Case 39

A 65-year-old female presented with a large submucosal mass in stomach.

What's the likely diagnosis and the immuno you would like to confirm?

IHC

• Keratin
• SMA, desmin
• CD117 (C-KIT)
• DOG-1

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Answer

This is a case of gastrointestinal stromal tumor (GIST). The differential diagnosis of a spindle cell neoplasm in GI submucosa include: GIST, schwannoma, leiomyoma/leiomyosarcoma, inflammatory fibroid polyp, synovial sarcoma, or inflammatory myofibroblastic tumor. It can show intramural, submucosal, or subserosal masses with spindle, epithelioid, or mixed cell types. They typically test positive for KIT and/or DOG1 markers, and SDHB loss is seen in SDH-deficient cases. Additionally, approximately 85% of GISTs have mutations in the KIT or PDGFRA genes. SDH-deficient GISTs typically display an epithelioid appearance and are often composed of multiple nodules with a plexiform pattern in the tumor cells. In contrast to standard GISTs, these tumors more frequently show invasion of lymphatic and blood vessels as well as metastasis to lymph nodes.

Differential Diagnosis

Key Features

Immunohistochemistry (IHC) Markers

Gastrointestinal Stromal Tumor (GIST)

Spindle cell or epithelioid morphology, often with a whorled or nested growth pattern

Positive: KIT (CD117), DOG1, CD34 (variable); Negative: S100, desmin, keratins

Leiomyoma / Leiomyosarcoma

Smooth muscle differentiation, interlacing fascicles of spindle cells with cigar-shaped nuclei, eosinophilic cytoplasm

Positive: SMA, desmin; Negative: KIT, DOG1

Schwannoma

Spindle cell tumor with Antoni A and B areas, Verocay bodies, thick-walled hyalinized vessels

Positive: S100 (diffuse), SOX10; Negative: KIT, DOG1, CD34

Fibromatosis (Desmoid Tumor)

Long fascicles of spindle cells, infiltrative growth pattern, bland nuclei, collagen deposition

Positive: β-catenin (nuclear), SMA (variable); Negative: KIT, DOG1

Inflammatory Myofibroblastic Tumor (IMT)

Spindle to stellate-shaped myofibroblasts with lymphoplasmacytic infiltration

Positive: ALK (60-70%), SMA, desmin; Negative: KIT, DOG1

Synovial Sarcoma

Biphasic (epithelial and spindle components) or monophasic spindle cell type

Positive: TLE1, cytokeratins (variable), EMA; Negative: KIT, DOG1

Solitary Fibrous Tumor (SFT)

Spindle cell tumor with a "patternless" architecture and prominent branching "staghorn" vessels

Positive: STAT6 (nuclear), CD34; Negative: KIT, DOG1

Melanoma (Metastatic or Primary)

Pleomorphic spindle or epithelioid cells, pigmentation, high mitotic rate

Positive: S100, SOX10, HMB-45, Melan-A; Negative: KIT, DOG1

Sarcomatoid Carcinoma

Poorly differentiated carcinoma with spindle cell morphology

Positive: Pancytokeratin, EMA; Negative: KIT, DOG1

Ewing Sarcoma / PNET

Small round blue cell tumor, necrosis, high mitotic rate

Positive: CD99, FLI1 (nuclear); Negative: KIT, DOG1

References: https://tumourclassification.iarc.who.int/chaptercontent/31/206

Case credit: UCSD Pathology

Author: Wangpan Shi, MD