Short communicationCould cathepsin-k be a driver of the myofibroblastic differentiation observed in dermatofibroma, atypical fibroxanthoma and pleomorphic dermal sarcoma?
Introduction
Dermatofibroma/benign fibrous histiocytoma (BFH), atypical fibroxanthoma (AFX) and dermal pleomorphic sarcoma (DPS) are soft-tissue neoplasms commonly encountered by dermatopathologists (Fig. 1) (Elder et al., 2018). Numerous studies have focused on the lineage of differentiation and/or cell of origin of these neoplasms, but this topic continues to be a matter of debate (Longacre et al., 1993; Harding-Jackson et al., 2015; Prieto et al., 1995; Sakamoto et al., 2002). Although they are commonly classified as “fibrohistiocytic” neoplasms, various electron microscopic and immunohistochemical studies pointed out how the cell of origin could be an undifferentiated mesenchymal cell able to trans-differentiate toward a histiocytic, dendritic, fibroblastic and myofibroblastic lineage (Elder et al., 2018; Longacre et al., 1993; Harding-Jackson et al., 2015; Prieto et al., 1995; Sakamoto et al., 2002). By contrast, other authors argue that these neoplasms are made up of neoplastic cells (fibroblasts and/or histiocytes) admixed with a great number of accompanying cells, which justifies the confusing and sometimes controversial results (Prieto et al., 1995; Sakamoto et al., 2002; Goldblum et al., 2014). In recent years, starting from an attempt to clarify the remodelling process after myocardial infarction, several authors analyzed the complex metabolic processes that regulate the genesis of the myofibroblasts during the tissue repair, highlighting the central role of the proteases of the “cathepsin family” (Hinz, 2007; Shephard et al., 2004; Chen et al., 2013; Tomasek et al., 2002). For this reason, we evaluated whether the expression of cathepsin-k supports the myofibroblastic differentiation of these neoplasms and its role in myofibroblastic trans-differentiation, also in a neoplastic background.
Section snippets
Materials and methods
We retrospectively analyzed 53 cases (25 BFH, 5 AFX, 4 DPS, 5 dermatofibrosarcoma protuberans-DFSP, 5 malignant melanoma-MM, 5 basal cell carcinomas-BCC and 5 squamous cell carcinomas-SCC) diagnosed from May 2018 to February 2019 at the Service of Pathology Unit and Dermatology Unit, University of Bologna. All the cases were evaluated with a large panel of antibodies including cathepsin-K, smooth-muscle-actin (α-SMA), desmin, S-100, cytokeratin AE1/AE3, CD68, CD34 and CD10. Clinical,
Results and discussion
Catepsin-K showed moderate and diffuse positivity in all cases of BFH (16: 3+; 9: 2+), AFX (3: 3+; 2: 2+) and DPS (2: 3+; 2: 2+), whereas it was completely negative (0) in all the other tumours (Fig. 2). Cathepsin-k stained all the different cellular compartments, regardless of their morphology (fibroblastic, myofibroblastic and histiocytic) and other immunohistochemical results. 18 tumors (53 %) showed a peculiar pattern of immunostaining for cathepsin-k, with a crescendo-pattern moving from
CRediT authorship contribution statement
Costantino Ricci: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing. Antonio De Leo: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing. Emi Dika: Writing - review & editing. Martina Lambertini: Writing - review & editing. Giulia Veronesi: Writing - review
References (12)
Formation and function of the myofibroblast during tissue repair
J. Invest. Dermatol.
(2007)- et al.
The myofibroblast: one function, multiple origins
Am. J. Pathol.
(2007) - et al.
Myofibroblast differentiation is induced in keratinocyte-fibroblast co-cultures is antagonistically regulated by endogenous transforming growth factor-beta and interleukin-1
Am. J. Pathol.
(2004) - et al.
Cathepsin-S mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction
Cardiovasc. Res.
(2013) - et al.
World Health Organization Classification of Skin Tumors
(2018) - et al.
Enzinger and Weiss’s Soft Tissue Tumors
(2014)
Cited by (2)
Relation Between Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Histopathologic Features and Review of the Literature
2021, Actas Dermo-SifiliograficasKeloidal dermatofibroma: Clinicopathological comparison of 52 cases with a series of 2077 other dermatofibromas
2023, Journal of Dermatology