Skin Cancer and Lymphoma: Why So Many Similarities?

Dermatologist doing a skin exam.

Why do lymphoma and skin cancer seem so interconnected? Juliana Fuller was diagnosed with Ewing's sarcoma at age 19, follicular lymphoma at age 26, and melanoma in situ at 27—and there was a basal cell carcinoma in there somewhere, too. So she knows what it's like to have both malignancies...and more.

Skin Cancer and Lymphoma

Odd and not-so-odd connections, distinctions and parallels:

  • The skin is a very important immune organ. And lymphoma is a cancer of one of the immune system’s cell types: lymphocytes, which are white blood cells that are important for battling invaders.
  • Follicular lymphoma, a very common type of non-Hodgkin lymphoma, or NHL, can emerge with symptoms that involve the skin.
  • A less common form of lymphoma, called cutaneous lymphoma, is actually a cancer of the skin, but not a “skin cancer.” That is, the cells that become cancerous are lymphoma cells, not skin cells.
  • Sometimes people who have been treated for lymphoma may develop skin cancers as 'secondary malignancies,' that is, after lymphoma, and possibly related to treatment for lymphoma.
  • Drug warnings sometimes include references to “lymphomas and cutaneous malignancies” in one fell swoop, as possible side effects. Examples include drugs that alter the immune system to allow for successful solid organ transplantation.
  • Sometimes therapies developed for treating skin cancers or melanomas may work well for lymphoma as well.

Why the Connections?

As you might have gathered from the list above, there is no one-size-fits-all answer that accounts for relatedness between these two cancers in all cases, but there are several theories and concepts that help to explain certain connections.

First, immunosuppressive chemotherapy, used to treat lymphoma, may help explain the link in some individuals, however not every case of skin cancer after lymphoma is due to immunosuppressive therapy, so there must be something more at work.

Second, common forms of skin cancer may share underlying genetic causes with lymphoma.

Indeed, the phrase “lymphomas and cutaneous malignancies” comes up frequently in medicine. There has been a well-documented link between certain blood cancers, including chronic lymphocytic leukemia, or CLL, and melanoma. There have also been multiple reports of aggressive skin cancers in the setting of lymphoma.

Some types of non-Hodgkin lymphoma and CLL have been linked to a variety of other cancers, including malignant melanoma, and non-melanoma skin cancers. And the link between the development of skin cancer after lymphoma seems to become stronger as people age. Some kind of defect of the immune system could theoretically be involved in both.

The Skin as Part of the Immune System

Lymphoma is a cancer of the immune cells—specifically the white blood cells known as lymphocytes that help fight foreign invaders. While blood and skin may seem like very different tissues—and they are—it is also true that the skin has become increasingly viewed as an immune organ.

The skin is exposed to a huge variety of antigens, or immune tags, that the immune system can “see” and act on, ignore for the time being and just 'keep tabs on.' These antigens or immune tags are virtually everywhere, whether from infections or exposure to plants or chemicals.

Also, the skin has special cells called Langerhans cells. Langerhans cells are members of a family of cells in the body called dendritic cells. They specialize in presenting antigen-tags to other members of the immune cell team, and they are an important part of the skin's immune system, since they capture the antigen-tags in the skin and shuttle them back to the lymph nodes where they can “talk to” T- lymphocytes, revving the T-cell warriors up for battle.

So, the skin and the lymphocytes, and more generally the immune system, are in many ways interconnected. These connections were described some time ago by Salmon and colleagues, albeit using scientific language:

“[the epidermis] ...is equipped with immune-competent cells: Langerhans cells, the macrophage-like antigen-presenting cells of the epidermis; keratinocytes [skin cells] with immune properties; dendritic epidermal T lymphocytes, resident cells that may serve as a primitive T-cell immune surveillance system; epidermotropic lymphocytes [lymphocyte travelers to the skin] migrants from vessels in the dermis; and melanocytes, epidermal pigment cells with immune properties.”

And, new connections between the skin and the immune system continue to be discovered.

Could UV Rays from the Sun Cause Lymphoma and Skin Cancer?

So, do the same things that cause skin cancer cause lymphoma? It doesn’t look that way—at least as far as sun and exposure to ultraviolet light is concerned.

Sun and Skin Cancer

Too much ultraviolet (UV) radiation from the sun or from tanning beds can damage the DNA in your skin cells. If enough damage builds up over time, this can cause cells to start growing out of control, which can lead cancer. Fortunately, your body has special enzymes to repair a lot of the damage that comes from sun exposure. Still, UV exposure carries a risk, and most skin cancers are a direct result of exposure to the UV rays in sunlight, according to the American Cancer Society.

Both basal cell and squamous cell cancers—the most common types of skin cancer—tend to be found on sun-exposed parts of the body. Their occurrence is typically related to lifetime sun exposure. The risk of malignant melanoma is also related to sun exposure, but the relationship does not appear to be as clear-cut as for some of the other skin cancers.

Sun and Lymphoma

But what about lymphomas? Over the last several generations, the incidence of malignant lymphomas has been increasing, and one of the theories was that exposure to UV radiation increases lymphoma risk. So in the mid 2000s, this theory was tested in Denmark and Sweden. In this study, researchers found the opposite was actually true: people with high UV exposure actually had less risk of developing non-Hodgkin lymphoma. The authors concluded that the positive association between skin cancer and malignant lymphomas was unlikely to be due to UV exposure.

In time, this finding was repeated in other studies, with at least some consistency. That is, lymphomas in the non-Hodgkin category seem to be less common in groups that have higher exposures to UV light, although the biological reasons for this relationship remain unclear. Based on these studies, it seems safe to at least say that there is no evidence that UV exposure causes non-Hodgkin lymphoma; but it is also true that exposing oneself to UV radiation in the interest of lymphoma prevention is not a good idea.

Sun and Hodgkin Lymphoma

Maybe because Hodgkin’s lymphoma is less common than non-Hodgkin’s lymphoma, less is known about UV exposure and Hodgkin’s disease. But a group of researches recently did some work with data from Europe, reporting that UV exposure is associated with reduced risk of HL, particularly Epstein-Barr virus (EBV)-positive HL.

Again, these studies are just trying to untangle the affects of sunlight on cancer risk. No one is suggesting that visiting a tanning salon is a good idea, much less something that can reduce your risk of Hodgkin lymphoma.

Conclusions

In short, the connections between skin cancer and lymphoma are varied, numerous and multifaceted. Some connections have been examined by scientists more thoroughly than others. Shared risk factors represent one promising lead—that is, genes or exposures that increase your risk one cancer could do the same for the other.

Sources

Monnereau A, Glaser SL, Schupp C, et al. Exposure to ultraviolet radiation and risk of Hodgkin lymphoma: a pooled analysis. Blood. 2013;122(20):3492-3499.

Morton LM, Freedman DM. Shedding light on UVR and Hodgkin lymphoma. Blood. 2013;122(20):3395-3397.

Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood 2007;110:1713–22.

Salmon JK, Armstrong CA, Ansel JC. The skin as an immune organ. Western Journal of Medicine. 1994;160(2):146-152.

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