CLL Complications

Squamous cell carcinoma (SCC) is the second most common skin cancer after basal cell carcinoma. In situ SCC is also known as "Bowen's disease". It typically occurs on sun-exposed areas of the body such as face, neck, the top of your no longer as luxuriantly endowed head, arms, etc. It is more common in light-skinned men, and seems to be more common in people older than 55 years. There is a correlation to the amount of UV present in sunlight, and therefore the  incidence of SCC increases as one gets closer to the Equator, all other things being constant. Some risk factors are a family history of skin cancer, smoking, old burn scars, immunosuppression because of chemotherapy or radiation therapy or AIDS, exposure to UV for long periods, and chemical carcinogens.   

If you have CLL, you are at a much higher risk of getting SCC too.

There is clear and unambiguous correlation between CLL and skin cancer, especially squamous cell carcinoma. Below is a table based on an ambitious study from Sweden and Denmark. 17,400 CLL patients were registered in this study, and incidence of SCC and malignant melanoma was recorded in this group.  As you can see, the actual rate of SCC in the CLL patient group was 120 cases, while the expected rate for the same size population without CLL is about 14. The break down by sex shows that male CLL patients are almost ten times as likely to have SCC than the general population (96 versus 9.8), the stats are a little less alarming for women, the relative risk is "only" six fold. While this study is based on very fair populations who are at more risk of skin cancer, do remember that the comparison is between Nordic people with CLL versus Nordic people without CLL. This is a huge risk factor, and I am deeply concerned that more oncologists do not read the  riot act to their CLL patients about UV exposure.

I guess after looking at the relative risks close to double digits for squamous cell carcinoma, it is a relief to see that the relative risk of getting malignant melanoma on top of CLL is a mere three-fold higher!

Risk of skin cancers after an initial diagnosis of CLL (Denmark and Sweden, 1943-89)

Link: http://bmj.bmjjournals.com/cgi/content/full/310/6993/1491

Why should we worry about SCC, it is easy to treat, right?

Wrong!

True, in otherwise healthy people SCC tends to remain localized and easy enough to treat. But aggressive forms of SCC can occasionally spread to other sites of the body. And when it does decide to metastasize, it generally does so through the lymphatic system. Aggressive forms of SCC are a lot harder to treat, and they can be a lot more dangerous. The abstract below from the Royal Marsden Hospital is dated 1996, and its message is quite clear. When SCC occurs in CLL patients, and the Swedish study above makes it abundantly clear that it is almost 10 times more likely to occur in CLL patients, it is likely to be much more aggressive and dangerous. 

My husband was diagnosed with CLL in 2024. Quite a few years after the Swedish report was published and 5 years after the Royal Marsden Hospital alarm was sounded. At the time of his diagnosis, we asked our CLL Research Consortium expert who confirmed the diagnosis what my husband should be doing by way of life style changes to maximize his chances of staying healthy. Our expert thought for a moment, and said PC should stay well hydrated. Good advice, as far as it goes - staying well hydrated is one way of protecting your kidneys and liver. But the expert did not say one word of warning about skin cancer, and life style changes to minimize UV exposure. I have no doubt our story is not unique, that the majority of you have never been warned by your local oncologists or even CLL experts about the specific risk of squamous cell carcinoma. In fact, one more reason why I am delighted with the "Best Practices" list from Mayo Clinic it sounds a clear and unambiguous warning to protect yourself from this malignant risk.

Abstract:

Laryngol Otol. 1996 Jul;110(7):694-5. 

Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia.

Hartley BE, Searle AE, Breach NM, Rhys-Evans PH, Henk JM.

Head and Neck Unit, Royal Marsden Hospital, London, UK.

We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.

PMID: 8759553
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What makes CLL patients such easy targets for aggressive SCC?

CLL patients are not the only group singled out, patients who have gone through solid organ transplants, AIDs patients, patients with other types of cancers who have gone through immune suppressive chemotherapy, all of these folks are at increased risk. The reason is quite simple. CLL patients (and some of the other risk groups above) have damaged immune systems. We are quick to jump to the conclusion that since we are talking about B-cell CLL, only the B-cells are compromised. Not so. As we discussed in previous articles ("Potential Risks of T-Cell Therapy"), there is a great deal of cross-talk between the B-cell and T-cell lines, these two arms of the immune system work hand in glove with each other. A heavy load of damaged and screwed up B-cells, as in the case of CLL patients, takes its toll on the proper functioning of the T-cells as well. Much of the autoimmune disease seen in CLL patients is due to improper functioning of T-cells. When the immune system cells can no longer make the fine distinction between when to attack and what to attack, one side of the coin is autoimmune disease where perfectly good and innocent cells of the body are attacked. The other side of the coin is when damaged and potentially malignant cells are not attacked and killed. Since the first line of defense in keeping squamous cell carcinoma contained is T-cells, it is easy to see why defects in T-cell function allows SCC to grow, metastasize and become a killer. 

It is not just the CLL that makes for a poorly functioning immune system, just about all the therapies associated with CLL also do a number on its proper functioning. The abstract below specifically cites fludarabine and 2-chlorodeoxyadenosine, but we can add just about all the standard chemotherapy drugs we are familiar with, including corticosteroids like prednisone and dexamethasone. Monoclonal antibody drugs are not exempt either. As we have seen in recent articles on Campath ("Campath - Looking Better and Better"), this very important CLL drug is justly famous for wiping out all of your B-cells as well as T-cells, not to mention precipitating neutropenia in a large percent of patients using this drug. No one would dream of administering Campath these days without protective pre-medications to prevent opportunistic viral, fungal and bacterial infections. But how about skin cancer? How many Campath patients are warned to be extra vigilant to protect themselves from UV exposure? Are there preventive measures one can take to decrease the odds of a flare up of squamous cell carcinoma?

Abstracts:

Back when I used to work for a living, my boss used to say  "Don't ever come into my office to tell me there is a problem, not unless you also have a recommendation on how to fix it".  Well, I am not sure I know how to fix SCC, that is way beyond my layperson reporter's abilities. But I think we can come up with a simple and sensible list of do's and don'ts, a list that most of us will recognize as sensible:

The short list above is pretty sensible stuff that you can implement yourself.  Below are some items you should discuss with your doctor before you act upon them.  Did you know that sulindac (like its better known counterpart aspirin, sulindac is also an NSAID) is a COX inhibitor too, and has shown interesting results as a protective agent in SCC? The first abstract below discusses a topical cream of 5% imiquimod and 200 mg of sulindac tablets twice a day as a therapy for SCC specifically in CLL patients. But do be aware that, like aspirin, sulindac also may irritate and damage the lining of your stomach. Something to think about and discuss seriously with your doctor, if you are prone to ulcers, have low platelets or other bleeding problems.

Abstract:

If instead of pills and drugs, chemoprevention is more your style, below is an interesting article from Tucson, AZ, where they know a thing or two about high intensity sunshine. It is interesting that two of the compounds they are talking about, EGCG (from green tea extracts) and limonene (from lemon / orange peel oil) are natural compounds we have discussed before. The second abstract below talks about "Solaraze", a topical gel that has just been approved by the FDA for "Actinic Keratoses". AK can be thought of as a pre-skin cancer lesion, and it is much easier to treat at this stage than when it becomes full fledged SCC or some other form of skin cancer. AK has been shown to be treated effectively by topical application of a gel containing small amount of diclofenac, another NSAID. Solaraze can be purchased by getting a prescription for it from your doctor.

Abstracts:

PMID: 10882869
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PMID: 14716439
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