Assessment of T-cell Clonality via T-cell Receptor-γ Rearrangements in Cutaneous T-cell–Dominant Infiltrates Using Polymerase Chain Reaction and Single-stranded DNA Conformational Polymorphism Assay

Abstract

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Usefulness of flow cytometry in the diagnosis of mycosis fungoides

“…16 Therefore, this study is the most comprehensive analysis of MF by flow cytometry from skin biopsy specimens and demonstrates the usefulness of flow cytometry for the diagnosis of MF. In all, 11 of the 14 analyzed specimens from patients with lesions suggestive for MF demonstrated a T-cell abnormality by flow cytometry (patients [1][2][3][4][5][6][7][8][9][10][11]. TCR gene rearrangement studies revealed clonally rearranged bands in 10 of the 11 patients in which a phenotypic abnormality was detected, supporting our flow cytometric interpretation.…”

“…Nevertheless, a clonal TCR gene rearrangement is not Sézary syndrome TCR: T-cell receptor detected in approximately 15% to 20% of MF/Sézary syndrome (SS) cases 5 and occasional reactive processes have identifiable rearrangements. [6][7][8] Clinical scoring systems have been suggested in efforts to improve the evaluation and diagnosis of MFs, including the criteria proposed by the International Society for Cutaneous Lymphoma (ISCL), which is based on a combination of clinical, pathologic, molecular, and immunoperoxidase findings. 9 We have also reported a similar system.…”

Mimics of Cutaneous Lymphoma

“…85,86,88,91 Therefore, extreme caution is advised when examining a purpuric eruption, particularly those in which no known cause is suspected clinically or when the clinical presentation is atypical and concerning.…”

Cutaneous T-Cell and NK-Cell Lymphomas

“…15,16 An extremely helpful technique is to compare the TCR pattern at 2 different involved skin sites, with identical gene rearrangements indicative of systemic MF. 17 Among other T-cell neoplasms, CD4 expression and epidermotropism are also features of adult T-cell leukemia/lymphoma (ATLL), in which papular or tumoral skin lesions are present in 50% to 60% of cases.…”