IUHS Student-2-Student USMLE Step 1 Recall
Reproduction
Female Breast
Acute
Mastitis
during the early weeks of nursing, the breast is rendered vulnerable to bacterial infeciton by the deveopment of cracks and fissures in the nipples...
from this portal of entry, staphylococcus aureus usually, or streptococci less commonly, invade the breast substance...
mastitis is rare outside the postpartum state and is often related to periductal mastitis with secondary bacterial infection...
surgical drainage and anti-biotic therapy may limit the spread of the infection, but when extensive necrosis occurs, the destroyed breast substance is replaced by fibrous scar as a permanent residual of the inflammatory process...
such scarring may create a localized area of increased consistency sometimes accompanied by retraction of the skin or the nippple, changes that may later be mistaken for a neoplasm...
often in postpartum period...
Periductal Mastitis
women
present with a painful erythematous subareolar mass,
usually clinically thought to be an infectous process...
recurrences are common if it is treated with incision and drainage alone...in recurrent cases, a fistula tract often tunnels under the smooth muscle of the nipple and opens onto the skin at the edge of the areola...
fibrosis and scarring usually occur, followed by nipple inversion...
keratatinzing squamous epithelim extending to an abnormal depth into the orifices of the nipple ducts...keratin is trapped within the ductal system and causes dilation and eventually rupture of the duct...
an intense chronic and granulomatous inflammatory response develops to keratin spilled into periductal tissue...
more than 90% of women with periductual mastitis are smokers, suggesting that tobacco use alters the epithelium of the lactiferous sinuses...this condition is not associated with lactation, a specific reproductive history, or age...
Mammary
Duct Ectasia
this disorder tends to occur in the fifth or sixth decade of life, usually in multiparous women, and, unlike periductal mastitis, is not associated with cigarette smoking....
patients present with a poorly defined palpable periareolar mass, sometimes with skin retraction, often accompanied by a
thick cheesy nipple secretion ...pain and erythma are uncommon...
mammary duct ectasia may simulate cancer clinically...it is a disorder of premenopausal age that manifests often with nipple retraction or inversion and sometimes with nipple discharge...
characteristic histologic features include marked dilatation (ectasia) of large ducts with fibrosis and chronic inflammation...
the pathogenesis is obscure but may be a reaction to stagnant colostrum...
Fat Necrosis
if
strict criteria are used to differentiate this entity from mammary duct ectasia,
many patients give a history of
trauma,
prior surgical intervention, or radiation therapy...
the lesion may consist of hemorrhage in ther early stages and, later, central liquefactive necrosis of fat...still later, it may be an ill-defined nodule of gray white, firm tissue containing small foci of chalky white or hemorrhagic debris..."microcalcifications"...
the central focus of necrotic fat cells is surrounded by lipid-filled macrophages and an intense neutrophilic infiltration...
then, during the next few days, progressive fibroblastic proliferation, increased vascularization, and hymphocytic and histiocytic infiltration wall off the focus...
by this time, the central necrotic fat cells have disappeared and may be represented only by foamy, lipid-laden macrophages and spicules of crystalline lipids....
subsequently, foreign body giant cells, calcium salts, and blood pigments make their appearance, and eventually the focus is replaced by scar tissue or is encysted and walled off by collagenous tissue...
Fibrocystic Changes of the Breast
fibrocystic changes represent the single most common disorder of the breast (40%) and account for more than half of all surgical operations on the female breast...
most often involves upper outer quadrant...
All of these are seen in fibrocystic changes:
Sclerosing adenosis...
Fibrosis...
Ductal epithelial proliferation...
Apocrine metaplasia...
the condition is unusual before adolescence, is diagnosed frequently between the ages of 20-40 years, peaks at or just before the menopause, and rarely develops after the menopause...however, premenopausal lesions may persist into the more advanced years...
hormonal imbalances are considered to be basic to the development of this multipatterned disorder...the excess of estrogens may represent an aboslute increase, as in the rarely associated functioning ovarian tumors, or may be related to a deficiency of progesterone, as seen in anovulatory women...
there is also some evidence of abnormal end organ metabolism of hormones in the pathogenesis of cystic disease...
oral contraceptive use decreases the risk of fibrocystic changes, presumably b/c it supplies a balanced source of progesterone and estrogen...
may form blue domed cysts...
no cartilaginous changes metaplasia...
Epithelial Hyperplasia of the Breast
in normal breast, only a double layer of myoepithelial and epithelial cells is present above the basement membrane...
epithelial hyperplasia is defined by an incrase in the layers of cells and may be due to increased proliferation or, more likely, failure of cells to undergo apoptosis...
if more than four cell layers are present, there is an increased risk of developing carcinoma...
this is not to say that all foci of epithelia hyperplasia (termed epitheliosis by british pathologists) are premalignant, leading ineveitably to carcinoma; indeed, only a small proportion apparently are...
but it is this pattern of alteration that should concern the pathologist, who is called to differentiate among benign hyperplasia, atypical but still noncancerous hyperplasia, and carcinoma...
Sclerosing Adenosis
this lesion is characterized histologically by increased numbers of distored and compressed acini...small lesions commonly present as mammographic calcifications, and larger lesions may form mammographic densities or, rarely, palpable masses...
areas of sclerosing adenosis sometimes have a hard cartilaginous consistency that begins to approximate that found in breast cancer...on section, the involved area is not well localized and does not have the chalky yellow-white foci and streaks that identify breast carcinoma, an important gross differential feature...
the number of acini per terminal duct is increased to atleast twofold the number found in uninvolved lobules...the lobular arrangement is maintained...the acini are compressed and distorted in the central portions of the lesion but characteristically dilated at the periphery...
myoepithelial cells are often prominent...on occasion, stromal fibrosis may totally compress the lumens to create the appearance of solid cords or double strands of cells lying within dense stroma, a histologic pattern that at times verges on the appearance of carcinoma...
although long thought to be a completely innocuous lesion, sclerosing adenosis has been shown to confer a slightly increased riak of subsequent cancer...
Small Duct Papillomas
small
papillomas occur deep within the breast and are often associated with the other
changes of proliferative breast disease...
these small papilloms are usually clinically silent and are probably etiologically distinct from the large duct papillomas associated with nipple discharge discussed later...
fibrovascular cores extend into small duct lumens and are lined by a normal two cell layer...
however, epithelial hyperplasia may also be present in papillomas...
the distinction between a benign but atypical small duct papilloma and an intraductal papillary carcinoma may be difficult in some cases...
in general, a monomorphic cell population, the absence of myoepithelial cells, delicate vascular connective tissue cores, the presence of cribriform or micropapillary areas, and the absence of hyalinization or apocrine metaplasia favor a malignant rather than benign papillary tumor...
Stromal
Tumor Known as Fibroadenoma
this is the most common benign tumor of the female breast...as the name implies, it is a new growth composed of both fibrous and glandular tissue...some fibroadenomas represent hyperplasia and are polyclonal in origin...
for examle, almost half of women receiving cyclosporin A after renal transplantation develop fibroadenomas...
the tumors are frequnetly multiple and bilateral and are likely to be due to drug-related growth stimulation...on the other hand, there is a subset of fibroadenomas that are benign neoplasms of stroma cells...
multple studies have shown that in some tumors, the fibrous (stromal) component is clonal and may have cytogenetic aberrations, but the epithelial component is polyclonal...
occuring at any age within the reproductive period of life, fibroadenomas are somewhat more common before age 30 years.....
young women usually present with a palpable mass and older women with a mammographic density...fibroadenomas are associated with a mild increase in the risk of subsequent breast cancer, especially when they ae associated with fibrocystic changes, proliferative breast disease, or a family history of breast cancer...
these
lesions originate from the terminal duct lobular
unit and histologically reveal a mixture of fibrous connective tissue and ducts...
the fibroadenoma grows as a spherical nodule that is usually sharply circumscribed and freely movable from the surrounding breast substance...
increase in size and tenderness in pregnancy...
these tumors frequenlty occur in the upper quadrant of the breast...they vary in size from less than 1 cm to giant forms 10-15cm in diameter (giant fibroadenoma), but most are surgically removed when they are 2-4 cm in diameter...on section, they are grayish white and often contain slit-like spaces...
the histologic pattern is essentially one of delicate, cellular, fibroblastic stroma resembling intralobular stroma, enclosing glandular and cystic spaces lined by epithelium...the epithelium may be surounded by stroma or compressed and distorted by it...
Cystosarcoma Phyllodes Tumor
Phyllodes tumors can reach a large size. The histologic elements resemble a fibroadenoma, but the stroma is more cellular, and pleomorphism with atypia of ductal or stromal elements may be present. Some may act in a malignant fashion.
These tumors can be quite large. The stromal component is more cellular than a fibroadenoma and may show atypia or frank malignancy...cellular stromal component along with an epithelial component...
phyllodes tumors, like fibroadenoams, arise from intralobular stroma...although they can occur at any age, most present in the sixth decade, 10-20 years later than the average presentation of a fibroadenoma...most are low grade tumors that may recur locally but only rarely metastasize...
rare high grade lesions behave aggressively, exhibiting local recurrences commonly and distant hematogenous metastases in about one third of cases...as is true of other stroma malignant neoplasms, lymph node metastases are rare...the term cystosarcoma phyllodes is sometimes used for these lesions; however, the majority of the tumors behave in a relatively benign fashion (85%)...
the larger lesions often have bulbous protrusions due to the presence of nodules of proliferation stroma covered by epithelium...this growth pattern can also occasionally be seen in larger fibroadenomas and is not an indicator of malignancy...
phyllodes tumors are distinguished from the more common fibroadenomas on the basis of cellularity, mitotic rate, nuclear pleomorphism, stroma overgrowth, and infiltrative borders....
lower grade lesions resemble fibroadenomas but with increased cellularity and mitotic figures...
high grade lesions may be difficult to distinguish from other types of soft tissue sarcomas and may have foci of heterologous mesenchymal differentiation...
Large Duct Papilloma (Intraductal Papilloma)
most of
these lesions are solitary and are found within the principal lactiferous ducts
or sinuses...they represent papillary clonal
proliferations of duct epithelia cells and are thus classified as
true neoplasms...
more than 80% present as spontaneous unilateral serous or bloody nipple discharge, the remainder as small palpable masses or mammographic densities...although nipple discharge is most commonly due to such benign papillomas, it is associated with carcinoma in 7% of women younger than 60 years and in 30% of woman older than 60 years...
the tumors are rarely more than 1cm in diameter and are composed of multiple branching papillae, each having a connective tissue axis covered by epithelial and myoepithelial cells...growth occurs within a dilated duct or lactiferous sinus close to the nipple...apocrine metaplasia is common...the papilloma can spontaneously infarct, possible b/c of torsion on the stalk, resulting in hemorrhagic discharge...
the present consensus is that most solitaty intraductal papillomas are benign and are not the precursors of papillary carcinoma...
however, multiple small duct papillomas should be distinguished from the group, since they are associated with an increased risk of development of carcinoma...
nipple adenoma and florid papillomatosis of the nipple are terms used to describe tumors of the nipple exhibiting adenosis of the duct epithelium sometimes associated with papillary areas...
they should be differentiated from intraductal papilloma, as they are associated with concomitant or subsequent carcinoma in 16% of cases, often found elsewhere in the breast...
Genetic Predisposition to Carcinoma of the Breast
two genes, BRCA1 and BRCA2 account for the majority of hereditary breast cancers...
BRCA-2 is exclusively with breast cancer...
In Situ
(Nonivasive) Carcinoma (Ductal Carcinoma in Situ, DCIS)
containing solid sheets of malignant cells, with central necrosis and calcification. There is no invasion...
the number of cases of dutal carcinoma in situ (DCIS) has rapidly increased in the past two decades from less than 5% of all carcinomas before mammographic screening to 15-30% of carcinomas in well-screened populations...
among mammographically detected cancers, almost half are DCIS...the lesion consists of a malignant population of cells that lack the capacity to invade through the basement membrane and, therefore, are incapable of distant metastasis...
however, these cells can spread throughout a ductal system and produce extensive lesions involving an entire sector of a breast...
when DCIS involves lobules, the acini are often distorted and unfolded and take on the apppearanc of small ducts...
DCIS has been divided into five architectual subtypes: comedocarcinoma, solid cribriform, papillary, and micropapilary....
some cases of DCIS will have a single growth pattern, but the majority demonstrate a mixture of patterns...
Invasive Ductal Carcinoma, No Special Type (NST)
invasive
ductal carcioma NST includes the majority of carcinomas (70-80%)
that cannot be
classified as any other subtype...
most of these cancers exhibit a marked increase in dense, fibrous tissue stroma, giving the tumor a hard consistency (scirrhous carcinoma)...these growth occur as fairly sharply delimited nodules of stony-hard consistency that average 1-2cm in diameter and rarely exceed 4-5cm...
on palpation, they may have an infiltrative attachment to the surrounding structures with fixation to the underlying chest wall, dimpling of the skin, and retraction of the nipple...
on histologic examination, the tumor consists of malignant cells disposed in cords, solid cell nests, tubules, anastomosing masses, and mixtures of all these invading into stroma...
The best overall survival is with intraductal carcinomas (those that have not invaded out from the ducts)...
desmoplasia characterizes invasive ductal carcinoma...
Lobular
Carcinoma in Situ (LCIS)
lobular carcinoma in situ is manifested by proliferation, in one or more terminal ducts or ductules (acini), of a monomorphic population of cells that are loosely cohesive, are somewhat larger than normal, and have oval or round nuclei with small nucleoli....
signet-ring cells containing mucin are commonly present...LCIS rarely distorts the underlying architecture, and the involved lobules remain recognizable...
LCIS is an incidental finding in biopsies performed for other reasons b/c it is only rarely associated with calcifications and never forms a mass...
thus, it remains infrequent (1-6% of all carcinomas) in mammographically screened populations...
LCIS is bilateral in 50-75% of women when both breasts are examined, compared with 10-20% in cases of DCIS...however, most incidentally detected lesions do not progress to clinically recognized disease...
women diagnosed with LCIS by biopsy develop invasive carcinomas at a frequency similar to that of women with untreated DCIS...in patients observed for more than 20 years, invasive carcinoma develops in 25-35%...however, unlike in DCIS, both breasts are at equal risk...
invasive carcinomas developing in women after a diagnosis of LCIS are threefold more likely to be of lobular type compared with carcinomas overall, but the majority do not show specific lobular differentiation...
Invasive Lobular Carcinoma
although making up only 5-10% of breast carcinomas, invasive lobular carcinomas are of partiuclar interest for the following reasons...
they tend to be bilateral far more frequently than other subtypes, the likelihood of cancer in the contralateral breast being on the order of 20%...
they tend to be multicentric within the same breast...they often have a diffusely invasive pattern that can make both primary tumors and metastase difficult to detect either by physical examination or by radiologic studies...they more frequently metastasize to cerebrospinal fluid, serosal surfaces, ovary and uterus, and bone marrow compared with other subtypes...
on histologic examination, strands of infiltrating tumor cells, often only one cell in width (in the form of a single file), are loosely dispersed througout the fibrous matrix...
classic well-differentiated invasive lobular carcinomas are usually diploid, exhibit hormone receptors, are associated with LCIS in more than 90% of cases, and have a better prognosis than carcinomas of no special type...virtually all invasive lobular carcinomas, as well as LCIS, lack the cell-cell adhesion molecule E-cadherin compared with only 52% of invasive ductal carcinomas...
Particularly when atypical, lobular or ductal hyperplasia is the component of fibrocystic disease that is associated with increased risk for carcinoma.
Medullary Carcinoma
little fibrosis surrounding sheets of large vesicular cells with frequent mitoses...
medullary
carcinoma accounts for 1-5% of all mammary carcinomas and occurs in younger than
average women...they are, however, disproportionately reported in women carrying
the BRCA1 gene, in which group they account for 13% of cancers...
these tumors do not have the striking desmoplasia of the usual carcinomas and, therefore, are distinctly more yielding on external palpation and on acute section...the tumor has a soft, fleshy consistency and is well circumscribed...
the carcinoma is characterized histologically by (1) solid, syncytium-like sheets (occupying more than 75% of the tumor) of large cells with vesicular, often pleomorphic nuclei, containing prominent nucleoli and frequent mitoses; (2) a moderate to marked lymphoplasmacytic infiltrate surrounding and within the tumor; and (3) a pushing (noninfiltrative) border...
medullary carcinomas have a slightly better prognosis than do carcinomas of no special type, despite the almost universal presence of poor prognostic factors including high nuclear grade, aneuploidy, absence of hormone receptors, p53 expression, and high proliferative rates...
the syncytial growth pattern and pushing borders may reflect retention or overexpression of adhesion molecules that could potentially limit metastatic potential...tumor cells have been reported to strongly express HLA-DR...
Colloid
(Mucinous) Carcinoma
this unusual variant (1-6% of all carcinomas) tends to occur in older women and grows slowly during the course of many years...
the tumor is extremely soft and has the consistency and appearance of pale gray blue gelatin...
colloid carcinomas are usually well circumscribed and may mimic benign lesions on physical examination and mammographically...
on histologic examination, there are large lakes of lightly staining, amorphous mucin that dissect and extend into contiguous tissue spaces and planes of cleavage...
floating within this mucin are small islands and isolated neoplastic cells, sometimes forming glands...
neuroendocrine differentiation in the form of argyrophilic granules is present in 14-50%...
colloid carcinomas are usually diploid, and the majority exhibit hormone receptors...the survival rate is appreciably greater in colloid carcinoma than in carcinomas of no special type, and lymph node metastases are present in less than 20% of patients...
Comedocarcinoma of the In Situ (Noninvasive) Carcinoma type
comedocarcinoma
is characterized by solid sheets of high-grade
malignant cells and central necrosis...
cheesy consistency of tumor tissue due to central necrosis...
the necrosis commonly calcifies and is detected on mammography as clusters or linear and branching microcalcifications...
commonly associated with the erb B2/neu oncogene and a poor prognosis...
traztuzumab (Herceptin) may be effective in treatment...
punctate areas of necrotic material ("come dome"-like) can be seen grossly...
periductal concentric fibrosis and chronic inflammation occur commonly, and extensive lesions are sometimes palpable as an area of vague nodularity...
Paget's
Disease of the Nipple
cells are PAS positive and diastase-resistant, stain positively for mucin...
paget's disease of the nipple is a form of DCIS that extends from nipple ducts into the contiguous skin of the nipple and areola...
always associated with intraductal carcinoma of the breast...often with adenocarcinoma...
the most striking gross characteristics of this lesion involve the skin of the nipple and areola, which is frequently fissured, ulcerated, and oozing...
there is surrounding inflammatory hyperemia and edema and, occasionally, total nipple ulceration...
an
underlying palpable mass is present in 50-60% of cases and usually indicates the
presence of invasive carcinoma...
the histologic hallmark of this entity is the involvement of the epidermis by malignant cells, referred to as Paget cells...
these cells are large and have abundant clear or lightly staining cytoplasm and nuclei with prominent nucleoli...the cells often contain mucin and are immunoreactive for epithelial membrane antigens, c-erb-B2 (Her2/Neu), and low-molecular weight keratins...
in addition to the paget cells, the other histologic criteria of ductal carcinoma are present...prognosis is dependent on the extent of the underlying carcinoma...