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Proliferative lesions of
ENDOMETRIUM
Endometrial polyp, hyperplasia,
endometrial carcinoma, leiomyoma &
leiomyosarcoma.
Dr...
Endometrial Polyps
Uterine polyp’ is clinical term used for a polypoid growth
projecting into the uterine lumen and may be...
Endometrial polyps
- are focal benign overgrowth of endometrium
- most commonly located on the fundus
- may protrude into ...
Endometrial Polyps
These sessile, usually hemispheric lesions range from
0.5 to 3 cm in diameter.
Larger polyps may projec...
Morphology
Grossly, endometrial polyps may be single or multiple, usually sessile
and small (0.5 to 3 cm in diameter) but ...
Morphology
On histologic examination, they are composed of endometrium resembling the
basalis, frequently with small muscu...
Endometrial polyp ( fibrous stroma harboring dilated glands
lined by columnar epithelium
Endometrial hyperplasia
- exaggerated endometrial proliferation due to excess of estrogen
- can be preneoplastic
- hyperpl...
A) Simple hyperplasia
- crowding of glands without atypia some of them are dilated (cystic hyperplasia)
:Swiss cheese
- on...
B) Complex hyperplasia
- crowding and branching of glands without cellular atypia
- 3% of cases progress to adenocarcinoma
C) Atypical hyperplasia
- complex hyperplasia with atypia ( hyperchromatic nuclei, mitotic figures )
- commonly progresses...
When hyperplasia with atypia is discovered, it must be carefully evaluated for the presence of
cancer and must be monitore...
Endometrial carcinoma
- endometrial carcinoma is the most frequent cancer of the female genital tract
Epidemiology and Pat...
4- Diabetes Hypertension Infertility: women tend to be nulliparous, often with
anovulatory cycles.
5- prolonged estrogen r...
Morphology:
- Endometrioid carcinomas: - closely resemble normal endometrium
- may be exophytic or infiltrative
- may infi...
Endometrial carcinoma. The most common histologic pattern is well-
differentiated adenocarcinoma showing closely packed
(b...
(A, B )Endometrioid carcinoma (C ) Serous carcinoma of the endometrium displaying
formation of papillae and marked cytolog...
Clinical course:- first clinical indication is marked leukorrhea and irregular bleeding
- With progression, the uterus bec...
Uterine Fibroids
LEIOMYOMA
Fibromyoma
MYOMA
Leio means smooth
Uterine Fibroids
Leiomyomas or fibromyomas, commonly called fibroids by
the gynaecologists, are the most common uterine tu...
These fibroids develop in the outer
portion of the uterus and continue to
grow outward
Subserosal uterine
fibroids
The mos...
[15%]
[20%]
[60%]
CLASSIFICATION
•Submucous
leiomyoma
•Pedunculated
submucous
•Intramural or
interstitial
•Subserous or
subperitoneal
•Pedun...
ETIOLOGY
•Unknown
•Each individual myoma is unicellular in origin
•Estogens no evidence that it is a causative factor , i...
Clinical Details
Leiomyoma, Uterus (Fibroid)
Most women with fibroids are asymptomatic. Only 10-20%
of patients require tr...
Menorrhagia may result in severe anemia and can be life
threatening, although this is rare. Menorrhagia usually results
fr...
Leiomyoma, Uterus (Fibroid)
Pain
Women may experience abdominal cramping. Pain usually
is felt during menstruation. Less o...
Morphology – Gross- location
Leiomyomas are most frequently located in the uterus
where they may occur within the myometri...
Morphology - Gross
Grossly, irrespective of their location,
leiomyomas are often multiple,
circumscribed , firm, nodular, ...
Gross -Characteristics
•Size
–from microscopic to very huge size filling the whole abdominal cavity (up to 40 kg was
recor...
Microscopy
Histologically, they are essentially composed of 2
tissue elements—
whorled bundles of smooth muscle cells
admi...
Leiomyoma uterus. Microscopy shows whorls of smooth muscle cells which are spindle-shaped, having
abundant cytoplasm and o...
Morphology
Cellular leiomyoma has preponderance of smooth
muscle elements and may superficially resemble leiomyosarcoma
bu...
Morphology – secondary changes
The pathologic appearance may be altered by
secondary changes in the leiomyomas; these incl...
Investigation of Fibroids
•Ultrasound
•MRI better than CT Imaging
•Laparoscopy and Hysteroscopy
Treatment Options for Fibroids
•Hysterectomy
–If the uterus is >10w size
–Or symptoms that are due to the fibroids
–Rapid ...
Pregnancy Complications Due to Leiomyoma
•Abortion
•Premature labor
•Disturbances in labor
Postpartum hemorrhage
(question...
LEIOMYOSARCOMA
Leiomyosarcomas arise de novo from the mesenchymal cells
of the myometrium, not from preexisting leiomyomas...
Morphology
Grossly, the tumour may form a diffuse, bulky,
soft and fleshy mass, or a polypoid
mass projecting into lumen.
Morphology
The histologic appearance varies
widely, from tumors that closely resemble leiomyoma to wildly
anaplastic neopl...
Histologically, though there are usually some areas
showing whorled arrangement of spindle-shaped smooth
muscle cells havi...
Recurrence & Prognosis
Recurrence after removal is common with these
cancers, and many metastasize, typically to the
lungs...
THANKS
Endometrial polyp, hyperplasia, carcinoma
Endometrial polyp, hyperplasia, carcinoma
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Endometrial polyp, hyperplasia, carcinoma

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Leiomyoma, leiomyosarcoma, endometrial hyperplasia, endometrial carcinoma, endometrial polyps.

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Endometrial polyp, hyperplasia, carcinoma

  1. 1. Proliferative lesions of ENDOMETRIUM Endometrial polyp, hyperplasia, endometrial carcinoma, leiomyoma & leiomyosarcoma. Dr Mohammad Manzoor Mashwani All tend to produce abnormal uterine bleeding as their earliest manifestation.
  2. 2. Endometrial Polyps Uterine polyp’ is clinical term used for a polypoid growth projecting into the uterine lumen and may be composed of benign lesions (e.g. endometrial or mucous polyp, leiomyomatous polyp and placental polyp), or malignant polypoid tumours (e.g. endometrial carcinoma, choriocarcinoma and sarcoma). The most common variety, however, is the one having the structure like that of endometrium and is termed endometrial or mucus polyp.
  3. 3. Endometrial polyps - are focal benign overgrowth of endometrium - most commonly located on the fundus - may protrude into vagina and may cause bleeding. Although endometrial polyps may occur at any age, they most commonly are detected around the time of menopause. Their clinical significance lies in abnormal uterine bleeding and, more important, in the risk (however rare) of giving rise to a cancer.
  4. 4. Endometrial Polyps These sessile, usually hemispheric lesions range from 0.5 to 3 cm in diameter. Larger polyps may project from the endometrial mucosa into the uterine cavity. Small endometrial polyps generally remain asymptomatic and are detected incidentally. The larger ones may ulcerate, degenerate and result in clinical bleeding
  5. 5. Morphology Grossly, endometrial polyps may be single or multiple, usually sessile and small (0.5 to 3 cm in diameter) but occasionally they are large and pedunculated. Have 2 patterns —localised polypoid tumour, or a diffuse tumour; the latter being more common. The tumour protrudes into the endometrial cavity as irregular, friable and grey-tan mass. Extension of the growth into the myometrium may be identified by the presence of soft, friable and granular tissue in cut section. In advanced disease, the involvement may extend beyond the physiologic limits—into the cervical canal, into the peritoneum, besides lymphatic metastases and haematogenous metastases to distant sites such as lungs, liver, bones and other organs.
  6. 6. Morphology On histologic examination, they are composed of endometrium resembling the basalis, frequently with small muscular arteries. Some glands have a normal endometrial architecture, but more often they are cystically dilated. The stromal cells are monoclonal, often with a rearrangement of chromosomal region 6p21, and thus constitute the neoplastic component of the polyp.
  7. 7. Endometrial polyp ( fibrous stroma harboring dilated glands lined by columnar epithelium
  8. 8. Endometrial hyperplasia - exaggerated endometrial proliferation due to excess of estrogen - can be preneoplastic - hyperplasia is classified based on crowding of glands and presence of atypia into: 1- simple hyperplasia 2- complex hyperplasia 3- atypical hyperplasia - these changes depend on the level and duration of the estrogen excess - risk factors: (estrogen excess) 1- failure of ovulation (e.g. around the menopause) 2- prolonged administration of estrogen 3- estrogen-producing ovarian lesions (polycystic ovaries) 4- Ovarian cortical stromal hyperplasia 5- granulosa-theca cell tumors of the ovary 6- obesity ( because adipose tissue processes steroid precursors into estrogens) Polycystic ovary syndrome (PCOS), also called hyperandrogenic anovulation (HA), or Stein– Leventhal syndrome, is a set of symptoms due to a hormone imbalance in women.
  9. 9. A) Simple hyperplasia - crowding of glands without atypia some of them are dilated (cystic hyperplasia) :Swiss cheese - only 1% of cases progress to adenocarcinoma Swiss cheese
  10. 10. B) Complex hyperplasia - crowding and branching of glands without cellular atypia - 3% of cases progress to adenocarcinoma
  11. 11. C) Atypical hyperplasia - complex hyperplasia with atypia ( hyperchromatic nuclei, mitotic figures ) - commonly progresses to adenocarcinoma - treated may be with Tamoxifen (antiestrogen) or hysterectomy
  12. 12. When hyperplasia with atypia is discovered, it must be carefully evaluated for the presence of cancer and must be monitored by serial endometrial biopsies. In time, the hyperplasia may proliferate autonomously, no longer requiring estrogen, and eventually may give rise to carcinoma. In a significant number of cases, the hyperplasia is associated with inactivating mutations in the PTEN tumor suppressor gene, an important brake on signaling through the PI-3-kinase/AKT signaling pathway Acquisition of PTEN mutations is believed to be one of several key steps in the transformation of hyperplasias to endometrial carcinomas, which also often harbor PTEN mutations. Phosphatase and tensin homolog(PTEN) is a protein that, in humans, is encoded by the PTEN gene.
  13. 13. Endometrial carcinoma - endometrial carcinoma is the most frequent cancer of the female genital tract Epidemiology and Pathogenesis: - common between the ages of 55 and 65 years - arises in two clinical settings: 1- in perimenopausal women with estrogen excess (endometrioid carcinoma) 2- in older women with endometrial atrophy (serous carcinoma) - Pathogenesis: 1) Endometrioid type: 80% - related to excess of estrogen - the risk factors: 1- nulliparity 2- early menarche or late menopause 3- obesity (increased synthesis of estrogens ) In the United States and many other Western countries, endometrial carcinoma is the most frequent cancer occurring in the female genital tract. In Asia Cervical cancer common. These tumors are designated endometrioid because of their histologic similarity to normal endometrial glands. UTERINE CANCER
  14. 14. 4- Diabetes Hypertension Infertility: women tend to be nulliparous, often with anovulatory cycles. 5- prolonged estrogen replacement therapy 6- estrogen-secreting ovarian lesions 7- endometrial hyperplasia - genetic abnormality: 1- mutations in DNA mismatch repair gene 2- mutations in PTEN, a tumor suppressor gene 2) Serous type: 15% - is a distinct type - It typically arises in a background of atrophy - sometimes arises in endometrial polyp - nearly all cases have mutations in the p53 tumor suppressor gene Cowden syndrome (also known as "Cowden's disease," and "Multiple hamartoma syndrome"[ is a rare autosomal dominantinherited disorder characterized by multiple tumor-like growths called hamartomas and an increased risk of certain forms of cancer (Endometrium, Breast, Thyroid). It is associated with mutations in PTEN, a tumor suppressor gene Whereas the decline in the incidence of cervical cancer in the developed countries is due to aggressive cervical screening programme leading to early detection and cure of in situ stage, increased frequency of endometrial carcinoma in these countries may be due to longevity of women’s life to develop this cancer of older females.
  15. 15. Morphology: - Endometrioid carcinomas: - closely resemble normal endometrium - may be exophytic or infiltrative - may infiltrate the myometrium and enter vascular spaces, with metastases to regional lymph nodes - four stages: stage I: confined to the corpus stage II: involvement of the cervix stage III: beyond the uterus but within the true pelvis stage IV: distant metastases or involvement of other viscera - Serous carcinoma: - forms small tufts and papillae rather than the glands - has much greater cytologic atypia - They behave as poorly differentiated cancers and are aggressive They include a range of histologic types, including those showing mucinous, tubal (ciliated), and squamous (occasionally adenosquamous) differentiation. Tumors originate in the mucosa and may infiltrate the myometrium and enter vascular spaces. They may also metastasize to regional lymph nodes. Endometrioid carcinomas are graded I to III, based on the degree of differentiation.
  16. 16. Endometrial carcinoma. The most common histologic pattern is well- differentiated adenocarcinoma showing closely packed (back-to-back) glands with cytologic atypia.
  17. 17. (A, B )Endometrioid carcinoma (C ) Serous carcinoma of the endometrium displaying formation of papillae and marked cytologic atypia (D )Immunohistochemical stain for p53 reveals accumulation of mutant p53 in serous carcinoma.
  18. 18. Clinical course:- first clinical indication is marked leukorrhea and irregular bleeding - With progression, the uterus becomes enlarged and affixed to surrounding structures. - metastases to cervix, tubes, ovaries, vagina, broad ligament, regional LN, lungs, liver These tumors usually are slow to metastasize, but if left untreated, eventually disseminate to regional nodes and more distant sites. With therapy, the 5-year survival rate for early-stage carcinoma is 90%, but survival drops precipitously in higher-stage tumors. The prognosis with serous carcinomas is strongly dependent on operative staging and cytologic screening of peritoneal washings; the latter is imperative, because very small or superficial serous tumors may nonetheless spread by way of the fallopian tube to the peritoneal cavity.
  19. 19. Uterine Fibroids LEIOMYOMA Fibromyoma MYOMA Leio means smooth
  20. 20. Uterine Fibroids Leiomyomas or fibromyomas, commonly called fibroids by the gynaecologists, are the most common uterine tumours of smooth muscle origin, often admixed with variable amount of fibrous tissue component. •Common – 25% of women in a lifetime •Usually multiple •Various sizes •Genetic predisposition •more common in black races •More common in the obese •Less common in smokers •More common in nulliparas •Accounts for ~30-75% of hysterectomies Malignant transformation occurs in less than 0.5% of leiomyomas. Because of their firmness, they often are referred to clinically as fibroids
  21. 21. These fibroids develop in the outer portion of the uterus and continue to grow outward Subserosal uterine fibroids The most common type of fibroid. These develop within the uterine wall and expand making the uterus feel larger than normal (which may cause "bulk symptoms) Intramural uterine fibroids These fibroids develop just under the lining of the uterine cavity. These are the fibroids that have the most effect on heavy menstrual bleeding and the ones that can cause problems with infertility and miscarriage Submucosal uterine fibroids Leiomyoma, Uterus (Fibroid) There are three primary types of uterine fibroids, classified primarily according to location in the uterus: Subserosal tumors may extend out on attenuated stalks and even become attached to surrounding organs, from which they may develop a blood supply (parasitic leiomyomas).
  22. 22. [15%] [20%] [60%]
  23. 23. CLASSIFICATION •Submucous leiomyoma •Pedunculated submucous •Intramural or interstitial •Subserous or subperitoneal •Pedunculated abdominal •Parasitic •Intraligmentary •Cervical
  24. 24. ETIOLOGY •Unknown •Each individual myoma is unicellular in origin •Estogens no evidence that it is a causative factor , it has been implicated in growth of myomas •Myomas contain estrogen receptors in higher concentration than surrounding myometrium •Myomas may increase in size with estrogen therapy & in pregnancy & decrease after menopause •& castration. They are not detectable before puberty •There may be genetic predisposition •Other possible factors implicated •in its etiology are human growth hormone and sterility.
  25. 25. Clinical Details Leiomyoma, Uterus (Fibroid) Most women with fibroids are asymptomatic. Only 10-20% of patients require treatment Fibroid symptoms are related to the number of tumors, as well as to their size and location Bleeding: (Menorrhagia)(Most common) Pain Pressure 1 2 3 4 Infertility
  26. 26. Menorrhagia may result in severe anemia and can be life threatening, although this is rare. Menorrhagia usually results from the erosion of a submucosal fibroid into the endometrial cavity. Rarely, dilated veins on the surface of a subserosal, pedunculated fibroid can cause sudden, massive intraperitoneal bleeding Bleeding: (Menorrhagia)(Most common) Leiomyoma, Uterus (Fibroid)
  27. 27. Leiomyoma, Uterus (Fibroid) Pain Women may experience abdominal cramping. Pain usually is felt during menstruation. Less often, pain occurs intermenstrually Pressure Urinary frequency, urgency, and/or incontinence result from pressure on the bladder Constipation, difficult defecation, or rectal pain results from pressure on the colon
  28. 28. Morphology – Gross- location Leiomyomas are most frequently located in the uterus where they may occur within the myometrium (intramural or interstitial), the serosa (subserosal), or just underneath the endometrium (submucosal). Subserosal and submucosal leiomyomas may develop pedicles and protrude as pedunculated myomas. Leiomyomas may involve the cervix or broad ligament.
  29. 29. Morphology - Gross Grossly, irrespective of their location, leiomyomas are often multiple, circumscribed , firm, nodular, grey-white masses of variable size. On cut section, they exhibit characteristic whorled pattern
  30. 30. Gross -Characteristics •Size –from microscopic to very huge size filling the whole abdominal cavity (up to 40 kg was recorded). •Shape –Spherical, flattened, or pointed according to the type. •Cut section: –On cut section,, whorly in appearance, and more pale than the surrounding uterine muscle. •Consistency: –firmer than the surrounding myometrium. –Soft fibroid occurs in pregnancy, cystic changes, vascular, inflammatory, and malignant changes. –Hard fibroid occurs in calcification. •Capsule: –Is a pseudo-capsule formed by compressed normal surrounding muscle fibres. –the blood supply comes through it, –it is the plain of cleavage during myomectomy –its presence differentiate the myoma from adenomyosis. •Blood supply: –Nourishes the myoma from the periphery, –The tumor itself is relatively avascular.
  31. 31. Microscopy Histologically, they are essentially composed of 2 tissue elements— whorled bundles of smooth muscle cells admixed with variable amount of connective tissue. The smooth muscle cells are uniform in size and shape with abundant cytoplasm and central oval nuclei
  32. 32. Leiomyoma uterus. Microscopy shows whorls of smooth muscle cells which are spindle-shaped, having abundant cytoplasm and oval nuclei.
  33. 33. Morphology Cellular leiomyoma has preponderance of smooth muscle elements and may superficially resemble leiomyosarcoma but is distinguished from it by the absence of mitoses
  34. 34. Morphology – secondary changes The pathologic appearance may be altered by secondary changes in the leiomyomas; these include: •hyaline degeneration, •cystic degeneration, •infarction, •calcification, •infection and suppuration, •necrosis, •Fatty change, and rarely, •sarcomatous change.
  35. 35. Investigation of Fibroids •Ultrasound •MRI better than CT Imaging •Laparoscopy and Hysteroscopy
  36. 36. Treatment Options for Fibroids •Hysterectomy –If the uterus is >10w size –Or symptoms that are due to the fibroids –Rapid growth –Abdominal or vaginal •Myomectomy –Best for single fibroid in a young woman –~50% come to hysterectomy within 5 years? •Hysteroscopic resection •Uterine artery embolisation (UAE) •Medical options –GnRH analogue –Mirena
  37. 37. Pregnancy Complications Due to Leiomyoma •Abortion •Premature labor •Disturbances in labor Postpartum hemorrhage (questionable •Ectopic pregnancy •Premature rupture of membrane •Dystocia secondary low segment myoma •Increase operative deliveries •Inversion of uterus
  38. 38. LEIOMYOSARCOMA Leiomyosarcomas arise de novo from the mesenchymal cells of the myometrium, not from preexisting leiomyomas. They are almost always solitary and most often occur in postmenopausal women, in contradistinction to leiomyomas,which frequently are multiple and usually arise premenopausally. Leiomyosarcoma is an uncommon malignant tumour as compared to its rather common benign counterpart. The incidence of malignancy in pre-existing leiomyoma is less than 0.5% but primary uterine sarcoma is less common than that which arises in the leiomyoma.
  39. 39. Morphology Grossly, the tumour may form a diffuse, bulky, soft and fleshy mass, or a polypoid mass projecting into lumen.
  40. 40. Morphology The histologic appearance varies widely, from tumors that closely resemble leiomyoma to wildly anaplastic neoplasms. Those well-differentiated tumors that lie at the interface between leiomyoma and leiomyosarcoma are sometimes designated smooth muscle tumors of uncertain malignant potential; in such cases, only time will tell if the tumor’s behavior is benign or malignant. The diagnostic features of overt leiomyosarcoma include tumor necrosis, cytologic atypia, and mitotic activity. Since increased mitotic activity is sometimes seen in benign smooth muscle tumors, particularly in young women, an assessment of all three features is necessary to make a diagnosis of malignancy.
  41. 41. Histologically, though there are usually some areas showing whorled arrangement of spindle-shaped smooth muscle cells having large and hyperchromatic nuclei, the hallmark of diagnosis and prognosis is the number of mitoses per high power field (HPF). The essential diagnostic criteria are: more than 10 mitoses per 10 HPF with or without cellular atypia, or 5-10 mitoses per 10 HPF with cellular atypia. More the number of mitoses per 10 HPF, worse is the prognosis.
  42. 42. Recurrence & Prognosis Recurrence after removal is common with these cancers, and many metastasize, typically to the lungs, liver, bone & brain yielding a 5-year survival rate of about 40%. The outlook with anaplastic tumors is less favorable than with well-differentiated tumors.
  43. 43. THANKS

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