Gastro-Intestinal Stromal Tumor (GIST) The experience of Chia-Yi Chang-Gung Hospital

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Gastro-Intestinal Stromal Tumor (GIST) The
experience of Chia-Yi Chang-Gung Hospital

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Introduction

• Gastro-intestinal Stromal Tumors (GISTs)
• Mesenchymal tumors which express specially
  c-kit (CD117) and/or CD34
• less than 0.1 of all colorectal malignancies.

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Cases Presented
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Case 1

• Name x x x
• Age 62 Y/O
• Sex Male
• Chart No. 360xx07

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Chief Complaint

• A perianal mass was noted for 2 years

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Brief history

• The 62 Y/O male patient was generally healthy
  before. A perianal mass was noted since 2 years
  ago. The mass became larger recently, and he came
  to our OPD for help.
• Past History denied history of systemic disease
• Personal History allergic history of penicillin
• Family history Non-contributory

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Physical examination

• Consciousness Clear
• HEENT Not icteric, not anemic
• Chest Symmetric expansion
• Heart RHB, No murmur
• Abdomen No palpable mass
• Extremities Full and free
• Perineum A perianal tumor over Lt lat. aspect
• Hard, fixed, pain ,
  tenderness ()
• Diameter 5 cm x 5 cm

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C X R Film
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Fibrocolonoscopy
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ABD CT Scan (I)
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ABD CT Scan (II)
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Trans-rectal ultrasound sonography
4 cm level
5 cm level
2 cm level
Anal verge
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Preoperative Diagnosis

• Para-rectal tumor R/O Rectal GIST

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Operative procedure

• Abdomino-Perineal Resection ( APR )

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Operative finding

• A para-rectal tumor over Lt lat. to Lt post.
• aspect, locating beneath the dentate line.
  
• Well circumscribed, lobulated, solid, light
  tan,
• firm, Adhering with the lower rectal wall
  
• and anal sphincter

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Pathological Report

• Anorectum, Abdominoperineal resection
• -- An anorectal tumor composed of lobules of
  spindle cells with mild nuclear atypia and high
  mitotic rate ( gt 20 MFS/10 HPF )
• Immunohistochemical Stain
• c-KIT (), CD34 (), S-100 (-), SMA (-)
  
• Lymph Node, Regional
• --Negative for malignancy ( 28/28 )
• Gastrointestinal Stromal Tumors

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H. E. Stain
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C-KIT Positive Stain
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CD34 Positive Stain
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ABD CT Scan follow up (I)
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ABD CT Scan follow up (II)
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Case 2

• Name x x x
• Age 69 Y/O
• Sex Female
• Chart No. 9208xx80

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Chief Complaint

• Lower back pain was noted for 2 months

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Brief history

• The 69 Y/O female patient was a case 0f malignant
  neurilemoma post ATH BSO at TCVGH 2 years ago.
  The post-operative courses was smooth. Lower back
  pain was noted since 2 months ago, and recurrent
  pelvic tumor was noted. She accepted therapy of
  STI-571 for 7 weeks at MMH. Then she came to our
  OPD for help.
• Past History denied history of systemic disease
• except thrombocytopenia
• Personal History Denied any allergic history
• Family history Non-contributory

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Physical examination

• Consciousness Clear
• HEENT Not icteric, not anemic
• Chest Symmetric expansion
• Heart RHB, No murmur
• Abdomen No palpable mass
• Extremities Full and free
• Perineum An extramural tumor over mid-rectum
• with moderate induration,
  pain
• Diameter 3 cm x 2 cm

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C X R Film
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Fibrocolonoscopy
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ABD CT Scan (I)
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ABD CT Scan (II)
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ABD CT Scan (III)
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ABD CT Scan (IV)
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Preoperative Diagnosis

• Recurrent pelvic Gastrointestinal Stromal Tumor
• (GIST)

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Operative procedure

• Restorative proctectomy with colonic-J-pouch anal
  anastomosis with diverting T-loop colostomy

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Operative finding

• A para-rectal tumor over Rt lat. pelvic side
  wall with mesorectal invasion, 2 cm above the
  dentate line. Vaginal stump invasion ()

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Pathological Report

• Rectum, restorative proctectomy
• -- A 2x1.5 cm induration tumor composed of
  lobules of spindle cells with mild nuclear atypia
  and low mitotic rate ( lt3 MFS/50 HPF )
• Invasion the rectal serosa, Vaginal (-),
  pelvic side wall (-)
• Immunohistochemical Stain
• c-KIT (), CD34 (), S-100 (), SMA (-)
• Lymph Node, Regional
• --Negative for malignancy ( 11/11 )
• Recurrent Gastrointestinal Stromal Tumors

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Case 3

• Name x x x
• Age 43 Y/O
• Sex Male
• Chart No. 354xx29

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Chief Complaint

• Tenesmus and perineal soreness were noted for
  several months

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Brief history

• The 43 Y/O male patient was a case of huge rectal
  GIST ( 9 x 8 x 5 cm3 ) post restorative
  proctectomy with T-loop colostomy at LKCGMH one
  and a half years ago. The post-operative courses
  was smooth. Frequent bowel movement, tenesmus and
  perineal soreness were noted for several months,
  and recurrent GIST was noted after trans-rectal
  needle biopsy. He came to our OPD for help.
• Past History denied history of systemic disease
• Personal History Denied any allergic history
• Family history Non-contributory

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Physical examination

• Consciousness Clear
• HEENT Not icteric, not anemic
• Chest Symmetric expansion
• Heart RHB, No murmur
• Abdomen No palpable mass, Op Scar
• Extremities Full and free
• Perineum An induration lesion over anastomotic
• ring, Rt post. Aspect .
• pain Tenderness
• Diameter 2 cm x 2 cm

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C X R Film
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ABD CT Scan (I)
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ABD CT Scan (II)
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Preoperative Diagnosis

• Recurrent Rectal Gastrointestinal Stromal Tumor
• (GIST)

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Operative procedure

• Abdominoperineal Resection (APR)

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Operative finding

• An induration lesion around previous
  anastomotic site with extension to Lt
  para-prostate tissue and Rt pelvic side wall
  with Rt ureter invasion ( U-V junction ), 1 cm
  above the dentate line.

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Pathological Report

• Anorectum, APR
• -- A 2x2 cm induration tumor composed of
  highly cellular spindle cells with moderate cell
  pleomorphism and high mitotic rate ( 1-2 MFS /
  HPF ), located within the muscular layer
• Local abscess formation()
• Immunohistochemical Stain
• c-KIT (), CD34 (), S-100 (-), SMA (-)
• Lymph Node, Regional
• --Negative for malignancy ( 11/11 )
• Recurrent Gastrointestinal Stromal Tumors

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H. E. Stain
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C-KIT Positive Stain
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CD34 positive stain
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Gastrointestinal Stromal Tumor

• G I S T

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INTRODUCTION (1)

• 1983 Mazur and Clark the term
• Describe gastrointestinal non-epithelial
  neoplasms lacking the immunohistochemical
  features of Schwann cells and the ultrastructural
  characteristics of smooth-muscle cell
• 1988 Hirota and colleagues
• Discovery of gain-of-function mutation in
  the KIT proto-oncogene in GISTs

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INTRODUCTION (2)

• Mesenchymal tumors of GI tract which express
  specially c-kit (CD117) and/or CD34
• Previously regarded as
• Leimyoma
• Leimyosarcoma
• Leiomyoblastoma
• Neurilemoma

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INTRODUCTION (3)

• Histology
• Highly cellular spindle cell or epithelioid
  mesenchymal tumors
• Immunohistochemical study
• Expression of c-kit protein
• CD34 70
• Smooth muscle actin 2030
• S-100 protein 10
• Desmin 24

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• Prevalence
• 0.2 of gastrointestinal (GI) tumours
• Incidence 3000 to 5000 cases in the US
• Similar male-to-female ratio
• Highest incidence in 5th to 7th decades of life

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• Distribution
• Stomach 60 70
• Small intestine 25 35
• Colon, rectum 5
• Esophagus lt 2
• Omentum, mesentery, retroperitoneum
• GISTs of the colon and the rectum are less than
  0.1 of all colorectal malignancies.

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Clinical Presentation

• Vague GI pain or discomfort
• GI hemorrhage
• Other symptoms include anorexia, weight loss,
  nausea, anemia, and additional GI complaints
• Often asymptomatic, especially early in tumor
  development

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• Malignant GISTs are about 20 30
• Prediction of malignancy
• gt 5 mitosis / 50 HPF
• Tumor size gt 5 cm
• -- High frequency of intra-abdominal
  recurrence
• and liver metastasis

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Malignant Behaviour of the GISTs

• Distant metastasis
• Liver
• Lung
• Bone
• Brain
• Local recurrence
• Intra-abdominal dissemination

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Treatment

• Surgical resection
• Resistant to chemotherapy
• Resistant to radiotherapy
• Imatinib mesylate (STI-571)

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Outcome of Surgical treatment

• Surgery is primary treatment modality for GISTs
• 5-year survival 50 to 65
• Recurrence after a decade or more
• If incomplete resection/metastatic at
  presentation
• Median survival lt1 year
• 5-year survival lt35
• If disease unresectable
• Median survival 9 to 12 months

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Outcome of Surgical treatmentof Rectal GISTs

• Local resection
• 67.5 86 local recurrence
• Abdominoperineal Resection
• 19.5 local recurrence

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Surgical Outcome of Rectal GISTs of CGMH

• 40 cases of rectal GISTs with radical resection

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Imatinib mesylate (STI-571)

• ( Gleevec, Glivec )
• A specific inhibitor of c-Kit tyrosine kinase
  activity, and blocks c-Kitmediated downstream
  signaling

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The Biology of c-Kit

• c-Kit is found in many normal tissues and is
  essential for
• Haematopoiesis
• Melanogenesis
• Gametogenesis
• Interstitial cells of Cajal development
• Activation of c-Kit plays a critical role in
  different cell functions
• Proliferation
• Differentiation
• Apoptosis/survival
• Adhesion/chemotaxis

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• Gain-to-function mutation in the c-kit
  proto-oncogene
• ? constitutive activation of Kit receptor
  tyrosine kinase
• ? induce cellular proliferation and decrease
  apoptosis

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Imatinib CML Phase II Results
Kantarjian et al. N Engl J Med.
2002346645-652. Talpaz et al. Blood.
2002991928-1937. Sawyers et al. Blood.
2002993530-3539.
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GIST Phase II Best Confirmed Responses-- July
10, 2001
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Summary

• Colon and rectal GISTs are rare colon and rectal
  malignancies
• Radical resection provide the only chance of
  curative treatment.
• STI-571 ( Glivec ) may be beneficial for the
  cases of unresectable tumors, distant metastasis,
  and carcinomatosis.

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Thank You !