| What is condyloma? | ➢ Two distinct forms :
Condylomata lata, not commonly seen today, are flat, minimally elevated lesions that occur in secondary syphilis
Condylomata acuminata papillary and distinctly elevated or
somewhat flat and rugose.
They may occur anywhere on the anogenital surface
sometimes as single but more often as multiple lesions.
When located on the vulva they range from a few millimeters to many centimeters in diameter and are red-pink to pink-brown. |
| What are hallmark features of koiolocytosis HPV infection? | • Characteristic cellular feature
• Large irregular nuclei in the upper part of the epithelium
• wrinkled nuclear contour)
• Multinuclation may be present |
| What is vulvulitis? | ➢ One of the most common causes of vulvitis is reactive
inflammation in response to an exogenous stimulus, which may be an irritant (contact irritant dermatitis) or an allergen (contact allergic dermatitis).
➢ Scratching-induced trauma secondary to associated intense "itching” (pruritus) often exacerbates the primary condition.
➢ Contact irritant eczematous dermatitis manifests as well defined erythematous weeping and crusting papules and plaques and may be a reaction to urine, soaps, detergents, antiseptics, deodorants, or alcohol.
➢ Allergic dermatitis has a similar clinical appearance and may result from allergy to perfumes; additives in creams, lotions, and soaps; chemical treatments on clothing; and other antigens.
➢ It may also bi caused by infections |
| What are Nonneoplastic Epithelial Disorders of the Vulva? (lichen scleroses) | ➢ Lichen Sclerosus characterized by :
• thinning of the epidermis,
• disappearance of rete pegs
• a zone of acellular, homogenized, dermal fibrosis
• a bandlike mononuclear inflammatory cell infiltrate
➢ It appears as smooth, white plaques (termed leukoplakia) or papules that in
time may extend and coalesce.
➢ When the entire vulva is affected, the labia become atrophic and stiffened, and the vaginal orifice is constricted.
➢ Occurs in all age groups but most commonly affects postmenopausal women and prepubertal girls.
➢ Lichen sclerosus is benign; however, 1% to 5% of women with symptomatic lichen sclerosus develop HPV negative squamous cell carcinoma of the vulva. |
| What are Nonneoplastic Epithelial Disorders of the Vulva? (lichen simplex chronicus) | • Marked by epithelial thickening (particularly of the stratum granulosum) and hyperkeratosis.
• Leukocytic infiltration of the dermis is sometimes pronounced.
➢ These nonspecific changes are a consequence of chronic
irritation, often caused by pruritus related to an underlying
inflammatory dermatosis.
➢ Appears as an area of leukoplakia.
➢ No increased predisposition to cancer has been demonstrated when lesions are isolated.
➢ The lesions of lichen sclerosus and lichen simplex chronicus must be biopsied to distinguish them from SqCC. |
| What are tumors of vulva? | I. Condylomas
II. Carcinoma of the Vulva
III. Extramammary Paget Disease |
| What is extramammary paget disease? | ➢ Paget disease is an Intraepidermal proliferation of epithelial cells that can occur in the skin of the vulva or nipple of the breast.
➢ Only a minority of cases of vulvar (extramammary) Paget disease have an underlying tumor.
➢ Manifests as a red, scaly, crusted plaque that may mimic the appearance of an inflammatory dermatitis.
➢ Histo :
• large cells with abundant pale, finely granular cytoplasm
• Occasional cytoplasmic vacuoles (DD with melanoma; PAS+++)
• Infiltrate the epidermis, singly and in groups
➢ May persist for years or even decades without evidence of invasion.
➢ However, when there is an associated tumor involving skin appendages, the Paget cells may invade locally and ultimately metastasize.
➢ After metastasis occurs, the prognosis is poor |
| How is vulva carcinoma? | ➢ 3% of all female genital tract cancers
➢ Mostly in women older than age 60.
➢ 90% of carcinomas are SqCC
➢ Most of the other tumors are adenocarcinomas or basal cell carcinomas.
➢ Two distinct forms of vulvar SqCC :
✓ form related to high-risk HPV strains (especially HPV type 16) less common and occurs in middle aged women, particularly cigarette smokers. Often preceded by VIN.
✓ second form of squamous carcinoma occurs in older women, sometimes following a long history of reactive epithelial changes, principally lichen sclerosus |
| How is presentation of vulva carcinoma? | ➢ VIN and early vulvar carcinomas commonly manifest as areas of leukoplakia.
➢ In about 25% of the cases, the lesions are pigmented owing to the presence of melanin.
➢ With time, these areas are transformed into overt exophytic or ulcerative endophytic tumors.
➢ HPV-positive tumors are often multifocal and warty and tend to be poorly differentiated SqCC
➢ Whereas HPV-negative tumors usually are unifocal and typically are well-differentiated keratinizing SqCC
➢ The risk of metastasis correlates with the depth of invasion. |
| What are pathology of vagina? | ➢ In adult females, the vagina is seldom a site of primary
disease.
➢ More often, it is involved secondarily by cancer or infections arising in adjacent organs (e.g., cervix, vulva, bladder, rectum).
➢ Congenital anomalies of the vagina fortunately are uncommon and include entities such as total absence of the vagina, a septate or double vagina (usually associated with a septate cervix and, sometimes, septate uterus), and congenital, lateral Gartner duct cysts arising from persistent wolffian duct rests. |
| What is vaginitis? | ➢ Vaginitis is a common condition that is usually transient and of no clinical consequence.
➢ It is associated with the production of a vaginal discharge (leukorrhea).
➢ A large variety of organisms have been implicated, including bacteria, fungi, and parasites
➢ Candidal (monilial) vaginitis is characterized by a curdy white discharge.
➢ This organism is part of the normal vaginal flora in about 5% of women
➢ The appearance of symptomatic infection is or related to a new, more aggressive or occur in a predisposing context (diabetes, ABtherapy, immunodeficiency, pregnancy, or recent abortion.)
➢ T. vaginalis is sexually transmitted;
➢ it produces a watery, copious gray-green discharge in which parasites can be identified by microscopy.
➢ Trichomonas also can be identified in about 10% of
asymptomatic women; thus, active infection usually stems from sexual transmission of
➢ a new strain |
| What are malignant neoplasms of vagina? | ➢ Squamous Cell Carcinoma :
extremely uncommon Vaginal intraepithelial neoplasia (VAIN) is a precursor lesion that is nearly always associated with HPV infection.
Invasive SqCC of the vagina is associated with the presence of HPV DNA in more than half of the cases.
➢ Clear Cell Adenocarcinoma
➢ Sarcoma Botryoides |
| What is clear cell adenocarcinoma? | ➢ Identified in 1970, in a cluster of young women whose mothers took DES during pregnancy to prevent threatened abortion.
➢ The incidence of this tumor in persons exposed to DES in utero is low (<1 per 1000, albeit about 40 times greater than in the unexposed population).
➢ In about 1/3 of exposed women, small glandular or microcystic inclusions develop in the vaginal mucosa.
➢ These lesions appear as red, granular foci lined by mucussecreting or ciliated columnar cells : This condition is called vaginal adenosis and is benign but is important to recognize because it is from such precursor lesions that clear cell adenocarcinoma arises. |
| What is botryoide sarcoma? | ➢ Rare form of primary vaginal cancer that manifests as soft polypoid masses.
➢ It usually is encountered in infants and children younger than 5 years of age, but may occur uncommonly in young women.
➢ Gross appearance : “grape – like) polypoid mass |
| What is cervix pathology? | ➢ Most cervical lesions are relatively banal inflammations
(cervicitis), but the cervix also is the site of one of the most
common cancers in women worldwide.
CERVICITIS
subclassified as infectious or noninfectious
Important non saprophyte organisms are : Chlamydia
trachomatis, Ureaplasma urealyticum, T. vaginalis, Neisseria gonorrhoeae, HSV-2 (the agent of herpes genitalis), and certain types of HPV, all of which are often sexually transmitted. |
| What is cervicitis? | ➢ C. trachomatis is by far the most common pathogen,
accounting for as many as 40% of cases of cervicitis
encountered in sexually transmitted infection clinics.
➢ Although less common, herpetic infections are noteworthy because maternal–infant transmission during childbirth may result in serious, sometimes fatal systemic herpetic infection in the newborn.
➢ Cervicitis commonly comes to attention on routine examination or because of leukorrhea.
➢ It often is treated empirically with antibiotics that are active against chlamydia and gonococcus. |
| How is neoplasia of the cervix? | ➢ Most tumors of the cervix are of epithelial origin and are
caused by oncogenic strains of HPV.
➢ During development, the columnar mucus-secreting epithelium of the endocervix is joined to the squamous epithelial covering of the exocervix at the cervical os.
➢ With the onset of puberty, the squamocolumnar junction
undergoes eversion, causing the columnar epithelium to
become visible on the exocervix.
➢ The exposed columnar cells, however, eventually undergo squamous metaplasia, forming a region called the transformation zone, where tumors most commonly arise |
| How is pathogenesis of cervical neoplasms? | ➢ 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 the host immune response.
➢ A subset of infections persists, however, and some cause squamous intraepithelial lesions (SILs), which are precursors from which most invasive cervical carcinomas develop.
➢ HPV is detectable by molecular methods in nearly all cases of CIN and cervical carcinoma.
➢ Important risk factors for the development of CIN and invasive carcinoma thus are directly related to HPV exposure and include:
• Early age at first intercourse
• Multiple sexual partners
• Male partner with multiple previous sexual partners
• Persistent infection by high-risk strains of papillomavirus
➢ HPV variants are classified as high-risk or low-risk
➢ types based on their propensity to induce carcinogenesis. |
| How is classification of cervical precursor lesions? | ➢ SIL is divided into low-grade squamous intraepithelial lesion (LSIL/CIN I, and high-grade squamous intraepithelial lesion (HSIL /CIN II and III.
➢ LSIL is associated with productive HPV infection and does not progress directly to invasive carcinoma.
➢ Most LSILs regress and only a small percentage progress to HSIL.
➢ HSIL demonstrates increased proliferation, arrested epithelial maturation, and lower levels of viral replication.
➢ LSIL is not treated as a premalignant lesion, whereas HSIL is considered at high risk for progression to carcinoma.
➢ LSIL is 10 times more common than HSIL
➢ While HSILs are precancerous, the majority of them fail to progress to cancer and may even regress |
| What is spectrum of squamous intraepithelial lesions? | In HSIL (CIN II), dysplasia extends to the middle third of the epithelium in the form of variation in cell
and nuclear size, heterogeneity of nuclear chromatin, and the presence of mitoses, some atypical, above
the basal layer extending into the middle third of the epithelium.
The superficial layer of cells still shows differentiation and occasional koilocytotic changes
HSIL (CIN III) is marked by almost complete loss of differentiation even greater variation in cell and
nuclear size, chromatin heterogeneity, disorderly orientation of the cells, and abnormal mitoses, changes
that affect virtually all layers of the epithelium.
Koilocytotic change usually is absent. |
| How is invasive carcinoma of cervix? | ➢ The most common cervical carcinomas are :
squamous cell carcinomas (75%), adenocarcinomas and mixed adenosquamous carcinomas (20%) small cell neuroendocrine carcinomas (<5%).
➢ All of these types of carcinomas are associated with HPV.
➢ SqCC has a peak incidence at the age of about 45 years, some 10 to 15 years after detection of precursor SIL.
➢ Progression of SIL to invasive carcinoma is variable and
unpredictable and requires HPV infection as well as mutations in tumor suppressor genes and oncogenes |
| What are uterus pathology? | ENDOMETRITIS
ENDOMETRIOSIS
ADENOMYOSIS :
Nests of endometrial stroma, glands, or both are found deep in the myometrium interposed between the muscle bundles.
This endometrial tissue induces reactive hypertrophy of the
myometrium, resulting in an enlarged, globular uterus, often with a thickened uterine wall.
Extensive adenomyosis may produce menorrhagia, dysmenorrhea, and pelvic pain, particularly just prior to menstruation, and can coexist with endometriosis. |
| What is endometriosis? | ➢ Defined by the presence of endometrial glands and stroma in a location outside the uterus
➢ This endometrium is functional and undergoes cyclic bleeding.
➢ Because blood collects in these aberrant foci, they appear grossly as red-brown nodules or implants.
➢ They range in size from microscopic to 1 to 2 cm in diameter and lie on or just under the affected serosal surface.
➢ Often, individual lesions coalesce to form larger masses.
➢ When the ovaries are involved, the lesions may form large, blood-filled cysts that turn brown (chocolate cysts) as the blood ages
➢ With seepage and organization of the blood, widespread fibrosis occurs, leading to adhesions among pelvic structures, sealing of the tubal fimbriated ends, and distortion of the fallopian tubes and ovaries.
➢ The diagnosis depends on finding both endometrial glands and stroma at sites external to the endometrium |
| What are proliferative lesions of endometrium and myometrium? | ➢ The most common proliferative lesions of the uterine
corpus are :
endometrial hyperplasia
endometrial carcinomas,
endometrial polyps,
smooth muscle tumors.
➢ All tend to produce abnormal uterine bleeding as their earliest manifestation. |
| How is endometrial hyperplasia? | ➢ An excess of estrogen relative to progestin, if sufficiently
prolonged or marked, can induce exaggerated endometrial proliferation (hyperplasia), which is an important precursor of endometrial carcinoma.
➢ Endometrial hyperplasia is placed in two categories based on the presence of cytologic atypia: hyperplasia without atypia and hyperplasia with atypia
➢ the presence of cytologic atypia correlates with the development or concurrent finding of endometrial carcinoma. 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%) |
| How is endometrial carcinoma? | ➢ It generally appears between the ages of 55 and 65 years and is uncommon before age 40.
➢ Endometrial carcinoma can be broadly divided into two histologically and pathogenically distinct categories:
endometrioid and serous carcinoma.
➢ There are other less common types of endometrial carcinoma, such as clear cell carcinoma and mixed Mullerian tumor (carcinosarcoma)
➢ Closely resemble normal endometrium and may be exophytic or infiltrative
➢ They include a range of histologic types, including those showing mucinous, tubal (ciliated), and squamous
differentiation.
➢ Endometrioid carcinomas often infiltrate the myometrium and can enter vascular spaces (lymphovascular invasion).
➢ They may also metastasize to regional lymph nodes
➢ Endometrioid carcinomas are graded 1 to 3, based on the degree of differentiation. |
| What are serous carcinmomas? | ➢ Typically grow in small tufts and papillae with marked
cytologic atypia.
➢ They can also form glands that at times create confusion with endometrioid carcinoma, however serous carcinomas exhibit much greater cytologic atypia.
➢ behave aggressively and thus are by definition high grade
➢ Immunohistochemistry often shows diffuse, strong staining for p53 in serous carcinoma a finding that correlates with the presence of TP53 mutations (mutant p53 accumulates and hence is more easily detected by staining) |
| What are endometrial polyps? | ➢ These polyps are usually sessile and range from 0.5 to3 cm in diameter.
➢ Larger polyps may project from the endometrial mucosa into the uterine cavity.
➢ They are composed of endometrium resembling the basalis, frequently with small muscular arteries.
➢ Some glands are normal architecturally, but more often they are cystically dilated.
➢ The stromal cells are monoclonal, often with a rearrangement of chromosomal region 6p21, and thus constitute the neoplastic component of the polyp.
➢ most common around the time of menopause. |
| What is leiomyoma? | ➢ Benign tumors that arise from the smooth muscle cells
in the myometrium
➢ Most common benign tumor in females, affecting 30% to 50% of women of reproductive age, and are considerably more frequent in black women.
➢ Associated with several different recurrent chromosomal
abnormalities.
➢ Estrogens and possibly oral contraceptives stimulate the
growth of leiomyomas; conversely, these tumors shrink
postmenopausally |
| How is leiomyoma presentation? | ➢ Typically sharply circumscribed, firm graywhite masses with a characteristic whorled cut surface.
➢ They may occur singly, but more often occur as multiple
tumors that are scattered within the uterus, ranging from small nodules to large tumors that may dwarf the uterus.
➢ Some are embedded within the myometrium (intramural), whereas others may lie immediately beneath the endometrium (submucosal) or the serosa (subserosal).
➢ On histologic examination, the tumors are characterized by bundles of smooth muscle cells mimicking the appearance of normal myometrium.
➢ Foci of fibrosis, calcification, and degenerative softening may be present. |
| What is leiomyosarcoma? | ➢ Virtually always arise de novo from the mesenchymal cells of the myometrium.
➢ They are almost always solitary and most often occur in
postmenopausal women, in contradistinction to leiomyomas, which frequently are multiple and usually arise premenopausally.
➢ Recurrence after surgery is common, and many metastasize, typically to the lungs,
➢ 5-year survival rate of about 40%.
➢ Leiomyosarcomas typically take the form of soft,
hemorrhagic, necrotic masses.
➢ The histologic appearance varies widely, from tumors that closely resemble leiomyoma to wildly anaplastic neoplasms.
➢ Well-differentiated tumors may lie at the morphologic
interface between leiomyoma and leiomyosarcoma and are sometimes designated smooth muscle tumors of uncertain malignant potential (STUMP) |
| How is dx of leiomyosarcoma? | ➢ The diagnostic features of leiomyosarcoma include :
tumor necrosis cytologic atypia, mitotic activity.
➢ Because increased mitotic activity is sometimes seen in benign smooth muscle tumors, particularly in young women, an assessment of all three features is necessary to make a diagnosis of malignancy |
