >200, 2 hour plasma glucose >200 during oral glucose tolerance test with 75 load, HgbA1C >6.5

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187
Q

What is prediabetes defined as

A

Fasting glucose btw 100-125, 2 hour plasma glucose btw 140-199 with 75gm OGTT, HbA1c btw 5.7-6.4

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188
Q

What mutations cause maturity onset diabetes of the young (MODY)

A

Hepatocytes nuclear factor (HNF4A), MODY1, glucokinase, MODY2

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189
Q

What exocrine pancreatic defects cause diabetes

A

Chronic pancreatitis, pancreatic trauma, neoplasia, CF, hemochromatosis, fibrocalculous pancreatopathy

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190
Q

What endocrinopathies cause diabetes

A

Acromegaly, Cushing syndrome, hyperthyroidism, pheochromocytoma, glucagonoma

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191
Q

What infections can cause diabetes

A

CMV, Coxsackie B, congenital rubella

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192
Q

What drugs can cause diabetes

A

Glucocorticoids, thyroid hormone, IFNalpha, protease inhibitors, beta agonists, thiazides, nicotinic acid, phenytoin

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193
Q

What genetic syndromes are associated with diabetes

A

Down syndrome, klinefelter, turner, prader-willi

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194
Q

What abs are seen in T1DM

A

Anti-insulin, anti-GAD, anti-ICA512

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195
Q

Instead of DKA, what are people with T2DM at risk for

A

Nonketotic hyperosmolar coma

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196
Q

What is the genetic diff in T1 vs T2DM

A

T1: HLA linked; also polymorphism in CTLA Nd PTPN22
T2: no HLA; links to candidate diabetognic and obesity relate genes

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197
Q

Which type of diabetes has amyloid deposition in the islets

A

T2DM

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198
Q

How does glucose enter the pancreatic beta cells

A

GLUT 2

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199
Q

How is insulin released

A

Metabolism of glucose generates ATP which inhibits te activity of the ATP sensitive K channel leading to depolarization and influx of Ca2+ which stimulates the secretion of insulin

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200
Q

What are the 2 incretins

A

Glucose dependent insulinotropic polypeptide (GIP) secreted by K cells and glucagon like peptide (GLP-1) secreted by L cells

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201
Q

What happens to the incretin effect in ppl with T2DM

A

Blunted; reason why treated with GLP-1 agonist and DPP 4 inhibitors (DPP 4 breaks down GLP)

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202
Q

What are the actions of insulin

A
  • adipose tissue: increase glucose uptake, lipogenesis and decrease lipolysis
  • striated m: increase glucose uptake, glycogen synthesis and protein synthesis
  • liver: decreased GNG, increased glycogen synthesis and lipogenesis
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203
Q

What pathway translocates GLUT 4 to the membrane

A

AKT and CBL

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204
Q

Which genes are seen with T1DM

A

HLA-DR3 or 4, CTLA4 and PTPN22

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205
Q

How does obesity lead to insulin resistance

A

Adipocytes release adipokines, FFA, and inflammation

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206
Q

What are the results of insulin resistance

A

Failure to inhibit GNG in the liver (leads to high fasting glucose levels), failure to uptake glucose (high post prandial glucose), an failure to inhibit hormone sensitive lipase which leads to excess triglyceride breakdown and excess circulating FFAs

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207
Q

How does exercise improve insulin sensitivity

A

Increased translocation of GLUT 4 to membrane of m cells

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208
Q

How do excess FFAs lead to insulin resistance

A

Overwhelm intracellular FA oxidation pathways leading to accumulation of diacylglycerol which can attenuate inhaling through the insulin receptor

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209
Q

What is not released from adipose tissue in obesity

A

Adiponectin

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210
Q

How does inflammation lead to insulin resistance

A

FFA in macrophage activate inflammasome -> IL-1beta

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211
Q

How does beta dysfunction occur in T2DM

A
  • excess FFA compromise beta function
  • chronic hyperglycemia
  • abnormal incretin effect leading to reduced GIP and GLP
  • amyloid exposition in islets
  • genetics
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212
Q

What is type A insulin resistance

A

Mutation in the insulin receptor; hyperisulinemia and diabetes; acanthosis Nigricans; females typically have polycystic ovaries and increased androgen levels

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213
Q

What is lipoatrophic diabetes

A

Hyperglycemia with loss of adipose tissue in subcutaneous fat; insulin resistance, diabetes, hypertriglyceridemia, acnthosis nigricans and abrnomal fat deposition in the liver

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214
Q

What can poorly controlled gestational diabetes lead to

A

Excessive birth weight (macrosomia), obesity and diabetes in child

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215
Q

What is the triad of type 1 diabetes

A

Polyuria, polydipsia, polyphagia

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216
Q

What hormones are increased in diabetes

A

Glucagon, growth hormone, epi

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217
Q

What kind of diuresis is seen in diabetes

A

Osmotic

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218
Q

How are ketones produced in DKA

A

Insulin def stimulates hormone sensitive lipase -> FFA to liver Nd are oxidized to Ketone bodies (acetoacetic acid an beta hydroxybutyric acid)

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219
Q

What are the manifestations of DKA

A

Fatigue, N/V, severe ab pain, fruity odor and Kussmaul breathing

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220
Q

How do you treat DKA

A

Insulin, correction of acidosis Nd treatment of underlying factors

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221
Q

What is hyperosmolar hyperosmotic syndrome

A

Seen with T2DM; due to severe dehydration resulting from sustained osmotic diuresis - occurs in ppl unable to maintain water intake; impaired mental status *hyperglycemia more severe than in DKA

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222
Q

What is the most common acute metabolic complication in either type of diabetes

A

Hypoglycemia - sx: confusion, sweating, palpitations, tachycardia

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223
Q

Where is microvascular dz related to diabetes seen

A

Kidneys, retina, peripheral nerves

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224
Q

What is the goal of HbA1C in diabetics

A

<7

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225
Q

What are advanced glycation end products

A

AGEs; formed as a result of freactions tw intracellular glucose precursors with amino groups; formation accelerated in presence of hyperglycemia bind to RAGE receptor on inflammatory cells, endothelium and smooth m causing lease of cytokines high leads to deposition of BM, VEGF, ROS, increased procoagulants, and proliferation of vascular smooth mm

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226
Q

How is atherogenesis accomplished in diabetes

A

AGE cross links and prevents efflux of LDL from vessel wall

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227
Q

What does hyperglycemia do to PKC

A

Increases its activation -> leads to production of VEGF, TGF-beta and procoagulants (PAI-1); contributes to microangiopathy

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228
Q

How does hyperglycemia affect tissues that do not require insulin for glucose transport

A

Metabolized by aldose reductase to sorbitol and polygon and eventually to fructose i a reaction that uses NADPH which compromises GSH regeneration and increases suceptibility to oxidative stress

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229
Q

What are the long term complications of diabetes

A

Microangiopathy, CVA, hemorrhage in brain, retinopathy, cataracts, glaucoma, MI, HTN, atherosclerosis, PVD, nephrosclerosis, pyelonephritis, peripheral and autonomic neuropathy

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230
Q

What is diabetic macrovascular dz

A

Atherosclerosis of aorta and large-medium sized arteries

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231
Q

What are the features of diabetic microangiopathy

A

Diffuse thickening of BM;; capillaries are more leaky than normal to plasma proteins; *involvement includes nephropathy, retinopathy Nd neuropathy

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232
Q

What is the morphology of diabetic nephropathy

A

Diffuse mesangial sclerosis, cap BM thickening, nodular glomerulosclerosis

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233
Q

What are the features of nodular glomerulosclerosis

A

Aka kimmelstiel-Wilson dz; nodules are PAS positive; usually accompanied by prominent accumulations of hyaline in cap loops (fibrin caps) or adherent to bowman capsules (capsular drops)

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234
Q

What is a unique feature of renal arteriosclerosis not seen in non-diabetics

A

Arteriosclerosis in efferent arterioles

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235
Q

What special form of pyelonephritis is seen in diabetics

A

Necrotizing papillitis

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236
Q

What are the most common causes of mortality in long standing diabetes

A

Macrovascular complications (CVA, MI, renal vascular insufficiency)

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237
Q

What CV risks are seen in diabetics

A

HTN, dyslipidemia, elevated levels of PAI-1 (inhibitor of fibrinolysis and is therefore procoagulant)

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238
Q

What population of diabetics is at higher risk of developing renal dz

A

non-whites

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239
Q

What is the earliest manifestation of diabetic nephropathy

A

Low albumin in the urine (microalbuminuria) - if see this should then be screened for macrovascular dz

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240
Q

What is the most frequent pattern of involvement of diabetic neuropathy

A

Distal symmetric polyneuropathy of the lower extremities; affects both motor and sensory; over time upper extremity may become involved - glove and stocking pattern

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241
Q

What is autonomic neuropathy

A

Produces disturbances in bowel and bladder function

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242
Q

What is diabetic mononeuropathy

A

Can manifest as footdrop, wristdrop, or isolated CN palsies

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243
Q

What infections are diabetics at increased risk for

A

Pneumonia and TB

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244
Q

What causes the long term complications of diabetes

A

Formation of advanced glycation end product (AGEs), activation of PKC, disturbance in polyol pathways, and overload of hexosamine pathway

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245
Q

What mutations (besides MEN1) are seen in pancreatic neuroendocrine tumors

A

Alpha-thalassemia/mental retardation syndrome, X-linked (ATRX) and death domain associated protein (DAXX)

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246
Q

What are the features of insulinomas

A

Most common; cause hypoglycemia (glucose <50); contusion, loss of consciousness; precipitated by fasting or exercise and relieved by feeding; benign with exception of bona fide carcinomas *deposition of amyloid

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247
Q

What are the features of gastrinomas

A

Most have already met or locally invaded at time of diagnosis; MEN1 associated are multifocal while sporadic are single; *when intractable jejunal ulcers are found, consider zollinger Ellison

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248
Q

What are the clinical manifestations of gastrinomas

A

Most have diarrhea, tx: H/K ATPase inhibitors and excision; if met to liver, short life expectancy

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249
Q

What are the features of alpha cell tumors (glucagonomas)

A

Diabetes, necrolytic migratory erythema, anemia; occur mostly in peri or post menopausal women

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250
Q

What are delta cell tumors (somatostatinomas)

A

Diabetes, cholithiasis, steatorrhea, hypocholrhydria

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251
Q

What are the feature of VIPomas

A

Watery diarrhea, hypokalemia and achlorhydria); some are locally invasive and met; causes severe secretory diarrhea

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252
Q

What are pancreatic carcinoid tumors

A

Produce serotonin

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253
Q

How do pancreatic polypeptide secreting tumors present

A

Mass effect

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254
Q

What is the most common cause of Cushing syndrome

A

Exogenous administration of glucocorticoids

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255
Q

Who does Cushing disease mostly affect

A

Women and younger adults

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256
Q

What causes Cushing disease most often

A

ACTH producing pituitary microadenoma

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257
Q

What is the most common cause of ectopic ACTH secretion

A

Small cell carcinoma; ectopic causes of Cushing more common in men

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258
Q

Do adrenal adenomas or carcinomas produce more hypercorticolism

A

Carcinomas

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259
Q

If the adrenal adenoma or carcinoma is unilateral, what happens to the other gland

A

It atrophied

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260
Q

What are the ACTH independent causes of cushing syndrome

A

Adrenal adenomas or carcinoma, macronodular hyperplasia, primary pigmented nodular adrenal dz, McCune Albright syndrome (GNAS mutation)

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261
Q

What is the morphology of cushing syndrome

A

Pituitary always shows change - crooke hyaline change (resulting from exogenous source) - becomes paler

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262
Q

What is the morphology of the adrenal glands in Cushing

A

Either become atrophic (exogenous), diffuse hyperplasia (ACTH dependent), macronodular or micronodular hyperplasia, or an adenoma/carcinoma

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263
Q

Who are adrenal adenomas/carcinomas more prevlanent in

A

Women in 30s-50s

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264
Q

What are the clinical features of cushing

A

Obesity, facial plethora, rounded face, thin skin, rebased libido, decreased linear growth in kids, menstual irregularity, HTN, hirsutism, depression, easy bruising, glucose intolerance (secondary diabetes), weakness, osteopenia or fracture, nephrolithiasis, proximal limb weakness, increased risk of infections

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265
Q

How do you dx cushing

A

24 hour urine free cortisol concentration is increased, loss of normal diurnal pattern of cortisol secretion

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266
Q

What happens to renin in primary hyperaldoseteronism

A

Decreases

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267
Q

What is b/l idiopathic hyperaldosteronism

A

B/l nodular hyperplasia of adrenal glands; tend to be older and have less severe HTN than those with adrenal neoplasms

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268
Q

What causes conn syndrome

A

Aldosterone producing tumor; more common in women

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269
Q

What is glucocorticoid remediable hyperaldosteronism

A

Cause of primary familial hyperaldosteronism; rearrangement in chrom 8; *suppressible by dexamethasone

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270
Q

What causes secondary hyperaldosteronism

A

Decreased renal perfusion (arteriolar nephrosclerosis, renal a stenosis)
Arterial hypovolemia and edema (CHF, cirrhosis, nephrotic syndrome)
Pregnancy

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271
Q

What is the morphology of aldosterone producing adenomas

A

More common on left in women; often do not produce visible enlargement; *spironolactone bodies found after treatment; NOT atrophic adjacent cortex

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272
Q

What are the long term complications of hyperaldosteronism

A

Left ventricular hypertrophy and reduced diastolic volumes

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273
Q

How is primary hyperaldosteronism diagnosed

A

Elevated ratios of aldosterone:renin activity; if positive, confirm with aldosterone suppression test

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274
Q

What is congenital adrenal hyperplasia

A

Stems from AR inherited metabolic errors -> dont produce cortisol -> shifts to androgen production; if also can’t make aldosterone, will have salt wasting; b/c not making cortisol, ACTH will increase and cause hyperplasia

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275
Q

What is salt wasting syndrome

A

Complete deficiency of 21 hydroxylase; cant make mineralocorticoids or cortisol; salt wasting, hyponatremia, hyperkalemia, acidosis, hypotension, CV collapse, virilization

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276
Q

What is simple virilizing adrenogenital syndrome without salt wasting

A

Presents as genital ambiguity; 21 hydroxylase deficiency; generate sufficient mineralocortoid but not enough cortisol; virilization

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277
Q

What is nonclassic or late onset adrenal virilism

A

Most common; only partial deficiency in 21 hydroxylase; mild manifestations such as hirutism, acne, or menstrual irregularities

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278
Q

What effect do adrenogenital syndromes have on the medulla

A

Cortisol is required to facilitate medullary catecholamines synthesis; so with severe salt wasting syndrome, causes adrenomedullary dysplasia which disposes people to hypotension and collapse

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279
Q

How do you treat congenital adrenal hyperplasia

A

Glucocorticoids; mineralocorticoids if salt wasting

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280
Q

What are the patterns of adrnocortical insufficiency

A

Primary acute adrenocortical insufficiency (adrenal crisis), primary chronic adrenocortical insufficiency (addisons), or secondary adrenocortical insufficiency

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281
Q

What can cause primary acute adrenocortical insufficiency

A
  • crisis in individuals with chronic insufficiency precipitated. By stress
  • in patients on exogenous corticosteroids whom rapidly withdraw treatment
  • as a result of massive adrenal hemorrhage (patients on anticoagulants, post surgical with DIC, Waterhouse friderichsen)
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282
Q

What are the features of Waterhouse friderichsen syndrome

A

Overwhelming bacterial infection, rapidly progressive hypotension leading to shock, DIC with widespread purpura, rapidly developing adrenocortical insufficiency

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283
Q

What diseases most commonly affect the adrenal cortex

A

Autoimmune adrenalitis, TB, AIDS, or metastatic cancers

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284
Q

What is autoimmune polyendocrine syndrome type 1

A

APECED; chronic mucocutaneous candidiasis and abnormalities of the skin, dental enamel and nails (ectodermal dystrophy), autoimmune adrenalitis, hypoparathyroidism, hypogonadism, pernicious anemia; mutation in AIRE; develop abs against IL-17 and IL-22 (reason for development of fungal infections)

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285
Q

What is autoimmune polyendocrine syndrome type 2

A

Combination of adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes

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286
Q

What are genetic causes of adrenal insufficiency

A

Congenital adrenal hypoplasia (X linked), adrenoleukodystrophy

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287
Q

What is the morphology of TB adrenalitis

A

Granulomatous

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288
Q

What are the clinical symptoms of addisons

A

Progressive weakness and fatigue, GI disturbances (anorexia, nausea, vomiting, weight loss, diarrhea), hyperpigmentation of skin (only in primary); hyperkalemia, hyponatremia volume depletion, hypotension

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289
Q

Do you see hyponatremia or hyperkalemia with secondary adrenocortical insufficiency

A

NO because aldosterone regulated separately

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290
Q

Are adrenal adenomas or carcinomas more common

A

Equal in adults; carcinomas more common in kids

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291
Q

What 2 syndromes carry an increased risk of adrenal carcinoma

A

Li-frumpiness syndrome (TP53) and beckwith wiedemann syndrome

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292
Q

Are carcinomas or adenomas of the adrenal most likely to be functional

A

Carcinomas

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293
Q

What is the prognosis for adrenal carcinoma

A

Poor; invades veins and lymphatics

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294
Q

What are adrenal myelolipomas

A

Benign lesions composed of fat and hematopoietic cells

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295
Q

What are the rules of 10 of pheochromocytomas

A

10%:

  • are extra adrenal - paragangliomas
  • of sporadic adrenal pheochromocytomas are b/l
  • are biologically malignant (defined by Mets) - more common in paragangliomas
  • are not associated with HTN
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296
Q

What genes are involved in pheochromocytomas

A

RET, NF1, VHL, SDHB,C,D

297
Q

How can you stain pheochromocytomas

A

Potassium dichromate

298
Q

How do the nuclei of neuroendocrine tumors stain

A

Salt and pepper

299
Q

What is the other name for MEN1

A

Wermer syndrome

300
Q

What is the most common kind of pancreatic tumor in MEN1

A

Pancreatic polypeptide

301
Q

What is the most common pituitary tumor in MEN1

A

Prolactinoma

302
Q

What is the other name for MEN2A

A

Sipple syndrome

303
Q

Does thyroid cancer in the setting of familial medullary thyroid cancer have a better or worse prognosis than MEN2

A

Better

304
Q

What does the pineal gland secrete

A

Melatonin

305
Q

What are tumors off the pineal gland called

A

Germinomas; embryonal carcinomas, choriocarcinoma, teratoma (usually benign)

306
Q

What are Gardner duct cysts

A

Failure of mesonephric ducts to regress in female - form cysts in cervix and vagina

307
Q

What is the epithelial lining of the female genital tract and ovaries?

A

Mesothelium

308
Q

What infections are implicated in preterm deliveries

A

Mycoplasma hominis and ureaplasma urealyticum

309
Q

What part of the female genital tract does HSV affect in order of frequency

A

Cervix, vagina, and vulva (lower genital tract)

310
Q

What are lesions of HSV associated ith

A

Fever, malaise and tender inguinal LN; cervical or vaginal lesions present with severe purulent discharge and pelvic pain; lays dormant in lumbo-sacral nerve Angelia

311
Q

What is the morphology of HSV ulcers

A

Epithelium is desquamated; histo shows multinuclated squamous cells containing viral inclusions with a ground glass appearance

312
Q

Are women or men more susceptible to STIs

A

Women

313
Q

Previous infection with HSV 1 _____ the chance of infection with HSV 2

A

Decreases BUT HSV 2 increases risk for HSV 1

314
Q

What must be done in a pregnant woman with HSV

A

C section

315
Q

What is detection of anti_HSV abs indicative of

A

Recurrent or latent infection

316
Q

What is Molluscum contagiosum

A

Skin or mucosal lesion cause by poxvirus; 4 types of MCVs (1 most prevalent and 2 is most often sexually transmitted); common in children btw 2-12 and transmitted through direct contact; most common on trunk, arms and legs; in adults, most commonly isn’t genital, lower abdomen, butt and inner thighs *pearly, dome shaped papules with a dimpled center - central waxy core has cytoplasmic vial inclusions

317
Q

What increases the risk of vaginal fungal infection

A

Diabetes, abx, pregnancy, compromised neutrophil or Th17 peons

318
Q

How do vaginal fungal infections present

A

Vulvovaginal pruritis, erythema, swelling and curdlike vaginal discharge; severe infection may result in mucosal ulceration

319
Q

How are fungal infections of the lower genital tract diagnosed

A

Inning pseudospores or filamentous fungal hyphae in wet KOH mounts of the discharge or Pap smear; not STI

320
Q

What is trichomonas vaginalis

A

Flagellated ovoid protozoan transmitted sexually and develops within 4 days to 4 weeks; yellow, frothy vagina discharge, vulvovaginal discomfort, dysuria, dyspareunia (painful intercourse); vaginal and cervical mucosa has fiery red appearance with marked dilation of cervical mucosal vessels *strawberry cervix

321
Q

What is gardnerella vaginalis

A

Gram negative bacillus; main cause of bacterial vaginosis/vaginitis; thin, green-grey malodorous discharge Pap smear reveals superficial and intermediate squamous cells covered with shaggy coating coccobacilli; in pregnant patients, leads to premature labor

322
Q

What are ureaplasma urealyticum and mycoplasma hominis implicated in

A

Vaginitis, cervicitis, chorioamnionitis and premature delivery

323
Q

What is the main manifestation of chlamydia trachomatis

A

Cervicitis

324
Q

What are the symptoms of pelvic inflammatory disease

A

Pain, adnexal tenderness, fever, vaginal discharge

325
Q

What is the most common cause of PID

A

Neisseria gonorrhea

326
Q

Besides chlamydia and gonorrhea, what are other causes of PID

A

Infections after spontaneous or induced abortions and deliveries (puerperal infections) - typically polymicrobial and aused by staph, strep, coliorms, and clostridium perfringens - spread via lymphatics or venous rather than mucosal surfaces; tend to produce more inflammation within deeper layers than gonococcal infections

327
Q

What is the morphology of gonococcal infection

A

Acute inflammation of mucosal surfaces; smears show phagocytosed gram negative diplococci within neutrophils; endometrium usually spared but within Fallopian tubes, acute suppurative salpingitis occurs -> spread to ovary (scalping-oophoritis); pus can accumulate and form tubo-ovarian abscess or pyosalpinx; over time, tubal plicae fuse and scar (chronic salpingitis) or hydrosalpinx

328
Q

What is a more frequent complication of strep or staph PID than gonococcal

A

Bacteremia

329
Q

What are the acute complications of PID

A

Peritonitis, bacteremia which can lead to endocarditis, meningitis and suppurative arthritis

330
Q

What is a bartholin cyst

A

Infection of bartholin gland produces acute inflammation (adenitis) and may result i abscess; relatively common; occurs at all ages; lined by transitional or squamous epithelium; can become large and produce pain and discomfort; either excised or opened permanently (marsupialization)

331
Q

What can cause leukoplakia

A

Inflammatory dermatoses (psoriasis, chronic dermatitis), lichen sclerosis and squamous hyperplasia, neoplasia such as vulvar intraepithlial neoplasia (VIN), Paget dz, and invasive carcinoma

332
Q

What is lichen sclerosus

A

Presents as smooth, white plaques or macules that can enlarge or coalesce producing a porcelain or parchment surface; when entire vulva affected, labia become atrophic and agglutinated and vaginal orifice constricts

333
Q

What is the histo of lichen sclerosus

A

Thinning of epidermis, degeneration of basal cells, hyperkeratosis, sclerotic changes of superficial dermis and bandlike lymphocytic infiltrate in underlying dermis; most common in post menopausal women autoimmune suggested *slightly increased change of developing SCC of vulva

334
Q

What is squamous cell hyperplasia of the vulva

A

Caused by rubbing or scratching presents as leukoplakia and histo release thickening of epidermis (acanthosis) and hyperkeratosis; no atypia; sometimes present at margins of vulvar cancer

335
Q

What is condyloma acuminatum

A

Papilloma induced lesion (HPV 6 and 11) aka genital wart; mostly multiple; can affect vulvar, perineal, perianal, vagina, cervix; papillary exophytic treelike cores of stroma covered by thickened squamous cells; *koilocytic atypia (nuclear enlargement, hyperchromasia, and cytoplasmic perinuclear halo)

336
Q

What is condyloma Latum

A

Caused by syphilis

337
Q

What are vulvar fibroepithelial polyps

A

Skin tags

338
Q

What are vulvar squamous papillomas

A

Benign exophytic proliferation’s covered by nonkeratinized squamous cells; can be numerous (papillomatosis)

339
Q

Who does vulvar carcinoma occur in

A

Women > 60

340
Q

What are the types of vulvar SCC

A
  • basaloid and warty related to infection with high risk HPVs (mostly 16); less common and occur at younger ages
  • keratinizing SCC unrelatedly to HPV; more common and occur in older women
341
Q

What is the precursor lesion for basaloid and warty carcinomas

A

Classic vulvar intraepithlial neoplasia (VIN); occurs mainly in reproductive age women - CIS or Bowen dz; risk: young age at first intercourse, multiple sexual partners, male partner with multiple sexual partners; can spontaneously regress; risk of cancer higher in those > 45

342
Q

Who does keratinizing SCC of the vulva most commonly occur in

A

Long standing lichen sclerosus or squamous cell hyperplasia; peak occurrence is 8th decade; arises from differentiated vulvar intraepithlial neoplasia (differentiated VIN) or VIN simplex

343
Q

What is the morphology of classic VIN

A

Discrete white hyperkeratosis pigmented lesions; epidermal thickening nuclear atypia, increased mitosis and lack of cellular maturation; basaloid has nests and cords; warty is exophytic and papillary with koilocytic atypia

344
Q

What is the morphology of differentiated VIN

A

Marked atypia of basal layer of squamous epithelium an normal appearing superficial layers

345
Q

What does the risk of cancer development in VIN depend on

A

Duration and extent of disease and immune status of the patient

346
Q

Where can vulvar cancer spread

A

Inguinal, pelvic, iliac, periaortic LN; then to lungs, liver

347
Q

What is the prognosis for vulvar cancer

A

Small lesions: good

Larger lesions w/ LN involvement: poor

348
Q

What is papillary hidradenoma

A

Presents as sharply circumscribed nodule most commonly on labia majora or interlabial folds; tends to ulcerate; histo: identical to intraductal papilloma of the breast - pap projection covered with 2 layers (upper layer of columnar secretory cells with deeper layer of flattened myoepithelial cells)

349
Q

What is extramammary paget dz

A

Presents as pruritic, red, crusted maplike area usually on labia majora; proliferation of malignant cells; pale cytoplasm containing mucopolysaccharide that stains with PAS, Alcian blue or mucicarmine stains; express cytokeratin 7; apocrine, eccrine and keratinocytes differentiation

350
Q

Is vulvar paget associated with underlying cancer

A

No; confined to epidermis of vulvar skin; treat with excision; rarely will invade and suggests poor prognosis

351
Q

What is septate vagina

A

Double vagina; failure of Müllerian duct fusion; accompanied by double uterus (uterus didelphys); can be manifestation of genetic syndromes or in utero exposure to diethylstilbestrol (DES)

352
Q

What is vaginal adenosis

A

When vagina is not completely replaced by squamous cells and still has some remaining columnar cell; presents as red granular areas; seen with exposure to DES; rarely will lead to clear cell carcinoma

353
Q

Where are gartner cysts located

A

Lateral walls of vagina; submucosal

354
Q

What age do most benign tumors of the vagina occur in

A

Reproductive age women; include stromal tumors (polyps), leiomyomas, and hemangiomas

355
Q

What is the most common malignant tumor to involve the vagina

A

Carcinoma spreading from the cervix

356
Q

What are primary carcinomas of the vagina

A

All are SCC associated with high risk HPVs; greatest risk factor is previous carcinoma of cervix or vulva; premalignant lesion: vaginal intraepithelial neoplasia; mostly affects upper vagina posterior wall; lesions in lower 2/3 met to inguinal nodes and upper met to iliac nodes

357
Q

What is embryonal rhabdoyosarcoma

A

Aka sarcoma botryoides; found in infants and children <5 ears. Grow as polyploid rounded bully masses (grapelike clusters); tumor cells resemble tennis racket; sometimes can see striations; tumor cells are in cambium layer or within loose fibroyxomatous stroma; invades locally and causes death hby penetration into peritoneal cavity or obstruction of urinary tract; tx: surgery with chemo

358
Q

What is the main flora of the cervix

A

Lactobacilli -> produce lactic acid and maintains vaginal pH <4.5; also produce bacteriotoxic H2O2; if pH becomes alkaline due to bleeding, sex, or douching, H2O2 producing decreases; abx therapy can also cause pH to rise

359
Q

What are endocervical polyps

A

Common benign exophytic growths that arise within endocervical canal; composed of loos fibromyxomatous stroma covered by mucus secreting endocervical glands; source of vaginal spotting; tx: simple curettage or surgical excision

360
Q

What cells does HPV infect

A

Immature basal cells of the squamous epithelium; but viral replication occurs in maturing squamous cells

361
Q

What are the roles of E7 and E6

A

E7 binds to activated Rb and degrades it and binds and inhibits p21 and 27
E6 binds to p53 an promotes its degradation; also upregulates telomerase

362
Q

What is the classification system for squamous cervical precursor lesion

A
  • mild dysplasia: CINI; Low grade SIL
  • moderate: CINII; high grade SIL
  • severe: CINIII; high grade
  • carcinoma in situ: CINIII; high grade
363
Q

What are the features of LSIL

A

Productive HPV infection; high level of viral replication but only mild alterations in growth of host cells; doesn’t progress directly to invasive carcinoma; *most regress spontaneously

364
Q

Are all HSILS at high risk for progression to carcinoma

A

Yes

365
Q

What is the morphology of squamous intraepithelial lesion (SIL)

A 
Nuclear atypia (nuclear enlargent, hyperchromasia, coarse chromatin granules, variation in nuclear size and shape); cytoplasmic halos - koilocytic atypia
-low vs high grade: low is if immature cells confined to lower 1/3 of epithelium
366
Q

What is the histo of LSIL

A
  • upper portion of epithelium express Ki-67 (normally confided to basal layer)
  • overexpression of p16
367
Q

What is the average age for cervical carcinoma

A

45

368
Q

What other kinds of cancer (besides SCC) can present in the cervix

A

Adenocarcinoma, adenosquamous, and neuroendocrine; all assoc with HPV; all have less favorable prognosis than SCC

369
Q

What is the morphology of invasive cervical carcinoma

A

Fungating or infiltrative mass; SCC: nests and tongues of malignant epithelium; adeno: glandular epith. Mucin depleted cytoplasm resulting in dark appearance; adenosquamous: glandular and squamous; neuroendocrine: looks like small cell

370
Q

How does cervical carcinoma spread

A

Direct extension; lymphovascular - liver, lungs, bone marrow

371
Q

How are microinvasive vs invasive cervical cancers treated

A

Microinvasive: cone
Invasive: hysterectomy with LN dissection; radiation and chemo

372
Q

What do people with cervical cancer die of

A

Ureteral obstruction, pyelonephritis, uremia

373
Q

What is the screening guideline for cervical cancer

A

First pap at age 21 and every 3 years; after age 30 if normal cytology, every 5 years; if test positive for HPV DNA, every 6-12 months

374
Q

What are the parts of the uterus

A

Myometrium: smooth m that forms the wall
Endometrium: internal cavity; composed of lands

375
Q

What is shed during menses

A

Superficial layer of endometrium (functionalis)

376
Q

What are the phases of the menstrual cycle

A
  • proliferative: growth of glands and stroma arising from basalis; glands are straight lined by pseudostratified columnar no mucus secretion; endometrial stroma composed of spindle cells
  • ovulation: proliferation stops differentiation in response to progesterone
  • postovulation: secretory vacuoles beneath nuclei in glandular epithelium; glands tortuous (saw toothed)
  • late secretory: impt for dating endometrium spiral arterioles; stromal hypertrophy and increased cytoplasmic eosinophilia (predicidual change)
377
Q

What is the most common cause of abnormal uterine bleeding

A

Dysfunctional uterine bleeding; lacks an underlying structural abnormality; disturbances in hormones

378
Q

What are the prepubertal causes of abnormal uterine bleeding

A

Precocious puberty

379
Q

What are the causes of abnormal uterine bleeding in adolescents

A

Anovulatory cycle, coagulation disorders

380
Q

What are the causes of abnormal uterine bleeding in reproductive years

A

Complications of pregnancy (abortion, trophoblastic dz, ectopic), anatomic lesions (leiomyoma, adenomyosis, polyps, endometrial hyperplasia, carcinoma), dysfunctional uterine bleeding (anovulatory cycle, ovulation dysfunctional bleeding)

381
Q

What are the causes of abnormal uterine bleeding in perimenopausal women

A

Dysfunction uterine bleeding (anovulatory cycle), anatomic lesions (carcinoma, hyperplasia, polyps)

382
Q

What are the causes of abnormal uterine bleeding in postmenopausal women

A

Endometrial atrophy, anatomic lesions (carcinoma, hyperplasia, polyps)

383
Q

What is the most common cause of dysfunctional bleeding

A

Anovulation - most common at menarche and postmenopausal period
Less common causes: endocrine disorders (thyroid, adrenal, pituitary), ovarian lesions (granulosa cell tumors or PCOS), generalized metabolic disturbances (obesity, malnutrition)

384
Q

How does anovulation cause bleeding

A

Results in excessive endometrial stimulation by estrogens unopposed by progesterone; repeat anovulation - biopsy shows stromal condensation and eosinophilic epithelial metaplasia; lacks progesterone dependent features (glandular secretory changes)

385
Q

What are the manifestations of inadequate luteal phase

A

Infertility associated with increased bleeding or amenorrhea; inadequate progesterone during post ovulation period

386
Q

What is acute endometritis

A

Uncommon; limited to bacterial infections after delivery or miscarriage; group A strep, staph

387
Q

What causes chronic endometritis

A

Chronic PID, retained gestational tissue, IUD, TB (miliary sprea or drainage of tuberculous salpingitis)

388
Q

How is the dx of chronic endometritis made

A

Plasma cells in stroma

389
Q

What are the most common sites of endometriosis

A

Ovaries, uterine ligaments, rectovaginal septum, cul de sac, pelvic peritoneum, large and small bowel and appendix, mucosa of cervix, vagina, and fallopian tubs, laparotomy scars

390
Q

What does endometriosis cause

A

Infertility, dysmenorrhea (painful menstruation), pelvic pain

391
Q

What is the regurgitation theory

A

Endometrial tissue implants at ectopic sites due to retrograde flow of menstrual endometrium

392
Q

What is the benign metastasis theory

A

Endometrial tissue can spread to distant sites via bv and lymph

393
Q

What is the meta plastic theory

A

Endometrium arises directly from coelomic epithelium (mesothelium of pelvis or abdomen)

394
Q

What is the extrauterine stem/progenitor cell theory

A

Bone marrow can differentiate into endometrial tissue

395
Q

When can endometriosis occur in men

A

Treated with estrogens for prostate cancer

396
Q

What do the endometria of women with endometriosis show that is not seen in normal endometria

A
  • Release of PGE2, IL-1beta, TNFalpha, IL-6 and 8, NGF, VEGF, MCP-1, MMPs, TIMPs
  • increased estrogen production by endometriotic stromal cells *high levels of aromatase (inhibitors of this used as treatment)
397
Q

What cancer has endometriosis been associated with

A

Ovarian cancer of the endometrioed and clear cell types; mutations in PTEN and ARID1A

398
Q

What is the morphology of endometriotic lesions

A

Bleed; produces nodule with red-blue to yellow-brown appearance on or just beneath the mucosa or serosa; organizing hemorrhage can cause fibrous adhesions; ovaries can become distorted by cystic masses (chocolate cysts or endometriomas)

399
Q

How do you make a diagnosis of endometriosis

A

Need glands and stroma or just stroma; if only glands, need to consider other causes

400
Q

What is atypical endometriosis

A

Precursor to endometriosis-related ovarian carcinoma

401
Q

What is adenomyosis

A

Presence of endometrial tissue within the uterine wall (myometrium); sx: menometrorrhagia (heavy menses), colicky dysmenorrhea, dyspareunia, and pelvic pain; can coexist with endometriosis

402
Q

What are endometrial polyps

A

Exophytic masses that project into endometrial cavity; can cause bleeding; neoplastic; have been observed in association with administration of tamoxifen (therapy for breast cancer) - has pro-estrogen affect on endometrium; atrophic polyps occur in postmenopausal women; rarely adenocarcinoma can result

403
Q

What is endometrial hyperplasia

A

Cause of abnormal bleeding; frequent precursor to most common typ of endometrial carcinoma; *increased proliferation of glands in ratio to stroma; assoc with prolonged estrogenic stimulation (anovulation, exogenous or endogenous)

404
Q

What associated conditions can cause endometrial hyperplasia

A
  • obesity (peripheral conversion of androgens to estrogens)
  • menopause
  • PCOS
  • functioning granulosa cell tumors of the ovary
  • excessive ovarian cortical function (cortical stromal hyperplasia)
  • prolonged administration of estrogenic substances
405
Q

What genetic mutation is seen in endometrial hyperplasia

A

PTEN (LOF); encodes lipid phosphatase that is negative regulator of PI3K/AKT pathway *Cowden syndrome

406
Q

What is the morphology of non-atypical endometrial hyperplasia

A

*increased gland to stroma ratio; rarely progress to adenocarcinoma; can evolve into cystic atrophy when estrogen is withdrawn

407
Q

What is the morphology of atypical endometrial hyperplasia

A

Aka endometrial intraepithelial neoplasia; complex patterns of proliferating glands displaying atypia; sometimes cannot distinguish from adenocarcinoma without hysterectomy

408
Q

How is atypical hyperplastia of the endometrium managed

A

Hysterectomy or in young women who desire fertility, trial of progestin therapy and close follow up

409
Q

What is the most common invasive cancer of the female genital tract

A

Endometrial carcinoma

410
Q

What is type I endometrial carcinoma

A

Most common; well differentiated; endometrioid carcinoma; assoc with obesity, diabetes, HTN, infertility, and unopposed estrogen; mutation in PTEN, PIK3CA (GOF - plays a role in invasion), KRAS, LOF in ARID1A (regulator of chromatin structure - also mutated in ovarian endometrioid and clear cell carcinomas)

411
Q

What is the age of onset of type I vs type II endometrial carcinoma

A
  • type I: 55-65

- type II: 65-75

412
Q

What is the clinical setting of type I vs type II endometrial carcinoma

A
  • type I: unopposed estrogen, obesity, HTN, diabetes

- type II: atrophy, thin physique

413
Q

What is the morphology of type I vs type II endometrial carcinoma

A
  • type I: endometrioid

- type II: serous, clear cell, mixed mullerian tumor

414
Q

What is the precursor of type I vs type II endometrial carcinoma

A
  • type I: hyperplasia

- type II: serous endometrial intraepithelial carcinoma

415
Q

What is the mutation of type I vs type II endometrial carcinoma

A
  • type I: PTEN, ARID1A, PIK3CA, KRAS, FGF2, MSI, CTNNB1, TP53
  • type II: TP53, aneuploidy, PIK3CA, FBXW7, CHD4, PPP2R1A
416
Q

What is the behavior of type I vs type II endometrial carcinoma

A
  • type I: indolent, spread via lymphatics

- type II: aggressive, intraperitoneal and lymphatic spread

417
Q

Who are endometrial cancers with mismatch repair genes mutations more common in

A

HNPCC (hereditary nonpolyposis colorectal carcinoma)

418
Q

What is the order of mutations for serous carcinoma of the endometrium

A

Atrophic endometrium -> TP53 and aneuploidy -> serous endometrial intraepithelial carcinoma -> FBXW7, PPP2R1A, CCNE1 mutations -> serous carcinoma

419
Q

What is type II serous carcinoma of the endometrium

A

Occur in women about 10 years older than type I;; arise in setting of endometrial atrophy; poorly differentiated (grade 3); mutations in TP53 (most missense); poorer prognosis b/c propensity to exfoliate and travel through Fallopian tubes and implant on peritoneal surfaces

420
Q

What is the clinical presentation of endometrial carcinoma

A

Bleeding with excessive leukorrhea

421
Q

Who does serous carcinoma of the endometrium occur more often in

A

African Americans

422
Q

What are malignant mixed mullerian tumors (MMMTs)

A

Aka carcinosarcomas; endometrial adenocarcinomas with a malignant mesenchymal component (can be stromal sarcoma, leiomyosarcoma or rhabdymyosaroma or chondrosarcoma); mutations PTEN, TP53 and PIK3CA

423
Q

What is the morphology of MMMTs

A

Bulky and can protrude through os; histo adenocarcinoma mixed with sarcomatous elements; *mets only contain epithelial components

424
Q

Who do MMMTs present in

A

Postmenopausal women; present with bleeding; prognosis based on depth of invasion, stage, and differentiation of mesenchymal component (those with heterologous mesenchymal components do worse)

425
Q

What are adenosarcomas of the endometrium

A

Malignant appearing stroma with benign but abnormally shaped glands; predominate in women btw 4th and 5th decade; low grade malignancy; estrogen-sensitive and responds to oophorectomy*

426
Q

What mutations are seen in low grade endometrial stromal sarcomas

A

Translocations in which portions of JAZF1 is fused to SUZ12

427
Q

Do stromal sarcomas recur

A

Yes

428
Q

What are uterine leiomyomas

A

Benign smooth m neoplasms; more often multiple; rearrangements involving HMGIC and HMGIY; mutations in MED122

429
Q

What is the morphology of leiomyomas

A

Sharply circumscribed; found within myometrium of the corpus; can occur within myometrium (intramural), beneath the endometrium (submucosal) or beneath the serosa (subserosal); *whorled pattern of smooth m; low mitotic index

430
Q

What is benign metastasizing leiomyoma

A

Uterine leiomyoma that extends into vessels and spreads hematogenously (mostly to the lung); benign

431
Q

What is disseminated peritoneal leiomyomatosis

A

Multiple small peritoneal nodules benign

432
Q

What are sx of leiomyomas

A

Bleeding, urinary frequency, sudden pain from infarction, impaired fertility; increased risk of spontaneous abortion, fetal Malpresentation, uterine inertia (failure to contract), and postpartum hemorrhage

433
Q

What are leiomyosarcomas

A

Arise from myometrium and endometrial stromal precursors; MED12 mutation; complex karyotypes; grow in 2 patterns bulky fleshy masses or polyploid that project into the lumen

434
Q

Who do leiomyosarcomas develop in

A

Both before and after menopause; 40-60; often recur following surgery and most met to lungs bone and brain

435
Q

What is the most common primary lesion of the Fallopian tube

A

Paratubal cysts (serous filled); larger varieties found near the fibrates end or in the broad ligaments (hydatids of Morgagni); arise from remnants of Müllerian duct

436
Q

What are the tumors of the Fallopian tube

A

Benign: adenomatoid (mesothelioma)
Malignant: primary adenocarcinoma

437
Q

What are cystic follicles of the ovary

A

Originate from unruptured Graafian follicles or in follicles that hav ruptured and immediately sealed; usually multiple; filled with serous fluid;

438
Q

What are luteal cysts

A

Present in normal ovaries of women of reproductive age; lined by bright yellow tissue containing luteinized granulosa cells; occasionally rupture and cause peritoneal reaction

439
Q

What is PCOS

A

Hyperandddrognism, menstrual abnormalities, polycystic ovaries, chronic anovulation and decreased fertility; assoc with obesity, T2DM, premature atherosclerosis; show insulin resistance; at risk for endometrial hyperplasia and carcinoma

440
Q

What is stromal hyperthecosis

A

Disorder of ovarian stroma seen in postmenopausal women but can overlap with PCOS in younger women; uniform enlargement of ovary; usually b/l and shows hypercellular stroma and luteinization of stromal cells; virilization may be more striking than PCOS

441
Q

What is theca lutein hyperplasia of pregnancy

A

Response to pregnancy hormones (gonadotropins), theca cells proliferate and the perifollicular zone expands; as follicles regress, May appear nodular

442
Q

What do most tumors of the ovary arise from

A
  • surface/Fallopian tube epithelium and endometriosis
  • germ cells (migrate from yolk sac)
  • stromal cells, including sex cords
443
Q

What are the surface epithelial stromal tumors of the ovary

A
  • serous (cystadenoma, cystadenofibroma, serous borderline, serous adenocarcinoma)
  • mucinous
  • endometrioid
  • clear cell
  • transitional cell
  • epithelial-stromal
444
Q

What are the sex cord stromal tumors of the ovary

A

Granulosa, fibromas, fibrothecomas, thecomas, sertoli-leydig cell tumors, steroid cell tumors

445
Q

What are the germ cell tumors of the ovary

A

Teratoma, dysgerminoma, yolk sac tumor, mixed germ cell tumor

446
Q

What are the metastatic cancers that affect the ovary

A

Colonic, appendiceal, gastric, pancreaticobiliary, breast

447
Q

What is the most common type of malignant ovarian tumor

A

Serous

448
Q

Where do most primary ovarian neoplasms arise from

A

Mullerian epithelium - 3 subtypes: serous, mucinous and endometrioid

449
Q

What are the types of ovarian carcinomas

A

Type I: low grade arise in associated with borderline tumors or endometriosis; type II: high grade serous carcinomas that arise from serous intraepithelial carcinoma

450
Q

What are the most common malignant ovarian tumors

A

Serous; can be benign, borderline (20-45) or malignant (later in life)

451
Q

What are the risk factors for malignant serous tumors of the ovary

A

Nulliparity, family hx, heritable mutations (BRCA1 and 2)

452
Q

What are the types of serous ovarian carcinoma

A

Low grade (well diff) - arise in assoc with serous borderline tumors and high grade - arise from in situ lesions in Fallopian tube fimbriae or serous inclusion cysts within the ovary

453
Q

What do women with BRCA mutation undergo

A

Salpingo-oophorectomy

454
Q

What mutations are seen in low grade vs high grade serous ovarian carcinomas

A
  • low grade: KRAS, BRAF, ERBB2; usually have wildtype TP53

- high grade: TP53 and lack KRAS or BRAF mutation; PIK3CA, RB, BRCA1/2 (but rare in sporadic)

455
Q

What is the morphology of serous tumors

A

Benign: smooth glistening cyst wall with no epithelial thickening
Borderline: increased papillary projections
Most are b/l especially if malignant

456
Q

What kind of invasion are ovarian serous tumors (both low and high grade) capable of

A

Spread to peritoneal surfaces and omentum; assoc with presence of ascites

457
Q

What is the prognosis of low vs high grade serous ovarian tumors

A

Low grade, even if mets progresses slowly; high grade usually has wide Mets at time of diagnosis

458
Q

Who do mucinous tumors of the ovary occur in

A

Mid life; rare before puberty and after menopause; most are benign or borderline

459
Q

What is the pathogenesis of mucinous tumors of the ovary

A

Mutations of KRASS

460
Q

How do mucinous tumors differ from serous

A

Mucinous rarely involve the surface and are not usually b/l; produce bigger masses

461
Q

What is the histo of mucinous tumors of the ovary

A
  • benign: most demonstrate gastric or intestinal differentiation; some show endocervical
  • borderline: distinguished from cystadenomas from epithelial stratification, tufting and papillary intraglandular growth
  • carcinomas: glandular growth (expansile invasion); non-invasive outside ovary - excellent prognosis; if spread beyond ovary, usually fatal
462
Q

What is pseudomyxoma peritonei

A

Mucinous ascites, cystic epithelial implants on peritoneal surfaces, adhesions and involvement of ovaries; can result in intestinal obstruction

463
Q

What are endometriod ovarian tumors

A

Distinguished from serous and mucinous tumors by presence of tubular glands resembling benign or malignant endometrium; can arise with endometriosis or borderline tumor; seen in conjunction with carcinoma of the endometrium but arise independently rather than spread

464
Q

What is the pathogenesis of endometrioid carcinoma of the ovary

A

Assoc with endometriosis (occurs early than not associated with); mutations in PTEN, PIK3CA, ARID1A, KRAS, CTNNB1

465
Q

What does b/l endometrioid carcinoma of the ovary usually suggest

A

Extension beyond the genital tract

466
Q

What are cystadenofibromas

A

Uncommon; more pronounced proliferation of fibrous stroma that underlies the columnar lining; benign; simple papillary processes; may contain mucinous, serous, endometrioid, and transitional (Brenner) epithelium

467
Q

What are transitional cell tumors

A

Contain neoplastic epithelial cells resembling urothelium and are usually benign; Brenner tumors; usually unilateral; if >50% of malignant cells, considered transitional cell carcinoma of ovary

468
Q

What serum marker is used to measure disease recurrence in ovarian cancers

A

CA-125

469
Q

What are the most common germ cell tumors of the ovary

A

Benign cystic teratoma

470
Q

What are the features of mature benign teratomas

A

Most are cystic and referred to as dermoid cysts; lined by skin structures; found in young women urging reproductive years; assoc with paraneoplastic syndromes - inflammatory limbic encephalitis

471
Q

1% of dermoids undergo malignant transformation t o what kind of cancer

A

Usually squamous cell; but can to thyroid or melanoma as well rarely

472
Q

What is the karyotype of most benign ovarian teratomas

A

46, XX

473
Q

What are the most common monodermal or specialized teratomas

A 
Struma ovarii - mature thyroid tissue (can cause hyperthyroidism)
and carcinoid (may also be functional - if >7cm can produce enough 5-hydroxytryptamine to cause carcinoid syndrome in the absence of liver mets b/c ovarian v leads to systemic circulation; can meet) *always unilateral although contralateral teratoma may be present
474
Q

What are immature malignant teratomas

A

Rare; resemble embryonal and immature fetal tissue found in prepubertal adolescents and young women; grade depends on about of immature neuroeptihelium; grow rapidly and spread; Stage I has excellent prognosis; high grade confined to ovary treated with chemo

475
Q

What are dysgerminomas

A

Ovarian counterpart of seminoma; most occur in 2nd to 3rd decade; some occur in patients with gonadal dysgenesis or pseudohermaphroditism; a few produce chorionic gonadotropin (presence of syncytiotrophoblastic giant cells); express OCT3,4, NANOG,KIT

476
Q

What is the morphology of dysgerminomas

A

Most are unilateral; composed of vesicular cells having clear cytoplasm and regular nuclei; grows in sheets or cords

477
Q

Are all dysgerminomas malignant

A

Yes; if unilateral and has not broken through capsule excellent prognosis after salpingooophorectomy; responsive to chemo

478
Q

What are yolk sac tumors

A

Aka endodermal sinus tumor; derived from malignant germ cells differentiating along the extraembryonic yolk sac lineage; elaborate alpha fetoprotein; *glomerulus like structure on histo with central blood vessel enveloped by tumor cells within a space lined. By tumor cells (Schiller-Duvall body); most are children or young women who present with ab pain and rapidly growing mass in single ovary; good prognosis with chemo

479
Q

What is choriocarcinoma

A

More commonly of placental origin; extraembryonic differentiation of germ cells; prepubertal; most exist in combo with other germ cell tumors; aggressive in the ovary and met to lungs, liver bone by hematogenous route; elaborate chorionic gonadotropins; *unresponsive to chemo when in the ovary

480
Q

What is embryonal carcinoma

A

Highly malignant tumor of primitive embryonal elements

481
Q

What is polyembryoma

A

Malignant tumor containing embroid bodies

482
Q

What is mixed germ cell tumor

A

Contains combo of dysgerminomas,teratomas, yolk sac. Tumor and choriocarcinoma

483
Q

What are granulosa cell tumors

A

Composed of cells that resemble granulosa cells of developing ovarian follicle; adult and juvenile forms; most occur in postmenopausal women; usually unilateral; if hormonally active, have yellow coloration to surface

484
Q

What is the histo of granulosa cell tumors

A

Can have small cuboidal to polygonal cells growing in cords, sheets or strands; can have glandlike structures filled with acidophilic material called call-exner bodies *staining with ab to inhibin

485
Q

What are the manifestations of granulosa tumors

A

In prepubertal girls -> precocious puberty
In adults: proliferative breast dz, endometrial hyperplasia, endometrial carcinoma; can produce androgens and masculinize the patient
All are potentially malignant (tumors composed predominantly of theca cells are almost never malignant)

486
Q

What is elevated as a result of granulosa Ellis

A

Inhibin

487
Q

What mutation is seen in granulosa cell tumors

A

FOXL2(only in adult type)

488
Q

What are fibromas and thecomas

A

Fibromas: composed of fibroblasts; hormonally inactive; unilateral
Thecomas: composed of plump spindle cells with lipid droplets
combo: fibrothecomas
*present as painful mass, ascites, hydrothorax usually on the right - Meigs syndrome; also associated with basal cell nevus syndrome

489
Q

What mutations are seen in sertoli-leydig tumors

A

DICER1 - encodes enonuclease that processes microRNAs

490
Q

What is the morphology of sertoli-leydig tumors

A

Usually unilateral; resemble granulosa tumors; does not usually recur or met; can block normal female sexual development or defeminization (atrophy of breasts, amenorrhea, sterility, and loss of hair)

491
Q

What are Hilus cell tumors (pure leydig cell tumors)

A

Derived from clusters of polygonal cells arranged around hilar vessels; unilateral; *reinke crystalloids; masculization (hirsutism, voice changes, and clitoral enlargement, but milder than sertoli-leydig); produce testosterone; benign

492
Q

What is pregnancy luteoma

A

Rare resembles corpus luteum of pregnancy; produce virilization in pregnant patients and their female infants

493
Q

What is gonadoblastoma

A

Uncommon; tumor composed of germ cells and sex cord stroma derivative resembling immature stroll and granulosa cells; occurs in individuals with abnormal sexual development and in gonads of indeterminate nature; most of phenotypic females, and the rest are phenotypic males with undescended testicles and female internal secondary organs; *coexistant dysgerminoma occurs in half of cases prognosis is excellent if excised

494
Q

what are the most common places that cancers metastasize from to the ovary

A

Mullerian origin: uterus, Fallopian tube, contralateral ovary, pelvic peritoneum

495
Q

What are the most what are the extra-mullerian sites that have ovarian mets

A

Breast, GI, pseudomyxoma peritonei

*krukenberg tumor - b/l met composed of mucin producing, signet ring cancer cells

496
Q

What is spontaneous abortion defined as

A

Pregnancy loss before 20 weeks gestation (most occur before 12 weeks)

497
Q

What are some causes of spontaneous abortion

A
  • fetal chromosome anomalies: aneuploidy, polyploidy, translocations
  • maternal endocrine factors: luteal-phase defect, poorly controlled diabetes
  • physical defect of uterus: submucosal leiomyomas, uterine polyps, or uterine malformations
  • systemic disorders affecting maternal vasculature: antiphospholipid ab syndrome, coaulapathies and HTN
  • infections with Protozoa (toxoplasma), bacteria (mycoplasma, listeria), ascending infection tends to occur in 2nd trimester loss
498
Q

Where is the most common site of ectopic pregnancy

A

extrauterine Fallopian tube (intrauterine is called cornual pregnancy)

499
Q

What is associated with increased risk of ectopic pregnancy

A

IUDs

500
Q

What is diagnosis of tubal pregnancy based on

A

Presence of chorionic gonadotropin, pelvic sonography, endometrial bx (shows deciduous without chorionic villi or implantation sites) and/or laparoscopy

501
Q

What are the types of twin placentas

A

Diamnionic dichorionic, diamnionic monochorionic, and monoamnionic monochorionic; monochorionic = monozygotic twins; dichorionic = either mono or dizygotic

502
Q

What is a complication of monochorionic twin pregnancy

A

Twin-twin transfusion syndrome; contain av shunts and if increases blood flow to one twin over another, one twin will be anemic and the other will be fluid overloaded

503
Q

What is placenta Previa

A

When placenta implants in lower uterine segment or cervix; complete covers internal cervical os and requires delivery via c section

504
Q

What is placenta accreta

A

Caused by partial or complete absence of decidua such that the placental villous tissue adheres directly to the myometrium which leads to allure of placental separation at birth; cause of severe postpartum bleeding ; disposing factor is placenta previa and previous c section

505
Q

How do placental infections occur

A

Either through ascending infection through the birth canal (most. Common - always bacterial) or hematogenous (transplacental) infection; causes preterm delivery; amniotic fluid many be cloudy; histo of corionamnion contains infiltrate of neutrophils with edema and congestion of vessels; elicited Vasculitis of umbilical and fetal chorionic plate vessels

506
Q

What are the TORCH infections

A

Toxoplasmosis, syphilis, TB, listeriosis, rubella, CMV, herpes; hematogenous; cause chronic villlitis

507
Q

What is preeclampsia

A

Widespread maternal endothelial dysfunction that presents with HTN, edema, and proteinuria; more common in primiparas (first pregnancy); can be complicated by hypercoagulability, acute renal failure, and pulm edema, microangiopathy hemolytic anemia, elevated liver enzymes, and low platelets (HELLP)

508
Q

What is the pathogenesis of preeclampsia

A

Diffuse endothelial dysfunction, vasoconstriction, and increased vascular permeability mediated by placental derived mediators

  • abnormal trophoblastic implantation and failure of remodeling of maternal vessels (trophoblastic cells don’t invade maternal decidua and destroy the vasclar smooth mm)
  • ischemic placenta releases factors (FMS-like tyrosine kinase - sFltl) and endoglin antagonize VEGF and TGFbeta - leads to endothelial dysfunction and vasoconstriction)
509
Q

Where are clots most likely to form in women with preeclampsia

A

Liver, kidneys, brain, pituitary; related to reduced production of PGI2 (because requires VEGF to be released)

510
Q

What is the morphology of the placenta in preeclampsia

A

Infarcts, exaggerated ischemic changes in villi nad trophoblastic consisting of incrased syncytial knots, retroplacental hematomas, abnormal decidua vessels

511
Q

What are the liver lesions seen in preeclampsia

A

Subcapsular and intraparenchmal hemorrhages fibrin thrombi in portal capillaries and hemorrhagic necrosis

512
Q

What are the kidney lesions seen in preeclampsia

A

Glomeruli show swelling of endothelial cells, amorphous dense deposits and mesangial cell hyperplasia; fibrin in glomeruli; can cause b/l renal cortical necrosis

513
Q

What are the clinical features of preeclampsia

A

Occurs most commonly after 34 weeks (occurs earlier in women with hydatidiform mole, preexisting kidney dz, HTN, or coagulopathies); for term infants, delivery is treatment regardless of disease severity; in preterm, monitor, but inf eclampsia, severe preeclampsia with maternal end organ dysfunction, HELLP, or fetal distress are indications for delivery

514
Q

What are long term consequences of preeclampsia

A

Some women develop HTN and microalbuminuria; increase in risk off vascular dz of heart and brain

515
Q

What are hydatidiform moles

A

Cystic swelling of chorionic villi with trophoblastic proliferation; diagnosed during early pregnancy by pelvic sonogram; higher risk at 2 extremes of reproductive life; more common in SE Asia

516
Q

What is a complete mole

A

Fertilization of egg that has lost its female chromosomes (46 XX - called androgenesis) or fertilization of empty egg by 2 sperm (46 XX or 46 XY); risk of choriocarcinoma and invasive mole

517
Q

What is a partial mole

A

Result from fertilization of an eg with 2 sperm (Triploid - 69 XXY or tetraploid - 92 XXXY); fetal tissue present; increased risk of persistent molar disease but NOT associated with choriocarcinoma

518
Q

What is the morphology of hydatidiform moles

A

Delicate, friable mass of thin-walled translucent cystic grapelike structures consisting of woolen edematous villi; complete: chorionic villi enlarged scallops w/ central cavitation (cisterns); partial: only fraction of ili are enlarged

519
Q

What is true of the HCG elaborated by complete moles

A

Higher. Than those of a normal pregnancy of similar gestational age; monitor level even after removal to see if persistent or invasive mole (seen more with complete rather than partial moles)

520
Q

What is an invasive moles

A

Penetrates or perforates the uterine wall; hydropic villi can embolize to distant sites such as lungs and brain but do not grow here as true mets and will regress; manifested by vaginal bleeding nad uterine enlargement; responds well to chemo but may result i uterine rupture

521
Q

What is gestational choriocarcinoma

A

Malignant neoplasm of trophoblastic cells derived rom previously normal or abnormal pregnancy; rapidly invasive and mets widely but responds well to chemo

522
Q

What is the morphology of gestational choriocarcinoma pale

A

Large pale areas of necrosis and extensive hemorrhage; histo: no chorionic villi; only proliferating syncytiotrophoblasts and cytotrophoblasts; mitosis abundant invades underlying myometrium, penetrate bv and extended onto uterine serosa

523
Q

What are the clincial features off gestational choriocarcinoma

A

Irregular vaginal spotting of bloody-brown fluid; high propensity for hematogenous spread (most common to lungs, vagina, brain, liver, bone and kidney)

524
Q

What is placental site trophoblastic tumor (PSTT)

A

Neoplastic proliferation’s of extravillous trophoblastic (intermediate trophoblasts); normally produce human placental lactogen and found in implantation site; presents as uterine mass accompanied by uterine bleeding or amenorrhea and moderately elevated HCG; can follow normal pregnancy (half of cases), spontaneous abortion, or hydatidiform mole; localized = good prognosis; disseminated - can die

525
Q

What happens to the breast after ovulation

A

Cell proliferation increases and the number of acini per lobule also increases; intralobular stroma becomes edematous

526
Q

When does the breast become completely mature

A

During pregnancy; lobules increase (by end of pregnancy hardly any stroma left), immediately after pregnancy, lobules produce colostrum (high in protein) and change to milk (higher in fat and calories)as progesterone levels drop; permanent changes explains reduction in breast cancer risk observed in those who gave birth to children at young ages

527
Q

What happens during the 3rd decade to the breast

A

Lobules and specialized stroma start to involute and the interlobular stroma converts from radiodense fibrous stroma to radiolucent adipose tissue

528
Q

What lesions occur in lobules and terminal ducts

A

Cysts, sclerosing adenosis, small duct papilloma, hyperplasia, atypical hyperplasia, carcinoma

529
Q

What lesions occur in large ducts

A

Duct ectasia, squamous metaplasia of lactifferous ducts, large duct papilloma, paget dz

530
Q

What lesions occur in intralobular stroma

A

Fibroadenoma and phyllodes tumor

531
Q

What lesions occur in interlobular stroma

A

Fat necrosis, lipoma, fibromatosis, sarcoma

532
Q

What are milk line remnants

A

Supernumerary nipples or breasts result from persistence of epidermal thickening along milk line (extends from axilla to perineum); heterotopic, hormone responsive foci - come to attention because of painful prementual enlargements

533
Q

What is accessory axillary breast tissue

A

In some women, normal ductal system extends into subcutaneous tissue of the chest wall or axillary fossa (axillary tail of Spence); because you may not be able to remove breast tissue from these areas, prophylactic mastectomies do not eliminate the risk for breast cancer in these people

534
Q

What is congenital nipple inversion

A

Failure of nipple to evert during development; common and may be unilateral; *acquired nipple retraction is of concern bc may be indicative of invasive cancer or inflammatory nipple dz

535
Q

What is mastalgia or mastodynia

A

Pain in the breast

536
Q

What are the most common palpable lesions of the breast

A

Cysts, fibroadenomas, invasive carcinomas

537
Q

Where are most malignancies located in the rest

A

Upper outer quadrant

538
Q

What aspect of nipple discharge makes it worrisome for carcinoma

A

When it is spontaneous and unilateral

539
Q

What is galactorrhea associated with

A

Pituitary adenoma, hypothyroidism, endocrine anovulatory syndromes, OCPs, tricyclic antidepressants, methyldopa, phnothiazines; not associated with malignancy

540
Q

What causes bloody or serous discharge from the nipples

A

Large duct papillomas and cysts; during pregnancy bloody discharge can result on rapid growth and remodeling of the feast; risk of malignancy assoc with discharge increases with age

541
Q

What are the mammographic signs of breast carcinoma

A

Densities
Calcifications: calcifications assoc with malignancy are usually small, irregular, numerous and clustered *ductal carcinoma in situ (DCIS) detected as calcifications

542
Q

What are some reasons carcinomas are not detected on mammogram

A

Presence of surrounding radiodense tissu, small size, diffuse infiltrative pattern with little or no desmoplastic response, location close to chest wall or in periphery of breast

543
Q

What is the use of US in breast masses

A

Can distinguish between cystic and solid lesions

544
Q

What is inflammatory breast cancer

A

Mimics inflammation by obstructing dermal vasculature with tumor emboli; always consider in women with erythematous swollen breast

545
Q

What is acute mastitis

A

Typically occurs during 1st month of breastfeeding caused by local bacterial infection (staph or strep); breast is erytheatous and painful and fever present; only one duct system or sector fo breast is involved -> if not treated, spread to entire breast; staph form abscesses strep forms cellulitis

546
Q

What is squamous metaplasia of lactiferous ducts

A

Aka recurrent subareaolar abscess, periductal mastitis, zuska dz; woman and sometimes men present with painful erythematous subareolar mass that appears to be an abscess; in recurrent cases, fistula can form under smooth m of the nipple and opens onto the skin; many have inverted nipple; *most are smokers (vit A def)

547
Q

What is the morphology of squamous metaplasia of lactiferous ducts

A

Keratinizing squamous metaplasia of the nipple ducts; keratin plugs ductal system causing dilation and rupture of the duct; chronic granulomatous response develops once keratin spills into surrounding periductal tissue

548
Q

How do you treat squamous metaplasia of lactiferous ducts

A

Incision to drain; recurrence is common; can do surgical removal of duct and contiguous fistula

549
Q

What is duct ectasia

A

Presents as palpable periareaolar mass assoc with thick white nipple secretions and skin retraction; pain and erythema uncommon; occurs in 5th-6th decade usually in multiparous women NOT assoc with smoking *mammogram mimics invasive carcinoma

550
Q

What is the morphology of duct ectasia

A

Dilated ducts filled with inspissated secretions and lipid laden macrophages; can rupture; granulomas can form; fibrosis produces irregular mass with skin and nipple retraction

551
Q

How does fat necrosis present

A

Can mimic cancer; painless palpable mass, skin thickening or retraction, mammographic densities or calcifications; *half have hx of breast trauma or prior surgery

552
Q

What is the morphology of fat necrosis

A

Acute lesions may be hemorrhagic and contain central areas of liquefactive necrosis with neutrophils and macrophages; then proliferation fibroblasts and chronic inflammatory cells come; then giant cells, calcifications and hemosiderin; replaced by scar tissue; film gray-white nodules containing small white foci are seen grossly

553
Q

What is lymphocytic mastopathy (sclerosing lymphocytic lobulitis)

A

Single or multiple hard palpable masses or mammographic densities; difficult to obtain needle bx b/c dense collagenized stroma; atrophic ducts and lobules have thickened BM and are surrounded by prominent lymphocytic infiltrate; *most common in women with T1DM or autoimmune thyroid dz

554
Q

What is granulomatous mastitis

A

Granulomatous lobular mastitis; uncommon; occurs ONLY in porous women; closely assoc with lobules (may be caused by hypersensitivity reaction); tx w/ steroids sometimes affective

555
Q

What causes cystic neutrophilic granulomatous mastitis

A

Corynebacteria

556
Q

What are the groups of benign epithelial lesions

A

Non proliferative breast changes, proliferative breast dz, atypical hyperplasia

557
Q

What are nonproliferative breast changes (fibrocystic changes)

A

Not associated with increased risk of breast CA; 3 kinds of change - cystic (often with apocrine metaplasia), fibrosis, and adenosis

558
Q

What is the morphology of cystic change

A

Dilation of lobules; contain turbid, semi-translucent fluid of brown or blue color (blue dome cysts); liked by atrophic epithelium or metaplastic apocrine cells (resemble sweat glands); calcifications common; concern when solitary and firm to palpation;; *dx confirmed if disappears after FNA

559
Q

What are fibrotic changes

A

Cysts rupture and release material into stroma; chronic inflammation and fibrosis occur; leads to nodularity

560
Q

What is adenosis of the breast

A

Increase in number of acini per lobule *normal feature of pregnancy; calcifications present within lumens; acini lined by columnar cells (flat epithelial atypia) assoc with del of chrom 16q - earliest recognizable precursor of low grade breast cancer, but ones not increased cancer risk

561
Q

What are lactational adenomas

A

Present as palpable masses in pregnant or lactating women; normal-appearing breast tissue with lactational changes; not neoplastic

562
Q

What is proliferative breast disease w/o atypia

A

Lesions characterized by proliferation of epithelial cells; assoc with small increase in risk of carcinoma in either breast

563
Q

What is the morphology of epithelial hyperplasia of the breast

A

Normal breast ducts and lobules lined by double layer of myoepithelial cells and luminal cells; distend ducts

564
Q

What is sclerosing adenosis of the breast

A

Type of proliferative breast dz w/o atypia; increased number of acini that are compressed and distorted in central portion; stromal fibrosis can compress the lumens to create appearance of solid cords or double strands of cells lying within dense stroma; palpable mass, radio density or calcification is presentation

565
Q

What is a complex sclerosing lesion of the breast

A

Proliferative dz w/o atypia; components of sclerosing adenosis, papillomas, and epithelial hyperplasia; *one member = radial sclerosing lesion (radial scar) can mimic invasive carcinoma; central Indus of entrapped glands in hyalinizd stroma surrounded by radiating projections; not assoc with prior trauma or surgery

566
Q

What is a papilloma

A

Proliferative dz w/o atypia; grow within dilated duct; composed of multiple branching fibrovascular cores;large duct papillomas found in lactiferous sinuses of the nipple and usually solitary - produce discharge sometime bloody if undergoes torsion; small duct commonly multiple and located deeper in ductal system - no discharge

567
Q

What is the morphology of gynecomastia

A

Subareaolar enlargement; uni or b/l; increase in dense collagenous connective tissue assoc with epithelial hyperplasia of duct lining with tapering micropapillae; *no lobule formation

568
Q

What is the histo diff btw sclerosing adenosis and invasive carcinoma

A

In sclerosing, acini are arranged in swirling pattern and outer border wall is well circumscribed

569
Q

What drugs can cause gynecomastia

A

Alcohol, weed, heroin, antiretroviral, anabolic steroids

570
Q

What syndrome causes gynecomastia

A

Klinefelter (XXY)

571
Q

Does gynecomastia increase risk for breast cancer

A

Yes

572
Q

What are the forms of proliferative breast dz with atypia

A

Atypical ductal hyperplasia (distinguished from DCIS by only partially filling involved duct) and atypical lobular hyperplasia (cells do not distend >50% of acini within a lobule) ; has some but not all features of CIS;

573
Q

What does atypical lobular hyperplasia show a loss of

A

E cadherin

574
Q

What are most breast malignancies

A

Adenocarcinomas; also most are based on expression of HER2

575
Q

What are the 3 groups of adenocarcinomas of the breast

A

Estrogen receptor positive, HER2 negative (most common)
HER2 positive
ER negative HER2 negative

576
Q

What is the correlation btw ER positive cancers and age

A

Increase with age; ER negative and HER2 positive remain the same across age groups

577
Q

Who is invasive breast cancer more common in

A

White women; but AA women have an earlier onset and higher mortality rate; also ER positive cancers have lower rate in non-white women

578
Q

What are the risks for breast cancer

A

Germline mutation, first degree relative (unless postmenopausal mother), race, age, age of menarche (<11 increases risk), late menopause, age at first live birth (<20 decreases risk), benign breast dz, estrogen exposure, oophretomy decreases risk, increased breast density, radiation to the chest, carcinoma of contralateral breast or endometrium, diet (alcohol increases risk), obesity (<40 decrease risk, postmenopausal increased risk), exercises decreases risk, breastfeeding reduces risk,

579
Q

What are the genes assoc with familial breast cancer

A

BRCA1/2, TP53, CHEK2 - all are tumor suppressor

580
Q

Which BRCA gene increases risk for ovarian carcinoma

A

1; 2 is seen more with male breast cancer; 1 and 2 at risk for prostatic and pancreatic cancer

581
Q

What are the features of BRCA1 assoc breast cancers

A

Poorly differentiated, have medullary features (syncytial growth pattern with pushing margins and lymphocytic response) basal like, have TP53 mutations; biologically similar to ER-neg/HER2 positive

582
Q

What are the features of BRCA2 cancers

A

Poorly differentiated but are more often ER positive; seen in prostate, stomach, melanoma, gallbladder, bile duct and pharynx cancers; can cause fanconi anemia as well

583
Q

What does mutation in STK11 cause

A

Peutz-jeghers; can cause familial breast cancer

584
Q

What other cancers are TP53 mutations seen in

A

Sarcoma, leukemia, brain tumors, adrenocortical carcinoma

585
Q

What other cancers are seen with CHEK2 mutations

A

Prostate, thyroid, kidney, colon; it is a checkpoint kinase; may increase risk for breast cancer after radiation

586
Q

What is the pathway of ER-positive HER2 negative cancers

A

Dominant pathway; most common in ppl with BRCA2; asoc with gain of chrom 1q, loss of chrom 16q and activating mutations in PIK3CA, precursors: atypical ductal hyperplasia and flat epithelial atypia “Luminal” b/c resemble normal breast luminal cells

587
Q

What is the pathway of HER2 positive cancers

A

Assoc with amplifications in HER2 on chrom 17q; most common in ppl with TP53 mutations; precursor: atypical apocrine adenosis

588
Q

What is the pathway of ER negative HER2 negative cancers

A

No precursor lesions; most common seen in BRCA1 mutations and AA; sporadic tumors of this type have TP53 mutations; have a basal like pattern of mRNA expression

589
Q

What are the most common DRIVER mutations of breast cancer

A

PIK3CA, HER2, MYC, and CCND1, TP53, BRCA1/2

590
Q

What has been shown to increase the risk of tumor invasion and facilitated the transition of CIS to invasive carcinoma

A

Remodeling of the breast during post pregnancy involution

591
Q

What are the features of DCIS

A

Myoepithelial cells intact although may be diminished in #; can be detected by mammography; calcifications

592
Q

What is the best predictor of local recurrence and progression of DCIS

A

Nuclear grade and necrosis rather than architectural subtype

593
Q

What are the subtypes of DCIS

A
  • comedo: detected on mammography as clustered or linear and branching areas of calcification; define by* tumor cells with pleomorphic, high grade nuclei and areas of central necrosis
  • noncomedo: lacks either high grade nuclei or central necrosis; cribriform DCIS may have rounded (cookie cutter like) spaces within ducts;; micropapillary produces bulbous protrusions within a fibrovascular core
594
Q

What is paget dz of the nipple

A

Rare manifestation of breast cancer; presents as unilateral erythematous eruption with a scale crust; pruritus common; malignant cells extend from DCIS within ductal system via lactiferous sinuses into nipple skin w/o crossing BM; almost all have underlying invasive carcinoma (usually poorly differentiated, ER negative, and HER2 positive*)

595
Q

How do you treat DCIS

A

Surgical excision with radiation - curative; mastectomy also curative

596
Q

What are the major risk factors for recurrent of DCIS

A

High nuclear grade and necrosis, extent of dz, and positive surgical margins

597
Q

What is lobular carcinoma in situ (LCIS)

A

Grow in discohesive fashion due to loss of E cadherin (mutation in CDH1); expand but do not distort involved spaces; *always an incidental bx finding; more b/l than DCIS; identical morphology to atypical lobular hyperplasia and invasiv lobular carcinoma

598
Q

What is the morphology of LCIS

A

Uniform cells; mucin-positive signet ring cells present lack of e-cadherin results in round shape w/o attachment to adjacent cells cannot form cribriform spaces or papillae (seen in DCIS); pagetoid spread seen but does not involve nipple skin; necrosis and calcifications not seen; almost always expresses ER and PR; no HER2 overexpression

599
Q

What is different about the risk of cancer with LCIS vs DCIS

A

In LCIS, risk is almost as high in contralateral breast as in ipsilateral breast

600
Q

What is the most common typ of invasive breast cancer

A

ER positive, HER negative (luminal)

601
Q

What are the 2 groups of ER positive HER negative breast cancers

A
  • low proliferation (more common): older women and men; most common detecte by mammogram and in women with hormonal therapy; lowest incidence of recurrence and cured by surgery; typically met to bone; respond well to hormone tx; incomplete response to chemo
  • high proliferation: *most common type assoc with BRCA2; 10% show complete response to chemo; met to bone
602
Q

Who are HER2 positive cancers more common in

A

Young non white women; TP53 (HER positive, ER positive); met early usually to viscera and brain

603
Q

Which kind of breast cancer has the best response to chemo

A

ER negative, HER2 negative

604
Q

Who do ER neg, HER2 neg occur in

A

Young, BRCA1, AA, Hispanic

605
Q

What are the histo types of ER neg HER2 neg cancer

A

Medullary, adenoid cystic, secretory, metaplastic

606
Q

What proteins are stained for in ER negative HER2 negative cancers

A

Basal keratin

607
Q

What chrom is HER2 located on

A

17q

608
Q

What is the prognosis for HER2 positive cancers

A

With ab therapy (trastuzumab - herceptin) to HER2, excellent

609
Q

Can recurrence of ER neg HER neg occur even after mastectomy

A

Yes; also some express ER and HER2 so need to test to target treatment

610
Q

What is the morphology of invasive breast carcinoma

A

Hard, irregular radiodense mass; *grating sound when cut (cutting chestnut) due to foci or streaks of chalky-white desmoplastic stroma and calcification

611
Q

What can larger carcinomas present as

A

Invasion of pectoralis m or dermis and cause dimpling of skin; if involves central portion of breast, nipple retraction;

612
Q

How are carcinomas graded

A

Tubule formation, nuclear pleomorphism, mitotic rate; Grade I to III
Grade I: tubule pattern or cribriform pattern; monomorphic nuclei
Grade II: some tubule formation but solid clusters or single infiltrating cells also present; mitotic figures present; pleomorphic nuclei
Grade III: invade as ragged nests or solid sheets; central necrosis

613
Q

What is the morphology of ER positive, HER2 negative carcinoma

A

Can be poor or well diff; mucinous, papillary, cribriform, and lobular all seen

614
Q

What is the morphology of HER2 positive cancer

A

Most are poorly differentiated; some apocrine, some micropapillary

615
Q

What is the morph of ER negative HER2 negative

A

Almost all poorly differentiated

616
Q

What is lobular carcinoma

A

Clearest assoc of phenotype and genotype; most show balletic loss of CDH1; fail to incite desmoplastic response; *met to peritoneum and retroperitoneum, leptomeninges (carcinomatous meningitis), GI, and ovaries and uterus; also have increased risk of gastric signet ring carcinoma

617
Q

What is medullary carcinoma

A

*BRCA associated (NOT mutation, but hypermethylation), good prognosis; lymphocytic infiltrates within tumor assoc with better outcome and response to chemo

618
Q

What is micropapillary carcinoma

A

*anchorage independent growth is characteristic; express E cadherin but are not adherent to the stroma

619
Q

What is the morph of lobular carcinoma

A

Almost always ER positive; forms irregular masses, but can hav e diffuse infiltrative pattern difficult to palpate; signet ring cells containing intractoplasmi mucin; no tubule formation

620
Q

What is the morph of mucinous (colloid) carcinoma

A

Almost always ER positive; soft or rubbery and has consistency and appearance of pale grey-blue gelatin; borders are pushing or circumscribed; arranged in clusters and small islands of cells within large lakes of mucin

621
Q

What is tubular carcinoma

A

Almost always ER positive consists only of well formed tubules; cribriform may also be seen; apocrine snouts seen; assoc with flat epithelial atypia, atypical lobular hyperplasia, LCIS and low grade DCIS

622
Q

Which 2 histo types of breast carcinoma overexpress HER2

A

Apocrine and micropapillary

623
Q

What are the features of inflammatory carcinoma

A

Extensive invasion within lymph channels causing swelling; usually of high grade but dont belong to any molecular subtype *poor prognosis

624
Q

What are male breast cancers assoc with

A

Klinefelter and testicular dysfunction, BRCA2; *ER positivity more common - usually presents as palpable subareolar mass

625
Q

What is the most important prognostic factor for invasive carcinoma in the absence of distant mets

A

Axillary LN involvement; drain first to sentinel nodes (identified with radiotracer or color dye) - if negative don’t need to do axillary LN bx

626
Q

When is size not an important prognostic factor for breast cancer

A

HER2 positive and ER negative

627
Q

What is peau d’orange

A

Seen in inflammatory carcinoma; when breast cancers presents with breast erythema and skin thickening; edematous skin tethered to breast by cooper ligaments - caused by dermal lymphatics filled with meet carcinoma that blocks lymph drainage *higher risk in AA and young women; most are ER neg HER2 pos

628
Q

What breast cancer histo types have a good vs poor prognosis

A

Tubular, mucinous, lobular, papillary, adenoid cystic - better than no special type
Metaplastic or micropapillary - poor
*in adenoid cystic, low grade adenosquamous, and secretory in young women histo subtype is more predictive of prognosis than molecular type

629
Q

What is the best vs worst molecular subtype for prognosis

A

Best: well diff ER positive, HER2 negative
Worst: poor diff ER negative and/or HER2 positive

630
Q

What is the staging for breast cancer

A

0: DCIS or LCIS
1: invasive carcinoma <2cm no mets
2: > 2cm w/1-3 positive LN, o >5 0-3 positive LN; no d instant mets
3: >5 cm w/ neg or pos LN & no distant mets; >4 positive LN, invasive of skin or Chet wall
4: distant met

631
Q

What type of breast carcinoma is proliferation rate an important prognostic factor

A

ER positive HER2 negative

632
Q

How is estrogen and progresterone receptors used as a prognostic factor in breast cancer

A

If positive in both, respond better to hormonal manipulation; strongly ER pos less likely to respond to chemo; dont have either, respond better to chemo than hormones

633
Q

What is carcinoma en cuirasse

A

Carcinoma of the breastplate; complication of breast cancer

634
Q

What are the 2 types of stroma in the breast

A

Inter and intralobular

635
Q

What are the stromal tumors of the breast

A

Intralobular: fibroadenoma and phyllodes tumor
Interlobular: lipomas and angiosarcomas; pseudoangioatous stromal hyperplasia, myofibroblastomas and fibrous tumors

636
Q

What is the most common benign tumor of the female breast

A

Fibroadenomas; multiple and b/l; younger present with palpable mass and older present with density or calcification; hormonally responsive (increase during pregnancy which can be complicated by infarction); absence of adipose tissue; *assoc with cyclosporin A; proliferative change w/o atypia

637
Q

What is phyllodes tumor

A

Present mostly in 6th decade; palpable masses;; sometimes called cystosarcoma phyllodes; gains in chrom 1q; overexpresion o HOXB13 assoc with more aggressive clinical behavior; *bulbous protrusions of large (leaflike); more mitotically active than fibroadenomas; ax LN dissection contraindicated - if met, only stromal portion mets

638
Q

What is unique about myofibroblastoma

A

Only tumor of the breast that is equally common in males

639
Q

What can fibromatosis be assoc with

A

Familial denomatous polyposis, hereditary Desmoid syndrome, Gardner syndrome

640
Q

What are the malignant stromal tumors of the breast

A

(All interlobular) angiosarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, chondrosarcoma, osteosarcoma; *angiosarcoma only one to be of concerned with in breast - result of therap; poor prognosis

641
Q

What type are most primary breast lymphomas

A

B cell; rare T cell can arise in scar capsule assoc with breast implants; young with Burkitt lymphoma can present with b/l breast involvement and are often pregnant or lactating

642
Q

What cancers form mets to breast

A

Melanomas or ovarian

643
Q

What are the 3 classes of hormones

A
  • proteins and peptides: store in secretory vesicles until released; water soluble
  • amines: derived from tyrosine
  • steroids: synthesized from cholesterol; lipid soluble; not stored
644
Q

Which hormones use a phospholipase C mechanics m

A

GnRH, TRH, GHRH, oxytocin

645
Q

What part of the hypothalamus contains the cell bodies of the axons in the posterior pituitary

A

Supraoptic nucleus (SON - secretes mostly ADH) and Paraventricular nucleus (PVN - mostly oxytocin)

646
Q

What are primary vs secondary vs tertiary endocrine disorders according to phys

A

Primary: peripheral
Secondary: pituitary
Tertiary: hypothalamus

647
Q

What hormone can increase the release of prolactin

A

TRH

648
Q

What patterns is growth hormone released in

A

Pulsatile; during sleep

649
Q

How is growth hormone negatively regulated

A

Somatomedins (IGF) inhibits release from ant pituitary and hypothalamus; and growth hormone increases release of somatostatin from hypothalamus

650
Q

What are the effects of growth hormone

A

Diabetogenic effect; insulin resistance; decreased glucose uptake; increased lipolysis in adipose tissue increased blood insulin levels; increased protein synthesis and organ growth (mediated by IGF); increased linear growth (mediated by IGF)

651
Q

Who is GH secretion increased in

A

Subjects who are malnourished or fasting

652
Q

What does hyperprolactinemia suppress

A

Release of GnRH (low FSH and LH0

653
Q

What receptors does ADH bind to

A

In the kidney: V2

In the blood vessels: V1 (vasoconstriction)

654
Q

What is the water deprivation test

A

Weigh the patient after allowing no fluid if patient drops weight or plasma osmolarity high, DI

655
Q

What is 3 beta hydroysteroid DH used for

A

Convert pregnenolone to progesterone -»> aldosterone; also convert 17 OH pregnenolone to 17 OH progesterone _»> cortisol; also converts DHEA -> androstenedione

656
Q

What is 17 alpha hydroxylase used for

A

Convert pregnenolone to 17 OH pregnenolone -> lead to cortisol or androgens

657
Q

What products do you get an increase of if you inhibit 21 beta hydroxylase

A

Progesterone, 17 OH progesterone and shunted to androgens

658
Q

What happens if you block 11 beta hydroxylase

A

Increased deoxycorticosterone and 11 deoxycortisol; still get some mineralocorticoids

659
Q

What enzyme deficiency leads to increased mineralocorticoids

A

17 alpha hydroxylase; increased BP, decreased potassium, decreased androstenedione; undescended tests, lack of secondary sexual characteristics

660
Q

What does 11 beta hydroxylase deficiency present with

A

Increased BP, decreased K+, virilization, decreased cortisol

661
Q

What are the effects of cortisol

A

Immune suppression, GNG in liver, protein catabolism in m, lipolysis in adipose tissue

662
Q

What time of day is cortisol released

A

Early morning (8 am)

663
Q

How do sulfonylurea drugs work

A

Promotes closing of ATP dep K+ channel; increases insulin secretion

664
Q

What conditions are assoc with T1 vs T2DM

A

Type I: autoimmune thyroid dz, celiac dz, addisons dz

Type II: obesity, lipid abnormalities, PCOS, NAFLD

665
Q

What can influence the calcium concentration

A

Changes in plasma proteins concentration (increases total calcium, no change in ionized), changes in anion concentration (decrease ionized), acid base abnormalities (changes fraction bound to albumin - more bound when alkalemia)

666
Q

What are the effects of PTH

A

Bone resorption
Kidney: decreases phosphate reabsorption, increases calcium reabsorption, increases urinary cAMP
Intestine: increases calcium absorption (indirect via vit D)

667
Q

What does vit D do to PTH

A

Increases its secretion

668
Q

Where are PTH receptors located on the bone

A

Osteoblasts - bone formation
Long term actions of PTH is bone resorption by indirect action on osteoclasts mediated by cytokines released from osteoblasts
*regulates M-CSF, RANKL, OPG production

669
Q

Where is calcium reabsorbed in the kidney

A

Thick ascending limb and distal tubule

670
Q

What are the actions of vit D on calcium and phosphate

A

Increases absorption of both from GI tact; sensitized osteoblasts to PTH, promotes phosphate reabsorption by proximal tubule (stimulates NPT2a); inhibits PTH gene expression and stimulates CASR gene sxpression

671
Q

what is the difference between secondary hyperparathyroidism caused by renal failure and vit d deficiency

A

Renal failure: phosphate will be increased

Vit D: phosphate will be decreased

672
Q

What is Albright hereditary osteodystophy

A

Pseudohypoparathyroidism; PTH receptor doesn’t function; hypocalcemia, hyperphosphatemia, decreaed vit D; increased PTH; short stature, obesity, subcutaneous calcifications, shortened metatarsal and metacarpals

673
Q

What happens to vitamin D level with hypercalcemia of malignancy

A

Decreased

674
Q

What are the types of congenital vitamin D deficiency rickets

A
  • pseudovitamin D deficienct rickets or vitamin D deficiency rickets type I: decrease in 1 alpha hydroxylase
  • pseudovitamin D defilement rickets or vit D dependent rickets type II: decreased vitamin D receptor
675
Q

What are the values you would see with vitamin D deficiency

A

Increased PTH, decreased calcium, decreased phosphate, increased urine phosphate and cAMP, decreased vit D, osteomalacia increased resorption

676
Q

How is T4 converted to T3

A

Deiodinase

677
Q

What do perchlorate and thiocynate do

A

Inhibit iodine trapping in follicular cells of thyroid; treatment for hyperthyroidism

678
Q

What is the effect of high levels of iodine on the thyroid

A

Inhibit orgnification and synthesis of thyroid hormones (Wolff chaikoff effect)

679
Q

What does PTU do

A

Inhibits peroxidase which inhibits several steps of thyroid hormone formation

680
Q

What are the main binding proteins for thyroid hormone.

A

Thyroxine binding protein (TBG) -synthesized in liver (higher affinity for T4)
Transthyretin (TTR)
Albumin

681
Q

What is the effect of liver failure on the thyroid

A

Increases free T4 which will inhibit release of thyroid hormone

682
Q

How does pregnancy affect thyroid

A

Increases TBG levels; increases bound thyroid hormone; causes increase in secretion of T3 and 4; but are euthyroid

683
Q

What initiates puberty

A

Pulsatile secretion of GnRH *needs to be pulsatile

684
Q

What are the seminiferous tubules

A

Forms by Sertoli cells with germ cells; spermatogonia most immature located near periphery; spermatozoa: mature located near lumen of tubule

685
Q

What are the functions of sertoli and leydig cells

A

Sertoli: nutrients to sperm; form tight junctions creation blood testis barrier; secrete acqueous fluid into lumen which helps to transport sperm through tubules
Leydig: synth and secretion of testosterone

686
Q

What enzyme do the testes have that converts androstenedione to testosterone

A

17 beta hydroxystoid

687
Q

What does testosterone bind to in the lumen of the seminiferous tubules

A

Androgen binding protein (ABP)

688
Q

What tissue is responsive to DHT rather than testosterone

A

Prostate; external genitalia of male fetus, skin, liver

689
Q

Where is estrogen produce in the male

A

Conversion from testosterone to estradiol by aromatase in Sertoli cells; role in spermatogensis

690
Q

What is the rate limiting step in the synthesis of testosterone

A

Conversion of cholesterol to pregnenolone

691
Q

What is testosterone bound to in the peripheral circulation

A

SHBG and albumin

692
Q

What stimulates the conversion of cholesterol to pregnenolone

A

LH; regulates rate of testosterone synthesis; *increases affinity for P450scc enzyme for cholesterol, stimulates synthesis of P450sc enzyme (long term) P450scc = cholesterol desmolase

693
Q

What does presence of testosterone in the embryo lead to

A

Development of penis and scrotum; fetal diff of internal tract; descent of testes into scrotum during last 2-3 months of pregnancy

694
Q

What are the actions of testosterone at puberty

A

Increased muscle mass, pubertal growth spurt, closure of epiphyseal plate, growth of penis and seminal vesicles, deepening of voice, spermatogenesis, libido

695
Q

What does a deficiency of 5alpha reductase result in

A

Ambiguous external genitalia

696
Q

What are the actions of DHT

A

Fetal differentiation of external genitalia; male hair distribution and male pattern baldness, sebaceous gland activity, growth of prostate

697
Q

What stimulates the Sertoli cells

A

Testosterone and FSH (cAMP PKA pathway) results in protein synthesis and production of inhibin, ABP, aromatase

698
Q

What does FSH stimulate the Sertoli cells to do

A

Secrete ABP into the lumen of the seminiferous tubules; provides local testosterone supply for developing spermatogonia

699
Q

What is the exocrine and endocrine function of Sertoli cells

A

Exocrine: production of fluid, production o ABP, determination of release of sperm from seminiferous tubule
Endocrine: expression of ABP, Testosterone and FSH receptors, production of anti mullerian hormone (AMH), aromatiation of testosterone to estradiol 17 beta; production of inhibin to regulate FSH levels

700
Q

What are the phases of spermatogenesis

A

Mitotic division (results in primary spermatocytes), meiotic division (haploid gamete - spermatids), spermiogenesis (spermatids undergo spermiogenesis and mature into spermatozoa)

701
Q

What stimulation is needed for spermiogenesis to occur

A

FSH

702
Q

What is the effect of growth hormone on spermatogenesis

A

Needed for metabolic function of testes;; promotes early division of sperm; without it spermatogenesis is deficient

703
Q

What nerves cause ejaculation

A

Somatic b.c need striated mm to ejaculate

704
Q

What changes occur during capacitation

A

Uterine and Fallopian tube wash away inhibitory factors, cholesterol loss around the acrosome, membrane of sperm more permeable to Ca+ which increases motility

705
Q

What is the sperm acrosome reaction

A

Hyaluronidae and proteolytic enzymes are stored in acrosome; hyaluronidase depolymerizes hyaluronic acid polymers in cement that hold the ovarian granulosa cells together; proteolytic enzymes digest proteins in structural elements of tissues that adhere toe ovum

706
Q

What are the different types of gonadal dysfunction in the male

A
  • if testosterone def in 2n-3rd month o gestation: ambiguity in male genitalia
  • if def in 3rd trimester: cryptorchidism and micropenis
  • if def in puberty: poor secondary sex development; eunuchoidism(persistence of prepubertal characteristics)
  • if def post puberty: decreased libido, erectile dysfunction, decreas in hair, low energy, infertility
707
Q

What is kallman syndrome

A

Genetic; GnRH neurons fail to migrate to hypothalamus; delayed or absent puberty and impaired sense of smell; *hypogonadotropic hypogonadism; more common in males

708
Q

What is Klinefelter syndrome

A

Males with extra X chromosome; normal at birth; androgen production low; gonadotropins high; primary hypogonadism; seminiferous tubules destroyed

709
Q

What is increased in men with benign prostatic hyperplasia

A

DHT receptors

710
Q

Which gonadotropin is released more in infancy and childhood vs puberty

A

Infancy and childhood: FSH more
puberty and reproductive years: LH
Menopause: FSH

711
Q

What does LH and FSH stimulate in the female

A

LH -> theca cells (secrete androgens and progestin)

FSH -> granulosa cells (secrete progestin, estrogens, inhibins and activins)

712
Q

What do inhibins and activins do in the female

A

Inhibins inhibit FSH secretion and activins activate it

713
Q

When do granulosa cells acquire LH receptors

A

Just before ovulation

714
Q

What is the prominent estrogen produced in the nonpregnant female

A

Estradiol

715
Q

What do the ovaries contain that is important for formation of estrogens

A

Can synthesize their own cholesterol; have aromatase, 17 beta hydoxysteroid DH which can. Convert estrone to estradiol

716
Q

What is the ovarian vs endometrial cycle

A

Ovarian follicular phase coincides with proliferative phase of endometrial cycle; ovarian luteal coincides with secretory endometrial

717
Q

What happens during the follicular phase

A

FSH stimulates a follicle; ends on day of LH surge; granulosa cells produce estradiol which stimulates endometrium to undergo growth

718
Q

What happens during the luteal phase

A

Follicle transforms into corpus luteum; luteal cells produce progesterone and estrogen which stimulate endometrial growth

719
Q

What cause the LH surge

A

Positive feedback from estrogens, progestin and activins

720
Q

How do estrogens and progestins assert negative feedback

A

Estrogens at any concentration, progestins only at high concentration

721
Q

What causes a change in basal body temperature during the menstrual cycle

A

High level of estrogen before ovulation lowers it; high levels of progesterone after ovulation raise it

722
Q

What does progesterone do in the late follicular phase

A

Opposes action of estrogen on epithelial cells; promotes proliferation of stroma of endometrium stimulates 17 beta HSD and sulfotranferase which converts estradiol to weaker compound

723
Q

What dos progesterone do in the secretory phase

A

Promotes differentiation of stromal cells into predecidual cells

724
Q

What is reduced during menopause

A

Estrogen and inhibins

725
Q

What are the hormone levels seen in PCOS

A

High LH, low FSH, elevated testosterone

726
Q

How does fertilization occur

A

Sperm head attaches to zone pellucida (sperm ZP3 interaction), acrosomal reaction (increase in calcium triggers fusion of outer acrosomal membrane with sperm cells plasma membrane and results in exocytosis of acrosomal contents), sperm penetrates zona pellucida, cell membrane of sperm fuses with cell membrane of oocyte, oocytes 2nd meiotic division and cortical reaction (increase in Ca2+), sperm nucleus decondenses and forms male pronucleus which fuses with female pronucleus

727
Q

What day is the embryo a morula

A

3 days; 16 cells

728
Q

When does the embryo reach a blastocyst stage

A

Day 4-5; implantation occurs day 6-7

729
Q

Which trophoblastic cell is adhesive and invasive

A

Syncytiotrophoblasts; cadherin; makes HCG (so corpus luteum can survive); makes progesterone to sustain pregnancy independent of corpus luteum

730
Q

When do HCG levels peak

A

Week 10; cause of morning sickness

731
Q

What are the features of human placental lactogen

A

Similar to growth hormone and prolactin; detected in serum 3 weeks of gestation; *antagonistic action to insulin contributing to diabetogenicity of pregnancy

732
Q

What is estrogen production dependent on during pregnancy

A

Healthy fetus; functions during pregnancy: increase uteroplacntal blood flow, enhance LDL receptor expression in syncytiotrophoblasts, induce prostaglandin and oxytocin receptors, increase growth of mammary glads

733
Q

What are the effects of estrogen on parturition

A

Increases degree of uterine contraction, stimulates oxytocin receptor synthesis

734
Q

Which prostaglandins initiate labor

A

PGF2alpha and PGE2

735
Q

What does oxytocin do after delivery

A

Causes uterus to contract to limit blood loss

736
Q

What is the role of relaxin during labor

A

Softens and dilates cervix

737
Q

What positive feedback mechanisms are seen during labor

A

Uterine contractions stimulate prostaglandin release; stretch of cervix stimulates oxytocin release (Ferguson reflex)

738
Q

What inhibits the effects of prolactin during pregnancy

A

Estrogen and progesterone

739
Q

What is the effect of oxytocin on breast feeding

A

Enhances milk ejection (galactokinetic)

Endo/Repro (2 decks)

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