An update on selected cutaneous (myo) fibroblastic mesenchymal tumors

Abstract

Cutaneous (myo)fibroblastic tumors constitute a group of tumors with overlapping clinicopathological features and variable biologic behavior. In the present review we focus on the histomorphology, immunohistochemical profile and molecular background of the following entities: dermatofibrosarcoma protuberans (DFSP), CD34-positive fibroblastic tumor (SCD34FT), myxoinflammatory sarcoma (MIFS), low-grade myofibroblastic sarcoma, solitary fibrous tumor and nodular fasciitis. Although some of these entities typically arise in deep-seated locations, they may occasionally present as cutaneous/superficial tumors and might be challenging to recognize. This review covers in depth the latest advances in molecular diagnostics and immunohistochemical markers that have significantly facilitated the correct classification and diagnosis of these neoplasms.

Keywords: Dermatofibrosarcoma protuberans; Low-grade myofibroblastic sarcoma; Myxoinflammatory fibroblastic sarcoma; Nodular fasciitis; Solitary fibrous tumor; Superficial CD34 fibroblastic tumor.

Figure 1. (DFSP)

A. Dermatofibrosarcoma protuberans typically arises in the dermis and infiltrates the subcutaneous adipose tissue (H&E, 1X) B. The tumor is composed of monomorphic spindle cells, arranged in short intersecting fascicles, with fat entrapment in a honeycomb pattern (H&E, 10X) C. The tumor cells do not show significant atypia, whereas collagen bundles are evident in the background (H&E, 20X) Inlet: The tumor is diffusely positive for CD34 (IHC, 5X) D. FISH break-apart (from a different case) is positive for the recently described PDGFD rearrangement (FISH pictures courtesy of Julia bridge MD, University of Nebraska).

Figure 2. (SCD34FT)

A. An example of SCD34FT involving the dermis (H&E, 2X) B. The tumor is composed of spindle and polygonal cells with glassy, eosinophilic cytoplasm arranged in intersecting fascicles (H&E, 10X) C. There is significant nuclear pleomorphism with prominent nucleoli and somewhat granular eosinophilic cytoplasm, but mitotic activity is typically low. Inflammatory cells may be seen (H&E, 40X). The tumor is diffusely positive for D. CADM3 and E. CD34 F. Focal positivity for AE1/AE3 may be seen in up to 70% of cases. (Pictures courtesy of Christopher Fletcher MD and David Papke MD, PhD, Brigham & Women’s Hospital).

Figure 3. (VGLL3- amplified MIFS)

A. This example of MIFS is located in the middle finger and is composed of cellular and hypocellular areas with nodules of myxoid material (H&E, 2X) B-C. The tumor cells have an epithelioid morphology with nucleomegaly and prominent nucleoli with a subset of them resembling Reed-Stenberg cells. Intermingled inflammatory cells/lymphocytes are evident (H&E, 20X & 40X) D. FISH shows amplification of the VGLL3 gene.

Figure 4. (Low grade myofibroblastic sarcoma)

A. This example of low-grade myofibroblastic sarcoma arises in the tongue and demonstrates mucosal ulceration as well as infiltration of the underlying skeletal muscle (H&E, 1X) B-C. The tumor is composed of spindle cells with pale eosinophilic cytoplasm arranged in fascicles. (H&E, 10X & 20X) D. There is minimal cytologic atypia with vesicular chromatin pattern and inconspicuous nucleoli (H&E, 40X) (Pictures courtesy of Cristina Antonescu MD, Memorial Sloan Kettering Cancer Center).

Figure 5. (Solitary fibrous tumor)

A. This example of solitary fibrous tumor is composed of monomorphic spindle to ovoid cells around staghorn-like blood vessels.(H&E, 5X) B-C The cells are arranged haphazardly and are embedded in a densely collagenous stroma. There is no overt cytologic atypia. (H&E, 10X&20X) D. The tumor is diffusely positive for STAT6 (IHC, 10X).

Figure 6. (Nodular Fasciitis)

A. This is an example of superficial nodular fasciitis arising in the dermis. (H&E, 5X) B. The tumor is composed of spindle-shaped monomorphic myofibroblastic cells arranged in short fascicles in a collagenous background. There is no nuclear pleomorphism, whereas typical mitoses are present (black arrow). Some scattered extravasated erythrocytes can be seen. (H&E, 40X) E. The tumor is diffusely positive for SMA with a characteristic tram-track pattern. F. FISH break-apart shows rearrangements of the USP6 gene (red arrows).