What is pleomorphic dermal sarcoma?
Pleomorphic dermal sarcoma (PDS) is a rare but very aggressive type of sarcoma, which is a type of cancer arising from connective tissues in the body such as bones, tendons, fat and skin.
PDS occurs on the skin, particularly in areas that are exposed to the sun and occurs more frequently in elderly individuals.
Despite being rare, the prevalence of PDS is increasing - the number of cases detected in 2019 was 4.9 times higher than in 2013. This data, alongside the well-known fact that early detection of a cancer leads to better clinical outcomes, underlines the importance of acting quickly and visiting the dermatologist or a primary care provider as soon as you discover a suspicious bump, mole or other lesion on the skin.
What are the signs and symptoms of pleomorphic dermal sarcoma?
PDS most commonly presents on areas that are exposed to the sun, such as the head, neck and face. Patients usually notice a rapidly-growing mass, or plaque that is spreading [1, 2, 3, 4].
The tumour is named 'pleomorphic', meaning that it can exhibit various characteristics. This is the case in its clinical presentation - PDS can present as an outward-growing lesion or bump (exophytic lesion), which can be covered by ulcers or attached by a stalk-like structure (penduculated) [3, 4, 5, 6, 7]. Sometimes, there may be multiple areas of tumour (multifocal), and PDS lesions are also known to bleed without cause [8].
PDS tumours are also known for their rapid growth - one case study describes a PDS in a 61-year-old man, which grew to 9cm in only 10 weeks [5].
Additionally, it is important to note that PDS is a very heterogeneous type of cancer and can present differently to what is described above. Therefore, it is very important to have any new or changing skin lesions checked out by a medical professional.
How is pleomorphic dermal sarcoma diagnosed?
The diagnosis of PDS is a challenging process due to the highly diverse nature of the tumour. The diagnostic pathway primarily consists of clinical examination and histopathological analysis, with diagnostic imaging and molecular (genetic) analysis also playing an important role.
On clinical examination, lesions will be evaluated, sometimes using a dermatoscope. Following clinical examination, especially if the decision is to proceed with surgery, imaging studies are performed (such as magnetic resonance imaging), which help with planning of the surgery. More extensive scans can be used to check for signs of distant metastasis [1].
The definitive diagnosis of PDS relies on histopathological examination. This involves sampling the tumour via a biopsy (where a thin needle is inserted into the tumour under local anaesthesia and cells are taken out), or after surgical removal. The tissue sample from the tumour is cut into very thin slices, and stained with various dyes that help visualise distinct cell types and expression of some molecules under the microscope.
PDS under the microscope: Common histological findings
Under the microscope, PDS tumours are poorly differentiated, meaning that the cells in the tumour do not resemble normal cells. This means that the cells stray from their biological roles when they grow (normally, cells would differentiate into distinct types such as muscle cells, fat cells, etc), and instead form a tumour. Lack of differentiation is a sign of very aggressive cancers.
Furthermore, PDS tumours contain a mixture of spindle cells (elongated cells with large nuclei), epithelioid cells (a form of cancer-associated monocyte, which is a cell of the immune system), and various bizzare, deformed cells.
It is important to note that PDS closely resembles another type of tumour, atypical fibroxanthoma based on cytomorphology (study of cell shapes and types) in the tumour. The key difference is that PDS is more invasive, and thus tumour cells will be present beyond the dermis (the top layer of the skin), whereas atypical fibroxanthoma is present in the dermis exclusively [9].
Genetic profile of Pleomorphic dermal sarcoma
On the genetic level, PDS is a highly mutated tumour - this may be a consequence of UV radiation damage from sun exposure, as is the case in melanomas. Commonly-observed mutations include genes FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter.
These are genes important for regulating cel growth and division, and tumour suppressor genes which sense damage leading to cancer and signal for the cell to apoptose (initiate cell death). Therefore, these mutations lead to rapid growth of the cancer. Additionally, other genes can be multiplied or lost (referred to as copy number variation) [10].
It is also important to note that the diagnosis of PDS can sometimes be a diagnosis of exclusion, meaning that all other options are exhausted and PDS is the last available diagnosis. This is due to the tumour being extremely heterogeneous - while the above describes common findings, the histological and molecular profile varies highly from patient to patient.
What is the treatment and prognosis?
PDS is a very aggressive and heterogeneous tumour, and therefore is difficult to treat. The standard treatment focuses on local management of the tumour via surgery.
In a study of 16 patients, Modified Mohs Micrographic Surgery (M-MMS) led to local disease control in 83% of cases [11]. Mohs surgery is a type of approach to skin cancer surgery, where the operation is continuously monitored under the microscope and the surgical approach is modified in real time based on detection of suspicious tissue.
However, PDS is known for its high recurrence rates - in the same study, the cancer came back in 69% of cases. This data highlights the importance of removing the tumour with very wide margins (healthy tissue around the cancer that is taken out to minimise chance of leaving potentially cancerous cells), as well as close monitoring after the surgery.
Unfortunately, as PDS is very rare, research on novel drug treatments is limited. There is one case study on the use of trabectedin (a cytotoxic chemotherapy) prior to surgery, which led to a reduction in tumour size allowing for a complete removal [12].
Furthermore, if the tumour metastasises (spreads to other parts of the body), radiotherapy may be indicated to the primary tumour and the metastasis, as well as systemic cytotoxic chemotherapy.
Prognosis of Pleomorphic dermal sarcoma
The prognosis of PDS varies and can be influenced by multiple factors such as tumour size, grade, sex, race and age at diagnosis. Male sex and white race are associated with decreased overall survival and worse prognosis, as are larger, high-grading tumours and older age at diagnosis [13].
Generally, the overall survival rate at 3 years is 53.3%, and 30% at 5 years from diagnosis [14]. PDS is indeed an aggressive tumour, however, early detection and clinical intervention leads to better clinical outcomes. Therefore, it is important to take care of your skin, and visit the dermatologist or a primary care provider frequently.
