Phenotypic Variability in Primary Cutaneous Anaplastic Large T-cell Lymphoma

Abstract

Primary cutaneous anaplastic large T-cell lymphoma (pcALCL) is a well-defined entity characterized by neoplastic cells expressing CD30, CD2, CD3, CD4, and CD5. Cases with different phenotype have been reported, including variable loss of CD2, CD3, and CD5, and expression of cytotoxic phenotype (CD8⁺) and/or of cytotoxic proteins. Aberrant phenotypes represent a diagnostic pitfall and may be the cause of misdiagnoses. We reviewed 35 cases of pcALCL (M:F = 19:16; mean age, 50.8 years; range, 14-92 years), to better characterize the immunophenotypic spectrum of the disease. Twelve cases (34%) had a T-helper phenotype (CD4⁺/CD8⁻), and TIA-1 was positive in 5 of 8 stained cases. Six cases (18%) had a T-cytotoxic phenotype (CD4⁻/CD8⁺) and were also positive for TIA-1. Positivity for both CD4 and CD8 was observed in 7 cases (20%), 4 of which were stained for TIA-1 and found to be positive, whereas both CD4 and CD8 were negative in 9 cases (26%, only 1/8 tested cases being TIA-1 positive). CD2 was positive in 21 of 27 tested cases (78%), CD3 in 21 of 34 cases (62%), and CD5 in 15 of 31 cases (48%). Interestingly, 11 cases (31%) showed a profoundly aberrant phenotype lacking simultaneously several T-cell markers. Our data allow a better characterization of pcALCL with aberrant phenotypes, showing the remarkable variability in expression of different markers.

Assessment of diagnostic criteria between primary cutaneous anaplastic large-cell lymphoma and CD30-rich transformed mycosis fungoides; a study of 66 cases

“…This is consistent with a recent study showing a frequent aberrant phenotype in cALCL. 47 cALCL and CD30 + LPD are known to express cytotoxic markers such as TiA1, perforin and granzyme with various frequencies depending on the positivity cut-off chosen for IHC staining. 19,20 Cytotoxic markers are sometimes expressed in MF and the cytotoxic phenotype has been suspected to be associated with worse prognosis and transformation.…”

Characterization of Primary Cutaneous CD8+/CD30+ Lymphoproliferative Disorders

“…The large cell portion comprised more than 50% of the infiltrate in both CD8 + LyP (9 of 15 cases) and PCALCL; however, it was more often found in cases of CD8 + PCALCL (11 of 11 cases, P = 0.0338). More cases of CD8 + PCALCL had 19 3 ALCL Cardoso et al 8 1 Lyp De Souza et al 9 11 LyP Fukunaga et al 20 1 ALCL Gelfand et al 21 1 ALCL Hellman et al 10 1 LyP Kadin et al 11 1 LyP Kikuchi et al 22 2 ALCL Magro et al 12 4 LyP Massone and Cerroni 23 6 ALCL McQuitty et al 14 26 8 ALCL, 18 LyP Plaza et al 13 20 8 ALCL, 12 LyP Plaza et al 25 1 ALCL Saggini et al 15 9 LyP Shimizu et al 26 1 ALCL Sim and Kim 16 1 LyP Wen et al 17 1 LyP Wu and Tsai 18 1 LyP Xu et al 27 There were no differences with regard to ulceration (P = 0.8728), spongiosis (P = 0.8578), parakeratosis (P = 0.5342), interface change (P = 0.4083), or pseudoepitheliomatous hyperplasia (P = 0.2143). Pseudoepitheliomatous hyperplasia was not a common feature in either CD8 + LyP or PCALCL.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][25][26][27] Clinical characteristics are shown in Table 3. Patients with CD8 + LyP were significantly younger than patients with PCALCL (mean = 39.14 vs. 54.12 years, P = 0.0013).…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18] LyP type D was first described by Saggini et al, 15 demonstrating features of dense infiltrates of medium-sized, pleomorphic epidermotropic lymphocytes in addition to the cytotoxic phenotype. 15 Cutaneous PCALCL with a CD8 + phenotype has also been described, 6,[19][20][21][22][23] which presents a particularly difficult diagnostic challenge since differentiation from primary cutaneous aggressive epidermotropic CD8 + cytotoxic T-cell lymphoma (CTCL) and CD8 + gamma/delta and natural killer/T-cell lymphoma is key to management. 13,14 Furthermore, the term LyP "type E" has also been proposed to describe angiocentric and angiodestructive patterns in LyP.…”

Primär kutane CD30+ lymphoproliferative Erkrankungen

“…Ältere Berichte geben einen vorherrschenden CD4 + /CD8 – ‐Phänotyp an. Dagegen weisen neuere Publikationen auf eine große phänotypische Variabilität bei der CD4 und der CD8 Expression hin, die in cALCLs entweder vorhanden oder abwesend sein kann . In cALCL‐Läsionen wird oft ein T‐Zell Rezeptor Rearrangement beobachtet und die Einzelzell‐PCR weist auf eine Mehrheit an monoklonalen großen CD30 + ‐Zellen hin .…”