Hodgkin Lymphoma: Pathogenesis, Clinical Features, and Modern Therapeutics

So, Hodgkin lymphoma—this one’s a bit odd. It’s not the most common cancer around (only about 10% of lymphomas fall under this type), but doctors have studied it a lot. It’s kind of become a success story in oncology. That’s mostly because, for whatever reason, it tends to respond better to treatment than a lot of other cancers. Even so, it’s got a strange personality. The key cell here, Reed-Sternberg—sometimes just called RS cells—are these massive, weird-looking things with multiple nuclei. You wouldn’t miss one under a microscope.

The strange part is, RS cells come from regular old B-cells. You know, the immune ones that are supposed to fight infections. But something in the genetic machinery flips, and they lose their ability to do any of that. Instead, they start growing, sticking around when they shouldn’t, and recruiting other cells to help. Not intentionally of course, but they sort of create a mini ecosystem that helps them survive. And while they technically “are” B-cells, they don’t act like it at all. It’s kind of like a firefighter starting fires instead of putting them out.

Part of the reason they don’t die off like they should is because of this molecular thing called NF-κB. It’s a signaling pathway that, in normal cells, turns on when you need to respond to damage or inflammation. But in RS cells, the pathway is constantly switched on. It just keeps telling the cell, “Yep, everything’s fine, keep going.” So instead of dying off like malfunctioning cells usually do, they stick around and divide. That’s not great.

Now, to make things messier, Epstein-Barr virus—EBV—shows up in about 40 to 50% of Hodgkin lymphoma cases. That’s the same virus that causes infectious mononucleosis, but here, it plays a more sinister role. It produces a protein called LMP1 that mimics the NF-κB pathway. It’s like faking the body’s security clearance. So these already weird RS cells get an extra layer of protection, making them even harder to kill.

Usually, people first notice HL because of swollen lymph nodes. They’re not painful, which makes them easier to ignore—neck, armpits, chest, that kind of thing. Some people also get what’s called “B symptoms”—stuff like night sweats (the soak-the-sheets kind), fever that comes and goes, and losing weight without trying. Those symptoms generally mean the disease is more active or widespread, though not always. It’s kind of a gray area sometimes.

The disease itself comes in a few subtypes. Nodular sclerosis is the most common, especially in younger folks. It’s got these fibrous bands in the lymph nodes and something called lacunar cells, which are a type of RS cell. Mixed cellularity is another one, often linked to EBV. There’s also lymphocyte-rich and lymphocyte-depleted forms—one’s slow and sneaky, the other’s aggressive and shows up late. And then there’s NLPHL (nodular lymphocyte-predominant Hodgkin lymphoma), which is technically different altogether. It doesn’t have typical RS cells and tends to move slower. Doctors sometimes treat it like a low-grade lymphoma instead of classic HL.

Now, as far as treatment goes, this is where HL kind of shines. Most cases, especially early ones, are curable. The standard chemo combo is ABVD—Adriamycin, Bleomycin, Vinblastine, Dacarbazine. Old-school, but it works. It’s been the go-to for years because it’s effective and doesn’t leave as many long-term side effects as some of the harsher older regimens. Though yeah, people still lose hair and feel wiped out for weeks.

There’s also a newer drug called brentuximab vedotin. It's basically an antibody attached to a chemo payload—kind of like a guided missile that hunts down CD30, which RS cells express, and delivers the toxic hit directly to them. Pretty clever stuff. This one tends to be used in relapsed cases or in patients who can’t tolerate regular chemo.

Then there’s immunotherapy, which has kind of changed the game in a lot of cancers, and HL is no different. Checkpoint inhibitors like nivolumab and pembrolizumab block PD-1—a molecule that RS cells use to hide from the immune system. So basically, these drugs help your T-cells "see" the cancer again and go after it. It doesn’t work for everyone, but for people who’ve failed other treatments, it can buy time—or even lead to long-lasting remission.

Radiation is still used sometimes, especially in early-stage disease. But it’s not the blanket treatment it once was. Doctors now try to minimize exposure, especially to the heart and lungs, because let’s be real: curing one cancer only to cause another 20 years later isn’t a great tradeoff. That’s why protocols have gotten tighter and more focused over the years.

So yeah, Hodgkin lymphoma isn’t simple. It’s weird, a little unpredictable, and sometimes tricky to treat. But it’s also one of the clearest examples of how far cancer treatment has come. From chemo to immune-based therapies to targeted antibodies, the whole landscape has changed in just a few decades. It’s still not perfect—some people relapse, others get long-term side effects—but compared to what it was like in the 1960s? It’s a whole different story. And if research keeps going the way it’s going, we might even see ways to treat HL without chemo someday. That’s the hope, anyway.

References

• Ansell, S. M. (2018). Hodgkin lymphoma: Diagnosis and treatment. Mayo Clinic Proceedings, 93(11), 1574-1585.

• Chen, R., Zinzani, P. L., & Fanale, M. A. (2017). Nivolumab for relapsed Hodgkin lymphoma. New England Journal of Medicine, 376(10), 2419-2429.

• Evens, A. M., & Sweetenham, J. W. (2020). Hodgkin lymphoma: Clinical presentations and management. Blood Reviews, 44, 100679.

• Gürkan, C., et al. (2017). NF-κB activation in Hodgkin lymphoma. Cancer Research, 77(14), 3834-3843.

• Küppers, R., et al. (2002). Biology of Reed-Sternberg cells in Hodgkin’s lymphoma. Annals of Oncology, 13(4), 11-18.

• Swerdlow, S. H., et al. (2016). The 2016 WHO classification of lymphoid neoplasms. Blood, 127(20), 2375-2390.

• Specht, L., et al. (2015). Long-term impact of radiotherapy in Hodgkin lymphoma survivors. Journal of Clinical Oncology, 33(6), 628-635.

• Vockerodt, M., et al. (2015). Epstein-Barr virus and Hodgkin’s lymphoma pathogenesis. Nature Reviews Cancer, 15(3), 172-183.

• Younes, A., et al. (2012). Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma. Journal of Clinical Oncology, 30(18), 2183-2189.

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1. https://www.mdc-berlin.de/news/press/why-hodgkins-lymphoma-cells-grow-uncontrollably