Surgical Pathology Criteria

Gastrointestinal Stromal Tumor (GIST)

Differential Diagnosis

General differential diagnostic features of GIST reactive antibodies (see Supplemental Studies):

Spindled, Bland GIST DDx

GI Leiomyoma GIST (spindled, bland)
Usually arises in muscularis mucosae Nearly always arises in muscularis propria
Cytoplasm usually distinct, eosinophilic Cytoplasm frequently indistinct
CD117 negative CD117 74-95%
CD34 negative CD34 70%
DOG1 negative DOG1 87-94%
Desmin 100% Desmin 1-2% overall but 20% in esophagus
DOG1 is more sensitive for GIST than CD117 in side by side comparison

 

GI Schwannoma GIST (spindled, bland)
Peripheral lymphoid cuff common Lacks lymphoid cuff
Frequent cell size variation Generally uniform cell size
No skeinoid fibers May have skeinoid fibers
S100 100% S100 5% (20% in small intestine)
GFAP 65-100% GFAP negative
CD117 negative CD117 74-95%
Palisading is more accentuated in GIST; CD34 stains 0-33% of GI schwannomas

 

Fibromatosis, Mesenteric or Retroperitoneal and Pelvic Gastrointestinal Stromal Tumor
CD34 negative CD34 60-70% positive
CD117 frequently negative, variable reports of focal/weak staining CD117 74-95% positive
DOG1 negative DOG1 87-94%
Beta-catenin positive 90% (nuclear) Beta-catenin negative
Low to moderate cellularity Moderate to high cellularity
Cytologically bland May be cytologically atypical
Prominent thin walled dilated veins Lacks prominent veins
Infiltrative margin Usually circumscribed, pushing margin
No cystic degeneration or necrosis May have cystic degeneration or necrosis
GIST with epithelioid or abundant spindled cytoplasm can be distinguished morphologically

 

Sclerosing Mesenteritis GIST (spindled, bland)
Lobulated paucicellular fibrosis Not typically lobulated, usually cellular rather than fibrotic
Prominent chronic inflammatory infiltrate Inflammation not typical
Entrapped fat and fat necrosis Lobules of entrapped fat and fat necrosis unusual
Both may be positive for CD117 and CD34

 

Inflammatory Fibroid Polyp GIST (spindled, bland)
Submucosal Intramural
Spindled and stellate cells Spindled but no stellate cells
Abundant stromal eosinophils Eosinophils infrequent
Perivascular concentric cuffing common Lacks concentric cuffing
Fibromyxoid background with regular vascular pattern May be myxoid but lacks regular vascular pattern
CD117 negative CD117 74-95%
DOG1negative DOG1 87-94%
Both are frequently CD34 positive

 

GIST (spindled, bland) Gastric Plexiform Fibromyxoma
Usually solitary nodule Multinodular, plexiform
Myxoid pattern rare Myxoid pattern predominates
KIT and/or DOG1 74-95% KIT and DOG1 negative
CD34 frequently positive CD34 negative

 

Gastrointestinal Stromal Tumor Solitary Fibrous Tumor
Spindled or epithelioid cytoplasm Scant cytoplasm
Skeinoid fibers, if present are irregular, globular and have prominent retraction Ropy collagen
Hemangiopericytoma-like vessels uncommon HPC-like vessels common
CD117 (KIT) 74-95%, DOG1 87-95% positive CD117, DOG1 negative
Actin 30-50% positive Actin rare and focal
CD34 is usually positive in both

 

Inflammatory Myofibroblastic Tumor Gastrointestinal Stromal Tumor
Usually in children Rare in children
Frequently associated with systemic signs and symptoms Not associated with systemic signs and symptoms
Prominent inflammatory cells Usually only scattered inflammatory cells
Frequently positive for desmin, keratin and ALK Desmin, keratin and ALK negative
CD117, DOG1, CD34 negative CD117 74-95%, DOG1 87-95%, CD34 70%

 

Endometrial Stromal Sarcoma (Metastatic) GIST (spindled, bland)
History of prior hysterectomy No such history

May arise in endometriosis Not associated with endometriosis
Prominent spiral arterioles Hyalinized larger vessels
CD10, ER and PR positive ER and PR negative
DOG1 negative DOG1 87-94%
Both may be CD117 positive

 

Calcifying Fibrous Pseudotumor GIST (spindled, bland)
Calcification frequently psammomatous Calcification dystrophic, not psammomatous
Patchy chronic inflammation Inflammation not typical
May form multinodular mass Not typically multinodular
Prominent hyalinized stroma Stroma occasionally sclerotic but not usually hyalinized

 

Spindled, Malignant GIST DDx

GI Leiomyosarcoma GIST (spindled, cytologically malignant)
Frequently markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
Frequently brightly eosinophilic cytoplasm Usually indistinct cytoplasm
CD117, DOG1 negative CD117 74-95%, DOG1 87-94%
Desmin variably positive Desmin 1-2%

 

Malignant Fibrous Histiocytoma GIST (spindled, cytologically malignant)
Markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
CD117, DOG1, CD34 negative CD117, DOG1, CD34 70-95%

 

Dedifferentiated Liposarcoma GIST (spindled, cytologically malignant)
Frequently markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
CD117, DOG1 negative CD117, DOG1 85-95%
CD34 may be positive in both

 

Epithelioid GIST DDx

Poorly Differentiated Carcinoma GIST (epithelioid)
May have a mucosal component or form glands No mucosal component or true glands
Frequently markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
Mucin stain may be positive No mucin
Keratin positive Keratin 1-2%
CD34 negative CD34 70%
DOG1 negative DOG1 87-94%%
CD117 stains many carcinomas

 

Melanoma or Clear Cell Sarcoma GIST (epithelioid)
Frequently markedly pleomorphic Pleomorphism infrequent, even in malignant lesions
S100 positive S100 5% (20% in small intestine)
HMB45, MelanA positive HMB45, MelanA negative
CD34 negative CD34 70%
DOG1rare DOG1 87-94%
CD117 stains most melanomas; melanocytic markers may have decreased reactivity in clear cell sarcomas

 

Glomus Tumor GIST (epithelioid)
Nuclei round and regular Nuclei usually oval or spindled
Distinct cell borders Cell borders may be indistinct
Mitotic rate usually <1/50 HPF Mitotic rate can be higher
CD117 negative CD117 74-95%
Smooth muscle actin positive Smooth muscle actin frequently negative
Both may have clear/retracted cytoplasm; both may be CD34 positive

 

Gangliocytic Paraganglioma GIST (epithelioid)
Three cell types: epithelioid, ganglion, spindled May be both spindled and epithelioid but rarely intermingled as discrete cell populations and lacks ganglion cells
Synaptophysin and chromogranin positive Synaptophysin and chromogranin negative
Keratin positive epithelioid cells Keratin 1-2%
CD117 negative CD117 74-95%

 

GI Endocrine Carcinoma GIST (epithelioid)
Nuclei round and regular Nuclei usually oval or spindled
Stippled (salt and pepper) chromatin Usually vesicular chromatin
Keratin positive cells Keratin 1-2%
Synaptophysin and chromogranin positive Synaptophysin and chromogranin negative
CD117 negative CD117 74-95%

 

Extramedullary Myeloid Tumor GIST (epithelioid)
Frequent history of leukemia Rarely associated with leukemia
Eosinophilic myelocytes frequently present No eosinophilic precursors
Infiltration along collagen fibers Infiltration through tissues
CD45, CD43, myeloperoxidase positive CD45, CD43, myeloperoxidase negative
CD34 and CD117 stain both

 

GI Mucosal Benign Epithelioid Nerve Sheath Tumor GIST (Epithelioid)
Centered in lamina propria or submucosa Most centered on muscularis propria
S100 positive S100 negative
CD117 negative CD117 74-95%
CD34 negative CD34 70%
Restricted to colon Most common in stomach

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