What do positive CD34 and factor XIIIa immunohistochemistry results indicate in a malignant setting?

Immunohistochemistry Profile in Malignant Dermatofibrosarcoma Protuberans

In malignant dermatofibrosarcoma protuberans (DFSP), CD34 is typically positive and factor XIIIa is negative, which is the characteristic immunohistochemical signature that distinguishes this low-grade malignant tumor from benign dermatofibroma. 1

Standard DFSP Immunohistochemistry Pattern

The typical malignant DFSP demonstrates the following immunoprofile:

• CD34 positivity is present in approximately 92% of DFSP cases, with diffuse staining (50-100% of tumor cells) 1, 2
• Factor XIIIa negativity is characteristic, with most cases showing very few or no reactive cells 1, 3
• When factor XIIIa-positive cells are present in DFSP, they are typically confined to the infiltrating tumor edges or represent entrapped non-neoplastic dermal dendrocytes rather than tumor cells 2

The NCCN explicitly states that immunohistochemistry for CD34 is "mostly positive" and factor XIIIa is "negative" in DFSP 1. This pattern is essentially the inverse of benign dermatofibroma, which shows factor XIIIa positivity (90-97% of cases) and CD34 negativity (60% negative) 3, 2.

Fibrosarcomatous Transformation Pattern

A critical caveat exists when DFSP undergoes fibrosarcomatous transformation (FS-DFSP), which represents a higher-grade malignant variant:

• CD34 becomes negative in areas of fibrosarcomatous transformation 1
• This loss of CD34 expression accompanies increased cellularity, cytologic atypia, and mitotic activity (>5/10 high-power fields) 1
• The histologic pattern transitions from storiform to herringbone architecture 1
• FS-DFSP carries higher metastatic risk and requires referral to soft tissue sarcoma specialists 1

Clinical Application Algorithm

When evaluating a suspected malignant spindle cell lesion:

1. If CD34 positive AND factor XIIIa negative → Strongly supports DFSP diagnosis 1, 4
2. If CD34 negative in a suspected DFSP → Consider fibrosarcomatous transformation and check S100 to exclude other spindle cell tumors 1
3. For equivocal cases → Obtain molecular testing for t(17;22)(q22;q13) translocation via FISH or PCR, which is present in >90% of DFSP cases 1, 4

Important Diagnostic Pitfalls

• CD34 can occasionally be positive in dermatofibroma (40% show some positivity), but staining is focal with ≤20% positive cells, unlike the diffuse pattern in DFSP 3, 2
• Factor XIIIa can be present in DFSP (75% show some staining), but represents entrapped normal dermal cells rather than tumor cells 2
• No single marker is 100% specific, which is why the NCCN recommends confirmatory immunostaining be performed in all suspected DFSP cases 1
• Margin assessment during excision may require CD34 immunohistochemistry supplementation to ensure complete tumor removal 1