What is the diagnosis for a lesion with IHC (Immunohistochemistry) results showing positivity for CD34, weak positivity for MDM2, and the presence of SMA (Smooth Muscle Actin) and CK4 (Cytokeratin 4)?

Diagnosis Interpretation

This immunohistochemical profile is NOT consistent with nodular fasciitis and instead suggests either an inflammatory fibroid polyp, dermatofibrosarcoma protuberans (DFSP), or a superficial CD34-positive fibroblastic tumor, depending on anatomic location and histologic features.

Why This is NOT Nodular Fasciitis

Nodular fasciitis characteristically shows the following IHC pattern that contradicts your findings:

• Positive for SMA (smooth muscle actin) - which matches your case 1, 2
• Negative for CD34 - this is the critical discrepancy, as nodular fasciitis is consistently CD34-negative 1, 2
• Negative for cytokeratins - your case shows CK4 positivity, which is atypical 2
• Negative for desmin in most cases 1

The presence of strong CD34 positivity is incompatible with nodular fasciitis and immediately shifts the differential diagnosis to other spindle cell lesions 1, 2.

Most Likely Diagnostic Considerations

1. Inflammatory Fibroid Polyp (If Gastrointestinal Location)

If this lesion is located in the gastrointestinal tract, inflammatory fibroid polyp is the leading diagnosis:

• IHC positive for CD34 - characteristic feature 3
• Negative for CD117 (c-kit) - essential to distinguish from GIST 3
• Shows spindle-cell proliferation with mixed inflammatory infiltrate (eosinophils, lymphocytes, plasma cells) 3
• Typically located in submucosa (3rd or 4th EUS layer) 3

2. Dermatofibrosarcoma Protuberans (If Cutaneous/Subcutaneous Location)

If this is a skin or soft tissue lesion, DFSP must be strongly considered:

• CD34 positivity is the hallmark - present in most cases 3
• Shows storiform or fascicular pattern of bland spindled cells 3
• Factor XIIIa negative - helps distinguish from dermatofibroma 3
• The weak MDM2 positivity is non-specific and does not indicate well-differentiated liposarcoma in this context 3

Critical caveat: Fibrosarcomatous transformation of DFSP (FS-DFSP) shows negative CD34, higher cellularity, and increased mitotic activity (>5/10 HPF), which would argue against this variant 3.

3. Superficial CD34-Positive Fibroblastic Tumor (If Superficial Soft Tissue)

This rare entity should be considered for superficial lesions:

• Diffuse CD34 positivity is the defining feature 4, 5
• May show focal cytokeratin expression (consistent with your CK4 positivity) 4, 5
• Contains pleomorphic giant cells with glassy cytoplasm 4, 5
• Low proliferative index (Ki-67: 4-5%) 4
• Negative for S100, CD30, CD31 4, 5

Critical Next Steps for Definitive Diagnosis

Essential Additional Information Needed:

1. Anatomic location - GI tract versus skin/soft tissue is decisive
2. Histologic architecture - storiform pattern (DFSP), inflammatory infiltrate (inflammatory fibroid polyp), or pleomorphic giant cells (superficial CD34+ fibroblastic tumor)
3. CD117 (c-kit) status - must be negative to exclude GIST 3
4. Factor XIIIa - negative in DFSP, may help narrow diagnosis 3

Molecular Testing to Consider:

• COL1A1-PDGFB fusion (t(17;22)) by FISH or PCR if DFSP is suspected 3
• USP6 gene rearrangement would support nodular fasciitis if clinical suspicion remains high despite CD34 positivity 2

Common Diagnostic Pitfalls

• Do not diagnose nodular fasciitis with CD34 positivity - this combination is essentially incompatible with published literature 1, 2
• Weak MDM2 positivity is non-specific and can occur in various benign and malignant lesions; it does not automatically indicate well-differentiated liposarcoma without appropriate morphology and strong/diffuse staining 3
• SMA positivity is seen in multiple entities including myofibroblastic lesions, DFSP, and inflammatory fibroid polyps, so it cannot be used as a sole discriminator 3, 1, 2
• Cytokeratin expression can be focal in superficial CD34+ fibroblastic tumor, so CK4 positivity does not exclude this diagnosis 4, 5