Understanding Morpheaform Basal Cell Carcinoma
Morpheaform basal cell carcinoma (mBCC), also sometimes referred to as sclerosing or fibrosing basal cell carcinoma, is a rare and aggressive subtype of basal cell carcinoma - the most commonly occurring skin cancer worldwide [1, 2]. The prevalence of mBCC is difficult to ascertain, however estimates range between 5-10% of basal cell carcinoma cases [1].
mBCC is a very aggressive cancer, characterised by difficult clinical presentation leading to later detection, which in turn leads to increased occurrence of metastasis and tumour recurrence. Additionally, mBCC tumours are very locally invasive and destructive to the surrounding tissue [1].
Signs and Symptoms of Morpheaform Basal Cell Carcinoma
mBCC most typically presents with a lesion resembling a scar. These lesions are white in colour with a waxy appearance and do not have a defined border [3, 4]. These lesions are mostly painless, and the only symptom may be growth and/or change to appearance of the skin.
These mBCC lesions develop on parts of the body that are frequently exposed to sunlight, such as the face, ears, shoulders, scalp, neck and arms, similarly to other types of basal cell carcinoma [3, 4].
If you notice a suspicious lesion or a scar that you believe you didn't have previously, it is highly important to have it examined by a primary care provider or a dermatologist. Early detection and treatment are highly important in treatment of mBCC and lead to better outcomes [5].
Diagnosis of Morpheaform Basal Cell Carcinoma
The primary diagnostic approach for mBCC is a biopsy. This is a simple, in-office procedure where the area is numbed with local anaesthesia, and a sample of the tissue is excised (cut away).
The tissue is then examined histologically (cut into thin slices and stained with dyes that allow for better visualisation of cells and expression of certain proteins under the microscope). If mBCC is confirmed, patients may require multiple biopsies, as mBCC tumours can change in their molecular characteristics over time [6].
The common histological findings in mBCC include a very dense, fibrous stroma (stroma is supportive tissue around the tumour composed of collagen, blood vessels and some immune cells with various roles) with elongated strands of basaloid cells (a deformed, cancerous version of basal cells which are cells forming the lower layer of the epidermis) [7, 8].
On a genetic level, mBCC is characterised by mutations in genes PTCH1 or SMOH, which are members of the Hedgehog signalling pathway. This is a pathway with roles in formation of a tumour, as well as rapid growth and cell differentiation, and the mutations in this pathway lead to its over-activation, promoting growth of the tumour. About half of the tumours also carry mutations in the tumour suppressor gene TP53, which are often associated with UV radiation damage [9].
Another key finding is high expression of cytokeratin 17 - a protein that forms the cytoskeleton (supportive structure of the cell). This can be used to distinguish mBCC from desmoplastic trichoepithelioma, a condition with similar presentation [10].
Additionally, mBCC can sometimes resemble metastasis from breast cancer. However, the genetic signature is different, underlining the importance of including genetics in the diagnostic pathway, as the genetic signature of mBCC is different to that of breast cancer [2].
Treatment for Morpheaform Basal Cell Carcinoma
The primary treatment for mBCC is surgical removal.
Mohs micrographic surgery is an effective approach for mBCC (and other high-risk lesions alike). This approach involves continuously monitoring the surgical field under the microscope, and adjusting the surgical approach in real time based on the observation under the microscope. The objective is to remove all of the tissue containing cancerous or suspicious cells, while preserving as much healthy tissue as possible [11]. The Mohs surgical approach is the most effective tool at managing mBCC, with the lowest recurrence rates compared to other treatments [12].
As mBCC is characterised by over-activation of the Hedgehog signalling pathway, its inhibition is a successful therapeutic strategy. Inhibitors such as vismodegib or sonidegib can be used either before surgery to reduce the size of the tumour [13], or can be used exclusively if surgery is not an option (either due to complicated anatomy around the tumour, or if the patient refuses surgery) [14, 15, 16]. These inhibitors have been shown to be effective in treating advanced mBCC [15].
Interestingly, radiotherapy is generally not recommended for mBCC, as the tumour doesn't respond to radiation, and there can also be damage to other anatomy surrounding the tumour (such as eyes if the tumour is close) [11, 17]. An alternative to radiotherapy may be photodynamic therapy, a type of approach where a light-sensitive agent is applied to the area and excited with a certain wavelength, leading to damage localised to the cancer only [18]. This, however, requires further research and development and is not currently the standard of care for mBCC.
Despite the cancer being aggressive, the modern treatment is successful. If detected early and treated, 80% of mBCC patients are expected to live for 5 years from the diagnosis. It is therefore highly important to take care of your skin, exercise adequate sun protection and visit the dermatologist routinely.
