It is all about soft tissue sarcoma and managment

1. Soft Tissue Sarcoma
Dr Junaid Ahmad

2. ∗ A heterogeneous group of tumors of connective
tissue
∗ Two third of Soft tissue sarcomas in extremities
∗ Constitute 1% of cancers in adults but 15% in children
∗ The overall 5-year survival rate 50% to 60%.
∗ Most of die with lung metastasis
Sarcomas

3. ∗ Malignant fibrous histiocytoma is most common type
in elderly
∗ Liposarcoma in middle age
∗ Leimayosarcoma in young
∗ Embryonal/alveolar rhabdomyosarcomas are the
most common type in children
Histological Subtypes

4. ∗ I. Fibrosarcoma
∗ 1. Adult fibrosarcoma
∗ 2. Inflammatory fibrosarcoma
∗ 3. Myxofibrosarcoma
∗ II. Fibrohistiocytic tumors
∗ 1. Dermato Fibro sarcoma Protruberans
∗ 2. Heterogenous tumors without specific differentiation(Formerly MFH)
∗ i. Undifferentitaed pleomorphic sarcoma.
∗ ii. Undifferentiated pleomorphic sarcoma with giant cells with inflammation.
∗ iii. Angiomatoid MFH
∗ III. Lipomatous tumors
∗ 1. Atypical lipoma
∗ 2. Liposarcoma
∗ i. Well differentiated
∗ a. Lipoma like
∗ b. Sclerosing
∗ c. Inflammatory
∗ ii. Dedifferentited liposarcoma
∗ iii. Myxoid or round cell LS
∗ iv. Pleomorphic LS
∗ IV. Smooth muscle
Classification

5. ∗ 1. Leiomyosarcoma
∗ 2. Epitheloid LMS
∗ V. Skeletal Muscle
∗ 1. RhabdoMayoSacroma
∗ i. Embryonal
∗ ii. Botryoid
∗ iii. Spindle call
∗ iv. Alveolar
∗ v. Pleomorphic
∗ 2. RMS with ganglionic differentiation (Ectomesenchymoma)
∗ VI. Blood and lymph vessels
∗ 1. Epitheloid hemangioendothelioma.
∗ 2. Angiosarcoma nd lymphangiosarcoma
∗ 3. Kaposi’ s sarcoma
∗ VII. Malignant perivasular tumors
∗ 1. Malignant glomus tumor or glomangiosarcoma.
∗ 2. Malignant hemangio pericytoma
∗ VIII. Malignant synovial tumors
∗ Malignant GCT of tendon sheath.
∗ IX. Malignant neural tumors
∗ 1. MPNST (Neurofibrosarcoma)
∗ 2. Malignant granular cell tumor
Classification

6. ∗ 3. PNET(primitive NET)
∗ i. Neuroblastoma
∗ ii. Ganglioneuroblastoma
∗ iii. nauroepithelioma
∗ X. Paraganglionic tumors
∗ Malignant paraganglioma
∗ XI. Extra skeletal Cartilaginous and oseeous tumors
∗ 1. Extra skeletal chondrosarcoma
∗ a. Myxoid
∗ b. Mesenchymal
∗ 2. Extraskeletal osteosracoma
∗ XII. Pluripotential malignant mesenchymal tumor
∗ 1. Malignant mesenchymoma
∗ 2. Alveolar soft part sarcoma
∗ 3. Epitheloid sarcoma
∗ 4. Malignant extra renal rhabdoid tumor
∗ 5. Desmoplastic small cell tumor
∗ 6. Extraskeletal Ewing s sarcoma
∗ 7. Clear cell sarcoma
∗ 8. GIST
∗ 9. Synovial sarcoma
Classification

7. ∗ Liposarcoma
∗ Leiomyosarcoma
∗ Unclassified sarcoma
∗ Synovial sarcoma
∗ Malignant peripheral nerve sheath tumor
∗ Rhabdomyosarcoma
∗ Fibrosarcoma
∗ Ewing sarcoma
∗ Angiosarcoma
∗ Osteosarcoma
∗ Epithelioid sarcoma
∗ Chondrosarcoma
∗ Clear cell sarcoma
∗ Alveolar soft part sarcoma
∗ Malignant hemangiopericytoma
Common Histological Subtypes

8. ∗ 20% of all Soft tissue sarcomas
∗ Thighs and retroperitoneum.
∗ Three principal groups:
∗ 1. Atypical lipomatous tumour/ WD LS and dedifferentiated
LS
∗ Adipocytic (lipoma like)
∗ Sclerosing
∗ Inflammatory
∗ Spindle cell.
∗ 2. Myxoid or round cell LS
∗ 3. Pleomorphic LS
Liposarcoma

9. ∗ Malignant tumors composed of spindle cells
∗ Showing smooth muscle features.
∗ Location: Retroperitoneal, intra abdominal pelvic
sites, uterus
∗ Smooth muscle actin and desmin.
∗ Grading of LMS difficult.
∗ Large tumor size, high grade and high mitotic rate are
the prognostic factors.
Leiomyosarcoma

10. ∗ 1. Embryonal
∗ Small cell tumor
∗ Orbit or genito urinary tract of children.
∗ Botyriod type usually in the mucosa lined visceral organs
vagina and urinary bladder
∗ Polypoid tumour
∗ Also seen in adults but poorer prognosis
∗ 2. Alveolar type:
∗ Extremities
∗ Young adults and adolescents.
Rhabdomyosarcoma

11. ∗ Malignant tumor with cells that resemble
morphologically and functionally endothelial cells.
∗ No clear distinction of those from lymphatics and
capillaries.
∗ Sometimes associated with lymphedema.
∗ Stewart treve syndrome
∗ Lymphangiosarcoma of skin in the lymphedematous
arm post mastectomy
∗ Radiation therapy
Angiosarcoma

12. ∗ Rare sporadically
∗ But 8 to 13% in those with NF-1
∗ Affect major nerves of extremities or chest wall.
∗ Originate from nerve sheath.
∗ Most are high grade
∗ Stain positive for S-100
∗ MPNST with Rhabdomayosarcoma elements termed
Triton tumor
Malignant Peripheral Nerve
Sheath Tumor

13. ∗ This concept is challenged now.
∗ Merely in histological appearance.
∗ None of them show histiocytic differentiation.
∗ Low grade- recur locally, but rarely metastasize.
∗ Slow and persisitent growth.
∗ Unpredicted radial extensions.
∗ Stains positive for CD34.
∗ Response with Imatinib
Fibrohistiocytoma

14. ∗ Spindle cell tumor
∗ Young adults 15-35 yrs of age
∗ 80% in extremities, 10 % in Head and Neck
∗ Unrelated to synovium
∗ Stain positive for keratin, vimentin, S-100+/-
Synovial sarcoma

15. ∗ Epitheloid sarcoma
∗ Unknown lineage
∗ Adolescent and young adults
∗ Extremity and perineal area
∗ Tends to propogate along tendon and nerve
sheaths.
∗ Lung and lymph nodal metastasis common.
∗ 5 year survival 66%.
Synovial sarcoma

16. ∗ Reserved for those undifferentiated
Pleomorphic sarcomas with no line of
differentiation by current technology.
∗ Aggressive course
∗ Many develop metastasis within 3 years of
diagnosis.
High grade undifferentiated pleomorphic
sarcoma/ pleomorphic MFH

17. ∗ Most of time cause is unknown
∗ Few known etiologies are
∗ Radiation Exposure
∗ Occupational Chemical Exposure
∗ Trauma
∗ Chronic Lymphedema
∗ Genetic Conditions (NF, RB)
Cause

18. ∗ Different type of known mutations are
∗ Point Mutations
∗ Translocations
∗ Amplifications
∗ Oncogenic Mutations
∗ Complex Genomic Rearrangements
Molecular Basis

19. ∗ Asymptomatic painless masses
∗ Venous thrombosis in extremities
∗ Compress adjoining structures
∗ Sometimes painful, edema and swelling when
bone or nearby neurovascular bundle involved
∗ Sometimes a traumatic even draws attention
to it
Clinical Picture

20. ∗ Lipoma
∗ Lymphangioma
∗ Leiomyoma
∗ Neurinoma
∗ Primary or metastatic carcinoma
∗ Melanoma
∗ Lymphoma
Differential Diagnosis

21. ∗ Superficial small lesions (<5 cm) that are new
or that are not enlarging as indicated by
clinical history can be observed.
∗ Enlarging masses and masses larger than 5 cm
or deep to the fascia should be evaluated with
a history, imaging, and biopsy.
Assessment

22. ∗ Size of tumor and skin involvement (defect)
∗ Pulses and sensation (for vascular and nerve
reconstruction)
∗ Involved muscle groups (for
tendon/vascularized muscle transfer)
∗ Age and fitness for surgery
∗ Lifestyle (for limb preservation)
Clinical Assessment

23. ∗ Should be before any invasive procedure
∗ MRI is the choice in extremities
∗ An x ray may help in bone involvement
∗ CT may be helpful in intra abdominal and few
types of sarcomas
∗ CT chest and MRI brain may be required to
see metastasis
∗ Ultrasonography if MRI is contraindicated
Diagnostic Imaging

24. ∗ PET scan is only a slight better than CT
∗ Follow up 3 monthly MRI are done to
see recurrence
Diagnostic Imaging

25. ∗ Fine-Needle Aspiration
∗ Core Needle Biopsy (choice)
∗ Incisional Biopsy (25% changed plan)
∗ Excisional Biopsy
Biopsy Techniques

26. ∗ Light Microscopy/Morphology (25-40% disagree)
∗ Electron Microscopy
∗ Cytogenetics; immunohistochemistry and molecular
genetic testing.
∗ Other molecular diagnostic techniques include Flow
cytometry, fluorescence in situ hybridization (FISH),
and polymerase chain reaction–based methods.
Pathologic Assessment and
Classification

27. ∗ Pathological classification is more important
∗ Type of tumor
∗ Histologic Grade of Aggressiveness
∗ Nodal Metastasis (Rare in adult sarcomas)
∗ Distant Metastasis (CT chest)
Staging and Prognostic Factors

28. ∗ Parameters by French federation of cancer centre
three tire system (FNCLCC)
∗ Differentiation score
∗ Mitoses
∗ Necrosis
∗ Some ungradable e.g. epitheloid, clear cell,
angiosarcoma
Grading

29. ∗ Primary:
∗ T1 tumour 5 cm or less in greatest dimension (a superficial, b
deep).
∗ T2 tumour more than 5 cm in greatest dimension (a
superficial, b deep).
∗ Regional nodes:
∗ N0 none.
∗ N1 regional nodes.
∗ Distant metastases:
∗ MX, M0, M1
TNM G Staging

30. ∗ Histological grade G
∗ GX cannot be assessed
∗ G1 well differentiated
∗ G2 moderately differentiated
∗ G3 poorly differentiated
∗ G4 undifferentiated
∗ G1/2 would be low grade tumors
TMN G

32. ∗ Kattan et al studied Prognostic Factors
∗ Age
∗ Histology
∗ Grade
∗ Location
∗ Depth
∗ Size
Prognostic Factors.

33. ∗ The treatment algorithm for soft tissue
sarcomas depends on tumor stage, site,
and histology.
Treatment

34. ∗ Surgery
∗ Limb sparing surgery / Wide Local Excision
∗ Locoregional Lymphadenectomy.
∗ Amputation.
∗ Isolated Regional Perfusion.
∗ Radiation Therapy
∗ Systemic Therapy
∗ Standard Chemotherapy.
∗ Novel Chemotherapeutic Agents.
∗ Targeted Therapies.
Treatment Modalities

36. ∗ Limb Salvage Technique
∗ 1-2 cm margins (Dermatofibrosarcoma Protuberance require 2-4cm)
∗ Biopsy site is resected
∗ Nerve and vessels are usually preserved by narrowing
the margins
∗ NV bundle if very near to tumor then epineurium and
adventitia are removed
∗ Tumor encircling NV bundles should be removed
∗ Nearby veins are not be spared usually
Wide Local Excision

37. ∗ Enucleation is discouraged and dissection must be in
grossly normal planes (even with radiation)
∗ Lin and colleagues studied that in absence of frank
cortical margins periosteum is the adequate surgical
margin with radiation
∗ Bone involvement is poor prognostic factor
∗ NV bundles reconstructed
∗ Free flaps and tendons/muscle transferred
∗ Skin covered
Wide Local Excision

38. ∗ Early physical therapy is essential
∗ Large sarcomas of distal parts of
extremities are difficult to treat and
amputations are considered
Wide Local Excision

39. ∗ Also limb sparing surgery
∗ Differ from wide local excision that
involved muscles are removed from
origin to insertion
Compartectomy

40. ∗ FNAC should be done US guided
∗ If involved selected lymphedenectomy done
∗ Proved increase survival rate
∗ Sentinel lymph node biopsy is controversial
Lymphedenectomy

41. ∗ 5% cases of extremity sarcomas
∗ Have no survival advantage
∗ Avoids local recurrence
∗ Large unresectable tumors
∗ Reserved only for cases when Limb
Salvage cannot be done
Amputations

42. ∗ Palliative treatment
∗ Artery and Veins of region involve are dissected and
connected to a pumping device
∗ Branches are ligated
∗ Perfused with TNF-alpha and Malaphalan
∗ Limb is kept warm with heater at 40C
∗ Systemic leakage checked with Tc labelled albumin
∗ Artery and vein repaired
∗ Expensive and controversial
Isolated Regional Perfusion

43. ∗ Indications
∗ Limb conservation or limited surgery
∗ Gross residual tumor or inadequate excision
margins
∗ Grade is high on histology
∗ Tumor 5 cm or more in any dimension
∗ Virtually all tumors in H&N
Radiation

44. ∗ Smaller than 5cm tumors with clear margins
can avoid radiation even if high grade
∗ Pre operative post operative and intra
operative techniques have debates
∗ Metallic clips during surgery help define
margins
Radiation

45. ∗ Post operative
∗ Large doses required
∗ Reconstruction is less
complicated
∗ Long time to complete
∗ Local Cure is comparable
Radiation
∗ Pre operative
∗ Difficulty in pathologic
assessment of margins
∗ Wound complications
increased
∗ Low doses required
∗ Better long term results
fibrosis
∗ Difficult reconstructions

46. ∗ No survival benefit
∗ Synovial and Myxoid sarcomas are most sensitive
∗ For those with significant risk of death
∗ Metastasis
∗ Non extremity tumors (unresectable)
∗ Intermediate to high grade with size larger than 5cm
∗ Docurubicine and ifosfamide are standard
∗ Hemorhagic cystitis, real tubular acidosis,
neurotoxicity are side effects of ifosfamide
Systemic Chemotherapy

47. ∗ Anti vascular endothelial growth factor is
particularly effective against angiosarcoma
∗ Trabectedin for leiomayosarcoma
∗ Imitanib for GI stromal tumor
∗ Use is contorversial as many trials even failed
to show benefits in disease free interval
Systemic Chemotherapy

48. ∗ Increase wound complications
∗ Decrease the size of tumor
∗ Tumors with high pathological necrosis on CT
respond better to neoadjuvant chemotherapy
Neoadjuvant (Preoperative)
Chemotherapy.

49. ∗ Theoratical benefit is short total
treatment time in high risk patients
Concurrent Chemoradiation Therapy

50. Thoracotomy and metstatectomy
3 year survival is 23 to 42 %
Indicated if
Primary tumor is controlled or controllable
Complete resection appears to be possible
No extra thoracic disease
No medical complicated disease
Lung Metastatic Disease

51. ∗ History Physical Chest CT or radiograph every
3 to 6 months
∗ Tumor site should be evaluated with MRI first
at 3 months then every 6 months
∗ First 2-3 years are most important
∗ Some prefer less aggressive radiological
approach for asymptomatic patients
Post treatment Surveillance

52. ∗ Biospy of any suspicious nodule
∗ Redical excision with or without
radiation is treatment for tumor
Management of Recurrent Sarcoma

53. Thank you