Multiple cutaneous precancerous lesions

presented by

Henry Foong, FRCP

Ipoh, Malaysia

January 11, 2009

Henry Foong, FRCP, Dermatologist, Foong Skin Specialist Clinic, Ipoh, Malaysia

 
Abstract 60-year-old man presented with multiple squamous cell carcinoma-in-situ.
Patient
60 yo man
Duration
>20 years
Distribution
trunk and upper limbs
History

A 60-year-old man presented with more than 20 years history of multiple scaly plaques on the chest wall, upper back, forearms and hands. Past 2 years he noted that the lesions had increased in number and size. There is no family history of skin cancer. He denied taking/applying any traditional chinese herbal medicine or drinking water from a well in the past.

He is a truck driver. He was once told to have "psoriasis" and were resistant to topical treatments for psoriasis.

Physical Examination

Multiple well defined scaly erythematous and hyperkeratotic plaques on the anterior chest wall, upper back, forearms and palms. Some were nodular, hyperpigmented and ulcerated. Few discrete hyperkeratotic plaques were noted on the palms.

Images

Laboratory Data

Blood counts and biochemistry normal

CXR normal

Histopathology

Punch biopsies were taken from the pigmented nodule on the anterior chest wall and large psoriasiform plaque on the upper back.

(1) Pigmented nodule in anterior chest wall - HPE

Epithelium shows dysplasia involving the entire thickness. Dermis infiltrated by few lymphocytes. Dysplastic cells seen at the margin.

(2) Large psoriasiform lesion on upper back - HPE

Epidermis composed of neoplastic epithelial cells which exhibit pleomorphism and loss of polarity. There is lack of of surface maturation involving the full thickness of the epidermis. Mitotic figures are seen. The basement membrane is intact. Infiltrates of mature lymphocytes are seen in the underlying dermis.


Diagnosis

Multiple Bowen's disease/ Squamous cell carcinoma-in-situ

Reasons Presented

In the case presented here, the presence of multiple cutaneous pre-cancerous lesions in a sun-protected areas could suggest that there could be past exposure to arsenic poisoning or possibly underlying immune suppression.

A high level of suspicion may be necessary to make an accurate diagnosis of arsenic poisoning.

Questions
  1. While this could be a case of chronic arsenic poisoning in the past, he denied taking any traditional chinese herbal medicine on repeated questioning. He had no past history of asthma or arthritis. ( Traditional Chinese medicine is a favourite for these disoders). He also had no history of drinking water from a well which may be contaminated from arsenic. Where is the source?
  2. Considering the extent and number of the lesions in him, how many biopsies would you consider in this patient? So far 2 biopsies had been done including one on the chest wall which look suspicious of BCC. Both were histologically bowen's.
  3. Would cryotherapy or electrocautery be adequate for th treatment of the SCCIS? Topical imiquimod (Aldara) would be theoretically useful but the extent and number of the lesions make this mode of therapy less practical.
  4. Does anyone has any experiece with photodynamic therapy in such cases?
References
  1. Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic arsenicism: review of seventeen cases. J Am Acad Dermatol 1998; 38: 179-185 BACKGROUND: Cutaneous complications arising from exposure to Chinese proprietary medicines known to contain inorganic arsenic have been rarely reported. OBJECTIVE: Our purpose was to study the nature, incidence, and sequelae of patients with chronic arsenicism and to review the literature on arsenic-induced skin diseases. METHODS: Case records of patients with cutaneous lesions related to chronic arsenicism seen from January 1990 to December 1996 were reviewed. Patients were interviewed and a complete skin and systemic examination was performed. Data on demography, history of arsenic ingestion, and type and distribution of skin lesions and visceral malignancy were collated. RESULTS: Seventeen Chinese patients (11 men, six women) were identified; their mean age was 64.5 years. Fourteen patients (82%) had exposure to Chinese proprietary medicines known to contain inorganic arsenic, and three had environmental arsenic exposure from well water. The mean age of these 14 patients was 17.6 years; mean duration of arsenic intake was 6.4 years. Seventeen patients had Bowen's disease; of these, 70% had 2 to 10 lesions. Of the 17 patients with arsenical keratoses on the palms, 76% had 2 to 10 lesions. Of the 14 patients (82%) with plantar arsenical keratoses, 64% had 11 to more than 50 lesions. Eleven patients (65%) had macular hypopigmentation. Seven patients (41%) had 11 squamous cell carcinomas (SCCs); three of the seven had more than one lesion. Fifty-five percent of SCCs arose from preexisting keratotic lesions (n = 4) or Bowen's disease (n = 2), and 45% arose de novo. One patient each (6%) had multiple basal cell carcinomas, laryngeal carcinoma, and metastatic SCC. The latency periods for the development of arsenical keratoses, Bowen's disease, and SCC were 28, 39, and 41 years, respectively. Patients with SCC were significantly older at the start of arsenic exposure and had significantly more palmar arsenical keratoses than those without SCC. CONCLUSION: Exposure to Chinese proprietary medicines containing inorganic arsenic poses a risk for the development of cutaneous and systemic malignancies. Long-term follow-up is necessary for tumor detection because of long latency periods. Surveillance programs are important to restrict the sale of Chinese proprietary medicines that may contain inorganic arsenic.
  2. Torchia D, Massi D, Caproni C, Fabbri P. Multiple cutaneous precancerous and carcinomas from combined iatrogenic/professional exposure to arsenic. Int J Dermatol 2008; 47: 592-593
  3. Vitharana K, Tay YK, Poh WT. Chronic arsenicism a forgotten entity? Mal J Dermatol 2007; 21: 64-65
Keywords bowen's disease, arsenic poisoning
Comments from Faculty and Members

Amanda Oakley MB ChB, FRACP, Clinical Associate Professor, University of Auckland, New Zealand on January 10, 2009

1. Cause may be unknown source of arsenic, or some other reason. We sometimes see similar patients and there is no known source of excessive arsenic in New Zealand. Has he had exposure to timber industry? Or lived near timber plant where arsenic is used to preserve the wood?

2. These lesions all look the same and are typical of intraepithelial carcinoma (Bowen's). Two biopsies are enough.

3. In this type of case I use curettage and diathermy or cautery, taking three to four visits to remove all the lesions under local anaesthetic. I then manage new small ones with cryotherapy when the patient visits me, and the patient applies fluorouracil cream between visits. Imiquimod would be very expensive in this situation and also take a long time as only one sachet can be used at a time.

4. PDT is useful where C&D will leave a bad scar or take a long time to heal e.g. face, lower legs.

Steven Deliduka MD, Dermatologist, Chicago, IL, USA on January 11, 2009

Agree with the previous comments. Consider topical 5-FU.

Ian McColl FRACP, Dermatologist, Gold Coast, Australia on January 11, 2009

I think Amanda has summed up the situation expertly. I would treat in a similar manner for the same reasons. Regular follow up is required. I would probably curette any small new lesions as well rather than use cryotherapy.

You should look for other internal malignancies due to arsenic as well, lung and bladder especially.

David Elpern MD, Dermatologist, Williamstown, MA, USA on January 11, 2009

While arsenic or another carcinogen is certainly a possibility there may be other causes. Going into his history in greater detail may help. If a carcinogen like arsenic, the exposure could have been as a child!

He may have some rare syndrome which predisposes him - such as an inability to handle HPV. Have blood studies been done to rule out chronic lymphocytic leukemia or some other immune deficit?

Need to research 5FU (maybe even systemic), imiquimod, acitretin -- there's a literature on this. Some smaller lesions could be treated with excision and C&E. Maybe all.

What is the risk for internal malignancy in a case like this. In the "old days" Bowen's disease was said to be associated with internal malignancies -- then this idea was abandoned -- but in truth, a subset of Bowen's disease may be related to malignancy and this is the group with Bowen's disease in sun-protected areas where the etiology was likely not UVL but a carcinogen or some other cryptogenic factor.

Sunil Dogra, Assistant Professor of Dermatology, PGIMER, Chandigarh, India on January 12, 2009

Thanks for sharing this very interesting clinical presentation. Encountered a similar case last week who had received some ayurvedic medicine for his vitiligo about 20 years back.

This seems to be chronic arsenic toxicity. Not so rare in India where drinking water is contaminated in some part of eastern states and alternative systems of medicine use heavy metals including arsenic for treatment of various dermatoses like psoriasis and vitiligo.

Biopsies from suspicious looking lesions at regular intervals, oral retinoids (acitretin) for 6 months to one year for its chemoprotective effect, topical imiquimod for any lesion on face, cryotherapy for hyperkeratotic lesions and close follow up will be required for this patient. Lab estimation of Arsenic levels (blood, hair,nail) may be tried.

Michael Albom MD, Clinical Professor, New York University Medical Center, New York, United States on January 12, 2009

Most of the pertinent commentary has already been made by the above colleagues. The lesions appear as those seen with arsenic toxicity. In this case, the source of exposure is not clear. Digging further into his medical history may or may be revealing. A 24 hour urine collection to measure arsenic would be advised if possible. It wasn't mentioned if he has other signs of arsenical toxicity such as peripheral neuropathy.

If arsenic toxicity is truly the underlying etiology, then other internal malignancies may become manifest as has already been mentioned by others. An oncology work up should be undertaken.

Henry was wise to do punch biopsies to establish the cutaneous diagnosis of 2 lesions. However, there may be sampling errors that can occur with a small diameter biopsy within a large lesion. It is not uncommon to find areas of actual invasive squamous cell carcinoma within some of the larger plaques of Bowen's disease.

Even if there is evidence of superficial invasion of SCC, treatment of the lesions, over time, by D&C would be most expeditious. I doubt that the patient would comply with topical agents as Efudex or Aldara since he would have to endure many weeks of severe discomfort with these topical agents. He would still need followup biopsies of multiple sites to know if the lesions had been truly eradicated.

This is a very interesting case. Hopefully, we can get a follow-up on his progress.

Khaled El-hoshy M.D., Consultant Dermatologist, Troy, Michigan, USA on January 13, 2009

Agree with electrodiathermy & curettage or cryotherapy. Would definitely consider Acitretin 10-25 mg/day with appropriate labs pre & during Rx. Reevaluate rate of tumor appearance after 6 months of Rx.

Amin Nurul M.D., Professor of Dermatology, Armed Forces Medical College, Dhaka, Bangladesh on January 14, 2009

Excellent presentation. Seems to me a case of arsenicosis.

Ted Rosen MD, Professor, Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA on January 14, 2009

Arsenic is high on the list. Also inquire about exposure to smelting ore (arsenic-containing gases can be released). In our area, this would be slam dunk case of Paris Green exposure (arsenical insecticide) if he grew up on a farm or arsenic-laced well water (in rural areas). He will be a mess if you try to C&D these.

My suggested method, despite some inconvenience, is to use combination therapy: 5-FU daily in AM, imiqumod 5% daily in PM. This reduces cost, hastens response and increases efficacy. We have in press a fellow who had both hands covered with SCCIS from chronic unshielded radiation exposure (radionuclide tech by trade) who completely cleared this way, as well as numerous well-water Bowen's patients similarly. Cosmesis is unsurpassed by any surgical intervention. Remember that there is a longer incubation time for internal cancer than for cutaneous neoplasia (should this be arsenic or other systemic carcinogen). Even if he is OK now, he is at increased risk of GI, GU or respiratiory cancer 10 or more years from now.

Yelva Lynfield MD, Dermatologist, Minneapolis, MN, USA on January 14, 2009

Long ago I had a patient with psoriasis who gave me a history of treatment for his psoriasis with Fowler's solution. It was a nightmare to decide which of his lesions were psoriasis and which were squamous cell carcinomas-in-situ . He died of lung cancer.

Recently at a Minnesota Dermatologic Society meeting I saw an immunosuppressed transplant patient with multiple cutaneous squamous cell carcinomas which responded to oral capecitabine. You should do a search on this drug, since it may be an answer to difficult problems with multiple skin cancers. It doesn't work on basal cell carcinoma though!

Andy Affleck MRCP (UK), Clinical Fellow, Dundee, UK on January 15, 2009

Thanks for sharing this case. I agree with most of comments so far - Amanda, do you not advise patients to reseal their aldara sachets with a paper clip so one can be used several times?

I would use topical therapy initially starting with efudix monotherapy used to small areas in a cyclical manner to minimise discomfort. If persistent areas remain - should I would aim for excision (as Ted says C+E will be most disfiguring). Imiquimod also should be tried (and results compared with efudix), combo approach worth considering as Ted says. I would start on prophylactic acitretin 20mg od if no contraindications. I would look for underlying immunocompromise, HPV PCR. Close follow-up eg. 3-monthly

Michael Albom MD, Clinical Professor, New York University Medical Center, New York, United States on January 15, 2009

With all due respect to my esteemed colleague, Dr. Ted Rosen, I don't agree that treatment by C&D will necessarily "be a mess." I would treat the largest lesions first and give the patient time to heal before treating the others with whatever other modalities might be chosen. There is no question that the patient will develop obvious scars at the treatment sites by any surgical technique, but the most important issue is efficacy. If we wanted the absolute highest cure rates, then Mohs micrographic surgery would be the best choice of treatment. However, except for possibly the largest of the lesions, Mohs is not really necessary with most of these lesions.

Here is the problem with topical agents as 5-FU or Imiquimod 5%. The pain with treatment is often very significant and it progressively increases over time since these agents have to be utilized for a prolonged period of time. The patient may not be able to comply with full treatment of many lesions with these agents. Of further concern is that we are now seeing recurrences of both basal cell and squamous cell carcinomas after treatment with these topical agents. Here is the bigger dilemma. Often, the recurrences are deep and sometimes there are no topographic changes to suggest the recurrences. Careful palpation over the treatment site has sometimes revealed a thickening of the skin. Many years ago, as a dermatology resident, I saw my first case of a recurrence of a basal cell carcinoma on a leg after a 3 month course of 5% 5-FU. There were no gross signs of recurrent disease. As part of the protocol, the entire site of treatment was excised to check for the efficacy of treatment. Here were the histological findings: there was subliminal persistence of basal cell carcinoma not only in the deep reticular dermis but the basal cell carcinoma had invaded into the superficial subcutaneous tissue.

Since then, I have seen other cases of recurrences of both basal and squamous cell carcinomas with treatment by 5-FU or Imiquimod. Among these were lesions that did not clinically recur until a year or two had elapsed since the original completion of treatment. Many of the published studies have follow-ups under a year so the efficacy of topical agents cannot be truly assessed. The bottom line is that, although these agents have a place in the treatment of some cutaneous neoplasms, they are not a panacea.

Lastly, Dr. Foong is in the best position to know his patient's level of compliance as regards any potential treatment(s). All the modalities that have been discussed have their benefits and liabilities. Obviously, this is a very interesting case as can be appreciated by amount and diversity of commentary by our colleagues.

Sunil Dogra, Assistant Professor of Dermatology, PGIMER, Chandigarh, India on January 19, 2009

Here is a useful review article on arsenicosis: diagnosis and treatment. You can download the article by clicking on it.

Ref: Nilay KD, Sujit RS. Arsenicosis: Diagnosis and treatment. Indian J Dermatol
Venereal Leprol 2008;74;6: 571-81.

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