Squamous Cell Carcinoma (SCC) in CLL Patients

It has been reported that SCC is nine times more likely in CLL patients than in the general population. When it occurs, it is also likely to be more dangerous and harder to control in our patient group. CLL patients often develop secondary cancers and skin cancer is the single most common second malignancy. Trust me, taking care of SCC or its kissing cousin basal cell carcinoma or more dangerous melanoma is not just a case of worrying whether it will leave a scar that does not look pretty. I have lost too many friends that could not win a two front war against CLL and aggressive skin cancer at the same time. 

What Causes the Increased Risk of SCC in CLL patients?

Most of us have small microscopic clusters of cancerous cells on our bodies due to the DNA damage from UV radiation. Did you know UV damage causes mutations in the 17p53 gene in skin cells? That’s right - the same dreaded 17p53 gene whose deletion in B-cells is a dangerous prognostic indicator for CLL is also involved in making skin cells cancerous. As we now know, 17p53 is the suicide gene that is crucial in forcing cancerous cells to kill themselves. Deficits in this department in sun damaged skin cells means the cancerous skin cells can grow unchecked. When the cluster becomes large enough it is diagnosed as actinic keratosis - beginning stages of SCC.

A certain amount of skin damage is unavoidable, part of normal wear and tear of life. In healthy people there is an ongoing process of immuno-surveillance that actively seeks and destroys cancerous skin cells wherever they lurk. But CLL patients often lack effective surveillance because of inherent immune defects due to the CLL, as well as further immune suppression due to chemotherapy drugs used to treat the CLL. Fludarabine and Campath in particular cause depletion of T-cells for many months, and because the T-cells play a crucial role in controlling SCC, using these two drugs may cause SCC and other forms of skin cancer to flare or metastasize rapidly.

Therapy Options

In people with healthy immune systems it is possible to get good control over SCC by freezing it off and / or surgically removing the cancerous tissue (“Moh’s surgery”). But both of these standard procedures may be inadequate in a CLL patient, leaving behind cancerous cells at the edges of the surgical excision that can grow back or metastasize to a different location. For this reason it is recommended that Moh’s surgery be aggressive in CLL patients, removing a larger than usual amount of tissue to get a generous margin of safety around the initial SCC lesion. More recently dermatologists have begun recommending use of imiquimod cream (trade name “Aldara”) at the site of SCC or actinic keratosis as further precaution.

Focused Radiotherapy to Control Recurrence

I came across this interesting and recent article from Canadian researchers discussing the specific needs of CLL patients with SCC issues. The abstract is below and you can read the full text article by clicking on this link. They recommend targeted radiation to give additional insurance to control recurrence of the SCC after surgery.

Curr Oncol. 2008 Oct;15(5):229-33.

Treating recurrent cases of squamous cell carcinoma with radiotherapy.
Wong J, Breen D, Balogh J, Czarnota GJ, Kamra J, Barnes EA.

Department of Radiation Oncology, University of Toronto, Faculty of Medicine, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON.

Patients with chronic lymphocytic leukemia (cll) are at a significantly increased risk of developing cutaneous squamous cell carcinoma (scc), in part because of their impaired immunosurveillance. Here, we report the cases of 4 patients with cll who had locally aggressive cutaneous scc managed with radiotherapy for local recurrence following surgical excision. All tumours were located in the head-and-neck region. All patients initially achieved complete regression of disease; however, 2 had local recurrence a mean of 8 months after treatment completion. One patient died from progressive scc. Our findings agree with the high rates reported in literature of multiple tumours, local recurrence, metastases, and mortality from scc in patients with cll. Radiotherapy plays an important role in patient management, and it is the recommended treatment modality when complete surgical excision of disease would result in anatomic and functional defects. Radiotherapy is often used in the case of local recurrence after one or more attempts at surgical excision. Dose escalation through intensity-modulated radiotherapy, hyperfractionation, or novel treatment techniques such as high-intensity focused ultrasound may be explored to improve local control of scc lesions. To optimize patient outcomes, cutaneous scc arising in patients with a history of cll should be managed and followed in a multidisciplinary clinic, with regular skin surveillance and prompt treatment.
PMID: 19008997

Editorial

Avoiding the problem in the first place is the name of the game, hence my repeated warnings about avoiding excessive UV exposure and sun damage. Forget about getting a “healthy” tan, unless it comes in a cosmetic jar. Remember that avoiding sun exposure also means you need to be proactive in getting your Vitamin D3 levels checked and correct any deficiency by taking a supplement. The present FDA recommended adult daily minimum requirements of this important vitamin are woefully inadequate. There is now a strong consensus that majority of older North Americans suffer from vitamin D3 insufficiency or downright deficiency and it may be at the root of many immune related diseases.

A quick Google search will yield a lot of good referenes about CLL.  Here is a credible Medscape reference that has a lot of information.  As a CLL patient if you have actinic keratosis / SCC, please take it seriously. Belt and suspenders approach seems to be the way to go. As the authors point out in the abstract above, localized and low dose radiation may be an important addition to Moh’s surgery. This is something to discuss with your doctors.

I used the word “doctors” (plural) deliberately. I think SCC is best treated in CLL patients by a team of doctors that include an oncological dermatologist, radiologist, plastic surgeon and hematologist. No one of these specialists is going to know all that needs to be considered in fighting a two front war. Silo mentality can be downright dangerous if your hematologist and dermatologist do not talk to each other and do not know enough about each other’s turf.