CASE REPORT

Occurrence of Squamous Cell Carcinoma in an Area of

Lichen Simplex Chronicus: Case Report and Pathogenetic

Hypothesis

Cesare Tiengo, Jenny Deluca, Anna Belloni-Fortina, Roberto Salmaso, Flavia Galifi, and Mauro Alaibac

Background: Lichen simplex chronicus is a common skin disorder characterized by circumscribed, lichenified, pruritic plaque

secondary to local repetitive trauma, notably rubbing and scratching.

Objective: We describe a case of a squamous cell carcinoma arising in a patient with a long-lasting history of lichen simplex

chronicus and discuss the potential role of the microenvironment in predisposing the malignant transformation.

Conclusion: Here we propose a hypothesis in which rubbing and scratching contribute to an excess of inflammatory mediators,

which in turn may lead to alterations in the processes of keratinocyte proliferation and differentiation.

Renseignements de base: Le lichen simplex chronique est une affection cutanee courante caracterisee par une plaque pruritique

lichenifiee circonscrite consecutive a des traumatismes locaux repetes, notamment le frottement et le grattage.

Objectif: Nous decrivons un cas de carcinome squameux chez un patient presentant depuis longtemps des antecedents de lichen

simplex chronique, et nous discutons du role potentiel du micro-environnement dans la predisposition de la transformation maligne.

Conclusion: Nous proposons ici une hypothese selon laquelle le frottement et le grattage contribuent a un exces de mediateurs

inflammatoires, lesquels peuvent a leur tour venir modifier les processus de proliferation et de differenciation des keratinocytes.

L ICHEN SIMPLEX CHRONICUS (LSC) is a chronic

and localized form of lichenification. LSC is not a

primary process but develops when skin gradually thickens

because of repetitive scratching and rubbing. Paroxysmal

attacks of itching often initiate from minor stimuli, such as

removing and putting on clothes, and scratching rapidly

becomes an unconscious habit. The most common sites of

lesions are areas that are easily accessible to scratching,

notably the nape and sides of the neck, lower legs and

ankles, scalp, upper thighs, genital region, and extensor

forearms. White scratch marks and excoriations are the

result of the mechanical injuries. The peak incidence

ranges between 35 and 50 years of age, and is in general

greater in women. LSC needs to be differentiated from

psoriasis, mycosis fungoides, lichen planus, and lichen

amyloidosis. The major histopathologic feature in lichen

simplex is the hyperplasia of all components of the

epidermis: hyperkeratosis, orthokeratosis, acanthosis, and

hypergranulosis with a regular elongation of the rete

ridges, whereas spongiosis is infrequent. Within the

dermis, there is a chronic inflammatory infiltrate, visible

as a perivascular infiltrate of lymphocytes and occasionally

of macrophages. LSC can last for years, unless the itch has

been improved by treatment.1–3

LSC is not considered a precancerous cutaneous

condition. We report a case of squamous cell carcinoma

(SCC) arising in long-lasting (35 years) LSC.

Case Report

A 51-year-old man was referred to our unit for the

appearance of a fast-growing, nodular, vegetating,

ulcerated lesion on his right leg. The lesion was located

on the lateral surface of the patient’s right ankle (Figure 1

and Figure 2). A surgical excision was performed, and the

histopathology revealed a SCC. The lesion developed in

an area of skin previously affected by long-lasting LSC

(35 years). On both legs, we could observe well-

demarcated lichenified plaques and small papules, whose

From the Units of Plastic Surgery, Dermatology, and Pathology,

University of Padua, Padua, Italy.

Address reprint requests to: Mauro Alaibac, MD, PhD, Unit of

Dermatology, University of Padua, Via Battisti 206, 35128 Padova,

Italy; e-mail: mauro.alaibac@unipd.it.

DOI 10.2310/7750.2011.11048

# 2012 Canadian Dermatology Association

350 Journal of Cutaneous Medicine and Surgery, Vol 16, No 5 (September/October), 2012: pp 350–352

histologic features were consistent with the diagnosis of

LSC. The same diagnosis was made for the skin lesion

surrounding the SCC. The patient did not reveal any

other associated local symptoms, except itching.

Histology demonstrated the presence of a moderately

differentiated SCC invading the reticular derma and

showing a warty aspect and a rich lymphoplasmocytic

infiltrate (Figure 3).

Discussion

LSC is not considered a premalignant skin condition,

although considerable epidermal hyperplasia is a char-

acteristic feature of this disorder. Hyperplasia is the

consequence of a disturbed growth of keratinocytes, which

is regulated by a delicate balance between signals controlling

proliferation and apoptosis. This alteration of the cell cycle

results in the increase in the volume of the cell mass due to

an enhanced cell production. A noncontrolled cell prolif-

eration is also the first step in the development of a

malignant lesion.

Recent studies investigated the presence of genetic

alterations in hyperplastic skin lesions and their possible

role in the degeneration of the lesions in a malignant

form. Bowen and colleagues performed a study that

revealed that LSC cells have the lowest proliferation rates,

and only half of the cases investigated for LSC are positive

for the expression of the apoptosis inhibitor survivin.4

Hussein and colleagues conducted a study concerning

hyperproliferative skin lesions; they demonstrated a low

level of both p53 and bcl-2 protein expression in both

normal skin and nontumorigenic keratinocytic lesions,

including LSC.5 However, other concomitant factors may

concur in the development of cancer, and beside the

genetic alterations, the local microenvironment may play

an important role. The origin of itching is related to the

production of inflammatory mediators, which are the

results of the close relationship between the central and

the peripheral nervous system and cells present in the

scratched skin.6 Moreover, scratching provokes skin

injuries, which in turn stimulates the repair process.

Keratinocytes respond to tissue damage by migrating into

the wound bed from the surrounding tissue. This process

implicates reduced cell-cell adhesiveness, impaired epi-

dermal terminal differentiation, and augmented cell

motility and appears to be regulated by transcriptional

Figure 1. Squamous cell carcinoma on the right ankle appears like avegetating and ulcerated lesion.

Figure 2. Presence on the same leg of well-circumscribed lichenifiedplaques surrounded by small papules.

Figure 3. Histologic image of the squamous cell carcinoma invadingthe reticular derma, which appears moderately differentiated with awarty aspect and a rich lymphoplasmocytic infiltrate (hematoxylin andeosin, 320 original magnification).

Occurrence of Squamous Cell Carcinoma in an Area of Lichen Simplex Chronicus 351

repressors of growth factors and cytokines, such as those

of the Snail family (Figure 4).7,8

Conclusion

It may be possible that in our case, the repeated

mechanical trauma to the skin determined an excessive

release of inflammatory mediators, which disturbed the

fine-regulated pathway of the repair process, promoting

carcinoma by an altered regulation of keratinocyte

proliferation.

Acknowledgment

Financial disclosure of authors and reviewers: None

reported.

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Figure 4. Proposed model of how inflammation associated withlichen simplex chronicus can promote the development of skin cancer.

352 Tiengo et al

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