Download METHODICAL INSTRUCTIONS

MINISTRY OF PUBLIC HEALTH OF UKRAINE
NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA
CHAIR OF OBSTETRICS AND GYNECOLOGY №1
METHODICAL INSTRUCTIONS
for practical lesson
« Malignant gynecological conditions. Malignant disease of the vulva, vagina,
cervix and ovary. Endometrial cancer. Cancer chemotherapy. Radiotherapy in
gynecological cancer. Palliative care»
MODULE 4: Obstetrics and gynecology
TOPIC 14
I. Scientific and methodical grounds of the theme
Early and active diagnosis of benign tumors and precancerous diseases of female
genitalia, their timely and correct treatment are the pledge for solution of cancer
problems.
II. Aim:
A student must know:
1. Classification of precancerous diseases.
2. Methods of examination for diagnosis of precancerous diseases.
3. Conservative methods of treatment.
4. What are considered precancerous diseases.
A student should be able to:
1. Diagnose precancerous diseases of female genitalia.
2. Carry out a vaginal speculum-examination, vaginal examination, put up
primary diagnosis.
III. Recommendations to the student
PRECANCEROUS CERVICAL DISEASES
All precancerous cervical lesions are termed as "dysplasia" by decision of
WHO (1973) Experts Committee. Leukoplakia with atypia of cellular elements,
erythroplakia and adenomatosis also belong to this group. There are many
synonyms of dysplasia such as: atypia, atypic hyperplasia, basal cell hyperplasia,
cervical intraepithelial neoplasia (CIN) and others. Risk factors of dysplasia, and
cervical cancer are: early beginning of sexual life, multiple sexual partners,
posttraumatic cervical changes in the result of abortions and deliveries, infecting
by HPV and VHS-2 viruses, change of hormonal balance (hyperestrogeny),
harmful working conditions and ecology. The disease most frequently is found into
women after 30 years. According to the localization dysplastic changes in young
patients appear in exocervix area and in women of climacteric age — in the
cervical canal, that is connected with the transitional zone migration.
Dysplasia
According to the degree of epithelium stinging, cultural atypia and saving of
epithelial layer architectonics three degrees of dysplasia have been distinguished.
There are:
 mild (CIN I)
 moderate (CIN II)
 severe (CIN III)
Hyperplasia and basal cell atypia occupies 1/3 of epithelium layer at CIN 1, at CIN
II the changes take about the half of mucous layer, and at CIN III all the epithelium
or not less than 2/3 of its layer is altered. The expressed atypia of the superficial
layers is considered to be the severe dysplasia.
The following types of epithelium changes are distinguished at colposcopy. They
are:
• areas of dysplasia:
areas of stratified squamous epithelium
areas of columnar epithelium metaplasia
• papillary zone of dysplasia:
papillary zone of stratified squamous epithelium hyperplasia
papillary zone of columnar epithelium metaplasia
precancer transformation zone
Diagnosis. Cytological research of smears allows to find the cells of basal and
parabasal layers with signs of dyskariosis.
Histochemical research in patients with dysplasia show a drastic lowering of
glycogen in cells up to full its absence and changes of tissue enzymes activity.
Cytogenetic researches testify that under this pathology the cells with tetraploid
and pentaploid number of chromosomes appeared.
For diagnosis verification it is necessary to perform biopsy with the following
histological research.
Leukoplakia with atypia
Clinically it does not differ from the simple leukoplakia. The processes of
keratinization of the cells in this disease are mistologicaly marked to be reinforced
as compared with leukoplakia. Cytological research of the stratified squamous
epithelium reveals cells without nucleus at simple leukoplakia. Basal and parabasal
cells without nucleoses are also present in the patients with leukoplakia and atypia.
Erythroplakia
It is a prettily heterogeneous form of dyskeratoses. The changes of cervical mucous
membrane are in thinning and keratinizing of epithelium. It looks like scarlet area
in the result of translucence of the basal membrane cells through thinned epithelial
layer. It easily bleeds at contact. The seats are single or plural with transition on
fornices and vaginal walls. Thinning of epithelial layer to 1-2 layers with nuclear
atypia and cellular polymorphism is revealed during the histological research.
Glandular hyperplasia with atypia
Local hyperplasy of the glands that looks like a clew, similar to endometrial glands
at histological research are found. The glands which have different form and size
are covered by epithelium, that is unlike the cervical one.
Treatment of precancer lesions is made by diathermic excision, cryosurgical
and laser destruction. The most radical and less traumatic method is laser
coagulation
PRECANCEROUS UTERINE DISEASES
(uterine carcinoma precursors)
According to international classification (1982), such processes as glandular
endometrial hyperplasia, cystic glandular endometrial hyperplasia, endometrial
polyps belong to benign endometrial diseases.
Glandular endometrial hyperplasia with cellular proliferation, adenomatous
hyperplasia and adenomatous polyps are precancerous utenne diseases
Cystic glandular hyperplasia, which is found in postmenopausal women or in
reproductive period belongs to precancerous uterine lesions
Glandular endometrial hyperplasia and cystic glandular endometrial hyperplasia
are different stages of the same process. Difference between them is presence or
absence of cysts in endometrial hyperplasia Atypical cellular signs at these
diseases are not present The common endometrial polyp is made up of endometrial
tissue.
Atypical adenomatous hyperplasia is characterized by structural rearrangement and
more intensive proliferation of glandular elements comparing with other types of
hyperplasia.
Ethiology. The main causes of endometrial hyperplastic processes are different
hormonal disorders at hypothalamic-pituitary-ovarian levels.
Factors affecting the risk of endometrial hyperplasia are diabetes melhtus, late
menopause, women who have never childbeared.
Clinic. The precancerous processes manifest with acyclic uterine bleeding which
can be either appreciable or insignificant, but they are continuous More often these
bleedings arise after some weeks or months delay of menses. Cyclic bleedings
which appear during menses and last for a long period of time may be also present
Reproductive age women complain of infertility as a result of anovulation
Diagnosis. Bimanual examination doesn't find out abnormalities. Sometimes,
insignificant enlargement of uterus may be revealed at the examination.
Ultrasound examination of uterine cavity determines the endometrial depth At
glandular-cystic hyperplasia echogenic inclusions are up to 1cm in size,
madenomatosis — up to 2-3 cm Endometrial heterogenity, presence of small
amount of inclusions are the characteristic signs for endometrial processes
Endometrial polyp is characterised by legible contours and distinct borders
between the formation in uterine cavity and its walls Hysteroscopy, hysterography
can also be used for diagnosis that gives a possibility to research uterine cavity,
determine the location of pathological process
It is necessary to start the treatment from the uterine curettage. Indication to
hormonal therapy is histological confirmation of uterine hyperplasia. Progestins
are the medications of choice because of hyperestrogenemia. Oxyprogesterone
acetate should be taken on the 12-14 days of reproductive cycle once per month
during 5-6 cycles at reproductive age. In case of polyposis it should be taken twice
per month at 12 and 19 days of reproductive cycle. In menopausal women it should
be prescribed once or twice per week during 5-6 months, then the dose is gradually
reduced. Androgens may be prescribed these menopausal patients. Surgical
intervention should be performed in case of no efficiency from hormonal therapy,
its contraindications.
IV. Control questions and tasks
1. Classification of precancerous diseases of the vulva.
2. What is erythroplakia?
3. What is leukoplakia?
4. Classification of dysplasia.
5. What diseases are considered precancerous uterine diseases?
6. Clinic, diagnostics, treatment of endometrial polyp.
7. Treatment of leukoplakia and kraurosis vulvae.
8. Therapeutic methods of uterus cervix erosion.
CERVICAL CARCINOMA
Epidemiology. Cervical carcinoma is a common gynecologic malignancy. The
average age of diagnosis for invasive cervical cancer is approximately 50. During
the last years a tendency to increasing incidence of cervical carcinoma in young
women is maked. Women relating to early sexual intercourse with multiple
partners have this disease more frequent. Squamous cell carcinoma is practically
never encountered in virgins. It is caused by the carcinogen or promoting factor
that is sexually transmitted.
Etiology. Sexually-transmitted diseases are infected by herpes simplex viruses of
2-serotype (HSV-2) or by human papillomavirus (HPV-16/18, 29/31, 35), that can
stay for a long time in the latent form. They are the causes of cervical cancer.
Cervical carcinoma may be intraepithelial (preinvasive), microinvasive (growth of
the process into stroma on the depth up to 0,5 cm beneath from basal membrane)
and invasive one.
Histologically there have been distinguished:
 squamous cell keratinous carcinoma
 squamous cell nonkeratinous carcinoma
 adenocarcinoma
 clear cell adenocarcinoma
 dimorphic adeno-squamous cell carcinoma
Highly-differentiated,
moderate-differentiated
and
low-
differentiated
(or
undifferentiated) cancers have been distinguished according to the potential
malignancy.
Forms of tumor growth are: endophytic, exophytic, mixed.
At exophytic form a tumor grows into vagina, resembling a cauliflower and is able
to fill into vagina. The endophytic form is characterized by tumor growing into the
muscular layer of the cervix. As a result of this cervix enlarges and consolidates.
During tumor disintegration a crater ulcer is formed. A mixed pattern of cervical
carcinoma growth has signs of both endophytic and exophytic ones. Cervical
carcinoma can be spread on the uterine body, parametrium and vagina.
Regional lymphatic nodes are situated around the cervix (obturator lymph nodes,
general iliac, sacral, parasacral ones.
Clinic. It depends on the process stage. The duration of preinvasive and
microinvasive cancer is without any symptoms (preclinical stage). Serous or
serous-bloody discharge, contact bleeding after sexual intercourse, vaginal
examination, speculum examination may be used in the first stage. Pain in the
hypogastrium and back, serous-purulent discharge, resembling meat slops with
unpleasant smell (caused by lymph and blood effluence during tumor
disintegration) on the second and third stage appears. Patients' general state is
suffered. Fast tiredness and irritability can appear. The tumor can erode urinary
bladder and rectum due to growing inside of them. Constipation and urinary
disorders can occur in the result of this.
Diagnosis. The diagnosis is made after the speculum examination. The form of
vaginal part of the cervix, its dimensions and anatomic state is determined. Patients
with suspicion of cervical carcinoma should be obligatory examined per rectum.
These examinations are called as rectovaginal and rectoabdominal. It allows to
estimate the state of lateral and back parametria and uterine cervix better.
The cytological examination of the cervical canal and uterine secretion is the
method of early diagnosis of the cervical carcinoma.
Microscopic evaluation of smears is made by Papanicolau method (Pap smear
screening):
 I type — unaltered epithelium
 II-a type — inflammatory process
 II-b type — proliferation, metaplasia, hyperkeratosis, (at suitable clinical
picture they are interpreted as polyp, simple leuloplakia, endocervicosis)
 III-a type — mild, moderate dyplasia on the background of benign process
and unaltered epithelium
 III-b type — severe dysplasia of squamosus epithelium on the background
of benign process and in the region of unaltered epithelium
 IV type — suspicion of malignization intraepithelial cancer
 V type — cancer
 VI type — the smear is uninformative (the material was taken wrongly)
For the patients with III-V types of smears for confirmation of diagnosis simple
and broadened colposcopy, and histological research must be held. Patients with III
type of smears undergo regular medical monitoring. Colposcopy (simple and
broadened) is used for the early diagnosis.
Treatment is performed by oncogynecologysts according to the process' invasion.
The intraepithelial and microinvasive cancer in young women undergo surgical
treatment by cervical conization or its amputation. In the middle-aged or elderly
women with uterine myoma, or ovarian cyst presence it is expedient to perform
total hysterectomy with adnexa. The I-b - II stage of cancer are treated by
combined (radiation + surgery) or combined-radical method (if contraindications
for surgical intervention are present). Surgical intervention foresees the total
hysterectomy or Wertheim's operation (removal of the uterus with its adnexa, the
upper third of vagina and cellular tissue with regional lymphatic nodes). Treatment
of cervical carcinoma at the III stage is performed by combined-radical method:
distant irradiation of the initial focus and parametria followed by intracavitary
curie-therapy. Patients with stage IV are treated individually, the therapy is usually
symptomatic.
ENDOMETRIAL CARCINOMA
Endometrial carcinoma belongs to hormone-sensitive diseases. Continuously
increased estrogen production leads to excessive endometrial proliferation with
trans formation -into malignant tumor. Immune status of organism, virus infection,
genetic disorders play an important role in the development of this disease.
Obesity, diabetes mellitus are classically associated with endometrial carcinoma
and, therefore, qualified as risk factors.
Morphologically: adenocarcinoma, adenoacanthoma, clear cell meso-nephroid
adenocarcinoma, adenosquamous carcinoma, undifferentiated cancer are the
subtypes.
According to International classification, adenocarcinoma is classified into well,
moderate and poorly differentiated tumors.
Clinic. Abnormal uterine bleeding is the most important symptom of endometrial
cancer. Women in menopause may have abnormal bleeding or watery discharge
(lymphorhea) from vagina. Pain is the late symptom of endometrial cancer. At first
it is the result of excretions accumulation in the uterine cavity. It is dull in case of
peritoneal, adjacent organs or nervous nodes involvement. If the pathological
process is extended into adjacent organs following symptoms would be present:
revealing of mucus and blood in the feces, coprostasis — in case of rectal tumor;
hematuria — in case of urinary bladder involvement; hydronephrosis as a result of
uterher's compression.
There are three types of cancer clinical course.
Slow, rather favourable clinical course. This form is observed in patients with
significant hyperestrogenemia and lipids and carbohydrates dysmetabolism
impairment. Continuous uterine bleeding as a result of endometrial hyperplasia is
the most common symptom. Lymphatic way of metastasing is absent.
Histologycally, it is well-differentiated cancer with superficial invasion of the
myometrium.
Unfavourable clinical course. Metabolism disorder is absent The course of the
disease is rather short Endometrial carcinoma involves all layers of myometrium,
extends to cervix, parametrium and vagina It is a poorly differentiated tumor
Acute, extremely unfavourable clinical course. It is characterised by
unfavourable factors combination, such as deep extension of tumor, lymph nodes
and peritoneal metastases "Ovarian" type of metastases would be present It is
characterised by ascitis and omentum metastases
Diagnosis is made basing on history, clinics, physical and pelvic examination.
Other additional examinations should be performed, including ultrasonography,
cytological sampling of the endometrial cavity, hysteroscopy , hysterography,
fractional curettage with the cytological examination
Treatment. Surgical, combined treatment, combining of radiation and hormones
should be used.
UTERINE SARCOMA
All not epithelial malignant tumors belong to sarcomas. Presence of uterine
myoma in pre- and postmenopausal women, especially during its fast growing
belong to the risk factors of uterine sarcomas. There are four histological types of
uterine sarcomas:
 leiomyosarcoma
 endometrial stromal sarcoma
 carcinosarcoma (malignant mixed homologous mesodermal tumor)
 mixed heterologous mesodermal tumor
 other types of sarcomas
Clinical findings. Uterine bleeding and pelvic pain are the most common
presenting symptoms.
General weakness, weight loss, subfebril temperature for a long period of time are
the symptoms of uterine sarcoma presence for a long period of time.
Metastasis. The preferential way of spread is via the bloodstream. Other less
frequent ways of spread are via the lymph nodes and by contiguity.
Diagnosis. In many cases, the diagnosis is an unexpected finding at the time of
hysterectomy done for other indications. Sampling research of the endometrial
cavity either by biopsy and curettage can assist in diagnosis less than 50% of cases
owing to the fact that many of these tumors are intramural and thus without
endometrial extension. Hysterography or hysterocervicography should be
performed. Investigation of the adjacent organs should be recommended in all
types of uterine sarcomas.
Plain film of breast, liver and X-ray examination of skeleton should be prescribed
for diagnostics of distant metastases.
Treatment. The preferred treatment is total abdominal hysterectomy and bilateral
salpingo-oophorectomy.
MALIGNANT OVARIAN NEOPLASMS
Most of the malignant neoplasms that arise in the ovary fall into three categories:
primary cancer (neoplasms derived from the ovarian surface epithelium, i.e.
epithelial
tumors),
secondary
(neoplasms
derived
from
papillary
or
pseudomucinous cystadenomas), metastatic (intestinal and breasts' metastasis).
Etiology. Ovarian tumors belong to hormonal active tumors. One should
remember that unblastomatic unproliferative processes (follicle, luteal cysts) are
the results of pituitary and ovarian hormones disbalance. The observation that
patients with breast cancer have a two fold increase in the risk of developing of
ovarian cancer supports the concept that hormones play an important role in the
cause of ovarian cancer.
Malignant ovarian neoplasms are usually categorized according to the origin of the
cell and are similar to their deign counterparts:
 malignant epithelial cell tumors, which are the most common type, 46-48%
 malignant germ cell tumors, 10-14%
 malignant stromal cell tumors, 4,7%
There are malignant tumors with inside and outside growing. Mixed tumors are
also common.
Epithelial cell ovarian carcinoma may reach both small and large sizes, they are
typically multiloculated and often have external excrescencies on otherwise
smooth capsular surface. The walls of malignant cysts have different thickness,
and, as a rule, have papillary injections on the inner surface. Epithelial tumors
haven't cysts, they are soft. They are small in sizes, with smooth surface and grow
in the direction of the adjacent organs.
Sometimes the metastatic cancer can appear in the ovaries. The term Krukenberg
tumor describes the ovarian tumor that is metastatic from other sites such as the
gastrointestinal tract (80% from stomach, remainder from colon, breast, and
endometrium). Most of these tumors are characterized as infiltrative, mucinous
carcinoma of predominantly signet-ring cell type and as bilateral and associated
with the widespread metastatic disease.
Ways of spread of ovarian cancer. Ovarian cancer can spread by means of
several pathways The neoplasm can directly invade adjacent organs such as the
small intestine, rectosigmoid, colon, peritoneum, omentum, uterus, fallopian
tubes, and broad ligament Spread can occur by means of the peritoneal fluid and
malignant cells can be implanted throughout the pelvis and abdominal cavity,
including the omentum, posterior cul-de-sac, mfundibulopelvic ligaments,
paracolic gutters, right diaphragm and capsule of the liver. Ascites can often
develop with peritoneal metasteses.
Dissemination may also occur through lymphatics to the uterine tube, uterus,
pelvic and paraaortic lymph nodes. Metastases occasionally are detected in distal
sites such as the supraclavicular or inguinal lymph nodes.
The least common way of spread is hematogenous dissemination. Hematogenous
metastases occur in the liver parenchyma, skin, and lungs.
Clinic. Early diagnosis of ovarian cancer is difficult, because symptoms are often
absent or vague until the neoplasm has attained a large size and metastasized. Even
large tumors usually produce nonspecific symptoms. Early symptoms include
vague sensations of pelvic or abdominal discomfort, urinary frequency, and
alterations in gastrointestinal function. Hemorrhage into the tumor or torsion of the
ovary containing neoplasm can produce sudden pain and other symptoms of acute
abdomen.
The physical findings in patients with ovarian neoplasms in early stages are similar
to benign ovanan cystadenomas. Usually, they are of small sizes, painless,
movable, with firm consistency. They are palpated on the back from the uterus.
The tumor may be palpated by means of rectal examination. One can feel the mass
within the cul-de-sac. The tumor may be fixed because it can fill the available
space in the pelvis or because the pedicle is very short (it looks like uterine
myoma).
Diagnosis. Pelvic examination is the main one in diagnostics of ovarian cancer
neoplasms. Physical findings in patients are absent if a tumor is of small sizes.
Bilateral tumors may be palpated on the sides of the pelvis, sometimes in the back
of the uterus. Malignant ovarian tumors are similarly irregular with nodular surface
and have the firm consistency. Ultrasonography should determine tumor location,
its internal surface. Ultrasonography is especially useful for uncertain physical
findings in case of obesity.
Laparoscopy with diagnostic purposes should be indicated for the patients for
revealing external peculiarities of the tumor, presence of dissemination and
metastases. Sometimes diagnostic laparotomy is necessary in the evaluation of
ovarian cancer.
Radiographic examination is valuable in the diagnosis of chest and abdominal
cavity revealing. X-ray examination of stomach and intestine is obligatory for
exception of metastatic ovarian cancer. Fibrogastroscopy and biopsy, pneumopelviog -aphy may be useful for diagnosis.
Lymphography is of value in the diagnosis of dysgerminoma when lymphogenic
way of spread is the main one. In 30% of patients sacral metastases are present.
Treatment. All histologic types of ovarian carcinoma are threated in the same
way. The standard surgical procedure for carcinoma of the ovary is total abdominal
hysterectomy and bilateral salpingoophorectomy. A partial or complete
omentectomy should be performed, and in the advanced disease, an attempt should
be made to resect as much metastatic tumor as possible.
The patient whose neoplasm has spread beyond the ovary is initially a candidate
for chemotherapy even if all tumor has been resected. Chemotherapy is usually
advocated for women with all stages of disease. A variety of drugs are active
against the ovarian cancer. Such of them as Methotrexate, Cyclophosphan,
Sarcolizine are emerhed as drugs for chemotherapy. Combination chemotherapy
may be more effective than single-agent chemotherapy in patients with bulky
residual tumor, but it is also more toxic. Combination of such agents as Cyclophosphane+Phtoruracil;
Cyclophosphane+Methotrexate+Phtoruracil;
Cyclophos-
phane+Adriablastine+Cisplatin should be prescribed. Tiotef and Cisplatin should
be administrated intraperitoneally.
Dysgerminoma
Dysgerminoma is the most common malignant germ cell tumor which is arising
from undifferenting gonades that are present in the ovarian sinus.
Clinic. The tumor is common in the infantile patients of 30 years of age. Patients
generally can observe pelvic or abdominal mass, abdominal enlargement or pain.
The duration of symptoms ranges from 1 month to 2 years with a median of 4
months. The metastases are present in lungs.
Diagnosis is difficult and it is based on the results of clinical findings, laparoscopy and histologic investigation results.
Treatment is surgical with the following radiation therapy and chemotherapy.
Ovarian teratoblastoma
Ovarian teratoblastoma is a rare malignant tumor which is found in childhood in
juvenile period.
Clinic. Pain in the lower part of the abdomen and general weakness are common.
In the advanced cases ascites is present. Metastatses arise very quickly.
Diagnosis is based on the histologic results.
Treatment is surgical with the following radiation therapy.
ADENOCARCINOMA OF THE FALLOPIAN TUBE
Adenocarcinoma of the fallopian tube is one of the rarest malignancies of the
female genital tract It may developed pnmanly (from utenne tube) secondary, or
metastatically (from lesions arising in the adjacent organs such as uterus and
ovanes). Primarily the disease affects the older women. The average age is 40-55
years that had chronic tubal inflammation for a long penod of time. The process is
always unilateral.
Adenocarcinoma of the fallopian tube has pappilary, glandular-papillarty,
papillary-solid and solid structure. The process can quickly metastase inside the
pelvis.
Clinic. Most patients with tubal carcinoma are asymptomatic, and diagnosis is
made only after the patient has undergone surgical exploration for a pelvic mass A
few patients have symptoms such as vaginal bleeding or discharge, lower
abdominal pain, abdominal distension and pressure. In many cases these symptoms
are vague and nonspecific.
Diagnosis. Ultrasonography and laparoscopy, cytologic investigation of the uterine
aspirate can prove the diagnosis.
Treatment is surgical.
CANCER OF EXTERNAL GENITAL ORGANS (VULVAR CANCER)
Cancer of external genital organs is a malignant epithelial tumor, that appears in
women during menopause and looks like infiltration, dense nodes or papilar
formations. Ulceration is possible. Precancer diseases come before the appearing
of neoplasm. Late puberty, early menopause and high fertility are typical for the
patients with vulvar carcinoma. Frequently vulvar carcinoma is combined with
obesity and diabetes mellitus.
Exophytic, nodular, ulcerous and infiltrative forms of the tumor are distinguished.
Clinical manifestations. The main symptoms are itching, burning, pain, purulenthemorrhagic discharge. Pain of tumors is usually localized in the region of clitoris.
Hemorragic discharge can appear at tumor disintegration.
Final diagnosis is made basing on the histological research.
Metastasing happens into nodes of inguinal-femoral collector.
Treatment is surgical. Vulvectomy and bilateral inguinal lymphadenectomy
(Ducken's operation), combined treatment (vulvectomy and radiotherapy) are used.
Radiotherapy is performed before the operation.
CARCINOMA OF THE VAGINA
Carcinoma of the vagina can be primary and metastatic. More frequently women
can have cancer in climacteric period and after menopause. Cancer canappear in
the aged women with long-termed decubital ulcer due to its infecting and
traumatizing. Exophytic (as cauliflower) or endophytic infiltrative growth is
observed. Histologically carcinoma of the vagina is divided into the squamous cell
keratinizing carcinoma, non-keratinizing and adenocarcinoma.
Clinical manifestations. The purulent-hemorrhagic discharge, pain, disturbance of
urination, signs of general intoxication are common unexpectable. Bleeding can
occur at disintegration of the tumor. Nerves are pressed, ruined and patients feel
pain if a tumor spreads to the underlying tissues, paravaginal cellular tissue.
Final diagnosis is made after biopsy.
Treatment. Carcinoma of the vagina is treated by the combined radiotherapy. Xray or gamma-ray telethepary with insertion of radioactive preparations into vagina
are used.
IV. Control questions and tasks
1. What is the Papanicolau method?
2. What are the forms of cervical carcinoma growth?
3. Diagnostic methods of vagina cancer.
4. Morphologically classification of endometrial carcinoma.
5. What kind the treatment should be used for endometrial carcinoma?
6. Stages of Primary Carcinoma of the ovary
7. What treatment is used for adenocarcinoma of the fallopian tube?
8. Stages of uterus cervix cancer.
9. Stages of uterus body cancer.
10. Classification of ovary cancer.
11. Methods of treatment.
OVARIAN TUMORS CLASSIFICATION
Only histologic signs can give a possibility to distinguish benign and malignant
ovarian tumor. From the prognostic or survival standpoint, however tumor grade
remains the most important factor for all the ovarian tumors.
Histologic classification of ovarian tumors is presented below.
I. Epithelial tumors:
A.
Serous
B.
Mucinous
C.
Endometriod
D.
Clear cell
E.
Brenner
F.
Mixed epithelial
G.
Undifferentiated
H. Unclassified.
There are benign and malignant tumors in each of these groups of neoplasms
II. Sex cord stromal tumors:
A.
Granulosastromal cell
B.
Androblastoma
C.
Gynandroblastoma
D.
Unclassified
III.Lipid cell tumors
IV. Germ cell tumors:
A.
Dysgerminoma
B.
Endodermal sinus tumor
C.
Embryonal carcinoma
D.
Polyembryoma
E.
Choriocarcinoma
F.
Teratoma
G.
Mixed forms
V. Gonadoblastoma:
A.
Only blastoma (without any forms);
B.
Mixed with disgerminoma and other forms of germ cell tumors.
VI. Soft tissue tumors not specific to the ovary.
VII. Unclassified tumors.
VIII.Secondary (metabolic) tumors.
VIII. Tumor-like conditions:
A.
Pregnancy luteoma
B.
Ovarian stroma hyperplasia and hyperkeratosis
C.
Considerable ovarian edema
D.
Functional follicle cyst and luteal cyst
E.
Multiple luteal follicle cysts and (or) luteal cysts
F.
Endometriosis
G.
Superficial
epithelial
cysts-inclusions
H. Simple cysts
I. Inflammatory processes
J. Paraovarian cysts
Adenoma
Malignum
Barrel-Shaped
Cervix
A virulent adenocarcinoma of the cervix that histologically
consists of glands that appear well differentiated (minimal
deviation adenocarcinoma).
A cervix containing a large carcinoma, generally of
endocervical origin, that has replaced much of the cervix,
causing its diameter to widen (usually > 4 cm).
A form of radiation therapy in which the source is placed close
to the tumor. The application may be in the form of needles
Brachytherapy
implanted into the tumor (interstitial therapy) or into the vagina
or cervical canal (internal therapy). For cervical tumors, an
intracervical tandem and vaginal ovoids (colpostats) are usually
used.
Endophytic
Exophytic
A term used to describe a tumor that begins in the endocervical
canal.
A term used to describe a cervical tumor that grows on the
outside surface primarily of the cervix (portio).
Extrafascial
An operation that develops the pubocervical fascia to allow
Hysterectomy
total removal of the cervix and uterus (class I hysterectomy).
A system that delivers brachytherapy to cervical carcinomas by
Fletcher-Suit
use of a tandem in the cervical canal and ovoids (colpostats) in
Applicator
Glassy
the vagina.
Cell A virulent adenosquamous carcinoma that occurs in the cervix
Carcinoma
Microinvasive
Carcinoma
Modified Radical
Hysterectomy
and metastasizes early in the course of the disease.
A small (stage IA) carcinoma detected by microscopic
examination with little or no risk of spread to regional lymph
nodes (see text for detailed discussion).
An operation that removes the uterus and cervix and some
paracervical tissues but does not dissect the ureters distal to the
uterine artery (class II hysterectomy).
An extensive pelvic operation usually employed to treat a
Pelvic
Exenteration
central pelvic recurrence of cervical carcinoma after radiation.
A total exenteration involves removal of the bladder, uterus,
cervix, and rectum. An anterior exenteration spares the rectum,
whereas a posterior exenteration spares the bladder.
Persistent Tumor
The identification of invasive disease at the site of primary
therapy less than 6 months after therapy.
A term used in radiation therapy of carcinoma of the cervix to
Point A
identify a point 2 cm above the external os of the cervix and 2
cm lateral to the cervical canal.
A term used in the radiation treatment of carcinoma of the
Point B
cervix to identify a point 3 cm lateral to point A or 5 cm from
the cervical canal.
Radical
An operation that removes the uterus, upper third of the vagina,
Hysterectomy
cervix, and paracervical-parametrial tissues. The pelvic ureters
are dissected to the uterovesical junction. It is usually combined
with a pelvic lymph node dissection (class III hysterectomy).
Recurrent Tumor
The identification of invasive disease 6 months or more after
therapy.
Stage I: Tumor confined to the cervix
Stage IA: Microinvasion (preclinical)
Stage IB: All other cases confined to the cervix
Stage IIA: Tumor spread to the upper two thirds of the vagina
Summary
of Stage IIB: Tumor spread to paracervical tissue but not to the
Stages
of pelvic walls
Carcinoma.
Stage IIIA: Tumor spread to the lower third of the vagina
Stage IIIB: Tumor spread to the pelvic wall or obstruction of
either ureter by tumor
Stage IV: Tumor spread to the mucosa of the bladder or rectum
or outside the pelvis.
A form of radiation with placement of the radioactive source at
Teletherapy
a distance from the patient (external therapy). It is usually used
to treat the pelvis and occasionally the paraaortic nodes in
patients with cervical carcinoma.
Verrucous
A wart-appearing, well-differentiated squamous malignancy
Carcinoma
that rarely metastasizes.
MALIGNANT OVARIAN NEOPLASMS
Most of the malignant neoplasms that arise in the ovary fall into three
categories: primary cancer (neoplasms derived from the ovarian surface epithelium,
i.e. epithelial tumors), secondary (neoplasms derived from papillary or
pseudomucinous cystadenomas), metastatic (intestinal and breasts' metastasis).
Ovarian cancer is the fourth most common of all cancers of women having the
frequency of 15-20%. The risk increases with age. More often it occurs in women
at the age of 45-50. Rarely it is found in women of ealier age. There is considerable
worldwide variation in the incidence of the ovarian cancer. There is a higher
incidence of ovarian cancer in Sweden 15,1 per 100.00 women, Estonia — 14,2 per
100.00 of population, in Ukraine — 7,3 per 100.000 women.
Etiology. Ovarian tumors belong to hormonal active tumors. Epidemiolog and
experimental investigations of ovarian cancer reveal impairment of menstru; function
in these tumors.
The certain epidemiologic factors associated with the development of ovarii
cancer include low parity, decreased fertility and delayed childbearing. All < these
factors lead to hormonal disbalance in the organism.
Recently, demonstration of the genetic inheritance of ovarian cancer h;
revealed an important information regarding the possible etiology of the diseas
The relationship between the benign ovarian neoplasm and its maligna]
counterpart is clinically important. If the benign counterpart is found in the patie: the
removal of both ovaries is necessary, because of the possibility of futu: malignant
transformation in the remaining ovary. The decision concerning tl removal of one
or both ovaries, however, must be individual and is based on tl age, type of tumor,
and future risks. Some investigators have suggested that bilateral oophorectomy in
the patients over 40 years should be performed, gives a possibility to decrease the
ovarian cancer development. There is connection between breast cancer and ovarian
tumors. The incidence of ovaric cancer in these women is in 10 times higher than in
healthy women. There dependence between endometrial hyperplastic processes and
ovarian cancer.
One should remember that unblastomatic unproliferative processes (follicl luteal
cysts) are the results of pituitary and ovarian hormones disbalance. Tl observation
that patients with breast cancer have a two fold increase in the ri: of developing of
ovarian cancer supports the concept that hormones play s important role in the
cause of ovarian cancer.
Malignant ovarian neoplasms are usually categorized according to the orig of the
cell and are similar to their deign counterparts:
• malignant epithelial cell tumors, which are the most common type, 46-48
• malignant germ cell tumors, 10-14%
• malignant stromal cell tumors, 4,7%
There are malignant tumors with inside and outside growing. Mixed tumo are
also common.
Epithelial cell ovarian carcinoma may reach both small and large sizes, thi are
typically multiloculated and often have external excrescencies on otherwi smooth
capsular surface. The walls of malignant cysts have different thicknes and, as a rule,
have papillary injections on the inner surface (fig. 176). Epitheli tumors haven't
cysts, they are soft. They are small in sizes, with smooth surfa and grow in the
direction of the adjacent organs.
Sometimes the metastatic cancer can appear in the ovaries. The ter Krukenberg
tumor (fig. 174) describes the ovarian tumor that is metastatic fro other sites such as
the gastrointestinal tract (80% from stomach, remainder frocolon, breast, and
endometrium). Most of these tumors are characterized as infiltrative, mucinous
carcinoma of predominantly signet-ring cell type and as bilateral and associated
with the widespread metastatic disease.
Ways of spread of ovarian cancer. Ovarian cancer can spread by means of several
pathways. The neoplasm can directly invade adjacent organs such as the small
intestine, rectosigmoid, colon, peritoneum, omentum, uterus, fallopian tubes, and
broad ligament. Spread can occur by means of the peritoneal fluid and malignant
cells can be implanted throughout the pelvis and abdominal cavity, including the
omentum, posterior cul-de-sac, infundibulopelvic ligaments, paracolic gutters, right
diaphragm and capsule of the liver. Ascites can often develop wit1! peritoneal
metasteses.
Dissemination may also occur through lymphatics to the uterine tube, uterus,
pelvic and paraaortic lymph nodes (fig. 175). Metastases occasionally are detected in
distal sites such as the supraclavicular or inguinal lymph nodes.
The least common way of spread is hematogenous dissemination. Hemato-
genous metastases occur in the liver parenchyma, skin, and lungs.
Clinic. Early diagnosis of ovarian cancer is difficult, because symptoms are
often absent or vague until the neoplasm has attained a large size and metastasized.
Even large tumors usually produce nonspecific symptoms. Early symptoms include
vague sensations of pelvic or abdominal discomfort, urinary frequency, and
alterations in gastrointestinal function. When the neoplasm attains a diameter of
about 15 cm, it rises into abdominal cavity, which leads to feelings of abdominal
fullness or distension and early safety. Abdominal enlargement can also be
secondary to ascites. General weakness, weight loss, continuos dull pain in the
lower part of abdomen are common. In 15% of patients they experience abnormal
vaginal bleeding.
Hemorrhage into the tumor or torsion of the ovary containing neoplasm can produce
sudden pain and other symptoms of acute abdomen.
The physical findings in patients with ovarian neoplasms in early stages are
similar to benign ovarian cystadenomas. Usually, they are of small sizes, painless,
movable, with firm consistency. They are palpated on the back from the uterus. The
tumor may be palpated by means of rectal examination. One can feel the mass
within the cul-de-sac. The tumor may be fixed because it can fill the available space in
the pelvis or because the pedicle is very short (it looks like uterine myoma). The
tumor reaches large sizes and rises out of the pelvis. It is palpated in the abdomen.
The surface of tumor is nodular. There may be irregularities or even solid portions.
It is immobile. There is a high temperature as a result of products' disintegration
absorption in the case of tumor destruction. Anemia, leukocytosis and increased
ESR are common symptoms in early stages of tumor. If the tumor reaches large
sizes the symptoms of intestinal obstruction may be present. The dyspnoe may be
present at ascites. Bilaterality or fixation arouse the suspicion of malignancy.
TNM Stages of Primary Carcinoma of the Ovary
Stage Tumor (T)
N,
charac
Nodul
teristi
us
cs
M, Metastasis
IA
IB
1С
Growth limited to one ovary, capsule intact T IA
Growth limited to both ovaries, capsule intact, TIB
T IA or T IB with capsule ruptured, or with ascites, TIC
NO
NO
NO
MO
MO
MO
II A
Growth, involving one or both ovaries with uterus and NO
MO
II В
ПС
tubes
extension,
T to
IIAother pelvic tissues.
-//- with
extension
Obvious parametrial involvement, T IIB
NO
NO
MO
MO
with NO
*
MO
histologically confirmed microscopic seeding of
III В abdominal
-//- with histologically
confirmed
implants of abdominal NO
peritoneal surfaces,
T IIIA
MO
peritoneal surface none exceeding 2 cm in diameter, T
III С IIIB
-//- abdominal implants > 2cm in diameter, and/or NO
MO
T IIA or T IIB, ascites containing malignant cells
III A Tumor grossly limited to the true pelvis
IV
positive
retroperitoneal
or inguinal
Any T with
distant metastasis,
T IVnodes, T IIIC
Any N Ml
Any T
N1
MO
Diagnosis. Pelvic examination is the main one in diagnostics of ovarian cancer
neoplasms. Physical findings in patients are absent if a tumor is of small sizes.
Bilateral tumors may be palpated on the sides of the pelvis, sometimes in the back
of the uterus. Malignant ovarian tumors are similarly irregular with nodular surface
and have the firm consistency. Ultrasonography should determine tumor location, its
internal surface. Ultrasonography is especially useful for uncertain physical
findings in case of obesity.
Percutaneous fine-needle aspiration is an accurate method of diagnosing of the
variety of tumors. It should not be used for the initial diagnosis of the ovarian tumor,
because the neoplasm should be treated by surgical excision. There is some risk
that a cystic neoplasm may rupture when aspirated.
Laparoscopy with diagnostic purposes should be indicated for the patients for
revealing external peculiarities of the tumor, presence of dissemination and
metastases. It is contrindicated for the patients that were previously operated, with
excessive weight, with large tumors.
Sometimes diagnostic laparotomy is necessary in the evaluation of ovarian
cancer. After skin incision a detailed inspection of pelvis and abdominal cavity
must be held. Smears for cytologic evaluation and biopsy should be performed. The
final diagnosis is made after cytologic and hystologic investigation.
Radiographic examination is valuable in the diagnosis of chest and abdominal
cavity revealing. X-ray examination of stomach and intestine is obligatory for
exception of metastatic ovarian cancer. Fibrogastroscopy and biopsy, pneumo-pelviog
-aphy may be useful for diagnosis.
Lymphography is of value in the diagnosis of dysgerminoma when lymphogenic
way of spread is the main one. In 30% of patients sacral metastases are present.
Treatment. All histologic types of ovarian carcinoma are threated in the same
way. The standard surgical procedure for carcinoma of the ovary is total abdominal
hysterectomy and bilateral salpingoophorectomy. A partial or complete
omentectomy should be performed, and in the advanced disease, an attempt should
be made to resect as much metastatic tumor as possible. The contralateral ovary and
fallopian tube are removed unless the conservation of fertility is important. The
contralateral ovary is resected because it has been shown to contain an occult
metastasis or primary carcinoma in 5% of patients.
It is a radical method of treatment for the patients with ovarian carcinoma in the I-II
stages. In the cases of advanced cancer (III-IV stages) the surgeon r^ust determine
the appropriate treatment after exploring the patient's abdomen. Some patients have
unrespectable cancer. In this case the surgeon should attempt to establish the
diagnosis by excising the involved ovary. If this is not feasible, a biopsy should be
obtained from the ovary or metastases. Several studies havе revealed that survival
of the patients with stage III-IV ovarian cancer is improved. Radiation therapy is
uneffective when there are large residual tumor masses, and treatment with many
chemotherapeutic regimens is also the most successful when residual tumor volume is
minimized. This type of surgery is referred to as cytore-ductive surgery.
Tla — cancer is limited by one ovary
Tib — cancer is limited by
two ovaries
T2a — cancer involves fallopian tube and uterus, but not extend to pelvic tissue
T3a — implants tumor grossly limited to the true pelvis, abdominal implants
Fig.175. Ovarian cancer (scheme of ovarian cancer).
Fig.176. Bilateral papillary cystadenocarcinoma
The patient whose neoplasm has spread beyond the ovary is initially a :andidate
for chemotherapy even if all tumor has been resected. Chemotherapy s usually
advocated for women with all stages of disease. A variety of drugs are ictive against
the ovarian cancer. Such of them as Methotrexate, Cyclophosphan, >arcolizine are
emerhed as drugs for chemotherapy. Combination chemotherapy nay be more
effective than single-agent chemotherapy in patients with bulky esidual tumor, but it
is also more toxic. Combination of such agents as Cyclopho-iphane+Phtoruracil;
Cyclophosphane+Methotrexate+Phtoruracil;
Cyclophos-
)hane+Adriablastine+Cisplatin should be prescribed. Tiotef and Cisplatin should )e
administrated intraperitoneally.
There is no difference between single-agent and combination therapy in the ;ases
of advanced cancer. You should remember that Cisplatin has Nephrotoxic effects,
and Adryamicin and Phtoruracil have cardiotoxic effects.
Prognosis. The overall survival rate for stage IA is 90-98%; for stage IB — t is
less than 68%, for stage II — 50%, for stage III — 10-15%. The overall survival
rate for ovarian cancer at 5 years is 28-30%.
Dysgerminoma
Dysgerminoma is the most common malignant germ cell tumor which is irising
from undifferenting gonades that are present in the ovarian sinus.
Clinic. The tumor is common in the infantile patients of 30 years of age.
3
atients generally can observe pelvic or abdominal mass, abdominal enlarge-nent
or pain. The duration of symptoms ranges from 1 month to 2 years with a nedian of
4 months. The metastases are present in lungs.
Diagnosis is difficult and it is based on the results of clinical findings, laparoscopy and histologic investigation results.
Treatment is surgical with the following radiation therapy and chemotherapy.
Ovarian teratoblastoma
Ovarian teratoblastoma is a rare malignant tumor which is found in childhood in
juvenile period.
Clinic. Pain in the lower part of the abdomen and general weakness are
common. In the advanced cases ascites is present. Metastatses arise very quickly.
Diagnosis is based on the histologic results.
Treatment is surgical with the following radiation therapy.
ADENOCARCINOMA OF THE FALLOPIAN TUBE
Adenocarcinoma of the fallopian tube is one of the rarest malignancies of the
female genital tract. It may developed primarily (from uterine tube) secondary, or
metastatically (from lesions arising in the adjacent organs such as uterus and
ovaries). Primarily the disease affects the older women. The average age is 40-55
years that had chronic tubal inflammation for a long period of time. The process is
always unilateral.
Adenocarcinoma of the fallopian tube has pappilary, glandular-papillarty,
papillary-solid and solid structure. The process can quickly metastase inside the
pelvis. Ascites is a rare associated finding. Distant metastases are relatively more
important for tubal carcinoma than for ovarian carcinoma. More than 50% of the
recurrences with tubal carcinoma appear outside the peritoneal cavity, although they
usually associated with intraperitoneal metastases.
Clinic. Most patients with tubal carcinoma are asymptomatic, and diagnosis is
made only after the patient has undergone surgical exploration for a pelvic mass. A
few patients have symptoms such as vaginal bleeding or discharge, lower
abdominal pain, abdominal distension and pressure. In many cases these symptoms are
vague and nonspecific. Postmenopausal bleeding or discharge may be a symptom.
The most common finding at examination is a pelvic or abdominal mass.
Diagnosis. Ultrasonography and laparoscopy, cytologic investigation of the
uterine aspirate can prove the diagnosis.
Treatment is surgical. Total abdominal hysterectomy and bilateral salpingo-ophorectomy
with the following radiation and chemotherapy are used.
BENIGN AND MALIGNANT TUMORS OF EXTERNAL
GENITAL ORGANS AND VAGINA
Benign tumors of external genital organs (fibroma, myoma, lypoma, fibromyoma, hydradenoma, myxoma, angiofibroblastoma) are found rarely in any age
and are asymptomatic. Nodes of the tumor on pedicle or on the wide base reach
considerable size, sometimes hang down between hips. Malignant transformation of
the tumor is possible. Edema, hemorrhage, necrosis, secondary infection can
develop due to violation of blood supply.
Fibroma is a rare tumor arising from connective tissue and smooth muscle
elements of the vaginal wall. Depending on the arrangement of fibres, these tumors
can be soft, solid and dermoid. A tumor is situated in the depth of labia major or
under the vaginal mucosa. It grows slowly and gives no clinical symptoms until it
reaches considerable size, that creats discomfort in walking and sexual intercourse.
Only dermoid fibroma can become malignant.
Lipoma develops from adipose and connective tissue. It consists of mature
adipose tissue, that is divided into lobules by partitions of connective tissue. It is
localized in the region of pubis or labia major. The tumor is of soft consistency, it is
round in shape, rather mobile and is not adhered with skin. It grows slowly.
Myxoma is formed from remnants of mesenchyme. It is localized in the region
of pubis and labia major. It occurs more frequently in the aged women.
Hemangioma appears on the basis of congenital anomaly of skin vessels and
mucosa of sexual organs. The capillary and cavernous hemangioma have been
distinguished. It is localized in the region of labia major as a nodule of red or blue
colour. It grows rapidly reaching considerable size, sometimes passing to vagina
and cervix.
Papilloma is formed from the epithelium of labia major, has fibroepithelial
structure. Macroscopically it is a single or plural tumor on the pedicle or wide base
with granular surface. It should be differed from condyloma acuminata. Prognosis
is usually favorable, but for some conditions malignization is possible.
Treatment of all the forms of benign tumors is surgical (tumor removal).
CANCER OF EXTERNAL GENITAL ORGANS (VULVAR CANCER)
Cancer of external genital organs is a malignant epithelial tumor, that appears in
women during menopause and looks like infiltration, dense nodes or papilar
formations. Ulceration is possible (fig. 180). Precancer diseases come before the
appearing of neoplasm. Late puberty, early menopause and high fertility are typical for
the patients with vulvar carcinoma. Frequently vulvar carcinoma is combined with
obesity and diabetes mellitus.
Fig. 180. Cancer of clitoris
Exophytic, nodular, ulcerous and infiltrative forms of the tumor are distinguished.
Clinical manifestations. The main symptoms are itching, burning, pain,
purulent-hemorrhagic discharge. Pain of tumors is usually localized in the region of
clitoris. Hemorragic discharge can appear at tumor disintegration.
Final diagnosis is made basing on the histological research.
Metastasing happens into nodes of inguinal-femoral collector.
Treatment is, surgical. Vulvectomy and bilateral inguinal lymphadenectomy
(Ducken's operation), combined treatment (vulvectomy and radiotherapy) are used.
Radiotherapy is performed before the operation, and then after it they irradiate the
regions of primary lesion and regional metastasing.
Regular medical check-up of patients must be made by the end of their life.
CARCINOMA OF THE VAGINA
Carcinoma of the vagina can be primary and metastatic. More frequently women
can have cancer in climacteric period and after menopause. Cancer can appear in
the aged women with long-termed decubital ulcer due to its infecting and
traumatizing (fig. 181). Exophytic (as cauliflower) or endophytic infiltrative growth
is observed. Histologically carcinoma of the vagina is divided into the squamous
cell keratinizing carcinoma, non-keratinizing and adenocarcinoma.
Fig.181. Carcinoma of the vagina
Clinical manifestations. The purulent-hemorrhagic discharge, pain, disturbance
of urination, signs of general intoxication are common unexpectable. Bleeding can
occur at disintegration of the tumor. Nerves are pressed, ruined and patients feel
pain if a tumor spreads to the underlying tissues, paravaginal cellular tissue.
Neoplastic process can be spread on the adjacent organs like urinary bladder and
rectum. Disintegration of the tumor can cause formation of bladder-vaginal and
recto-vaginal fistulas. Hydro- and pyonephrosis, and later — uraemia can develop on
condition that the ureters are compressed.
One should differ carcinoma from decubitus, syphilitic and tuberculosis ulcers,
condilomas, endometriosis, chorioepithelioma, metastases of cervical and uterine
cancer into vagina.
Lymphatic cancer spread is more common: from upper one-third into iliac and
hypogastric lymph modes; from middle one-third into the sacral ones; from the
lower one-third into the inguinal lymphatic nodes.
Final diagnosis is made after biopsy.
Treatment Carcinoma of the vagina is treated by the combined radiotherapy. X-ray or
gamma-ray telethepary with insertion of radioactive preparations into vagina are
used.
Gestational Trophoblastic Disease : Hydatidiform Mole, Nonmetastatic and
Metastatic Gestational Trophoblastic Tumor: Diagnosis and Management
KEY TERMS AND DEFINITIONS
Impregnation of an inactive egg by a paternal haploid
Androgenesis
sperm that duplicates its chromosomes to provide a
diploid complement. This results in a complete mole.
A morphologic term applied to a highly malignant type of
Choriocarcinoma
trophoblastic neoplasia in which both the cytotrophoblast
and syncytiotrophoblast grow in a malignant fashion.
Complete Mole
Gestational
Trophoblastic Disease
(GTD)
A molar pregnancy with swelling of all placental villi.
Fetal tissues are absent.
Disease that results from the abnormal proliferation of
trophoblast associated with pregnancy. The disease is
considered persistent or recurrent if it remains active or
returns after therapeutic intervention.
A placental abnormality involving swollen placental villi
Hydatidiform Mole
and trophoblastic hyperplasia with loss of fetal blood
vessels. There are two types: partial and complete.
A variant of hydatidiform mole in which the hydropic villi
Invasive Mole
invade the myometrium or blood vessels. It may spread to
extrauterine sites.
Partial Mole
Placental-Site
Trophoblastic Tumor
A molar pregnancy with some normal and some swollen
villi plus fetal, cord, and/or amniotic membrane elements.
A rare type of GTD arising in the uterus that secretes
human
placental
lactogen
and
human
chorionic
gonadotrophin (HCG).
Gestational trophoblastic disease (GTD) refers to the spectrum of
abnormalities of the trophoblast associated with pregnancy. These neoplasias have
been known for hundreds of years, and they specifically secrete HCG. The
availability of extremely sensitive and specific assays to measure HCG allows
prediction of the clinical status of the disease as well as monitoring of treatment.
The initial use of methotrexate in 1956 by Li and associates to successfully treat
malignant trophoblastic disease completely altered the prognosis of patients with
these tumors and represented a milestone in the cure of human tumors by
chemotherapeutic agents.
KEY POINTS
•
Persistent abnormal bleeding following normal pregnancy, abortion, or ectopic
pregnancy should lead to a consideration of the diagnosis of GTD. The finding
of pulmonary nodules on chest radiograph after normal pregnancy suggests
GTD. The HCG is elevated in these situations.
•
A young woman with an unknown primary neoplasm or poorly explained
hyperthyroidism should have her serum HCG tested.
•
Approximately half the cases of GTD follow molar pregnancy, one fourth
follow normal pregnancy, and one fourth follow abortion or ectopic pregnancy.
•
The major risk factors for molar pregnancy include maternal age (older than 40
and younger than 20 years) and a history of molar pregnancy. There appears to
be an increased frequency of these diseases in Southeast Asia and Mexico.
•
The risk of hydatidiform mole is approximately 0.75 to 1.0 per 1000
pregnancies in the United States.
•
The risk of developing a second molar pregnancy after a primary mole is
approximately 20 to 40 times greater than the initial risk.
•
The monitoring of trophoblastic disease and its follow-up is accomplished by
the measurement of в-HCG.
•
Complete moles are of paternal origin, are diploid, and carry a 20% risk of
GTD sequelae.
•
Partial moles are of maternal and paternal origin, are triploid, and rarely are
followed by GTD, but require the same follow-up for potential malignant
sequelae as a complete mole.
•
The diagnosis of a molar pregnancy can be established with ultrasonography
and may coexist with a normal pregnancy.
•
Hydatidiform moles are effectively and safely evacuated from the uterus using
suction curettage.
•
Medical complications of hydatidiform mole include anemia, toxemia,
hyperthyroidism, hyperemesis gravidarum, cardiac failure, and rarely
pulmonary insufficiency.
•
Patients are classified into low- or high-risk categories. Low-risk categories
receive single agent chemotherapy, usually methotrexate. High-risk patients
receive combination chemotherapy, usually EMA/CO.
•
Low-risk patients have a cure rate of greater than 90%.
•
Patients with high-risk metastatic GTD are successfully treated with
chemotherapy in more than 70% of the cases.
•
Patients treated for GTD should not become pregnant for approximately 6 to
12 months after treatment to allow accurate assessment of HCG levels.
•
Fertility rates and pregnancy outcomes are similar in patients treated for GTD
compared with the general population.
•
Patients treated with EMA/CO regimens have an increased rate of second
malignancies, particularly hematologic.
CHARACTERISTICS
Trophoblastic
tissue
normally
shares
certain
characteristics
with
malignancies, such as the ability to divide rapidly, to invade locally, and
occasionally to metastasize to distant sites such as the lung, yet these activities
usually cease at the end of preg-nancy, and the trophoblasts disappear. However, in
GTD, abnormal growth and development continue beyond the end of pregnancy.
Hydatidiform Mole
A hydatidiform mole has three morphologic characteristics: (1) a mass of
vesicles (distended villi) that appear as large, grapelike dilations; (2) a loss of fetal
blood vessels, which are either diminished or absent from the villi; and (3)
hyperplasia of the syncytiotrophoblast and cytotrophoblast.
The terms complete mole and partial mole have been used to describe the
variations of molar pregnancies. With a complete mole, all placental villi are
swollen, and the fetus, cord, and amniotic membranes are absent. With partial
molar pregnancy, only some chorionic villi are swollen, and fetal tissues are
present, such as amniotic membrane, cord, or even rarely a full-term fetus. The
fetus is usually chromosomally abnormal. With a partial mole, the trophoblastic
hyperplasia is limited to the syncytiotrophoblast.
The genetics of molar pregnancy has been extensively studied. In normal
pregnancy, half the chromosomes of the conceptus are paternal and the other half
are maternal, resulting in a diploid content. In complete mole, only paternal
chromosomes are believed to be present; there are 46 chromosomes and nearly
always 46,XX, although a few moles with 46,XY karyotype have been reported.
The development of complete mole appears to result from the fertilization of an
“empty egg,” one with an absent or inactive nucleus. The haploid paternal set of
chromosomes from the sperm impregnate the inactive egg. These paternal
chromosomes then duplicate to give the diploid number, a process known as
androgenesis, the development of an embryo due only to chromosomes from an Xbearing sperm ( Fig. 35-2 ). In the rare case of complete mole with an XY
chromosomal content, the empty egg appears to be fertilized by two haploid sperm,
one X and one Y.
Incomplete, or partial, moles are usually triploid and have 69 chromosomes
of both maternal and paternal origin. The most common mechanism for the origin
of partial mole is a haploid egg being fertilized by two sperm, resulting in three
sets of chromosomes. Alternatively, triploidy could result when an abnormal
diploid sperm fertilizes the haploid egg. It is also possible for an abnormal diploid
egg to be fertilized by a haploid sperm, but this latter mechanism usually results in
an abnormal conceptus with congenital abnormalities rather than a partial mole.
Partial mole is often difficult to diagnose and may present as a missed abortion in
the second trimester. Although these fetuses are usually abnormal, Watson et al.
noted that some partial moles have occurred with phenotypically normal fetuses. In
such cases, the uterus is small for dates. As noted by Lage and associates, a few
partial moles are diploid, and these very rare cases may be less sensitive to
chemotherapy than triploid moles if subsequent GTD develops.
Partial moles are rarely associated with the subsequent development of
GTD. Bagshawe and colleagues reported that neoplasia requiring chemotherapy
occurs in approximately one in 200 cases of partial mole compared with one in 12
with complete mole. However, Rice and coworkers noted 16 of 240 partial moles
(6.6%) had malignant sequelae, all of which responded to chemotherapy. Goldstein
and colleagues summarized a number of published reports that indicated that GTD
followed partial mole in 39 of 1125 (3.5%) cases. Despite rare subsequent
malignancy, patients with partial moles need the same follow-up as those with
complete moles.
Choriocarcinoma
Choriocarcinomas are malignancies that occur after or in association with
pregnancy, although the same histologic tumor can develop without pregnancy as a
primary neoplasm in the ovaries. The prognosis for primary gonadal
choriocarcinomas, which also occur in testes, is worse than for those associated
with gestation.
The diagnosis is made histologically, and the term is applied to the finding
of malignant cytotrophoblast and syncytiotrophoblast. Chorionic villi are absent.
These tumors tend to be hemorrhagic and necrotic. The latter is common because
these tumors frequently outgrow their blood supply. Metastases are common.
Most, but not all, gestational choriocarcinomas develop after molar
pregnancies. Trophoblastic tissue normally regresses within 2 to 3 weeks after
delivery, including cells that may have spread to the lung. The normal processes
leading to this regression are unknown, but the finding of trophoblastic cells in the
uterus more than 3 weeks after delivery should lead one to consider the possibility
of choriocarcinoma.
It is important to recognize that persistent or metastatic GTD has several histologic
patterns. The level of HCG determines tumor activity and guides therapeutic
intervention.
Placental-Site Trophoblastic Tumor
The term placental-site trophoblastic tumor (trophoblastic pseudotumor) was
introduced by Young and Scully to describe a rare tumor that consists of excessive
groups of mononucleate and multinucleate trophoblastic cells at the implantation
site accompanied by an inflammatory cell reaction. Immunohistochemical studies
have shown that the cells of these tumors tend to stain more for human placental
lactogen than for HCG, and both HCG and human placental lactogen should be
monitored. The tumor can lead to hemorrhage and uterine perforation. It tends to
be locally invasive, and most patients do not develop metastases. Hysterectomy is
the treatment of choice. Baergen and associates reported 55 of their own patients,
and an additional 180 cases from a literature review. In the results of the combined
studies, there were 186 treated with hysterectomy. Ninety-four also received
chemotherapy. In the combined patient population, there was an 80% to 86%
survival rate at 48 months.
Chemotherapy is usually administered for metastatic disease when it occurs,
but is less effective with these tumors than with other gestational trophoblastic
tumors, which is another reason for prompt operative treatment. EMA/CO
(etoposide, high-dose methotrexate with citrovorin (folinic acid) rescue,
actinomycin D, cyclophosphamide, and vincristine [Oncovin]) has been reported
on by Ajithkumar and colleagues for the treatment of metastatic placental-site
trophoblastic tumor, achieving a response rate of 71% and a complete response rate
of 38%.
Materials for Self- assessment:
5.2 Questions for self-assessment.
1.
Clinic and diagnostics of precancerous diseases of the female reproductive
organs.
2.
Treatment of leukoplakia and vulvar kraurosis.
3.
Precancerous diseases of neck of uterus: clinic, diagnostics.
4.
Methods of treatment of cervical erosion.
5.
Classification of endometrial hyperplasia .
6.
Etiology, clinic, diagnostics, GPE.
7.
Principles of treatment of GPE.
8.
What processes on the neck of uterus do attribute to the diseases of
backgrounds?
9.
Basic clinical symptoms of vulvar cancer.
10.
Methods of diagnostics of vulvar cancer.
11.
Methods of treatment of vulvar cancer.
12.
Basic clinical symptoms of vulvar cancer.
13.
Methods of diagnostics of cancer of vagina .
14.
Pathogeny of cancer of neck of uterus.
15.
Stages of cancer of neck of uterus.
16.
Basic clinical symptoms of cancer of neck of uterus.
17.
Methods of diagnostics of cancer of neck of uterus.
18.
Methods of treatment of cancer of neck of uterus are depending on the stage of
distribution of process.
19.
What does result in the origin of cancer of body of uterus?
20.
Stages of cancer of body of uterus.
21. Transfer the symptoms of cancer of body of uterus.
22.Give description of clinical and histological forms of cancer of body of uterus..
23.What additional methods of diagnostics do use for suspicion on the cancer of
body of uterus?
24.Principles of treatment of cancer of body of uterus.
25.Classification of cancer of ovaries.
26.What basic clinical symptoms of cancer of ovaries do you know?
27.Transfer signs, what characteristic for the metastatichnogo, second and primary
cancer of ovaries.
28.Stages of distribution of cancer of ovaries.
29.Principles of diagnostics of cancer of ovaries.
30.Methods of treatment of cancer of ovaries.
31.Prognosis and prophylaxis of malignant diseases of womanish privy parts.
32.Principles of clinical supervision are after patients. Labour examination.
5.3. Practical works (task) which are executed on employment
1.Kuratsiya and thematic analysis of patients.
2.Improvement of practical skills of inspection.
3.To revise the set of educational sliding seats (tumours of uterus).
4.Conduct a differential diagnosis between the tumour of uterus and tumour of
appendages.
5.Take a swab on cytology.
6.Pick up necessary instruments for taking of aiming biopsy, aspiratsiynoy biopsy,
to aspiratsiynogo kyuretazhu.
7.Conduct the test of Shillera and estimate its results.
8.Untie a situation task.
5.4. Materials for self-control
Tasks for self-assessment.
№ 1. At sick And., at colposcopy research found out moderate displaziya on the
neck of uterus. What modern methods of treatment can be used for this pathology?
Answer: СО2 is a laser .
№ 2. At sick., 54 years, after the separate diagnostic scraping off of mucus shell of
uterus and cervical channel in connection with non-cyclic uterine bleeding found
out adenocarcinoma. What volume of inspection and treatment does it follow to
offer this patsientsi? What does the volume of medical interference depend vid?
Answer: the volume of medical interference depends on the stage of cancer
of neck of uterus.
№ 3. Sick 52, which during 7 did not have monthly, noticed periodic appearance
of insignificant blood colors excretions from vagini. At a review doctor – a
gynaecologist found out no changes from the side of genitaliy. However, taking
into account age of sick and appearance of blood colors excretions after 7- of
annual menopauzi, suspected the cancer of body of uterus and took a selection
from an uterus for cytological research. On a next day an answer is got, that
atypical cages are present in a stroke. The sick was immediately directed to
gynaecological permanent establishment
for the separate diagnostic scraping off of cavity of uterus with the purpose of
clarification of diagnosis. Diagnosis.
Answer: cancer of body of uterus.
№ 4. For the last 3 years with a medical and diagnostic purpose the separate
diagnostic scraping off of cervical channel and cavity of uterus was 5 times
conducted. An answer of histological research after every scraping off is polipoz of
endometria. Conservative treatment is uneffective. Diagnosis. Plan of subsequent
treatment.
Answer: adenomatoz of uterus. Ekstirpatsiya of uterus.
№ 5. Sick., 50 years, acted to the gynaecological separation with complaints about
pain at the bottom of stomach. For 5-6 months noticed multiplying a stomach. Had
3 births, 4 abortions. Long time treated oneself concerning inflammation of
appendages of uterus. Last 2 years for a gynaecologist did not inspect. Objectively:
a skin is pale. Lights, heart without features. A stomach is sickly in lower
departments, a free liquid is determined in an abdominal region. At a vaginal
inspection neck and vagina without features. An uterus is included in the
conglomerate of tumours, separately not konturuet'sya, a tumour achieves the level
of belly-button, dense, sickly. Put a previous diagnosis. Produce the plan of
research and treatment of sick.
Answer: A cancer of ovaries is in the started stage. Treatment must begin
from a chemotherapy.
Tests for self-assessment.
1. The sick 59 years appealed to the doctor in woman consultation by зI complaints
about the blood colors selection of sexual ways. Postmenopause 12 years. At a
vaginal inspection: external privy parts with the signs of age-old involution, neck
of uterus of not erosion, from a cervical channel there are insignificant blood
colors excretions. The uterus of ordinary sizes, appendages, not palpation. Vaults
are deep, no pain. What additional methods of research do need to be conducted
for clarification of diagnosis?
A. Diagnostic fractional curettage.
B. Laparоscopy.
C. Culdocentesis.
D. Broadened colposcopy.
E. Culdoscopy.
2. The sick 60 years grumbles about multiplying the sizes of stomach, wait loss,
asthenia, appearance of mazhuchikh of blood colors excretions from a vagina after
10 of menopauzi. Vaginal: an uterus is megascopic to 16 weeks pregnancy, dense.
Appendages are not determined. What diagnostic method of research must be
conducted?
A Laparoscopy.
B Ultrasonography.
C Diagnostic fractional curettage.
D Hysterosalpingography.
E Research of sex hormones.
3. The sick 58 years appealed to the doctor in woman consultation by complaints
about the blood colors selection of the sexual ways. Menopauza 8 years. At
gynaecological research: uterus something megascopic, dense by touch, limited in
mobile, the appendages of uterus are not determined, parametrii is free. At the
factious scraping off from the cavity of uterus it is got considerable
мозкоподIбний scraped off. What most credible diagnosis?
A. Cervical carcinoma.
B. Adenomyosis.
C. Chorionepitelioma.
D. Uterine sarcoma.
E. Ovarian carcinoma to produce hormones.
4. Sick 64 hospitalized with the uterine bleeding and anaemia. After 12-years-old
absence of menstruation 7-8 months ago at first watery discharge appeared from a
vagina, then - serozno- blood colors, to the type of "meat slops", there was pain at
the bottom of stomach. What pathology is most reliable?
A.
Uterine sarcoma.
B.
Uterine fibromioma.
C.
Molar pregnancy.
D.
Chorionepitelioma.
E.
Internal pelvic endometriosis.
5. Sick 52 hospitalized in a gynaecological separation complaints about a general
weakness, pain at the bottom of stomach. Menopauza 2 years. At a review,
multiplying the sizes of stomach, sign of astsitu is set. At bimanual research: the
neck of uterus is cylinder, clean. Body of uterus of small sizes, it is declined to the
right. On the left and behind hilly, painless immobile education pal'puet'sya vid an
uterus, dense consistency, by a size 12х15 see. What most credible diagnosis?
A. Uterine fibromioma.
B. Ovarian carcinoma.
C. Ovarian cyst (left).
D. Tuboovarian аbscess.
E. Pelvic endometriosis.
6. Sick 43 grumbles about the contact bleeding during the last 6 months At
bimanual research: the neck of uterus is megascopic in a size, limited in mobility.
In mirrors is a neck of uterus as a cauliflower. Tests of Worm and Shillera are
positive. What most reliable diagnosis?
A. Cervical pregnancy.
B. Cervical polyp.
C. Cervical carcinoma.
D. Cervical protruding myoma.
E. Leukoplakia.
7. On a reception to the doctor of woman consultation a woman appealed 50 years
with complaints about insignificant blood colors excretions from sexual ways after
sexual contacts. Menopauza 5 years. At a review it is discovered in mirrors: neck
of uterus of normal sizes, for peripheries on 13 hour is tumular education 0,5х1,0
see with unequal edges as a cauliflower, bleeds easily. At bimanual research of
pathology it is not discovered from one side an uterus and appendages. Your
diagnosis?
A Cervical carcinoma.
B Cervical erosion.
C Polyp of cervical canal.
D Еctropion.
E Erythroplakia.
8. For a woman the cancer of neck of uterus of in is 37 years diagnosed situ (0
stage). What most optimum volume of operative interference?
A Cervical conization.
B Hysterectomy whith not bilateral salpingooophorectomy.
C Total hysterectomy.
D Cervical cryosurgical destruction.
E Cervical laser destruction .
9. During an operation at sick 50 years found out papilyarna kistoma with the
germination of capsule. What most expedient volume of operative interference?
A Supracervical hysterectomy and bilateral salpingooophorectomy.
B Total hysterectomy.
C Adnexectomy.
D Removal of the ovarian cystoma.
E Removal of the ovarium.
10. The sick 55 years inspected for operative treatment in connection with the
cancer of body of uterus. It is discovered at chromocystoskopia, that the back wall
of urinary bladder infil'trovana and covered ulcers. In the analysis of urine found
out mikrohematuria. What stage of distribution of cancer process at sick?
AII а.
B III б.
C IV а.
D IV б.
E I.
11. A woman 49 years appealed to the gynaecologist. At a review – the
hypertrophy of vaginal part of neck of uterus, infiltration, spreads on part of
vagina. At a biopsy found out invasion ploskoklitinnu carcynoma. At vaginal
research found out the compression of parametrium area business, without
distribution on the lateral wall of cavity of pelvic. Specify the stage of cancer
process.
AІ А.
B ІІ Б.
C І Б.
D ІІ А.
E ІІІ.
12. a 52-years-old woman appealed with complaints about bleeding in menopauzi.
The separate diagnostic scraping off of cervical channel and cavity of uterus is
conducted is length of uterus on a probe 7 sm, in scrape it is not discovered from
the cervical channel of pathology, at histological research found out fabrics of
endometria elements of high-differentiated adenocarcynoma. It is not discovered
metastasis. What method of treatment is most rational?
A Chemotherapy.
B Hysterectomy.
C Radiation therapy.
D Hysterectomy and bilateral salpingooophorectomy.
E Hormonal therapy.
13. Be ill 23 hysterosalpingoskopia is done concerning primary sterileness. On a
sciagram: cavity of uterus of Т-similar form, uterine pipes are shortened, beady,
the output of contrasting matter in an abdominal region is not observed. For what
disease the most characteristic similar changes?
A Adenomyosis and endometriosis of the fallopian tube.
B Chronic salpingit by chlamidial ethiology.
C Malignant tumor of the fallopian tube.
D Tuberculosis of genital organs.
E All.
14. A woman 45 years grumbles about a making progress weakness during the last
6 weeks, discomfort and swelling of stomach. Did not lose mass of body, but
became apathetical. Constantly uses an alcohol. Objectively: a stomach is
megascopic in sizes, tense. Defecation is not broken. BRIDLES of organs of
abdominal region is a two-bit of astsitichnoy liquid; liver, buds, spleen without
changes, there are a few cysts in a left ovary, right – not vizualizuet'sya through
education, related to the stuffing-box. In urine is a norm. What most reliable
diagnosis?
A. Lіmphomа товстої кишки.
B. Cancer сигмоподібної кишки.
C. Carcinoma of the ovarian.
D. Alcohol diseases of liver.
E. Кrоna diseases.
15. Laparotomiya is executed the woman of 54 concerning large education at a
pelvis, which appeared the one-sided tumour of ovary with considerable metastases
in a stuffing-box. The most acceptable intraoperativna tactic provides for:
A. Removal of the сальника, uterus and boath ovarians with fallopian tube.
B. Biopsy сальника.
C. Ovarian biopsy.
D. Removal of the ovarian and metastasis у сальнику.
E. Removal of the сальника and boath ovarian with fallopian tube.
16. At sick 36 years during a prophylactic review in mirrors found out deformation
of neck of uterus by old post-natal breaks. At colposcopy research on a back lip
found out the fields of dysplasia. What must be done for clarification of diagnosis?
A. Cervical biopsy.
B. Diagnostic fractional curettage.
C. Cystoscopy.
D. Bacterioscopic examination.
E. Ultrasonography .
Variants of faithful answers: 1. A, 2. C 3.D, 4.A, 5.B, 6.C, 7.A, 8.A, 9.B, 10.C,
11.B, 12.D, 13.C, 14.C, 15.A, 16.A.
V. List of recommended literature
1. Danforth’s Obstetric and gynaecology.-Seventh edition.-1994.-P.959-1121
2. Gynecology.-Stephan Khmil, Zina Kuchma, Lesya Romanchuk.-2003.P.240-244; 276-279
3. Gynaecology illustrated. David McKay Hart, Jane Norman.-Fifth Edition.2000.-P.170-172