DISEASES OF THE VULVA. VULVA: NON-NEOPLASTIC EPITHELIAL DISORDERS There are two forms of NNED: There...

DISEASES OF THE DISEASES OF THE VULVAVULVA

VULVA: NON-NEOPLASTIC VULVA: NON-NEOPLASTIC EPITHELIAL DISORDERSEPITHELIAL DISORDERS

There are two forms of NNED: There are two forms of NNED: lichen sclerosuslichen sclerosus lichen simplex chronicus. lichen simplex chronicus.

Both Both may coexist in different areas in may coexist in different areas in the same patient, and both may the same patient, and both may appear macroscopically as appear macroscopically as depigmented white lesionsdepigmented white lesions, referred , referred to as to as leukoplakia.leukoplakia.

Condylomas and Low-Grade Vulvar Condylomas and Low-Grade Vulvar Intraepithelial Neoplasia (VIN I)Intraepithelial Neoplasia (VIN I)

The more common may be The more common may be papillary and papillary and sometime flatsometime flat..

They occur anywhere on the They occur anywhere on the anogenital anogenital surfacesurface, sometimes singly but more , sometimes singly but more often in often in multiplemultiple sites. sites.

The histologicThe histologic appearance: perinuclear appearance: perinuclear cytoplasmic vacuolization with nuclear angular cytoplasmic vacuolization with nuclear angular pleomorphism-koilocytosis. pleomorphism-koilocytosis.

Cause: HPV infection. there is a strong Cause: HPV infection. there is a strong association with at least two types of HPV (association with at least two types of HPV (HPV HPV 6 and HPV 116 and HPV 11), closely related to the virus that ), closely related to the virus that causes common warts. causes common warts.

Not precancerousNot precancerous but may coexist with foci of but may coexist with foci of intraepithelial neoplasia in the vulva and cervix.intraepithelial neoplasia in the vulva and cervix.

Carcinoma of the VulvaCarcinoma of the Vulva

Carcinoma Carcinoma of the vulva represents of the vulva represents about about 3%3% of all genital tract cancers of all genital tract cancers in womenin women

occurring mostly in women occurring mostly in women older than older than age 60age 60 years. years.

Approximately Approximately 90%90% of carcinomas are of carcinomas are squamous cell carcinomassquamous cell carcinomas; the ; the remainder are adenocarcinomas, remainder are adenocarcinomas, melanomas, or basal cell carcinomasmelanomas, or basal cell carcinomas

Carcinoma of the VulvaCarcinoma of the Vulva

2) The other subgroup of vulvar 2) The other subgroup of vulvar carcinoma occurs in carcinoma occurs in olderolder women. women.

It is It is not associated with HPVnot associated with HPV but is but is often preceded by years of non-often preceded by years of non-neoplastic epithelial changes, neoplastic epithelial changes, principally principally lichen sclerosus and, lichen sclerosus and, rarely, lichen simplex chronicus.rarely, lichen simplex chronicus.

TUMORS OF THE TUMORS OF THE CERVIXCERVIX

Cervical carcinomaCervical carcinoma, , despite despite dramaticdramatic improvementsimprovements in early in early diagnosis and treatment, continues diagnosis and treatment, continues to be one of the to be one of the major causesmajor causes of of cancer-related cancer-related deathsdeaths in women, in women, particularly in the developing world. particularly in the developing world.

Cervical Intraepithelial Neoplasia and Cervical Intraepithelial Neoplasia and Squamous Cell CarcinomaSquamous Cell Carcinoma

Cervical carcinoma Cervical carcinoma was once the most frequentwas once the most frequent form of cancer in women around the world. but form of cancer in women around the world. but the widespread use of Papanicolaou (cytologic) the widespread use of Papanicolaou (cytologic) screening of women has dramatically screening of women has dramatically lowered lowered the incidencethe incidence of invasive tumors and by contrast, of invasive tumors and by contrast, the incidence of precursor cervical intraepithelial the incidence of precursor cervical intraepithelial neoplasia (neoplasia (CIN) has increasedCIN) has increased

MostMost invasive cervical squamous cell carcinomas invasive cervical squamous cell carcinomas arise from precursorarise from precursor epithelial changes referred epithelial changes referred to as CIN. to as CIN.

However, However, not all cases of CIN progressnot all cases of CIN progress to to invasive cancer, and indeed many persist without invasive cancer, and indeed many persist without change or even regress.change or even regress.

CERVICAL INTRAEPITHELIAL NEOPLASIA CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SQUAMOUS INTRAEPITHELIAL (CIN), SQUAMOUS INTRAEPITHELIAL

LESION (SIL)LESION (SIL) However, in However, in cytologic smearscytologic smears the precancerous lesions are the precancerous lesions are

separated into only two groups: separated into only two groups:

The low-gradeThe low-grade lesions correspond to CIN I or flat condylomas lesions correspond to CIN I or flat condylomas (described later(described later

The high-gradeThe high-grade lesions to CIN II or III. lesions to CIN II or III.

CIN ICIN I the likelihood of: the likelihood of: regression is 50% to 60%; regression is 50% to 60%; persistence, 30%; persistence, 30%; progression to CIN III, 20%. progression to CIN III, 20%. Only 1% to 5% become invasive. Only 1% to 5% become invasive.

CIN IIICIN III, the likelihood of regression is only 33% and of , the likelihood of regression is only 33% and of progression 6% to 74% (in various studies). progression 6% to 74% (in various studies).


LESION (SIL)LESION (SIL)

Epidemiology and Pathogenesis.Epidemiology and Pathogenesis. The The peakpeak age incidence of CIN is about age incidence of CIN is about 30 years30 years, whereas that of , whereas that of

invasive invasive carcinoma carcinoma is about is about 45 years.45 years. precancerous changes take precancerous changes take many years, to evolvemany years, to evolve into overt into overt

carcinomas.carcinomas.Prominent risk factors for the development of CIN and Prominent risk factors for the development of CIN and

invasive carcinoma are as follows: invasive carcinoma are as follows: Major risk factorsMajor risk factors HPV infectionHPV infection Early age at first intercourse Early age at first intercourse Multiple sexual partners Multiple sexual partners A male partner with multiple previous sexual partners A male partner with multiple previous sexual partners Minor risk factorsMinor risk factors lower socioeconomic groupslower socioeconomic groups cigarette smokingcigarette smoking exogenous or endogenous immunodeficiency including HIV infectionexogenous or endogenous immunodeficiency including HIV infection Rarity among virgins, and association with multiple pregnancies. Rarity among virgins, and association with multiple pregnancies.



Epidemiology and Pathogenesis.Epidemiology and Pathogenesis. HPV HPV can be detected in 85% to 90% of can be detected in 85% to 90% of

precancerousprecancerous lesions and invasive lesions and invasive neoplasms, and more specifically, certain neoplasms, and more specifically, certain high-risk high-risk types, including types, including 16, 18, 31, 33,16, 18, 31, 33, 35, 39, 45, 52, 56, 58, and 59. 35, 39, 45, 52, 56, 58, and 59.

By contrast, By contrast, condylomascondylomas, which are benign , which are benign lesions, are associated with infection by lesions, are associated with infection by low-risklow-risk types (i.e., types (i.e., 6, 11,6, 11, 42, and 44) 42, and 44)

In In low-risk low-risk types , the viral DNA does types , the viral DNA does not not integrateintegrate into the host genome, remaining into the host genome, remaining in the free episomal form. in the free episomal form.



CIN II (moderate dysplasia)CIN II (moderate dysplasia) The dysplasia is more severe, affecting most layers The dysplasia is more severe, affecting most layers (2/3)(2/3) of of

the epithelium. the epithelium. It is associated with some It is associated with some variation in cell and nuclear sizevariation in cell and nuclear size

and with normal-looking mitoses above the basal layer. and with normal-looking mitoses above the basal layer. The The superficial layersuperficial layer of cells is still of cells is still well differentiatedwell differentiated, but , but

in some cases it shows the in some cases it shows the koilocytotickoilocytotic changes described. changes described.

CIN III, (severe dysplasia & carcinoma in situ) CIN III, (severe dysplasia & carcinoma in situ) affect virtually affect virtually all layersall layers of the epithelium. of the epithelium.

Cervical Cervical cytologycytology and cervical examinations and cervical examinations (colposcopy) remain the mainstays of cervical (colposcopy) remain the mainstays of cervical cancer prevention.cancer prevention.

INVASIVE CARCINOMA OF INVASIVE CARCINOMA OF THE CERVIXTHE CERVIX

75% to 75% to 90%90% are are squamous cellsquamous cell carcinoma, carcinoma,

peak incidence at about 45 years, peak incidence at about 45 years, some 10 to 15 years after detection some 10 to 15 years after detection of their precursors. of their precursors.


MORPHOLOGYMORPHOLOGY

GROSSGROSS:: Develop in the region of the Develop in the region of the transformation zonetransformation zone Range from Range from microscopic foci to grosslymicroscopic foci to grossly conspicuous conspicuous

tumors tumors May be May be invisible or exophytic.invisible or exophytic. Tumors encircling the cervix and penetrating into the Tumors encircling the cervix and penetrating into the

underlying stroma produce a "underlying stroma produce a "barrel cervixbarrel cervix," which ," which can be identified by direct palpation. can be identified by direct palpation.

Extension Extension into the parametrial soft tissues, pelvic into the parametrial soft tissues, pelvic lymph nodes, bladder or rectum.lymph nodes, bladder or rectum.

Distant Distant metastasesmetastases, including para-aortic nodal , including para-aortic nodal involvementinvolvement

stagedstaged from 1 to 4 depending on clinical spread from 1 to 4 depending on clinical spread

Here is a normal cervix with a smooth, Here is a normal cervix with a smooth, glistening mucosal surface. There is a small glistening mucosal surface. There is a small rim of vaginal cuff from this hysterectomy rim of vaginal cuff from this hysterectomy specimen. The cervical os is small and round, specimen. The cervical os is small and round, typical for a nulliparous woman. The os will typical for a nulliparous woman. The os will have a fish-mouth shape after one or more have a fish-mouth shape after one or more pregnancies.pregnancies.

This is the gross appearance of a cervical This is the gross appearance of a cervical squamous cell carcinoma that is still limited to squamous cell carcinoma that is still limited to the cervix (stage I). The tumor is a fungating the cervix (stage I). The tumor is a fungating red to tan to yellow mass.red to tan to yellow mass.

Here is another cervical squamous cell Here is another cervical squamous cell carcinoma. Note the IUD string protruding carcinoma. Note the IUD string protruding from the cervix. This implies that someone from the cervix. This implies that someone could have done a Pap smear when it was could have done a Pap smear when it was inserted. There is a natural history of inserted. There is a natural history of progression of dysplasia to carcinoma, so don't progression of dysplasia to carcinoma, so don't leave dysplasias alone.leave dysplasias alone.

This is a larger cervical squamous cell This is a larger cervical squamous cell carcinoma which spread to the vagina. A total carcinoma which spread to the vagina. A total abdominal hysterectomy with bilateral abdominal hysterectomy with bilateral salpingo-oopherectomy (TAH-BSO) was salpingo-oopherectomy (TAH-BSO) was performed.performed.

This is a pelvic exenteration This is a pelvic exenteration done for stage IV cervical done for stage IV cervical carcinoma. At the left, dark carcinoma. At the left, dark vulvar skin leads to vagina vulvar skin leads to vagina and to cervix in the center, and to cervix in the center, where an irregular tan tumor where an irregular tan tumor mass is seen infiltrating mass is seen infiltrating upward to the bladder. A slit-upward to the bladder. A slit-like endometrial cavity is like endometrial cavity is surrounded by myometrium surrounded by myometrium at the mid-right. The rectum at the mid-right. The rectum and sigmoid colon are at the and sigmoid colon are at the bottom extending to the bottom extending to the right.right.


MICROSCOPIC:MICROSCOPIC: The most common cervical carcinomas are:The most common cervical carcinomas are:

squamous squamous cell carcinomas (75%), followed by cell carcinomas (75%), followed by adenocarcinomas adenocarcinomas and adenosquamous carcinomas and adenosquamous carcinomas

(20%)(20%) small cell neuroendocrinesmall cell neuroendocrine carcinomas (less than carcinomas (less than

5%). 5%). With the exception of neuroendocrine tumors, With the exception of neuroendocrine tumors,

which are uniformly aggressive in their which are uniformly aggressive in their behavior, cervical behavior, cervical carcinomas are graded carcinomas are graded from 1 to 3from 1 to 3 based on cellular differentiation. based on cellular differentiation.

This is why you do Pap smears--to prevent This is why you do Pap smears--to prevent invasive squamous cell carcinomas from invasive squamous cell carcinomas from occurring. With Pap smears, pre-neoplastic occurring. With Pap smears, pre-neoplastic and neoplastic cervical lesions can be detected and neoplastic cervical lesions can be detected when small and treated. Nests of squamous when small and treated. Nests of squamous cell carcinoma have invaded underlying stroma cell carcinoma have invaded underlying stroma at the center and left.at the center and left.

Diseases of Uterine Diseases of Uterine CorpusCorpus

Endometrial hyperplasiaEndometrial hyperplasia Endometrial PolypEndometrial Polyp Endometrial carcinomaEndometrial carcinoma EndometritisEndometritis Endometriosis and adenomyosisEndometriosis and adenomyosis Dysfunctional uterine bleedingDysfunctional uterine bleeding Leiomyoma and leiomyosarcoma.Leiomyoma and leiomyosarcoma.

Endometrial CarcinomaEndometrial CarcinomaPathogenesisPathogenesis

Two general groupsTwo general groups of endometrial cancer can of endometrial cancer can be identified. be identified.

The first and the most common develops on a The first and the most common develops on a background of prolonged estrogen stimulation background of prolonged estrogen stimulation and endometrial and endometrial hyperplasia.hyperplasia. ( (Type 1Type 1 endometrial carcinoma).endometrial carcinoma).

Both hyperplasia and cancer, are closely Both hyperplasia and cancer, are closely related. related.

Type 1 endometrial carcinoma is associated Type 1 endometrial carcinoma is associated with a more with a more favorable prognosis.favorable prognosis.

Endometrial CarcinomaEndometrial CarcinomaPathogenesisPathogenesis

Endometrial carcinomas that are associated with Endometrial carcinomas that are associated with hyperplasia hyperplasia and the mentioned risk factors tend to and the mentioned risk factors tend to be be well differentiatedwell differentiated and mimic normal and mimic normal endometrial glands endometrial glands (endometrioid)(endometrioid) in histologic in histologic appearance. appearance.

Type 2Type 2 endometrial carcinoma is seen in a subset endometrial carcinoma is seen in a subset of patients of patients with no risk factorswith no risk factors that lead to that lead to hyperestrinism, no preexisting hyperplasia, and hyperestrinism, no preexisting hyperplasia, and acquires the disease at an acquires the disease at an older older average age. average age.

In type 2 group, tumors are generally In type 2 group, tumors are generally more poorlymore poorly differentiated, and have differentiated, and have worse outcome.worse outcome.

Chronic EndometritisChronic Endometritis

It is chronic inflammation of It is chronic inflammation of endometrium.endometrium.

Causes:Causes: Seen in the following setting:Seen in the following setting:

In patients with chronic In patients with chronic PIDPID In In postpartal or postabortalpostpartal or postabortal endometrial cavities, endometrial cavities,

usually due to retained gestational tissueusually due to retained gestational tissue In patients with intrauterine In patients with intrauterine contraceptive devicescontraceptive devices In patients with In patients with tuberculosis.tuberculosis.

Clinically Clinically some women with chronic some women with chronic endometritis complain of endometritis complain of abnormal abnormal bleeding, pain, discharge, and infertilitybleeding, pain, discharge, and infertility

Chronic EndometritisChronic Endometritis

Histologically, it Histologically, it is characterized is characterized by presence of by presence of chronic chronic inflammatory inflammatory cells primarily cells primarily plasma cells.plasma cells.

Theories of Theories of Endometriosis OriginEndometriosis Origin

EndometriosisEndometriosisGrossGross

Endometriosis of Endometriosis of the ovary the ovary The ovaries may The ovaries may

become markedly become markedly distorted by large distorted by large cystic spaces (3 to cystic spaces (3 to 5 cm in diameter) 5 cm in diameter) filled with brown filled with brown blood debris to blood debris to form so-called form so-called chocolate cystschocolate cysts

Follicular and Luteal CystFollicular and Luteal Cyst(Functional cyst)(Functional cyst)

Very common.Very common. Originate on the ovarian cortex in Originate on the ovarian cortex in

unruptured graafian follicles (follicular unruptured graafian follicles (follicular cyst) or follicles that ruptured and cyst) or follicles that ruptured and resealed immediately (Luteal cyst).resealed immediately (Luteal cyst).

Usually small, 1- 1.8 cm. filled with clear Usually small, 1- 1.8 cm. filled with clear fluid.fluid.

Occasionally rupture causing pain & Occasionally rupture causing pain & intraperitoneal bleeding.intraperitoneal bleeding.

Lined by granulosa or luteal cells. Lined by granulosa or luteal cells.

Serous TumorSerous Tumor

These are the These are the most commonmost common ovarian tumors. ovarian tumors. They are usually They are usually cystic cystic filledfilled with clear serous with clear serous

fluid.fluid. Together the benign, borderline, and malignant Together the benign, borderline, and malignant

types types account for about 30% of all ovarian tumors.account for about 30% of all ovarian tumors. About About 75% are benign75% are benign or of borderline or of borderline

malignancy, and 25% are malignant. malignancy, and 25% are malignant. Serous cystadenocarcinomasSerous cystadenocarcinomas account for account for

approximately approximately 40% of all cancers of the ovary40% of all cancers of the ovary and and are the most common malignant ovarian tumors. are the most common malignant ovarian tumors.

Benign and borderlineBenign and borderline tumors are most common tumors are most common between the ages of between the ages of 20 and 5020 and 50 years. years.

Cystadenocarcinomas occur later in lifeCystadenocarcinomas occur later in life on on average.average.

Serous TumorSerous TumorGrossGross

DISEASES OF THE VULVA. VULVA: NON-NEOPLASTIC EPITHELIAL DISORDERS There are two forms of NNED: There...

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