28. soft tissue sarcomas

Question 1

Soft Tissue Sarcomas general information

Answer 1

• mesoderm origin
• usually on extremities or trunk
• hematogeneous spread→ lymph node metastasis is very low <%5
• abdominal sacromas have high recurrence rates and poor prognosis
• LUNG METASTASIS IS VERY COMMON WITH %80 chance
• centrifugal growth pattern
• generally asymptomatic
• retroperitoneal nes are detected at larger sizes

Question 2

Risk factors of soft tissue sarcomas

Answer 2

• radiation exposure
  
  • mutated p53
  • risk of sarcomas are 8-10 times more common in patients who have received radiotherapy for breast, cervix, cervical, testicular cancers
  • directlyt related to radiation dose
  • mean time between exposure to sarcoma is 10 years
• chemical exposure
  
  • phenoxyacetic acid (insecticide), chlorophenol (wood preservative)
• chronic lymphedema

Question 3

Molecular mechanism of soft tissue sarcomas

Answer 3

• translocations are very common
  
  • ewing sarcoma 11;22
• amplification
  
  • MDM2—> in liposarcoma
• Oncogenic mutations
  
  • gist→ cKit or PDGFR-alpha
  • mostly kit mutations on exon 11
• Complex genomic rearrangements
  
  • Rb gene mutation→ retinoblastoma
  • p53 germ line mutation
  • NF1

Question 4

Diagnostic imaging in soft tissue sarcomas

Answer 4

• USG→ when mri can not be perfomed
• MRI→ benign lessions can be differentiated, extremity sarcomas
• CT→ metastasis, invasion can be assessed, trunk, intraabdominal and retroperitoneal
• PET-CT → not recommended for initial evaluation, staging and evaluation
• LUNG METASTASIS→ THORAX CT
• angiosarcoma tends to metastize to brain→ brain mri

Question 5

Diagnostic Biopsy in soft tissue sarcomas

Answer 5

• genelde core needle biyopsi kullanılır→ %90 diagnostic accuracy
• fine needle biyopsi yeterli değildir ve tercih edilmez

Question 6

Pathologic Evaluation of soft tissue sarcomas

Answer 6

• limited metastasis potential
  
  • desmoid tumor
  • well differentiated liposarcoma
  • dermatofibrosarcoma protuberans
  • solid fibrous tumor
• moderate metastatic potential
  
  • myxoid liposarcoma
  • myxofibrosarcoma
  • myxoid chondrosarcoma
• significant
  
  • angiosarcoma
  • clear cell sarcoma
  • pleomorphic and dedifferentiated liposarcoma
  • leiomyosarcoma

Question 7

Staging in Soft Tissue sarcomas

Answer 7

• GRADE IS THE MOST IMPORTANT FACTOR
  
  • grade of aggressivenes
    
    • cellularity
    • differentiation
    • pleomorphism
    • necrosis
    • mitose count
  • tumor depth and size
  • lymph node metastasis
    
    • rare
    • angiosarcoma
    • epitheloid sarcoma
    • clear cell sarcoma
    • synovial sarcoma
    • Ln suspicion→ FNAB or core biopsy preop
  • distant organ metastasis
    
    • mostly lungs
    • kemik
    • beyin
    • karaciğer

Question 8

Prognostic factors in soft tissue sarcomas

Answer 8

• grade
• size
• depth
• surgical margin→ we should aim for R0 because they infect everything they touch
• histology
• localization
• Ki-67
• age
• CD100 positivity , e- cadherin loss→ poor prognostic

Question 9

Treatment of soft tissue sarcomas

Answer 9

• SURGERY
  
  • additional RT is beneficial
  • resection of microscopic residual disease
  • rt is ineffective in macroscopic disease
  • r0 yapmak çok önemli
  • clean surgical margin 1-2 cm olmalı
  • psudocapsule varsa o bırakılmalıdır ve açılmamalıdır
  • perinöral sheath ve vascular adventitia haricindeki diğer majör nörovasküler yapılar bırakılmalıdır
  • ekstremite sarkomalarda→ radikal lenfadenectomi
• Radioterapi
  
  • 5 cm altında safe surgical margin varsa verilmeyebilir
  • neoadjuvant tercih edilir
• kemoterapi
  
  • high mortality risk
    
    • high grade at diagnosis
    • ekstremite dışı sarkom
    • 5 cmsen büyük yüksek histopatolojik grade
  • kt sensitif→ synovial sarcoma, myxoid liposarcoma, uterine leiomyosarkom
  • kt resistant→ round cell tumor, pleomorphic liposarcoms, epitheloid sarcoms
  • EN İYİ İLAÇLAR
    
    1. doxorubicin→ cardiotoxic
    2. ifosfamide (nephrotoxic)
    3. trabectedin→ hepatotoxic
    4. second line targeted → bevacizumab ve pazopanib (ANTİ- VEGF ve inhibitor of PDGFR and c-kit)

Question 10

Follow up of soft tissue sarcomas

Answer 10

• ilk 2 yıl; 3 ayda bir ct
• 2-5 yıl sonra 6 ayda bir

Question 11

Retroperitoneal Sarkomlar

Answer 11

• 2/3ü high grade
• en sık görülen→ liposarkom ve leimyosarkom
• %70’i → 10 cmden büyük olduğu zaman diagnosed edilir
• sistemik lenf nod metastazı ve testikular examination are mandatory
• LDH yükselmesi→ lymphoma
• B- HCG ve AFP yükselmesi→ germ cell tumors
• kontrastlı BT çekilir
• tedavi cerrahdir
• tanı anında %30u akciğer metastazı yapmıştır
• en-bloc multivisceral rezeksiyon yapılır
• kemoterapi işe yaramaz
• neoadjuvant RT → tekrar olmasındaki olasılığı düşürür

Question 12

Breast Sarcoma

Answer 12

• rare
• subtipleri vardır
  
  • anjiyosarkoma
    
    • %50’si
    • related to the radiotherapy given in the treatment of the primary tumor
    • 3-20 yıl içinde gelişir
  • stromal sarkoma
  • fibrosarkoma
  • malignant fibröz histiocytoma
  • cytosarcoma phyllodes
    
    • originates from hormone sensitive stromal cells of the breast
    • generally benign
• tumor size AND GRADE ARE PROGNOSTİC FACTORS
• axillary dissection is useless

Question 13

GIST

Answer 13

• torakoabdominal BT
• FDG PET
• baseline PET→ before starting the treatment
• THE TREATMENT IS SURGERY
• LYMPHADENOCTOMY → GEREKSİZ
• TUMOR SIZE AND MITOTIC ACTIVITY ARE PROGNOSTIC FACTORS
• KIT protein kinase inhibitor (IMANITIB) is highly effective in unresectable diseases
• if imanitib resistance develops → inhibitor of many tyrosine kinases such as PDGFA, VEGF receptor, KIT
• third line tretament→ REGORAFENIB
• they originate from the interstitial cells of cajal
• CD34 (hematopoetic progenitor cell marker)
• c-KİT (growth factor receptor expression)
• CD117 protein tanıda kullanılır c-Kit’in bir ürünüdür
• Genelde karındadır %60 sonra ince bağırsak %30
• MUTASYONLAR
  
  • c-kit exon 9 ya da 11
  • PDGFR-alpha → exon 18
• en sık metastaz→ karaciğer ve intraabdominal boşluk

Question 14

Desmoid Tümörler

Answer 14

• lokal olarak agresif ama metastaz yapmaz
• APC gen mutasyonları veya FAP, gardner sendromu
• abdominal wall desmoid tümörleri hormonlarla ilişkilidir ve hamilelik ile ilgilidir
• sporadikse→ beta catenin CTNNB1 mutasyonludur
• tamoxifen, NSAIDS ve methotrexate tedavide kullanılabilir
• tedavi cerrahidir ama cerrahi işlem uygulanamazsa radyoterapi kullanılabilir

Question 15

Dermatofibrosarcoma Protuberance

Answer 15

• dermisten gelişen nadir tümörler
• lokal olarak agresif, metastaz oranı düşük
• PDGF-beta mutasyonu
• yavaş ama sürekli bir büyüme patterni
• tedavi wide excision
• imatinib beneficialdır