This document summarizes information about uterine sarcomas, with a focus on leiomyosarcomas and endometrial stromal sarcomas. It discusses the clinical presentation, diagnostic challenges, classification, staging, prognostic factors, surgical management, and adjuvant therapies for these rare but aggressive uterine cancers. Key points include the difficulty of pre-operative diagnosis, the importance of surgical staging and cytoreduction, and the limited but emerging role of adjuvant therapies like radiation and chemotherapy.

1. UTERINE
SARCOMAS
Presented by:
DR KIRAN PANDEY
MBBS MS FRCOG FIMSA FICMCH MAMS
•PROF & HOD, DEPT OF Obs & Gyne, GSVM
MC
•PRESIDENT KANPUR OB&GYN SOCIETY
2016-18
DR PAVIKA LAL
ASSISTANT PROFESSOR
DEPT OF Obs & Gyne, GSVM MC

2. Prof. & Head. Department of OB/GY., G.S.V.M Medical College, Kanpur
Head of the Department since 10 years
DR. KIRAN PANDEY
M.D., FICOG, FICMCH, FIMSA, MAMS
ACADEMIC ACTIVITIES & RESEARCH ACTIVITIES
Published > 100 research Papers in National & International Journals, and presented 45 Research Presentation
in National Conferences. Best prize for 3 papers in AICOG.
 As Secretary KOGS & Scientific Secretary IMA organized several CMEs & workshop.
•Important Project for in vivo detection of cervical pre cancers with
IIT Kanpur.
•Evaluation of Progesterone vaginal ring (PVR) in India with ICMR
• Active participation in Govt. programs like ICMR, SIFPSA, PPTCT ,IYCF, NRHM.
 Special Areas Of Interest-Menopausal problems, Oncology, Infertility, Adolescent health, Gynae plastic surg.
 Contributed a chapter – Gestational diabetes in “Current trends” in Obst. & Gynae.
AWARDS ACHIEVED
 Received 9 National, 6 State level & 8 District level Awards & more than 25 awards at IMA.
 Felicitated on World women’s day for being a “WOMEN OF SUBSTANCE”.
MEDICO SOCIAL ACTIVITIES
Received 8 awards from various Social Organization & is Actively participating in Health campus, Awareness seminars on
female feticide ,organ donation and Adolescent Health.
Actively involved in Kanpur Obstetrics & Gynaecological Society in various capacities & is presently working as Honorary
President, KOGS.
Nominated as central zone coordinator 2013-14 by National Adolescent Health Committee of FOGSI.
1995-AICOG: Chairman poster committee, 2006- UPCON: Chairman Scientific committee, 2011- FORCE: Organizing se

3. CLASSIFICATION
Uterine
sarcomas
Leiomyosarcomas(LMS)
most common(25-36%)
Arise from the smooth
muscle of the
myometrium
Endometrial stromal
tumours(ESS)
Arise From the
endometrial stroma.
Incidence (.2%)
Mixed mesodermal
tumour /
Carcinosarcomas (MMT)
Arise from both epithelial &
mesenchymal components
Incidence (.6%)

4. LEIOMYSARCOMA-
EMERGING CHALLENGES

5. INTRODUCTION
Uterine sarcomas accounts for 3–7% of all
malignant diseases of the uterine corpus
Incidence of LMS is <2/100,000women
 Notorious for their aggressive nature and poor prognosis,
because of their location in the vascular myometrium of
the uterus
early invasion and widespread metastases, particularly to
the lungs.

6. Learning objectives-
 To appreciate the diagnostic challenges
faced with LMS especially in view of the
similarities with uterine fibroids.
 To learn about the current views on
surgical treatment and adjuvant therapy.
 To have an understanding of the novel
therapies currently under investigation.

7. CLINCIAL PRESENTATION
Median Age – 47-56 years
Risk factors:-
i) Nulliparity.
ii) Increasing age
iii) Obesity.
iv) History of pelvic radiation.
v) Exposure to tamoxifen.

8. Symptoms:-
No symptoms specific for LMS
Abnormal vaginal bleeding &
Pelvic/abdominal pain are m/c c/p but
similar to fibroids further
compounds the difficulty in diagnosis
Incidental finding of LMS at surgery
remains the m/c form of presentation
as preop dx remains inadequate.

9. PITFALLS IN DIAGNOSIS
As conservative non-surgical techniques (eg.-
Uterine artery embolisation & use of GnRH )of
treating fibroids are becoming more popular, non-
detection of LMS is a major concern delay in
diagnosis delay in instituting the appropriate
treatment.
• Mostly detected at time of HP evaluation of a
hysterectomy or myomectomy
specimen(incidence of LMS in women operated
for uterine fibroids is about 0.5%*)
• *Leibsohn S, d’Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of
hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol
1990;162:968–74;discussion 974–6.

10. DIAGNOSIS
 MRI&CECT are not specific difficult to distinguish LMS
from degenerating uterine fibroids.
 Combined use of dynamic MR(gd enhanced)I and serum
measurement of LDH(3) isozyme the diagnostic value
to 100 %.
T1 T2
Fibroid homogeneous and
hypointense
homogeneous and
hypointense
LMS heterogeneous
hyperintense
irregular borders
and areas of
haemorrhage or
necrosis

11. Dynamic MRI Image(gadolinium enhanced)
T2-weighted imaging in preop pelvic MRI (A) Sagittal slice showing an irregular tumor
with high-signal intensity extending from the cavity to the right posterior wall of the
uterus (arrow 1). (B) Axial slice showing extension of the tumor to the right adnexa and
vessels (arrow 2) and the right internal iliac vein (arrow 3).

12. MRI image of uterine fibroid
A degenerating fibroidMRI showing normal fibroid

13. .
LMS LEIOMYOMA
CYTOLOGICAL ATYPIA
+
Moderate to severe
-
HIGH MITOTIC INDEX
+
≥10 per 10 HPF
+/-
COAGULATIVE TUMOUR
CELL NECROSIS + -
Leiomyoma showing spindle shaped cells
with elongated nuclei uniform in size with
Varying amount of connective tissue
HISTOLOGY

14. Leiomyosarcoma
1- Interface between viable and necrotic tumor is sharp
2&3- Cytologic atypia is noted within the necrotic area.

15. STUMPs(smooth muscle tumours of unknown
malignant potential) have some characteristic
features of LMS, but do not meet full criteria
The absence of coagulative necrosis and atypia
suggest a fibroid, even if the mitotic count is as
high as 20
Histological diagnosis by endometrial sampling
is unreliable as it cannot provide an accurate
result unless the tumour has reached the
surface of the endometrial cavity which gives a
low sensitivity of approximately 30%

16. IMMUNOHISTOCHEMISTRY
LMS stain +ive for SMA(smooth muscle actin),
desmin and caldesmon.
ER and PR expression is significantly lower in
LMS than leiomyoma (ER:40%vs78%; PR: 38% vs
88%).
Immunopositivity for p16 and p53 with a high
Ki-67 proliferation index also has been shown to
have high sensitivity and specificity for
differentiating LMS and leiomyomas.
(Differentiates LMS from leiomyoma)

17. A&B- IHC staining of diagnosed LMS for antibodies Against smooth muscle Actin and Desmin.
C&D- Staining negative for SMA and Desmin (leiomyoma)

18. FDG SUV correlates with greatest dimension of tumor & tumor grade . So it is
important in terms of prognostication

20. FIGO( International Federation of Gynecology and Obstetrics) STAGING
I Tumour limited to the uterus
IA Tumour 5 cm or less in greatest dimension
IB Tumour more than 5 cm
II Tumour extends beyond uterus but within pelvis
IIA Tumour involves adnexa
IIB Tumour involves other pelvic structures
III Tumour infiltrates abdominal tissue
IIIA One site
IIIB More than one site
IVA Tumour invades bladder and/or rectum
IVB Tumour with distant metastasis
FIGO STAGING(2009)

21. Tumour stage and grade main prognostic
factors that have been shown to influence
disease specific mortality. Role of other
factors unproven
Overall, tumour stage has been confirmed
as the strongest prognostic variable.
The 5-year OS is 62–65% in studies that
included predominantly stage I disease, but
in studies with a higher proportion of
advanced disease it is as low as 29%.*
* Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine
leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer
2008;112:820–30.

22. Other Prognostic factors
Age
Vascular space involvement
Mitotic count
 Residual disease at surgery
Adjuvant chemotherapy

23. PRINCIPLES OF MANAGEMENT
It is universally accepted that surgery is primary
treatment for LMS.
A TAH and BSO and appropriate surgical staging,
including peritoneal washings and sampling of
suspicious nodules, should be carried out .
It is recommended that aggressive surgical
cytoreduction at the time of initial diagnosis offers
the best possibility of prolonged survival.

24. SURGICAL MANAGEMENT
Three areas of contention with regard to
surgery are:-
 i) Oophorectomy in the premenopausal
women.
 II) Incidental finding of LMS in myomectomy
specimen.
 iii) Role of Pelvic lymphadenectomy(PLND) in
early LMS

25. DILLEMMAS IN SURGICAL Mx
1.Oophorectomy in the premenopausal
women(still debatable) ??????
 Some LMS express ERs with concern for the effect of
hormonal stimulation of tumour inclination to BSO
– Low reported incidence of ovarian mets in uterine LMS.
– Several studies show no difference in OS and recurrence rates in
early stage disease with ovarian conservation
consider ovarian conservation in young
women with early stage disease

26. 2.Incidental finding of LMS in myomectomy
specimen?
a completion procedure with total hysterectomy,
trachelectomy and/or bilateral salpingo-
oophorectomy is recommended.
A conservative approach following myomectomy
should only be taken for specific and accurately
selected women who strongly desire pregnancy
and well counselled about the risks involved.

27. ETHICAL ISSUE (effect of morcellation)
 morcellation may lead to
dissemination of
undiagnosed malignancies,
in particular LMS.
 Risk of undetected uterine
malignancy is 0.27% in
women undergoing
minimally invasive
hysterectomy for presumed
benign disease*, & 0.09% in
women undergoing
myomectomy with
morcellation**
*Wright JD, Tergas AI, Burke WM, Cui RR, Ananth CV, Chen L, et al.Uterine pathology in women
undergoing minimally invasive hysterectomy using morcellation. JAMA 2014;312:1253–5.
**Wright JD, Tergas AI, Cui R, Burke WM, Hou JY, Ananth CV, et al. Use of electric power
morcellation and prevalence of underlying cancer in women who undergo myomectomy. JAMA
Oncol 2015;1:69–77

28. THE MORCELLATION CONTROVERSY
• Amy Reed (an anesthesiologist) was diagnosed with fibroids and was
advised TLH with morcellation but things didn't go as expected. Dr.
Reed learned that she had a uterine leiomyosarcoma and THE
MORCELLATION MAY HAVE WORSENED HER PROGNOSIS
• Since then, Dr. Reed's husband, has led a campaign calling for a ban
on morcellation.
• FDA on April 2014 announced that it discourages the use of
laparoscopic power morcellators in most hysterectomy and
myomectomy procedures especially in suspected or confirmed
uterine malignancies/ peri or post menopausal women with fibroid
because of the risk of spreading unsuspected cancerous tissue.

29. Role of Pelvic lymphadenectomy(PLND) in
early LMS
Incidence of LN mets from uLMS is very low &
unlikely in the absence of extrauterine disease.
Routine PLND is not usually done for women with
the disease confined to the uterus and with
normal LNs on observation and palpation
LN status may have a role as a staging procedure
& in determining the need for adjuvant pelvic RT
but its therapeutic benefit is still to be proven

30. Management of Early uterine LMS
SURGERY
ADJUVANT
PELVIC RT
SYSTEMIC CT
EORTC trail(55874) – 13 years study -224
patients- 2 groups – observation & RT(51Gy
in 28# over 5 weeks)
No beneficial impact on OS
Premenopausal women:- TAH
+/- PLND ( in presence/absence
of extrauterine disease
respectively)
Postmenopausal female:- TAH +
BSO

31. Limited studies available- ongoing phase III
trial(NCTO1533207*)
Observation 4 cycles of adjuvant GEMCITABINE+ DOXORUBICIN
additional 4 cycles of DOXORUBICIN( regimen well tolerated)
This trial is still underway
*A RCT of adjuvant CT vs observation to determine
if adjuvant CT can improve OS in early uLMS
CT

32. ADVANCED OR METASTATIC UTERINE LMS
SURGERY
ADJUVANT
PELVIC RT
No role
LMS recurs only at
Metastatic sites
Secondary cytoreduction
surgery
Pulmonary mets
resection
Improved OS
SYSTEMIC CT
met. disease beyond the
Pelvis- not surgical candidates
OTHER MODALITIES
gemcitabine + docetaxel
- best regimen

33. OTHER MODALITIES
Targeted
therapies
Hormonal
therapies
Epigenetic
regulators
Pazopanib, Bevacizumab, Alisertib
Expression of ER and PR -70–80%
of uterine LMS
Aromatase inhibitors
Belinostat,
(HDAC inhibitor)
Needs further research

34. Conclusion-
m/c uterine sarcoma
Notoriously aggressive in nature.
Preop dx is difficult & usually detected as an
incidental finding at surgery.
Tumour stage is the most important prognostic
factor.
Primary treatment is surgical(in early/
advanced/ recurrent ) while role of adjuvant
therapy(RT/CT) is still to be clearly defined.
Gemcitabine + docetaxel- best regimen for
adjuvant CT.

35. ENDOMETRIAL STROMAL
SARCOMA

36. • ESS - very rare(.2%) of all uterine malignancies
• Annual incidence - 1–2 per million women
• An indolent tumor with local recurrences and
distant metastasis can occur even 20 years
after initial diagnosis. Median age-36-48yrs

37. ENDOMETRIAL STROMAL NODULE:
Well circumscribed, non encapsulated
Finger like projections into the myometrium <3mm & <3 in no.
No vascular invasion
LOW GRADE ESS:
irregular nodular growth in endometrium
Infiltrates(worm like) myometrium, myometrial & parametrial
veins
Cellular atypia & pleomorphism absent
Mitotic activity <5/10HPF
UNDIFFERENTIATED ESS(earlier k/a high grade ESS)
Resemble sarcomatous component of carcinosarcomas
Lack typical growth patterns and vascularity
Displaces myometrium(in contrast to infiltration in low gr ESS)
Abundant mitotic activity & marked cellular atypia
Shows prominent hemorrhages & necrosis within polypoidal
fleshy endometrial masses.

38. CLINICAL FEATURES
abnormal uterine bleeding(90%)
pelvic pain
dysmenorrhoea
• asymptomatic in 25% individuals
• 30 to 50% cases - extra uterine spread at the
time of the diagnosis
• Rarely ESS is initially present at an extra
uterine site(m/c ovary) – primary/ metastatic
lesion from an occult tumor of endometrium
or from a previously undiagnosed case where
a hysterectomy was done for a benign
leiomyoma of the uterus.

39. DIAGNOSIS
• similarity of ESS with normal endometrium+ the
lesion is almost always intra-myometrial
impossible to diagnose it with certainty on
curettage fragments
definitive diagnosis can be made only on a
hysterectomy specimen
• RADIOLOGY: USG –unreliable;
MRI
useful in preop diagnosis.
Bands of low signal intensity within myometrium.
Continuous extension of lesions into adjascent
structures(vessels & ligaments)

40. Endometrial stromal nodule-
Multiple collagen bundles are
interspersed among the
neoplastic stromal cells
high-grade endometrial stromal
sarcoma. Tumor cells with an
epithelioid morphology (left)
are juxtaposed to areas of
endometrial stromal neoplasia
with a fibroblastic appearance.
HISTOLOGY

41. IMMUNOHISTOCHEMICAL FEATURES
Low-grade endometrial stromal sarcoma
with smooth muscle differentiation.
Desmin immunoreaction highlights the
smooth muscle component (‘starburst’)
with minimal reaction of the background
endometrial stroma
high-grade endometrial stromal sarcoma.
CD10(cell surface neutral endopeptidase)
Positivity- helps in differentiating from
leiomyoma .H-ESS is almost always + for
ER & PR
IMMUNOHISTOCHEMISTRY: Strong and/or diffuse positivity for CD10 ; ESS is almost
always positive for both ER & PR

42. MRI image of ESS showing
increased intensity of the tumor
In comparison to normal
endometrium. It also shows
Continuity of tumor into broad
and round ligaments

43. stage Definition
Stage 1 CONFINED TO UTERUS
1A Tumor limited to endometrium/endocervix. No myometrial invasion
1B <= half of myometrial invasion
1C >half of myometrial invasion
Stage 2 EXTENDS TO PELVIS
2A Adnexal involvement
2B Extra uterine pelvic tissues
Stage 3 INVADES ABDOMINAL TISSUES
3A One site
3B > One site
3C Metastasis to pelvic & para aortic lymph nodes
Stage 4
4A Invades bladder &/or rectum
4B Distant metastasis
FIGO STAGING OF ESS

44. PROGNOSTIC FACTORS
• older patients (>50 yrs)
• black race
• advanced stage
• nodal metastasis
• high mitotic count(>5/10HPF)
• CD10 negative
• lack of ER&PR
• Lack of primary surgery
INDEPENDENT
POOR
PROGNOSIS
ESS has a better life expectancy than other sarcomas

45. TREATMENT
• TAH + BSO (aggressive cytoreduction) is the
most effective treatment for ESS
• Considering the adverse effects of early
surgical menopause, retention of ovarian
function may be an option for premenopausal
women with stage-I ESS.
• In all other stages, BSO is recommended
• PLND - for both prognostic and treatment
purposes

46. ADJUVANT THERAPY

47. HORMONAL & TUMOR DIRECTED
THERAPY
The mechanism of action of progestins is to bind
progesterone receptors and down regulate gene
transcription leading to decreased endometrial
gland and stromal proliferation. GnRH agonists
down regulate GnRH receptors in the anterior
pituitary leading to a hypoestrogenic state.
megestrol/medroxy progesterone(160mg/d)
gonadotropin releasing hormone (GnRH)
analogues(7.5mg/month IM)
aromatase inhibitors

48. MALIGNANT MIXED
MÜLLERIAN
TUMOURS

49. MALIGNANT MIXED MÜLLERIAN TUMOURS

50. • MMT is a rare(0.6/1,00,000 women), highly
aggressive, rapidly progressing neoplasm
associated with a poor prognosis
• MMT is a biphasic tumour of the female genital
tract, composed of epithelial and mesenchymal
tissues. Median age- 62yrs.
• two categories: homologous and heterologous.
The homologous type: has tissues native to the
uterus(endometrium or smooth muscle)
The heterologous type: cartilage, skeletal muscle, or bone
is present which is not native to the uterus.

51. RISK FACTORS
• Nulliparity
• Advanced age
• Obesity
• Exposure to exogenous estrogens
• Long-term use of tamoxifen
• Pelvic RT

52. Stage Extent
Stage 1 Tumor confined to corpus uterii
1A <half of myometrium
1B >= half of myometrium
Stage 2 Invasion of cervical stroma but does not extend beyond uterus
Stage3 Loco-regional spread
3A Invades serosa of uterus / adnexa
3B Vaginal or parametrial involvement
3C Mets to pelvic &/or para aortic nodes
3C1 Pelvic nodes +
3C2 Para aortic nodes +
Stage4 Distant metastasis
4A Invasion of bladder orbowel mucosa
4B Intra abdominal &/ or inguinal nodes
CLASSIFICATION- MMTs are staged like CA endometrium

53. TYPICAL PATIENT PROFILE PRESENTING WITH UTERINE
CARCINOSARCOMA
Elderly female (usually 60–70 years), usually
postmenopausal
Presents with pyometra with vagina bleeding,
bloody/watery discharge, abdominal pain, and/or
mass (symptom triad)
Often past history of tamoxifen use
May be obese, hypertensive, nulliparous, and/or
diabetic
No previous history of uterine problems

54. DIAGNOSIS
• HISTOLOGY: unique biphasic morphology-both
epithelial and mesenchymal elements
• IHC: express epithelial membrane antigen (EMA),
pancytokeratin and stromal lineage markers in
relation to their histological appearances such as
desmin in muscle differentiation or S100 in areas
with chondroid or lipomatous differentiation
• Overexpression of tyrosine kinase receptors such
as HER-2(human epidermal growth factor
receptor ), EGFR(Epidermal growth factor
receptor), and KIT(a part of tyrosine kinase
receptor)

55. A-F:Homogeneous hyperintense intrauterine mass, enhancing with gadolinium,invades the myometrium
Lymphadenopathies are present, Surgery : large irregular mass Gross specimen: endometrial cavity
completely occupied by a polypoid lobulated tumor gray and dun with white areas (4,5x3,5 cm). It
invades the whole thickness of the uterine wall on the left side. On microscopic exam poorly
differentiated areas predominate over areas of adenocarcinoma with squamous spots mixed with
sarcomatous areas with muscular differentiation

56. • on MRI uterine MMTs may be indistinguishable
from endometrial carcinomas
• Enhancement equal to or greater than that of
the myometrium suggests the possibility of this
tumour-type
• CECT & 18F-Fluorodeoxyglucose Positron
Emission Tomography (18F-PDG PET) Scans are
other modalities useful in diagnosis

57. TREATMENT
• The primary treatment option is surgery
• High rates of relapse and metastases
postoperatively necessitate effective adjuvant
therapies
• surgical practice recommended for uterine
carcinosarcoma is surgical staging with TAH
with BSO, pelvic lymphadenectomy, and para-
aortic lymph-node sampling with peritoneal
washings.

58. • Radiotherapy contributes to decreased pelvic
recurrences
• Controversies still remain regarding the
techniques of radiation: localized pelvic radiation
by vaginal brachytherapy versus whole abdominal
radiation by external beam
• chemotherapy has a definitive role to minimize
both local and distal recurrence
• A combination of paclitaxal & carboplatin results
in RR of 80% and median disease free interval of
18months

59. SURGICAL STAGING(AGGRESSIVE CYTO-REDUCTION)
(TAH+BSO+PLND+PERITONEAL WASHING+OMENTAL BIOPSY)
STAGE 1&2 STAGE 3 STAGE 4
CYTO-REDUCTION SURGERY + RADIATION
(VAGINAL BRACHY/ EB RT)
? ROLE OF CYTO-REDUCTION SURGERY
ADJUVANT CHEMOTHERAPY
+HARMONAL THERAPY+MOLECULAR TARGETED
THERAPY