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A 70-year-old patient comes to the clinic because of night sweats and weight loss. He denies cough, hemoptysis, and shortness of breath. His temperature is 38.2°C (100.8°F), pulse is 90/min, respirations are 16/min, and blood pressure is 120/80 mm Hg. Physical examination shows lymphadenopathy of 2 contiguous anterior cervical lymph nodes. The enlarged lymph nodes are non-tender to palpation. The remainder of the physical examination shows no abnormalities. A biopsy of the one of enlarged lymph nodes is performed, which shows the following (see image below).
Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
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.
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.
The plasma cells settle in the medulla of the lymph node.
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.
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.