Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous

soft-tissue sarcoma A soft-tissue sarcoma (STS) is a malignant tumor, a type of cancer, that develops in soft tissue. A soft-tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained ...

. 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.

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 spreading 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, ...

(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. * Trunk/torso – 42% * Lower extremity – 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 This article describes the anatomy of the head and neck of the human body, including the brain, bones, muscles, blood vessels, nerves, glands, nose, mouth, teeth, tongue, and throat. Structure Bones The head rests on the top part of the vertebr ...

– 13% *

Genitals A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...

– 1%

Variants

The

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

in 2020 classified the fibro sarcomatous DFSP (DFSP-FS) variant (also termed dermatofibrosarcoma protuberans, fibro sarcomatous) of the dermatofibrosarcoma protuberans as a specific form of the intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumors and other variants of this disorder as a specific form of the intermediate (locally aggressive) fibroblastic and myofibroblastic tumors.

Bednar tumors

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

melanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...

-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 *Dendri ...

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

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

Myxoid DFSP

Myxoid DFSP has areas of myxoid degeneration in the stroma.

Giant cell fibroblastoma

Giant cell fibroblastoma 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 Morphea is a form of scleroderma that mainly involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, usually with no internal organ involvement. However, in Deep Morphea inflammation and sclerosis ...

, idiopathic atrophoderma, atrophic scar, anetoderma or

lipoatrophy Lipoatrophy is the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections of insulin in the treatment of diabetes, from the use of human growth hormone or from subcutaneous injections of copaxone u ...

. 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 is 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 three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...

t(17;22). The translocation fuses the

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

( COL1A1) 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 bloo ...

( PDGF) gene. The

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

, the cell of origin of this tumor, expresses the fusion gene in the belief that it codes for collagen. However, the resulting fusion protein is processed into a mature

which is a potent

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

. Fibroblasts contain the

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

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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, but it creates a self-stimulatory growth signal. The cell divides rapidly and tumor forms. The tissue is often positive for

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first desc ...

Diagnosis

DFSP is a

malignant tumor Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ...

diagnosed with a

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

, 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 generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

(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 Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery ...

, with

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

used if clear

resection margin A resection margin or surgical margin is the edge or "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 th ...

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 Mohs surgery, developed in 1938 by general surgeon Frederic E. Mohs, is microscopically controlled surgery used to treat both common and rare types of skin cancer. During the surgery, after each removal of tissue and while the patient waits, the ...

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

Wide local excision

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 targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...

) for the treatment of DFSP. As is true for all medicinal drugs with name ending 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 targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...

, 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 spreading 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, ...

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 was ''Perspectives of Patients With Dermatofibrosarcoma Protuberans on Diagnostic Delays, Surgical Outcomes, and Nonprotuberance''. The lead researcher, Jerad Gardner, spoke at a TED Talk in February 2020 on the topic.

History

R. W. Taylor, 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, Ferdinand-Jean Darier and Ferrand identified it as a progressive recurrent dermatofibroma. In 1925, E. Hoffmann coined the term ''dermatofibrosarcoma protuberans''. Bednar tumor was first described by Bednar in 1957.

ICD coding

The following are the

ICD-10 ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...

medical codes: * 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, or 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 ma ...

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 ri ...

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

References

External links

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