Anaplastic Large Cell Lymphoma: The Shifting Sands of Diagnostic Hematopathology

Abstract

Anaplastic large cell lymphoma (ALCL) is a paradigm for the process used to define new disease entities, and provides a model that is applicable to all areas of pathology. ALCL was first recognized based on characteristic histologic features (sinusoidal invasion) and a distinctive immunophenotype (CD30؉). However, neither sinusoidal invasion nor CD30-positivity proved to be entirely specific. Subsequently, a characteristic cytogenetic abnormality was identified, the t(2;5), that led to identification of the genes involved in the translocation (NPM/ALK) and insights into the pathogenesis. Generation of monoclonal antibodies to the aberrantly expressed anaplastic large cell lymphoma kinase (ALK) such as ALK-1 can be used diagnostically, and have led to improved definition of the diagnostic entity with important clinical and prognostic implications. These studies also have clarified the relationship of ALCL to Hodgkin's disease, another lymphoid malignancy associated with CD30 expression. We have learned that the ultimate histologic spectrum of ALCL is both narrower and broader than originally believed. The small cell and lymphohistiocytic variants of ALCL are ALK-positive, and are an accepted part of the disease entity, although the neoplastic cells may appear neither large nor anaplastic. Conversely, most cases of Hodgkin's-like ALCL have proved to be more closely related to true Hodgkin's disease, and are unrelated to ALCL.

Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma

“…5 Expression of CD30 is not specific for systemic large-cell anaplastic lymphoma, and identification of abnormally expressed anaplastic large-cell lymphoma kinase 1 (ALK-1) is favored. 6 However, in skin lymphomas, owing to the usual absence of ALK expression, CD30 is still a valuable marker. 4 Little is known about mechanisms leading to accumulation of large numbers of transformed lymphocytes in skin.…”

Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas: insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma

“…10,11 A derivation from interfollicular CD30 þ T-cell blasts is also discussed. 12 Substantial morphological and immunophenotypical overlap exists between ALK À ALCL and some variants of classical Hodgkin lymphoma (cHL). The neoplastic Hodgkin and Reed-Sternberg (HRS) cells of cHL also express CD30, are commonly derived from germinal centre B cells, but lack expression of most B-cell markers and may express T-cell molecules.…”

An approach to diagnosis of T‐cell lymphoproliferative disorders by flow cytometry

“…T-cell disorders are a heterogeneous group of lymphoid tumors that can present as adenopathy, a mass involving a variety of organs (e.g., skin, gastrointestinal [GI] tract, and liver), or as leukemia (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Morphologically and clinically, they can mimic both benign conditions and nonhematopoietic malignancies.…”

“…Morphologically and clinically, they can mimic both benign conditions and nonhematopoietic malignancies. Therefore, the diagnosis may be difficult and may require the use of multiple sophisticated methodologies (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Flow cytometry plays an important role in diagnosis and classification of malignant T-cell disorders (16,19 -25).…”

“…In contrast to B-cell populations in which analysis of surface immunoglobulins can determine clonality, there are no specific flow cytometric markers of T-cell clonality or of malignant T cells. Therefore, the flow cytometric analysis of T-cell disorders requires a broad panel of markers and experience, as well as correlation with cytomorphology and relevant clinical and laboratory data, especially molecular studies for T-cell receptor gene rearrangement (1)(2)(3)(4)(5)(7)(8)(9)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). We present the most useful criteria for identification of abnormal T-cell populations, including CD45 expression, altered expression of pan-T antigens (CD2, CD3, CD5, CD7, with special attention to dual-parameter analysis of CD3 and CD7), T-cell subset restriction (CD4 with respect to CD8), the presence of additional markers (e.g., T-cell receptors [TCRs], blastic markers CD34 and terminal deoxynuleotidyl transferase [TdT], CD30, CD56, CD57), and cellular changes that are reflected by altered light scatter properties.…”