IUHS Student-2-Student USMLE Step 1 Recall
Reproduction
Female Reproductive Organs
Pelvic
Inflammatory Disease (PID)
PID is a common disorder characterized by pelvic pain, adnexal tenderness, fever, and vaginal discharge; it results from infection by one or more of the follwing groups of organisms: gonococcus, chlamydiae, and enteric bacteria...
the gonococcus continues to be a common cause of PID, the most serious complication of gonorrhea in women...
chlamydia infection is now another well recognized cause of PID...besides these two, infections after spontaneous or induced abortions and normal or abnormal deliveries (called puerperal infections) are important in the production of PID...such PID is polymicrobial and is caused by staphylocci, streptococci, coliform bacteria, and clostridium perfringens....
gonococcal inflammation usually begins in bartholin and other vestibular glands or periurethral glands; cervix involvement is common and frequently asymptomatic...from any of these loci, the organisms may spread upward to invovle the tubes and tubo-ovarian region...
the adult vagina is remarably resistant to the gonococcus, but in the child, presumably b/c of a more delicate lining mucosa, vulvovaginitis may develop...
the nongonococcal bacterial infections that follow induced abortion, dilation and curettage of the uterus, and other surgical procedures on the female genital tract are thought to spread from the uterus upward through the lymphatics or venous channels rather than on the mucosal surfaces...these infections therefore tend to produce less mucosal involvement but more reaction within the deeper layers...
once the infection is in the tubes, an acute suppurative salpingitis ensues...
the tubal serosa becomes hyperemic and layered with fibrin, the tubal fimbriae are similarly involved, and the lumen fills with purulent exudate that may leak out of the fibriated end...
peritonitis...
intestinal obstruction due to adhesions between the small bowel and pelvic organs...
bacteremia, which may produce endocarditis, meningitis, and suppurative arthritis...
infertility, one of the most commonly feared consequences of long standing chronic PID...
in the early stages, gonoccal infections are readily controlled with antibiotics, although penicillin-resistant strains have regrettabley emerged...when the infection becomes walled off in suppurative tubes or tubo-ovarian abscesses, it is difficult to achieve a sufficient level of antibiotic within the centers of such suppuration to control these infections effectively...
postabortion and postpartum PIDs are also amenable to antibiotics but are far more difficult to control than the gonococcal infections...sometimes becomes necessary to remove the organs surgically...
Fitz-Hugh-Curtis Syndrome (perihepatitis) characterized by "violin-string" adhesions between the fallopian tube and liver capsule...
Vulva -
Bartholin Cysts
acute infection of the bartholin gland produces an actue inflammation of the gland (adenitis) and may result in a bartholin abscess...
bartholin cysts are relatively common, occur at all ages, and result from obstruction of the bartholin duct, usually by a preceding infection...
these cysts may become large, up to 3 to 5 cm in diameter...
the cyst is lined by either the transitional epithelium of the normal duct or squamous metaplasia...
the cysts produce pain and local discomfort; the cysts are either excised or opened permanently (marsupialization)...
Vulva - Vestibular Adenitis
the vulvar vestibule is located in the posterior introitus at the entrance to the vagina and contains small glands in the submucosa (vestibular glands)...
inflammation of these glands is associated with a chronic, recurrent, and exquisitely painful condition known as vestibular adenitis...
the inflammatory condition, which involves the glands and mucosa, produces small ulcerations, which account for extreme point tenderness in the vestibule...
the cause of the condition is unknown, and the condition is relieved, in some but not in all cases, by surgical removal of the inflamed mucosa...
Vulva -
Lichen Sclerosus
lichen sclerosus leads to atrophy, fibrosis, and scarring, and is also called chronic atrophic vulvitis...
the skin becomes pale gray and parchment-like, the labia are atrophied, and the introitus is narrowed...
on histologic examination, there is usually thinning of the epidermis, with disappearance of the rete pegs and replacement of the underlying dermis by dense collagenous fibrous tissue...
there is often marked hyperkeratosis and a mononuclear cell infiltrate about blood vessels...
lichen sclerosus occurs clinically in all age groups but is most common after menopause...
the pathogenesis is unclear, but genetic predisposition, autoimmunity, and hormonal factors have been implicated...at all ages, the disorder tends to be slow in developing, insidious, and progressive...it causes considerable discomfort and predisposes to acute infection but is usually of little systemic significance...
lichen sclerosus is not recognized as a precancerous condition, but it increases the risk of subsequent carcinoma...a small proportion of patients (about 1% to 4%) have been observed to develop carcinoma...
Vulva - Squamous Hyperplasia
previously
called hyperplastic dystrophy, this lesion denotes
hyperplasia of the vulvar squamous epithelium frequently with hyperkeratosis...
the epithelium is thickened and may show increased mitotic activity in both the basal and prickle cell layers with variable leukocytic infiltration of the dermis...
similar to lichen sclerosus, squamous hyperplasia is sometimes associated with carcinoma...
it is not, however, considered a significant cancer precursor unless there is coexisting epithelial atypia, in which case it is classified as a precancerous lesion (vulvar intraepithelial neoplasia)...
the pathogenesis of squamous hyperplasia is unknown...b/c the lesions may present as white vulvar plaques, they may be indistinguishable clinically from more serious disorders...thus, biopsy is indicated in all lesions, even those that are remotely suspicious...
Vulva - Papillary Hidradenoma
like the breast, the vulva contains modified apocrine sweat glands...in fact, the vulva may contain tissue closely resembling breast ("ectopic breast") and develop two tumors with counterparts in the breast...
one of these, papillary hidradenoma, is identical in appearance to intraductal papillomas of the breast...
hidradenoma presents as a sharply circumscribed nodule, most commonly on the labia majora or interlabial folds, and may be confused clinically with carcinoma b/c of its tendency to ulcerate...
on histologic examination, hidradenomas consist of tubular ducts lined by a single or double layer of nonciliated columnar cells, with a layer of flattened "myoepithelial cells" underlying the epithelium...
these myoepithelial elements are characteristic of sweat glands and sweat gland tumors...
occur along the milk line...
Vulva -
Condyloma Acuminatum
benign raised or wartlike (verrucous) conditions of the vulva occur in three forms (1) by far the most common is the condyloma acuminatum, a papillomavirus-induced squamous lesion also called venereal wart...(2) another consists of mucosal polyps, which are benign stromal proliferations covered with squamous epithelium...(3) another raised lesion, the syphilitic condyloma latum...
condylomata acuminata are sexually transmitted, benign tumors that have a distinctly verrucous gross apearance...although they may be solitary, they are more frequently multiple and often coalesce; they involve perineal, vulvar, and perianal regions as well as the vagina and, less commonly, the cervix...
the lesions are identical to those found on the penis and around the anus in males...
on histologic exaination, they consist of branching, treelike proliferation of stratified squamous epithelium supported by a fibrous stroma...acanthosis, parakeratosis, hyperkeratosis, and, most specifically, nuclear atypica in the surface cells with perinuclear vacuolization (called kioilocytosis) are present...
condylomata are caused by HPV, principally type 16 and 18, which are associated with benign genital lesions and replicate in the squamous epithelium...
Vulva - Extrammary Paget Disease
this
curious and rare lesion of the vulva, and sometimes the perianal region, is
similar in its skin manifestations to Paget disease of
the breast...
as a vulvar neoplasm, it manifests as a pruritic red, crusted, sharply demarcated, maplike area, occurring usually on the labia majora...
it may be accompanied by a palpable submucosal thickening or tumor...the diagnostic microscopic feature of this lesion is the presence of large tumor cells lying singly or in small clusters within the epidermis and its appendages...
intraepidermal malignant cells with pagetoid spread...
these cells are distinguished by a clear separation, halo, from the surrounding epithelial cells and a finely granular cytoplasm containing periodic acid schiff stain, alcain blue, or mucicarmine positive mucopolysaccharide...
ultrastructurally, paget cells display apocrine, eccrine, and keratinocyte differentiation and presumably arise from primitive epithelial progenitor cells...
in contrast to pagets disease of the nipple, in which 100% of patients show an underlying ductal breast carcinoma, vulvar lesions are most frequently confined to the epidermis of the skin and adjacent hair follicles and sweat glands...
Adenocarcinoma of the Vagina
adenocarcinomas are rare but have received attention b/c of the increased frequency of clear cell adenocarciomas in young women whose mothers had been treated with diethylstillbestrol (DES) during pregnancy (for a threatened abortion)...
vaginal adenosis is the precursor to clear cell carcinoma...
fortunately, less than .14% of such
DES-exposed young women develop adenocarcinoma...these tumors are usually discovered between the ages of 15-20 years and are often composed of vacuolated, glycogen containing cells, hence the term clear cell carcinoma...
b/c of its insidious, invasive growth, vaginal cancer (squamous and adenocarcinomatous) is diffucult to cure...thus early detection by careful follow-up is mandatory in DES-exposed women...
surgery and irradiation have successfully eradicated DES-related tumors in up to 80% of patients...
extension of cervical carcinoma to the vagina is much more common than are primary malignant neoplasms of the vagina...
accordingly, before a diagnosis of primary vaginal carcinoma can be made, a preexisting cervical lesion must be ruled out...
Vagina
- Embryonal Rhabdomyosarcoma
Sarcoma botryoides is a form of embryonal rhabdomyosarcoma seen in the vagina of young girls
also called sarcoma botryoides, this is an interesting but uncommon vaginal tumor most frequently found in infants and in children younger than 5 years...the tumor consists of predominantly of malignant embryonal rhabdomyoblasts and is thus a type of rhabdomyosarcoma...
these tumors tend to grow as polypoid, rounded, bulby masses that sometimes fill and project out of the vagina; they have the appearance and consistency of grapelike clusters (hence the designation botryoides, meaning grapelike)...
on histologic examination, the tumor cells are small and have oval nuclei, with small protrusions of cytoplasm from one end, so they resemble a tennis racket...
striations can rarely be seen within the cytoplasm...beneath the vaginal epithelium the tumor cells are crowded in a so-called cambium layer; but in the deep regions, they lie within a loose fibromyxomatous stroma that is edematous and may contain many inflammatory cells...for this reason, the lesions can be mistaken for benign inflammatory polyps, leading to unfortunate delays in diagnosis and treatment...these tumors tend to invade locally and cause death by penetration into the peritoneal cavity or by obstruction of the urinary tract...
conservative surgery, coupled with chemotherapy, appears to offer the best results in cases diagnosed sufficently early...
Acute or Chronic Cervicitis
the
bacterial growth produces a drop in vaginal pH..the
exposed endocervix is sensitive to these changes in chemical environment and
bacterial flora and responds by undergoing a transformation from columnar to
squamous epithelium, as detailed previously...
the process of transformation is also hastened by trauma and other infections occuring in the reproductive years...as the squamous epithelium overgrows and obliterates the surface columnar papillae, it covers and obstructs crypt openings, with the accumulation of mucus in deeper crypts (glands) to form mucous (nabothian) cysts...
this process is invariably associated with an inflammatory infiltrate composed of a mixture of polymorphonuclear leukocytes and mononuclear cells, and if the inflammation is severe, it may be associated with loss of the epithelial lining (erosion or ulceration) and epithelial repair (reparative atypia or dysplasia of repair)...all of these components characterize what is known as chronic cervicitis...
some degrees of cervical inflammation may be found in virtually all multiparous and in many nulliparous adult women, and it is usually of little clinical consequence...
the pathologic correlates of acute and chronic cervicitis include epithelial spongiosis (intercellular adema), submucosal edema, and a combination of epithelial and stromal changes...
acute cervicitis includes acute inflammatory cells, erosion, and reactive or reparative epithelial change...
chronic cervicitis includes inflammation, usually mononuclear, with lymphocytes, macrophages, and plasma cells...
necrosis and granulation tissue may also be present...
Endocervical Polyps
endocervical polyps are relatively innocuous, inflammatory tumors that occur in 2-5% of adult women...
perhaps the major significance of polyps lies in their production of irregular vaginal "spotting" or bleeding that arouses suspicion of some more ominous lesion...
most polyps arise within the endocervical canal and vary from small and sessile to large, 5cm masses that may protrude through the cervical os...
all are soft, almost mucoid, and are composed of a loose fibromyxomatous stroma harboring dilated, mucus-secreting endocervical glands often accompanied by inflammation and squamous metaplasia...
in almost all instances, simple curettage or surgical excision effects a cure...
Squamous Neoplasia of the Cervix Risk Factors, Etc.
early
age at first intercourse...
multiple sex partners...
a male partner with multiple previous sexual partners...
all other risk factors are subordinate to these three influences, primarily multiple sexual partners...potential risk factors that remain poorly understood include oral contraceptive use, cigarette smoking, parity, family history, associated genital infections, and lack of circumcision in the male sexual partner...
CIN -1 (mild dysplasia)...
CIN - 2 (moderate dysplasia)...
CIN - 3 (carcinoma in situ)...
HPV is currently considered an important factor in cervical oncogenesis...as noted earlier, this virus is the known cause of the sexually transmitted vulvar condyloma acuminatum and has been isolated from vulvar and vaginal squamous cell carcinomas; it is also suspected of being an oncogenic agent in a variety of other squamous tumors or proliferative lesions of skin and mucous membranes...
there is mounting evidence linking HPV to cancer in general and cervical cancer in particular...first, HPV DNA is detected by hybridization techniques in approximately 85% of cervical cancers and in approximately 90% of cervical condylomata and precancerous lesions...
second, specific HPV types are associated with cervical cancer (high risk) versus condylomata (low risk); low risk types include types 6, 11, 42, 44, and high risk types include 16, 18, 31, 33, and others...
third, in vitro
studies indicate that the high risk HPV types have the capability to transform
cells in culture, and this ability is linked to specific viral oncogenes
(E6-binds to p53 and E7-binds to Rb genes), which differ in sequence
between the high-risk and low risk HPV types...
invasive cervical carcinoma manifests in three somewhat distinctive patterns: fungating (or exophytic), ulcerating, and infiltrative cancer...
the most common variant is the fungating tumor, which produces an obviously neoplastic mass that projects above the surrounding mucosa...
it is apparent from the preceding discussion that cancer of the cervix and its precursors evolve slowly in the course of many years...
during this interval, the only sign of disease may be the shedding of abnormal cells from the cervix...for these reasons, it is generally acknowledged that periodic papanicolaou smears should be performed on all women after they become sexually active...
reduction in cervical cancer deaths would theoretically be greatest if all women were screened and if the accuracy of detecting papanicolaou smear abnormalities was maximized...
cytologic examination merely detects the possible presence of a cervical precancer or cancer; it does not make an absolute diagnosis, which requires histologic evaluation of appropriate biopsy specimens...identificaiton of abnormalities is facilitated by colposcopic examination of the cervix, in which CIN lesions are characterized by white patches on the cervix after the application of acetic acid...
in addition, distinct vascular mosaic or punctuation patterns regularly accompany invasive cervical cancer...ultimately, when these cancers become clinically overt, they usually produce irrregular vaginal bleeding, leukorrhea, bleeding or pain on coitus, and dysuria...
Uterus/Endometrium
- Adenomyosis
the endomyometrial interface is usually sharply demarcated...some endometrial glands, however, may extend beneath this interface to form nests deep within the myometrium, producing a condition known as adenomyosis....
the cause is unknown; it occurs in approximately 15-20% of uteri...
may cause diffuse enlargement...
adenomyosis causes expansion (enlargement) of the uterine wall and may be visible on gross examination as numerous small cysts...
on microscopic examination, irregular nests of endometrial stroma, with or without glands, are arranged within the myometrium, separated from the basalis by at least 2-3mm...
in some patients, the most important consequence of adenomyosis relates to shedding of the endometrium during the menstrual cycle...
hemorrhage within these small adenomyotic nests results in menorrhagia, colicky dysmenorrhea, dyspareunia, and pelvic pain, particularly during the premenstrual period...
Endometriosis
endometriosis
is the term used to describe the presence of
endometrial glands or stroma in abnormal locations outside the uterus....it
occurs in the following sites, in descending order of requency:
(1) ovaries; (2)
uterine ligaments; (3)
rectovaginal septum; (4) pelvic
peritoneum; (5) laparotomy scars; and (6)
rarely in the umbilicus, vagina, vulva, or appendix...
It may cause dyspareunia (pain of varying types)...
often causes infertility, dysmenorrhea, pelvic pain, and other problems...the disorder is principally a disease of women in active reproductive life, most often in the third and fourth decades, and afflicts approximately 10% of women....
genetic, hormonal, and immune factors have also been postulated to increase susceptibility of some women to endometriosis...based on the finding of aromatase cytochrome P450 in endometriotic tissue but not in normal endometrium, it has been suggested that the endometriotic tissue per se possesses the capacity to produce its own estrogens via this enzyme...
this and other studies suggest important biochemical differences between endometriosis tissue and normal uterine endomtrium...
Asherman Syndrome - cause of infertility b/c of scarring of the uterus when a curettage of the uterus has occurred...there is an inability for the ovum to implant...
Endometriosis clinical signs and symptoms usually consist of severe dysmenorrhea, dyspareunia, and pelvic pain due to the intrapelvic bleeding and periuterine adhesions...
pain on defacation reflects rectal wall invovlement, and dysuria reflects involvement of the serosa of the bladder...
intestinal disturbances may appear when the small intestine is affected...menstrual irregularities are common, and infertility is the presenting complaint in 30-40% of women....
rarely, malignancies may develop in endomtriotic lesions...
Endometrial Polyps
endomtrial polyps are sessile masses of variable size that project into the endomtrial cavity...they may be single or multiple and are usually .5-3.0cm in diameter but occasionally large and pedunculated...
polyps may be asymptomatic or may cause abnormal bleeding if they ulcerate or undergo necrosis...
they are generally of two histologic types made up of (1) functional endomtrium, paralleling the adjacent cycling endometrium, or (2) more commonly hyperplastic endomtrium mostly of the cystic dilated variety...
such polyps may develop in association with generalized endometrial hyperplasia and are responsive to the growth effect of estrogen but exhibit no progesterone response...
rarely, adenocarcinomas may arise within endometrial polyps...
endometrial polyps have been observed in association with the administration of tamoxifen, an antiestrogen frequently used in the therapy of breast cancer...
cyotgenetic studies indicated that the stromal cells in endomtrial polyps ar clonal with chromosome (6p21) rearrangements, indicating that genetic alterations may play a role in their development....
Carcinoma of the Endometrium
endometrial carcinoma is the most common invasive cancer of the female genital tract and accounts for 7% of all invasive cancer in women, excluding skin cancer....
there are now 34,000
new endometrial cancers per
year,
compared with 13,000 new invasive cervical cancers...
despite their high frequency, endometrial cancers arise mainly in postmenopausal women, causing abnormal (postmenopausal) bleeding...this permits early detection and cure at an early age...
carcinoma of the endometrium is uncommon in women younger than 40 years...
the peak incidence is in the 55-65 year old woman...a higher frequency of this form of neoplasiais seen with (1) obesity, (2) diabetes (abnormal glucose tolerance is found in more than 60%), (3) hypertension, and (4) infertility (women who develop cancer of the endometrium tend to be single and nulliparous and to give a history of functional menstrual irregularities consistent with anovulatory cycles)...in frequently, both endometrial and breast carcinomas arise in the same patient...
in terms of potential pathogenesis, two general groups of endometrial cancer can be identified...the first develops on a background of
prolonged estrogen stimulation and endometrial hyperplasia...
both conditions, hyperplasia and cancer, appear closely related...support for this conclusion includes the following...
first, both are also linked with obesity and anovulatory cycles...second, women with ovarian estrogen-secreting tumors have a higher risk of endometrial cancer...third, endometrial cancer is extremely rare in women with ovarian agenesis and in those castrated early in life...fourth, estrogen replacement therapy is associated with increased risk in women, and prolonged administration of DES to laboratory animals may produce endometrial polyps, hyperplasia, and carcinoma...fifth, in postmenopausal women, there is greater synthesis of estrogens in body fats from adrenal and ovarian androgen precursors, and finding that may partly explain why there is increased risk of endometrial cancer with age and obesity...
most endometrial carcinomas (about 85%) are adenocarcinomas characterized by more or less well defined gland patterns lined by malignant stratified columnar epithelial cells...
carcinoma of the endometrium may be asymptomatic for periods of time but usually
produces irregular vaginal bleeding with excessive
leukorrhea...
uterine enlargement in the early stages may be deceptively absent...cytologic detection of an papanicolaou smears is variable and most likely with serous carcinomas, which she discohesive clusters of cells...the diagnosis must ultimately be established by curettage and histologic examination of the tissue....
as would be anticipated, the prognosis depends heavily on the clinical stage of the disease when it is discovered and its histologic grade and type...
in the united states, most women (about 80%) have stage I disease clinically and have well-differentiated or moderately well differentiated lesions histologically...
surgery, alone or in combination iwth irradiation, yields close to 90% 5 year survival in stage I disease...
this rate drops to 30% to 50% in stage II and to less than 20% in any of the other more advanced stages of the disease...
invasion of myometrium is prognostically important...
Leiomyomas (fibroids)
leiomyomas
are the most
common benign tumors in women
and are
referred to in coloquial usuage as fibroids...the tumors are found in at least
25% of women in active reproductive life and are more
common in blacks....
these tumors are estrogen responsive; they regress or even calcify after castration or menopause and may undergo rapid increase in size during pregnancy...their cause is unknown, although, similar to the pathogenesis of endometrial polyps, chromosome aberrations may play a role...
tumor of smooth muscle...
leiomyomas are composed of benign smooth muscle tissue that, has the capaqcity to enter the cell cycle and divide under the stimulus of estrogen...another unusual feature is that the lack of a capsule, which is unlike most benign tumors...
Parovarian cysts (Paratubal Cysts) , also called paratubal cysts, these are common incidental findings. They are embryologic remnants of the wolffian duct...they are translucent, smooth-surfaced, thin-walled, fluid-filled cysts near the fimbriated end of the right fallopian tube
leiomyomas are sharply circumscribed, discrete, round, firm, gray-white nodules to massive tumors that fill the pelvis...except in rare instances, they are found within the myometrium of the corpus...
only infrequently do they involve the uterine ligaments, lower uterine segment, or cervix...
they can occur within the myometrium (intramural), just beneath the endometrium (submucosal) or beneath the serosa (subserosal)...
the leiomyomas is composed of whorled bundles smooth muscle cells that resemble the architecture of the uninvolved myometrium...
Leiomyosarcomas
Leiomyosarcomas are uncommon malignant neoplasms. They do not arise from leiomyomas. They are large and more cellular than leiomyomas, and have mitotic figures
these uncommon malignant neoplasms arise de novo directly from the myometrium or endometrial stroma, which undergoes smooth muscle differentiation...
their origin from a preexisting leiomyomas is a controversial issue, and most believe that such occurrences are extremely rare...
leiomyosarcomas are equally common before and after menopause, with a peak incidence at 40-60 years of age...
Suppurative and Tuberculous Salpingitis
s
uppurative
salpingitis may be caused by any of the pyogenic organisms, and often more than
one is involved...
the gonococcus still accounts for more than 60% of cases of suppurative salpingitis, with chlamydiae less often a factor...these tubual infections are a a part of PID...
tuberculous salpingitis is extremely uncommon in the united states and accounts for probably not more than 1% to 2% of all forms of salpingitis...it is more common, however, in parts of the world where tuberculosis is prevalent and is an important cause of infertility in these areas...
the most common primary lesions of the fallopian tube (excluding endometriosis) are minute, .1-2cm translucent cysts filled with clear serous fluid, called paratubal cysts (parovarian cysts)....
larger varieties are found near the fimbriated end of the tube or in the broad ligaments and are referred to as hydatids of Morgagni...these cysts are presumed to arise in remnants of the mullerian duct and are of little more than academic significance...
Polycystic Ovaries and Stromal Hyperthecosis
in polycystic ovarian disease, the central pathologic abnormality is numerous cystic follicles or follicle cysts...when it is associated with oligomenorrhea, the clinical term Stein-Leventhal syndrome has been applied...
these patients have persistent anovulation, obesity (40%), hirsutism (50%), and, rarely, virilism...
on histiologic examination, there is a thickened superficial cortex beneath which are numerable follicle cysts with hyperplasia of the theca interna (follicular hyperthecosis)...corpura lutea are frequently but not invariably absent...
High LH...Low FSH...
the initiating event in polycycystic ovarian disease is not clear, but increased secretion of luteinizing hormone theoretically stimulates the theca-lutein cells of the follicles, with excessive production of androgen (androstenedione), which is converted to estrone...
Ovarian Tumors
mutations in BRCA1 and BRCA2 increase susceptibility to ovarian cancer...most of these cancers are cysadenocarcinomas...approximately 30% of ovarian adenocarcinomas express high levels of HER2/neu oncogene, which correlates with a poor prognosis...mutations in a host tumor suppressor gene p53 are found in 50% of ovarian carcinomas...
CA-125 is also present for cancer detection...
Serous
Tumors of the Cystadenocarcinoma Variety
40% of all ovarian tumors are serous...
Ovarian carcinomas are often associated with ascites, because they seed throughout the peritoneal cavity. Psammoma body formation is common.
bilateral mass lesions of the ovaries which are unilocular, filled with watery fluid, and covered with papillary excresences on all surfaces...
serous ovarian tumors are composed of ciliated columnar serous epithelial cells, which are similar to the lining cells of the fallopian tubes...
papillary structures with psammona bodies...stratified serous or mucinous lining with tufting...
STRONG ASSOCIATION WITH THE BRCA-1 GENE MARKER...
Mucinous Ovarian Tumors
these
tumors closely resemble their serous counterparts...they are somewhat less
common, accounting for about 25% of all ovarian
neoplasms...
they occur principally in middle adult life and are rare before puberty and after menopause...
80% are benign or borderline, and about 15% are malignant...
mucinous cystadenocarcinomas are relatively uncommon and account for only 10% of all ovarian cancers...
they appear grossly as multiloculated tumors filled with sticky, gelatinous fluid rich in glycoproteins...
a condition associated with mucinous ovarian neoplasms is pseudomyxoma peritonei...this disorder combines the presence of an ovarian tumor with extensive mucinous ascites, cystic epithelial implants on the peritoneal surfaces, and adhesions...
pseudomyxoma peritonei, if extensive, may result in intestinal obstruction and death...
recent evidence strongly supports an extraovarian (usually appendiceal) primary mucinous tumor in many cases, with secondary ovarian and peritoneal spread...
Endometrioid Tumors
these neoplasms account for approximately 20% of all ovarian cancers, excluding endometriosis, which is considered non-neopastic...
most endometrioid tumors are carcinomas...less commonly, benign forms usually cystadenofibromas...they are distinguished from serous and mucinous tumors by the presence of tubular glands bearing a close resemblance to benign or malignant endometrium...
for obscure reasons, 15-30% of endometrioid carcinomas are accompanied by a carcinoma of the endometrium, and the relatively good prognosis in such cases suggests that the two may arise independently rather than by metastatic spread form one another...
about 15% of cases with endometriod carcinoma coexist with endometriosis, although an origin directly from ovarian coelomic epithelium is also possible...
forty percent involve both ovaries, and such bilaterality usually, although not always, implies extension of the neoplasm beyond the female genital tract...
Cystadenofibroma
cystadenofibromas
are variants in which there is more pronounced proliferation of the fibrous
stroma that underlies the columnar lining epithelium...
these benign tumors are usually small and multilocular and have simple papillary processes that do not become so complicated and branching as those found in the ordinary cystadenoma...
they may be composed of mucinous, serous, endometrioid, and transitional (brenner tumors) epithleium...
borderline lesions with cellular atypia and, rarely, tumors with focal carcinoma occur, but metastatic spread of either is extremely uncommon...
Brenner
Tumors
brenner tumors are uncommon adenofibromas in which the epithelial component consists of nests of transitional cells resembling those lining the urinary bladder...
less frequently, the nests contain microcysts or glandular spaces lined by columnar, mucin-secreting cells...for reasons not clear, brenner tumors are occasionally encountered in mucinous cystadenomas...
these neoplasms may be solid or cystic, are usually unilateral (90%)....
benign...
Brenners Bladder...
Germ Cell Tumors in the Ovaries
germ
cell tumors constitute 15-20% of all ovarian tumors...
most are benign cystic teratomas, but the remainder, which are found principally in children and young adults, have a higher incidence of malignant behavior and pose problems in histiologic diagnosis and in therapy...
they bear remarkable homology to germ tumors in the male testis and arise from germ cell differentiation in a similar manner...
Mature
(Benign) Teratomas
most benign teratomas are cystic and are beter known in clinical parlance as dermoid cysts...these neoplasms are invariabley benign and are presumably derived from the ectodermal differentiation of totipotential cells...cystic teratomas are usually found in young women during the active reproductive years...
they are unilocular cysts containing hair and cheesy sebaceous material...on section, they reveal a thin wall lined by an opaque, gray-white, wrinkled, apparent epidermis...from this epidermis, hair shafts frequently protrude...within the wall, it is common to find tooth structures and areas of calcification...
increased Thyroxine...
The hair is typical for an ectodermal component of a mature cystic teratoma, but mesodermal and endodermal components will also be present. This one probably has thyroid tissue, also called struma ovarii when the majority of the teratoma is composed of thyroid tissue. It is a rare cause for hyperthyroidism
Metastases are unlikely to be present
Immature (Malignant) Teratomas
these
are rare tumors that differ from benign teratomas in that the
component tissue resembles
that observed in the fetus or embryo rather than the adult...
the tumor is found chiefly in prepubertal adolescents and young women, the mean age being 18 years...
the tumors are bulky and have a smooth external surface...on section, they have a solid or predominantly solid structure...there are areas of necrosis and hemorrhage...
hair, grumous material, cartilage, bone, and calcification may be present...
on microscopic examination, there are varying amounts of immature tissue differentiatng toward cartilage, glands, bone, muscle, nerve, and others...
an important risk for subsequent extraovarian spread is the histologic grade of tumor, which is based on the proportion of tissue containing immature neuroepithelium...
immature teratomas grow rapidly and frequently penetrate the capusle with spead or metastases...stage I tumors, however, particularly those with low grade (grade I) histology, have an excellent prognosis...higher grade tumors confined to the ovary are generally treated with prophylactic chemotherapy...most recurrences develop in the first 2 years, and absence of disease beyond this period carries an excellent chance of cure...
Specialized Struma Ovarii and Carcinoid Teratomas
they are always unilateral, although a contralateral teratoma may be present...
struma ovarii is composed entirely of mature thyroid tissue...
interestingly, these thyroidal neoplasms may be hyperfunction, producing hyperthyroidism...
can cause thyrotoxicosis with a low uptake of iodine in the thyroid bed but uptake in the pelvis can be seen...
the ovarian carcinoid, which presumably rise form intestinal epithelium in a teratoma, might in fact be functioning, particularly in large (greater than 7cm) tumors, producing 5-hydroxytryptamine and the carcinoid syndrome...
primary ovarian carcinoid can be distinguished from metastatic intestinal carcinoid, the latter virtually always bilateral...
even more rare is the strumal carcinoid, a combination of struma ovarii and carcinoid in the same ovary...primary carcinoids are uncommonly (less than 2%) malignant...
Dysgerminoma of the Ovaries
the
dysgerminoma is best remembered as the ovarian counterpart of the seminoma of
the testis...similar
to the seminoma, it is composed of large vesicular cells having a cleared
cytoplasm, well-defined cell boundaries, and centrally
placed regular nuclei...
relatively uncommon tumors, the dysgerminomas account for about 2% of all ovarian cancers yet form about half of malignant germ cell tumors...
they may occur in childhood, but 75% occur in the second and third decades...some occur in patients with gonadal dysgenesis, including pseudohermaphroiditism...most of these tumors have no endocrine function, a few produce elevated levels of chorionic gonadotropin and may have syncytiotrophoblastic giant cells on histologic examination...associated with Turner Syndrome...
all dysgerminomas are malignant, but the degree of histologic atypia is variable, and only about one third are aggressive...thus, a unilateral tumor that has not broken through the capsule and has not spread has an excellent prognosis (up to 96% cure rate) after simple salpingooophorectomy...
these neoplasms are extremely radiosensitive, and even those that have extended beyond the ovary can generally be controlled by radiotherapy...overall survival exceeds 80%...
Endodermal Sinus (Yolk Sac) Tumors
this tumor is are but is the second most common malignant tumor of germ cell origin...it is thought to be derived from multipotential embryonal carcinoma by selection and differentiation toward yolk sac structure...
similar to the yolk sac, the tumor is rich in alpha-fetoprotein and alpha1-antitrypsin...
its characteristic histologic feature is a glomerulus like structure composed of a central blood vessel enveloped by germ cell within a space similarly lined by germ cells (schiller-duval body)...
similar structures are observed in the yolk sac of the rat placenta...conspicuous intracellular and extracellular hyaline droplets are present in all tumors, and some of these can be stained for alpha-fetoprotein by immunoperoxidase techniques...
most patients are children or young women presenting with abdominal pain and a rapidly developing pelvic mass...the tumors usually appear to involve a single ovary but grow rapidly and aggressively...these tumors were once almost uniformly fatal within 2 years of diagnosis, but combination chemotherapy has measurably improved the outcome...
Choriocarcinoma
more commonly of placental origin, the choriocarcinoma, similar to the endodermal sinus tumor, is an example of extraembryonic differentiation of malignant germ cells...it is generally held that a germ cell origin can be certified only in the prepubertal girl b/c after this age, an origin from an ovarian ectopic pregnancy cannot be excluded...
most ovarian choriocarcinomas exist in combination with other germ cell tumors, and pure choriocarcinomas are extremely rare...
they are histiologically identical with the more common placental lesions...these ovarian primaries are ugly tumors that generally have metastasized widely through the bloodstream to the lungs, liver, bone, and other viscera by the time of diagnosis...
like all choriocarcinomas, they elaborate high levels of chorionic gonadotropins that are sometimes helpful in establishing the diagnosis or highlighting recurrences...
in constrast to choriocarcinomas arising in placental tissue, those arising in the ovary are generally unresponsive to chemotherapy and are highly fatal...
Granulosa-Theca Cell Tumors
this designation embraces ovarian neoplasms composed of varying proportions of granulosa and theca cell differentiation...
these tumors are composed almost entirely of granulosa cells or a mixture of granulosa and theca cells...
collectively, these neoplasms account for about 5% of all ovarian tumors...although they may be discovered at any age, approximately two thirds occur in postmenopausal women...
granulosa-theca cell tumors have clinical importance for two reasons: (1) their potential elaboration of large amounts of estrogen and (2) the small but distinct hazard of malignancy in the granulosa cell forms...
functionally active tumors in young girls (juvenile granulosa cell tumors) may produce precocious sexual development in prepubertal girls...
formation of follicle like structures (Call-Exner bodies)...
in adult women, they may be associated with endometrial hyperplasia, cystic disease of the breast, and endometrial carcinoma...about 10-15% of patients with steroid-producing tumors eventually develop an endometrial carcinoma...occasional granulosa cell tumors produce androgens, masculinizing the patient...
the additional clinical significance of these tumors lies in the fact that all are potentially malignant...it is difficult, from the histologic evaluation of granulosa cell tumors, to predict their biologic behavior...the estimates of clinical malignancy (recurrence, extension) range from 5-25%...
in general, malignant tumors pursue an indolent course in which local recurrences may be amendable to surgical therapy...recurrences within the pelvis and abdomen may appear many years (10-20) after removal of the original tumor...the 10 year survival rate is approximately 85%...
tumors composed predominantly of theca cells are almost never malignant...
Thecoma-Fibromas in the Ovaries
tumors arising in the ovarian stroma that are composed of either fibroblasts (fibromas) or more plump spindle cells with lipid droplets (thecomas) are relatively common and account for about 4% of all ovarian tumor types...
b/c many tumors contain a mixture of these cells, they are termed fibroma-thecomas...pure thecomas are rare, but tumors in which these cells predominate may be hormonally active...most are composed principally of fibroblasts and are for practical purposes hormonally inactive...
fibroma-thecomas of the ovary are unilateral in about 90% of cases and are usually solid, spherical or slightly lobulated, encapsulated, hard, gray-white masses covered by glistening, intact ovarian serosa...
on histologic examination, they are composed of well-differentiated fibroblasts with a more or less scant collagenous connective tissue interspersed between the cells...areas of thecal differentiation may be identified and can be confirmed by fat stains...this exercise, however, is considered unnecessary on clinical grounds...
in addition to the relatively nonspecific finding of pain and pelvic mass, the tumors may be accompanied by two curious associations...the first is ascites, found in about 40% of cases, in which the tumors measure more than 6cm in diameter...uncommonly, there is also hydrothorax, usually on the right side...
this combination of findings (ovarian tumor, hydrothorax, and ascites) is designated Meigs Syndrome...
Krukenberg Tumor
a metastatic carcinoma of the ovary, usually bilateral and secondary to a mucous carcinoma of the stomach, which contains signet-ring cells filled with mucus...