• FXIIIa is widely expressed in a variety of cell types; however, it is most commonly recognized as a marker of fibrohistiocytic proliferations
• Derived from monocyte / macrophage myeloid lineage and expressed in dermal dendrocytes, primarily surrounding microvasculature in the adventitial dermis near the dermoepidermal junction and near skin appendages (Int J Mol Med 2008;22:403)
• Active form of factor XIII, the last enzyme in the coagulation cascade

• Cytoplasmic marker with expression in normal epithelial tissue and various pathologic states
• Mainly used to distinguish dermatofibroma from dermatofibrosarcoma protuberans
• Generally expressed (with some variation) in benign sebaceous neoplasms, fibroblasts in fibrovascular tumors and a proportion of histiocytomas
• Generally negative (with some variation) in malignant sebaceous neoplasms and clear cell tumors

• Factor XIIIa, FXIIIa, F13a, fibrin stabilizing factor

• Synthesized by cells in the bone marrow, FXIIIa exists as a tetrameric molecule with 2 A subunits and 2 B subunits in plasma and a dimer composed of 2 A subunits in cells (J Thromb Haemost 2007;5:181)
• Zymogen that crosslinks fibrin molecules which stabilizes blood clots
• Enhances proliferation and inhibits apoptosis of peripheral monocytes and fibroblasts (Cell Physiol Biochem 2007;19:113)
• Participates in wound healing and keloid formation (Thromb Haemost 2002;88:967, Pathol Int 2007;57:337)

• FXIII has been shown to have a role in metastatic potential by impeding NK cell mediated clearance of tumor cells (J Thromb Haemost 2008;6:812)
• Lung squamous cell carcinoma: plays a role in cell invasion and disease progression; extensive fibrin linkage correlated with worse prognosis (Nat Commun 2018;9:1988)
• Low levels of FXIIIa following an acute myocardial infarction have been correlated with worse prognosis with increased complications, such as heart failure and death (Thromb Haemost 2015;114:123)

• Cytoplasmic staining ranging from focal to diffuse and weak to strong

Contributed by Brandon Umphress, M.D.

A 37 year old woman presents with a 1 year history of a lumpy mass on her midback. On physical exam, the lesion is 3 cm, slightly raised, resembling a scar that feels rubbery upon palpation. Histologic examination shows a spindle cell neoplasm that is diffusely positive for CD34 and negative for factor XIIIa and S100 staining. Which of the following is the most likely diagnosis?

1. Cutaneous melanoma
2. Dermatofibroma
3. Dermatofibrosarcoma protuberans
4. Myxoid liposarcoma

C. Dermatofibrosarcoma protuberans is CD34+, factor XIIIa- and S100-. Dermatofibroma is typically CD34- and factor XIIIa+. Myxoid liposarcoma is usually vimentin+, S100+ and CD34-. Cutaneous melanoma would express S100.

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Reference: Factor XIIIa

Which of the following features regarding factor XIIIa is true?

1. Commonly differentiates melanoma from basal cell carcinoma
2. Marker of fibrohistiocytic proliferations
3. Part of the coagulation cascade aiding in plasminogen crosslinking
4. Stains negatively for normal dermal dendrocytes

B. Factor XIIIa is a general marker for fibrohistiocytic proliferations

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Reference: Factor XIIIa