Endometrial Carcinoma

As part of MTP

1.   Ans. is b i.e. Ovarian carcinoma  

Clinical Consequences of Persistent Anovulation

1. Infertility°
2. Menstrual bleeding problems ranging from amenorrhea to irregular, heavy bleeding° (DUB). Most common menstrual disorder associated with anovulation is oligomenorrhea.°
3. Hirsutism°, Alopecia° and Acne.
4. Increased risk of Endometrial cancer° and perhaps, Breast cancer°.
5. Increased risk of Cardiovascular disease°.
6. Increased risk of Diabetes mellitus° in patients with insulin resistance.

Extra Edge :

Recommended investigations in case of anovulatory hyperandrogenic women (to exclude specific causes and problems).

In the presence of clinical signs of excess androgen stimulation – Two tests which should be done are :

1. Total testosterone levels
2. 17 – hydroxy progesterone morning and fasting.

Endometrial carcinoma

Ans. is d i.e. Early menopause

Friends, this is the most frequently asked question on Endometrial cancer. Mug up predisposing factors by heart. Endometrial carcinoma occurs as a result of unopposed estrogen exposure in body.

Predisposing factors are :

Family               Family history

Has                Hypertension

m                  Obesity

L                   Late menopause / Early menarche Diabetes

A                   Atypical endometrial hyperplasia

U                   Unopposed estrogen or increased estrogen in body as in :

• HRT
• Fibroid
• PCOD
• Feminizing ovarian Tumour

N                       Nulliparity

H/o infertility / menstrual irregularity

Mnemonic : Family has OLD AUNT

• Oral contraceptive pills (combined addition of Progesterone to HRT).
• Smoking (as it decreases leygir_tpf estrogen, decreases weight& is associated with earlier age at menopause).

• HRT
• Fibroid
• PCOD
• Feminizing ovarian Tumour

Ans. is a i.e. Predisposed by Diabetes mellitus, hypertension and obesity

Endometrial cancer :

• Most common in nulliparous females.°
• Age group : Peak incidence 60 years (6′”-7′^h decade most common).°

But in 25% cases can occur before menopause or in young females.

• Race : Most common in Jews (Unlike Ca cervix).
• Predisposing Factors : Already discussed in detail earlier. A combination of hypertension, diabetes and obesity in association with Endometrial Ca is known as Corpus Cancer Syndrome.
• Associated diseases : — Fibroid uterus° (as it also occurs in Nulliparous females)

— Cervical Polyps°

Pathology : Most common variant is Adenocarcinoma° (known as Endometroid and not Adenosquamous). Only 15-20% of Adenocarcinomas may have squamous differentiation.

Histology :

Endometrial carcinoma can be distinguished from hyperplasia by :

• Back to back arrangement of Glands°
• No intervening stroma°
• Desmoplastic stroma
• Extensive papillary pattern Squamous epithelium differentiation° Clinical features : A female of perimenopausal age group( 6^th -7¹” decade) presents with :
• Abnormal bleeding (90% cases) in the form of metrorrhagia menometrorrhagia, intermenstrual spotting, postmenopausal bledding
•  Discharge (1%) P/V : — Brown, watery offensive discharge — Watery discharge free from blood (hydrorrhea°).
• Pelvic pressure/discomfort.
• Referred pain in hypogastrium or both iliac fossae (Simpson’s pain).Pain           tsevere and tends to occur at the same time each day, lasting on 1-2 hrs (Important).
• In some older patients, bleeding may not occur due to cervical stenosis. causing hematometra/pyometra.

• Desmoplastic stroma°
• Extensive papillary pattern
• Squamous epithelium differentiation°

Clinical features : A female of perimenopausal age group( 6^th -7¹” decade) presents with :

• Abnormal bleeding (90% cases) in the form of metrorrhagia menometrorrhagia, intermenstrual spotting, postmenopausal bledding.
• Discharge (1%) P/V : — Brown, watery offensive discharge

— Watery discharge free from blood (hydrorrhea°).

• Pelvic pressure/discomfort.
• Referred pain in hypogastrium or both iliac fossae (Simpson’s pain).

Pain           tsevere and tends to occur at the same time each day, lasting on 1-2 hrs (Important).

In some older patients, bleeding may not occur due to cervical stenosis. causing hematometra/pyometra.

Ans. is c i.e. Stage IV

Ans. is a, b and c i.e. Penetration into half of myometrium; Clear cell tumour; and Papillary serous carcinom

Indications for lymph node (Pelvic and Para-aortic) dissection in Endometrial cancer (also Indications of poor Prognosis).

1. Tumour histology :

• Clear cell carcinoma
• Papillary serous carcinoma
• Squamous carcinoma
• Adenocarcinoma (Endometriod) grade II and Ill.

1. More than half of myometrial Invasion
2. Isthmus- cervix extension
3. Tumour size > 2cms
4. Extrauterine disease.

As far as Peritoneal metastasis is concerned :

“Positive Peritoneal cytology in itself is not a marker of poor prognosis i.e. is not an indication for lymph node dissection unless and until associated with other poor prognostic markers as above.”

Ans. is d i.e. Clear cell carcinoma

Endometrial cancers can be histologically classified as :

Features                                          Type I                                                   ‘Type II

Unopposed estrogen                         Present                                                 Absent

Menopausal status                            Pre-and perimenopausal                 Postmenopausal

Hyperplasia                                      Present                                                 Balck

Race                                               White                                                    Black

Grade                                              Low                                                       High

Myometrial invasion                          Minimal                                                Deep

Specific subtypes                              Endometrioid                                      Serous, clear cell

Behavior                                         Stable                                                   Aggressive

non ednometriod / type II endometrial cancer (clear cell carcinoma) have poor prognosis. Also know : Clear cell carcinoma :

• It accounts for < 5% of all endometrial carcinoma.
• The cells have highly atypical nuclei and abundant clear or eosinophilic cytoplasm.
• The cells have hobnail configuration.
• It characteristically occurs in older women and is very aggressive type of endometrial cancer.
• Prognosis is similar to or worse than papillary serous carcinoma.

Radiotherapy, Chemotherapy and hormonal therapy

Multiparity

Carcinoma in situ cervix

All

Endometrial carcinoma REF: Berek and Novak’s gynecology by Jonathan S. Berek, Emil Novak page 1349, Blueprints Obstetrics and Gynecology by Tamara L. Callahan, Aaron B. Caughey page 238

• “The most common cause of post-menopausal bleeding is endometrial and/or vaginal atrophy (not in options), not cancer. Endometrial cancer accounts for only 10-15% of cases”
• “However since endometrial malignancy can coexist with atrophic changes and with HRT, endometrial carcinoma must be ruled out in any case of post-menopausal bleeding”
• The most common malignancy to present with postmenopausal bleeding is Endometrial carcinoma
• The most common cause of post coital vaginal bleeding is cervical cancer.

Causes of post-menopausal bleeding: 

Tamoxifen reduces the recurrence rate of breast cancer in ipsilateral as well as contralateral breasts.

Adverse effects associated with the use of tamoxifen are:

• 2-3 fold increased risk of thromboembolism
• 2-3 fold increased risk of endometrial carcinoma
• Hot flushes, vomiting, vaginal discharge, menstrual irregularities
• Cataract, dermatitis, depression, mild leucopenia

Patients with stage 1A grade I endometrial carcinoma, tumor is limited to the endometrium and is effectively managed by total abdominal hysterectomy with bilateral salphingo- oophorectomy.

Ref: Textbook of Obstetrics By D.C.Dutta, 6th Edition, Pages 329-334.

o PTEN is a tumor suppressor gene which is implicated in the causation of endometrial and prostate carcinoma.

Ans. is ‘b’ i.e., Smoking

Endometrial carcinoma

o Endometrial carcinoma is the most common invasive cancer of the female genital tract and accounts for 7% of all invasive cancer in women.

o The peak incidence is in the 55- to 65-year-old woman.

o Clinicopathological studies & molecular analysis support its classification into two major broad categories.

Type-I Carcinoma

o Most common type.

o Majority are well differentiated & mimic proliferative endometetrial glands.

o They are associated with- obesity, diabetes, hypertension, infertility and unopposed estrogen stimulation. Tamoxifen also increases the risk of endometrial cancer.

o Endometrial hyperplasia is a precursor to endometroid carcinoma.

o Mutation in PTEN tumor suppressor gene have been seen in 30-80% of endometeriod carcinoma & 20% patients with endometrial hyperplasia.

o Additional molecular changes that are common are microsatellite instability & mutations in KRAS & beta catenin oncogenes.

Type-H Carcinoma

o These occur in women a decade later than type I carcinoma.

o These usually arise in setting of endometrial atropy.

o They are poorly differentiated. The most common subtype is serous carcinoma, clear cell type & malignant mixed mullerian tumor.

o The most frequent alteration described is mutation in p53 tumor suppressor gene.

Ans. C: Complex hyperplasia with atypia

Simple hyperplasia progresses to cancer in 10-20% whereas atypical hyperplasia is a precursor of cancer in 60-70% of cases.

Classification

Most endometrial cancers are carcinomas (usually adenocarcinomas

Endometrial carcinomas can be classified into two pathogenetic groups:

• Type I: These cancers occur most commonly in pre- and peri-menopausal women, often with a history of unopposed estrogen exposure and/or endometrial hyperplasia. They are often minimally invasive into the underlying uterine wall, are of the low-grade endometrioid type, and carry a good prognosis.
• Type II: These cancers occur in older, post-menopausal women, and are not associated with increased exposure to estrogen. They are typically of the high-grade endometrioid, papillary serous or clear cell types, and carry a generally poor prognosis

Risk factors

• High levels of estrogen
• Endometrial hyperplasia
• Polycystic ovary syndrome
• Nulliparity
• Infertility
• Early menarche
• Late menopause
• Endometrial polyps or other benign growths of the uterine lining
• Tamoxifen
• Hyperplasia
• Pelvic radiation therapy
• Breast cancer
• Ovarian cancer

Clinical evaluation

• A Pap smear may be either normal or show abnormal cellular changes.
• Endometrial curettage is the traditional diagnostic method.
• If endometrial curettage does not yield sufficient diagnostic material, a dilation and curettage (D and C) is necessary for diagnosing the cancer.
• Endometrial biopsy or aspiration may assist the diagnosis.
• Transvaginal ultrasound to evaluate the endometrial thickness in women with postmenopausal

Pathology

The most common finding is a well-differentiated endometrioid adenocarcinoma, which is composed of numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification.

Further evaluation

Colonoscopy is recommended due to the etiologic factors common to both endometrial cancer and colon cancer.

Staging

Endometrial carcinoma is surgically staged using the FIGO cancer staging system.

i a. Stage IA: tumor is limited to the endometrium

i b. Stage IB: invasion of less than half the myometrium

i c. Stage IC: invasion of more than half the myometrium

ii a. Stage IIA: endocervical glandular involvement only

ii b. Stage IIB: cervical stromal invasion

iii a.Stage IIIA: tumor invades serosa or adnexa, or malignant peritoneal cytology

iii b.Stage IIIB: vaginal metastasis

iii c. Stage IIIC: metastasis to pelvic or para-aortic lymph nodes

iv a. Stage IVA: invasion of the bladder or bowel

iv b.Stage IVB: distant metastasis, including intraabdominal or inguinal lymph nodes

Treatment

Abdominal hysterectomy is recommended over vaginal hysterectomy because it affords the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer.

Ans. B: Stage III b

This histological pattern is of endometrial hyperplasia

Ans. C: Complex hyperplasia with atypia

Simple hyperplasia progresses to cancer in 10-20% whereas atypical hyperplasia is a precursor of cancer in 60-70% of cases.

Classification

Most endometrial cancers are carcinomas (usually adenocarcinomas

Endometrial carcinomas can be classified into two pathogenetic groups:

• Type I: These cancers occur most commonly in pre- and peri-menopausal women, often with a history of unopposed estrogen exposure and/or endometrial hyperplasia. They are often minimally invasive into the underlying uterine wall, are of the low-grade endometrioid type, and carry a good prognosis.
• Type II: These cancers occur in older, post-menopausal women, and are not associated with increased exposure to estrogen. They are typically of the high-grade endometrioid, papillary serous or clear cell types, and carry a generally poor prognosi