ONCOLOGICAL

GYNECOLOGY
English version

Prof. Dr. Vesna Antovska

Skopje, 2022
 MALIGNANT DISEASES OF THE VAGINA

Prof. Dr. Vesna Antovska

Types of malignant diseases of the vagina:

Squamous cell carcinoma is the most common cancer of the vagina. It spreads slowly and occurs mainly
in the elderly population (as much as 50% is in women ˃60 years).
Adenocarcinoma: it has a greater tendency to spread to the surrounding tissue and regional lymph nodes.
Clear cell carcinom occurs less frequently than adenocarcinoma. It is more common in women whose
mothers received diethylstilbestrol during pregnancy.
Sarcoma and melanoma can also occur in the vagina.
Risk factors: HPV infection, sexually transmitted diseases, age over 60 years, in utero exposure to
diethylstilbestrol, alcohol and cigarette consumption, history of cervical cancer, HIV, presence of
intraepithelial vaginal neoplasia (VAIN).
Signs and symptoms: vaginal bleeding unrelated to menstruation, pain during intercourse, postcoital
bleeding, increased vaginal stinky or bloody discharge, spontaneous pelvic pain, swelling or tumor in the
vagina, dysuria, constipation. As many as 20% of patients have no symptoms.
Diagnosis: history, bimanual vaginal examination and speculum examination; PAP test, HPV typing and
colposcopy; biopsy of suspicious sites and its histopathological analysis. To determine the extent of the
disease are used: lung radiogram, computed tomography (x-ray and expanded by injection of vital color
into a vein), magnetic resonance, PET scan (positron emission tomography scan) with injection of
radioactive intravenous glucose (malignant cells appear brighter because they are more receptive to
glucose); cystoscopy and rectosigmoidoscopy to rule out involvement of surrounding organs, bladder, and
rectum.
Factors influencing the prognosis are: stage of the disease, size of the tumor, grade of the tumor (degree
of cell differentiation), location of the tumor, whether at the time of diagnosis the tumor was symptomatic
or asymptomatic, whether it is a recurrent disease, histological type of the tumor, whether the patient had
previous pelvic radiotherapy for another cancer.
Stages of the disease:
Stage 0-intraepithelial vaginal neoplasia (VAIN)
 VAIN 1-abnormal cells are present in the lower 1/3 of the epithelium
 VAIN 2-abnormal cells are present in the lower 2/3 of the epithelium
 VAIN 3-abnormal cells are present in more than 2/3 of the epithelium
 In situ Ca-abnormal cells are present throughout the thickness of the epithelium
Stage 1 - the tumor is confined to the vaginal wall and has a perforation of the basement membrane, no
involvement of regional lymph nodes
Stage 2 The tumor has spread to the surrounding tissue of the vagina, but not yet to the pelvic wall, there
is no involvement of regional lymph nodes
Stage 3 The tumor has spread to the pelvic wall and / or the regional lymph nodes are involved
Stage 4
 Stage 4A The tumor has spread to the bladder and rectum, uterus, ovaries
 Stage 4B - there are distant haematogenous metastases

TYPES OF VAGINAL CANCER:

squamous cell carcinoma: it is the most common type (80%). It is most commonly located in the upper
1/3 of the vagina, near the uterine cervix. It presents clinically with nodular formation or ulceration. It is
almost always associated with HPV infection and has a preclinical stage of intraepithelial vaginal
neoplasia (VAIN). Verucous type is a rare type of squamous cell carcinoma, which resembles a broad
condylomatous cauliflower. It shows slow growth and rarely spreads to surrounding structures, so it has a
better prognosis.
Adenocarcinoma is less common than squamous cell carcinoma (10%). It begins in the glandular
formations of the vagina. It occurs in the young population. Differential diagnostics should be taken into
account are implantation metastases or per continuitatem spread of cancers from adjacent organs, so
histopathological diagnosis is very important, but at the same time very difficult. There are 4 types of
vaginal adenocarcinoma:
Clear cell carcinoma: is very rare and occurs only in young women in puberty or adolescence whose
mothers received diethylstilbestrol (DES) during pregnancy. That is why this drug was banned in 1970.
Papillary carcinoma tends to grow in the connective tissue around the vagina and is less likely to
metastasize to regional lymph nodes.
Mucosal carcinoma under a microscope shows the presence of mucus into and around the cells. It
presents as a tumor formation covered with mucus.
Adenosquamous carcinoma microscopically shows the presence of squamous and glandular cells. It is
very rare, has very fast growth and poor prognosis.

VAIN Stage 1 Stage 2

Stage 3 Stage 4А Stage 4В

Fig. 1 Clinical stages of vaginal cancer 1

LEVEL OF CANCER DIFFERENTIATION: This feature reflects the similarity of cancer cells to
normal tissue and is extremely important in terms of the rate of evolution, and thus the prognosis.
Grade 1 (G1) - the cells look almost normal and / or the tumor cells are separated from normal tissue in
groups. It has a slow growth and a good prognosis.
Grade 2 (G2) - cells look less like normal cells, the tumor has a medium tendency to grow.
Grade 3 (G3) - the cells are very abnormal, the tumor spreads rapidly in the surrounding tissue and
quickly metastasizes.

TREATMENT:
Surgical treatment: laser surgery, local wide excision, partial or total vaginectomy, total hysterectomy
with partial vulvectomy, radical hysterectomy and pelvic lymphadenectomy, radical vulvectomy, pelvic
exenteration. Which operation will be performed depends on the stage of the disease.
Partial and total simplex vaginectomia involves removal of the vaginal epithelium without dissection the
surrounding connective tissue-paracolpium, and the dissection area provides a layer thickness of ˂5 mm.
Radical vaginectomy involves removal of the paracolpium, and the dissection depth is ˃5 mm. This
intervention is usually also performed in conjunction with a radical hysterectomy for advanced cervical or
endometrial cancer.

Fig.3 Technique of total vaginectomy 3

Total vaginectomy technique:

It is indicated for vaginal malignancy and is the only alternative for recurrent microinvasive vaginal
cancer after total pelvic irradiation. Due to previous irradiation, tissue dissection is difficult to make and
associated with an increased risk of rectovaginal and vesicovaginal fistula. Therefore, it is best to perform
the intervention per vias vaginalis. Per vias abdominalis surgical approach is reserved only if the
vaginectomy is performed in combination with a radical or simple hysterectomy.
First an incision is made around the introitus along the entire circumference in depth to the pubocervical
fascia and to the perirectal fascia. The vaginal branches of the pudendal artery are identified, clamped
and ligated. The exact dissection between the vaginal mucosa and the perivesical fascia is at the level of
the fascia vaginalis-Halban, which remains attached to the vaginal mucosa. Accurate dissection in this
layer allows bloodless dissection. Pulling the vagina down and sliding the scissors along the vaginal wall
facilitates this step of the operation and avoids injury to the bladder and rectum.
In this way the vagina is pulled out and twisted similar to taking off a glove. Back dissection in the
perirectal fascia avoids injury to the hemorrhoidal plexus, and if bleeding occurs, it is controlled by
ligation or cauterization. When the dissection reaches the plica vesicouterina and Douglas area, the vagina
is clamped in a few bites and the clamps are replaced with sutures.
In the case of a young patient, the termination of the vagina is by placing several terminals in a circular
manner, and then the operation continues with the operation Neovagina sec. Mc Indoe by placing a skin
Thiersch graft from the thigh and placing a vaginal model.
In the case of an elderly patient, removal of the vagina is followed by closure of the newly acquired
opening by interconnection of the pubovesical and rectal fascia as in Le Fort-Neugebauer surgery. If there
is some degree of genital prolapse, it is recommended that vaginal hysterectomy be continued.
If the lesion is in the upper 1/3 of the vagina and there is no accompanying genital prolapse, an
abdominal approach is recommended, in which a radical hysterectomy is performed first with ureter
release, followed by a partial upper vaginectomy.
If there is genital prolapse, a vaginal approach is recommended where the separation of the vagina starts
from the top down, with an initial circular incision through the vaginal fornixes, the vagina dissected with
midsections of the anterior and posterior vaginal wall, followed by a vaginal hysterectomy and finally
total excision of the previously dissected anterior and posterior vaginal wall.

Fig.4 Treatment of vaginal cancer in the upper third-radical hysterectomy with radical partial vaginectomy 4

Fig. Intracavitary radiotherapy 2

Radiotherapy: external radiotherapy and internal radiotherapy with the help of radium needles that are
placed directly in the tumor or with radium cylinders that irradiate the entire length of the vagina.
Intracavitary vaginal radiation is used as primary neoadjuvant therapy in vaginal cancer and endometrial
cancer, and the external radiotherapy as a postoperative adjuvant therapy for irradiation of the lymph
nodes. For vaginal cancer, a cylinder which is applied should be of the widest diameter, which does not
cause pain, and intimately touches the mucosa.
For the treatment of endometrial cancer the vaginal cylinder is combined with an intrauterine tandem. The
applied dose should be 4000cGy at a depth of 1.5 cm. The cylinder is fixed by mutual suturing of the
labia.
Chemotherapy: topical in the form of cream or systemic in tumors with distant metastases.
New types of treatment: application of radiosensitizers, which make malignant cells more sensitive to
radiotherapy.
Recommended treatment according to the stage of the disease:
intraepithelial vaginal neoplasia:
 laser ablation or CO2 at a depth of at least 1.5 mm → negativity is the difficult visualization and
identification of lesions that can be overlooked
 extensive local excision,
 partial or total vaginectomy,
 internal radiotherapy with radium needles,
 topical chemotherapy with 5% 5-fluorouracil cream 1x1 weekly for 8 weeks. With this therapy the
negatives of ablation are overcome. 5-FU therapy shows a very high cure rate of 85% and a lowest
recurrence rate of 15%.
 Topical treatment with the immunomodulator imiquimod 3x1 / week for 8 weeks has a cure rate of
75%.
Stage 0 (VAIN 3, Ca in situ) - local intracavitary radiotherapy (brachyterapia) in disseminated VAIN 3,
and in a single local lesion, extensive local excision, CO2 laser vaporization, or cryotherapy is performed.
Stage 1:
1).In squamous cell carcinoma, the following are recommended: internal radiotherapy, external
radiotherapy, extensive local excision, partial or total vaginectomy depending on the size and location of
the tumor.
 If the tumor is ˂5 mm thick, only brachyradiotherapy is sufficient,
 in deeper lesions a combination of intracavitary and external radiotherapy is performed.
 If the tumor is located in the upper 1/3 of the vagina and fornix, a radical hysterectomy, bilateral
pelvic lymphadenectomy, and a radical partial / or total vaginectomy are performed. This is followed
by external radiotherapy.
2).In adenocarcinoma:
 for tumors in the upper 1/3 of the vagina and fornix, a radical hysterectomy is performed, partial or
radical vulvectomy, pelvic lymphadenectomy → is followed by interstitial and external radiotherapy.
 For tumors in the lower part of the vagina, a partial / total radical vaginectomy is performed →
followed by external radiotherapy for the inguinal and pelvic lymph nodes and interstitial / or
intracavitary radiotherapy if a neovagina is made
Stage 2
 if it is a small cancer, a radical vaginectomy or pelvic exenteration is recommended, followed by
radiotherapy to the inguinal and pelvic lymph nodes. The recommendations are the same for
squamous cell carcinoma and adenocarcinoma: surgical therapy (radical vaginectomy or pelvic
exenteration) / or internal + external radiotherapy.
 Adjuvant chemotherapy or neoadjuvant therapy may be given before surgery for larger tumors.
Stage 3 and Stage 4A - neoadjuvant radiotherapy → pelvic exenteration followed if the tumor becomes
operable
Stage 4B - chemoradiotherapy and use of radiosensitizers.
Treatment of recurrent squamous and adenocarcinoma of the vagina: if the tumor recurs in the primary
site it is called local recurrence, and if it recurs elsewhere in the body it is called distant recurrence.
 Local recurrence of stage 1 and 2 vaginal cancer is treated with pelvic exenteration, and if this
operation is done in the first act, then radiotherapy is an option. The treatment of recurrent disease
mainly consists of radiotherapy with radiosensitizers, chemotherapy and pelvic exenteration if
technical possibilities are available.
 Relapses of G3 tumors with high malignancy potential and strongly undifferentiated cells can not be
cured, so palliative measures are applied to facilitate the life of patients.
 In distant relapses, local extirpation of metastases, radiotherapy, and chemotherapy are used.
Regarding vaginal melanoma, the data are limiting, as only 115 cases of this cancer have been published
in the literature. There are 4 different therapeutic strategies:
1) surgery only, which is technically extremely difficult and risky for the patient due to retroperitoneal
access to the tumor and close collision with large pelvic blood vessels, upper and middle paracolpium
blood network, bladder and rectum;
2) only radiotherapy, which is most acceptable for the patient;
3) combination of surgery and radiotherapy, which gives the best results;
4) sandwich therapy with: chemotherapy → surgery → radiotherapy, which is reserved for very advanced
cases.
Surgical therapy depends on the location of the tumor (upper, middle or lower third of the vagina), so a
radical hysterectomy can be performed with partial colpectomy, local excision, partial vaginectomy,
radical vaginectomy with pelvic exenteration, that is, amputation of the rectum and bladder. There is no
difference in survival and disease-free interval between radical mutation surgeries and a more
conservative surgical approach. Therefore, today the view holds that in the case of vaginal melanoma the
patient should be offered a radical excision of the tumor, which will provide satisfactory free margins of
the excised sample, both in depth and width, a recommendation that also applies to vulvar melanoma:
 1cm horizontal margins for invasion depth ˂1mm and
 2cm horizontal margins for invasion depth of 1-4mm,
 as well as ≥1cm vertical margins in depth.

VAGINAL SARCOMAS:
Sarcomas are very rare (3% of all vaginal malignancies), 2/3 of which are leiomyosarcomas.
Vaginal rhabdomyosarcomas present with 3 subtypes:
1) the embryonic type (sarcoma botryoides), which shows microscopic features of the presence of
rhabdomyoblasts with transverse stripes resembling a muscle cell, arranged in dense groups below the
vaginal epithelium (G1) or presence of desmin-positive spindle-cell tumors (G3);
2) alveolar subtype, which occurs mainly in the muscles of the extremities, but also in the bladder,
vagina, paratesticular and in the prostate and is presented with normal muscle cells present in an embryo
of 10 weeks gestation. This type has faster growth than the embryonic type;
3) anaplastic subtype, which is very rare and almost never occurs in children. He has the worst prognosis.
SARCOMA BOTRYOIDES is a subtype of embryonic rhabdomyosarcoma, which is very rare and
occurs exclusively in children ˂8 years. It typically occurs on the mucous membranes of openings in the
body, such as the nasopharynx, biliary trunk, bladder, vagina, and cervix, around the prostate, and
testicles in boys. Its name comes from the Greek language for grape because it is presented as soft knots
like grape formation, which sometimes comes out of the vaginal introitus. This tumor is rapidly growing
tumor and has a poor prognosis.
Clinically it presents with vaginal bleeding unrelated to menstruation, infection with impure bloody, foul-
smelling discharge because the tumor is very fragile, urinary retention, pink-red mole tumor that
protrudes from the vaginal opening and bleeds to the touch. Distant metastases to the lungs, bones, and
regional lymph nodes may already be present at the time of diagnosis.
Differential-diagnosis: adenocarcinoma, edematous mesodermal polyp (pseudosarcoma botryoides),
rhabdomyoma are considered. The disease is highly fatal, and the 5-year survival is 10-35%.
Prognosis: compared to cervical rhabdomyosarcoma, vaginal has a significantly better prognosis. Genetic
factors seem to play a role because the presence of this tumor has been observed in several members of
one family, as well as the presence of other tumors, e.g. Sertoli-Leydig tumors.
Treatment: Radical removal of the genitals has already been abandoned by most schools, which prefer
extensive excision with clean margins and postoperative chemotherapy or radical surgery by sacrificing
generative function.

Fig. 5 sarcoma botryoides with pleomorphic spindle-shaped cells with eosinophilic fibrillar cytoplasm and irregular
fascicular growth of fibrinogen filaments (left and middle) 5, 6

Fig.6 Vaginal melanoma (left) 7 and small cell carcinoma of the vagina (right) 8

VAGINAL MELANOMA is also very rare (3% of vaginal malignancies and 1% of all melanomas in
women). Occurs mainly in the lower 1/3 of the vagina. It most often occurs in the 5th decade. It originates
from the melanocytes of the vaginal epithelium. This tumor has a very poor prognosis with a median
survival of 16 months. The most important prognostic factor is lymph node involvement. It presents as a
dark irregular lesion, usually T-shaped. Ammelanotic melanoma is present in 7%, which presents as a
bright lesion.
Histology involves the presence of cells, which resemble epithelial cells in shape or are spindle-shaped,
grouped in nests or leaves, melanin is present in the cells, and the nuclei are large and abnormal.
The diagnosis is made by biopsy of all suspected sites with immunohistochemistry of the tissue, which is
(+) of Ѕ-110 protein, NMV 45, and melan A.
Treatment consists of surgical extirpation and target therapy with checkpoint inhibitors, MEC inhibitors,
and BRAF. Chemotherapy is not effective in treating this cancer.
SMALL-CELL CARCINOMA is extremely rare, only 30 cases have been described. The tumor is
presented macroscopically as a dark red fragile with hemorrhagic zones and has no continuity with the
cervix, but grows from the vaginal wall. The tumor is very similar histopathologically to primary
pulmonary small cell carcinoma. Alveolar solid areas of atypical small cells with sparse cytoplasm and
rich in chromatin, with a high N / C ratio, with rosette-like structures are present. The tumor is
immunohistochemical (+) for SK20, cytokeratin, chromogranin A, synaptophysin.
To make a differential diagnosis between primary vaginal carcinoma and metastatic vaginal from
pulmonary small cell carcinoma, a full-body PET scan is required. Treatment consists of surgical
treatment and chemo-radiotherapy. Тhe chemotherapy regimen includes cisplatin + etoposide, a
combination that is most effective in the pulmonary type. The prognosis is bad and death occurs in 2
years in most cases.
This tumor has neuroendocrine features and may show ectopic hormone production in 5% of cases, e.g.
Cushing syndrome due to ACTH production with edema, muscle weakness, hypertension and
hyperglycaemia.

Literature:
1.https://www.cancerresearchuk.org/about-cancer/vaginal-cancer/stages/stage-3
2.http://www.atlasofpelvicsurgery.com/10MalignantDisease/
4ApplicationofVaginalCylindersforIntracavitaryRadiationTherapy/cha10sec4.html
3. http://www.atlasofpelvicsurgery.com/10MalignantDisease/11TotalVaginectomy/cha10sec11.html
4. https://www.dana-farber.org/vaginal-cancer/
5. Azamsadat Mousavi and Setare Akhavan. Sarcoma botryoides (embryonal rhabdomyosarcoma) of the uterine
cervix in sisters. J Gynecol Oncol. 2010 Dec 30; 21(4): 273–275. . doi: 10.3802/jgo.2010.21.4.273
6.https://www.slideshare.ne/nermineamin/prepubertal-bleeding
7. Pankaj, S., Kumari, A., Nazneen, S. et al. Malignant Melanoma of Vagina: A Report and Review of Literature. J
Obstet Gynecol India 66, 394–396 (2016). https://doi.org/10.1007/s13224-015-0755-0
8.Ryosuke Tamura, Yoshihito Yokoyama, Asami Kobayashi, Yuuki Osawa, Tatsuhiko Shigeto, Masayuki
Futagami, Hideki Mizunuma. A Case of Small Cell Carcinoma of the Vagina. Rare Tumors. 2013 Dec; 5(4): e58