Hodgkin lymphoma

Definitions & Key takeaways

Hodgkin lymphoma is a cancer of the lymphatic system typically arising from B-cells. It is commonly seen in immunodeficient individuals, such as those with HIV, and is usually associated with the Epstein-Barr virus. Symptoms may include fever, night sweats, weight loss, and painless and swollen cervical lymph nodes.

Chapters:

Watch video only

Introduction0:00–0:26

The term Hodgkin lymphoma -can be broken down. Lymph- refers to lymphocytes and oma- refers to a tumor.
So, Hodgkin lymphoma is a tumor derived from lymphocytes - specifically B-cells which mainly reside in lymph nodes. In case you’re wondering, the disease gets its name from the English physician Thomas Hodgkin, who first described these tumors.

Physiology0:26–2:48

B-cell development begins in the bone marrow, which is a primary lymphoid organ. That’s where young precursor B-cells mature into naive B-cells.
The naive B cells then leave the bone marrow and circulate in the blood and eventually settle down in lymph nodes. Humans have hundreds of lymph nodes, scattered throughout the body, and they’re considered secondary lymphoid organs.
Each lymph node has B-cells which group together in follicles in the cortex or outer part of the lymph node, along with T-cells in the paracortex just below the cortex.
B-cells differentiate into plasma cells, which are found in the medulla or center of the lymph nodes. Plasma cells release antibodies or immunoglobulins.
Antibodies bind to pathogens like viruses and bacteria, to help destroy or remove them. Various immune cells, including B-cells have surface proteins or markers that are called CD, short for cluster of differentiation, along with a number - like CD19 or CD21.
In fact, the combination of surface proteins that are on an immune cell works a bit like an ID card. Now, a B cell is activated when it encounters an antigen that binds just perfectly to its surface immunoglobulin.
Some of these activated B-cells mature directly into plasma cells and produce IgM antibodies. Other activated B-cells go to the center of a primary follicle in the lymph node and they differentiate into B-cells called centroblasts and start to quickly proliferate or divide.
These proliferating centroblasts form a germinal center, located in the center of the follicle of the lymph node. These centroblasts have a rearrangement of their immunoglobulin genes, and some of them undergo a class switch where they change from producing IgM antibodies to producing IgG or IgA antibodies.
Within the germinal center, centroblasts mature into centrocytes; and the centrocytes that make antibody with high affinity for the antigen, differentiate into either plasma cells which go to the medulla, or memory B-cells which circulate in the blood and reside in lymph nodes, spleen, and mucosa-associated lymphoid tissue, also called MALT.

Pathology2:48–5:04

In classical Hodgkin lymphoma, a B cell in the germinal center has an abnormal antibody gene rearrangement, and whenever something abnormal happens, the cell’s supposed to go through apoptosis, or programmed cell death.
Instead of apoptosis, though, the cell starts to divide uncontrollably - becoming a neoplastic cell. The exact mechanism of how this happens is unclear, but in some people there seems to be a link with viruses like HIV and Epstein barr virus or EBV.
Generally speaking, lymphomas are grouped into two categories. The first category is Hodgkin lymphomas which tend to spread in a contiguous manner, meaning it spreads to nearby lymph nodes, but rarely involve extranodal sites, and have distinctive Reed-Sternberg cells.
The second category is non-Hodgkin lymphomas which sometimes spread non-contiguously, can involve extranodal sites like the skin, gastrointestinal tract, and the brain, and don’t usually contain Reed-Sternberg cells.
In Hodgkin lymphomas, neoplastic cells are large mononuclear cells called Hodgkin cells or multinucleated cells called Reed-Sternberg cells.
Classically the Reed-Sternberg cells are two cells that are fused together, forming a large cell with two nuclei - which looks like owl eyes.
Neoplastic cells are considered "crippled" because they don't produce antibodies, like a normal B-cell would. In addition, the neoplastic cells are usually surrounded by non-neoplastic inflammatory cells - mostly T cells which are attracted by chemokines.
The neoplastic cells also activate fibroblasts which make collagen, as well as eosinophils. Hodgkin lymphoma includes two major subgroups, the first and more common is classical Hodgkin lymphoma.
In classical Hodgkin lymphoma, the Hodgkin and Reed-Sternberg cells don’t express CD45 or CD20, which are typically seen on B-cells.
In addition, these neoplastic cells do express CD15 and CD30. Classical Hodgkin lymphoma can be further divided into four histologic subtypes based on the composition of the reactive background inflammatory cells and whether fibrosis is present.

Classical Hodgkin lymphoma5:04–6:36

Nodular sclerosis Hodgkin lymphoma is the most common subtype of classical hodgkin lymphoma, which gets its name because neoplastic cells and inflammatory cells get surrounded by collagen from fibroblasts - forming nodules.
Also in nodular sclerosis Hodgkin lymphoma, a unique Reed-Sternberg cell, called a lacunar cell can be seen. When the tissue is fixed in formalin, the cytoplasm shrinks and it makes the nucleus look like it’s sitting in the middle of a lake or lacunae.
The second most common type is mixed cellularity Hodgkin lymphoma. It’s named for the mixed inflammatory background composed of variable numbers of eosinophils, neutrophils, lymphocytes, plasma cells, and histiocytes, that surround the Reed-Sternberg cells.
The third type is lymphocyte-rich Hodgkin lymphoma, and it’s named for having mostly lymphocytes surround the Reed-Sternberg cells.
It generally has the best prognosis of all of the classical Hodgkin lymphoma subtypes. The fourth type is lymphocyte-depleted Hodgkin lymphoma, and it’s the least common type.
It’s named for the lack of reactive lymphocytes and the abundance of Hodgkin and Reed-Sternberg cells. The other major sub-group of Hodgkin lymphoma is nodular lymphocyte predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma6:36–7:19

This type is more common in men. In contrast to classical Hodgkin lymphoma, in this subtype, the abnormal B cells express CD20 and CD45 on their surface, and don’t have CD15 and CD30, and there’s a variant of Reed Sternberg cells called lymphocyte predominant cells.
The lymphocyte predominant cells have a lobulated nucleus that looks like popcorn, so they're called “popcorn cells.” Nodular lymphocyte-predominant Hodgkin lymphoma is called that because of the large groups of lymphocytes that form nodules around the popcorn cells.

Symptoms7:19–7:52

As far as symptoms go, individuals with classical Hodgkin lymphoma usually develop painless cervical lymphadenopathy, and with the nodular sclerosis subtype, \mediastinal lymphadenopathy is common\.
The release of cytokines causes symptoms like fever, drenching night sweats, and weight loss. In contrast, nodular lymphocyte predominant Hodgkin lymphoma is rarely associated with these symptoms and usually only affects only a few cervical lymph nodes.
For diagnosis, identifying Hodgkin lymphoma often begins with imaging studies, like a CT scan, which can help establish the stage of the lymphoma.

Diagnosis7:52–8:05

A lymph node biopsy is required for diagnosis. The treatment of classical Hodgkin lymphoma depends mostly on the extent of lymphoma, or stage, as well as other factors like the age and general health of the individual and other illnesses they may have.

Treatment8:05–8:47

Options include chemotherapy and radiation therapy. In nodular lymphocyte predominant Hodgkin lymphoma, Rituximab can also be used.
Rituximab is a monoclonal antibody that binds CD20 and induces complement-mediated lysis, direct cytotoxicity and apoptosis.
Overall, prognosis for Hodgkin lymphoma is better than that of non-Hodgkin lymphoma. All right, as a quick recap, there are two major types of Hodgkin lymphoma, classical Hodgkin lymphoma and nodular lymphocyte predominant Hodgkin lymphoma.

Review8:47–9:34

Classical Hodgkin lymphoma can be further subdivided into four subtypes classified according to histologic features—nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted hodgkin lymphoma.
Hodgkin cells and Reed-Sternberg cells are neoplastic B-cells that define Hodgkin lymphoma. In nodular sclerosis, the Reed-Sternberg cells are called lacunar cells.
In nodular lymphocyte-predominant Hodgkin lymphoma the Reed-Sternberg variant cells look like popcorn.