Gastrointestinal stromal tumours

Ans. is ‘a’ i.e., CD 117

lmmunohistochemistry

o Following markers are present in GISTs:

i)        CD 117 (c kit)                     —>95%

ii)      CD 34                                 —> 70%

iii)    Smooth muscle actin                  5%

• CD 117 (c kit) is considered the most specific marker

o CD 117 (c kit) immunoreactivity is the best defining feature of GISTs distinguishing them from true smooth muscle tumors (leiomyoma) and tumors arising from neural crest.

o Although CD 117 (c kit) is considered the most specific marker for GIST, it is not pathognomonic of GIST as other tumors may also express CD 117. These tumors include mast cell tumor, germ cell tumors (seminomas), leukemias, malignant melanoma, angiolipomas, and some sarcomas.

Ans. is ‘a’ i.e., C-KIT

Pathogenesis of GISTs

o Approximately 75% to 80% of all GISTs have oncogenic, gain-of-function mutations of gene encoding the tyrosine kinase c-KIT

o Approximately 8% of GISTs have mutations that activate a related tyrosine kinase, platelet derived growth factor receptor a (PDGFRA).

o Consitutively active c-KIT or PDGFRA receptor tyrosine kinases activate RAS and P13K/AKT pathways and thereby promote tumor cell proliferation.

Ans. is ‘b’ i.e., High proportion of malignant change

The prognosis depends on tumor size, mitotic index & location.

o Recurrence or metastasis common for mitotic active tumors & more than 10cm but not for others.

Ans. is ‘b’ i.e., Imatinib

Tyrosine kinase inhibitors imatinib and sunitinib are approved for the treatment of Gastrointestinal Stromal Tumors (GIST)

Ans is ‘b’ i.e. CD 117 

GISTs: MC mesenchymal tumor of the GI tract
• MC primary site for GIST: Stomach (60–70%) > small bowel (20–25%) > colorectum and esophagus (5% each).
• Most GISTs are positive for CD-117 (95%), BCL-2 (80%), CD-34 (70%).
• Types: Spindle cell (70%) and Epitheloid (30%)Q
Pathology:
• Arise from the muscularis propria and most likely originate from the cells of Cajal
• Expression of the receptor tyrosine kinase KIT (CD 117), 5% express platelet derived growth factor receptor alpha (PDGFRA).
• PDGFRA mutations in GIST appear to confer a very favorable prognosis with a low risk of recurrence.
• Spindle cell pattern (70%) of GIST is more common than epithelioid or round cell pattern (30%).
• New tumor markers of GIST: DOG-1 (discovered on GIST-1) and protein kinase C-theta
Clinical features:
• Patients usually present after the fourth decade, with the mean age of 60 years at diagnosis.
• MC presentations of gastric GISTs: GI bleeding and pain or dyspepsia.

Ans. A i.e. CD117

Gastrointestinal stromal tumor (GIST)

• It is one of the most common mesenchymal tumorsof the gastrointestinal tract (1-3% of all gastrointestinal malignancies).
• They are typically defined as tumors whose behavior is driven by mutations in the Kit gene or PDGFRA gene, and may or may not stain positively for Kit.
• When GIST is suspected — as opposed to other causes for similar tumors — the pathologist can use immunohistochemistry (specific antibodies that stain the molecule CD117 [also known as c-kit] — see below).
• 95% of all GISTs are CD117-positive (other possible markers include CD34, DOG-1, desmin, and vimentin).
• Other cells that show CD117 positivity are mast cells

Ans. is ‘d’ i.e., Least common mesenchymal neoplasm of gastrointestinal tract

Gastrointestinal stromal tumors (GISTs)

GISTs are the most common mesenchymal neoplasm of gastrointestinal tumor.

GIST represents a distinct group of gastrointestinal tumors that originate from the interstial cells of cajal which control gastrointestinal peristalsis.

GISTs can occur anywhere in the gastroinstestinal tract; the most common site being the stomach followed by small intestine.

Ans. is ‘b’ i.e., High propensity of malignant change

Pathogenesis of GISTs

• Approximately 75% to 80% of all GISTs have oncogenic, gain-of-function mutations of gene encoding the tyrosine kinase c-KIT
• Approximately 8% of GISTs have mutations that activate a related tyrosine kinase, platelet derived growth factor receptor a (PDGFRA).
• Consitutively active c-KIT or PDGFRA receptor tyrosine kinases activate RAS and P131f/AKT pathways and thereby promote tumor cell proliferation.
• The prognosis depends on tumor size, mitotic index & location.
• Recurrence or metastasis common for mitotic active tumors & more than 10cm but not for others.

Ans. d. ALK gene mutation is seen in most of the cases

Most common mesenchymal tumor of the abdomen
Commonly occur in stomach (mc site) and duodenum
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract.
Arise from the interstitial cells of Cajal or pacemaker cells
Size and mitotic index are the best predictors of metastasis
Tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%) or BRAF kinase (rare)