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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now, onto the episode.
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[Dr. Handy] Hi everyone. Welcome back to Harrison's Podclass. We're your co-hosts, I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine.
[Dr. Handy] Welcome to episode 99. Today's episode is about a 29-year-old woman with adenopathy.
[Dr. Wiener] Hi Cathy. Today's patient is a 29-year-old woman who comes to your office because she's developed palpable, non-tender cervical lymph adenopathy that has not resolved after a month, and in fact, it might have been increasing in size and now she's pretty worried. On taking a further history, she does report that she has had some intermittent night sweats, but otherwise, she denies any symptoms, such as rash, arthralgias, or excessive fatigue, weight loss, or anorexia.
[Dr. Handy] Okay, so the non-tender adenopathy in the neck and axilla with night sweats is certainly worrisome. Infection and cancer are at the top of the differential, but autoimmune diseases and then rare causes, like sarcoid can also be considered. Any notable risk factors or other medical conditions?
[Dr. Wiener] Well, she has no history of any other medical conditions. She works as a bus driver and has not left the city in three years. She's never traveled outside the United States. She takes no medications, does not use any illicit drugs or alcohol, and she's only been sexually active with her husband of six years.
[Dr. Handy] All right, and what'd you find on exam or any basic labs?
[Dr. Wiener] So her physical examination is within normal limits, other than the fact that she has a number of palpable firm lymph nodes in her right anterior cervical and right axillary areas. The nodes are each about two centimeters in diameter. They're mobile, but they're painless. She has no detectable splenomegaly or hepatomegaly. We did perform a CBC and a metabolic panel and both of those are within normal limits. Also, we performed an HIV test and that's negative. So what do you want to do next?
[Dr. Handy] Next, I would do imaging to get a sense of how diffuse the adenopathy is, and that should include the neck, the mediastinum and abdomen. And while I know that you didn't palpate a spleen on exam, the absence of that on physical exam is not really sensitive, so I'd want to know about splenomegaly, which you would get with imaging.
[Dr. Wiener] Okay, well, a CT scan demonstrates pathologically enlarged lymph nodes in the neck, axilla and mediastinum. There is no splenomegaly. What do you think about getting a PET-CT given that she has diffuse adenopathy and B symptoms? You think that's a good idea?
[Dr. Handy] Yeah, so a PET-CT in this setting is totally reasonable. Now, PET-CTs without clear indication is likely to identify harmless findings that just lead to more tests, biopsies, or unnecessary surgery. The likelihood of finding cancer in healthy adults with PET-CT used as a screening test is extremely low, so the Society of Nuclear Medicine and Molecular Imaging and Choosing Wisely have guidelines for PET-CT use, but again, in this case, it would be very reasonable to do.
[Dr. Wiener] Well, we did do a PET-CT as you suggested and it demonstrated that all of the lymph nodes were FDG avid. So what would you do next?
[Dr. Handy] Next, I would recommend that she go for biopsy.
[Dr. Wiener] Would you get an excisional biopsy or just a fine needle aspiration?
[Dr. Handy] Well, I would be concerned about lymphoma in this case, so when that is high on the differential, we should do an excisional biopsy for two reasons. So the first is that even in the era of molecular diagnosis, the architecture of the lymph node is important and you get that with an excisional biopsy, but you would not get that with just fine needle aspiration. The second reason is that we need enough tissue for special stains in molecular testing.
[Dr. Wiener] Okay, done. An excisional biopsy shows large cells with bilobed nucleus and prominent nucleoli surrounded by pleomorphic cellular infiltrate.
[Dr. Handy] All right, so that was helpful. What's the question asking? And then we can probably talk more about what that biopsy means.
[Dr. Wiener] Okay, so the question asks, which of the following statements regarding this patient's diagnosis is true? Option A. is that HTLV-1 is associated with the development of this disease; option B. the existence of the T1418 mutation and abnormal expression of BCL-2 protein are confirmatory for this diagnosis; C. the majority of patients will not be cured with chemotherapy alone; D. the PD-L1 protein is often overexpressed and may contribute to the immune evasion in this disease; and E. the disease is of T cell origin. So obviously, you got to start with telling me, what do you think the diagnosis is?
[Dr. Handy] Okay, so the biopsy that was described is the classic description of a Reed-Sternberg cell and that's diagnostic of Hodgkin's lymphoma.
[Dr. Wiener] Ah, the Reed-Sternberg cell, which is named partially after Dorothy Reed, who is a graduate of the Johns Hopkins School of Medicine where you went to school also.
[Dr. Handy] Shout out to Johns Hopkins.
[Dr. Wiener] She was not a classmate of yours, but in 1901, she described the cell and determined that it was characteristic of Hodgkin's lymphoma. Not surprisingly, Dorothy Reed Mendenhall's story is one of overcoming many obstacles, including at Hopkins. She eventually trained in pediatrics in New York City and was on the faculty at the University of Wisconsin for many years where she had a tremendous career focused on child and maternal health.
[Dr. Handy] I didn't know all that history about her.
[Dr. Wiener] Yep, it's a great story. Back to lymphoma, tell me more about Hodgkin's specifically.
[Dr. Handy] All right, Hodgkin's lymphoma is a malignancy of mature B lymphocytes. The patient's presentation of the right cervical and mediastinal adenopathy is very typical. The overwhelming majority of patients with Hodgkin's will be cured with either chemotherapy alone or a combination of chemotherapy and radiation. Epstein-Barr virus is associated with the development of Hodgkin's, and interestingly, 97% of Reed-Sternberg cells in classical Hodgkin's lymphoma harbor genetic aberrations in the PD-L1 locus on chromosome 9p24.1, resulting in overexpression of PD-L1 protein, the ligand for the inhibitory PD-1 receptor on immune cells. This is one mechanism whereby the Hodgkin's Reed-Sternberg cells may be able to avoid immune destruction in its inflammatory microenvironment and may contribute to the generalized immune suppression in Hodgkin's lymphoma patients.
[Dr. Wiener] Okay, so the answer to this question is D., the PD-L1 protein is often overexpressed and may contribute to immune evasion. You also told us why options C. and E. are not true. The disease is one of B cell origin and most patients are cured with systemic treatment. What about the other options?
[Dr. Handy] Option A. mentions HTLV-1. So this retrovirus infects T cells and is not associated with Hodgkin's lymphoma. And option B. mentions the T1418 mutation and abnormal expression of the BCL-2 protein. These are confirmatory tests for follicular lymphoma, not Hodgkin's.
[Dr. Wiener] Okay, great. So the teaching point in this case is that we must choose wisely when we're ordering PET-CT scans, but in the appropriate patient, they may be helpful for localizing where to do a biopsy and help with the diagnosis. The other teaching point is that in a patient with adenopathy that is suspected of having lymphoma, it's vital to perform an excisional biopsy. Hodgkin's lymphoma is a B cell malignancy that has the capacity to evade the immune system via the PD-L1 pathway. Nevertheless, with appropriate therapy, the disease is highly curable.
[Dr. Handy] And you can read more about Hodgkin's lymphoma in the chapter with the same name in Harrison's. And for additional reading, you can check out the chapter on Dorothy Reed Mendenhall in our colleague Ralph Hruban's book, A Scientific Revolution.
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[Dr. Shapiro] Thanks for listening to Harrison's Podclass. You can listen to this episode and more on AccessMedicine.com, which includes the complete Harrison's Principles of Internal Medicine text, Harrison's review questions, which compliment and expand upon the questions in this episode and much more. AccessMedicine.com may already be available to you via your academic institution. Check it out.
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