Heteroduplex analysis of T-cell receptor γ gene rearrangement as an adjuvant diagnostic tool in skin biopsies for erythroderma

Abstract

Erythroderma, defined as red skin covering most of the body surface often accompanied or followed by exfoliation, is the clinical manifestation of at least six different underlying etiologies with allergic or irritant contact dermatitis, atopic/asteotic dermatitis, pityriasis rubra pilaris (PRP), psoriasis, and seborrheic dermatitis accounting for the majority of cases. Approximately 10% of cases are due to adverse drug reactions with roughly another 10% due to cutaneous T-cell lymphoma (CTCL), predominantly mycosis fungoides, or leukemia. It is clear from multiple studies that the clinical diagnosis of the underlying entity is often difficult, as these diseases can present in a very similar fashion. A skin biopsy is usually employed in this setting as a diagnostic tool. However, the histopathologic diagnosis of the underlying cause is complicated by the subtlety of the distinguishing histologic features. In this situation, an ancillary technique demonstrating the presence of a monoclonal T-cell proliferation could help to rule in or out CTCL in cases that clinically and histopathologically do not allow a definitive diagnosis. Methods: We retrospectively studied 25 biopsies from sixteen patients who presented to the Stanford Dermatology Clinic with erythroderma. We examined the specimens morphologically and analyzed the gamma chain of the T-cell receptor (TCR- γ) by polymerase chain reaction (PCR) followed by heteroduplex analysis for clonality. We then correlated the results of our PCR and heteroduplex analyses with the patients’ clinical outcomes. Results: Four biopsies, from three patients, contained clonal TCR-γ rearrangements; the four biopsies, all of which were equivocal histologically, correlated to diagnoses of mycosis fungoides (MF) or SÉzary syndrome (SS). Twenty-one biopsies contained polyclonal T-cell populations. Eighteen of these biopsies represent patients with inflammatory dermatoses. Three of these biopsies, all of which were taken from a single patient, correlate to a diagnosis of MF. Conclusion: TCR-γ PCR heteroduplex analysis seems to represent an important adjuvant diagnostic tool that, used in conjunction with histopathology and clinical history, could help to clarify the underlying etiology of erythroderma.