Case Review: Small Cell Lung Cancer Following LEMS


An oncologist reviews the case of a 57-year-old man diagnosed with small cell lung cancer after Lambert-Eaton myasthenic syndrome.

David Gerber, MD: Let’s continue to the second case because it raises an important point—perhaps the most important point of this entire session. In our second case, a 57-year-old man presents to his primary care physician [PCP]; he is experiencing weakness in his legs and arms over the last 2 months, he’s able to walk, but he finds it difficult to stand up at his desk. He smoked 40 pack-years, and he has some well-controlled hypertension. The PCP refers him to a neurologist.

The neurologist does as you described, repetitive nerve stimulation tests, and finds abnormal detrimental responses with low-rates stimulation and incremental responses with high-rate stimulation, suggestive of LEMS [Lambert-Eaton myasthenic syndrome]. The patient begins treatment and experiences improvement in the symptoms. Six months later, the patient presents to his PCP with chest pain… and a cough. He’s referred to oncology, and the work-up reveals small cell lung carcinoma.

When I read this case, it made me cringe. Does this bother you as much as it does me?

Steven Vernino, MD, PhD: It does because they forgot an important part of this work-up.

David Gerber, MD: If you were that neurologist, I’m sure you would perform similar neurologic diagnostic analyses and start similar treatments, but what else might you have done at that point?

Steven Vernino, MD, PhD:When we consider the diagnosis of Lambert-Eaton myasthenic syndrome, we recognize that some of them will be autoimmune, not cancer related, and others will be paraneoplastic and often related to small cell lung cancer. This is a case where after making the diagnosis of Lambert-Eaton myasthenic syndrome, we should recognize that this is an older man with a smoking history and the chances of him having paraneoplastic are extremely high. Just because he doesn’t currently have chest symptoms, I would look at that as an opportunity to make an early cancer diagnosis. The error here was waiting around until the cancer presented itself.

My approach to this would be chest imaging to start with, and in a case like this, I am highly suspicious for a paraneoplastic form, even if a chest x-ray and routine CT are not revealing that. I might proceed with a PET [positron emission tomography] imaging scan because we know that it’s more likely to pick up localized or low-volume small cell lung cancer earlier than routine CT imaging.

David Gerber, MD: We’ve shared a couple of these cases—whether you’re calling me and ordering the initial imaging study or vice versa, one of us gets it done. I often go straight to a PET scan, and people listening may ask how I get a PET CT scan on a patient who doesn’t have symptoms, but it’s because the likelihood of diagnosing small cell lung cancer is so high.

When small cell lung cancer is early stage, it may be embedded in the soft tissues of the media Steiner, not out in the [INAUDIBLE] of the lungs, surrounded by air, and the PET CT helps you pick it out. This is 1 of the 2 reasons why patients with small cell lung cancer who also have an aplastic neurologic condition like LEMS do better than patients who don’t have the paraneoplastic condition. We can diagnose it at an exceptionally early stage. You may say limited stages are limited stage, but if it’s a single area of tumor, we could be more aggressive with our radiation. There’s a decreased risk for toxicity, and we can aim for a cure. The other aspect of their better outcomes is probably the cross-reactivity. If their body has reacted to the cancer and it’s cross-reacting with the nervous system, some of that heightened immune status is also attacking the cancer as well. When it comes to paraneoplastic syndromes with cancers, the humoral ones that I discussed, those are the chemical high-calcium, low-sodium, Cushing syndrome, they’re almost always diagnosed after the cancer is recognized.

Paraneoplastic neurologic syndromes almost always come to clinical attention before the cancer, which is why if someone’s diagnosed with LEMS, we’re immediately looking for small cell lung cancer. If someone’s found to have myasthenia gravis, we’re immediately looking for a thymic tumor, for example.

Steven Vernino, MD, PhD: On the neurologic side, there’s been a consensus expert opinion on this topic in Lambert-Eaton myasthenic syndrome. It’s recommended to start with at least CT chest imaging and repeat that every 3 months for at least 2 years before you can say that you didn’t find a cancer. In high-risk cases, those with antibodies and those with cancer risk factors, should proceed immediately to a PET scan in the current state.

This is a time that we should mention the importance of having a relationship between neurology and oncology. If you don’t have that as a neurologist, there can be frustration when you contact your local oncologist and ask, “Can you screen this patient for small cell lung cancer?” because, unfortunately, some oncology practices say they don’t see patients who don’t have cancer and will turn them away. It’s crucial to have an oncologist that knows that this is a special situation, where the likelihood of cancer is high and that it’s important to evaluate this patient. Ultimately, we may not find a cancer, but that is not wasted effort.

Transcript edited for clarity.

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