Term
| what is thelarche? what does it mark? |
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Definition
| the rapid growth of breasts at the onset of puberty - usually around 10-11 y/o. this marks entry into the tanner stage II of development and consists of fat deposition, periductal connective tissue, elongation and thickening of the ductal system. |
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Term
| what hormones are involved in thelarche? |
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Definition
| estrogens, growth hormone and prolactin - not progesterone (more involved in uterine development) |
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Term
| what is premature thelarche? |
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Definition
| breast development prior to 9 y/o which may be isolated or part of precocious puberty. no lobules are present (development is too haphazard). |
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Term
| where does most breast disease occur histologically? |
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Definition
| the terminal duct-lobular units |
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Term
| what influences changes in breast tissue? what structures are subject to changes? |
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Definition
| sex steroids, pituitary peptide hormones, and autocrine/paracrine effects instill changes in the breast epithelium, myoepithelium, and stroma with each menstrual cycle, pregnancy, lactation, and menopause. |
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Term
| what is the progression of breast lobules over time in a female? |
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Definition
| type 1 at birth (least branches), type 2 after puberty (more branches), type 3 with 32 wks pregnancy (lobules = more developed), and type 4 nursing (lobules engorged w/milk) |
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Term
| what are the main lobular subdivisions of breast tissue? how does pregnancy affect this? |
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Definition
| the breast is composed of 15-25 lobes - which each empty into separate major ducts that terminate at the nipple. these lobes are composed of lobules, which are divided into 10-100 alveoli. pregnancy increases lobuloacinar differentiation. |
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Term
| what is the function of the myoepithelial cells? how does malignancy affect them? |
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Definition
| the myoepithelial cells surround the glandular acini and help express secretory products into the duct system. they are present in benign tissue, but lost in malignancy. |
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Term
| what characterizes premature thelarche histologically? |
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Definition
| haphazard proliferation of ducts *w/o lobules surrounded by a lot of connective tissue and fat |
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Term
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Definition
| a condition where the breasts undergo a rapid and massive enlargement at puberty - characterized by exuberant connective tissue w/minimal lobular formation (similar to premature thelarche) |
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Term
| when is reduction mammoplasty performed? |
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Definition
| cosmetic purposes or relief of discomfort. the tissue removed needs to be sent to pathology. |
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Term
| what are supernumerary nipples/breasts? |
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Definition
| these persistent epidermal thickenings can be found along the milk line (axilla to perineum) and arise from primordial breast cells that fail to involute during development. they may be glandular tissue and nipple, but are usually just nipple. these may enlarge w/pregnancy. |
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Term
| what are diagnostic techniques for breast lesions? |
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Definition
| mammogram, fine needle aspiration (if lesion is palpable), core biopsy (stereotactic), needle localization (guide wire w/radiographic guidance, then excision), and open bx/frozen section (if core bx fails) |
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Term
| how do benign vs malignant lesions appear on mammography? |
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Definition
| benign lesions: well-circumscribed and round. malignant lesions: either stellate or w/calcifications or both |
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Term
| what does it mean to say that a core bx is stereotactic? how is this performed? |
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Definition
| this means radiology is used to isolate the lesion. usually the pt lies prone and the breast will hang through an opening in the table for better visualization - b/c usually this is done w/lesions visible on mammogram, but are *not palpable. the small bx size can sometimes be problematic. |
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Term
| what are the inflammatory conditions which affect the breast? what is the main concern with this? |
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Definition
| acute mastitis, duct ectasia, fat necrosis, foreign body reaction, fungal infections, granulomatous mastitis, and lymphocytic mastitis. the main concern w/these conditions is being able to r/o malignancy. |
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Term
| what characterizes acute mastitis? how would it appear on bx? |
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Definition
| this is the most common inflammatory condition of the breast and is associated with lactation and cracks in the nipple (which the oral flora of newborn invade). it is usually unilateral and most often due to staphylococcus. this can lead to abscess formation. on bx: many neutrophils and keratinized squamous epithelium due to inflammation (which may lead to duct dilation/rupture). |
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Term
| what characterizes duct ectasia? |
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Definition
| this generally occurs in older, multiparous women and occurs when ducts are dilated due to retained colostrum (fatty debris). calcification may occur as well as nipple retraction, so CA needs to be r/o. |
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Term
| what characterizes fat necrosis? |
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Definition
| this may be the result of trauma, duct ectasia or fibrocystic disease - all of which may lead to rupture of ducts/cysts and an inflammatory reaction. clinically this appears as dimpling and histologically as foamy macrophages. |
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Term
| what characterizes foreign body reaction? |
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Definition
| this appears similar to fat tissue necrosis. the lesion will not be encapsulated but will likely contain giant cells, other inflammatory cells, fat necrosis, calcification, cholesterol clefts, and hemosiderin (from breakdown of blood). these are often *bx-related, to either sutures or talc from gloves. silicone breast implants may also cause this reaction (esp if they leak). |
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Term
| what are possible infections of the breast? |
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Definition
| TB, actinomycosis, coccidioidomycosis, histoplasmosis, and sarcoidosis -> all of which can cause sinus tracts and necrotic lesions (r/o CA). |
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Term
| what characterizes granulomatous mastitis? |
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Definition
| this is rare and a dx of exclusion (r/o wegener's, sarcoidosis, other infections). it will usually happen in young women w/other inflammatory breast processes and may be due to corynebacterium. these may appear as stellate lesions on mammography and thus CA will need to be r/o. |
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Term
| what characterizes lymphocytic mastitis? |
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Definition
| this is usually seen in DM pts (also known as *diabetic mastopathy) and presents as a breast lump where lymphocytes are surrounding ductal tissue. these are usually bilateral. |
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Term
| what are the more common benign ductal breast diseases? |
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Definition
| fibrocystic "disease", duct hyperplasia, lobular hyperplasia, adenoma, intraductal papilloma (can cause bloody discharge), nipple adenoma, and adenosis. |
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Term
| how does incidence of the different kinds of benign nonproliferative disease relate to CA risk? |
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Definition
| single nonproliferative lesions (fibrocystic, papilloma, fibroadenoma) are not associated w/increased CA risk - but if multiple, the risk may increase modestly. (proliferative = overproducing ducts and lobules). proliferative lesions w/o cytologic atypia (complex fibroadenoma, florid hyperplasia, sclerosing adenosis, intraductal papillomas) have a slightly increased CA risk and proliferative lesions w/atypia have a higher risk of CA (atypical lobular/ductal hyperplasia). these risks are higher when the atypia is multifocal. |
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Term
| what characterizes fibrocystic breast "disease"? |
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Definition
| this is frequently seen in childbearing age women, usually white. the exact pathogenesis is unknown (possibly hormonal). this aberration of normal development mainly affects the terminal duct lobular unit and is usually bilateral. |
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Term
| how does fibrocystic breast "disease" appear grossly? |
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Definition
| blue dome cysts containing turbid fluid that feel "lumpy bumpy" (can make mammography more difficult). |
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Term
| what may decrease fibrocystic breast "disease"? |
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Definition
| OCPs due to balanced estrogen/progesterone effect |
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Term
| how does fibrocystic breast "disease" appear histologically? |
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Definition
| the cysts may be microscopic as well as grossly visual and should have a unicellular layer of epithelial cells that may rupture, cause fibrosis and scar. they can have a thick fibrous wall. apocrine metaplasia may also be apparent in the lining cells, causing them to become more eosinophilic, have fluffier cytoplasm and become taller. fibrosis, calcification, chronic inflammation, and epithelial hyperplasia (distinguishes proliferative from nonproliferative) may also be visible. |
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Term
| what would be most likely seen on fine needle aspiration of fibrocystic "disease"? |
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Definition
| apocrine cells w/granular cytoplasm and a nucleolus |
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Term
| what characterizes fibrocystic "disease" in terms of CA risk? |
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Definition
| if non-proliferative: no significant increase in breast CA risk. if there is epithelial hyperplasia, there is a slightly increased risk of breast CA. |
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Term
| what is apocrine "snouting"? |
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Definition
| a part of nonproliferative fibrocystic change where apocrine parts of cells stick out - benign |
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Term
| what is florid duct hyperplasia? breast CA risk? |
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Definition
| filling of the ducts w/epithelial cells in streaming patterns. normal ducts have 1-2 cell layers, therefore, 4+ is considered duct hyperplasia. histologically, this appears like a glomerulus. ~2x breast CA risk. |
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Term
| what is the CA risk w/atypical ductal hyperplasia? |
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Definition
| this carries an increased risk of breast CA (4-5x) in both breasts, which is higher if a 1st degree relative has had breast CA. thus, excision is recommended (associated w/ductal CA in situ - DCIS). |
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Term
| what are the cytologic features of atypical ductal hyperplasia? |
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Definition
| the cells are relatively bland, but are more haphazardly arranged (no streaming pattern). there may be some mitotic figures and this can resemble DCIS (send these bxs to a specialist to differentiate). |
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Term
| how does intraductal hyperplasia (IDH) compare to atypical duct hyperplasia (ADH)? |
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Definition
| cell proliferation: IDH - mixed, ADH - monotonous. secondary lumina: IDH - slit-like/irregular, ADH - roman bridges/cookie cutter. cell borders: IDH - indistinct, ADH - distinct. nuclei: IDH - variable, ADH - round. nucleoli: IDH - absent, ADH - present. necrosis: IDH - no, ADH - *if present, DCIS*. myoepithelial stain: IDH - throughout lesion, ADH - at periphery. |
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Term
| what is ductal carcinoma in situ (DCIS)? how is it often detected? how does DCIS incidence affect breast CA risk? |
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Definition
| DCIS is CA confined to the ducts (has not broken into stroma) and is often detected via calcifications on mammography. pts w/DCIS have a 8-10x increased risk of breast CA. |
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Term
| how does DCIS compare to ADH? |
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Definition
| in DCIS, comedo necrosis may occur (cells packing the ducts outstrip the blood supply = central necrosis) |
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Term
| how does DCIS compare to ductal CA? |
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Definition
| DCIS will still maintain the myoepithelial cell layer, while ductal CA loses that. |
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Term
| how is DCIS treated? what is the prognosis? |
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Definition
| sx+radiation therapy (lumpectomy - breast conserving) after which there is a low risk of local recurrence. the radiation may be deferred for lesions <1 cm/low grade, but it can help reduce ipsilateral recurrence as well as other precursor lesions (like ADH). |
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Term
| how does atypical lobular hyperplasia appear? |
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Definition
| the lobules become larger, more round, darker, more monotonous, and more solid - decreasing the level of connective tissue in the lobe. |
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Term
| what characterizes the prognosis w/atypical lobular hyperplasia? tx? |
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Definition
| atypical lobular hyperplasia or lobular intraepithelial neoplasia (LIN1) has a ~4-5x increased risk for breast CA (which is more likely if in a younger pt/on ipsilateral side). however, 42% are special subtype w/a good prognosis. excision is recommended mainly b/c some cases are associated w/DCIS. |
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Term
| what characterizes lobular CA in situ? prognosis? |
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Definition
| similar to DCIS, this is CA confined to the lobules, but is not usually associated w/microcalcifications. the risk of invasive breast CA w/this is 5x increased but watchful waiting is the treatment protocol unless there is a fam hx of invasive CA (then consider excision or b/l mastectomy). |
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Term
| what characterizes intraductal papilloma? how do they present clinically/grossly/histologically? |
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Definition
| these benign polyploid lesions protrude into dilated ducts on fibrovascular stalks and may often be seen grossly. *a common clinical presentation is bloody nipple discharge.* histologically, they are composed of arborizing architecture, generally bland nuclei, and possible minor pleomorphism. |
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Term
| what characterizes a nipple adenoma? |
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Definition
| nipple adenomas appear similar to intraductal papillomas, but appear right under the nipple. these are also benign, but can look more malignant - due to their more complex arborizing pattern. |
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Term
| what is a lactating adenoma? |
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Definition
| these generally present as a <5 cm mass (lobular, yellow, vascular) in reproductive age pts. they generally recede on their own, but if large, excision may be indicated. histologically: hyperplastic lobules (compacted, less fibrous tissue) w/cytoplasmic vacuolization. |
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Term
| what is sclerosing adenosis? |
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Definition
| this proliferation of glands is relatively common, often bilateral and usually associated w/other forms of proliferative fibrocystic change. the masses are less than 2 cm, well circumscribed/round and can be palpable - though usually a microscopic finding. they do retain lobulocentric architecture even though they are compressed and lack some fibrous tissue. like other benign lesions, sclerosing adenosis does retain myoepithelial cells. breast CA risk: ~ 1.7x higher. |
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Term
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Definition
| these benign lesions radiographically and grossly will mimic stellate breast CA lesions and are often multifocal or b/l. histologically, radial scars are normal breast structures surrounding and entrapped by *central scar tissue. CA risk: ~ 1.8 |
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Term
| what are the more common benign stromal breast diseases? |
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Definition
| fibroadenoma and phyllodes tumor |
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Term
| what characterizes fibroadenomas? |
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Definition
| these are the most common benign tumor of the breast and are seen in young women. their size will increase w/pregnancy, and they tend to regress w/age. they appear sharply demarcated, white, and tan w/a bulging surface. usually < 3 cm. |
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Term
| how do fibroadenomas appear histologically? |
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Definition
| cellular, fibroblastic stroma whirling and encasing patterns of slit-like glandular/cystic spaces. the nuclei are generally bland. the cells are so cohesive, they will stick together in "staghorn" configuration on needle aspiration. |
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Term
| can fibroadenomas be drug related? |
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Definition
| yes, they may be an unusual side effect of cyclosporin A after renal transplant |
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Term
| what is a juvenile fibroadenoma? |
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Definition
| juvenile/giant fibroadenoma are often seen in adolescents, particularly afro-americans. they may be bilateral, w/rapid growth 10 cm+. these may have ADH, suggestive of DCIS, therefore f/u is recommended (also r/o phyllodes tumor). |
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Term
| how do juvenile fibroadenomas appear histologically? |
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Definition
| the stroma may be more cellular (more visible nuclei) than a typical fibroadenoma and the ducts may show epithelial hyperplasia. |
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Term
| what is a benign phyllodes tumor? |
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Definition
| a polypoid tumor w/a leaf-like pattern. histologically, the stroma is similar to a fibroadenoma - more more cellular (even more so than juvenile fibroadenoma). 75% are benign and these are usually treated by local excision. |
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Term
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Definition
| lactation in men/women who are not breastfeeding, generally due to pituitary adenomas which secrete prolactin (or primary hypothyroidism: thyroid releasing hormone increases prolactin). dx: prolactin levels/imaging. tx: tumor inhibition w/dopamine agonist drugs or resection of adenoma. most pituitary adenomas are < 10 mm (microadenoma), grow slowly, and are considered benign. they may invade the cavernous sinus, sphenoid sinus, and the base of the brain. they are classified by their hormone production (GnRH, prolactin, TSH, ACTH, FSH). |
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Term
| what drugs might galactorrhea be associated with? |
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Definition
| phenothiazines, anti-hypertensives (methyldopa, opioids) |
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Term
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Definition
| enlargement of the male breast (fat+glandular tissue), due to an imbalance of androgens and estrogens. it can be associated with klinefelter's, anabolic steroids, psychoactive drugs (marijuana, heroin), hormone-secreting adrenal/testicular tumors, paraneoplastic gonadotropin production, and liver disease+hyperthyroidism (increased conversion of androstenedione->estrogen) |
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Term
| how does gynecomastia appear histologically? |
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Definition
| proliferation of ducts w/o lobules, dense periductal stromal fibrosis (very lumpy), and myoepithelial cells are preserved (benign). there may be stromal edema w/micropapillary hyperplasia and mild lymphocytic infiltrate. |
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Term
| what is pseudoangiomatous stromal hyperplasia (PASH) of the breast? |
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Definition
| this benign lesion is usually incidental, but may be detected as a nodule. histologically, they appear as complex, anastomosing, slit-like spaces which can be acellular or composed of spindle cells (these appear as vascular channels = pseudoangiomatous, but are just due to separation of stromal collagen fibers). these may be due to hormonally induced stromal overgrowth and are seen in women as well as men w/gynecomastia. |
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