Villegas, Jose Bernabe A.

GYNECOLOGY
Vinluan, Joseph David
Dr. Trinidad
Wong, Deo Adiel 3rd Year
–D
Yague, Glenn Sept. 5,
2007
Yang, Caprice

Case #15
73 year old G2P2 (2002) complained of vulvar pruritus for 3 years.
PMH: (+) DM, HPN on medication. She consulted a private
physician and was prescribed with Fluconazole, which afforded no
relief. PPE: (+) 3x2 cm hyperpigmented patch with excoriation on
the left mid portion of the vulva extending up to the left labia
majora. Spec. exam: vagina- pale; cervix: flushed to the vaginal
wall; uterus: small, movable; and (-) mass (-) tenderness

1. What other information should be sought for?

Since the patient complains of vulvar pruritus, it is imperative to

expound more on causes of vulvar pruritus specifically, chronic causes. Ask
the patient if the typical gradual onset of chronic vulvar pruritus is present.
Moreover, ask the patient if there have been any previous inflammatory
conditions such as a history of vulvitis or vaginitis. Although inflammatory
conditions are typified by their acute presentation, recurrences, reinfection or
reactivation of latent disease cannot be ruled out unless inquiry is further
delved into.

In parallel with this, since dermatoses occur anywhere in the body, ask
for other similar pruritic lesions in other parts of the body that accompanied
or came before/after the vulvar lesion. It is also very helpful to ask if there are
accompanying symptoms like redness, dryness, scaling, small red bumps,
swelling, skin plaques, blisters/ulcers and/or oozing/crusting. These are
helpful when ruling in/out primary inflammatory conditions but not
exclusively as malignancy may as well present with some of these.

Moreover, assess hygienic practices (also if inadequate). Douching or

substances use to clean the vagina as may reveal any allergies that present
with pruritus. This is particularly important whenever considering contact
allergies. Inadequacy of hygiene may also present with pruritus.

Since both hereditary and environmental factors are thought to play a

role in developing skin lesions, ask for a history of malignancy and exposure
to carcinogenic substances. This may all point to malignant causes of chronic
vulvar pruritus.

In this light, consider asking for characteristic sites of preponderances

of skin lesions accompanying pruritic vulvar or genital lesions such as in the
 perineum, axillae, and external auditory canal which are rich in apocrine
glands (common in Paget’s disease), or lesions in sun-exposed areas
(common in squamous cell carcinoma). Asking the patient if there had been
any trial of medications aimed at relieving bacterial, fungal or viral causes
that was unsuccessful may reveal more of the nonresolving character of
neoplastic conditions. Possibly reinforcing but not exclusive is the presence of
pain and bleeding in long-standing lesions, and the presence or absence of
which should be asked also.

Even further, ask for symptoms of diabetes such as polyuria, polydipsia

and polyphagia or a history of it. Diabetes can also present with chronic
vulvar pruritus, especially in cases of atrophic vulvovaginitis. Ask also for
mechanical causes of pruritus such as occasional habitual/compulsive
scratching or trauma that may be healing.

Finally, an increased tendency for depressive and obsessive-

compulsive disorder has been identified in patients with chronic pruritic
conditions. Asking about day-to-day practices or experiences may reveal
symptoms or traits meeting the criteria of which of the two mentioned above,
might point to psychogenic causes of atrophic vulvovaginitis presenting as
chronic vulvar pruritus.

2. What is the probable diagnosis?

In the history, the patient presented with chronic vulvar pruritus for a
period of 3 years; and on PE, a hyperpigmented patch on the vulva was
noted. She was previously prescribed with fluconazole, an antifungal agent,
but afforded no relief. From this data, we can set aside fungal infection from
our considerations. Considering her age, 73 years old, which is in the
postmenopausal period, this is most likely a neoplastic process, probably
malignant.

The most probable diagnosis in this

case is Extramammary Paget’s Disease
(EMPD). Although squamous cell carcinoma of
the vulva is the most common type of vulvar
carcinoma and is also associated with
pruritus, it usually presents as an exophytic
or papillomatous mass or an endophytic ulcer
that may be confused with condyloma
acuminata. However, in this patient, a
hyperpigmented patch (flat lesion) was
appreciated. SCC patients usually have
identifiable risk factors such as, previous
Human Papilloma Virus infection, smoking,
Extramammary Paget’s immunosuppression and lichen sclerosis. In
Disease this patient, only immunosuppression is
present as accounted by the positive family history of diabetes. However, in
the history, it was stated that she is on medications and we can say that the
diabetes is most likely controlled.
 Extramammary Paget’s Disease presents most commonly as a unifocal
process; though multifocal lesions may also occur. The lesions typically affect
apocrine sites, including the groin (vulva,
scrotum, perianal, penis, inguinal folds) and
axilla, but rare cases can affect other
anatomic locations. EMPD normally affects
persons older than 50. EMPD often
misdiagnosed as fungal infection or intertrigo. A
nonhealing banal eczematous patch persisting
in the anogenital or axillary region should raise
concern for EMPD. Intense pruritus is common.
Bleeding is a late sign. Lesions may simulate Vulvar Intraepithelial
lichen simplex chronicus or leukoplakia. EMPD Neoplasia
can remain within the epithelium or invade the dermis. “Invasive” EMPD has
a high rate of metastasis and very poor prognosis. Sentinel node examination
of patients with invasive EMPD should be considered as it predicts risk for
metastasis. (Andrew’s Clinical Dermatology 10th ed).

Sir James Paget first described Paget's disease

of the nipple in 1874 in 15 patients with underlying
ductal breast cancers. In 1889, Crocker described the
first case of extramammary Paget's disease affecting
the scrotum and penis. Extramammary Paget's
disease (EMPD) is a rare form of adenocarcinoma
observed mostly in areas with numerous apocrine or
eccrine glands. It is presumed to be a variant of the
epithelial carcinoma, with potential to develop from
or to be the cause of an underlying adenocarcinoma.

EMPD arises as a primary

cutaneous adenocarcinoma in most
cases. The epidermis becomes
infiltrated with neoplastic cells
showing glandular differentiation.
Tumor cells may originate from
apocrine gland ducts or from
keratinocytic stem cells.

Approximately 25% of the cases of EMPD (range, 9-32%) are

associated with an underlying in situ Medium power view. The cells are large and have a
or invasive neoplasm. In all patients, rather bland appearance in this area. Some are found
singly in a pagetoid distribution, and others are in
the neoplasm most likely to be clusters. The intervening keratinocytes are free of
associated with EMPD is an adnexal atypia.
apocrine carcinoma. This associated
neoplasm probably represents infiltration of the deeper adnexa by epidermal
Paget cells. In addition to cutaneous adnexal carcinoma, other associated
malignancies include the following: carcinoma of the Bartholin glands,
urethra, bladder, vagina, cervix, endometrium, or prostate.
 The anatomic location of EMPD plays a role in predicting the risk of
associated carcinoma. For instance, about 4-7% of patients with genital
disease have an associated carcinoma. Perianal disease is associated with
underlying colorectal carcinoma in 25-35% of cases.

Rare cases of EMPD associated with tumors arising in distant organs

without direct epithelial connection to the affected epidermis have been
reported. No clear evidence supports a causal link between these distant
tumors and cutaneous EMPD.

Surgical removal is the treatment of choice, which may require Mohs

microsurgery. Despite what appears to be adequate margins, recurrence
rates are high because of the multifocal nature of EMPD. The recurrence rate
following micrographic surgery exceeds 25%. Radiation therapy,
photodynamic therapy, and laser treatments have also been used.

3. What are the differential diagnoses?

For a patient presenting with vulvar pruritus for 3 years, a lot of

conditions could be considered. Vulvar pruritus is defined as itching of the
female external genitalia. It is a common symptom in females of all ages and
may occur in the presence of a dermatological disease or with just a few skin
findings. Moreover, chronic vulvar pruritus often has a long history with
gradual onset, and may include a large variety of disorders ranging from
nonneoplastic to neoplastic.

Nonneoplastic epithelial disorders

of the vulva include: lichen sclerosus,
squamous cell hyperplasia and other
dermatoses. Terms like vulvar dystrophy,
kraurosis vulvae, leukoplakia,
hyperplastic vulvitis, and lichen sclerosus
et atrophicus, goes under this group and
should no longer be used as was
discussed in several meetings of
international societies which lead to the
use of a standardized nomenclature.
Conditions characterized by atypia are part of the neoplastic group.

Lichen sclerosus (Figure 1) appears as a white, usually symmetric,

lesion with a wrinkled, parchment-like surface and causes atrophy of the labia
minora pudendi. Pathologic examination shows thinning of squamous
epithelium, loss of rete pegs, and deep dermal inflammatory cells. On the
other hand, squamous cell
hyperplasia (Figure 2) on pathologic
examination reveals thickening of the
squamous epithelium, elongation of
rete pegs (acanthosis), and
hyperkeratosis. Also, the lesions are
white and are believed to be a
reaction to chronic pruritus from a variety of stimuli (e.g., recurrent
candidiasis, eczema, chemical irritation from soaps). Both lichen sclerosus
and squamous cell hyperplasia presents with pruritus and occurs most
commonly in postmenopausal women. However, in our patient, the lesion
presented with a hyperpigmented patch (as opposed to the white lesions
found in the nonneoplastic group); and is not responsive to fluconazole.
Additionally, the shrunken introitus because of the fusion of the labia minora
in lichen sclerosus is not found in our patient. The unresponsiveness to
fluconazole indicates that squamous cell hyperplasia due to a fungal infection
might not possibly be the diagnosis.

Other nonneoplastic dermatoses like psoriasis, seborrheic dermatitis

and tinea cruris could also be ruled because of their unlikely presentation
which can be seen in the history. Psoriasis is a multifocal disease that may
affect vulvar tissue as well as skin of the joints, knees, and scalp. Seborrheic
dermatitis, another multifocal disease of the sebaceous glands commonly
affecting the scalp, may affect the labia majora pudendi only. Tinea cruris
begins as raised, sharply demarcated, red lesions on the thighs and can
spread to the labia.

Neoplasms of the vulvar area are often slow growing and can cause
low-grade
Pruritus which includes squamous intraepithelial neoplasia and nonsquamous
intraepithelial neoplasia. Under squamous intraepithelial neoplasia is VIN. VIN
can be grouped into two: those associated with HPV infection and those that
are associated with squamous cell hyperplasia and lichen sclerosus (leading
directly to carcinoma). As was discussed above, the latter group is not
probable because of certain factors in the history of our patient.

Vulvar intraepithelial neoplasia associated with HPV infection has its

grading based on the basis of cellular immaturity, nuclear abnormalities,
maturation disturbance and mitotic activity. Grades: VIN I: mildly abnormal
changes in the skin cells (mild dysplasia), VIN II: moderately abnormal
changes in the skin cells (moderate dysplasia), and VIN III: severely abnormal
changes in the skin cells (severe dysplasia) and carcinoma in situ. Clinically,
these lesions usually present as multiple small white or pigmented papules
and/or plaques (usually <5mm in diameter) on the vulva. VIN is appearing
with increasing frequency in women younger than 40 years of age. Likewise,
the presentation in VIN is not consistent with our patient’s (i.e. age, absence
of hx of HPV infection and characteristic lesion).

The rare variants of squamous cell carcinoma such as verrucous

carcinoma and basal cell carcinoma occur less frequently. Verrucous
carcinoma is warty and basal cell carcinoma is associated with increased sun-
exposure. Both presentations are absent in the patient’s history and PE.

Under nonsquamous intraepithelial neoplasia are melanomas and

extramammary Paget’s disease (our diagnosis). The second most common
type of vulvar cancer (about 2% to 4%) is melanoma. Melanomas develop
from the pigment-producing cells that determine the skin's color. About 5% to
8% of melanomas in women occur on the vulva. Their peak incidence is in the
sixth and seventh decade. In contrast to our patient’s lesion, melanomas are
more common in the labia minora and clitoris.

Management

Clinical staging
The International Federation of Gynecology and Obstetrics (FIGO) has
adopted a surgical staging system for vulvar cancer. The stage of cancer is
determined after surgery. The previous clinical staging system for vulvar
cancer is no longer used. Vulvar cancer is categorized into five stages (0, I, II,
III, and IV) which may be further subdivided (A and B) based on the depth or
spread of cancerous tissue. The FIGO stages for vulvar cancer are:

• Stage 0. Vulvar intraepithelial neoplasia.

• Stage I. Cancer is confined to the vulva and perineum. The lesion is less than
2 cm (about 0.8 in) in size.
• Stage II. Cancer is confined to the vulva and perineum. The lesion is larger
than 2 cm (larger than 0.8 in) in size.
• Stage III. Cancer has spread to the vagina, urethra, anus, and/or the lymph
nodes in the groin (inguinofemoral).
• Stage IV. Cancer has spread to the bladder, bowel, pelvic bone, pelvic lymph
nodes, and/or other parts of the body.

Treatment Options
Treatment for vulvar cancer will depend on its stage and the patient's
general state of health. Surgery is the mainstay of treatment for most cases
of vulvar cancer. However for our patient who is in Stage II vulvar carcinoma,
surgery is the best possible treatment (wide excision); in addition, Mohs
surgery has provided good results. Radiotherapy and Chemotherapy may also
be indicated especially in advanced stages.

SURGERY. The primary treatment for stage I and stage II vulvar cancer
is surgery to remove the cancerous lesion and possibly the inguinofemoral
lymph nodes. Removal of the lesion may be done by laser, to burn off a
minimal amount of tissue, or by scalpel (local excision), to remove more of
the tissue. The choice will depend on the severity of the cancer. If a large
area of the vulva is removed, it is called a vulvectomy. Radical vulvectomy
removes the entire vulva. A vulvectomy may require skin grafts from other
areas of the body to cover the wound and make an artificial vulva. Because of
the significant morbidity and the psychosexual consequences of radical
vulvectomy, there is a trend toward minimizing the extent of cancer excision.
The specific inguinofemoral lymph node that would receive lymph fluid from
the cancerous lesion, known as the sentinel node, may be exposed for
examination (lymph node dissection) or removed (lymphadenectomy),
especially in cases in which the cancerous lesion has invaded to a depth of
more than 1 mm. Surgery may also be followed by chemotherapy and/or
radiation therapy to kill additional cancer cells.
 RADIATION THERAPY. Radiation therapy uses high-energy radiation
from x rays and gamma rays to kill the cancer cells. The skin in the treated
area may become red and dry and may take as long as a year to return to
normal. Fatigue, upset stomach, diarrhea, and nausea are also common
complaints of women having radiation therapy. Radiation therapy in the
pelvic area may cause the vagina to become narrow as scar tissue forms.
This phenomenon, known as vaginal stenosis, makes intercourse painful.

CHEMOTHERAPY. Chemotherapy uses anticancer drugs to kill the

cancer cells. The drugs are given by mouth (orally) or intravenously. They
enter the bloodstream and can travel to all parts of the body to kill cancer
cells. Generally, a combination of drugs is given because it is more effective
than a single drug in treating cancer. The side effects of chemotherapy are
significant and include stomach upset, vomiting, appetite loss, hair loss,
mouth or vaginal sores, fatigue, menstrual cycle changes, and premature
menopause. There is also an increased chance of infections.

Alternative treatment
Although alternative and complementary therapies are used by many
cancer patients, very few controlled studies on the effectiveness of such
therapies exist. Mind-body techniques such as prayer, biofeedback,
visualization, meditation, and yoga have not shown any effect in reducing
cancer but can reduce stress and lessen some of the side effects of cancer
treatments. Clinical studies of hydrazine sulfate found that it had no effect on
cancer and even worsened the health and well-being of the study subjects.
One clinical study of the drug amygdalin (Laetrile) found that it had no effect
on cancer. Laetrile can be toxic and has caused death. Shark cartilage,
although highly touted as an effective cancer treatment, is an improbable
therapy that has not been the subject of clinical study.

The American Cancer Society has found that the "metabolic diets"
pose serious risk to the patient. The effectiveness of the macrobiotic, Gerson,
and Kelley diets and the Manner metabolic therapy has not been scientifically
proven. The FDA was unable to substantiate the anticancer claims made
about the popular Cancell treatment.

There is no evidence for the effectiveness of most over-the-counter

herbal cancer remedies. However, some herbals have shown an anticancer
effect. As shown in clinical studies, Polysaccharide krestin, from the
mushroom Coriolus versicolor, has significant effectiveness against cancer. In
a small study, the green alga Chlorella pyrenoidosa has been shown to have
anticancer activity. In a few small studies, evening primrose oil has shown
some benefit in the treatment of cancer.

REFERENCES:
• Berek & Novak’s Gynecology, 14th Edition.
• Andrew’s Clinical Dermatology, 10th Edition.
• Robbins & Cotran’s Pathologic Basis of Disease, 7th Edition.
• Nonneoplastic Epithelial Disorders of the Vulva
http://www.emedicine.com/med/topic3294.htm
• Malignant Vulvar Lesions
http://www.emedicine.com/med/topic3296.htm
• Vulvar pruritus: Differential diagnostic in medical practice
http://www.tellmed.ch/include_php/previewdoc.php?file_id=956
• Postgraduate Medicine Online: “Vulvar problems in elderly women”
http://www.postgradmed.com/issues/1997/09_97/barhan.htm
• American Cancer Society: “What is Vulvar cancer?”
http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_vulvar_cancer_
45.asp