Chapter 18 – female

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• The most common cancer in women breast cancer
• The least common cancer om female reproductive system? Vaginal cancer
• second most common cancer of female R.S.? cervical cancer
• Third most common cancer of female R.S.? uterine body (corpus)
• arises during lactation fr. cystic dilation of an obstructed duct. Painful “lumps” that may rupture & initiate a local inflammatory reaction → Produce an indurated focus that falsely suggest malignancy Galactocele
• The most common breast abnormality seen in premenopausal women arising during reproductive age because of the cyclic breast changes that occur normally in the menstrual cycle fibrocyctic changes
• Nonproliferative changes & Proliferative patterns fibrocyctic breast changes can be subdivided into
• Oral contraceptives & estrogenic therapy decrease their incidence fibrocystic changes of breast AND surface epithelial origin tumors of ovary
• The most common type of fibrocystic lesions characterized by: an incr. in fibrous stroma associated w/ dilation of ducts & formation of variably sized cysts Nonproliferative Changes
• multifocal, bilateral, foci of fibrosis in the stroma with blue dome cycts (filled with watery, turbid fluid that may calcify) AND apocrine mataplasia Morphology of nonproliferative fiborcyctic Changes
• seen in the lining cells, benign, cells look: large & polygonal w/ abundant granular, eosinophilic cytoplasm and small, round, deeply chromatic nuclei Apocrine metaplasia
• Epithelial hyperplasia & sclerosing Adenosis Proliferative fibrocystic changes in breast include
• 2 layers of cells (ductal & myoepitehlial), maturation in the center, atypical ductal hyperplasia, may resemble carcinoma in situ, fenetsration & ductal papillomatosis can be seen, rarely microcalcifications are seen morphology of epithelial hyperplasia of ( in breast) proliferative fibrocystic change
• Least common of the fibrocystic changes in the breast sclerosing adenosis
• "bland ducts", more glands that are back to bakc, may resemble invasive breast carcinoma, apocrine metaplasia seen, fibrosis morphology of sclerosing adenosis
• Fibroadenoma, phyllodes tumor, intraductal papilloma tumors of the breast
• Age & sex of people affected by fibroadenomas? (breast) young females, in 3rd decade of life
• Most common benign neoplasm of the female breast? fibroadenoma
• Biphasic tumors = of 2 elements fibroblastic stroma & epithelium-lined glands, tan-white color punctuated by pink specks, intact BM morphology of fibroadenoma
• increase in estrogen – may regress & calcify after menstruation or enlarge during pregnancy & menstruation cause of fibroadenoma
• biphasic (neoplastic stromal cells & epithelium lined gland), arise de novo, remains localized, ncr. stromal cellularity, anaplasia, high mitotic activity, rapid increase in size & infiltrative margins morphology of phyllodes Tumor (“leaflike”/cystcarcinoma)
• within the principal lactiferous ducts or sinuses, solitary & composed of multiple papillae, apocrine metaplasia is seen, epithelium looks quite normal, has multiple papillae Morphology of intraductal papilloma
• (1) Serous or bloody nipple discharge (2) small subareolar tumor a few millimeters in diameter (3) Nipple retraction clinical presentation of intraductal papilloma
• Which mutations can be found in female breast carcinomas? HER2(ERBB2)/NEU, RAS & MYC, RB & TP53 , Estrogen receptor gene, Li-Freuman syndrome, Cowden (PTEN), ataxia telangietacia gene carriers
• 1. Luminal A (ER-positive, HER2/NEU negative) 2. Luminal B (ER-positive, HER2/NEU positive) 3. HER2/NEU positive (ER-negative, HER2/NEU pos) 3. Basal like/tripple-negative (ER-negative, HER2/NEU negative) molecular subtypes of breast carcinoma
• Ashkenazi jews + genetic changes + hormonal influences + environmental variables + postmenopausal age + Western lifestyle (stress, high calory, lack of physical), Positive family history, Nulliparity, Unopposed, long-term estrogen therapy, late menopause risk factors for breast carcinoma
• upper quadrant location of most breast carcinomas
• Non-invasive (= LCIS, DCIS) & invasie (Lobular, ductal, medullary, colloid, tubular, other) Grouping of breast carcinoma according to morphology
• Includes DCIS & LCIS, Arise fr. cells in the terminal duct lobular unit, confided by basememt mebrane, Don’t invade into stroma or lymphovascular channels non-invasive breast carcinoma
• comedo necrosis, cribriform pattern, calcifications, fill & disort ductlike spaces, confined by BM Morphology of ductualr carcinoma in situ
• excellent, 97% survival after masterectomy prognosis for DCIS
• a variant of DCIS, caused by the extension of DCIS up the lactiferous ducts and into the contiguous (adjacent) skin of the nipple causes fluid to exit which forms crusts Paget disease
• mild behavior, signet ring cells sometimes form, usually expands but does not alter the acini of lobules, monomorphic, rarely calcify, found incidentally morphology of LCIS (breastI
• 1/3 develops invasive carcinoma Prognosis for LDCIS
• 70 - 80% of carcinoma, associated with DCIS, have desmoplstic responese & overexpression of HER2/NEU in 1/3 of cases and estrogen & progesterone receptors also expressed in 2/3 Invasive ductal carcinoma
• 20% of all breast carcinomas, associated with LCIS,has mutation in gene for E-cadherine & HER2/NEU mutation. Morphology includes "single file/indian file" patterns Invasive lobular carcinoma (breast)
• Not a distinct type but more of a clinical diagnosis. Manifests as an enlarged, swollen, erythematous breast, usually without a palpable mass. many metastize to distant, 5-year survival is under 50%, even lower in those with metastatic disease at diagnosis Inflammatory carcinoma (breast)
• Very rare, has poor prognosis, make up 1 % of the breast carcinomas. Morphology of sheets of large anaplastic cells w/ well- circumscribed, “pushing” borders. Have BRCA1 mutation or be tripple negative Medullary carcinoma of breast
• curdy, white leukorrhea in vaginitis by candida albicans
• watery, copious, gray-green Leukorrhea in vaginitis with trichomonas vaginalis infection
• uncommon cancer arising from vaginal intraepithelial neoplasia (arising from HPV) and occurs in women over 60 years squamous cell carcinoma of the vagina
• Rare cancer arising from vaginal adenosis (small inclusions in the vaginal mucosa lined by mucous-secr. or ciliated columnar cells) occuring in young females whose mothers took diethylstilbestrol to prevent sponataneous abortions clear cell adenocarcinoma of vagina
• Rare primary vaginal cancer also know as embryonal rhabdomyosacroma seen in infants and young children (under 5 years). Can be seen in bladder & bile duct as well. Forms soft polypoid masses. Sarcoma botryoides
• Non-neoplastic disorder appearing as leukoplakia and a stiffened & atrophic labia. It's characterized by thinning of the epidermis, disappearance of rete pegs, hydropic degenertation of basal cells, dermal fibrosis, mononuclear infiltrate. Causes is unknow but T cells are present and it's seen in females with other autoimmune conditions Lichen sclerosis
• Nonneoplastic lesion manifested as leukoplakia at the rim of an already existing vulvular cancer. It's marked by hyperkeratosis & epithelial thickening (& incr. mitotic activity, no atypia, leukocytic infiltration Lichen simplex chronicus
• most common warty lesion of vulva caused by HPV 6 & 11. Morphologic features include elevated lesions with koilocytosis condylomata acuminata
• Perinuclear cytoplasmic vacuolization, wrinkled nuclear contours, acanthosis, hyperkeraatosis Koilocytic changes (in condylomata acuminata)
• Diffuse epidermal hyperplasia in vulva (condylomata acuminata– koilocytosis) acanthosis
• Most common type of squamous cell carcinoma of the vulva The non-hpv related one (associated to lichen sclerosus)
• Lichen sclerosis are bengin lesions that may transform to suwamous cell carcinoma of the vulva in 1-5 % of patients with sympomatic kinds.
• unifocal, manifest as a well-differentiated keratinizing carcinoma morphology of HPV negative squamous cell carcinoma of vulva
• mutlifocal, warty, poorly differentiated, lichen simplex sclerosis may be found at its rim morphology of HPV positive squamous cell carcinoma of vulva
• epidermal progenitor cells (not an underlying tumor) extramammary paget disease arises from
• tumor of fallopian tube that may be of serous of serous or endometriod type and is increased in females with BRCA1 mutations primary adenocarcinoma
• uncommon innocuous lesions in ovaries originating fr. unruptured graafian follicle or from fr. follicles that ruptured & then become immediately sealed follicle & luteal cysts
• disorder of ovaries where multiple cystic follicles in the ovaries produce excess androgens & estrogen leading to inhibition of FSH fr. pituitary. Look like enlrged ovary with cysts lined by granulosa cells W/ hyperplastic luteinized theca interna stein–leventhal syndrome
• growth of the endometrium into the myometrium – no cyclic bleading, just a thick globular uterus Adenomyosis
• Endometrial glands or stroma utside of the endometrium leading to cyclic bleeding and even fibrosis and sealing of the tubes and pigment formation . Seen in 50 % of infertile women endometriosis
• Endometrial tissue in endometriosis is not just misplaced but also abnormal cause it produces inflammatory mediators e.g. prostaglandins and increased estrogen which increases their survial in other tissues.
• chocolate cyst endometriosis
• . Hyperplasia without cellular atypia carries a low risk (between 1% and 3%) for progression to endometrial carcinoma , whereas hyperplasia with atypia, also called endometrial intraepithelial neoplasia (EIN), is associated with a much higher risk (20%–50%)
• hyperplasia with atypia (high risk of malignancy) endometrial intraepithelial neoplasia
• mucinous, tubal, squamous types of enometrioid carcinomas
• Mutations in endometrioid and serous carcinomas? TP53 (serous mostly), PTEN (enodmetrioid mostly), missmatch repair gene, Lynch syndrome
• Genes involved in endometrial hyperplasia leading to an "independent" hyperplasia? PTEN
• Carcinoma arising in the setting of endometrial atrophy in posmenopausal women that has an agressive behavior caus eit mostly has TP53 mutation Serous carcinoma of endometrium
• most common benign tumor in in females arise from the smooth muscle cells in the myometrium leiomyoma
• arise de novo from the mesenchymal cells of the myome- trium. They are almost always solitary and most often occur in postmenopausal women, in contradistinction to leiomyoma (which occur in premenopausal) leimyosarcoma
• "fish-fleash appearance", atypical, necrotic, hemorrhagic morphology of leiomyosarcoma in myometrium
• molar lesions & nonmolar lesions categories of gestational trophoblastic disease
• hydatiform mole, invasive mole, choricarcinoma – all elaborate hCG categories of molar gestational trophoblastic disease
• partial & complete mole categories of hydatiform molar gestational trophoblastic disease
• Voliminous, cystcally dilated chronic villi take the "grape-fruit" appearance hydatiform mole
• A form of molar gestational that are not compatible with embryogenesis and rarely contain fetal parts. All of the chorionic villi are abnormal, and the chorionic epithelial cells are diploid (46,XX or, uncommonly, 46,XY). Never contain fetal parts. complete hydatiform mole (gestational trophoblastic disease)
• "Snowstorm appearnace" is seen on microscopic examination of the complete mole also shows hydropic swelling of poorly vascularized chorionic villi with a loose, myxomatous, edematous stroma. The chorionic epithelium typically shows a proliferation of both cytotrophoblasts and syncytiotrophoblasts. Histologic grading to predict the clinical outcome of moles has been supplanted by monitoring of hCG levels.
• In partial mole , villous edema involves only a subset of the villi, and the tropho- blastic proliferation is focal and slight. In most cases some fetal cells are present, ranging from fetal red cells in placental villi to, in rare cases, a fully formed fetus.
• The partial hydatidiform mole is compatible with early embryo formation and there- fore may contain fetal parts, has some normal chorionic villi, and is almost always triploid (e.g., 69,XXY)
• age & race of those people mostly affected by gestational trophoblastic disease asian, before 20 and after 40 years
• Elevated hCG and lack of fetal heart sounds is common for both hydatiform moles.
• invasive moles are complete moles that are locally invasive but lack the metastatic potential of choriocarcinoma.
• On microscopic examination, the epithelium of the villi of invasive moles show atypical changes, with proliferation of trophoblastic and syncytiotrophoblast components
• A very tumor that is rare in the western but common in asian population. An aggressive malignant tumor, arises from gestational chorionic epithelium or, less fre- quently, from totipotential cells within the gonads (as a germ cell tumor). gestational choriocarcinoma
• usually appear as hemorrhagic, necrotic uterine masses. Sometimes the necrosis is so extensive that little viable tumor remains. Indeed, the primary lesion may “self- destruct, ” and only the metastases tell the story. Very early, the tumor insinuates itself into the myometrium and into vessels. In contrast with hydatidiform moles and invasive moles, chorionic villi are not formed; instead, the tumor is com- posed of anaplastic cuboidal cytotrophoblasts and syncytiotrophoblasts morphology of choriocarcinoma
• The development of hypertension, accompanied by pro- teinuria and edema in the third trimester of pregnancy, is referred to as preeclampsia and occurs in 5% to 10% of pregnancies, particularly with first pregnancies in women older than 35 years.
• In pregant woman in 3rd trimester with severe hyertension, proteinuria, edema and seizures the eclapmisa (the simplex complex) can occur.
• referred to as toxemia of pregnancy eclampsia & preeclampsia
• Placental infarction, hypercoagulability, Hypertension, End-organ failure, serious consequences of preeclampsia
• found in 10% of the patients with severe pre-eclampsia, elevated liver enzymes, microangio- pathic hemolytic anemia, thrombocytopenia due to platelet consumption, and sometimes fullblown dis- seminated intravascular coagulation (DIC) “HELLP syndrome”
• HPV, the causative agent of cervical neoplasia, has a tropism for the immature squamous cells of the transformation zone. Most HPV infections are transient and are eliminated within months by an acute and chronic inflammatory response. A subset of infections persists, however, and some of these progress to cervical intraepithelial neoplasia (CIN),
• High risk HPV 16, 18, 33, 31, 35
• Low risk HPV 6 &11
• 75 % of invasive cacinomas of cervix are squamous cell carcinoma arising from CIN or HSIL
• Genes mutated in CIN? TP53, RB, LDK1 (peutz-Jeghers syndrome)
• age of peak of squamous cell carcinomas of the cervix? 45 years (10-15 years after CIN)
• Barrel cervix gross morphology of squamous cell carcinomas of cervix
• Most common ovarian tumors? those of surface epithelial origin
• Age of peak of ovarian tumors of surface epithelial origin? above 20
• serous, mucinous, endometrioid, clear cell, brenner, cystadenofibroma Types of Surface Epithelial Tumors:
• cysts form & then the cysts undergo metaplasia or neoplastic transformation process of tumor formation of Surface Epithelial Tumors
• Genes involved in Surface Epithelial Tumors (ovary)? BRCA1, BRCA2, TP53
• most common of the ovarian epithelial tumors of Surface Epithelial origin? serous
• age of peak of serous type of Surface Epithelial Tumor? 30-40 years
• "Hobnails cells", The serosal covering is smooth and glistening, small cystic tumors may have a single cavity, larger ones frequently divided by multiple septa into multiloculated masses, Papillary projections can be found, Psammoma bodies can be found morphology of serous tumors of surface-epithelilal originating ovarian kind
• age of peak of malignant serous type of Surface Epithelial Tumor? between 45 and 65 years
• The low-grade & The high-grade two types of serous carcinomas of surface epithelilal ovary tumors
• Mostly benign tumor very similar to the serous tumors of ovary except for the mucin and usual unilateral appearance. Also look like krukenberg tumors of GI (this one is usally bilateral). Pseudomyxoma peritonei also seen. mucinous tumors of ovaries
• Implantation of mucinous tumor cells in the peritoneum with production of copious amounts of mucin, mostly caused by metastasis from the GI (primarily the appendix) Pseudomyxoma peritonei
• A tumor of ovary sometimes develop in assoc. w/ endometriosis. Usually malignant and 15% to 30% of women with these tumors have a accompanying endometrial carcinoma. Has mutation of PTEN and cysts filled with blood. Endometrioid tumor (of surface epithelial ovarian origin)
• age of peak of Germ cell Tumors 0-25 years
• Teratoma, dysgerminoma, endodermal sinus tumor, choriocarcinoma types of Germ cell Tumors of ovaries
• age of peak of teratoma of female ovary the first 2 decades of life – the younger the bigger risk of malignancy
• teratoma composed entirely of mature thyroid tissue that may produce hyperthyroidism. small, solid, unilateral brown ovarian masses. struma ovarii
• age of peak of sex cord stromal tumors in ovary all ages
• Fibroma, granulosa-theca cell tumor, sertoli-ledyg cell tumor Types of Sex cord -Stromal tumors
• Uncommon mostly benign tumor of ovary that may arise from the surface epithelium or from urogenital epithelium trapped within the germinal ridge brenner tumors
• most characteristic for postmenopausal women? Serous carcinoma of uterine corpus & Leiomyosarcoma

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