Understanding Extranodal Lymphoma

Although lymphomas are all cancers that affect the lymphocytes—a type of white blood cell—sometimes that is where the similarity ends. There are many different types and subtypes of lymphoma. The two main categories are Hodgkin’s lymphoma, or HL, and non-Hodgkin’s lymphoma, or NHL. The majority of both NHL and HL are nodal lymphomas, meaning they originate in the lymph nodes. It’s possible, however, for lymphomas to arise almost anywhere.

Primary Extranodal Lymphoma

When lymphoma is believed to have originated outside the lymph nodes, it’s called extranodal lymphoma, or more precisely, primary extranodal lymphoma. At times, it can be difficult to pinpoint where in the body a lymphoma began. In these cases, doctors may follow a more approximate definition: If the lymphoma at one time had its major tumor mass—its most obvious bulk—in an extranodal site, then it may be considered an extranodal lymphoma.

Important Differences

Of the lymphomas that start in the lymph nodes, or nodal lymphomas, almost all can have extranodal involvement—that is, they can spread to extranodal sites. A lymphoma that spreads to other organs from the lymph nodes is NOT considered a primary extranodal lymphoma. In order to be primary extranodal, the lymphoma has to have originated outside the lymph nodes.

Overview

Primary extranodal lymphomas are much more common in NHL than in Hodgkin’s lymphoma. Up to 33% of all NHL is considered primary extranodal lymphoma, while in HL, primary extranodal disease is thought rarer.

The most frequent site of primary extranodal lymphoma is in the gastrointestinal tract, and almost all of these are NHL. The next most frequent site after the GI tract is the skin. However, when the NHL starts only in the skin, it's called a skin lymphoma, or cutaneous lymphoma.

Extranodal lymphoma can also arise in the lymphoid tissue of the spleen, bone marrow, thymus, tonsils, and adenoids—small patches of tonsil-like tissue hidden up where the nasal passages meet the throat.

Immune or lymphoid cells in the stomach, lung, in structures around the eyes, in the thyroid gland, salivary glands, and small intestine can also give rise to primary lymphomas. Lymphomas in these areas include the ‘marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue,’ or MZBCL of MALT, for short.

Primary lymphomas of the nose and throat include MZBCL of MALT, diffuse large B-cell lymphoma or DLBCL, and natural killer/T-cell lymphomas.

Primary lymphomas can affect the testes in men and are called primary testicular lymphomas. Lymphoma in the brain, or CNS lymphoma, may also be primary. While primary extranodal lymphoma of the brain and testes has been associated with harder-to-treat disease, recent studies have shown that treatment specially tailored to these sites may result in significant improvements especially for testicular lymphoma. 

Primary extranodal follicular lymphomas that aren’t skin lymphomas occur rather infrequently. Primary bone lymphoma is a rare condition where the lymphoma starts in a bone.

Primary cardiac lymphoma is one of the rarest tumors of the heart. Primary cardiac lymphoma is thought to compose just 1.3% of all cardiac tumors and only 0.5% of all extranodal lymphomas. When it does occur, the most common type of this tumor is diffuse large B cell lymphoma, and usually, the right atrium and right ventricle are involved.

One observation of primary extranodal lymphomas, in general, is that they increased dramatically with the emergence of HIV and AIDS.

Prognosis of Primary Extranodal Lymphoma

The fact that a lymphoma is a primary extranodal lymphoma may be a factor in the treatment plan and prognosis, but other factors may be equally important or of greater importance. The lymphoma subtype, the B cell or T cell type, and the primary organ or tissue of origin can all be important prognostic factors.

Prognosis of Extranodal Involvement

Almost all nodal lymphomas can spread to extranodal sites, but in these cases, they are not considered primary extranodal lymphomas.

In NHL, the most effective treatment plans depend on a number of factors, and extranodal involvement may be one of them. Sometimes a lymphoma that is confined to the lymph nodes is more treatable and has a more favorable prognosis than lymphoma that has spread outside of the lymph nodes. However, the wide variety of possibilities for extranodal primary NHL–along with many other factors that influence treatments and outcomes—means that the treatment plan and prognoses can be highly individual.

In some cases, extranodal involvement is more indicative of advanced disease. In Hodgkin’s disease, for instance, extranodal involvement—except in the spleen and thymus—indicates stage IV Hodgkin disease. Even late-stage Hodgkin's disease is treatable, however, and sometimes can be cured.