Immunophenotypic Correlation Between Skin Biopsy and Peripheral Blood Findings in Mycosis Fungoides

Abstract

In mycosis fungoides (MF) with blood involvement, T-cell immunophenotypes in skin and blood have not been compared. Our aim was to evaluate T-cell immunophenotypes in skin by immunohistochemical analysis and compare results with flow cytometric (FC) findings in blood. Of 20 patients with MF with blood involvement, the immunophenotype was discrepant in 11 (55%). Compared with FC findings in blood, immunohistochemical analysis of skin samples failed to detect partial deletion of CD2 (5/11 [45%]), CD3 (3/11 [27%]), and CD5 (3/11 [27%]) and overrepresented deletion of CD7 in 2 (18%) of 11 patients. In addition, CD8+ MF was missed by immunohistochemical analysis in 2 (18%) of 11 patients. Identical T-cell populations were demonstrated by T-cell gene polymerase chain reaction in skin and blood in 8 of the 11 patients who had a discrepant immunophenotype. Awareness of the limitations of immunohistochemical analysis of skin samples is of practical value for pathologists interpreting skin biopsies in MF patients. In addition, our findings suggest CD8+ MF to be more common than previously reported.

Flow Cytometric Identification of Immunophenotypically Aberrant T-Cell Clusters on Skin Shave Biopsy Specimens From Patients With Mycosis Fungoides

“…[3][4][5][6] Nevertheless, the utility of immunohistochemistry for the diagnosis of MF has recently been questioned, given the high frequency of similar antigen loss in benign chronic dermatoses and the limited sensitivity to detect immunophenotypic aberrancies in the presence of background reactive T cells. 7,8 Multiparameter flow cytometry (FC) overcomes some of the limitations of immunohistochemical analysis by simultaneously assessing the expression of multiple antigens on individual cells in a high-throughput platform. Indeed, FC has an established role in the identification of neoplastic T cells in peripheral blood from patients with advanced CTCL, 9 largely replacing the less reliable morphologic quantitation of atypical lymphoid cells on peripheral blood smears.…”

Tumor microenvironment in mycosis fungoides and Sézary syndrome

“…This is supported by the classic histopathologic feature of 'Pautrier's microabscesses', a diagnostic hallmark of mycosis fungoides that consists of Langerhans cells surrounded by malignant cells. CD1a is expressed in both Langerhans cells and dermal dendritic cells, and a high expression of CD1a has been seen in skin samples of patients with mycosis fungoides [13]. There is upregulation of antigen-presenting cell ligands such as B7, CD40, as well as their costimulatory molecules CD28 and CD40 l in mycosis fungoides lesions supporting an inflammatory milieu.…”

“…Sézary syndrome consists of CD4 þ atypical lymphocytes with loss of CD5, CD7, and/or CD26 which circulate in the peripheral blood and frequently invade the skin and lymph nodes causing erythroderma and lymphadenopathy [3 13]. This malignant phenotype is presumed to arise from a background of chronic antigenic stimulation with underlying cytogenetic abnormalities that leads to clonal proliferation and accumulation of malignant T cells that manifest as mycosis fungoides and Sézary syndrome [1 && ].…”

Atypical lymphoid proliferations: the pathologist’s viewpoint

“…Also, other pan-T-cell markers (CD2, CD5 and CD7) are usually expressed by AtLP. However, deficiency (less than 50% loss) or complete loss of expression of pan-T-cell markers (CD2, CD5 and CD7) favors the diagnosis of lymphoma rather than AtLP [71][72][73][74]. CD7 deficiency can be seen in benign cutaneous lymphoid infiltrate and therefore this criterion in isolation is not discriminatory.…”

“…CD7 deficiency can be seen in benign cutaneous lymphoid infiltrate and therefore this criterion in isolation is not discriminatory. However, when used together with other immunophenotypic (loss of other pan T-cell markers, discordance of dermal and epidermal expression of CD5) and molecular (such as T-cell receptor gene rearrangements) features, CD7 deficiency or loss can be useful [71,73,74]. Also, double-positive phenotype CD4 + /CD8 + or double-negative CD4/CD8-phenotype favors the diagnosis of T-cell lymphomas [71,73,74].…”