Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations

Abstract

ConclusionsSeverely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30 + lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30 + lymphoproliferations.Key words: systemic and cutaneous CD30 + lymphoproliferations, anaplastic large cell lymphoma, lymphomatoid papulosis, ALCL, LyP, TCR.Citation: Geissinger E, Sadler P, Roth S, Grieb T, Puppe B, Müller N, Reimer P, Vetter-Kauczok CS, Wenzel J, Bonzheim I, Rüdiger T, Müller-Hermelink HK, and Rosenwald A. Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30+ T-cell lymphoproliferations. Haematologica 20010;95(10):1697-1704. doi:10.3324/haematol.2009 This is an open-access paper. Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30 + T-cell lymphoproliferations © F e r r a t a S t o r t i F o u n d a t i o nIntroduction CD30 + T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALCL) as well as primary cutaneous CD30 + T-cell lymphoproliferative disorders. Morphologically, these entities are characterized by the proliferation of highly atypical, anaplastic CD30 + T cells. Despite the frequent detection of clonally rearranged Tcell receptor (TCR) genes, the expression of T-cell-specific antigens in the tumor cells is not consistently detectable. 1 Systemic ALCL comprise approximately 15% of all peripheral T-cell lymphomas (PTCL) in Europe 2 and are divided into anaplastic lymphoma kinase (ALK) positive and negative subgroups (ALK + and ALK -systemic ALCL), whereas primary cutaneous CD30 + T-cell lymphoproliferative disorders represent a spectrum of skin lesions with diverging and in part overlapping clinical and morphological features. CD30 + T-cell lymphoproliferative disorders include primary cutaneous ALCL, lymphomatoid papulosis and so-called borderline lesions, [3][4][5] but even with the knowledge of the clinical presentation and a detailed morphological and immunohistochemical picture it is sometimes difficult, if not impossible, to classify a particular cutaneous lesion correctly.While the transforming properties of ALK over-expression have been clearly demonstrated ,6,7 the transformation mechanisms in ALK -systemic ALCL and primary cutaneous CD30 + T-cell lymphoproliferative disorders are poorly understood. CD30 itself, a cytokine receptor belonging to the tumor necrosis factor receptor superfamily, has been a research focus over the past years, but whether CD30 signaling lea...

T-cell receptor diversity prevents T-cell lymphoma development

“…Marker loss is a common feature in NPM/ALK-induced ALCL. 25,26 Moreover, in a previous study, we also observed a downregulation of mature T-cell markers after immortalization of a mature T-cell clone. 27 To further exclude an immature T-cell contamination in our experimental setting, we transduced OT-I T cells with the immature T-cell proto-oncogene LMO2.…”

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

“…ALCL is a T-cell lymphoma that shows little or no expression of the T-cell receptor and its associated molecules, such as CD3. 26,30 Although the expression of membranous T-cell markers in ALCL is low or undetectable, expression of CD3, CD5 and CD8 was detectable in a subset of ALCL.…”

CD30+ lymphoproliferative disorders

“…8 In this issue of the journal, Geissinger et al expand their previous work and report on the disturbed expression of the TCR/CD3 complex and associated signaling molecules in CD30 + T-cell lymphoproliferations. 9 The analysis was conducted by immunohistochemistry on a large series of tissues comprising 71 cases of systemic ALCL (33 ALKpositive and 38 ALK-negative) and 19 primary cutaneous CD30 + lymphoproliferative disorders (10 cases of primary cutaneous ALCL and 9 of lymphomatoid papulosis) in comparison to 20 cases of PTCL, NOS. They found random losses in various combinations of the TCRa/β and the four CD3 subunits (γ, δ, ε and ζ chains) in most cases of systemic and cutaneous CD30 + lymphoproliferative disorders, contrasting with the homogeneous expression in most cases of PTCL, NOS.…”