Dermatofibrosarcoma protuberans

Template:Infobox medical condition (new) Dermatofibrosarcoma protuberans (DFSP)<ref name="NCI Dictionary of Cancer Terms">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year.<ref>Template:Cite journal</ref><ref name="Kreicher S24–31">Template:Cite journal</ref> In the United States, DFSP accounts for between 1 and 6 percent of all soft-tissue sarcomas<ref>Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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 (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.<ref name="Kreicher S24–31"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Trunk/torso – 42%
• Lower extremity – 21%
• Upper extremity – 21%
• Head and neck – 13%
• Genitals – 1%

Variants

The World Health Organization 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.<ref name="pmid33179614">Template:Cite journal</ref>

Bednar tumors

Bednar, or pigmented DFSP, is distinguished by the dispersal of melanin-rich dendritic cells of the skin. It represents 1–5 percent<ref>Template:Cite journal</ref> 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 dendritic cells. It occurs at the same rate as DFSP on fairer skin and should be considered to have the same chances of metastasis.<ref>Template:Cite journal</ref>

Myxoid DFSP

Myxoid DFSP has areas of myxoid degeneration in the stroma.<ref>Template:Cite journal</ref><ref name=":0">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Giant cell fibroblastoma

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Giant cell fibroblastoma<ref name="NCI Dictionary of Cancer Terms"/> contains giant cells, and is also known as juvenile DFSP.<ref>Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=":0" />

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.<ref name=":0" /><ref>Template:Cite journal</ref>

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.<ref name=":0" />

Granular cell variant is a rare type in which spindle cells are mingled with richly granular cells, the granules being lysosomal, with prominent nucleoli.<ref name=":0" />

Fibrosarcomatous DFSP (DFSP-FS)

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Fibrosarcomatous DFSP is a rare variant of DFSP involving greater aggression, high rates of local occurrences, and higher metastatic potential.<ref>Template:Cite journal</ref> DFSP-FS are considered to be intermediate-grade sarcomas,<ref>Template:Cite journal</ref> although they rarely metastasize (fewer than 5 percent of cases).

Pathophysiology

More than 90% of DFSP tumors have the chromosomal translocation t(17;22). The translocation fuses the collagen gene (COL1A1) with the platelet-derived growth factor (PDGF) gene. The fibroblast, 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 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 it creates a self-stimulatory growth signal. The cell divides rapidly and tumor forms.

The tissue is often positive for CD34.<ref name="pmid12661001">Template:Cite journal</ref><ref name="pmid17950782">Template:Cite journal</ref>

Diagnosis

File:Histopathology of cartwheel pattern in dermatofibrosarcoma protuberans, annotated.jpg

The pattern of tumor cells radiating from a center is described as "cartwheel pattern".

DFSP is a malignant tumor diagnosed with a biopsy, 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Clinical palpation is not entirely reliable for ascertaining the depth of a DFSP infiltration. Magnetic resonance imaging (MRI) is more sensitive addressing the depth of the invasion on some types of DFSP, particularly large or recurring tumors,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref name=":2">Template:Cite journal</ref>

Currently, a majority of patients (53%) receive a misdiagnosis by health care providers. The most frequent prebiopsy clinical suspicion included cyst (101 [47.2%]), lipoma (30 [14.0%]), and scar (17 [7.9%]).<ref name=":2" />

It has been suggested an alternative term for DFSP should be dermatofibrosarcoma, often protuberant.<ref name=":2" />

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.<ref>Template:Cite journal</ref>

Treatment

File:Dermatofibrosarcoma protuberans CT cor.jpg

Dermatofibrosarcoma protuberans of the left axilla. CT, coronal reconstruction

Treatment is primarily surgical, with chemotherapy and radiation therapy used if clear resection margins are not acquired.<ref name="pmid31466588">Template:Cite journal</ref>

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<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

Chemotherapy

DFSP was previously regarded and nonresponsive to standard chemotherapy.<ref>Template:Cite journal</ref> In 2006 the US FDA approved (imatinib mesylate) for the treatment of DFSP.<ref>Template:Cite journal</ref> As is true for all medicinal drugs with name ending in "ib," imatinib is a small molecular pathway inhibitor; imatinib inhibits tyrosine kinase. It may be able to induce tumor regression in patients with recurrent DFSP, unresectable DFSP, or metastatic DFSP.<ref>Template:Cite journal</ref> There is clinical evidence that imatinib, 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).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Metastatic disease

Distant hematogenous metastases are extremely rare.<ref>Template:Cite journal</ref> Metastases to regional lymph nodes are rarer and are most likely in patients who have had multiple local recurrences after inadequate surgical resection.<ref>Template:Cite journal</ref> 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,<ref>Template:Cite journal</ref> bone,<ref>Template:Cite journal</ref> 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.<ref name=":2" /> The lead researcher, Jerad Gardner, spoke at a TED Talk in February 2020 on the topic.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

History

R. W. Taylor, in 1890,<ref>Template:Cite journal</ref> first identified DFSP as a keloid sarcoma. Later in 1924, Ferdinand-Jean Darier and Ferrand identified it as a progressive recurrent dermatofibroma. In 1925, E. Hoffmann<ref>Template:Cite journal</ref> coined the term dermatofibrosarcoma protuberans. Bednar tumor was first described by Bednar in 1957.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref>

ICD coding

The following are the ICD-10 medical codes:

• ICD-0: 8832/3<ref name=":1">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref> – dermatofibrosarcoma protuberans, NOS

• ICD-0: 8833/3<ref name=":1" /> – pigmented dermatofibrosarcoma protuberans
• ICD-0: 8834/1<ref name=":1" /> – giant cell fibroblastoma
• Fibrosarcomatous dermatofibrosarcoma protuberans: no distinct coding identified

Additional images

• SkinTumors-P9280838.JPG

  Subcutaneous tissue infiltration (i.e. "honeycomb" growth pattern)

• SkinTumors-P9270828.JPG

  Monotonous, plexiform structure of tumour

• SkinTumors-P9280834.JPG

  DFSP formed both by fibroblastic and histiocytic elements

• SkinTumors-P9270830.JPG

  Hemosiderin deposits beneath the tumour

• Dermatofibrosarcoma protuberans (5) CD34.JPG

  Immunostain positive for CD34

See also

• List of cutaneous conditions

External links

• Dermatofibrosarcoma protuberans in NIH Genetic and Rare Diseases Information Center