Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.
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.
Chen
Michael
M
College of Medicine and Public Health, Ohio State University, Columbus, Ohio, USA.
Deng
April
A
Crowson
A Neil
AN
Srinivasan
Mythily
M
Yearsley
Kurtis H
KH
Jewell
Scott
S
Morrison
Carl
C
Long
Susan
S
Werling
Robert
R
Magro
Cynthia
C
D002999:Clone Cells / Q000502:physiology; D003937:Diagnosis, Differential; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D006801:Humans; D017254:Leukemic Infiltration / Q000175:diagnosis / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology
D016692:Receptors, Antigen, T-Cell, gamma-delta