What is the most likely diagnosis for a patient with a 12 cm free-floating abdominal mass showing spindle cell architecture and fibrous components on pathology?

Most Likely Diagnosis: Gastrointestinal Stromal Tumor (GIST)

A 12 cm free-floating abdominal mass with spindle cell architecture and fibrous components is most consistent with a gastrointestinal stromal tumor (GIST), which represents the most common intramural subepithelial mass in the upper gastrointestinal tract and characteristically presents as a large, mobile abdominal mass with spindle cell morphology. 1

Diagnostic Reasoning

Why GIST is the Primary Diagnosis

• Size and presentation: GISTs commonly present as large tumors with abdominal pain/discomfort and a palpable mass, particularly when they reach significant size (>10 cm) 1

• Spindle cell architecture: Approximately 70% of GISTs demonstrate spindle cell morphology on pathology, making this the predominant histologic pattern 1

• Free-floating characteristic: Larger GISTs often arise from the muscularis propria and can appear as exophytic, mobile masses that seem to "float" within the abdomen, especially when they originate from the stomach or small bowel 1

• Midline location: The stomach is the most common location for GISTs, and gastric GISTs frequently present in the midline abdomen 1

Essential Confirmatory Testing

Immunohistochemistry is mandatory to confirm the diagnosis, as GIST relies on both morphology and specific markers 1:

• CD117 (c-kit) positivity: Present in approximately 95% of GISTs 1
• DOG1 positivity: Should be performed if CD117 is negative, as it identifies the remaining 5% of CD117-negative GISTs 1
• CD34 positivity: Found in approximately 70% of cases, providing supportive evidence 1

Mutational analysis is strongly recommended before any systemic treatment consideration 1:

• KIT mutations (present in 80% of cases, most commonly exon 11) 1
• PDGFRA mutations (present in 10% of cases) 1
• This testing has both prognostic and predictive value for imatinib sensitivity 1

Critical Differential Diagnoses to Exclude

While GIST is most likely, the following must be considered:

Leiomyoma/Leiomyosarcoma: These also demonstrate spindle cell architecture with fibrous components 1, 2:

• However, leiomyomas are most common in the esophagus (two-thirds of esophageal spindle cell tumors), not the midline abdomen 1, 2
• Differentiation requires immunohistochemistry: leiomyomas are typically desmin-positive and CD117-negative 1
• Giant leiomyomas (>15 cm) of the colon are extremely rare 3

Other considerations that can be excluded:

• Inflammatory fibroid polyp: Located in deep mucosa/submucosa without muscularis propria involvement, typically smaller 1
• Desmoid tumor: Would require different treatment strategy, excluded by immunohistochemistry 1
• Schwannoma: Would be S-100 positive, CD117 negative 1

Management Algorithm for This Patient

Immediate Next Steps

1. Complete the pathologic diagnosis 1, 4:

   • Confirm CD117 and/or DOG1 positivity
   • Obtain mitotic count per 5 mm² (critical prognostic factor) 1
   • Perform mutational analysis for KIT and PDGFRA genes 1

2. Staging workup 4, 5:

   • Contrast-enhanced CT scan of abdomen and pelvis to assess for metastatic disease (liver and peritoneum are most common sites) 4, 5
   • Evaluate relationship to surrounding structures and determine resectability 4

Treatment Planning

For a 12 cm mass, surgical resection is the standard treatment for localized GIST 5:

• If easily resectable: Proceed directly to complete surgical resection with negative margins 1, 5
• If requiring multivisceral resection or potentially morbid surgery: Consider neoadjuvant imatinib to downstage the tumor, but this requires confirmation of imatinib-sensitive mutations (avoid if PDGFRA D842V or KIT exon 17 D816V mutations present) 1

Critical Surgical Principles

• Avoid tumor rupture: Intra-abdominal spillage dramatically increases recurrence risk 5
• Achieve complete resection with negative margins: This is the primary goal 5
• Surgery should be performed by appropriately trained surgeons in or linked to a sarcoma specialist center 1

Common Pitfalls to Avoid

• Do not proceed with definitive surgery before obtaining tissue diagnosis for masses requiring complex resection, as this allows proper surgical planning and may avoid unnecessary surgery for non-surgical diseases like lymphoma or desmoid tumors 1, 4

• Do not use Bouin fixation for tissue samples, as it prevents molecular analysis; always use 4% buffered formalin 1

• Do not assume all spindle cell tumors are GIST: Immunohistochemistry is essential to differentiate from leiomyoma, leiomyosarcoma, schwannoma, and other entities that require different management 1

• Do not skip mutational analysis: This has critical implications for treatment planning, particularly if systemic therapy is being considered 1