Sunday, July 27, 2008

Skin Cancer Observation from Baghdad

Case presentation by:
Professor Khalifa Sharquie,
Baghdad, Iraq

I have had the opportunity to see many cases of skin grafting on the face after excision of multiple skin solar keratosis and skin malignancy. Some of these have been in patients with xeroderma pigmentosa (XP). The grafts remained free of actinic disease and have stayed clear for many years, in some cases for more than 20 years. I have never observed them to develop solar damage, solar keratosis or malignancy.

Today, I am presenting one of these cases. A 65 yo man with history of marked sun damage since early life. During the course of his illness, he has developed frequent and multiple solar keratosis and squamous cell carcinoma. Positive family history was seen in his son. Excisions and graftings have been carried out for big cancers since 1982 but he has never developed any solar damage or skin malignancy in the grafts.





Questions:
1. Is it justifiable to excise the skin of such patients with multiple keratosis and malignancies, especially in patients with XP early in life as a part of preventive measures against skin malignancy especially malignant melanoma.
2. What is the mechanism behind this odd observation. Could fibroblasts of the graft share in prevention?
3. Is there any role in the use of imiquimod in these patients? (last question from DJ Elpern)

9 comments:

  1. AnonymousJuly 28, 2008

    Based upon the photographs, I am doubtful that this patient has xeroderma pigmentosa. However, he obviously has marked photodamage and a history of multiple actinic keratoses and squamous cell carcinomas.

    I can't readily explain why he has not developed additional neoplastic lesions in his skin grafts.

    I would not suggest excising the remaining skin on the patient's face and repairing the wounds with skin grafts as a prophylactic means of treating him. He would appear very disfigured akin to patients who have had full facial grafting after third degree burns of the skin.

    He needs a careful examination of all of his skin with ongoing surveillance every 3 months if possible. Multiple biopsies of suspicious lesions with photographic documentation of all of the sites would be helpful to discern actinic keratoses from early squamous cell carcinomas or other cutaneous neoplasms.

    Once careful mapping and photograpy of multiply biopsied sites with corresponding diagnoses has been made, then appropriate choices of treatment can be entertained.

    For zones of actinic keratoses, Efudex or Aldara can be utilized but not on the eyelids. The patient has to be given detailed instructions of the use of these drugs and what to expect clinically during the course of treatment. He may need to be seen more frequently during treatment to be sure of compliance and correct use of the medicaments.

    For actinic keratoses on the eyelids, consider topically administered liquid nitrogen with a probe. If a pinpoint spray is used, then a protective device as a plastic Yaeger retractor is needed to shield the ocular globe.

    After completion of any of these treatments, long term follow-up every 3 months is required to evaluate the patient. Perhaps, strong sunscreens, hats and limited sun exposure during peak hours could be suggested to begin to limit the high level of additional photodamage that will continue to occur.

    For true neoplastic lesions, surgical excision with careful histologic margin control is important. I don't know if Mohs micrographic Surgery is an available modality for this patient, but if it is, it would be most beneficial for high cure rates and the benefit of sparing normal surrounding skin. The latter plays a role when determining which reconstructive procedures are to be used after an excision (eg primary closure, local flaps or skin grafts). If cancers occur on the eyelids, then careful excision (or Mohs surgery) combined with ophthalmic reconstructive surgery would be optimal.

    I would be concerned about using either Efudex or Aldara to treat invasive basal cell or squamous cell carcinomas on the face especially periorbitally. I have seen recurrences with both of these topical drugs. Also, there is a tendency for these drugs to destroy the most superficial layers of the neoplasm while the deeper layers of disease continue to grow and invade below the surface of the skin.

    Compliance for treatment and frequent clinical surveillance are vital for this patient. All of the above comments would apply to managing other family members with a similar condition.

    Michael Albom, M.D.
    New York University Medical Center

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  2. AnonymousJuly 28, 2008

    This comment has been removed by a blog administrator.

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  3. AnonymousJuly 28, 2008

    Sorry to say that I am not asking about therapy or diagnosis regarding the present case????.It is not xeroderma pigmentosa.I am asking why skin graft does not develop malignancy like the adjacent original face skin?,The aim I am presenting this case is to stimulate our minds to deeply think about it and to do further clinical and academic researches
    to help our future patients
    Prof khalifa Sharquie

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  4. AnonymousJuly 28, 2008

    Observations in these cases do raise valid pertinent issues. It is interesting to think why the skin grafts seem immune to developing malignancies. As we know certain body sites/areas are preferentially more prone to develop BCCs and melanomas; this might imply that skin in these areas behaves differently to other areas. Now what exactly explains this is a matter of conjecture (atleast to me). It might be that skin actually is different in some respects anatomically or physiologically in some areas or that interaction with external factors (e.g. sunlight) induces some peculiar alterations in skin in certain areas.
    A graft replaces the 'abnormal' skin with a piece of 'normal' skin. It is not surprising that the graft remains free of any malignancies if the donor area has been remote to the recipient area. However it sure stimulates us to investigate what confers this immunity.
    As has been stated in some cases grafts have been free of malignancies for even 20 years;this is very interesting. No other therapeutic modality, medical or surgical would offer such a wonderful result at follow up in BCCs or MMs of the face. In such a scenario skin grafting assumes a pride of place as one of the first line therapies for such malignancies.
    If these observations extend to cases with XP also then that would be a great boon to these people. In the few cases I have seen, malignancies have recurred over the skin grafts very soon.
    Imiquimod remains an alternative therapeutic modality for skin malignacies however recurrences are expected to occur more often than not in my experience.

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  5. Professor Sharqui always presents interesting cases and brings up thought provoking questions.
    Yes, early excisions plus sun protection measures are important for the treatment and prevention of SKs and SCCs in such patients.
    THis is also interesting to note that the grafts are usually not affected by the solar damage. It also suggests that the skin of the face and dorsal hands is prone to solar damage because of some inherent properties to respond differently to chronic sun exposure. This also opens anew window of reserach at molecular level to compare the DNA damage and repair properties of the sun exposed and covered skin.
    Imiquimod is worth trying to reduce to size of the lesions before an excision is planned but the definite treatment is excision in my opinion.

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  6. Dear Sir
    At best I would label the patient as pigmented xerodermoid. Secondly, Imiquimod is something which I have seen has worked in prevevnting malignancy in a patient of xeroderma pigmentosum. I used it sparingly after an irritant reaction 3 nights a week anf realized to my astonishment , that at 9 weeks , after excision of a Basal cell Ca, he had fewer 'red spots!'
    Regarding the grafts being free of malignancy, well that is great. could it be similar to the Phenomenon of donor dominance, could reflect the grafts not having the precancerous lesions!
    Dr Manish Pahwa
    MD DNB, India

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  7. AnonymousJuly 30, 2008

    I'd love to be able to say I know why this happens. Patients who have multiple SCC's on the dorsal hand, esp organ transplant patients, who get grafted seem to be the same way. They usually don't get additional SCC's on the graft. The patient pictured looked like he had so many malignancies on the skin above the grafts to the eyelid margin, that he would undoubtably need a graft to that area after surgical excision. It would be hard to justify excision and grafting prophylactically, though. I don't think I could do that. Have not tried Aldara on an XP patient. Jenny Stone, M.D., Mohs Surgeon

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  8. AnonymousJuly 30, 2008

    This is an important presentation.
    1) It illustrates a family that likely has a defect in DNA repair or exposure to a carcinogen. There are XP and Cockayne syndrome variants with different expressions, but I don't think they are autosomal dominant as would be suggested here or possibly X-linked. (Obviously, I have to review my genetics)
    2) These lesion appear to have a low potential to metastasize, otherwise the father would have had worse problems by now.
    3) Aldara and/or 5% 5FU may have some role but more important is a close relationship with a knowledgeable dermatologist such as Dr. Sharquie.
    4) The donor site remaining free of keratoses and SCC may indicate that exposure to UVL may have to occur early in life to initiate the neoplastic process. UVL exposure in adulthood may not be enough of a carcinogen.

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  9. no, not justifiable at all

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