Approach to lymphoma: Clinical sciences

Lymphoma refers to a group of hematologic malignancies characterized by the abnormal proliferation of clonal lymphocytes. These lymphocytes can infiltrate various lymph nodes, leading to lymph node enlargement or masses. They can also infiltrate extranodal sites, such as the skin and the gastrointestinal tract including the liver, and spleen, giving rise to extranodal signs and symptoms, like skin ulcers, hepatosplenomegaly, and gastrointestinal bleeding. Based on the clinical features and biopsy results, lymphomas can be divided into two major categories which include Hodgkin and non-Hodgkin lymphomas.

Now, if your patient presents with a chief concern suggesting lymphoma, first perform an ABCDE assessment to determine if they are unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. If needed, provide supplemental oxygen.

Now, let’s go back to the ABCDE assessment and discuss stable patients. First, obtain a focused history and physical examination. Your patient will typically report painless swelling or a mass, possibly in combination with abdominal pain or discomfort. Additionally, they might report B symptoms, which include fever, night sweats, and unexplained weight loss. History could also reveal risk factors for lymphoma, such as autoimmune conditions, like systemic lupus erythematosus; HIV or EBV infections; use of immunosuppressive medications; or a prior history of chemotherapy or radiation therapy. Additionally, the physical exam often reveals nontender peripheral lymphadenopathy, and sometimes hepatosplenomegaly, as well as a palpable mass.

With these findings, consider lymphoma, and order imaging depending on the location of the suspected mass or lymphadenopathy. These might include chest X-ray, ultrasound, or CT scan. If the imaging reveals a mass or enlarged lymph nodes, biopsy them using either a fine needle aspiration, core needle biopsy, or excisional biopsy. Keep in mind that an excisional biopsy is by far the preferred method, as the architecture of the lymph node or mass is maintained, optimizing the chance of identifying the type of lymphoma.

Now, if the biopsy doesn't reveal neoplastic lymphocytes, consider an alternative diagnosis, such as metastatic solid organ carcinoma, or an inflammatory or autoimmune condition.

On the other hand, if the biopsy shows neoplastic lymphocytes, diagnose lymphoma.

Now, once you diagnose lymphoma, your next step is to assess the type.

Let’s start with Hodgkin lymphoma! Most patients are either in their twenties or more than sixty years old. Patients will usually present with enlarged lymph nodes which become painful when they consume alcohol. In addition, they might have a prior history of being diagnosed with an EBV infection. The physical exam may reveal localized, non-tender peripheral lymphadenopathy, mainly in the cervical, supraclavicular, or axillary regions. Keep in mind that this category of lymphomas tends to spread in a contiguous manner, meaning it spreads to nearby lymph nodes, but rarely involves extranodal sites.

Next, the imaging may show mediastinal lymphadenopathy. Finally, if the biopsy reveals Reed-Sternberg cells, which are large binucleated B cells with an owl’s eyes appearance, diagnose Hodgkin lymphoma. Once you diagnose Hodgkin lymphoma, your next step is to assess surface markers on lymphocytes using immunophenotyping! If immunophenotyping reveals a lymphoma that is CD15 and CD30 positive, and CD20 negative, diagnose Classic Hodgkin lymphoma! On the flip side, if lymphocytes are CD15 and CD30 negative, but CD20 positive, diagnose nodular lymphocyte-predominant Hodgkin lymphoma!

Now, switching gears and moving on to non-Hodgkin lymphoma. This category of lymphoma tends to spread non-contiguously, and can affect extranodal sites like the gastrointestinal tract, or the skin. For example, if the gastrointestinal tract is affected, your patient may experience gastrointestinal bleeding, such as hematochezia. If lymphoma affects the skin, they might also report the presence of ulcers or plaques. Additionally, history might reveal immunosuppressive conditions, such as HIV infection, being an organ transplant recipient, or a history of chemotherapy or radiation therapy. Next, the physical exam might reveal widespread nontender lymphadenopathy or masses. Finally, if the biopsy shows the absence of Reed-Sternberg cells, diagnose non-Hodgkin lymphoma.

Once you diagnose non-Hodgkin lymphoma, your next step is to obtain immunophenotyping and cytogenetics. If lymphocytes are CD19 and CD20 positive, diagnose mature B-cell lymphoma.

Mature B-cell lymphoma covers several different types, including Burkitt lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, MALT lymphoma, and mantle cell lymphoma.

Let’s start with Burkitt lymphoma! These patients will generally present with a rapidly enlarging mass and a history of prior EBV or HIV infection. The physical exam may reveal a visible or palpable mass, usually affecting the jaw or facial bones, which is an endemic form typically seen in Africa. However, in the US and Europe, this type of lymphoma is typically associated with a palpable abdominal mass, often with abdominal distention and ascites.