This document discusses uterine sarcoma, its classification, features, diagnosis, and management. The main points are: 1. Uterine sarcoma arises from the myometrium or connective tissue of the endometrium. It includes leiomyosarcoma, endometrial stromal sarcoma, and other rare subtypes. 2. Diagnosis involves imaging such as ultrasound, MRI and biopsy. Treatment depends on the subtype and stage but generally involves a hysterectomy with or without chemotherapy or radiation for advanced stages. 3. Prognosis is generally poor, even in early stages, with high recurrence rates. Ongoing research focuses on improving staging systems and adjuvant therapies to

1. Uterine Sarcoma
And Its
Management
G . Lakshmi Deepthi

2. Sarcoma : ( sarx -"flesh")
is a cancer that arises from transformed cells
of mesenchymal origin
Uterine sarcomas arise from dividing cell
populations in the myometrium or connective
tissue elements within the endometrium
Uterine sarcomas :
1% of female genital tract cancers
3-7% of uterine cancers

3. WHO classification
2014

4. WHO classification 2014

5. Uterine Sarcoma Classification :
NCCN 2016
• Low grade endometrial stromal sarcoma(ESS)
• High grade ESS
• Undifferentiated Uterine Sarcoma(UUS)
• Uterine Leiomyosarcoma (uLMS)
Other Rare Uterine Mesenchymal Sarcoma Subtypes :
• Adenosarcoma
• PEComas
• Rhabdomyosarcoma

7. General Features :
 Each group of tumors is distinct with respect to pattern of
spread, pathologic features, prognostic factors and response to
treatment.
 Incidence : carcinosarcomas (45%) > leiomyosarcomas,
(40%) > endometrial stromal sarcomas(15%)
 Age-related incidences vary among the histologic types. The
mean age at diagnosis for endometrial stromal sarcoma is 41
years, for leiomyosarcoma 53.5 years, for adenosarcoma
57.4 years, and for carcinosarcoma 65 years
 Staging system different for each
Leiomyosarcoma and ESS
Adenosarcoma
Carcinosarcoma

8. Rare sarcomas
 Clinical features
 Pathology
 Diagnostic workup
 Treatment
• Leiomyosarcoma
• ESS
• Carcinosarcoma

9. Leiomyosarcoma
malignant neoplasm composed of cells demonstrating smooth muscle
differentiation true sarcomas
 1-2% of all uterine tumors
 30% of all uterine sarcomas
 >40yrs of age
 Presentation :
vaginal bleeding (56%)
pelvic mass(54%)
pelvic pain (22%)

10. Diagnosis:
 Preoperative– endometrial sampling
pelvic ultrasound
MRI
CT chest
 Postoperative –
---No second surgical procedure for the sole purpose of
staging.
---postop CT of the chest, abdomen, and pelvis.

11.  Pelvic ultrasound is typically the first-line study
 S/o sarcoma --mixed echogenic and poor echogenic
parts; central necrosis
 Color Doppler -- irregular vessel distribution, low
impedance to flow, and high peak systolic velocity
 CT does not reliably differentiate between leiomyomas
and uterine sarcomas

12. T1 MR T2 MR
• MRI vary and include a lobulated mass of high-signal intensity on T2-
weighted images,
• scattered foci of haemorrhages or necrosis
• These necrotic areas are -- slightly higher intensity on T1-weighted
images and as heterogeneous areas on T2-weighted images.
• A consistent finding -- the absence of calcifications.

13. Pathology :
Gross:
 solitary intramural masses
 Average 8cm in diameter
 fleshy with poorly defined margins.
 Cut section : typically soft, bulging, fleshy, necrotic,
hemorrhagic, and lacks the prominent whorled
appearance of leiomyomas.
Microscopic :Stanford criteria
High nuclear atypia
Coagulative necrosis
High mitotic rate

14. Variants :
Epitheloid :
Necrosis absent
Mild nuclear atypia
Less mitotic rate
Myxoid :
hypo cellular
Mild nuclear atypia

15. IHC :
 Positive for smooth muscle markers
Desmin ,H-Caldeson , actin, histone deacetylase 8
 Epitheloid and myxoid variants are less immunoreactive
 Epitheloid –keratin ,EMA positive
 ER+,PR +,androgen receptor + --30-40 % of cases
 Ki 67 increased
 P16 overexpressed – differentiate between benign and
malignant

16. Staging :FIGO 2009

17. Total abdominal Hysterectomy
+/-
B/L Salpingo-oopherectomy
TREATMENT
Disease confined to uterus Disease extending outside uterus
TAH with BSO and surgical
cytoreduction of intra-
abdominal and
retroperitoneal disease

18. Lymphadenectomy
???
 If the pelvic nodes are palpably enlarged intraoperatively
 there is evidence of extrauterine disease
LN involvement <5%
1992

19. Prognostic factors :
 Tumor size (>10cm)
 Mitotic rate (20 MF/10HPF)
 Ki 67 (>10%)
 Bcl 2 (Negative)
Overall prognosis :
 Poor even in stage I disease
 Recurrence – 53-71% ---lungs -40%
Pelvis – 13%
 5yr survival – 15-25% of cases
 Median survival – 10 months
STAGE 5YR OS
I 76%
II 60%
III 45%
IV 29%

20. Adjuvant Treatment :
 Chemotherapy or Pelvic radiation can be considered
following surgery for leiomyosarcoma (LMS).
 However, whether any form of adjuvant therapy
improves survival compared with observation is not
known.
 Early stage disease (I or II)– it is not clear if any
intervention improves the survival outcomes compared
with post-surgical surveillance.
Observation is preferred

21. Neither PFS, nor OS nor pelvic control was
improved by radiotherapy. Therefore, radiation
therapy is not indicated in patients with stage I or
II LMS after complete resection

22. Stage I or II sarcomas, varied histology
• women treated with doxorubicin had a lower
recurrence rate compared with those not treated
with chemotherapy (41 versus 53 percent), this was
not statistically significant.
• In addition, adjuvant doxorubicin had no impact on
progression-free or overall survival.

23. • To estimate 2yr and 3yr PFS….n=46
• 4 cycles of gemcitabine plus docetaxel f/b 4 cycles of
doxorubicin
• 2yr PFS – 78% 3yr PFS – 57%
• median time to recurrence was 27 month
N=27
Single arm,phase II
Completely resected I-IV2yr PFS-59% Median PFS -39months

24. Advanced stage – Radiotherapy??
• Sampath et al.--significantly reduced local
failure rate at 5 years of 2%, compared with
16% in the surgery-alone group

25. NCCN– 2B Recommendation in LMS
 high rates of initial metastatic failure in LMS
 adjuvant pelvic radiotherapy does not appear to have a
survival benefit in LMS,
 although it may reduce local pelvic recurrences, possibly
for disease that has spread beyond the uterus (FIGO
stages II–IV)
so might be considered for these higher risk
women in order to improve local disease control.

26. Chemotherapy In Uterine
Leiomyosarcomas :
GOG 277

27.  chemotherapy with doxorubicin or
docetaxel/gemcitabine is now used for advanced or
recurrent disease, with response rates ranging from
27% to 36%

28. • Early-stage --leiomyosarcoma,
carcinosarcoma, and
endometrial stromal sarcoma
• CRT arm--increased 3-year DFS
(55% vs 41%; P=0.048),
• But no improvement in 3-year
OS
Combined Modality

29. Metastatic or inoperable disease
:
 Palliative intent.
 Chemotherapy --good performance status and in
whom organ function permits the use of
cytotoxic chemotherapy.
 For other patients--palliative care
 Doxorubicin-based treatment first-line choice.
 Gemcitabine plus docetaxel--first- or second-
line therapy

31. Alternatives Or Second Line Therapy:
 Doxorubicin based
 Gemcitabine alone RR-20%
 Ifosfamide alone – RR-17%
 Ifosfamide + Doxorubicin – RR 30%
 Trabectedin –progression on anthracyclines –ORR-
16%
 Pazopanib
 Erbulin
 Endocrine Therapy– ORR<10%--Aromatase
inhibitors can be considered for ER/PR- expressing
uLMS

32. Follow Up:
 Physical exam every three to four months and
chest, abdomen, and pelvic imaging every three
to four months for two to three years,
 every 6 to 12 months for the next two years.
Recurrence

33. STUMP :Smooth Muscle Tumors Of
Uncertain Malignant Potential
 Have high malignancy features but not falling into
diagnostic criteria for leiomyosarcoma .
 Microscopic : tumor cell necrosis
necrosis of uncertain type >10 MF/10HPF
diffuse atypia
borderline mitotic counts
 Favorable prognosis
 Treatment – only follow up after total hysterectomy

34. Endometrial Stromal Sarcoma
• 0.2–1% of all uterine malignancies
• 6–20% of all uterine sarcomas

35. Norris and Taylor 1965 (old
terminology)
 Endometrial Stromal Nodule
 Endometrial Stromal Sarcoma
– Low grade (< 10 mits/10 hpf)
High grade (>10 mits/10 hpf)
 Undifferentiated Uterine Sarcoma
Mitotic rate does not predict recurrence
WHO Classification 2004

36. WHO 2004
 Endometrial Stromal Nodule
 Endometrial Stromal Sarcoma (“low grade”)
 Undifferentiated Uterine Sarcoma
WHO 2014
 Endometrial stromal nodule (ESN)
 Low grade ESS
 High grade ESS
 Undifferentiated
Cytogenetics

37.  2nd most common mesenchymal uterine
tumors (<10%)
 ESN and low grade ESS are similar in
morphologic ,IHC , molecular features
differentiation based on
the myoinvasive growth pattern
and LVI

38. ESN :
 Rare ,benign
 Premenopausal
 Presentation – abnormal bleeding or abdominal or pelvic
pain
 10% - asymptomatic
 Gross – well circumscribed
non encapsulated
fleshy yellow to tan nodule
 Location – myometrium ,protruding into endometrium
 Infarct type necrosis – 60%
 Cyst formation – 30%

39. CD 10+
Microscopic :
 Expansile
 non infiltrative border
 Compresses surrounding myometrium and
endometrium
 Has finger like projections into myometrium
Length -3mm
Number < 3

40.  If length >3mm
number > 3
LVI +
 satellite nodules
focal infiltrative growth
Treatment :
 Hysterectomy only– Benign
 Follow up
Low grade ESS
ESN with
limited invasion

41. LGESS
 History and presentation same as ESN
 Premenopausal
 Intial presentation – mostly intrauterine
rarely with metastasis to lungs and ovaries
 lymph node metastasis – 10%
 Gross – involves endometrium
soft ,tan to yellow polyp- infarcted/haemorrhagic
Invades myometrium

42. Microscopic :
 Formation of irregular , pink ,tan yellow cords or
nodules of tumor
 Involves endometrium and infiltrates myometrium as
irregular tongues with LVI
 Well differentiated endometrial stromal cells
 Mild nuclear atypia
 Necrosis rare

43. IHC :
 ER+ PR+ Androgen + WT-1 +
 CD 10 ++
 Smooth muscle actin +
 Desmin less positive,30%
 Negative – HDAC8 , H caldesmin
 Nuclear Beta catenin + in 40% of cases

44. Cytogenetics :
 The most common translocation involves the short arm of
chromosome 7 and the long arm of chromosome 17 [t(7;17)] leading
to fusion of two zinc finger genes, JAZF1 and JJAZ1 (also referred to
as SUZ12), and the production of the JAZF1/JJAZ1 gene fusion
protein.
 This is characteristic of ESS
 Function of JAZF1, JJAZ1, or the JAZF1/JJAZ1 gene fusion has not
been determined; however, in cultured cells, the fusion gene appears to
modulate cell survival and proliferation
 Other gene fusion proteins :
t(6;7) JAZF1/PHF1
t(6;10) EPC1/PHF1

45. Nature : LGESS
 low grade
 Favorable prognosis
 Stage is prognostic
STAGE 5Yr survival
I, II 90%
III, IV 50%
Course :
 Indolent
 Late recurrences – early stage – 36-56% recurrences
 Median time for recurrence – stage I-65months
stage III,IV -9 months

46. High Grade ESS :
 Features between low grade ESS and undifferentiated
 Age -28-67yrs
 Presentation – abnormal vaginal bleeding
enlarged uterus
pelvic mass
 Gross – intracavitatory polypoid
and pelvic mass
size upto 9cm
 Shows extrauterine extension at time
Of diagnosis

47. Cut section :
 Fleshy with extensive areas of necrosis and haemorrhage
Microscopic:
 High grade round cells with low grade spindle cell
component – fibromyxoid
 Mitotic activity - >10/10HPF
 Necrosis +

48. IHC :
 C Kit +
ER - PR - CD 10 -
CYCLIN D1 ++

49. Cytogenetics :
 The t(10;17) rearrangement results in a 14-3-3 fusion to
FAM22 (known as YWHAE-FAM22), leading to
aberrant localization of 14-3-3 in the nucleus and
possible oncogenic transformation
 is associated with a high-grade variant of ESS
 Clinically more aggressive and carries a worse prognosis
 However, it does not display prominent nuclear
pleomorphism, which is generally seen with UES

50. Undifferentiated :
 Heterogeneous group of sarcomas lacking diagnostic
criteria for:
ESS
LMS
Adenosarcoma with sarcomatous overgrowth
Carcinosarcoma/poorly differentiated carcinoma
 UES also expresses the receptor tyrosine kinase CD117
(c-KIT) and human epidermal growth factor receptor 2
(HER2 or ERBB2), which are not typically found in ESS.
 Unlike ESS, there are no known chromosomal
abnormalities associated with UES.

51.  Rare
 Post menopausal -60yrs
 Presentation : post menopausal bleeding
complaints secondary to extra-uterine disease
 Usual presentation with Stage III,IV disease
UES is always a
diagnosis of exclusion

52. Microscopic :
 Myometrial invasion
 Nuclear pleomorphism
 High mitotic activity
 Tumor cell necrosis
lack smooth muscle or endometrial stromal
differentiation
 They lack the typical growth pattern and vascularity of
low grade ESS and displace the myometrium in contrast
to the infiltrative pattern of low grade ESS

53. Uniform type Pleomorphic type

55. Imaging :
• Ultrasound—non specific
typically characterized as a heterogeneous
hypoechoic endometrial mass, which can show
extensive myometrial involvement

56. larger size, more contrast enhancement, irregular margin,
nodular extension into the myometrium, and marginal
nodularity due to tumor extension along vessels and
lymphatics

57. Staging :FIGO 2009

58. Diagnosis
BIOPSY POST HYSTERECTOMY
• Baseline imaging
• Confined to uterus– TAH+BSO
• Extra uterine disease +
Maximal Cytoreduction
NO MORCELLATION
NO Ovary Sparing
• Baseline imaging
• No second surgery
for staging

59. 2

60. Role of Cytoreduction !!!
• High-grade ESS,
<2 cm of residual disease -- longer median OS –
52 versus 2 months
• Low grade ESS – No clear role

61.  older patients
 black race
 advanced stage
 higher grade
 lack of primary surgery,
 nodal metastasis

62. Adjuvant Therapy :
 ESN – None
 Low grade ESS –
Stage I –observation
Stage II-IV – hormonal therapy
Radiotherapy can be given to reduce local
recurrences
 High grade ESS and Undiferrentiated ESS
Adjuvant therapy to be given in all stages

63. Low Grade ESS :
no significant differences in the rate of recurrence
between surveillance vs. adjuvant RT vs. progestin
therapy
STAGE 5yr OS 10yr OS
I 84% 77%
II 62% 49%
III 58% -
IV 37% -
STAGE I

64. Hormonal Therapy
 Only in Low grade ESS
Options :
 Progestins--megestrol/medroxy progesterone
 Aromatase inhibitors– Letrozole/Anastrazole
 Gnrh Analogues
Tamoxifen, as well as hormonal replacement
therapy containing estrogens are contraindicated in
patients after treatment of ESS

65. Basis :
Primary ESS
ER α
PR α
PR β
ERα
ERβ
PRα
PRβ
STEROIDS
Proliferation and
Differentiation of
endometrial
Stromal cells
Normal endometrium
Recurrent ESS
ER α
PR α
PRβ
Progestin's -- antiestrogenic activity after binding to progesterone
receptor
Medroxyprogesterone acetate (MPA)(250mg daily)
Megestrole acetate (160mg daily)
• Side effects :
dramatic weight gain related to glucocorticoid activity, severe depression
and thrombo- embolic complications

66. • Aromatase inhibitors :-- reduce estrogen levels by
inhibiting estrogen synthesis in peripheral sites and tumor
tissues, which leads to reduced receptor-mediated growth
stimulation
1st generation—aminoglutethemide
2nd generation—formestan,fadrozol
3rdgen. –nonsteroidal -- exesmestane(25mgday)
letrozole(2.5mg/day)
steroidal– anastrazole(1mg/day)
• Gnrh Analogues :-they suppress ovarian estrogen
production.
additional growth inhibitory effect via intratumoral
modulation of mitogenic signaling of growth factor receptors
leuprolide, gosereline, triptorelin

68. Drug of choice –Aromatase inhibitor

69. Cytotoxic chemotherapy:
ifosfamide , doxorubicin –most active
 Hormonal options is exhausted
 in the absence of hormonal receptors
 when progression into a high-grade malignancy
occurs
Duration???

70. Radiotherapy???
Radiotherapy helps to improve local control
Can be given in stage II-IV ESS

71. ESS :
 Sampath et al.--showed a significant decrease in 5-
year local–regional recurrence rate
 Most studies--improvement in local control with
adjuvant radiotherapy

72. Undifferentiated ESS:
 Poor OS regardless of stage
 Due to high risk of recurrence
regardless of stage , adjuvant
chemotherapy should be given to all patients with
UES.
 Combination regimen eg: gemcitabine plus
docetaxel is preferred
STAGE MEDIAN PFS MEDIAN OS
I 15months 27months
II-IV 7months 12months

73. Follow Up : NCCN
• physical exam every three months for the first
two years and then every 6 to 12 months.
• CT scans of the chest, abdomen, and pelvis
every 6 to 12 months (or as clinically
indicated) for the first five years
• Long term surveillance with CT scans
shouldn't be done.

74. Recurrent disease :
 abdomen/pelvis (40 to 50 %)
 lung ( 25 %)
 Rare- spine
 Treatment naïve --- hormone therapy
• Recurrent disease post
treatment
• Metastatic disease
Cytotoxic
chemotherapy
STAGE MEDIAN
TIME
I AND II 65 months
III AND IV 9 months

75. Carcinosarcoma

76. Mixed epithelial and mesenchymal
tumours :
Tumours of the uterine corpus composed of an epithelial
and a mesenchymal component.
 Carcinosarcoma **
 Adenosarcoma
 Carcinofibroma
 Adenofibroma
 Adenomyoma
Atypical polypoid variant

77. Carcinosarcoma(MMMT)
 composed of an admixture of malignant epithelial and
mesenchymal components.
 <5 percent of all uterine malignancies
 7th decade
 Most common among sarcomas
 Risk factors : obesity , diabetes , nulliparity,tamoxifen
prior pelvic radiation
 Presentation : vaginal bleeding >abdominal mass>pelvic
pain
 Examination : polypoid mass protruding through cervix
and presents as upper vaginal mass

78. There are 4 main theories regarding the histogenesis of CS:
(1) the collision theory,
(2) the combination theory,
(3) the conversion theory
(4) the composition theory .
Now its clear that CS arises through
conversion and metaplasia
Dedifferentiated or Metaplastic endometrial
carcinoma

79. Imaging :
 Ultrasound - hyperechoic compared with the
myometrium. In addition, expansion of the
endometrial canal is seen
• CT scan —a heterogenous, ill defined, hypodense
mass with concomitant
dilatation of the
endometrial canal..

80. MRI :
 enlarged uterus with a widened endometrial cavity and
evidence of deep myometrial invasion.
 Heterogenous bulky mass protruding into cervix
 Prolonged intense enhancement
CT

81.  FDG PET/CT –useful for diagnostic and initial
staging purposes. CS is generally positive on PET
scan; the mean standardized uptake value (SUV) of
10+/-5.5
 CA-125:
 Preoperative CA125 elevation is a marker of
extrauterine disease and deep myometrial invasion.
 Postoperative CA125 elevation is an independent
prognostic factor for poor survival

82. Macroscopic :
Polypoid , bulky, necrotic and
hemorrhagic filling endometrium
and invading myometrium
Epithelial Mesenchymal
Glandular Non glandular Homologous Heterologous
endometroid squamous Undifferentiated
Endometrial
sarcoma
Rhabdomyosarc
oma
serous undifferentiated Leiomyosarcoma chondrosarcoma
Clear cell ESS liposarcoma
Microscopic – Biphasic
• Most common combination :
high-grade serous carcinoma and an endometrial stromal sarcoma

83. Uterine carcinosarcoma is a histologic
diagnosis
IHC : epithelial—anticytokeratin + mesenchymal –vimentin +

84. Staging :FIGO 2009

86. Treatment :
 Complete surgery -- total hysterectomy, bilateral
salpingo-oophorectomy, pelvic and para-aortic
lymph node dissection, cytology of peritoneal
washings, omentectomy, and biopsies of
peritoneal surfaces
• Lymphadenectomy is significantly associated with
improved overall survival in patients with Stage I-
III uterine carcinosarcoma
• No survival benefit with radiotherapy

87. Adjuvant therapy :
Stage Ia :
 No trials have evaluated the value of adjuvant
chemotherapy specifically in women with stage
IA disease
 GOG 20– adjuvant doxorubicin vs surveillance.
Low recurrence rates
 GOG 55874- Adjuvant RT vs surveillance
low local recurrence

88. Stage IB-IV :
 Adjuvant chemotherapy is preferred rather
than RT or observation .
Local relapse-- 44%-24%

89.  whole abdominal- pelvic irradiation - 30.6 Gy to the whole
abdomen and pelvis, f/b a 19.8 Gy pelvic boost or three cycles
of cisplatin, ifosfamide and mesna (CIM)
 No statistically significant difference was found in OS (45%
CIM v 35% WAI) or DFS---58% WAI v 52% CIM
 WAI led to a decline - vaginal failures (4% v 10%),
no difference in pelvic failures (13%).
 Estimated 5yr survival– 35% (WAI) vs 45% ( chemotherapy)
 Adjuvant radiotherapy –more late complications
Uncertain Role

90. Chemotherapy regimen:
Single Agent Chemotherapy :
 Ifosfamide (36%)
• etoposide (6.5%)
• doxorubicin (9.8%)
• cisplatin (18%)
• paclitaxel (18%)
• topotecan (10%)
The regimen of chemotherapy recommended for
use in early stage disease is the same as for late
stage disease

91. GOG trials for Carcinosarcoma:
GOG 261, a Phase 3 randomized trial of
ifosfamide and paclitaxel versus carboplatin
and paclitaxel is ongoing…

92. Role of radiotherapy!!!
• Smith et al. & Nemani et al.—no survival benefit
associated with adjuvant radiotherapy in stage I–III
carcinosarcoma,
• whereas Smith et al-- overall survival benefit -stage IV
disease
• Sampath et al.-decrease in local failure
no change in overall survival

93. EORTC : GCG 55874 study –CS
• 224 patients –LMS(99), CS(92), and ESS(30).
• External beam pelvic radiotherapy with observation in
FIGO stage I and II disease .
• With a median follow- up of 6.8 years, no difference was
found in overall survival or disease-free survival .
pelvic recurrences local recurrences
Surgery alone 24% 47%
Surgery + RT 4% 24%

94. Rare Sarcomas :
 Adenosarcoma
 PEComa
 Rhabdomyosarcoma

95. Adenosarcoma :
 Mixed tumor of low malignant potential
 Benign glandular elements +low grade sarcoma
 5-10% of all sarcomas
 all ages, ranging from 15-90 years --median age at
diagnosis of 58.
 Risk factors :tamoxifen therapy for breast cancer
prior pelvic radiation
 Origin : endometrium in lower uterine segment
rare-endocervix
 Presentation :abnormal vaginal bleeding, an enlarged
uterus and tissue protruding from the external os

96. Gross :
polypoid tumors of approximately 5–6 cm in maximum
diameter (range, 1–20 cm) that typically fill and distend
the uterine cavity
Cut section –
• tan brown with foci of
haemorrhage and necrosis.
• Small cysts
• mostly do not invade
myometrium

97. Microscopic :
 Periglandular cuffs—stroma
concentrates around glands
 Mild nuclear atypia
 Few or no mitosis
 Mesenchymal elements -10-
15% cases
• Adenosarcoma With Sarcomatoid Overgrowth :
Pure sarcomatous component >25% of total tumor volume
• IHC : CD 10+
PR+
Ki 67+
cytokeratins

98. FIGO staging 2009 :

99.  low grade
 Recurs --25-40% of cases, typically in the pelvis or
vagina, and distant metastasis 5%
 Poor prognostic -- extrauterine spread,
deep myometrial invasion
sarcomatous overgrowth.
Vascular invasion
 Long- term follow-up is necessary because recurrences
may manifest after many years.
TREATMENT :
 TAH+BSO
 If sarcomatous overgrowth – adjuvant pelvic
radiotherapy.

100. PEComa(Perivascular epithelioid
cell tumor):
 Poorly defined, rare tumors characterized by varying
amounts of epithelioid and spindle cells with clear to
eosinophilic, granular cytoplasm that is HMB45+ in a
diffuse or focal pattern
 Mean age of 45 years (range, 9 - 79 years)
 ~50 cases reported in English language literature
 Sites-uterus and retroperitoneum
 2 types – Benign & Malignant
 Etiology unknown
 Aggresive in nature and recurs post hysterectomy

101. Gross:
 polypoid mass
 Solitary or rarely multifocal mass in uterine
corpus from 0.6 to 12.0 cm (mean of 4.7 cm)
 Cut sections may be grayish white, tan or
yellow with whorled or soft, fleshy, ill defined
or rarely circumscribed margins
BENIGN:
• tongue-like growth pattern similar to LGESS;
• well defined cell borders, abundant granular or clear to
eosinophilic cytoplasm,
• Usually no / mild pleomorphism.no mitotic figures,no necrosis
• Strong, diffuse cytoplasmic HMB45 expression and focal
muscle marker expression
Microscopic : BENIGN OR MALIGNANT

102. Malignant :
 diffuse sheets of cells, separately by occasional small,
hyalinized bundles and plaques of stroma;
 contain primarily perivascular epithelioid cells (> 50% are
round or polygonal)
 focal HMB45 expression, and
 strong, extensive muscle marker expression
 malignant features include mitotic activity > 1/10 HPF,
necrosis, tumor size > 5 cm, infiltrative growth pattern, high
nuclear grade, cytologic atypia, high cellularity,
lymphovascular invasion, infiltration

103. Positive Stains :
 HMB45, SMA (73%), p53 (50%), melanA / MART1
(24% - 67%)
 Also calponin, vimentin, h-caldesmon; PR (50%),
desmin (49%), muscle specific actin (36%), ER (33%),
CD10 (25%)
Treatment :
Hysterectomy, with or without adjuvant chemotherapy and
radiotherapy

104. Rhabdomyosarcoma :
 Pure rhabdomyosarcoma arising in the uterus is a very
rare tumor
 mainly in elderly women,
 highly malignant tumors with frequent extrauterine
spread at presentation.
 Patients rarely survive beyond 15 months.

105.  uterine cervix and corpus are the most frequent locations
of RMS in adult women.
 Three categories: embryonal, alveolar, and pleomorphic
 In postmenopausal women, uterine RMSs appear to be
entirely the pleomorphic type with extremely poor
clinical outcome.
 The median progression-free survival (PFS) and disease-
specific survival was 9 months and 21 months respectively.
 The 5- year disease-specific survival was only 29%

106. Radiotherapy practice:
 No role of upfront Radiotherapy
 It is given in adjuvant settings post surgery
Indications :
 High grade and undifferentiated endometrial sarcomas
 Adenosarcomas, especially with sarcomatous
overgrowth.
 Carcinosarcomas
early-stage comprehensively staged patients,
intravaginal RT and chemotherapy
stage III concurrent pelvic RT and cisplatin followed
by carboplatin/paclitaxel.

108. Technique :
 CT based planning with CT taken with
full bladder

109. PTV final = ITV Vault + PTV total

110. Dose to PTV final : 50Gy/25#/5wks
 In case of carcinosarcoma
We usually give Radiotherapy in a sandwich
pattern with chemotherapy

111. Chemotherapy in practice:
 LMS
 High grade ESS
 Carcinosarcoma – Inj paclitaxel 175mg/m2
Inj carboplatin 5 AUC
 Low grade ESS – Letrozole 2.5mg OD
IAP 3 weekly for 6 cycles
Inj ifosfamide 1.2gm/m2
Inj adriamycin 20mg/m2
Inj Cisplatin 50mg/m2

112. Targeted Treatment :

113. • Retrospective review of medical records of patients of uterine sarcoma
(20022007)
• 42 (15 CS, 12 ESS, 11 LMS, 3 UES, and 1 mixed sarcoma
• Adjuvant radiation, chemoradiation, and chemotherapy were offered.
Pelvic radiation: 46 Gray/23 fractions/4.5 weeks and vincristine,
adriamycin, cyclophosphamide (VAC) regimen were most commonly used
• Median OS of only 6.57, 6.8, and 9.38 months, respectively, in patients
with carcinosarcoma, leiomyosarcoma, and UES
• Disease stage (p = 0.005) and response to therapy (p = 0.01)—predictors of
OS
• Small series, poor treatment compliance and socioeconomic constraints in
the indian scenario were the limiting factors

114. Conclusion :
 Uterine sarcomas are very aggressive neoplasms
 No imaging modality can offer a reliable preoperative
diagnosis
 As a result, centralisation, large series, and randomised
trials are problematic.
 Aggressive surgical cytoreduction at the time of initial
diagnosis offers the best survival
 To date, no effective adjuvant therapy has been found to
prolong the survival of women with uterine sarcomas.
 More RCTs are needed to determine the value and
regime of adjuvant therapy

115. Thank you…