Dermatofibrosarcoma protuberans
Encyclopedia
Dermatofibrosarcoma protuberans (DFSP)
is a very rare tumor
. It is a rare neoplasm of the dermis
layer of the skin, and is classified as a sarcoma
. There is only about 1 case per million per year. DFSP is a fibrosarcoma
, more precisely a cutaneous 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 malignant
potential. It occurs most often in adults in their thirties; it has been described congenitally, in children, and the elderly. It accounts for approximately 2-6% of soft tissue sarcoma cancers.
(fewer than 5% do metastasise), but DFSPs can recur locally. DFSPs most often arise in patients who are in their thirties, but sometimes have been described in children or the elderly.
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 codes for 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.
The tissue is often positive for CD34
.
and radiation therapy
sometimes being used.
The NCCN guideline recommends CCPDMA
or Mohs surgery
for the best cure rate of DFSP.
Mohs surgery
can be extremely effective. It will remove the tumor and all related pathological cells without a wide-area excision that may overlook sarcoma cells that have penetrated muscle tissue.
The standard of care for patients with DFSP is surgery. Usually, complete surgical resection with wide margins is performed. The addition of adjuvant
radiotherapy (irradiation) improves local control in patients with close or positive margins during the surgery. A special surgical technique, the "Mohs micrographic surgery" (MMS), can be employed in patients with DFSP. MMS is technically possible if the DFSP is in an anatomically confined area. A high probability of cure of DFSP can be attained with MMS as long as the final margins are negative. Patients who have a recurrent DFSP can have further surgery, but the probability of adverse effects of surgery and/or metastasis is increased in these patients.
Imatinib
is approved for treatment. As all medicinal drugs which have a name that ends on -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. There is clinical evidence that imatinib
, which inhibits PDGF-receptors, may be effective for tumors positive for the t(17;22) translocation.
is a very rare tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
. It is a rare neoplasm of the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
layer of the skin, and is classified as a sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
. There is only about 1 case per million per year. DFSP is a fibrosarcoma
Fibrosarcoma
Fibrosarcoma is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells.Usually in males ages 30 to 40. Originates in fibrous tissues of the bone. Invades long or flat bones such as femur, tibia,...
, more precisely a cutaneous soft tissue sarcoma
Soft tissue sarcoma
A soft-tissue sarcoma is a form of sarcoma that develops in connective tissue, though the term is sometimes applied to elements of the soft tissue that are not currently considered connective tissue.-Risk factors:...
. In many respects, the disease behaves as a benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
, but in 2-5% of cases it can metastasize
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
, so it should be considered to have malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
potential. It occurs most often in adults in their thirties; it has been described congenitally, in children, and the elderly. It accounts for approximately 2-6% of soft tissue sarcoma cancers.
Presentation
About 90% of DFSPs are low grade sarcomas. About 10% are mixed; they contain a high-grade sarcomatous component (DFSP-FS); therefore, they are considered to be intermediate-grade sarcomas. All DFSPs rarely lead to a metastasisMetastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
(fewer than 5% do metastasise), but DFSPs can recur locally. DFSPs most often arise in patients who are in their thirties, but sometimes have been described in children or the elderly.
Pathophysiology
Over 90% of DFSP tumors have the chromosomal translocationChromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
t(17;22). The translocation fuses the collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
(COL1A1
COL1A1
Collagen, type I, alpha 1, also known as COL1A1, is a human gene that encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, including cartilage....
) with the platelet-derived growth factor gene. The fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
, the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
of origin of this tumor, expresses the fusion gene
Fusion gene
A fusion gene is a hybrid gene formed from two previously separate genes. It can occur as the result of a translocation, interstitial deletion, or chromosomal inversion...
in the belief that it codes for collagen. However the resulting fusion protein
Fusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...
is processed into mature platelet-derived growth factor which is a potent growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
. Fibroblasts contain the receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for this growth factor. Thus the cell "thinks" it is producing a structural protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, but in fact produces a self-stimulatory growth signal. The cell divides
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
rapidly and a tumor forms.
The tissue is often positive for CD34
CD34
CD34 molecule is a cluster of differentiation molecule present on certain cells within the human body. It is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells...
.
Treatment
Treatment is primarily surgical, with chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
sometimes being used.
The NCCN guideline recommends CCPDMA
CCPDMA
CCPDMA is the acronym for "complete circumferential peripheral and deep margin assessment". It is the preferred method for the removal of certain cancers, especially skin cancers.A classical example of CCPDMA is Mohs surgery...
or Mohs surgery
Mohs surgery
Mohs surgery, also known as chemosurgery, created by a general surgeon, Dr. Frederic E. Mohs, is microscopically controlled surgery used to treat common types of skin cancer. It is one of the many methods of obtaining complete margin control during removal of a skin cancer using frozen section...
for the best cure rate of DFSP.
Mohs surgery
Mohs surgery
Mohs surgery, also known as chemosurgery, created by a general surgeon, Dr. Frederic E. Mohs, is microscopically controlled surgery used to treat common types of skin cancer. It is one of the many methods of obtaining complete margin control during removal of a skin cancer using frozen section...
can be extremely effective. It will remove the tumor and all related pathological cells without a wide-area excision that may overlook sarcoma cells that have penetrated muscle tissue.
The standard of care for patients with DFSP is surgery. Usually, complete surgical resection with wide margins is performed. The addition of adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
radiotherapy (irradiation) improves local control in patients with close or positive margins during the surgery. A special surgical technique, the "Mohs micrographic surgery" (MMS), can be employed in patients with DFSP. MMS is technically possible if the DFSP is in an anatomically confined area. A high probability of cure of DFSP can be attained with MMS as long as the final margins are negative. Patients who have a recurrent DFSP can have further surgery, but the probability of adverse effects of surgery and/or metastasis is increased in these patients.
Imatinib
Imatinib
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
is approved for treatment. As all medicinal drugs which have a name that ends on -ib, imatinib is a small molecular pathway inhibitor; imatinib inhibits tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
. 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
Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...
, which inhibits PDGF-receptors, may be effective for tumors positive for the t(17;22) translocation.
External links
- humpath #346 (Pathology images)
- Dermatofibrosarcoma Protuberans in the Sarcoma Learning Center
- Thesis on DFSP