Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas and 18 percent of all cutaneous soft tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to

Kaposi sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limite ...

Presentation

Dermatofibrosarcoma protuberans begins as a minor firm area of skin most commonly about to 1 to 5 cm in diameter. It can resemble a bruise, birthmark, or pimple. It is a slow-growing tumor and is usually found on the torso but can occur anywhere on the body. About 90% of DFSPs are low-grade sarcomas. About 10% are mixed, containing a high-grade sarcomatous component (DFSP-FS); therefore, they are considered to be intermediate-grade sarcomas. DFSPs rarely lead to a

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

(fewer than 5% metastasize), but DFSPs can recur locally. DFSPs most often arise in patients who are in their thirties but this may be due to diagnostic delay.

Location

Commonly located on the chest and shoulders, the following is the site distribution of DFPS as was observed in Surveillance, Epidemiology, and End Results (SEER

database between 2000 and 2010. * Torso, Trunk / Torso – 42% *

Lower extremity The human leg, in the general word sense, is the entire lower limb of the human body, including the foot, thigh or sometimes even the hip or gluteal region. However, the definition in human anatomy refers only to the section of the lower lim ...

– 21% *

Upper extremity The upper Limb (anatomy), limbs or upper extremities are the forelimbs of an upright posture, upright-postured tetrapod vertebrate, extending from the scapulae and clavicles down to and including the digit (anatomy), digits, including all the musc ...

– 21% * Head and neck – 13% * Genitals – 1%

Variants

The World Health Organization, 2020, classified the fibrosarcomatous DFSP (DFSP-FS) variant (also termed

dermatofibrosarcoma protuberans, fibrosarcomatous Dermatofibrosarcoma protuberans, fibrosarcomatous (DFSP-FS), also termed fibrosarcomatous dermatofibrosarcoma protuberans, is a rare type of tumor located in the dermis (i.e. layer of the skin below the epidermis). DFSP-FS tumors have been viewe ...

) of the dermatofibrosarcoma protuberans as a specific form of the intermediate (rarely metastasizing)

fibroblastic and myofibroblastic tumors Fibroblastic and myofibroblastic tumors (FMTs) develop from the mesenchymal stem cells which differentiate into fibroblasts (the most common cell type in connective tissue) and/or the myocytes/myoblasts that differentiate into muscle cells. FMTs ...

and other variants of this disorder as a specific form of the intermediate (locally aggressive)

Bednar tumors

Bednar, or pigmented DFSP, is distinguished by the dispersal of

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

-rich

dendritic Dendrite derives from the Greek word "dendron" meaning ( "tree-like"), and may refer to: Biology *Dendrite, a branched projection of a neuron *Dendrite (non-neuronal), branching projections of certain skin cells and immune cells Physical * Dendr ...

cells of the skin. It represents 1-5 percent of all DFSP occurring in people with rich in melanin pigments. Bednar characterized by a dermal spindle cell proliferation like DFSP but distinguished by the additional presence of melanocytic

cells. It occurs at the same rate of DFSP on fairer skin and should be considered to have the same chances of metastasis.

Myxoid DFSP

Myxoid DFSP, which has areas of myxoid degeneration in the stroma

Giant cell fibroblastoma

Giant cell fibroblastoma that contains giant cells, and is also known as juvenile DFSP. Giant cell fibroblastomas are skin and soft tissue tumors that usually arise in childhood. They are sometimes seen in association with dermatofibrosarcoma protuberans (DFSP, hybrid lesions) or may transform or recur as DFSP.

Atrophic DFSP

Atrophic DFSP resemble other benign lesions such as morphea, idiopathic atrophoderma, atrophic scar, anetoderma or lipoatrophy. It behaves like classic DFSP. It commonly favours young to middle aged adults. It has a slow infiltrative growth and a high rate of local recurrence if not completely excised.

Sclerosing DFSP

Sclerosing DFSP is a variant in which the cellularity is low, and the tumor consists of uniform bundles of collagen interspersed with more typical DFSP cells. Granular cell variant is a rare type in which spindle cells are mingled with richly granular cells, the granules being lysosomal, with prominent nucleoli.

Fibrosarcomatous DFSP (DFSP-FS)

Fibrosarcomatous DFSP, a rare variant of DFSP involving greater aggression, high rates of local occurrences, and higher metastatic potential. DFSP - FS are considered to be intermediate-grade sarcomas. Although they rarely metastasize (fewer than 5 percent of cases)

Pathophysiology

More than 90% of DFSP tumors have the

chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...

t(17;22). The translocation fuses the

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

(

COL1A1 Collagen, type I, alpha 1, also known as alpha-1 type I collagen, is a protein that in humans is encoded by the gene. ''COL1A1'' encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, including c ...

) with the

platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...

(

PDGF Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...

) gene. The

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

, the cell of origin of this tumor, expresses the fusion gene in the belief that it codes for collagen. However, the resulting

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...

is processed into a mature

which is a potent growth factor. Fibroblasts contain the

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

for this growth factor. Thus the cell "thinks" it is producing a structural

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

, but it creates a self-stimulatory

growth signal Growth may refer to: Biology * Auxology, the study of all aspects of human physical growth * Bacterial growth * Cell growth * Growth hormone, a peptide hormone that stimulates growth * Human development (biology) * Plant growth * Secondary growth ...

. The cell divides rapidly and tumor forms. The tissue is often positive for CD34.

Diagnosis

DFSP is a malignant tumor diagnosed with a

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

, when a portion of the tumor is removed for examination. In order to ensure that enough tissue is removed to make an accurate diagnosis, the initial biopsy of a suspected DFSP is usually done with a core needle or a surgical incision. Clinical palpation is not entirely reliable for ascertaining the depth of a DFSP infiltration.

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) is more sensitive addressing the depth of the invasion on some types of DFSP, particularly large or recurring tumors. Though MRI is less accurate for identifying infiltration to head and neck tumors.

Diagnostic delay and misdiagnosis

Due to the rarity, initial presentation of flat plaque (skin hardening) and the slow-growing nature of DFSP, it may be months to years without a protuberance (bump). The dissonance between the name of the neoplasm and its clinical presentations may cause a majority of patients to experience a diagnostic delay. A 2019 research study found out of 214 patients a range between less than a year to 42 years before diagnosis (median, four years) from patients noticing a symptom to diagnosis. Currently, a majority of patients (53%) receive a misdiagnosis by health care providers. The most frequent prebiopsy clinical suspicion included cyst (101 7.2%, lipoma (30 4.0%, and scar (17 .9%. It has been suggested an alternative term for DFSP should be ''dermatofibrosarcoma, often protuberant''

Pregnancy

It is suggested that DFSPs may enlarge more rapidly during pregnancy. Immunohistochemical stains for CD34, S-100 protein, factor XIIIa, and estrogen and progesterone receptors were performed on biopsy specimens. The tumors showed the expression of the progesterone receptor. As with many other stromal neoplasms, DFSPs appear to express low levels of hormone receptors, which may be one factor that accounts for their accelerated growth during pregnancy.

Treatment

Treatment is primarily surgical, with

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

and

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

used if clear

resection margin A resection margin or surgical margin is the margin of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so that no portio ...

s are not acquired.

Surgical treatment

The type of surgical treatment chosen is dependent on the location of the DFSP occurrence and possible size.

Mohs surgery

Mohs Micrographic Surgery (MMS) has a high cure rate and lowers the recurrence reduction of DFSP if negative resection margins are achieved.

Wide local excision

WLE was the gold standard for treating DFSP but is currently under reevaluation. Presently in the United States, WLE may be suggested after the recurrence of MMS. Larger resection margins are suggested for WLE than MMS. Recurrence rate with WLE is about 8.5% with a lower recurrence rate related to wider excision.

Resection margin

DFSP characteristic features are its capacity to invade surrounding tissues, to a considerable distance from the central focus of the tumor in a "tentacle-like" fashion. This fact, coupled with diagnostic delay, may lead to inadequate initial resection. Inadequate initial treatment results in larger, deeper recurrent lesions, but these can be managed by appropriate wide excision.

Radiation therapy

DFSP is a radioresponsive tumor, radiation therapy (RT) is not used as the first choice for treatment. Conservative resection through MMS or WLE is attempted first. If clear margins are not achieved RT, or Chemotherapy is recommended.

Chemotherapy

DFSP was previously regarded and nonresponsive to standard chemotherapy. In 2006 the US FDA approved (

imatinib mesylate Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kin ...

) for the treatment of DFSP. As is true for all medicinal drugs that have a name that ends in "ib," imatinib is a small molecular pathway inhibitor; imatinib inhibits

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

. It may be able to induce tumor regression in patients with recurrent DFSP, unresectable DFSP, or metastatic DFSP. There is clinical evidence that

imatinib Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kin ...

, which inhibits PDGF-receptors, may be effective for tumors positive for the t(17;22) translocation. It is suggested that imatinib may be a treatment for challenging, locally advanced disease and in the rare metastatic cases It was approved for use by adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP).

Metastatic disease

Distant hematogenous metastases are extremely rare.

Metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

to regional lymph nodes are rarer and are most likely in patients who have had multiple local recurrences after inadequate surgical resection. Repeatedly recurring tumors have an increased risk for transformation into a more malignant form (DFSP-FS). The lungs are most frequently affected, but metastases to the brain, bone, and other soft tissues are reported.

Studies

DFSP is not extensively studied due to its rarity and low mortality. The majority of studies are small size case studies or meta-analysis. The most extensive research study to date wa
''Perspectives of Patients With Dermatofibrosarcoma Protuberans on Diagnostic Delays, Surgical Outcomes, and Nonprotuberance''
The lead researche
Jerad Gardner
spoke at a Ted Talk in February 2020 on the topic.

History

Taylor, RW, in 1890. first identified DFSP as a

keloid Keloid, also known as keloid disorder and keloidal scar, is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation t ...

sarcoma. Later in 1924, Darier, J and Ferrand, identified it as a progressive recurrent dermatofibroma. In 1925 it was E Hoffmann who coined the term Dermatofibrosarcoma protuberans. Bednar tumor was first described by Bednar in 1957.

ICD Coding

* ICD-0: 8832/3 - dermatofibrosarcoma protuberans, NOS * ICD-0: 8833/3 - pigmented dermatofibrosarcoma protuberans * ICD-0: 8834/1 - giant cell fibroblastoma * Fibrosarcomatous dermatofibrosarcoma protuberans: no distinct coding identified

Additional images

File:SkinTumors-P9280838.JPG,

Subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...

infiltration (i.e. "honeycomb" growth pattern) File:SkinTumors-P9270828.JPG, Monotonous, plexiform structure of tumour File:SkinTumors-P9280834.JPG, DFSP formed both by

ic and histiocytic elements File:SkinTumors-P9270830.JPG,

Hemosiderin Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise ...

deposits beneath the tumour File:Dermatofibrosarcoma protuberans (5) CD34.JPG,

Immunostain In biochemistry, immunostaining is any use of an antibody-based method to detect a specific protein in a sample. The term "immunostaining" was originally used to refer to the immunohistochemical staining of tissue sections, as first described by A ...

positive for CD34

References

External links

Dermatofibrosarcoma protuberans
in NIH Genetic and Rare Diseases Information Center {{Chromosomal abnormalities Dermal and subcutaneous growths Rare cancers Sarcoma