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© 2000 European Academy of Dermatology and Venereology

CAS E REPOR T

JEADV

(2000)

14

, 298–300

Blackwell Science, Ltd

Photodynamic therapy for

in situ

squamous cell carcinoma on chronic radiation dermatitis after photosensitization with 5-aminolaevulinic acid

Carlos

Guillen

,

* Onofre

Sanmartin, Angel

Escudero, Rafael

Botella-Estrada, Amparo

Sevila, Pilar

Castejon†

Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain,

†

Hospital San Francisco de Borja, Gandia, Valencia,

Spain.

*

Corresponding author, Servicio Dermatologia, Instituto Valenciano de Oncologia, c/Beltran Baguena 19, 46009 Valencia, Spain,

E-mail: cguillen@comv.es

ABSTRACT

The accessibility of the skin to light treatment, as well as the developments made by dermatologistsin photodynamic therapy (PDT), creates an exciting apportunity to include it as a part of our standardtherapeutic armamentarium. We report a 63-year-old man with an

in situ

squamous cell carcinoma locatedon a chronic radiodermitis area in a finger, treated successfully with PDT.

PDT appears to be a viable altern

-

ative to conventional therapy for

in situ

squamous cell carcinoma as well as for other superficial tumours of

the skin.

Key words

:

photodynamic therapy

,

ALA-PDT

Received: 20 December 1999, accepted 1 June 2000

Introduction

Chronic X-ray dermatitis is occasionally seen in retired doctors

who used radiotherapy or radioscopy devices without proper

protection. In such patients radiodermatitis tends to appear

on the dorsal surface of hands and fingers, and frequently

is associated with painful ulcers and superficial squamous cell

carcinoma. Surgery with excision and grafting provide the

only satisfactory treatment for extensive radionecrosis. In fact,

most references in the literature reviewed include various sur-

gical alternatives for chronic radiodermatitis.

1

Surgical therapy

is more difficult when chronic radiodermatitis appears on the

hands, especially when it is associated with skin cancer.

2

Conejo-Mir

et al

. obtained good results with cryosurgery

in six cases of professional chronic radiodermatitis.

3

They

proposes a double 30-s freeze–thaw cycle, using a cryospray

for atrophic areas and a probe for keratomas, under local

anaesthesia. This treatment is extremely painful and pro-

duces long-lasting wounds.

We describe a case of

in situ

squamous cell carcinoma

on chronic radiation dermatitis treated with photodynamic

therapy (PDT) after the topical application of the porphyrin

precursor 5-

δ

-aminolaevulinic acid (5-ALA). Our experience

in treating four similar cases was satisfactory. We believe that

topical PDT can be considered an excellent treatment for

professional chronic radiodermatitis.

Case report

A 63-year-old male paediatrician had a 7-year history of

chronic radiodermatitis on his right hand. This physician had

used radioscopy in his clinical practice for 20 years during the

1960s and 1970s, occasionally handling children without the

protection of leaded gloves.

Clinical features consisted of skin atrophy, poikiloder-

matous changes, complete loss of skin appendages, erythema

and fragmented nails. During the last 2 years he experienced

painful ulcerations on his right middle finger with functional

impairment (Figure 1). He therefore always covered his finger

with a dressing to avoid pain derived from contact.

The patient underwent several treatments over the last

2 years, including topical 5-fluorouracil, antibiotic cream,

cryotherapy, applications of topical corticosteroids and emul-

sions with urea. Failure of these treatments and the progressive

and disabling symptoms urged him to seek radical treatment,

even, if necessary, amputation of the finger.

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Photodynamic therapy for

in situ

squamous cell carcinoma

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, 298–300

The patient was referred to us for treatment. Skin biopsy

revealed typical histopathological findings consistent with

chronic radiodermatitis: hyperkeratotic and patchy paraker-

atosis, nuclear atypia and individual keratinization with the

presence of horn pearls. A second biopsy of an ulcerated lesion

showed epidermal changes consisting of an

in situ

epidermoid

carcinoma with prominent nuclear atypia, loss of polarization

of keratinocytes, dyskeratosis and atypical mitosis in the upper

layer of the epidermis.

Materials and methods

Topical PDT was the treatment we chose for our patient with

topical application of the porphyrin precursor 5-ALA for the

induction of endogenous porphyrin synthesis.

4

After cleaning

the lesion with sterile saline solution and removing crusts,

an oil-in-water with ethylenediamine tetraacetic acid based

cream containing 20% 5-ALA was applied under an occlusive

dressing and then covered with adhesive aluminized tape to

prevent exposure to light. Four hours after 5-ALA application

the tape was removed and the area wiped to remove excess

cream from the skin. Immediately before light treatment, the

lesion was examined using a ultraviolet (UV) lamp (0.45

µ

m)

and the fluorescence spectrum was determined by a spectro-

fluorometer to check the presence of the typical fluorescent

spectrum of protoporphyrin IX (PPIX) on the affected skin.

Irradiation was performed with a light source consisting of a

halogen lamp with a red filter and fibre-optic device. Irradiance

was at 140 mW/cm

2

. A light-delivered system was used for

tumour irradiation. Red light in the range of 585–720 nm was

filtered and transmitted through an optical fibre. Together

with the red light, a near-infrared irradiation in the range

of 1.25–1.60

µ

m was used during the treatment, account-

ing for 50% of total irradiance, in order to induce local

hyperthermia.

5

Light power was measured regulated to a

range of 1.2–1.6 W. Light power density was 140 mW/cm

2

.

Time of irradiation was 20 min for each cycle with a light

dose of 252 J/cm

2

. During photoirradiation the fibre was

maintained in a stationary position. Because of an intense

burning sensation, digital block anaesthesia was performed.

Six cycles of treatment were done in a 1-year period to treat

both sides of the finger and the persistence of the tumour.

No pain, inflammation, discomfort or adverse effects were

noticed following PDT treatment. Only an antibiotic cream

was applied in the following 2 days after each treatment. One

month later, the ulcerations had disappeared completely, as

did the pain and burning sensation. A biopsy performed

3 months after failed to reveal any residual tumour. No recur-

rence of the lesion has been observed in 18 months of follow-

up and the patient is now in complete remission (Figure 2).

Discussion

Topical application of 5-ALA leads to the synthesis of PPIX in

epidermal cells, both in normal and neoplastic keratinocytes.

6

PPIX is characterized by a bright orange–red fluorescence

when illuminated with a UV lamp and a characteristic

fluorescence spectrum that can be visualized in lesional skin

with a spectrofluorometer. PPIX may act as an endogenous

photosensitizer when exposed to red light.

7

The tissue-specific

phototoxic effects resulting from topical administration of 5-

ALA and posterior light irradiation form the basis of topical

PDT.

8

Light irradiation of tumour lesions treated with 5-ALA

cream leads to tumour destruction.

9

As the malignant cells

have an enhanced ability for PP biosynthesis, topical PDT has

been used for selective eradication of malignant skin tumours,

preserving normal surrounding tissue.

10

Also, it has been

suggested that hypothermia associated with PDT can enhance

the phototoxic effect of this treatment, increasing its therapeutic

effect.

5

As opposed to conventional radiotherapy, no cumulative

effects of radiation are produced, and thus it is possible to

repeat the treatment if necessary.

PDT using topical 5-ALA has proven efficacious in the

treatment of superficial basal cell carcinoma,

in situ

squamous

cell carcinoma, and actinic keratosis as well as other dermatolog-

ical conditions. To our knowledge this is the first case of

in situ

squamous cell carcinoma on chronic radiodermatitis treated

with topical PDT.

In contrast to standard PDT, where the intravenous injec-

tion of porphyrin-based photosensitizers such as Photofrin®

fig. 1 Finger before photodynamic therapy treatment, showing skin atrophy,

hyperkeratosis and ulcerations. fig. 2 Clinical appearance after photodynamic therapy treatment; there is

erythema and moderate skin atrophy.

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Guillen

et al

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leads to generalized and often severe photosensitivity over several

weeks, photosensitization with endogenous porphyrins after

topical application of ALA usually vanishes within 24 h.

11

Thus we consider topical PDT an adequate treatment for

professional chronic radiodermatitis with ulcerations and

incipient squamous cell carcinomas, especially when it appears

on the hands. Its use may prevent further radical surgical

treatment, such as amputations, ensuring the preservation of

finger function as well as avoiding the immediate complica-

tions of conventional surgery or cryosurgery.

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