LabMed

Mixed Cellularity Classical Hodgkin Lymphoma (MCCHL)

At a Glance

Mixed cellularity classical Hodgkin lymphoma (MCCHL) is a histologic subtype of classical Hodgkin lymphoma (CHL), comprising about 20-25% of all CHL cases. It is seen more often in older adults (older than 55 years of age), in males, and in immunosuppressed patients, as compared with the nodular sclerosis subtype of CHL. It is also seen more frequently in children (younger than 14 years of age) but is less frequent in adolescents and young adults. MCCHL is a more common subtype of CHL in developing countries compared to nodular sclerosis CHL.

Patients with MCCHL present most often with peripheral lymphadenopathy, whereas mediastinal involvement is less common. Presentation with lymphadenopathy below the diaphragm and splenomegaly are more common than in other types of CHL, particularly in older patients. About one-half of patients have systemic B symptoms.

MCCHL may occur as a subtype of post-transplant lymphoproliferative disorder (PTLD) in patients after solid organ or bone marrow transplantation; MCCHL PTLD may exhibit a long latency post-transplant, even several years. Unlike MCCHL in immunocompetent patients, which is usually nodal-based, about one-half of MCCHL PTLD cases may present in extranodal locations, such as the lung, liver, or tonsil.

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

A biopsy of involved tissue should confirm a clinical suspicion of MCCHL. (Table 1)

Table 1.

Test Results Indicative of the Disorder
Tissue Biopsy Immunohistochemistry on Tissue Biopsy
Presence of Reed-Sternberg cells and mononuclear variants in a mixed inflammatory background lacking collagen sclerosis.{{3565_MCCH Reed-Sternberg cells are CD30+, CD45-, usually CD15+, and PAX5+, but usually negative for other B-cell markers.

After diagnosis, the disease should be staged (see chapter on Classical Hodgkin Lymphoma).

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?

As with all types of CHL, a fine needle aspiration, limited tissue biopsy, such as a core biopsy, or biopsy of a small, partially involved node may yield false-negative results in MCCHL.

What Lab Results Are Absolutely Confirmatory?

A biopsy of involved tissue confirms a diagnosis of MCCHL.

The Reed-Sternberg cells of MCCHL resemble those of other CHL subtypes and are usually frequent. The inflammatory background in MCCHL characteristically includes numerous eosinophils, as well as lymphocytes, histiocytes, plasma cells, and neutrophils in varying proportions. There may be some background fibrosis, but dense collagenous fibrous bands are absent. The background lymphocytes are mostly CD3+ T-cells with CD4+ cells predominating over CD8+ cells.

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

In about 75% of MCCHL cases, Epstein-Barr virus (EBV) is found in the Reed-Sternberg cells by EBV-encoded RNA (EBER) in situ hybridization or EBV latent membrane protein-1 (LMP1) immunostaining. This incidence of EBV positivity in MCCHL is higher than that observed in nodular sclerosis CHL.

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?

The mixed inflammatory background in MCCHL may mimic an inflammatory process, such as an infection. For example, cases with numerous neutrophils may resemble an abscess if the diagnostic Reed-Sternberg cells are missed. The frequently EBV-positive Reed-Sternberg cells may suggest a diagnosis of infectious mononucleosis. Conversely, lymph node biopsies from patients with acute infectious mononucleosis may contain Reed-Sternberg-like cells in a mixed inflammatory background, leading to an erroneous diagnosis as MCCHL. Attention to the clinical picture (usually a young patient in infectious mononucleosis versus an older patient population in MCCHL) and other laboratory tests, such as circulating atypical lymphocytes and positive IgM EBV titers in acute infectious mononucleosis, can help guide the correct diagnosis.

Granulomas may be present in tissue involved by MCCHL and can be seen in non-neoplastic tissues in patients with MCCHL (for example, in an enlarged but uninvolved spleen or in bone marrow). The presence of granulomas may distract from the diagnosis, leading to an erroneous diagnosis of sarcoidosis or an infection.

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