PATOLOGIA GINECOLÓGICA MICROBIOLOGIA 2015

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PATOLOGIA GINECÓLOGICA
• vulva 
• vagina
• cuello
• cuerpo uterino
• trompas
• ovarios
endometrio
pared uterina
CLASIFICACION
Inflamatorias/infecciosas
Neoplásicas 
Preneoplásicas 
TRACTO GENITAL EXTERNO: 
VULVA Y VAGINA
TRACTO GENITAL INFERIOR
ENFERMEDADES 
INFECCIOSAS
ENFERMEDADES 
INFLAMATORIAS
….
liquen escleroso y 
atrófico
liquen simple crónico
…
1. herpes 
2. sífilis 
3. blenorragia 
4. granuloma inguinale 
5. candidiasis 
6. etc…
women. Height and weight do not influence clitoral
size [236]. Clitoral hypertrophy may occur as an isolated
finding or in association with generalized vulvar enlarge-
ment. Clitoral enlargement in a newborn suggests
adrenogenital syndrome, exogenous maternal androgen
therapy, or some form of hermaphroditism. A clitoral mass
from an infant has been identifiedwith chromosomalmosa-
icism in which the clitoral skin had a hyperdiploid chromo-
somal abnormality with normal chromosomes being found
in the ovary; this is an example of ambiguous genitalia
resulting froma somatic cellmutationwithmaldevelopment
of the clitoris [211]. Clitoral enlargement also has been
reported associated with lipodystrophy (Lawrence–Seip
syndrome) [193]. In addition to developmental abnormal-
ities, a variety of tumors including granular cell tumors,
hemangiomas, and vascular, neural, and smooth muscle
tumors may cause clitoral enlargement [171, 220].
Hypertrophy and asymmetry of the labia minora may
occur without demonstrable etiology and, in some cases,
may be associated with chronic irritation, as may be seen in
women wearing indwelling urethral catheters. True hypo-
plasia occurs infrequently and may be a sign of defective
steroidogenesis. Slight fusion of the labia minora may be
seen in infants without apparent cause and typically
responds to topical estrogen cream. Labial fusion, like cli-
toral hypertrophy, also may be present with intersex disor-
ders. In these situations, the defect is developmental, but
such fusion also may be acquired secondary to lichen
sclerosus (LS), lichen planus (LP), or inflammatory condi-
tions, with subsequent adhesion formation [107]. A low
transverse vaginal septum may occlude the vaginal lumen
and result in hematocolpos with the onset of menstruation.
Excision of the septum is the usual therapy of choice.
Imperforate hymen is remarkably rare, with a reported fre-
quency of 0.014%, and usually is discovered at the onset of
menarche between 10 and 18 years of age. Limited surgical
excision of the hymen is the usual treatment. Duplication of
the vulva is extremely rare and usually is associated with
duplication of the internal mu¨llerian system and rectum as
well. In mu¨llerian agenesis, the hymen and vagina usually
are represented by only a depression in the vestibular area.
Congenital absence of the clitoris and external genitalia has
also been described. The urethra may open into the vagina
rather than into the vestibule. Ectopic urethral orifices are
seen occasionally adjacent to the hymen [107].
Inflammatory Diseases of Vulvar Skin
Inflammatory diseases of vulvar skin can be generally
categorized into infectious and noninfectious groups
(> Table 1.1). Further classification of infectious dis-
eases according to etiologic agents is summarized in
>Table 1.2. The most prevalent infectious diseases of the
vulva in North America include human papillomavirus
(HPV), typically manifested as condyloma acuminatum,
. Table 1.1
Inflammatory disorders of the vulva
Infectious diseases Noninfectious dermatoses
Viral Papulosquamous disorders
Fungal Noninfectious bullous dermatoses
Bacterial Miscellaneous
Parasitic
. Table 1.2
Infectious diseases of vulva skin
Viral infection
Human papillomavirus (HPV) (genital subtype)
Herpes virus (simplex and zoster)
Molluscum contagiosum
Others (rare)
Human papillomavirus (nongenital subtype)
HIV-associated plaques and ulcers
Cytomegalovirus (CMV)
Epstein–Barr virus (EBV)-associated ulcer
Coxsackie virus (hand-foot-mouth disease)
Bacterial infection
Syphilis
Granuloma inguinale
Lymphogranuloma venereum (LGV)
Chancroid
Malakoplakia
Others
Tuberculosis
Erythrasma
Fungal infections
Dermatophytosis
Candidiasis
Parasitic infection
Scabies
Pubic lice
Others
Enterobius vermicularis
Schistosomiasis
Demodex
HIV, human immunodeficiency virus.
Benign Diseases of the Vulva 1 5
women. Height and weight do not influence clitoral
size [236]. Clitoral hypertrophy may occur as an isolated
finding or in association with generalized vulvar enlarge-
ment. Clitoral enlargement in a newborn suggests
adrenogenital syndrome, exogenous maternal androgen
therapy, or some form of hermaphroditism. A clitoral mass
from an infant has been identifiedwith chromosomalmosa-
icism in which the clitoral skin had a hyperdiploid chromo-
somal abnormality with normal chromosomes being found
in the ovary; this is an example of ambiguous genitalia
resulting froma somatic cellmutationwithmaldevelopment
of the clitoris [211]. Clitoral enlargement also has been
reported associated with lipodystrophy (Lawrence–Seip
syndrome) [193]. In addition to developmental abnormal-
ities, a variety of tumors including granular cell tumors,
hemangiomas, and vascular, neural, and smooth muscle
tumors may cause clitoral enlargement [171, 220].
Hypertrophy and asymmetry of the labia minora may
occur without demonstrable etiology and, in some cases,
may be associated with chronic irritation, as may be seen in
women wearing indwelling urethral catheters. True hypo-
plasia occurs infrequently and may be a sign of defective
steroidogenesis. Slight fusion of the labia minora may be
seen in infants without apparent cause and typically
responds to topical estrogen cream. Labial fusion, like cli-
toral hypertrophy, also may be present with intersex disor-
ders. In these situations, the defect is developmental, but
such fusion also may be acquired secondary to lichen
sclerosus (LS), lichen planus (LP), or inflammatory condi-
tions, with subsequent adhesion formation [107]. A low
transverse vaginal septum may occlude the vaginal lumen
and result in hematocolpos with the onset of menstruation.
Excision of the septum is the usual therapy of choice.
Imperforate hymen is remarkably rare, with a reported fre-
quency of 0.014%, and usually is discovered at the onset of
menarche between 10 and 18 years of age. Limited surgical
excision of the hymen is the usual treatment. Duplication of
the vulva is extremely rare and usually is associated with
duplication of the internal mu¨llerian system and rectum as
well. In mu¨llerian agenesis, the hymen and vagina usually
are represented by only a depression in the vestibular area.
Congenital absence of the clitoris and external genitalia has
also been described. The urethra may open into the vagina
rather than into the vestibule. Ectopic urethral orifices are
seen occasionally adjacent to the hymen [107].
Inflammatory Diseases of Vulvar Skin
Inflammatory diseases of vulvar skin can be generally
categorized into infectious and noninfectious groups
(> Table 1.1). Further classification of infectious dis-
eases according to etiologic agents is summarized in
>Table 1.2. The most prevalent infectious diseases of the
vulva in North America include human papillomavirus
(HPV), typically manifested as condyloma acuminatum,
. Table 1.1
Inflammatory disorders of the vulva
Infectious diseases Noninfectious dermatoses
Viral Papulosquamous disorders
Fungal Noninfectious bullous dermatoses
Bacterial Miscellaneous
Parasitic
. Table 1.2
Infectious diseases of vulva skin
Viral infection
Human papillomavirus (HPV)(genital subtype)
Herpes virus (simplex and zoster)
Molluscum contagiosum
Others (rare)
Human papillomavirus (nongenital subtype)
HIV-associated plaques and ulcers
Cytomegalovirus (CMV)
Epstein–Barr virus (EBV)-associated ulcer
Coxsackie virus (hand-foot-mouth disease)
Bacterial infection
Syphilis
Granuloma inguinale
Lymphogranuloma venereum (LGV)
Chancroid
Malakoplakia
Others
Tuberculosis
Erythrasma
Fungal infections
Dermatophytosis
Candidiasis
Parasitic infection
Scabies
Pubic lice
Others
Enterobius vermicularis
Schistosomiasis
Demodex
HIV, human immunodeficiency virus.
Benign Diseases of the Vulva 1 5
LIQUEN ESCLEROSO10 GYNECOLOGIC PATHOLOGY
“drop-out” become apparent (Figure 1.10). As the 
homogenization of the papillary dermis progresses, the 
infl ammatory infi ltrate is pushed downward, and 
the overlying epidermis undergoes rete effacement and 
eventuates in pronounced epidermal atrophy (Figure 
1.11). Shear injury to the epidermis may result in hem-
orrhagic subepidermal bullae.
DIFFERENTIAL DIAGNOSIS
While early lesions of LS may resemble LP, the presence 
of pointed rete, basal layer squamatization, wedge-
shaped hypergranulosis, and preservation of the super-
fi cial elastic tissue favors a diagnosis of LP over LS. In 
FIGURE 1.10
Advanced lichen sclerosus. Marked 
papillary dermal sclerosis with 
homogenization, pallor, and vascular 
“drop-out” are present.
FIGURE 1.11
Late-stage lichen sclerosus. Exten-
sive papillary dermal homogenization 
forces the infl ammatory infi ltrate 
downward.
CHAPTER 1 Infl ammatory Diseases of the Vulva 9
men 10 : 1). Classical lesions appear in a “fi gure-of-eight” 
distribution as “porcelain-white” plaques with a wrin-
kled surface and follicular plugs, often with intralesional 
ecchymoses. Long-standing lesions result in vanishing 
of the labia minora, and urethral stenosis.
MICROSCOPIC FEATURES
Early lesions feature psoriasiform epidermal hyperpla-
sia accompanied by a band-like lymphocytic infi ltrate, 
papillary dermal fi brosis, and hyperkeratosis (Figure 
1.9). As the lesions develop, the hallmark fi ndings of 
papillary dermal homogenization, pallor, and vascular 
LICHEN SCLEROSUS – FACT SHEET
Defi nition
! Fibrosing dermatitis with a predilection for the anogenital skin in 
women
Incidence
! Uncommon
Morbidity
! Vanishing of the labia minora and urethral stenosis may occur in 
long-standing lesions
! Secondary epithelial dysplasia and squamous cell carcinoma (4%)
Gender, Race, and Age Distribution
! Female predominance (10 : 1)
! More common in Caucasians
! More common in fi fth decade (perimenopausal)
Clinical Features
! “Figure-of-eight” distribution and “porcelain-white” plaques with 
a wrinkled surface and follicular plugging
Prognosis and Treatment
! Chronic waxing and waning clinical course
! Topical steroids and calcineurin inhibitors for local control, but 
uncommon complete resolution
! Regular observation of dysplastic areas with conservative 
treatment (cryotherapy)
! Surgery for severe introital stenosis or if carcinoma evolves within 
dysplastic areas
LICHEN SCLEROSUS – PATHOLOGIC FEATURES
Microscopic Findings
! Psoriasiform epidermal hyperplasia with band-like 
lymphohistiocytic infi ltrate, papillary dermal fi brosis, and 
hyperkeratosis in early lesions
! Papillary dermal homogenization, pallor, and vascular drop-out 
with epidermal atrophy in mature lesions
Differential Diagnosis
! Lichen planus
! Morphea
! Chronic radiation dermatitis
FIGURE 1.9
Early lichen sclerosus. Psoriasiform 
epidermal hyperplasia is accompa-
nied by a dense band-like lympho-
cytic infi ltrate, papillary dermal 
fi brosis, and hyperkeratosis.
1. es una causa 
frecuente de 
prurito vulvar
2. placas blancas “de 
porcelana”
3. causa desconocida 
(autoinmune?)
LIQUEN SIMPLE CRÓNICO
24 GYNECOLOGIC PATHOLOGY
gen arranged in vertical streaks within the papillary 
dermis (Figure 1.25), although this feature is less well 
developed in the mucocutaneous surfaces of the vulva 
and perineum.
DIFFERENTIAL DIAGNOSIS
Superimposed changes of LSC can be observed in virtu-
ally all dermatoses, therefore careful evaluation to 
exclude a primary dermatosis is essential before render-
ing a diagnosis of idiopathic LSC.
LICHEN SIMPLEX CHRONICUS – PATHOLOGIC FEATURES
Microscopic Findings
! Compact orthokeratosis and focal parakeratosis
! Hypergranulosis with subjacent irregular psoriasiform epidermal 
hyperplasia
! Thick eosinophilic bundles of collagen in “vertical streaks” in 
papillary dermis
Differential Diagnosis
! Lichen simplex chronicus may be superimposed on virtually all 
dermatoses
! Frequently present in patients with an underlying atopic 
diathesis
FIGURE 1.24
Lichen simplex chronicus. There is 
broad compact orthokeratosis and 
hypergranulosis. The psoriasiform epi-
dermal hyperplasia does not exhibit 
suprapapillary plate thinning.
FIGURE 1.25
Lichen simplex chronicus. Thick eosinophilic bundles of collagen are 
arranged in vertical streaks within the papillary dermis.
CHAPTER 1 Infl ammatory Diseases of the Vulva 23
DIFFERENTIAL DIAGNOSIS
Late-stage lesions of LSC (see below) can usually be 
differentiated from psoriasis by the presence of thicker 
suprapapillary plates, hypergranulosis, and the presence 
of thickened vertically oriented collagen bundles within 
the papillary dermis. Differentiation from seborrheic der-
matitis is sometimes very diffi cult. Attention to the 
anatomic location and the presence of spongiosis involv-
ing the rete ridges will often allow the observer to 
exclude psoriasis. Chronic candidiasis and dermatophy-
toses may feature neutrophil exocytosis and psoriasi-
form epidermal hyperplasia. Therefore, a PAS-D or 
methenamine silver stain is recommended to exclude 
the presence of fungal elements.
PROGNOSIS AND TREATMENT
The frustrating chronic course requires long-term man-
agement focused on balancing the extent of disease 
involvement with the potential side-effects of therapy. 
Topical therapies are utilized for localized plaques. They 
include emollients, corticosteroids, tars, and, more 
recently, vitamin D analogs and tacrolimus. Systemic 
therapies for severe disease include methotrexate, reti-
noids, and cyclosporine. Phototherapy and photoche-
motherapy (psoralen with ultraviolet A) are also 
frequently used in these cases.
LICHEN SIMPLEX CHRONICUS
CLINICAL FEATURES
Lichen simplex chronicus is an idiopathic condition in 
which scaly plaques are formed in response to repetitive 
rubbing of affected sites. Anatomic sites of predilection 
include the perianal and genital regions, as well as the 
posterior neck, forearms, and pretibial areas. The cause 
of the apparent underlying pruritus is unknown, 
although patients with underlying atopic dermatitis 
appear to be at increased risk.
MICROSCOPIC FEATURES
There is broad compact orthokeratosis with subjacent 
hypergranulosis. Focal parakeratosis is often present 
(Figure 1.24). There is irregular psoriasiform epidermal 
hyperplasia composed of thick rete ridges without supra-
papillary plate thinning. The lesions may demonstrate 
focal abrasions or ulceration. A characteristic feature is 
the presence of thickened eosinophilic bundles of colla-
PSORIASIS – PATHOLOGIC FEATURES
Microscopic Findings
Early Lesion
! Epidermal spongiosis
! Papillary dermal vascular congestion and edema
! Sparse perivascular dermatitis
Advanced Lesion
! Regular acanthosis with increased basal mitotic activity
! Mounds of neutrophil-rich parakeratosis
! Hypogranulosis
Mature Lesion
! Marked regular psoriasiform epidermal hyperplasia with thinned 
suprapapillary plates
! Confl uent neutrophil-rich parakeratosis, “Munroe microabscesses”, 
and “spongiformpustules of Kogoj”
! Papillary dermal vascular ectasia
! Lymphocytic-rich perivascular dermatitis
Differential Diagnosis
! Lichen simplex chronicus
! Seborrheic dermatitis
! Dermatophytosis and candidiasis
LICHEN SIMPLEX CHRONICUS – FACT SHEET
Defi nition
! Idiopathic condition in which scaly plaques are formed in 
response to repetitive rubbing of affected sites
Incidence
! Common
Morbidity
! Cosmetic
! Superinfection if abraded and ulcerated lesions
Gender, Race, and Age Distribution
! More common in women than men
! No racial predilection
! Peak incidence between 30 and 50 years
Clinical Features
! Hyperpigmented scaly plaques at sites of repetitive rubbing
! Perianal and genital regions, posterior neck, forearms, and 
pretibial areas are anatomic sites of predilection
Prognosis and Treatment
! Cessation of the itch–scratch cycle
! Emollients, topical steroids, and barrier occlusion
! Behavior modifi cation and psychopharmacologic agents may be 
benefi cial in select patients
TRACTO GENITAL EXTERNO: 
VULVA Y VAGINA
TRACTO GENITAL INFERIOR
ENFERMEDADES 
INFECCIOSAS
ENFERMEDADES 
INFLAMATORIAS
….
liquen escleroso y 
atrófico
liquen simple crónico
…
1. herpes 
2. sífilis 
3. blenorragia 
4. granuloma inguinale 
5. candidiasis 
6. etc…
herpes genitalis, syphilis, and molluscum contagiosum
(> Table 1.3). Clinical diagnosis does not necessarily
require specific organism characterization in all these
conditions.
Human Papillomavirus Infection
General Features
Human papillomavirus (HPV) infection is responsible for
benign tumors, that is, condylomata acuminata and pre-
cursor lesions of certain types of vulvar carcinoma (i.e.,
vulvar intraepithelial neoplasia, VIN) [56, 118, 185]. (The
latter types are described in >Chap. 2, Premalignant and
Malignant Tumors of the Vulva.) Condylomata acuminata
(genital warts) are predominately sexually transmitted
benign neoplasms that may involve the vulva, vagina,
cervix, urethra, anal canal, and perianal skin [164]. The
prevalence of HPV infection varies greatly, depending on
the population studied. In most studies, clinically evident
vulvar involvement is less common than cervical HPV
infection [69, 124]. Molecular biologic methods have
identified HPV-6 as the most common HPV type in typ-
ical genital condylomata acuminata. HPV-11 has been
found in approximately one fourth of genital warts
[25, 255]. These two HPV types are responsible for over
90% of condyloma acuminata.
Clinical Features
Condylomas present as papillary, verrucous, or papular
lesions of the skin and mucous membrane that are nearly
alwaysmultiple and frequently confluent (> Fig. 1.3). Most
lesions are asymptomatic unless secondarily infected.
Condylomata acuminata are commonly associated with
vaginitis, pregnancy, diabetes mellitus, oral contraceptive
use, poor perineal hygiene, immunosuppression, and
sexual activity with multiple partners or a partner exposed
to other partners [8, 39, 151, 169]. Approximately 30–50%
of women with vulvar condyloma acuminatum have asso-
ciated cervical HPV infection [240]. The presence of
vulvar condyloma acuminatum in children may be related
to sexual abuse [58, 163, 254].
Approximately 40–60% of children with laryngeal
papillomatosis are born from mothers with a history of
genital HPV infection [70]. However, the true incidence of
infection of the larynx of the newborn infant, from
a mother with genital papillomavirus infection is
. Table 1.3
Infectious diseases of the vulva
Disease
Causative
microorganism Salient features Diagnostic methods
Condyloma
acuminatum
Papillomavirus Acanthosis, hyperkeratosis, parakeratosis,
papillomatosis, perinuclear halo (koilocyte)
Histopathology,
Immunohistochemistry, Molecular
hybridization
Herpes genitalis Herpes simplex
hominis type II
Intranuclear inclusions Cytopathology, culture, serology,
Immunohistochemistry
Syphilitic chancre Treponema pallidum Ulceration, chronic inflammation, vasculitis Dark-field, fluorescence, silver stain,
serology
Condyloma lata Treponema pallidum Like chancre, with epithelial hyperplasia Same as syphilitic chancre
Molluscum
contagiosum
DNA poxvirus group Intracytoplasmic inclusions Cytopathology, histopathology
Granuloma
inguinale
Calymmatobacterium
granulomatis
Donovan bodies, granulomatous reaction
without caseation, pseudoepitheliomatous
hyperplasia
Giemsa stain, silver stain
Lymphogranuloma
venereum
Chlamydia (TRIC
agent)
Granulomatous reaction without caseation Serology
Tuberculosis Mycobacterium
tuberculosis
Acid-fast bacilli (AFB), granulomatous
reaction with caseation
AFB stain, AFB culture, PCR
Chancroid Hemophilus ducreyi Granulomatous reaction without caseation Culture, Gram stain
6 1 Benign Diseases of the Vulva
HERPES - HVS1
• se puede observar en el PAPANICOLAOU, aun 
cuando es asintomático
• lesiones vesiculosas
CANDIDIASIS
• detectable en el PAP
• puede ser asintomática 
o presentarse como 
prurito
• leucorrea blanquecina 
“en leche cortada”
CUELLO UTERINO
ENFERMEDADES 
INFECCIOSAS
1. herpes 
2. sífilis 
3. blenorragia 
4. granuloma inguinale 
5. candidiasis 
6. etc…
ENFERMEDADES 
NEOPLÁSICAS Y 
PRENEOPLÁSICAS
“DIPLASIAS”
EPITELIO 
ESCAMOSO
CARCINOMA 
EPIDERMOIDE
“DIPLASIAS”
EPITELIO 
GLANDULAR
ADENOCARCINOMA
• MORFOLOGIA DEL CUELLO UTERINO
endocervix
exocervix
CU	exocervix
exocervix
CU	endocervix-”glándula”
ZONA DE UNIÓN DE LOS EPITELIOS
METAPLASIA 
ESCAMOSA
ZONA DE 
TRANSFORMACION
HPV
• el virus del papiloma humano infecta las células 
madre de la zona de transformación: las células 
que pueden diferenciarse o madurar hacia epitelio 
escamoso o cilíndrico endocervical
• LESIONES POR VIRUS DEL 
PAPILOMA HUMANO
• el virus del papiloma humano causa el 99% de 
los casos de cancer de cuello uterino.
The Human Papillomavirus (HPV) in Human Pathology The Open Dermatology Journal, 2009, Volume 3 95 
of sub-clinical expression, identifiable by cytological 
changes, colposcopy and/or vulvoscopy and/or vaginoscopy, 
and finally peniscopy together with urethroscopy. The 
clinical forms, usually caused by low-risk oncogenic HPV 
types (6-11), tend to be benign. The sub-clinical forms may 
include both benign lesions as injuries with premalignant 
potential, and tend to be caused by high-risk oncogenic HPV 
types (16-18). HPV infection-16 is the most prevalent in 
European women. Finally, great heterogeneity with regard to 
the HPV types of the groups studied was revealed [32-34]. 
 HPV is a necessary cause but not enough for the 
development of a cervical cancer. HPV is responsible for the 
100% of the cervical, squamous or glandular cancers; there 
is no possibility of development of a cervical cancer in the 
absence of HPV. In addition, it is incidentally related with 90 
percent of anal canal cancers, 40 per cent of vulvar and 
penile cancers, and 12 percent of cancers of the oropharynx. 
Its relationship with other cancers (non-melanoma skin, 
retinoblastoma, etc.) is being investigated. 
 An increased prevalence of HR-HPV types 16, 18, 31, 
33, 35, 45, 51, 52, 58, 59 is found in Africa and Latin 
America. HPV 16 is the most common in the world, except 
Indonesia and Algeria, where HPV 18 is the most common. 
HPV 45 shows high frequency in West Africa types 33, 39, 
and 59 are concentrated in Central and South America. 
 In men, the limited data on prevalence and natural history 
of HPV indicate that the average prevalence accumulated 
over the life in heterosexual men between 18 and 44 years-
old ranges between 56 and 65 percent, with 26 - 50 percent 
for the HR-HPV. Homosexuals and bisexualshave higher 
prevalences. The most prevalent are 16, 31, 51 and 84. The 
average duration of the infection is 4-5 months, this being 
equal for both HR and LR viruses. The epithelium of the 
penis, without conflicting epithelium/epithelium zones as in 
the cervix, is less receptive to infection. Multiple infection 
and location in balanoid fold/preputial are variables, which 
are positively linked to persistence. 
 Although the prevalence of HPV DNA in the genital tract 
of men seems to be similar to that observed in the uterine 
cervix of the same population and age group, the presence of 
HPV in the male genital tract generally produces latent sub-
clinical infections, which can be detected only after the 
application of acetic acid. Due to these diagnostic difficulties 
and to the fact that male genital HPV infections have 
generally limited pathological consequences for healthy 
men, the majority of male HPV infections usually escape 
clinical observation. 
 It is known that the risk of infection is associated with 
sexual activity. Epidemiological studies have shown that 
more than one half of male partners of women with cervical 
intraepithelial neoplasia (CIN) presented penile lesions. It 
follows that the sex partners of men infected with HPV have 
increased the risk of having a genital cancer. Anyway, there 
are not enough studies to establish the biology and the 
dynamics of sexual transmission. The few studies on sexual 
partners of women infected by HPV-associated diseases 
generally include both symptomatic and asymptomatic men 
and fail to take into account any possible geographical or 
ethnic differences, known to be of importance in the 
prevalence of HPV and in the distribution of certain 
genotypes. In fact, the potential of large numbers of 
asymptomatic virus carriers may exist. Therefore, a man may 
considerably increase the risk that his sexual partner 
Table 2. Viral Types of Human Papilloma Virus (HPV) Associated with Invasive Carcinoma 
 
Type of Lesions Most Frequent Lesions Least Frequent Lesions 
Oral papilloma 2, 6, 11, 16 7 
Laryngeal papillomatosis 6, 11 
Conjunctive papilloma 6, 11 16 
Benign pathology of the cervix 
Nasal papilloma Under study 6, 11, 57 
 
Types of carcinoma Most frequent HPV Least frequent HPV 
Cervical carcinoma 16, 18, 31, 45 
6, 10, 11, 26, 33, 35, 39, 51, 52, 55, 56, 58, 59, 
66, 68, 73? and other unclassified 
Vulvar, vaginal, anal and penile carcinoma 16, 18 11, 31, 33, 35, 39, 45, 51, 52, 56, 58, 66 
Basal and squamous cell carcinomas 2, 3, 5, 8, 9, 10, 17 12, 14, 15, 17, 19, 20, 21-25, 36-38, 47, 50 
Amygdala cancer 16 18, 33 
Oropharyngeal 
cancer 
16 3, 6, 11, 18, 33, 57 
Laryngeal cancer 16 6, 11, 18, 35 
Oesophageal cancer 16, 18 6, 11 
Mammary cancer (intraductal invasive) Probably 33 
Prostate cancer 16, 18 Under study 
Carcinomas 
Urethral cancer 5,8, 16 14, 17, 20, 47 
Se dividen en tres grupos dependiendo del o de 
los órganos comprometidos: 
a. Grupo mucocutáneo 
b. Grupo de la epidermodisplasia 
verruciforme 
c. Grupo anogenital (cervical) 
• el contagio se da por contacto de una 
superficie infectada con una superifice 
sana
• debe haber ruptura del epitelio?
GRUPO MUCOCUTÁNEO 
• 1, 2, 4, verrugas plantares 
palmares 
• 13 hiperplasia epitelial focal 
oral o enfermedad de Heck
32
•Los de la región anogenital se dividen en tres 
grupos: 
•1. Bajo riesgo:6,11,42,43,44 
•2. : Alto riesgo: 16, 18, 45, 56 
•3. otros de alto riesgo: 31,33,35,51,52
Anogenital 
•6, 11 :condiloma acuminado. LEIBG 
•16 y 18 :todos tipos de LEI y carcinoma 
epidermoide 
•42 :lesiones aplanadas de pene.
35
36
37
38
39
40
41
42
43
LESIONES PRENEOPLÁSICAS 
DEL CUELLO UTERINO
DISPLASIAS
• SON LESIONES QUE TIENEN EL 
POTENCIAL DE TRANSFORMARSE EN 
UNA NEOPLASIA MALIGNA.
DISPLASIA
LPN 
● La existencia de lesiones preneoplásicas del CU fueron 
identificadas desde 1886 por Sir John Williams. 
● Luego apareció el término CARCINOMA IN SITU (Broders,
1930)
displasia...¿qué es?
● características histológicas: 
a. alteración en la relación núcleo citoplasma 
b. hipercromatismo y pleomorfismo nucleares 
c. mitosis atípicas 
d. pérdida de la relación núcleo citoplasma
• en región genital, se considera une 
enfermedad de transmisión sexual
• la infección inicia con la primera 
relación sexual por lo general
• el hombre casi no padece lesiones 
pero es reservorio
• las lesiones más severas se ven en 
mujeres. 
• las vacunas son efectivas si se ponen 
antes de iniciar la vida sexual
• el preserativo no protege
• factores de riesgo: 
• a- mujeres con múltiples compañeros 
sexuales
• b- mujeres con parejas sexuales con 
multiples compañera(o)s sexuales
• inicio temprano de las relaciones 
sexuales
• cofactores:
• 1- fumado
• 2- hombres no circuncisos
• 3-embarazos multiples
• 4- uso de gestágenos orales
EPIDEMIOLOGIA
56
Infección en el hombre.
Prevalencia de 3,5 a 45% en todos las cepas 
Prevalencia de 2,3 a 35% en cepas de alto 
riesgo 
La cepa más frecuente es la 16 
Hombres que tienen sexo con hombres 
tienen una mayor prevalencia de cepas de 
alto riesgo. 
mayor riesgo de lesiones anales incluido 
cancer ano-rectal 
57
factors characteristic of a sexually transmitted disease
(STD). The prevalence of SIL in different countries and
populations within a country varies widely depending on
the underlying risk factors in the population and the
extent of cytological screening. Although SIL is not
a reportable disease, good estimates of the prevalence of
cytologic abnormalities in women undergoing screening
in the USA are available from a number of sources. One of
the most comprehensive surveys is the College of Ameri-
can Pathologists (CAP) ‘‘Q-Probes’’ study that compiles
rates of cytological abnormalities diagnosis from over 300
U.S. cytology laboratories. According to this survey, in
2003 the mean reporting rate of LSIL was 2.6% and it
was 0.7% for HSIL [47]. Age has a profound impact on
both the rate of detection of cytological abnormalities as
well as the histologically confirmed SIL lesions. In the
Kaiser Permanente health plan, the highest rate of LSIL
vd
a
. Fig. 5.3
HPV-infected cells. Electronmicroscopy of cells productively infectedwith HPV. (a) There are intranuclear aggregates of HPV
in a koilocytotic, superficial cell of an HSIL. The marginated nuclear chromatin is agglutinated, and the cytoplasmic
substance displays vacuolar degeneration (vd). The latter corresponds to koilocytotic ballooning on light microscopy. (b)
Higher magnification of HPV particles in the nucleus
. Table 5.1
Terminologies for cervical cancer precursor lesions
Older
classification
WHOa
classification
Bethesda system
terminology
Mild dysplasia CIN 1 Low-grade squamous
intraepithelial lesion
(LSIL)
Moderate
dysplasia
CIN 2 High-grade squamous
intraepithelial lesion
(HSIL)
Severe dysplasia/
Carcinoma in situ
CIN 3 HSIL
aWorld Health Organization.
CIN, cervical intraepithelial lesion
Precancerous Lesions of the Cervix 5 197
transcribed early in the viral life cycle (hence its name) and
encodes predominately for proteins that are important in
viral replication, whereas the late region encodes for viral
structural proteins that are produced late in the viral life
cycle.
The early region open reading frames (ORFs) encode
for proteins required for viral replication and mainte-
nance of a high viral copy number in infected cells [52].
The early region also includesthe transforming regions of
the HPV genome: E5, E6, and E7. The E6 and E7 ORFs
encode the major transforming genes of HPV [213]. The
E5 ORF encodes a protein with weak transforming capac-
ity. Both, the E6 and E7 proteins are small zinc-binding
proteins that lack endogenous enzymatic activity and
exert their transforming activity through binding to cell
regulatory proteins. E6 can bind to p53 and results in
rapid proteolytic degradation of p53 through an
ubiquitin-dependent pathway, thus blocking apoptosis.
E7 binds to the retinoblastoma (Rb) gene product, as
well as other ‘‘Rb-like proteins.’’ Binding of E7 to Rb
blocks the cell proliferation inhibiting function of these
endogenous tumor suppressors. E7 can also activate
cyclins A and E as well as block the cell proliferation
inhibiting functions of WAF-1 and p27, two cyclin-
dependent kinase inhibitors. The end result of over-
expression of E6 and E7 within cells is unrestricted cell
proliferation and a blockage of apoptosis.
The late region of HPV is downstream of the early
region and contains two ORFs termed L1 and L2 that
encode capsid proteins. The L1-encoded protein is the
major capsid protein and is highly conserved among pap-
illomaviruses from all species. The L2-encoded protein is
a minor capsid protein that is much more variable among
viral types. Transcription from the L1 and L2 ORFs occurs
as a late event in the viral life cycle at a time when infec-
tious virus is being produced. L1 capsid proteins produced
in in vitro culture systems are capable of associating and
forming viral-like particles (VLPs) that are similar to
native virions, but lack the viral genome. VLPs composed
of L1 capsid proteins have recently been introduced as
prophylactic HPV vaccines.
50%
40%
30%
20%
10%
0%
60%
50%
30%
40%
20%
10%
0%
Pe
rc
en
ta
ge
 o
f c
as
es
Pe
rc
en
ta
ge
 o
f c
as
es
6 11 16 18 31 33 35 39 45 51 52 56 58 59 66 68 73 82 6 11 16 18 31 33 35 39 45 51 52 56 58 59 66 68 73 82
HPV type HPV typea b
. Fig. 5.10
Prevalence of anogenital HPV types. (a) HSIL. (b) Invasive cervical cancer (Modified from [175])
L1
L2
E6
E7
E1
E4
E2E5
PolyA signal 1
PolyA signal 2
Long control region
TATA signal 1, 2
HPV-16
7904 bp
. Fig. 5.11
Genomic organization of HPV. HPV is a double-stranded,
circular, DNA tumor virus whose genome can be
divided into three regions: the upstream regulatory
region (URR), the early region, and the late region
202 5 Precancerous Lesions of the Cervix
Life Cycle of HPV
Although the HPV life cycle is not completely character-
ized, the rough outlines of the process are known,
> Fig. 5.12 [167, 176]. The initial site of infection is
thought to be either basal cells or primitive ‘‘basal-like’’
cells of the immature squamous epithelium that HPV
reaches presumably through defects in the epithelium.
Localization in the basal layer may be due to the presence
of specific receptors for HPVon the basal cells. Once HPV
enters into the basal cells, it can exist within the cells in two
distinct biological states. One is as a nonproductive infec-
tion in which HPV DNA continues to reside in the basal
cells, but infectious virions are not produced. In the liter-
ature, nonproductive HPV infections have frequently been
referred to as latent infections. Usually in nonproductive
latent infections a small number of copies of the HPV
genome remain in the nucleus in a free circular form called
an episome. Replication of the episomal DNA in latent
infections is tightly coupled to the replication of the epi-
thelial cells and only occurs in concert with replication of
the host cell’s chromosomal DNA. Since complete viral
particles are presumably not produced in latent infections,
the characteristic cellular effects of a HPV infection are not
present and HPV can only be identified using molecular
methods. Latently infected epithelium displays no mor-
phologic abnormality. Thus, latent infection is used to
characterize HPV infections in which there is no gross or
microscopic evidence of a HPV-induced epithelial lesion,
and the virus is present at such low copy number in the
epithelium that it cannot be detected with routine molec-
ular detection methods.
The other form of HPV infection is a productive viral
infection. In productive viral infections, viral DNA repli-
cation occurs independently of host chromosomal DNA
synthesis. This independent viral DNA replication pro-
duces large amounts of viral DNA and results in infectious
virions. Viral DNA replication takes place predominantly
. Fig. 5.12
HPV life cycle (Source: Kahn JA (2009) HPV vaccination for the prevention of cervical intraepithelial neoplasia (CIN). N Engl
J Med 361:273)
Precancerous Lesions of the Cervix 5 203
infección por 
HPV
infección 
latente
infección 
productiva
desparece sin 
cambios 
morfológicos
infección 
transitoria
infección 
persistente
infección 
transitoria
HPVBR
HRHPV
HPVAR
HRHPV
LEIBG
infección 
persistente
HRHPV
16/18 LEIAG
histological changes that shared a common etiology, biol-
ogy, and natural history. Furthermore, the diagnostic
term CIN implied that such lesions, if untreated, had
a significant, albeit individually unknown risk of develop-
ing into invasive carcinoma in the future. As a corollary, it
was presumed that when the histological changes of CIN
were diagnosed and the lesion adequately treated, the
development of invasive cancer could be prevented. The
CIN terminology became the most widely used histolog-
ical terminology for cervical cancer precursors in the
1970s and the 1980s. However, over the last 2 decades,
there has been an explosion of information about the
etiology of cervical cancer and its precursor lesions. It is
now widely accepted that both invasive squamous cell
carcinomas and adenocarcinomas of the cervix, as well
as their respective precursor lesions, are caused by specific
types of high-risk human papillomavirus (HPV) that
infect the anogenital tract [213, 214]. Since infection
with specific high-risk types of HPV plays a critical role
in the development of cervical cancer, a new model of
cervical carcinogenesis has been developed (> Fig. 5.1).
This model has three discrete steps: (1) initial infection
with a high-risk type of HPV, (2) progression to
a histologically defined precursor lesion that requires per-
sistence of the HPV infection, and (3) invasion [167, 176,
209]. Based on this biological model, it is highly unlikely
that cervical cancer develops according to a stepwise pro-
gression that envisions CIN 1, progressing to CIN 2, to
CIN 3, and on to cancer. Moreover, it now appears that the
basic premise underlying the CIN terminology is incor-
rect; the spectrum of histological changes that are referred
to as CIN do not represent a single disease process at
different stages in its development but instead two dis-
tinct biological entities, one a productive viral infection
and the other a true neoplastic process confined to the
epithelium [202].
Productive HPV infections of the cervical squamous
epithelium are self-limited in the majority of patients
and commonly result in flat cervical lesions (> Fig. 5.2)
and less frequently in exophytic ones (condylomata
acuminata). Flat HPV-associated lesions in which produc-
tive viral infection is occurring display cytoplasmic cavi-
tation and nuclear abnormalities. Traditionally, flat and
exophytic condylomas were not classified as CIN 1 since
they do not have the degree of nuclear atypia usually
present in CIN. However, in the 1980s, it was found that
the HPV types foundin the cervical flat and exophytic
condylomas are the same types that can be found in CIN 1
lesions [43]. Moreover, flat condylomas and CIN 1 lesions
are similar with respect to their ploidy status [63]. There-
fore, both exophytic and flat condylomatous lesions of the
cervix were combined into the CIN 1 category. These
lesions have been designated in the past as koilocytotic
atypia, koilocytosis, or flat condyloma.
The other entity subsumed within the morphologic
CIN spectrum is histologically ‘‘high grade.’’ High-grade
Normal cervix
The three steps of cervical carcinogenesis.
The steps can be conceptualized as infection with specific high-risk types of human papillomavirus (HPV), progression
to a precancerous lesion, and invasion, HPV infections are usually transient and are often associated with mild cytologic
abnormalities. Persistent infection with high-risk types of HPV is uncommon and is required for progression.
Initial
infection
Clearance
HPV-infected cervix
Mild cytologic
abnormalities
Progression
Precancerous
lesion
Invasion
Cancer
Regression
HPV
Transient infection Persistent HPV infection
. Fig. 5.1
Steps in the development of cervical cancer. Three steps in cervical carcinogenesis (Used with permission from [209])
Precancerous Lesions of the Cervix 5 195
DETECCIÓN DE HPV
• LA HERRAMIENTA QUE REFLEJA MEJOR LA 
BIOLOGIA DE LA LESIÓN. 
• PUEDE SER POR PCR. O CAPTURA DE 
HIBRIDOS. 
PAPANICOLAOU
PAPANICOLAOU
BAJA SENSIBILIDAD
ALTA ESPECIFICIDAD
MEJORA SI SE 
COMBINA CON 
DETECCIÓN DE 
HPV
79
The Bethesda System for Reporting Cervical Cytology
6
SPECIMEN TYPE
Indicate conventional smear vs liquid-based preparation vs other
ADEQUACY OF THE SPECIMEN
 • Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other 
quality indicators, e.g., partially obscuring blood, inflammation)
 • Unsatisfactory for evaluation … (Specify reason)
– Specimen rejected/not processed (specify reason)
– Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason)
GENERAL CATEGORIZATION (OPTIONAL)
 • Negative for intraepithelial lesion or malignancy
 • Other
 • Epithelial cell abnormality: see Interpretation/Result (specify squamous or glandular as appropriate)
INTERPRETATION/RESULT
Negative for intraepithelial lesion or malignancy
(when there is no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result 
section of the report—whether or not there are organisms or other non-neoplastic findings)
ORGANISMS
 • Trichomonas vaginalis
 • Fungal organisms morphologically consistent with Candida spp.
 • Shift in flora suggestive of bacterial vaginosis
 • Bacteria morphologically consistent with Actinomyces spp.
 • Cellular changes associated with herpes simplex virus
OTHER NON-NEOPLASTIC FINDINGS (OPTIONAL TO REPORT; LIST NOT INCLUSIVE)
 • Reactive cellular changes associated with:
– Inflammation (includes typical repair)
– Radiation
– Intrauterine contraceptive device (IUD)
 • Glandular cells status posthysterectomy
 • Atrophy
Other
 • Endometrial cells (in a woman > 40 years of age) (specify if “negative for squamous intraepithelial lesion”)
Epithelial cell abnormalities
SQUAMOUS CELL
 • Atypical squamous cells
– of undetermined significance (ASC-US)
– cannot exclude HSIL (ASC-H)
 • Low-grade squamous intraepithelial lesion (LSIL) (encompassing: HPV†/mild dysplasia/CIN 1)
 • High-grade squamous intraepithelial lesion (HSIL) (encompassing: moderate and severe dysplasia, CIS/CIN 2 and CIN 3)
– with features suspicious for invasion
 • Squamous cell carcinoma
GLANDULAR CELL
 • Atypical
– endocervical cells (NOS or specify in comments)
– endometrial cells (NOS or specify in comments)
– glandular cells (NOS or specify in comments)
 • Atypical
– Endocervical cells, favor neoplastic
– Glandular cells, favor neoplastic
 • Endocervical adenocarcinoma in situ
 • Adenocarcinoma
– endocervical
– endometrial
– extrauterine adenocarcinoma
– not otherwise specified (NOS)
Other malignant neoplasms (specify)
Table 6.1 The 2001 Bethesda System
(continued)
• tinción con p16 por IHQ. . 
DETECCIÓN EN TEJIDOS
cuerpo uterino
Fase proliferativa: efecto 
estrogènico
Ciclo endometrial
Estrógenos: estradiol
• Se adhiere al receptor de estrogeno de la 
célula estroma 
• Aumenta la sintesis de RNAm. 
• Sintesis de tres proteínas: 
• Receptores de estrogenos 
• Receptores de progesterona 
• Factores de crecimiento epitelial (aumentan 
cambios endometriales
sangrado uterino: 
términos 
• menorrea- menorragia 
• hipermenorrea 
• polimenorrea 
• proiomenorrea 
• dismenorrea 
• oligomenorrea 
SUD
• 1. ciclos anovulatorios 
menarca 
perimenopausia 
hiperestrogenemia: endometrio 
desordenadamente proliferativo 
hiperplasia
SUD
• 2. fase lútea insuficiente: endometrio secretor 
• 3. asociado a GO 
• 4. alrededor de la menopausia: descartar ca.
endometritis
• aguda: ETS o restos retenidos 
• crónica: DIU, EPI, restos retenidos, TB 
histología: células plásmáticas en el epitelio
ENDOMETRIOSIS
• presencia de glándulas endometriales y de 
estroma endometrial fuera de la cavidad 
endometrial
endometriosis 
interna:adenomiosis
• presencia de glándulas endometriales en el 
espesor del miometrio
endometriosis: teorías
• regurgitación 
• metaplasia 
• diseminación vascular o linfática
endometriosis externa
endometriosis: síntomas
• dolor pélvico severo en el momento de la 
menstruación 
• dispareunia
pólipos endometriales
hiperplasia endometrial
• causas: hiperestrogenismo (perimenopausia, 
anovulación prolongada, tumores de ovario 
productores de estrógenos)
hiperplasia endometrial
• clasificación: 
a. simple 
b. compleja 
c. Atípica- EIN
hiperplasia endometrial
• 50% se persisten post Tx 
• 25%recurren 
• 25% evolucionan a carcinoma
carcinoma del endometrio
• el 85% son adenocarcinomas (bien 
diferenciados: endometrioides) 
• 20% tienen tejido escamoso benigno: 
adenoacantoma 
• 10% tienen tejido escamoso maligno: 
carcinoma adenoescamoso. 
• Serosos (independientes de estrogenos)
clasificación
Carcinoma Tipo I: endometrioide 
Carcinoma tipo II: seroso- papilar
Características 
• Entre 55 a 65 años (síntesis de estrogenos a 
partir de adrenales y grasa) 
• Obesidad 
• Diabetes mellitus 
• HTA 
• Infertilidad 
sintomas
• Sangrado irregular postmenopausico 
• A veces puede ser detectado por PAP 
• Diagnóstico: curetaje y biopsia 
• Px: depende de la extension: 
Los endometrioides tienen buen px 
Los serosos son muy agresivos.
TUMORES DEL 
MIOMETRIO
• LEIOMIOMA
leiomioma micro
leiomioma
• 25% de todas las mujeres en edad fértil 
• síntomas: hiperproiomenorrea
leiomiosarcoma
• es poco frecuente 
• son malignos de novo
trompas uterinas
• salpingitis aguda: gonococo 
• crónica: TB
absceso tubo ovárico
absceso tuboovárico
• es una emergencia ginecológica
embarazo ectópico
tumores de ovario
frecuencia
65-70% son de origen epitelial (epitelio 
superficial) 
20% se originan de las células germinales 
5-10% cordones sexuales. estroma 
5% metastásicos
frecuencia
• de todos los malignos, el 90% son originados 
del epitelio superficial. 
• el más frecuente es el cistadenoma seroso 
benigno.
cistadenoma seroso
teratoma
disgerminomatumor de células de la 
granulosa
fibrotecoma
fibrotecoma
• síndrome de Meigs: fibrotecoma, hidrotorax 
derecho y ascitis:
mestastásicos
• carcinoma de cuello uterino 
• carcinoma del endometrio 
• tubo digestivo: Krukenberg
clínica
• por lo general son asintomáticos 
• sensación de peso