Name:
A 55-Year-Old with Chest Radiographic Findings
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A 55-Year-Old with Chest Radiographic Findings
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T00H09M07S
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Upload Date:
2022-02-28T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
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CATHY: Hi, welcome to Harrison's Podclass where we discuss important concepts in internal medicine. I'm Cathy Handy.
CHARLIE: And I'm Charlie Wiener,
CHARLIE: and we're coming to you from the Johns Hopkins School of Medicine. ♪ (music) ♪
CATHY: Welcome to Episode 40: A 55-Year-Old with Chest Radiographic Findings
CHARLIE: Okay, so a 55-year-old woman presents to the emergency department after a minor motorcycle collision. She's complaining of diffuse chest pain. She obtains a chest radiograph, and it shows that she has multiple 2-4 cm nodules and masses without cavitations, and these nodules and masses are present in all lobes. Cathy, let's take a minor detour here before all the rest of the question and talk about pulmonary nodules, because that's one of our favorite topics.
CATHY: Yeah, and there's some discussion on pulmonary nodules in the diagnostic approach in episode 27. But you mentioned that the nodules are 2-4 cm in size, and those are relatively big nodules. Thinking back to the previous episode, we learned that low-risk solid nodules are those that are under 6 mm, and for those patients there's no routine follow-up that's needed if patients are low risk. Once someone has a solid nodule that's over 8 mm-- obviously, in this case, we've met that-- you'd either want to follow it up in a very short period of time, like three months, or do at least additional imaging or try and get a tissue diagnosis.
CATHY: In this case, the nodules are up to 4 cm. and the fact that they are multiple, I would say we need additional workup.
CHARLIE: Okay. Her physical examination is totally normal other than some diffuse chest pain from the accident. She has no past medical history and takes no medications other than a daily multivitamin. She exercises regularly and had a negative colonoscopy and a negative mammogram within the last two years. She works as a librarian and rides motorcycles for recreation. There's no history of cigarette or illicit drug use. So, Cathy, you mentioned additional diagnostic imaging. What are you thinking?
CATHY: So I'm concerned now that this may be metastatic disease, so we'd start with a CT, abdomen and pelvis to see if there is an obvious primary lesion. It's probably not a primary lung cancer, given the multiple lesions in all lobes, and a biopsy is going to be needed, and complete imaging will help you decide at least what to biopsy.
CHARLIE: Okay, abdominal, pelvic, and head imaging shows no likely primary lesions. A bronchoscopic biopsy of the lung lesion is performed, and it shows the histology consistent with a moderately well-differentiated adenocarcinoma. There are no airway abnormalities. An FDG-PET scan shows no lesions other than those that are known in the lung. She also received a repeat colonoscopy and a repeat mammogram, and both of those were normal.
CATHY: So, just to summarize, we have a 55-year-old woman. She has no significant past medical history, a past social history notable for motorcycle riding, and she comes in with chest pain that's related to a motorcycle accident, but in the workup of the etiology of that pain is found to have a well-differentiated adenocarcinoma of unknown primary. So, common primary adenocarcinomas would be breast cancer, but we heard she had a normal physical exam and a negative mammogram.
CATHY: Colon cancer, you want to think of, but we heard that there's no primary found on colonoscopy. And if this were a male patient, you'd also want a check-up PSA. I'm thinking about prostate cancer, although prostate cancer doesn't usually go to the lungs first. But those are the three most common adenocarcinomas that I would think of for this patient.
CHARLIE: What about other tumor markers?
CATHY: So, most tumor markers, including CEA, CA 125, CA 99, and CA 15-3, when elevated are non-specific, and they're not really that helpful in determining the primary tumor site. In male patients who have an undifferentiated or poorly differentiated carcinoma, especially if you see a midline tumor, you should check beta-hCG and AFP levels because that can suggest the possibility of a testicular tumor. But that obviously doesn't apply in this case.
CHARLIE: So, it's important to state that this is a carcinoma of unknown primary, or a CUP, because she has a biopsy-proven malignancy, but the anatomic site of origin is unknown after evaluations to look for primaries.
CATHY: Yeah, and cancer of unknown primary is actually not that infrequent. It's one of the ten most frequently diagnosed cancers worldwide, and it accounts for about 3-5% of all cancers. Now, it's limited to epithelial cancers, and it really doesn't include lymphomas, metastatic melanomas, or sarcomas, because these cancers have specific histology and stage-based treatments that would guide the management.
CHARLIE: Why do we think people develop carcinomas where we can't find the primary?
CATHY: The reasons are really still unclear. One hypothesis is that the primary tumor either regresses after seeding the metastasis, or it remains so small that it's just not detected by our clinical metrics that we have available to us now. It is possible that cancer of unknown primary falls on the continuum of cancer presentation where the primary has been contained or eliminated by natural immune defenses. But another theory is also that it represents a specific malignant event that results in an increase in metastatic spread or survival relative to the primary tumor.
CHARLIE: Okay, so let's get to the question. The question states: "All of the following statements regarding her carcinoma are true except..." So, again, there'll be four correct statements and one incorrect statement. Option A says, gene expression profiles may help determine the original primary carcinoma and aid in determining the most appropriate therapy.
CHARLIE: Option B says, immunohistochemical staining, a cytokeratin 7, or CK7, and cytokeratin 20, or CK20, may help determine the most appropriate therapy. Option C says, median survival of patients with carcinoma of unknown primary is approximately 18 months. Option D says, moderately differentiated adenocarcinoma is the most common histology of carcinoma of unknown primary.
CHARLIE: Option E says, prognostic factors, including performance status and LDH level, may identify patients most amenable to therapy.
CATHY: Okay, well, let's start with answer choice D because we did already talk about her histology. So, this is true, adenocarcinoma is the most common histology, so that's not the correct answer in this case, because we're looking for the false answer. But let's go down the list. So, A, I would also say is true. So, gene expression profiling offers the promise of increasing the likelihood of identifying the site of origin. The treatment is mostly-- although it's changing-- based on site of origin, so getting that information is helpful in choosing therapy.
CATHY: So, technically, this statement is true, although it's important to point out that the literature on the overall clinical benefit of doing this is really not well established, and it's not a current recommendation to do this by the NCCN Guidelines. And actually, there was a paper that was just published in the Journal of Clinical Oncology that actually compared site-specific chemotherapy treatment versus empiric chemotherapy, and there was no survival benefit found in those patients.
CATHY: So, the clinical benefit of gene expression profiling in terms of overall survival is still unclear.
CHARLIE: What about Option B which asked about immunohistochemical staining for CK7 and CK20?
CATHY: This statement is true, so commonly used CK stains in adenocarcinoma are CK7 and CK20. Now, CK7 is found in tumors of the lung, ovary, endometrium, breast, and upper GI tracts, and this includes pancreaticobiliary cancers. CK20, on the other hand, is normally expressed in the GI epithelium in the uroepithelium, so the two together can be used to help identify a therapy as well.
CHARLIE: Okay, what about Option C, median survival is approximately 18 months?
CATHY: Unfortunately, this is not true, and actually, it's quite a bit shorter, on the order of 6-12 months. Option E also talks about prognostic factors, including performance status in LDH levels. That option is true, so prognostic factors would include performance status. Also includes the site and number of metastases, response to chemotherapy, and also serum LDH levels, with high levels being a poor prognosis. So, some people do better overall, but generally, the survival is less than a year. And systemic therapy with chemotherapy is a primary treatment modality in most patients who have disseminated disease.
CATHY: But sometimes careful integration of surgery, radiation therapy, and even periods of observation can be used, and it's important in the overall management of cancer of unknown primary.
CHARLIE: So, the teaching point here is that carcinoma of unknown primary is most commonly adenocarcinoma. Immunohistochemical staining for the CK7 and CK20 may be helpful in determining the site of the origin. However, those tests and gene profiling to determine site-specific therapy are controversial in the literature, and the proven clinical benefit is still uncertain at this point. Unfortunately, the median survival of patients with carcinoma of an unknown primary is poor and is typically less than one year.
CATHY: And to learn more about this, you can read about it in the Harrison's chapter on Oncology and Hematology. But you can also read more on nccn.org, where they have guidelines for the workup and treatment of carcinoma of unknown primary, and then the article that I mentioned was published in the Journal Of Clinical Oncology and released online, January 17th, 2019. ♪ (music) ♪