Dermatofibrosarcoma protuberans
Synonyms and keywords: Darier-Ferrand tumor, Darier-Hoffmann tumor, Dermatofibrosarcoma, DFSP, Intermediate fibrous histiocytoma, Borderline fibrous histiocytoma

# Overview
Dermatofibrosarcoma protuberans (DFSP) is a rare non-hereditary neoplasm of the dermis layer of the skin which is sometimes described as having the tentacles growing into the surrounding fat, muscle and even bone and is therefore, classified as a soft tissue sarcoma. In many respects, the disease behaves as a benign tumor, but in 2-5% of cases it can metastasize, so it should be considered to have a malignant potential. Over 95% of DFSP tumors have the chromosomal translocation t(17;22). The translocation fuses the collagen gene (COL1A1) with the platelet-derived growth factor gene. The fibroblast, the cell of origin of this tumor, expresses the fusion gene in the belief that it is collagen. However, the resulting fusion protein is processed into mature platelet-derived growth factor which is a potent growth factor. Fibroblasts contain the receptor for this growth factor. Thus, the cell "thinks" it is producing a structural protein, but in fact produces a self-stimulatory growth signal. The cell divides rapidly and a tumor forms. In dermatofibrosarcoma protuberans, the tumor has a tendency to return after being removed. However, it does not often metastasize to other parts of the body.

# Classification
There are several variants of dermatofibrosarcoma protuberans in which different cell types are involved in the tumor.

# Pathophysiology

## Epigenetics
- Dermatofibrosarcoma protuberans is associated with the genetic rearrangement (i.e. translocation) between chromosomes 17 and 22
- t(17;22)(q21;q13.1) leads to fusion of a part of COL1A1 gene from chromosome 17 with a part of the PDGFB gene from chromosome 22
- The translocation is found on one or more extra chromosomes that can be either the normal linear or circular in shape
- Circular extra chromosomes are known as supernumerary ring chromosomes (which form after a chromosome breaks in two places and the ends of the chromosomal arms fuse together to form a circular structure)
- Other genes from chromosomes 17 and 22 can be found on the extra chromosomes, but the role of these genes in the  development of this condition is unclear
- Translocation is acquired during a person's lifetime and the chromosomes containing the translocation are present only in the tumor cells, this type of genetic change is known as somatic mutation
- In normal cells, the COL1A1 gene provides instructions for making part of a large molecule called type I collagen, which strengthens and supports many tissues in the body
- The PDGFB gene provides instructions for making one version (isoform) of the platelet derived growth factor (PDGF) protein which by attaching to its receptor, becomes activated and stimulates many cellular processes, including cell growth and division (proliferation) and maturation (differentiation)
- The abnormally fused COL1A1-PDGFB gene provides instructions for making an abnormal combined (fusion) protein that ultimately functions like the PDGFB protein
- This gene fusion leads to the production of an excessive amount of protein that functions like the PDGFB protein
- In excess, this fusion protein stimulates cells to proliferate and differentiate abnormally, leading to the tumor formation as seen in dermatofibrosarcoma protuberans
- COL1A1-PDGFB fusion gene is found in more than 90% of the dermatofibrosarcoma protuberans cases
- In the remaining 10% of the cases, changes in some other unidentified genes may be associated with this condition such as complex t(5;8) involving the CSPG2 and PTK2B genes

## Gross Pathology
Gross features of dermatofibrosarcoma protuberans include:
- Nodular, polypoid or plaque-like mass
- Centered in the dermis
- Can also occur in deep soft tissue
- Mean size is 5 cm
- Gray-white, or brown/black in color (if melanocytes are present)
- May appear to be circumscribed
- Rarely shows:
Hemorrhage
Necrosis
- Hemorrhage
- Necrosis

## Histopathology
Microscopic features include:
- Non-circumscribed
- Highly cellular with cells having following characteristics:
Monomorphic
Thin
Spindly
Scant eosinophilic cytoplasm
Hyperchromatic nuclei (resembling neurofibroma)
- Monomorphic
- Thin
- Spindly
- Scant eosinophilic cytoplasm
- Hyperchromatic nuclei (resembling neurofibroma)
- Tight storiform pattern (cells radiating in spokes at right angles around a central point that often contains a vessel) infiltrating deeply into subcutaneous tissue and entraping fat cells to form a characteristic honeycomb pattern
- Areas of fascicular growth (seen in some cases)
- The early plaque stage may lack the particular storiform pattern
- Many non-atypical mitotic figures may be present
- Non-polarized, thin collagen
- Mild pleomorphism (not significant)
- Focal atypia
- May coexist with giant cell fibroblastoma
- Absent or rare histiocytes
- Following cell types are absent:
Histiocyte-like cells
Foam cells
Giant cells
Other inflammatory cells
- Histiocyte-like cells
- Foam cells
- Giant cells
- Other inflammatory cells
- Different variants include:
Atrophic (depressed lesion)
Collagenous (with central thick collagen bundles)
Granular cell (S100 negative)
Myxoid
Palisading
Pigmented
Sclerosing
- Atrophic (depressed lesion)
- Collagenous (with central thick collagen bundles)
- Granular cell (S100 negative)
- Myxoid
- Palisading
- Pigmented
- Sclerosing

## Cytology
Cytology of dermatofibrosarcoma has following characteristics:
- Homogeneous
- Isolated spindle cells
- Tissue fragments often present with storiform pattern
- Fibrillary stromal fragments
- Naked nuclei
- Slight to moderate atypia (occasionally)

## Electron microscopy
- Stellate or spindle cells are present which have long, slender, ramified cell processes which are joined by primitive junctions, often with subplasmalemmal densities
- Multivesicular buds are also present commonly

## Immunohistochemistry
- Immunhistochemical staining of dermatofibrosarcoma protuberans shows:
Positive staining for:
CD34 (strong in 95%)
Vimentin
Focal actin
ApoD
Bcl2
NKI-C3
CD99
CD99
Nestin
Tenascin
CD163
Factor XIIIa
CD10
Negative staining for:
Factor XIIIa (usually)
Keratin
EMA
S100
HMB45
Desmin
CD117
- Positive staining for:
CD34 (strong in 95%)
Vimentin
Focal actin
ApoD
Bcl2
NKI-C3
CD99
CD99
Nestin
Tenascin
CD163
Factor XIIIa
CD10
- CD34 (strong in 95%)
- Vimentin
- Focal actin
- ApoD
- Bcl2
- NKI-C3
- CD99
- CD99
- Nestin
- Tenascin
- CD163
- Factor XIIIa
- CD10
- Negative staining for:
Factor XIIIa (usually)
Keratin
EMA
S100
HMB45
Desmin
CD117
- Factor XIIIa (usually)
- Keratin
- EMA
- S100
- HMB45
- Desmin
- CD117

# Epidemiology and Demographics
- Dermatofibrosarcoma protuberans is estimated to occur in 1 in 100,000 to 1-5 in 1 million people per year
- It usually occurs in adults of 20 - 40 years of age
- It affects twice more commonly the blacks than whites in US
- It can also occur in infants and children
- It has a stable incidence which is highest among women
- Worse survival is associated with:
Increased age
Male sex
Black race
Anatomic location of the limbs and head
- Increased age
- Male sex
- Black race
- Anatomic location of the limbs and head

# Risk Factors
- Common risk factors for the development of dermatofibrosarcoma include:
A scar developing after surgery or a burn
Female sex
Age of 30-50 years
African-American race (Bendar or pigmented variant)
Pregnancy
- A scar developing after surgery or a burn
- Female sex
- Age of 30-50 years
- African-American race (Bendar or pigmented variant)
- Pregnancy

# Diagnosis

## History and symptoms
- Symptoms include:
Flat or a slightly raised skin patch (first sign)
1 to 5 centimeters in diameter
Rubbery (hard to touch)
Gives the appearance of a scar or a wrinkled skin patch
Skin-colored, violet or reddish-brown
Soft, depressed skin area (rarely, makes it difficult to diagnose)
Grows very slowly over the period of years
- Flat or a slightly raised skin patch (first sign)
- 1 to 5 centimeters in diameter
- Rubbery (hard to touch)
- Gives the appearance of a scar or a wrinkled skin patch
- Skin-colored, violet or reddish-brown
- Soft, depressed skin area (rarely, makes it difficult to diagnose)
- Grows very slowly over the period of years

### Common sites of involvement
- Tumors commonly involve the following body parts:
Torso/trunk (most common)
Arms
Legs
Head
Neck
- Torso/trunk (most common)
- Arms
- Legs
- Head
- Neck

## Physical examination
- On physical examination, it can be felt as a small, purplish, reddish, or flesh-colored, flat or raised skin patch or nodule almost 1-5 centimeters in diameter

### Skin

## Diagnostic studies
- These include:
FNAC 
Biopsy
Immunohistochemistry
CD34 staining 
- FNAC 
- Biopsy
- Immunohistochemistry
CD34 staining 
- CD34 staining 
- MRI
CT scan
- MRI
- CT scan

# Treatment
- Treatment includes:

# Differential Diagnosis
Dermatofibrosarcoma protuberans must be differentiated must be differentiated from the following:
- Neurofibroma
- Schwannoma
- Ganglioneuroma
- Dermal neurotized melanocytic nevus
- Myxoid liposarcoma
- Solitary circumscribed neuroma/palisaded encapsulated neuroma
- Traumatic neuroma
- Superficial angiomyxoma
- Nerve sheath myxoma
- Malignant peripheral nerve sheath tumor (MPNST)/malignant schwannoma
- Spindle cell lipoma
- Leiomyoma
- Inflammatory myofibroblastic tumor
- Fibroepithelial polyp/acrochordon (aka skin tag or soft fibroma)