Discussion Inflammatory myofibroblastic tumor of gall bladder
BEYOND GIST: RECENT ADVANCES IN GASTROINTESTINAL...
Transcript of BEYOND GIST: RECENT ADVANCES IN GASTROINTESTINAL...
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BEYOND GIST:RECENT ADVANCES IN GASTROINTESTINAL
MESENCHYMAL TUMORSJason L. Hornick, M.D., Ph.D.
Brigham and Women’s Hospital and
Harvard Medical SchoolBoston, MA
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Disclosure of Relevant Financial Relationships
The faculty, committee members, and staff who are in position to control the content of this activity are required to disclose to USCAP and to learners any relevant financial relationship(s) of the individual or
spouse/partner that have occurred within the last 12 months with any commercial interest(s) whose products or services are related to the CME content. USCAP has reviewed all disclosures and resolved
or managed all identified conflicts of interest, as applicable.
The following faculty reported no relevant financial relationships: Dr. Jason L. Hornick
USCAP staff associated with the development of content for this activity reported no relevant financial relationships.
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Tumors Not to be Confused with GIST
Relatively common Rare
LeiomyomaLeiomyosarcoma
Inflammatory fibroid polyp
Desmoid fibromatosisInflammatory myofibroblastic tumor
PEComa
Schwannoma
Glomus tumor
Gastrointestinal neuroectodermal tumor
Plexiform fibromyxoma
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Tumors Not to be Confused with GIST
Relatively common Rare
LeiomyomaLeiomyosarcoma
Inflammatory fibroid polyp
Desmoid fibromatosisInflammatory myofibroblastic tumor
PEComa
Schwannoma
Glomus tumor
Gastrointestinal neuroectodermal tumor
Plexiform fibromyxoma
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Inflammatory Fibroid Polyp
• Most common in antrum and ileum• Wide age range• Intussusception (small bowel)• Polyp > mural mass• Often ulcerated• Most often submucosal• Ill-defined margins• Benign – do not recur
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Stomach Inflammatory Fibroid Polyp
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Stomach Inflammatory Fibroid Polyp
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Ileum Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp
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Inflammatory Fibroid Polyp:Molecular Findings
• Long debate: neoplastic or reactive
• Activating mutations in PDGFRA
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Inflammatory Fibroid Polyp
PDGFRA
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Inflammatory Myofibroblastic Tumor
• Most common in children and young adults
• Outside of lung, most common sites: abdomen (mesentery, GI tract, omentum), pelvis, retroperitoneum
• May be multifocal at presentation in abdominal cavity
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Inflammatory Myofibroblastic Tumor: Prognosis
• WHO: Intermediate biologic potential, rarely metastasizing
• Local recurrence:<2% lung25% extrapulmonary (intra-abdominal++)
• Metastasis:1-2% (lung, brain, liver, bone)
• In general, poor correlation between histology and behavior
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Inflammatory Myofibroblastic Tumor
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Inflammatory Myofibroblastic Tumor
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SMA desmin
Inflammatory Myofibroblastic Tumor
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ALK in Inflammatory Myofibroblastic Tumor
• ALK gene rearrangement in 60% IMT<10% in adults >50 yrs
• Heterogeneous fusion partners
• Strong correlation between detection of ALK expression by IHC and ALK rearrangement in IMT
• ALK negative in other myofibroblastic and smooth muscle tumors, GIST
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Inflammatory Myofibroblastic Tumor
ALK
TPM3-ALK
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FISH
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Epithelioid Inflammatory Myofibroblastic Sarcoma
• Distinctive aggressive variant of inflammatory myofibroblastic tumor (rapid recurrences)
• Predilection for young male adults
• Nearly all intra-abdominal (mesentery, omentum)
• Epithelioid morphology
• Often myxoid stroma; prominent neutrophils
• Nuclear membrane >> perinuclear pattern of ALK
• RANBP2-ALK >> RRBP1-ALK fusion
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Epithelioid Inflammatory Myofibroblastic Sarcoma
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Omentum
Epithelioid Inflammatory Myofibroblastic Sarcoma
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Mesentery
Epithelioid Inflammatory Myofibroblastic Sarcoma
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Mesentery
Epithelioid Inflammatory Myofibroblastic Sarcoma
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desmin
Epithelioid Inflammatory Myofibroblastic Sarcoma
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Epithelioid Inflammatory Myofibroblastic SarcomaRANBP2-ALK
ALK
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ALK
Epithelioid Inflammatory Myofibroblastic SarcomaRRBP1-ALK
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N Engl J Med 2010;363:1727-33.
3 months
Multifocal Recurrent EIMS Treated with Crizotinib
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ALK-Negative Inflammatory Myofibroblastic Tumors?
• Until recently, molecular pathogenesis unknown
• Recent reports identified fusions involving receptor tyrosine kinase genes other than ALK
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Inflammatory Myofibroblastic TumorTFG-ROS1
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ROS1
Inflammatory Myofibroblastic TumorTFG-ROS1
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Inflammatory Myofibroblastic Tumor
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Gastrointestinal Neuroectodermal Tumor• Also known as clear cell sarcoma-like tumor• ~50 reported cases, increasingly recognized• Young to middle-aged adults• Mean age 40 years• Small bowel (70%), stomach, colon• Large infiltrative masses• May be mistaken for GIST• Aggressive sarcoma• Lymph node and liver metastases
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Ileum
Courtesy of Mee Joo, MD
Gastrointestinal Neuroectodermal Tumor
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Small bowel
Gastrointestinal Neuroectodermal Tumor
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Gastrointestinal Neuroectodermal Tumor
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Gastrointestinal Neuroectodermal Tumor
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Jejunum
Gastrointestinal Neuroectodermal Tumor
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Ileum Gastrointestinal Neuroectodermal Tumor
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Gastrointestinal Neuroectodermal Tumor:Immunophenotype and Molecular Genetics
• Diffuse strong reactivity for S100 protein and SOX10
• Lacks melanocytic markers (HMB-45, melan A, MiTF)
• t(12;22) with ATF1-EWSR1 or t(2;22) with CREB1-EWSR1
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HMB-45S100
Gastrointestinal Neuroectodermal Tumor
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Lymph node
Metastatic Gastrointestinal Neuroectodermal Tumor
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PEComa• Family of related mesenchymal lesions:
• Angiomyolipoma (AML)
• Lymphangiomyomatosis (LAM)
• PEComa NOS
• All share distinctive cell type: “perivascular epithelioid cell” (PEC)
• Evidence of myogenic (smooth muscle) and melanocytic differentiation
• No known normal tissue counterpart
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PEComa:Clinical Features
• Female predominance (5:1 overall, but no gender predilection in GI tract)
• Middle-aged adults
• Rarely associated with TSC (unlike AML and LAM)
• Most common sites: abdomen/pelvis, retroperitoneum, visceral sites (especially GI tract and uterus)
• Minority (25%) in somatic soft tissue and skin
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Pancreas PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa
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PEComa:Immunophenotype
• Mixed melanocytic/myogenic phenotype
• Nearly all HMB-45 positive
• Most positive for MiTF
• SMA most sensitive myogenic marker
• Some lack smooth muscle markers (especially epithelioid/clear cell)
• Focal S100 protein in 10-20%
• TFE3 positive in 10-15%
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desminSMA
PEComa
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Melan AHMB-45
PEComa
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PEComa:Criteria for Malignancy
•Features associated with malignant behavior in GI tract:
• Mitotic activity (≥ 2 per 10 HPF)
• Marked nuclear atypia
• Diffuse pleomorphism
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Courtesy of Joon Choi, MD
Colon Malignant PEComa
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Malignant PEComa
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Malignant PEComa
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Metastatic Malignant PEComa
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Metastatic Malignant PEComa
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Metastatic Malignant PEComa
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PEComa:Molecular Findings
• Frequent deletions of TSC2 at 16p13
• Activation of mTOR (mammalian target of rapamycin) signaling pathway
• Therapeutic implications for patients with clinically aggressive PEComas
• mTOR inhibitors
• Small subset with TFE3 rearrangement
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9 months
Courtesy of Andrew Wagner, MD, PhD
Malignant PEComa treated with sirolimus
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Practice points
• Not all GI mesenchymal tumors are GIST
• Critical distinctions owing to marked differences in behavior and treatment
• After first considering GIST, ask yourself if there are any distinctive histologic features that might suggest an alternative diagnosis
• Order IHC based on differential diagnosis
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