Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in vivo reflectance confocal microscopy: A preliminary study

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Summary

Background

Superficial BCCs (sBCCs) usually appear as multiple lesions in chronic sun-damaged skin of elderly people and may show a destructive growth if left untreated. Non-invasive treatment modalities, such as cryotherapy have been employed for sBCCs, all failing to provide tissue for confirming diagnosis and assessing adequacy of tumour removal. Reflectance confocal microscopy (RCM), a new non-invasive imaging technique has proven to be a useful tool for detection of basal cell carcinoma in vivo.

Objective

To non-invasively assess efficacy of cryotherapy for sBCCs by cytomorphologic analysis using RCM.

Methods

We examined 10 histologically proven sBCCs located on the trunk of 5 consecutive patients with a mean age of 84.6 years. SBCCs were frozen twice using a spray nitrogen cryoprobe. RCM imaging was performed in each sBCC before cryotherapy and after 5 and 24 h to monitor resulting tissue injury. Distinct cytomorphologic characteristics were determined by three observers allowing non-invasive evaluation of therapeutic efficacy of treatment immediately after cryotherapy. Tumour clearance was assessed by RCM imaging 3 months after therapy followed by histopathologic examination.

Results

Characteristic RCM-features of BCC were present in all lesions before cryotherapy. Five hours after cryotherapy, all 10 sBCCs showed small bright round to polygonal structures at basal layer and black round to oval areas of varying size with such bright structures floating therein, correlating to cell necrosis and incipient blistering. Eight sBCCs showed also cell necrosis in upper dermis. After 24 h all sBCCs showed necrotic cells beneath collagen bundles. Tumour clearance on later histopathologic examination was only proven in those lesions showing damage to the upper dermis after 5 h with RCM.

Conclusion

Early cell necrosis within upper dermal structures seems to correlate with ablation of overlying tumour tissue. When it is not produced by cryotherapy, a second treatment should be considered.

Introduction

Basal cell carcinoma (BCC) is the most common cancer in white populations comprising 75% of non-melanoma skin cancer. There are three main subtypes of BCC: superficial, solid/nodular and fibrosing/infiltrating. Superficial BCCs (sBCCs) clinically appear as round to oval erythemato-squamous, sharply demarcated macules or plaques. On microscopic examination sBCCs are characterized by multifocal small buds of basaloid tumour cells extending from the epidermis with peripheral palisading of basaloid cells and a rather uniform appearance of nuclei. sBCCs tend to show horizontal growth, usually just infiltrating the upper papillary dermis. The surrounding connective tissue proliferates forming the tumour stroma.

The differentiation of BCC subtypes is important for therapy and prognosis: sBCCs have the lowest recurrence risk after excision [1]. Treatment options for sBCCs include surgical and non-surgical modalities; the choice of treatment mainly depends on location, number and diameter of lesions, and age and health status of patients. A variety of new non-invasive therapeutic approaches have been employed for sBCC, especially for multiple tumours in sun-damaged skin, although little research is available which compares these methods [2]. As diagnosis and tumour margins cannot always be reliably determined by clinical examination, a biopsy is often performed before using a non-invasive therapy.

The popularity of cryotherapy in the treatment of sBCCs has dropped in recent years among both physicians and patients following the introduction of “modern” non-invasive treatment modalities, such as photodynamic therapy and topical imiquimod. Cryotherapy is still an excellent choice for treatment of many superficial premalignant and malignant skin lesions, producing high cure rates with minimal patient discomfort [3], [4]. Because of the greater sensitivity of premalignant and malignant cells to low temperatures as compared to surrounding skin structures, the method results in good cosmetic outcomes. Additionally, cryotherapy is a quick, simple, inexpensive therapy for sBCCs which does not require high patient compliance. Cryotherapy is therefore especially useful for elderly people with multiple lesions which usually requires just a single treatment. As with other non-invasive treatment modalities, cryotherapy fails to provide tissue for confirming diagnosis and assessing adequacy of tumour removal.

Reflectance confocal microscopy (RCM) is a new non-invasive imaging technique enabling the visualization of structures and individual cells of the epidermis and papillary dermis in vivo at nearly histologic resolution. Thus, many of the structures seen on RCM correlate closely to histopathologic findings especially for superficial tumours. González et al. first described RCM features of BCCs in 2002; a larger multicenter study with 152 cases validated these results [5], [6]. Typical findings of sBCCs in RCM include elongated nuclei of tumour cells oriented along the same axis (“streaming”), presence of small tumour nodules, bright dendrites or dendritic cells within the epidermis or tumour nodules, increase of tortuous vessels and presence of prominent tumour stroma, consisting of bright, fine, elongated and parallel oriented, “gossamer-like” collagen bundles [6], [7]. The bright dendritic structures and/or dendritic cells seen within the epidermis are Langerhans cells, whereas similar structures within tumour islands may represent both Langerhans cells and melanocytes in pigmented sBCCs [8]. We investigated the value of RCM for monitoring of superficial BCC after cryotherapy.

Section snippets

Patients

We included 5 consecutive patients with a total of 10 histological proven superficial BCCs at our outpatient clinic at the Department of Dermatology, University Hospital Graz, Austria. A single punch biopsy of each superficial basal cell carcinomas was done before study inclusion for diagnostic and therapeutic purposes. Clinical images of each sBCC were obtained before cryotherapy and before RCM imaging at each follow-up visit. All sBCCs were located on the trunk with a mean lesion diameter of

RCM features before cryotherapy

All examined sBCCs showed characteristic RCM-findings before cryotherapy (see Table 1). Eight sBCCs showed 4 different distinct criteria, the remaining two cases showed 3 different criteria within one lesion. Streaming of cells at basal epidermal layers was seen in 9 out of 10 cases, whereas small tumour nodules could be visualized in 6 cases. Bright epidermal dendritic cells or dendrites were detected in 4 cases. All sBCCs showed an increase of tortuous vessels, whereas gossamer-like collagen

Discussion

sBCCs usually appear as multiple lesions in chronic sun-damaged skin of elderly people, which is also reflected in the age and number of included lesions in our patients [12]. Even though most sBCCs will not metastasize if left untreated, they may show a destructive growth and ulceration after slow enlargement over years. The diagnosis is usually made by clinical and dermoscopic examination [13]. However, in some cases differentiation from actinic keratoses or squamous cell carcinomas can only

Conclusion

Our preliminary results suggest that early cells necrosis within basal epidermal layers and upper dermal structures is indicative of effective cryotherapy with ablation of tumour tissue. RCM-imaging was not useful for assessment of tumour clearance after 3 months as previously observed after treatment with imiquimod, which seems to result in more moderate scarring. The main limitation of RCM-imaging is that nuclear features cannot be visualized and therefore discrimination between malignant

Acknowledgement

We are indebted to Walter Burgdorf, MD, for critical review and editing.

References (20)

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