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.
22 comments on "Squamous Cell Carcinoma in CLL Patients"
Hi Chaya,
I developed squamous cell carcinoma on the back of my left hand, just below the index and middle fingers, and had the lesion removed via Mohs Surgery. No reoccurrence since I had the surgery last year.
Some great news. My mini-allogeneic stem cell transplant is a success. I learned today (6-month bone marrow biopsy and flow cytometry) that I am in complete remission! There is no sign of lymphoproliferative disease. I’m CLL-free.
Thanks again for another great article…
bill howard
Bill:
Thanks for letting us know about your mini-allo CURE!!!! It is good to hear such news, gives the rest of us reason to hope. May you live long and prosper, enjoy your CLL free life.
I am diagnised as CLL stage 0. Myonly problem is WBC 22500. I am absolutly normal. I do my exercise reguarly for 1 hour and walk for 45 minutes every day.
Is there a cause of worry. I am told by my Doctor that I may carry on in the same state for 10 years or more. Now I am 69.
Please advice.
Thanks so much, Chaya.
I did have two skin cancers – actinic keratosis removed three months ago but never went back. You have prodded me to make an appt. for a full body check TODAY. Thanks
Marci
That’s great news Bill, it’s nice to hear positive stories.
Krishnakumar, read everything you can on CLL, this site is
a good place to start. Whether or not you need to worry depends
on a lot of variable factors.
F Henry
Dear Chaya
As a 78 year old, first diagnosed 7 years ago, your work has given me much hope and understanding about my condition. Over the years I had severl encounters with chemo (Rituxan + Fludarabine and about 20 months ago I was given Rituxan Fudarabine Plus Cytoxan) This last treatment produced a deeper remission but resulted in extremly low RBC and platlet counts which required blood transfusions ie 2 units of blood on three occasions. I was able to recover and gain my strength but my WBC counts are once again increasing. Six months ago I had a squamous cell lesion removed from my back. I have also had two maglinant melanomas surgically excised from my leg back in 1980 with no reoccurrance, Luckey me. please keep up your work educating us on CLL and giving us hope and understanding. I will be attending my 60th high school reunion this october. Life sure is sweet FHM
‘I think SCC is best treated in CLL patients by a team of doctors that include an oncological dermatologist, radiologist, plastic surgeon and hematologist.’ Did you mean radiotherapist Chaya?
I am lucky, the dermatologist and haematologist have clinics within a minutes walk. The exercise does them good!Diagnosis and management were jointly discussed and 2 years after excision of my SCC which flared up after Campath,I am seen by the dermatologist at 3 monthly intervals.The dermatologist has surgical training.So the NHS ain’t all that you read it to be.
Interestingly my dermatologist holds the view that ‘normal sunlight exposure’is acceptable but then the British weather IS all that you read it to be.
Adrian.
Chaya, you show a picture of a fingernail but I see no mention of it in the article. I have a fingernail that looks just like that, also two toenails. I visit a dermatologist regularly, but have never asked about the appearance of this nail. I thought it was caused by nail fungus. Is this photo an example of Squamous cell carcinoma? If it is, I need to go back to the doc or find a new one.
Betty
Betty:
Yes, that is squamous cell carcinoma causing the nail to look funky. I got the picture from a whole lot of SCC pictures – the ones I chose were the least scary of the lot. Whether your nail problem is fungus or SCC I do not know, you have to ask your dermatologist about it.
Chaya,
Thanks so much for the heads-up. I’m getting an early appointment with her to ask specifically about this problem. It had never occurred to me it could be anything other than a fungus related problem. I have regularly had skin cancers and precancerous skin spots removed at what seems to me to be an alarming rate. I also understand CLL has made me susceptible to fungal infections.
Bless you for educating me,
Betty
Hi Chaya,
Thanks for bringing up this subject again. CLL patients can never get enough information on skin cancer. As I was having FCR in 2004 I noticed a plain freckle grow in by the top of my Knee. Nothing unusual but a small pucker at the edge. I insisted it be removed and much to the shock of my doctor it was Melanoma. Ever since I get checked by two doctors at different health care systems every six months. Then I have a plastic surgeon who is aware of my cancer history who removes
the hard to reach spots and things on my face.
CLL patients have their skin marked up with odd things as we live with this disease. I have red dots small and medium and skin tags that grow weird places. Our skin must be checked often. I get the doctor to take pictures to compare to what is seen in my current appointments. You could even take your own digital pictures to track changes.
I just had a lower eye rim (clear bump) taken off that was a pre cancerous spot usually caused by sun exposure.
The worst experience I had was a tan flat lesion near the Urethra. It burned and I just could feel trouble. After a biopsy it was squamous cell carcinoma that continued inside the Distal Urethra in two more places. I had 33 radiation treatments in 2007 and so far no reocurrance. I have small biopsies taken every six months under sedation.
CLL patients do need the exact Team of doctors that you recommend. It seems overwhelming but it is necessary! My point is that the most important person on the Team is the Patient! I know my body and have caught three cancers myself.
You want to prevent skin cancer when you have CLL not just get it early! I was told at M. D. Anderson if the spot is raised or dark get it off. If the doctor does not agree find one that will. Skin surgery is a way of life like getting your teeth cleaned.
It will always be something. So look out for yourselves. Colleen
Hi Chaya,
I am a 55 year old male diagnosed over two years ago with CLL stage 0.
This article has appeared at a most opportune time. A little over a week ago I had a Bcc removed from my upper right cheek by a dermatologist on a recommendation from my family Physician. The dermatologist who took the sample suggested that I would be best to prepare to have Moh’s surgery. The biopsy results are now in and I will be returning to my family Physician next week to discuss these results.
This will be the second time having Moth’s surgery, two years ago I had Moth’s surgery on the same side of my face at the hair line, so perhaps your suggestion of the cancerous edge cells being left behind to grow back to a different location are well heeded. This time I will ask about the imiquimod cream and the radiation option.
Hi Chaya,
You perform a great service. Keep it up.
I recall in early 2005, I contacted you regarding my concerns with undergoing Sub-Q Campath, self-administerd injections, because of my history of Squamous Cell skin cancers (SCC). You and Dr. Lundin of Sweden both recommended extreme caution. Despite your good advise, I proceeded with the Campath (as consolidation after HDMP+R-all part of a clinical trial).
Afterwards, I have experienced a deep remission which continues to last for going on five years. However, my T-Cells were decimated and are still at a low level. Since 2005, I have had multible SCCs, MOH surgeries and Efudex type creams (Aldara is supposed to stimulate our immune system to attack the skin lesions, but with CLL patients, our weakened immune system doesn’t stimulate very well).
I am not certain, because I already had SCCs before Campath, whether that treatment accelerated the SCCs or not. However, my Dermatoligist and I are extremely vigilent and I see her at least every three months and sooner, if something suspicous appears. I apply gobs of sun screen but as they say the damage was done years ago and our CLL, plus the treatment we receive opens the gate for SCCs.
It is extremely important to take care of anything that appears around the mouth and other areas close to underlying Lymph nodes as those are convenient avenues for Metastasis.
Thanks again for your invaluable service to the CLL community.
Jerry Fisher
Hi,
I forgot to add the following.
Recently, my Dermatologist has suggested considering a retinoid drug called Acitretin as an anti-Squamous cell cancer drug. In a double-blind, placebo controlled study of organ transplant patients, whose immune systems were deliberately suppressed to prevent rejection, they found that the post transplant occurrence of Squamous cell cancers were reduced from 47% of patients to 11 percent.
Have you heard of this drug and whether it would be efficacious for CLL patients?
Thanks
Chaya,
I also wonder about Acitretin and locally cannot come up with a clear yes or no. Hem/onc doesn’t care one way or the other. Dermatologist believes it might be worth a try, but once on it, one has to stay on it or risk acceleration of SCCs upon stopping. Could you keep your ear to the ground on this one for us? Thanks AGAIN.
Ann
Chaya….appreciate your article. I’ve had a couple basal cells and one squamous (ear)that required MOH’s surgery.
Doctor said to get check ups every 6 months. After 3 years, no reoccurance.
Am in 14th year of CLL, one Rituxan treatment 7 years ago.
Take a lot of antioxidants, dark chocolate, Vit D3, pomagarnte/green tea
White count around 85,000
Don in Concord, CA
Chaya,
Thank you for this wonderful article on skin cancer. I too had Mohs Surgery on the bridge of my nose in May. All was taken out(basal cell) and so far I am doing ok with no other problems. Knock on wood!!
I also have a fingernail on my left ring finger that doesn’t look quite like the one in your picture, but it looks as if it is lifting under the skin. I have been putting tea tree oil on it regularly and trimming it back. I am not sure if it might be the squamous or not.But I will have to ck with my dermatologist and see what he thinks. Keep up the good work. We certainly appreciate any and all information related to CLL.
Anita
Jerry, Ann:
Your question about Acitretin is very valid and worth responding in detail. In the next day or two I will write a full length article about it. Thanks for bringing it to my attention. I have been reading about it and it is indeed an interesting option for systemic chemoprevention of SCC. There are some issues to think about, nothing is a slam dunk in this business.
Housekeeping Notes:
As some of you may remember, I am on an extended visit to India to take care of my Mom. On September 1 we shift house to a new apartment (with a terrific view of the Bay of Bengal!) and phone / internet connectivity will be interrupted for several days. Please bear with me during this blackout period; I will be back as soon as possible.
Bocabob
Dear Chaya,
WOW, I’ve had two Mohs in the last three years and neither doctor suggested that do to my CLL much more
vigilance is required. Thank you for the wake up call, I’ll be on the case immediately.
Bob
Friends,
I see the derm every 6 months. So far so good. Just like a diabetic must see the eye doctor annually to prevent problems, so the CLL patient should see the skin doctor at least twice a year.
On a different front, my CLL is back post HSCT. 2.8% of the bone marrow and the nodes on CT scan have grown a bit.
To be expected after losing the graft. but I hoped against the odds for a a different outcome.
Looks like I am heading for a second transplant, this time with more chemo. And ATG.
More later
Be well
Brian
Hello Chaya – I showed your article to my Dermatologist and he was very interested. He wondered about the availability of the article about which you wrote “It has been reported that SCC is nine times more likely in CLL patients than in the general population”
Thanks, Mal
Mal:
We reviewed the epidemiological link between CLL and skin cancer in an earlier article “Dying to get a tan?” ( http://www.clltopics.org/Complications/Dying.htm ) on our website http://www.clltopics.org. We based our observations on a detailed article in the BMJ. Here is the citation: BMJ 1995;310:1491-1495 (10 June). We also provided a link to the full text of the BMJ article as well as key statistics from it in our earlier “Dying to get a tan?” review.
For example, in Table 2 of the BMJ article, the authors cite overall incidence of SCC after initial diagnosis of CLL at 120 in this very large cohort. The number expected in general population without CLL is 13.9. That is a 8.6 fold increase in expected versus observed incidence of SCC. The increased risk is even higher in CLL patients under the age of 65 at the time of diagnosis. The authors conclude “These data provide evidence of a close association between non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia and squamous cell skin cancer or malignant melanoma.” Several subsequent reports have validated these conclusions.
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