Weatherly's Woes - Lymphoma

LYMPHOMA

Lymphoma is white blood cell cancer that starts in the lymph nodes. The patient usually presents to their doctor with painless lymphadenopathy. Lymphomas are always of the lymphoid lineage.

The key strategy you should use when studying leukemias and lymphomas is to stick to the buzzwords. That’s because these cancers are much too complicated. The science around them is evolving rapidly. If you try to do independent research on them, you’ll fall down a very deep rabbit hole. The boards know this, and they are almost exclusively going to ask you questions with buzzwords. Specifically focus on translocations (like t(9;22)), Auer rods, Multiple Myeloma and Reed-Sternberg cells. Treatments are generally low yield, with the exception of ATRA for AML and Imatinib for CML.

The next big picture point I’d like to make is that you should learn the layout of a lymph node. The different lymphomas will affect different parts of the nodes, and test makers like to hit you on that.

HODGKIN LYMPHOMA

Hodgkin Lymphoma is a cancer of lymphocytes that makes tumors inside of lymph nodes. The thing with Hodgkins is that the tumors are weird. They aren’t large uniform masses of cancer cells. There are rare isolated cancer cells called Reed-Sternberg Cells (RSCs). RSCs secrete cytokines, which attract inflammatory cells that create the bulk of the tumor. The cytokines released by RSCs can cause “B symptoms.” B symptoms refers to the symptoms in our General ROS (fever, chills, night sweats, weight loss). The patient may present with painless localized lymphadenopathy.

HL begins in a single lymph node. Then it spreads to its neighboring nodes. It spreads from lymph node to lymph node. Non-HL spreads through the blood, but HL spreads through lymph. The treatment is surgical removal of the affected lymph nodes, followed by chemo and radiation. 5 year survival is about 90%. The relatively long survival in Hodgkin disease means patients have time to develop second malignancies (most commonly acute myeloid leukemia) related to chemotherapy and radiation. These are very hard to cure.

Reed-Sternberg Cells (High-Yield)

The characteristic cell in Hodgkin disease is a bizarre cell called the Reed-Sternbern Cell (RSC). Hodgkin is a strange disease, because when you look at a lymph node under the microscope, only about 1 to 2% of the cells you see are cancerous! You usually have to hunt around a bit to find RSCs! They are sitting in a sea of non-cancerous WBCs (like eosinophils, plasma cells, and histiocytes). The morphology of the RSC is very unusual. It’s a very very large cell, and it has two or more nuclei (owl-eyes) with surrounding, clear “halos,” big nucleoli (as big as the adjacent normal lymphocytes!), and abundant cytoplasm. For a long time, nobody knew what the heck kind of cell it was (hence the name “Hodgkin disease” instead of “Hodgkin lymphoma”). Even now, its exact origin is unknown, but the current consensus is that it is a lymphoid cell of some type, probably a bizarro B cell. RSCs or variants are present in all cases of Hodgkin disease. They are CD15+ and CD30+.

Subtypes of Hodgkin Lymphoma (Low-Yield)

The RSC is seen in varying frequencies in the different subtypes of Hodgkin disease. Some subtypes have classic RSCs in relative abundance; others have variants of the RSC. The four subtypes, discussed below, are:

Nodular Sclerosis (70%) - This type of Hodgkin disease has a special RSC variant called the lacunar cell. It’s called a lacunar cell because formalin fixation makes the cytoplasm retract, and the cell appears to be sitting in a little space, or lacuna. Classic RSCs are rare in this type. Collagen bands divide lymph node tissue into nodules (hence, "nodular sclerosis"). Enlarging neck+mediastinal LAD in a young adult female.
Lymphocyte-Rich - tons of lymphocytes in the tumor. Best prognosis
Lymphocyte-Depleted - few lymphocytes in the tumor. Worst prognosis. Seen in AIDS and the elderly
Mixed-Cellularity - a wide variety of WBCs seen in the tumor (especially eosinophils)

Reed-Sternberg Cell

RS CELLS ARE HIGH YIELD

Here is a small discussion on lymphadenopathy (LAD), or swollen lymph nodes.

Is it painful? Painful lymphadenopathy is actually a good sign. It pretty much rules out cancer! It usually suggests an acute infection (e.g., strep throat). The pain is caused by inflammation, as inflammation sensitizes those pesky nociceptors. Painless lymphadenopathy is a terrible sign. It suggests cancer or a weird chronic autoimmune disease.

Is it generalized or local? Generalized LAD is less common than localized LAD. It can be seen in cancers of the blood, autoimmune disorders and sometimes with viral illnesses. Local LAD is much more common. Any nearby inflammatory or cancerous process may be causing it.

Where is it? Anterior cervical lymphadenopathy is reassuring. Minor ENT infections like the common cold cause anterior cervical lymphadenopathy. Posterior cervical lymphadenopathy is a common finding with Mono. Supraclavicular lymphadenopathy is an ominous sign. In adults, the presence of supraclavicular lymphadenopathy is reasonably specific for cancer. There are many many lymph nodes, but most of them are low-yield.

NON-HODGKIN LYMPHOMA (B-CELLS)

BURKITT LYMPHOMA

Burkitt cells contain lots of little lipid droplets. Nobody knows why, but you have to be able to recognize it on an image. As Burkitt cells turnover, the lipid droplets are swept up by macrophages, which eventually swell into big white foam cells. The second image that you have to know is a zoomed-out view called the “starry sky.” The purple-blue Burkitt cells represent the night sky, and the fatty white macrophages represent stars. Burkitt Lymphoma is caused by a smoldering Epstein Barr Virus (EBV). There is an African variant that causes jaw tumors, and an American variant that causes belly tumors.

Burkitt Cells with lipid droplets

Starry Night

FOLLICULAR LYMPHOMA

Follicular Lymphoma obliterates the architecture of the lymph node, replacing it with lots of Follicles. Follicular Lymphoma is also unique because it causes lymphadenopathy that waxes and wanes.

NON-HODGKIN LYMPHOMA (T-CELL)

Non-Hodgkin Lymphoma (NHL) refers to the many lymphomas which aren’t Hodgkin Lymphoma. 15% of NHL’s are cancers of T cells. T cell lymphomas cause rashes, and have funny looking nuclei.

ADULT T-CELL LYMPHOMA causes a skin rash. The nuclei are shaped like flowers. It’s usually caused by a virus with the convenient name of Helper T-cell Lymph Virus (HTLV-1). HTLV-1 spreads through IV drug use, and is common in Japan / Caribbean (T-cell in Tokyo / Trinidad). Also causes lytic bone lesions.

MYCOSIS FUNGOIDES causes a nasty skin condition. Patients have skin plaques that resemble eczema (or a fungal rash,which is how it earned its name), but in advanced cases will look like unsightly mushroom-shaped lumps. On histology, the tumor cells clump up in little balls (Pautrier microabscesses) that tuck into the dermis underneath the epithelium. The nucleus looks like a little human brain (cerebriform nuclei). Prognosis is good. When it does turn into a whopping lymphoma, the disease is sometimes called Sezary Syndrome. Fun fact, Mycosis Fungoides means “mushroom mushroom.”

Pautrier Microabscess

Cerebriform nuclei