CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans

Abstract

The histological distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) may be extremely difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP. However, there is an overlap and relative lack of specificity of their expressions. CD44 is a widely distributed integral membrane glycoprotein, which is expressed as a multitude of isoforms generated by alternative splicing of at least 10 different variant exons and post-translational modifications. CD44 is currently thought to be the principal cell surface receptor for hyaluronate (HA), the major component of the extracellular matrix. In this study we aimed to assess the expression of standard CD44 (CD44s) and its isoforms (CD44v3, CD44v4, CD44v5, CD44v6, CD44v7, CD44v7v8, and CD44v10), and HA in DF and DFSP. Immunohistochemical staining was performed on the biopsy specimens of 15 cases of DF and four cases of DFSP, using antibodies that recognize the CD44s, different CD44 isoforms and the hyaluronate binding protein (HABP). Tumor cells displayed a strong CD44s immunoreactivity in all cases of DF whereas a faint HA positivity was observed in the tumor stroma. The DF cells were negative for CD44v3, CD44v4, CD44v6, CD44v7 and CD44v7v8 but showed a strong reactivity for CD44v5 and CD44v10. In contrast, CD44s' expression was significantly reduced or absent in all DFSP lesions and the tumor stroma displayed strong staining for HA. Our results indicate that CD44 and HA can be used as additional diagnostic markers to distinguish DF from DFSP.

The Roles of Hyaluronan/RHAMM/CD44 and Their Respective Interactions along the Insidious Pathways of Fibrosarcoma Progression

“…Indeed, a striking difference in hyaluronan stromal expression was reported between the benign dermatofibroma and the malignant dermatofibrosarcoma protuberans. Thus, whereas the dermatofibroma specimens show just a faint hyaluronan staining of the tumor stroma, the dermatofibrosarcoma protuberans specimens exhibit high HA deposition [66]. …”

“…Thus, the dermatofibroma cells are negative for CD44v3, CD44v4, CD44v6, CD44v7, and CD44v7v8 but show a strong reactivity for CD44v5 and CD44v10. In contrast, CD44s' expression was significantly reduced or absent in all dermatofibrosarcoma protuberans lesions [66]. …”

Dermatofibrosarcoma protuberans

“…20 At times, it may be difficult to draw a histologic distinction between DFSP and other mesenchymal tumors, such as dermatofibroma and benign fibrous histiocytoma. 21,22 DFSPs tend to stain positively for CD34 and negatively for factor XIIIa, whereas dermatofibromas generally have negative CD34 status and positive factor XIIIa status. 21 In addition, dermatofibromas tend to stain positively for CD44, a membrane glycoprotein that is thought to be the cell surface receptor for hyaluronate, the major component of the extracellular matrix.…”

“…21,22 DFSPs tend to stain positively for CD34 and negatively for factor XIIIa, whereas dermatofibromas generally have negative CD34 status and positive factor XIIIa status. 21 In addition, dermatofibromas tend to stain positively for CD44, a membrane glycoprotein that is thought to be the cell surface receptor for hyaluronate, the major component of the extracellular matrix. In dermatofibromas, stromal cells typically exhibit faint staining for hyaluronate, whereas DFSPs tend to exhibit strongly positive staining for this marker.…”

“…Furthermore, unlike dermatofibromas, DFSPs tend to have absent or significantly reduced CD44 immunostaining. 21 Fanburg-Smith and Miettinen 22 analyzed 1150 tumors, as well as fetal and normal adult tissue samples, for the expression of p75, a low-affinity nerve growth factor receptor. Those investigators reported that a wide variety of mesenchymal and epithelial tumors stained positively for p75, a finding that indicates that p75 expression is not specific to nerve sheath tumors.…”