Approach to lymphoma: Clinical sciences

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Introduction0:00–0:46

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.

Unstable0:46–1:11

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.

Stable - H&P1:11–2:01

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.

Imaging and Biopsy2:01–2:33

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.

Consider alternative diagnoses2:33–2:46

Diagnose Lymphoma2:46–2:51

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.

Assess Type2:51–2:55

Hodgkin Lymphoma2:55–4:21

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!

Non-Hodgkin Lymphoma4:21–5:14

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.

B-Cell Lymphomas/ Assess Subtype5:14–5:41

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

Burkitt Lymphoma5:41–6:34

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.
Next, the biopsy will reveal a high degree of cell replication, and a starry sky appearance, referring to a background of lymphoma cells interspersed with macrophages filled with debris.
Finally, if the cytogenetic testing shows translocation of chromosomes 8 and 14, diagnose Burkitt lymphoma, which is an aggressive form of Non-Hodgkin lymphoma.

Diffuse Large B-cell Lymphoma6:34–7:06

Alright, now let’s move on to diffuse large B-cell lymphoma. These patients typically report a rapidly enlarging mass, while their physical exam reveals a mass or enlarged lymph nodes in the neck region.
The biopsy reveals large, atypical B-cells with prominent nucleoli and basophilic cytoplasm. Additionally, you’ll notice a high degree of replication and loss of normal nodal architecture.
With these findings, diagnose diffuse large B-cell lymphoma, which is another aggressive form of Non-Hodgkin lymphoma. Next up is follicular lymphoma!

Follicular Lymphoma7:06–7:55

In this case, the history will reveal waxing and waning lymphadenopathy, meaning the size of lymph nodes will fluctuate over time.
The physical exam might reveal a mass or enlarged lymph nodes in unusual sites, such as the epitrochlear lymph node chain of the upper arms.
The biopsy will reveal neoplastic centrocytes and centroblasts, which are B-cells located in the germinal center of the lymph nodes, organized in a follicular, or nodular, growth pattern.
Additionally, you’ll notice a low degree of replication. Finally, if the cytogenetic testing reveals translocation of chromosomes 14 and 18, and an overexpression of BCL-2, diagnose follicular lymphoma.
Next up is mucosa-associated lymphoid tissue, or MALT lymphoma, which is also called extranodal marginal zone lymphoma. These tumors arise outside the lymph nodes, so the symptoms depend on location.

MALT Lymphoma7:55–8:43

However, most patients will report epigastric pain or discomfort. If the biopsy reveals a polymorphous infiltrate of small B cells, diagnose MALT lymphoma.
Now, here is a high-yield fact! MALT lymphoma is thought to be caused by chronic inflammation from an infection, most commonly H.
pylori, or autoimmune diseases like Sjögren disease. The stomach is by far the most common site of origin, while less common locations include the small intestine, skin, lung, and eye.
Finally, let’s take a look at mantle cell lymphoma. In this case, patients are typically older biologically male individuals who report widespread lymph node enlargement.

Mantle Cell Lymphoma8:43–9:20

The physical exam might reveal splenomegaly, while the biopsy will show monomorphic small or intermediate lymphoid cells with irregular nuclei.
Additionally, there will be a diffuse or vaguely nodular growth pattern. If the cytogenetic testing reveals a translocation of chromosomes 11 and 14, with an overexpression of the cell growth-stimulating protein cyclin D1, diagnose mantle cell lymphoma.
Alright, now let’s switch gears and take a look at lymphomas where the immunophenotyping is CD3 and CD4 positive. In this case, your patient has mature T-cell lymphoma, which covers several different types, including cutaneous T-cell lymphomas and adult T-cell leukemia/lymphoma.

T-Cell Lymphoma9:20–9:37

Let's start with cutaneous T-cell lymphomas, which are further subdivided into mycosis fungoides and Sézary syndrome! As the name suggests, this subtype primarily affects the skin.

Cutaneous T-cell Lymphoma9:37–10:42

Patients usually present with patchy or plaque-like, scaly skin lesions. The physical exam might show erythroderma, which is a generalized erythematous, pruritic rash; and hepatosplenomegaly.
Next, check the skin biopsy, which will show a band-like infiltrate of small, atypical helper T-cells with cerebriform nuclei, meaning an irregular shape with lots of folds.
With these findings, diagnose cutaneous T-cell lymphoma. Now, to tell whether it is Sézary syndrome or mycosis fungoides, obtain a peripheral blood smear.
If the peripheral smear reveals neoplastic lymphocytes with cerebriform nuclei in the circulation, also known as Sézary cells, diagnose Sézary syndrome.
On the flip side, if Sézary cells are absent, diagnose mycosis fungoides. Finally, let's look at adult T-cell leukemia/lymphoma!

Adult T-cell Leukemia/Lymphoma10:42–11:46

In this case, your patient will present with widespread lymph node enlargement, which is often accompanied by bone pain and skin lesions.
During the physical exam, your patient will show generalized lymphadenopathy and hepatosplenomegaly. To confirm the diagnosis, check the biopsy, which will show lymphocytes with flower-like nuclei.
With these findings, diagnose adult T-cell leukemia/lymphoma. Okay, here’s a clinical pearl to keep in mind!
Adult T-cell leukemia/lymphoma is uniformly caused by chronic infection with the human T-cell lymphotropic virus type 1, or HTLV-1 for short, which is spread through bodily fluids.
This type of lymphoma is an overlap between leukemia and lymphoma, and usually presents with both lymphadenopathy as well as blood and bone marrow involvement.
It has a rapidly progressive course and can cause lytic bone lesions, hypercalcemia, and opportunistic infections. Alright, as a quick recap… Lymphomas are a group of hematologic malignancies that primarily affect the lymph nodes, but can also involve extranodal sites such as the skin and gastrointestinal tract including the liver, and spleen.

Review11:46–12:39

Based on the presence of Reed-Sternberg cells on biopsy, there are two major categories of lymphomas. If the biopsy reveals Reed-Sternberg cells, diagnose Hodgkin lymphomas.
However, if there are no Reed-Sternberg cells, diagnose non-Hodgkin lymphomas. Non-Hodgkin lymphomas can be further subdivided into mature B-cell lymphoma, which includes Burkitt lymphoma, Diffuse large B-cell lymphoma, follicular lymphoma, MALT lymphoma, and mantle cell lymphoma; and mature T-cell lymphoma, which includes cutaneous T-cell lymphoma and adult T-cell lymphoma/leukemia.
Approach to lymphoma: Video, Causes, and Symptoms | Osmosis