Cancers of the Uterine Corpus SUNY Downstate Medical Center Division of Gynecologic Oncology Mark...

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Cancers of the Uterine Corpus

SUNY Downstate Medical Center

Division of Gynecologic Oncology

Mark Borowsky, MD

American Cancer SocietyFemale Cancers: 2000 Statistics

• Cancers of the uterine corpus are the 4th most common cancer in American women

• Lifetime incidence ~2-3%

Lifetime risk

Country Risk (%)

U.S. White 3.05

U.S. Black 1.34

South East Asia

0.2

Post MenopausalAge 40-50 y/oAge <40 y/o

•Median Age 61•25% diagnosed before the menopause•5% diagnosed before age 40

American Cancer SocietyFemale Cancers: 2000 Statistics

6,500 Deaths per year 8th cause of female cancer death 2% of all female cancer death Uterine corpus cancer cases and deaths have increased 25% and 12% respectively from 1994 to 2004

American Cancer SocietyFemale Cancers: 2000 Statistics

Cancers of the Uterine Corpus:Histologic Types

• Carcinoma (94%)– Endometrioid (87%)– Adenosquamous (4%)– Papillary Serous* (3%)– Clear Cell* (2%)– Mucinous (1%)– Other (3%)

• Sarcoma (6%)– Carcinosarcoma* (60%)– Leiomyosarcoma* (30%)– Endometrial Stromal Sarcoma (10%)– Adenosarcoma (<1%)

*poor prognosis histology

Endometrial Cancer:Type I/II Concept

• Type I– Estrogen Related– Younger and heavier patients– Low grade– Background of Hyperplasia– Perimenopausal– Exogenous estrogen

• Type II (~10% of total cases)– Aggressive– High grade– Unfavorable Histology– Unrelated to estrogen stimulation– Occurs in older & thinner women

• Familial/genetic (~15% of total cases)• Lynch II syndrome/HNPCC• Familial trend

Endometrial Cancer: Type I Risk Factors

Characteristic Relative Risk [X]

Atypical Hyperplasia 29

Obesity >50 LBS 10

Obesity >30 LBS 3

Unopposed Estrogen 9.5

E use <5yrs vs. >7yrs 5-14

Late Menopause (>52 y/o) 4

Diabetes 2.8

Nulliparous 2

Early Menarche (<12 y/o) 1.6

OCP 0.5

• Replaced Clinical Staging 1989• Conceptual rationale

– Better defines extent of disease (metastases, depth of invasion, cervix involvement, etc.)

– Minimizes over/under treatment– Minimally increases perioperative

morbidity/mortality– Decreases overall Rx risks and costs– Better allows comparison of therapeutic results

Uterine Cancer: Surgical Staging

• Clinical Stage I will be upstaged 30% of the time at laparotomy– 5% for positive adnexa (Surgical Stage IIIa)– 6% for positive para-aortic lymph nodes (Surgical Stage IIIc)– 9% for positive pelvic nodes (Surgical Stage IIIc)– 12% for positive cytology on pelvic washings (Surgical Stage

IIIa)– 6% other {eg. cervical (St II) or abdominal disease (St IV)}

• Clinical Stage II or III will be upstaged 60% of the time at laparotomy

Uterine Cancer: Surgical Staging

Endometrial Cancer: Clinical vs. Surgical Staging

Clinical assessment No. 5-yr OS (%)

Stage I 245 88

Stage II/III 47 83

Surgical assessment No. 5-yr OS (%)

Stage I/II 231 93

Stage III 61 67

Lanciano et al: Radiother Oncol 28:189,1993

Stage I

(73%)Confined to uterus

Stage II

(11%)Cervix involved

Stage III

(13%)

Uterine serosa, adnexae, positive cytology, vaginal metastases, pelvic/aortic node metastases

Stage IV

(3%)Bladder, bowel, inguinal node, distant metastasis

Endometrial Cancer: FIGO Surgical Stage

Endometrial Cancer Prognosis:

Survival by Stage:Stage % 5yr

survival

IA 91

IB 88

IC 81

IIA 77

IIB 67

IIIA 60

IIIB 41

IIIC 32

IVA 20

IVB 5

Survival by Grade:

Grade % 5yr survival

1 92

2 87

3 74

•Overall 5Yr Survival 84%

•Stage and Grade are the most important prognostic factors

•Altered oncogene/tumor suppressor gene expression is now being evaluated (molecular staging concept)

• Aggressive Histologic Subtypes (Clear-cell, Serous)

• Increasing age (over 65)• Vascular invasion• Aneuploidy• Altered oncogene/tumor suppressor gene

expression ( “molecular staging” concept- p53, PTEN, microsatellite instability, MDR-1, HER2/neu, ER/PR, Ki 67, PCNA, CD 31,EGF-R, MMR genes)

• Race?

Endometrial Cancer: Poor Prognostic Factors

Molecular Genetics

• PTEN mutations: 32%– Tumor suppressor gene (chrom 10)

• Phosphatase

– Early event in carcinogenesis

• Associated with:– endometrioid histology– early stage– favorable survival

Molecular Genetics• p53 tumor suppressor gene

– Cell cycle and apoptosis regulation– Most commonly mutated gene in human

cancers– Overexpression (marker for mutation)– Associated with poor prognosis– early stage: 10% have p53

mutation– advanced stage: 50% have p53

mutation– not found in hyperplasias– late event in carcinogenesis

Genetic Syndromes: HNPCCHereditary Non-Polyposis Colon Cancer

Lynch II Syndrome• Autosomal dominant inheritance

– MMR (mismatch repair) mutations• Genetic instability leads to error-prone DNA replication

– hMSH2 (chrom 2)– hMLH1 (chrom 3)

• Early age of colon Ca: mean 45.2 years• Endometrial Ca: second most common

malignancy– 20% cumulative incidence by age 70– Earlier age of onset than sporadic cases

• Other: ovary (3.5-8 fold), stomach, small bowel, pancreas, biliary tract

Five Year Survival by Race:

Stage White Black

All Stages 85 54

I 93 73

II 76 27

III 55 17

IV 23 13

Matthews RP, Hutchinson-Colas J, Maiman M, et al.: Papillary Serous and Clear Cell Type Lead to Poor Prognosis of Endometrial Carcinoma in Black

Women. Gynecol Oncol. 65: 206-212, 1997.

• Retrospective review 401 patients (60% black)• 5 yr Survival

– Black women: 56% Other races: 71%• Black women were more likely to have clear cell or

UPSC histology.• After controlling for stage only clear cell and UPSC

histology independently predicted poor outcome.• Race not predictive of survival when stage and

histology controlled for.

Five Year Survival by Race:

Diagnosis of disease: Patient Awareness*

• More than 95% of patients with Endometrial Cancer report having symptoms– Postmenapausal bleeding– Menorrhagia– Metrorrhagia– Bloody Discharge

• Endometrial biopsy is the main diagnostic tool – performed either in the office or via D&C in OR

Post menopausal bleeding

ETIOLOGY (%)

Exogenous estrogen 30

Atrophy (uterus/vag) 30

Endo. Ca. 15

Polyps 10

Hyperplasia 5

Miscellaneous 10

Postmenopausal Bleeding

Diagnosis of Any Uterine Corpus Cancer, Hawwa et al., 1970

Age Group # Cases # Cancer %

<50 34 0 0.0

50-59 161 15 9.3

60-69 92 15 16.3

70-79 43 12 27.9

>80 5 3 60.0

Uterine Cancer:Diagnosis/Screening

• Patient Symptoms/Awareness*• Cytology – Not a satisfactory screening test• Sonography – Not Cost effective• Hysteroscopy – Not Cost effective• Histology – Secondary to symptoms (not as a

screening test)

Cytology – Not sensitive, nor specific

Endometrial Pathology in Women With Any Endometrial Cells Seen on Pap (Yancey, et al. 1990) Menopause Status Number of patients Number (%) of

hyperplasia or any type malignancy

Premenopausal 61 6 (10%)

Postmenopausal 127 39 (31%)

•Less than 50% of patients with endometrial Ca have endometrial cells on Pap smear

•Endometrial cells and/or AGCUS on a pap are frequently a sign of endometrial pathology and deserve further investigation

Endometrial Cancer:Transvaginal Ultrasound Screening

Endometrial Cancer:Transvaginal Ultrasound Screening

Fleischer AC, Wheeler JE, Lindsay I, et al.: An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms. American Journal of Obstetrics and Gynecology 184(2): 70-75, 2001.

•Study of 1,926 asymptomatic postmenopausal women on idoxifene for transvaginal u/s screening

•All patients agree to biopsy after u/s (1,792 biopsies)

•Using 6 mm cutoff for “Abnormal” the sensitivity of the test was 33% (missed 67% of atypical hyperplasia and cancer)

•45% of women were > or = 6mm

•PPV was only 2%

•NPV>99%

Endometrial Cancer:Transvaginal Ultrasound Screening

Langer RD, Pierce JJ, O'Hanlan KA, et al.: Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. New England Journal of Medicine 337(25): 1792-1798, 1997.

•448 Women, all asymptomatic and all on HRT

•All agree to TV u/s and biopsy

•Threshold of 5mm used

•4% incidence of cancer

•Test Sensitivity was 90% at threshold of 5mm

•But >50% of women had endometrial thickness of 5mm or more

Endometrial Cancer:Transvaginal Ultrasound Screening

N=250

Endometrial Stripe Thickness

Diagnosis <5mm 6-10mm11-

15mm>15mm

Atrophy 93% 7%

Hyperplasia 58% 42%

Polyp 53% 47%

Cancer 18% 41% 41%

Grigoriou: Maturitus 23:9-14,1996

Endometrial Cancer:Transvaginal Ultrasound Screening

Rebecca Smith-Bindman, MD; Karla Kerlikowske, MD; Vickie A. Feldstein, MD, etal: Endovaginal Ultrasound to Exclude Endometrial Cancer and Other Endometrial Abnormalities. JAMA. 1998;280:1510-1517

•Meta-analysis 35 studies, 5,892 women

•All with PMB, HRT use varied

•5mm threshold used

•Sensitivity 92%

•Specificity 92% for non HRT users

•Specificity 77% for HRT users

Endometrial Cancer:Transvaginal Ultrasound Screening

Endometrial Cancer:Transvaginal Ultrasound Screening

• Normal endometrial stripe:• Postmenopausal 4- 8 mm

• Postmenopausal on HRT 4- 10 mm

• U/S for Detection of any uterine pathology

• Sensitivity: 85-95%

• Specificity: 60-80%

• PPV 2-10%

• NPV 99%

Summary: Endometrial Cancer:Transvaginal Ultrasound Screening

Hysteroscopy – Not satisfactory for screening test

•Studies of the efficacy of hysteroscopy as a diagnostic tool vary widely

•Sensitivity reported ranging from 60-95% compared to D&C obtained at the same time

•Specificity 50-99%

Normal Endometrium

Endometrial Polyp

Polyp and Atypical Hyperplasia

Focal Simple Hyperplasia

Grade 3 Endometrial cancer

Hysteroscopy and Positive Cytology?

•Studies have been mixed:

•Some studies suggest an increase in positive peritoneal cytology seen at staging laparotomy in patients who have had hysteroscopy

•Other studies have failed to find a difference in positive cytology in patients diagnosed via hysteroscopy as compared to office biopsy or D&C

Positive Studies:

Bradley WH, Boente MP, Brooker, D, et al.: Hysteroscopy and Cytology in Endometrial Cancer. Obstet Gynecol 2004;104:1030-3

Zerbe M, Zhang J, Bristow RE, et al.: Retrograde seeding of malignant cells during hysteroscopy in presumed early endometrial cancer. Gynecol Oncol 2000;79:55-8

Obermair A, Geramou M, Gucer F, et al.: Does hysteroscopy facilitate tumor cell dissemination. Cancer 2000;88:139-43

Increase in positive cytology from ~2-3% to ~10%(RR 3-4)

Negative Studies:

Gu M, Shi W, Huang J, et al.: Association between initial diagnostic procedure and hysteroscopy and abnormal peritoneal wahisngs in patients with endometrial carcinoma. Cancer 2000;90:3:143-7

Selvaggi L Cormio G, Ceci O, et al.: Hysteroscopy does not increase the risk of microscopic extrauterine spread in endometrial carcinoma. Int J Gynecol Cancer 2003;13:223-7

Hysteroscopy – Not satisfactory

• Too much cost and risk to be used as a screening test.

• Useful for evaluation of abnormal uterine bleeding where office biopsy is unrevealing.

• Use in conjunction with uterine curettage• Useful to see and resect polyps and small

submucous fibroids• Useful to perform directed biopsy of small

lesions.

Endometrial Cancer:Who Needs an Endometrial Biopsy?

• Postmenopausal bleeding• Perimenopausal intermenstrual bleeding• Abnormal bleeding with history of anovulation• Postmenopausal women with endometrial

cells on Pap• Thickened endometrial stripe via sonography

Sampling of the Endometrium• Office biopsy procedures (Pipelle, Vabra aspirator,

Karman cannula) will agree with a D&C performed in the OR ~95% of the time

• Office biopsy has a 16% false negative rate when the lesion is in a polyp or the cancer covers less than 50% of the endometrium– Guido et al. J Reprod Med. 1995;40:553

• Patients with persistent PMB after negative office biopsy should have D&C (+/- hysteroscopy)

• D&C is the gold standard sampling method – preoperative D&C will agree with diagnosis at

hysterectomy 94% of the time

Endometrial cyclic changesProliferative phase

Endometrial cyclic changesProliferative phase

Endometrial cyclic changesEarly secretory

Endometrial cyclic changesmid-secretory

Endometrium: Post-menopausal atrophy

Endometrial Simple Hyperlasia

Endometrial Hyperlasia - Complex

Endometrial Hyperplasia - Atypical

Endometrial Atypical Hyperplasia

Endometrial Hyperplasia Classification and Risk of Progression to Cancer:

Kurman, et al. (Cancer. 1985 Jul 15;56(2):403-12.)Type of Hyperplasia

Total Cases (n=170)

Years of Follow up (mean=13.4)

# Progressed to Cancer

% Progressed to Cancer

%

Persistent Hyperplasia

% Spont. Regression

Simple 93 15.2 1 1% 19% 80%Complex 29 13.5 1 3% 17% 80%Atypical,

simple13 11.4 1 8% 23% 69%

Atypical, complex

35 11.4 10 29% 14% 57%

Combined No Atypia (n=122) 1.6%

Combined with Atypia (n=48) 23% (P=0.001)

Mean age at study entry= 40y/o Mean study F/U=13.4yrs

Treatment for Endometrial Hyperplasia without atypia:

•Progestin therapy continuous or cyclical•Childbearing age:

•Progestin dominant OCPs or•Depo-Provera 150mg IM q3 months or•Provera 10mg po 10 days/month and•May follow with ovulation induction after normal biopsy if pregnancy desired

•Peri or Postmenopausal:•Provera 20mg po 10 days/month or•Depo-Provera 200mg IM q2 months

•Repeat biopsy in 3-4 months

Treatment for Atypical Endometrial Hyperplasia:

•23% risk of progression to carcinoma (over 10 years) if untreated.

•Standard treatment when childbearing is complete is total hysterectomy (abdominal or vaginal)

•Frozen section to rule out carcinoma (up to 20% have coexisting endometrial cancer)

Treatment for Atypical Endometrial Hyperplasia:

• Conservative medical therapy can be attempted in younger patients who request preservation of fertility.

• D&C prior to initiation of medical therapy to rule out carcinoma

• Megace 40-80mg/day, Norethindrone acetate 5mg/day

• Conservative therapy may also be attempted in young patients with early, well differentiated endometrial carcinomas.

• Megace 120-200mg/day, Norethindrone acetate 5-10mg/day

Conservative/Medical Therapy:

• Objective– Determine efficacy of conservative treatment of

AH/ECA in patients <40 yrs. of age

• Methods– Retrospective Study of pathology records of women

age < 40 diagnosed with AH or ECA at Johns Hopkins Jan/90 - Jan/96

Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol. 1997 Sep;90(3):434-40.

Conservative/Medical Therapy:

• Results– Among 29 pts treated with progestins

16/17 (94%) w/ AH regressed

9/12 (75%) w/ ECA regressed– Median length of treatment required for

regression was 9 mos.

T.C.Randall, R.J.Kurman. Obstet Gynecol 1997;90:434-440

Conservative/Medical Therapy:

• Results– At a mean f/u of 40 mos all pts were alive

w/o evidence of progressive dz.– 5 of 25 women attempting pregnancies

delivered healthy full term infants.

T.C.Randall, R.J.Kurman. Obstet Gynecol 1997;90:434-440

Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature. Cancer. 1997 Jan 15;79(2):320-7.

•13 of 20 patients (62%) with well differentiated endometrial carcinoma regressed with progestins (3 later recurred).

Conservative/Medical Therapy:

Gotlieb WH, Beiner ME, Shalmon B, Korach Y, Segal Y, Zmira N, Koupolovic J, Ben-Baruch G. Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer. Obstet Gynecol. 2003 Oct;102(4):718-25.

•13 of 13 patients regressed with progestin therapy, 6 later recurred

• Conclusion– Treatment of AH/ECA with progestins

appears to be a safe alternative to hysterectomy in women < 40 yrs of age in whom fertility is desired.

– Perform hysterectomy after childbearing is completed.

Conservative/Medical Therapy:

Endometroid carcinoma, Grading

• FIGO- Gr 1 - < 5% solid tumor

- Gr 2 - 6 % - 50% solid

- Gr 3 - > 50% solid tumor• NUCLEAR GRADE

– Size, shape , staining and chromatin, variability, prominent nucleoli.

– High nuclear grade adds one point to FIGO grade

Grade 1 Endometroid Carcinoma

Grade 3 Endometroid Carcinoma

Endometrial carcinoma:Poor Prognosis Cell Types - Papillary Serous

Endometrial Carcinoma - Poor Prognosis Cell Types Clear Cell

•CA125•Chest X-ray•Mammograms•Colon Evaluation•Others as indicated

Uterine Cancer: Pre-op Evaluation

Uterine Cancer: Pre-op Evaluation

•Transvaginal U/S?

•CT Scan?

•MRI?

Uterine Cancer: Pre-op Evaluation

Uterine Cancer: Surgical Staging

• Preoperative preparation• Antimicrobial prophylaxis• DVT prophylaxis• Steep Trendelenburg• Long instruments available

• Availability of frozen section to determine the extent of staging procedure.

• Capability of complete surgical staging• Capability of tumor reduction if indicated

Endometrial Cancer: Intra-operative Surgical Principals

Situation % Positive Nodes

G1, inner 1/3 myometrial invasion, no extrauterine disease.

<1%

G2 or G3, inner 1/3 invasion, no extrauterine disease

5-9% Pelvic

4% Aortic

G3 with outer 1/3 invasion, and/or extrauterine disease

20-60% Pelvic

10-30% Aortic

Endometrial Cancer: Nodal Involvement

Endometrial Cancer: Surgical Approach

• TAH-BSO/washings only– Endometrioid*– Grades 1 and < 50% myometrial invasion*– or Grade 2 and no or minimal invasion

and < 2 cm tumor diameter*

*Verified via frozen section

Endometrial Cancer: Surgical Approach

• Complete Surgical Staging*– All Grade 3– Any > 50% myometrial invasion– Any >2 cm tumor diameter– All Serous/clear cell subtype**– Pre operative assessment of advanced

disease (gross cervical or vaginal dz, etc)

*TAH-BSO, washings, lymphadenectomy **omental/peritoneal biopsy

Laparoscopic Staging:Magrina JF, Weaver AL. Laparoscopic treatment of endometrial cancer:

five-year recurrence and survival rates. Eur J Gynaecol Oncol. 2004;25(4):439-41.

Holub Z, Jabor A, Bartos P, Eim J, Urbanek S, Pivovarnikova R. Laparoscopic surgery for endometrial cancer: long-term results of a multicentric study. Eur J Gynaecol Oncol. 2002;23(4):305-10.

GOG LAP2 Protocol: Randomized study of Total Hysterectomy, BSO and Staging via Laparotomy vs. Laparoscopy- study still open

• Previous studies show:– Similar blood loss– Same incidence of complications– Low incidence of conversion of laparoscopy to laparotomy– Longer operative times for laparoscopy (160 min vs.

115min)– Shorter hospital stay (4 vs 7 days) for laparoscopy– No difference in recurrence risk.

Endometrial Cancer: Adjuvant Therapy

• Brachytherapy• External beam radiotherapy• Hormonal therapy• Cytotoxic chemotherapy• Combination therapy

Endometrial Cancer: Adjuvant Radiation

•Stratify patients into risk for recurrence based on Grade and Stage

•Low Risk (<5% recurrence): Stage IA or superficial IB, Grade 1 or 2, no LVSI -these patients require no further treatment after surgery

•Intermediate Risk (5-10% recurrence): Grade 1 with at least middle third invasion or Stage IB Grade 2 and no LVSI. No consensus exists for this group.

•High Risk (>10% recurrence): Any Grade 3, Any Stage IC or greater, Grade 2 with middle third invasion or LVSI- these patients should get adjuvant radiation with either WPR 4,500-5,000 cGy and/or vaginal brachy therapy.

Endometrial Cancer: Adjuvant Radiation

•GOG 99

•390 patients, Stage IB, IC, IIA or IIB, all grades (UPSC and clear cell excluded)

•Patients randomized to 5,040 cGy WPR (no brachy therapy) vs. no RT

•3yr survival 96% vs 89% for RT vs control group (p=0.009)

• Among patients with Grade 2 or 3, or > middle third invasion or + LVSI the 5yr recurrence free percentage was 87% for the RT group vs 73% for the control group

Endometrial Cancer: Adjuvant Postop Radiotherapy

• Estimated cost 5,040 cGy PRT: $20,000• Treatment duration: 25 to 30 days• Morbidity compounded by recent surgery

Endometrial Cancer: Adjuvant Hormonal Therapy

Number Deaths

Progestagens x 1 yr 553 61

Placebo 531 62

Vergote et al: Cancer 64:1011, 1989

Endometrial Cancer: Single Agent Chemotherapy Response Rates

Agent Response Agent Response

Paclitaxel 37% HMM 17%

Carboplatin 28% Vincristine 16%

Doxorubicin 26% Etoposide 14%

Cisplatin 25% Ifosfamide 14%

5-FU 21% Cytoxan 11%GOG Symposium July 1999 Goff

Endometrial Cancer: Chemotherapy Response Rates

Single Agent 11-37%

CAP 45-56%

AP 33-81%

CA 31-46%

TAX/CARBO 63%

TEP 73%

AP-VP-16 75%

GOG Symposium July, 1999, Goff

Endometrial Cancer: ERT/HRT• 3 small published studies prior to GOG 137• GOG 137- closed after WHI study results• Preliminary results (April 2004: 32 mos F/U) of GOG 137

agree with prior studies: No evidence that ERT/HRT adversely influences the disease-free survival of women treated for endometrial cancer

Treatment ERT (Premarin) Placebo

Number Patients (n) 618 618

Disease Recurrence 14 (2.3%) 10 (1.6%)

Cancer Deaths 5 (0.8%) 4 (0.6%)

Total Deaths 23 (3.7%) 16 (2.6%)

Endometrial Cancer: Recurrence

• Pelvic examination• Pap smears• CA125 (high-risk)• Chest X-ray (high-risk)

Endometrial Cancer: Site of RecurrenceIn Radiated Patients

Site %

Distant 65

Pelvic and distant 15

Pelvis only 15

Vagina 5

Endometrial Cancer: Follow-Up

• 75-95% of recurrences are in first 36 months• 60% of patients have symptoms (pain, wgt

loss, vaginal bleeding) • Rare to cure distant recurrences• 50% vaginal recurrences cured

Uterine Sarcomas

• Account for fewer than 10% of all corpus cancers

• Abnormal vaginal bleeding most frequent presenting symptom for all histologic types

• No specific staging system (commonly use staging of endometrial carcinoma)

Uterine Sarcomas• Order of incidence: Carcinosarcoma (60%),

leiomyosarcoma (30%), endometrial stromal sarcoma (10%), and adenosarcoma (<1%)

• Higher rates of MMMT and LMS seen in Black women (2X greater than whites)

• Exposure to radiation may enhance the development of pelvic sarcomas (seen mainly in mixed sarcomas)

• Mean age between 65-75 for carcinosarcoma but earlier for LMS and ESS

Carcinosarcoma

• Contains both carcinomatous and sarcomatous elements

• In homologous MMMT, sarcomatous element is stromal sarcoma in 60% and LMS in the remainder.

• In heterologous MMMT rhabdomyosarcoma most common element (others: chondrosarcoma, osteosarcoma and liposarcoma).

• Carcinomatous element usually adenocarcinoma (endometrioid,clear cell, PSA)

Carcinosarcoma (MMMT): Homologous

Carcinosarcoma (MMMT): Heterologous

Carcinosarcoma

• Overall 5 year survival poor (25%) and strongly associated with degree of myometrial invasion.

• ~60% have spread outside the uterus at time of diagnosis

• ~35% regional lymph node spread in clinical stage 1 patients

• Early hematogenous spread to liver and lung is common

• In pts without extrauterine disease, 40% chance of distant recurrence

Leiomyosarcoma

• LMS represent ~30% of uterine sarcomas• LMS rarely arises from benign leiomyomata• Arises in the myometrium, unlike all the other

uterine sarcomas (less likely to be detected on EMC)

Leiomyosarcoma

Leiomyosarcoma

• Tumors usually show high cellularity, marked pleomorphism, and atypical mitotic figures.

• Two thirds of LMS are intramural and 10% submucosal

• Need >10 mitoses/ 10hpf for diagnosis

Endometrial Stromal Sarcoma

• Accounts for ~10% of uterine sarcomas• Tumor group divided into benign stromal

nodule , low-grade ESS and high grade ESS• Areas of hemorrhage, necrosis, and deep

myometrial invasion common in high grade ESS and 40% extend beyond the uterus at the time of diagnosis

Endometrial Stromal Sarcoma

Endometrial Stromal Sarcoma

Endometrial stromal sarcoma

Adenosarcoma

• First described in 1974• Rare• Composed of a benign epithelial and a

malignant non-epithelial component• Mean age between 55 and 60 years• Tend to be solitary masses in uterine

fundus

Adenosarcoma

• Disease usually limited to endometrium, but myometrial invasion is possible

• Sarcomatous element usually homologous and of lower grade compared to MMMT

• Adenosarcoma with Sarcomatous Overgrowth is a poor prognostic feature

Management of Uterine Sarcomas

• Surgery is the hallmark of treatment with TAH/BSO being the standard procedure

• For patients with advanced or recurrent disease, aggressive surgical intervention is unlikely to influence outcome.

• Bilateral oopherectomy is strongly recommended for patients with Low grade ESS

Management of Uterine Sarcomas

•Indications for adjunctive RT or primary RT parallels the indications for endometrial CA•Adjuvant RT has been shown to improve local control, effect on overall survival unknown

Management of Uterine Sarcomas

• MMMT- Ifosfamide (25% response), cisplatinum(18% response).

• LMS- only adriamycin appears to have significant activity (25% response rate)