Anaplastic Large Cell Lymphoma (ALCL)

At a Glance

Anaplastic large cell lymphoma (ALCL) is a type of T cell lymphoma characterized by large, bizarre, pleomorphic neoplastic cells with abundant cytoplasm (referred to as “Hallmark cells”). However, there is a wide morphologic spectrum with a “small cell” pattern also described. In the latest 2008 classification, the World Health Organization (WHO) has now separated ALCL into two distinct categories based on the expression of the anaplastic lymphoma kinase (ALK).

The ALK positive variant is more frequent in childhood and has a more favorable prognosis than the ALK negative (80% vs. 48% 5-year survival). Both can present within lymph nodes or unusual extra notable sites, such as skin, bone, soft tissues, lungs, and liver. Therefore, a biopsy of a mass from any of the sites can render the diagnosis. Rarely, a bone marrow biopsy is the initial diagnostic material, as in cases of fever of unknown origin. However, this diagnosis may be challenging as the neoplastic cells might morphologically mimetic megakaryocytes. Even within lymph nodes, the involvement can be clearly sinusoidal and may mimic anaplastic carcinoma or melanoma in extremely rare cases. Lymphoma cells can be found circulating within the peripheral blood.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The characteristic and essential pathologic diagnostic marker is an immunohistochemical stain for CD30, which is a protein also expressed by the cells of classical Hodgkin lymphoma. Sometimes, distinguishing between ALK negative ALCL and classical Hodgkin lymphoma can be a differential diagnostic challenge, particularly in cases without expression of the T cell markers CD2, CD4, or CD5 (“null ALCL”), aided by PAX-5 (a B cell marker) and/or CD15 expression by classical Hodgkin lymphoma. ALCL cases are also negative for Epstein-Barr virus, in contrast to some cases of classical Hodgkin lymphoma.

Other considerations include nonhematopoietic malignancies, notably embryonal carcinoma, which is strongly CD30 positive. ALK expression is a surrogate for the presence of a chromosomal translocation involving the ALK gene on chromosome 2 with various partners (the vast majority, 85% of cases, involving the nucleophosmin/NPM gene on chromosome 5, t(2;5) (p23;q35)). ALK is not expressed in any normal postnatal tissues. However, rare nonhematopoietic tumors may be positive.

CD 30 positivity also aids in the sometimes difficult distinction between ALK-negative ALCL and peripheral T-cell lymphoma not otherwise specified, which carries a worse prognosis (32% vs. 49% for ALK negative ALCL). Flow cytometry might miss this diagnosis if correlation with the morphologic compression is not readily available as neoplastic cells are often CD3 (the typical T-cell marker) negative and might fall in the monocyte “gate,” as opposed to the typical lymphocyte “gate.” Most flow cytometry laboratories do not include CD 30 within their diagnostic/triage panels.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

A staging bone marrow biopsy is typically performed. Both ALK positive and negative variants frequently show bone marrow involvement at the time of diagnosis. This can be subtle, and a CD 30 immunohistochemical stain is routinely used for detection. A clinical diagnostic challenge is determining if ALK-negative cases diagnosed on a skin biopsy represent limited primary cutaneous involvement versus systemic disease. Therefore, a bone marrow biopsy is important. Involvement of regional lymph nodes does not indicate systemic disease and carries the same favorable prognosis as primary cutaneous tumors.

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