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Table 2 Current diagnostic challenges in T-cell lymphomas

From: MicroRNA expression signature as a biomarker in the diagnosis of nodal T-cell lymphomas

Diagnostic parameter

Supportive features of

T-cell lymphoma

Limitations and Pitfalls

Morphology

â–ª Architectural effacement

â–ª RLH can have architectural alterations (marked interfollicular expansion) that resemble T-cell lymphomas.

â–ª Some T-cell lymphomas exhibit minimal changes to tissue architecture that can be similar to those seen in reactive hyperplasia.

â–ª Cytological atypia

â–ª Cytologic atypia, particularly in nTFHL, may be minimal and display overlapping features with reactive T-cell proliferation.

â–ª On the other hand, certain reactive lymph node conditions may present with increased numbers of large nucleolated (immunoblastic) cells that can be mistaken as neoplastic infiltrate.

Immunophenotype

â–ª Aberrant T-cell immunophenotype, i.e., lost, or reduced expression of T-cell antigens.

â–ª Aberrant pattern of expression of normal physiological markers e.g., CD30, TFH markers (PD1, ICOS, CXCL13) etc.

â–ª Some T-cell lymphomas (particularly nTFHL) may retain full expression of T-cell antigens.

â–ª Difficulty to interpret staining in small biopsy samples.

â–ª Significant inter- and intra-observer variability.

â–ª Quality of lab processing and IHC protocol will significantly affect results.

â–ª A good understanding of protein biology and expression pattern is required for accurate interpretation.

Clonality

â–ª Monoclonal TCRB or TCRG gene rearrangements in T-cell lymphomas.

â–ª Monoclonal TCRB or TCRG rearrangements may be detected in reactive T-cell proliferations, for example in viral infections.

â–ª Conversely, false negativity can occur in some T-cell lymphomas with significant reactive inflammatory background, and in small biopsy samples with low volume of neoplastic T-cells.

  1. *RLH: Reactive lymphoid hyperplasia; nTFHL: nodal T follicular helper cell lymphoma; TFH: T follicular helper; IHC: Immunohistochemistry: TCRB: T cell receptor Beta; TCRG: T cell receptor Gamma