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
Presentation about the the second most common type of ovarian tumors which have a very unique property of being similar to the testicular germ cell tumors.
Presentation about the the second most common type of ovarian tumors which have a very unique property of being similar to the testicular germ cell tumors.
Presentation at Chittaranjan Seva Sadan, Kolkata where Dr Dasgupta was invited as faculty in the CME organized by Medical Education and research Committee, Bengal Obstetrics and Gynaecological Society
Presentation at Chittaranjan Seva Sadan, Kolkata where Dr Dasgupta was invited as faculty in the CME organized by Medical Education and research Committee, Bengal Obstetrics and Gynaecological Society
A brief description on cancer.Cancer – a large group of diseases characterized by the uncontrolled growth and spread of abnormal cells,Some topics are genesis of cancer,types of cancer,causes of cancer like Heredity,Immunity,Chemical,Physical,Viral Bacterial,Lifestyle.
,sign&symptom:*Change in bowel habits or bladder function,*Sores that do not heal,*Unusual bleeding or discharge,*Thickening or lump in breast or other parts of the body,Indigestion or trouble swallowing,*Recent change in a wart or mole,Nagging cough or hoarseness,
diagnosis and staging,treatment:Surgery,Radiation,Chemotherapy,Immunotherapy,Hormone therapy, Gene therapy,side effect of cancer treatment,prevention of cancer
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
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
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
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.
27. chemotherapy with doxorubicin or
docetaxel/gemcitabine is now used for advanced or
recurrent disease, with response rates ranging from
27% to 36%
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
30.
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
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
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
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
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
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???
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
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 +
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%
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
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.
107.
108. Technique :
CT based planning with CT taken with
full bladder
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