clinical cases

[GrassrootMaltan]

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So here's a weird one that I don't really know what to do with. For background (in case you forgot), rural, solo practice Hem/Onc with no other Hem/Onc for 60-200 miles in any direction, so I get a lot of crazy stuff and a lot of BS just because I'm also the only medicine sub specialist other than Cards and 1 day a week nephrologist.

Referral was for elevated B12. 40-something, healthy, no meds, no drugs/alcohol woman. Went to ED for abd pain. Workup there was negative (but also pretty minimal, no labs other than normal CBC/CMP, no imaging other than normal AXR). Saw PCP (PA) in f/u who ordered a broad lab workup including B12 levels, TVUS and referral for colonoscopy. Only abnormal finding on labs was markedly elevated B12 (>3000). Told her to stop supplements, repeat in 3w, still crazy high. Repeats one more time 2 months later, still high.

I get the referral and think "WTF am I going to do with this? Who cares if her B12 is high if everything else is normal?" But then I do a little reading to find out what I might be missing and discover that markedly elevated B12 levels are associated with heme malignancies, but almost never in the setting of normal labs and essentially asymptomatic people. But I went ahead and did an SPEP, peripheral flow and repeated everything and added MMA/HC as well. Everything, except the B12 (still >2500) is normal.

But then I read a little further and found a couple of cohort and retrospective studies that found a ~20% solid tumor incidence over a 1-5y period in people with repeatedly elevated B12 levels, in the absence of other explanations. She's had mammo, colo, pap and TVUS (fibroids, otherwise normal) all within the last 12 months. Not a smoker, so not high lung cancer risk. No family cancer history she knows of. Totally asymptomatic.

So now what do I do? If she were in her 70s or 80s, I'd just say to stop checking it and let her live her life. But she's in her 40s, so I feel like a little whole body low dose radiation therapy might be in order.

Back when I worked in the city, I would have drawn a CBC, found it normal and called it a day. But this practice setting is definitely making me think more deeply about the things I come across, since it's highly likely that everyone I see in clinic is 1-2 degrees of separation from me socially now.

Check serum tryptase.

 

[gutonc]

In agreement with the above approach. Would y'all have a different approach for cervical vs. thoracic esophagus, other than going straight to CRT rather than the initial peri-op approach?

Not really. I think all esophageal cancers and potential surgeries are a horror show, just a different horror.

 

[gutonc]

Not asking a question about a case, just noting that I have 3 new extramedullary plasmacytomas on my schedule today.

I work in a town of <10K people and our catchment area (6 counties) is only a little over 100K. Plasmacytoma incidence in the US is 0.3-0.4/100000. That's 10x the expected rate, just today.

 

[whoknows2012]

Not that I'm aware of. And honestly, I have no idea why a B12 level was even ordered in the first place. Yes, it can be associated with other inflammatory states and liver disease. But to date, no evidence of any of that.

Found this today

 

[gutonc]

Thanks! That was informative. She's getting a CT scan.

 

[lifeofpi1]

Question regarding cisplatin eligibility:

My understanding is that the usual criteria used for “cisplatin eligibility” with respect to kidney function across the different tumor types such as bladder, lung, h&n, etc. is CrCl >60 mL/min. Borderline eligibility seems to be quoted at usually but not always 50-60 mL/min with sometimes 40-60 mL/min being determined okay for cisplatin use for example when split dosing is used in bladder. The method of choice for calculating CrCl in the clinic seems to be Cockroft-Gault with ideal body weight for normal BMI, adjusted body weight for overweight and above, and actual weight for underweight.

Would love to hear if anyone has any input on how cisplatin eligibility related to kidney function is approached or any other nuances they would share?

 

[gutonc]

Question regarding cisplatin eligibility:

My understanding is that the usual criteria used for “cisplatin eligibility” with respect to kidney function across the different tumor types such as bladder, lung, h&n, etc. is CrCl >60 mL/min. Borderline eligibility seems to be quoted at usually but not always 50-60 mL/min with sometimes 40-60 mL/min being determined okay for cisplatin use for example when split dosing is used in bladder. The method of choice for calculating CrCl in the clinic seems to be Cockroft-Gault with ideal body weight for normal BMI, adjusted body weight for overweight and above, and actual weight for underweight.

Would love to hear if anyone has any input on how cisplatin eligibility related to kidney function is approached or any other nuances they would share?

With the data for safety/efficacy of split dose in bladder/urothelial cancer, I've pretty much moved to CrCl 40-60 (however my pharmacist wants to calculate it) gets split dose and everyone else gets full dose, pretty much regardless of the disease state.

 

[bobsmith]

Not asking a question about a case, just noting that I have 3 new extramedullary plasmacytomas on my schedule today.

I work in a town of <10K people and our catchment area (6 counties) is only a little over 100K. Plasmacytoma incidence in the US is 0.3-0.4/100000. That's 10x the expected rate, just today.

Sounds like something in the water

(Only half joking)

 

[gutonc]

Sounds like something in the water

(Only half joking)

Or the air. This is an agricultural area.

I have a meeting with the county health department medical director next week.

 

[HemeOncHopeful19]

Found this today

Can you find me an infographic on incidental PTHrP 😀

 

[bobsmith]

Bizarre coincidence (or a PCP who happens to be reading a random SDN heme/onc clinical cases thread?) - I have a new consult for a pt with elevated B12 next week

 

[whoknows2012]

Bizarre coincidence (or a PCP who happens to be reading a random SDN heme/onc clinical cases thread?) - I have a new consult for a pt with elevated B12 next week

Woah

 

[gutonc]

Bizarre coincidence (or a PCP who happens to be reading a random SDN heme/onc clinical cases thread?) - I have a new consult for a pt with elevated B12 next week

Well...you're welcome for the head start. And good luck.

On a somewhat random note, I saw 2 new patients yesterday, one with a Grade 1 follicular lymphoma and one with waxing/waning lymphadenopathy and a single FNA showing a low level of monoclonal B cells, both of whom have had B12 levels checked in the last 6 months and both of which were >2x ULN.

Is this something I've been sleeping on for over a decade?

 

[ONC2023]

Had a benign heme question.

67 year old. No PMH. Asymptomatic, no infections. One year of worsening neutropenia now ANC 800, fluctuating 800-1.6. WBC 3-4.5. Other counts rock solid, HgB 14, platelets 200.

The WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past.

Copper, folate, B12 normal. Peripheral smear without dysplasia. Hep B/C, HIV negative. No medications that are likely culprits. No rheumatologic symptoms. No autoimmune conditions.

No obvious lymphadenopathy but my lymph node exam isn’t amazing.

The family history of cancer is extremely long including solid and liquid malignant first and second degree regatives.

Any reversible causes I’m missing? I checked all the nutritional labs - copper, B12, folate. I checked drugs. I checked infections.

I’m left with either congenital (unlikely, was normal in early 2020s) versus something in bone marrow, right?

Flow cytometey next?

Thank you

 

[gutonc]

Had a benign heme question.

67 year old. No PMH. Asymptomatic, no infections. One year of worsening neutropenia now ANC 800, fluctuating 800-1.6. WBC 3-4.5. Other counts rock solid, HgB 14, platelets 200.

The WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past.

Copper, folate, B12 normal. Peripheral smear without dysplasia. Hep B/C, HIV negative. No medications that are likely culprits. No rheumatologic symptoms. No autoimmune conditions.

No obvious lymphadenopathy but my lymph node exam isn’t amazing.

The family history of cancer is extremely long including solid and liquid malignant first and second degree regatives.

Any reversible causes I’m missing? I checked all the nutritional labs - copper, B12, folate. I checked drugs. I checked infections.

I’m left with either congenital (unlikely, was normal in early 2020s) versus something in bone marrow, right?

Flow cytometey next?

Thank you

I'd throw in a peripheral flow and an SPEP but I'd also just get them set up for a marrow.

 

[whoknows2012]

Had a benign heme question.

67 year old. No PMH. Asymptomatic, no infections. One year of worsening neutropenia now ANC 800, fluctuating 800-1.6. WBC 3-4.5. Other counts rock solid, HgB 14, platelets 200.

The WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past.

Copper, folate, B12 normal. Peripheral smear without dysplasia. Hep B/C, HIV negative. No medications that are likely culprits. No rheumatologic symptoms. No autoimmune conditions.

No obvious lymphadenopathy but my lymph node exam isn’t amazing.

The family history of cancer is extremely long including solid and liquid malignant first and second degree regatives.

Any reversible causes I’m missing? I checked all the nutritional labs - copper, B12, folate. I checked drugs. I checked infections.

I’m left with either congenital (unlikely, was normal in early 2020s) versus something in bone marrow, right?

Flow cytometey next?

Thank you

LGL? Flow will likely be unhelpful outside of that (and should comment on looking for these guys so pathologists can be aware) bc even if negative you’ll likely need a deeper eval (ie bmbx). Of all the cell lines isolated neutropenia is least likely to be associated with CCUS/mds/aml.

No infections is reassuring. Can also assess for response to gcsf if no etiology uncovered.

Make sure RF and ANA sent even in absence of symptoms

 

[whoknows2012]

He has one for every hematological abnormality

 

[ONC2023]

60 year old with colon cancer with widespread liver met. Uric acid high at 16, surprisingly with AKI - I’ve never seen high uric acid with colon? But it’s not TLS, other lytes normal. Has only gotten 1 chemo.

How reliable is a G6PD level within 2 weeks of 2 unit blood transfusion? Came back normally 15 (which borderline high).

I want to give rasburicase, but has ethnic background with high risk of deficiency. The test came back normal at the high end but I’m wondering the PRBCs gave me a falsely normal result.

I could sequence it but that takes 2-3 weeks.

 

[bobsmith]

WBC and ANC were normal in early 2020s. I was thinking Duffy null associated neutropenia but she was normal in the past

Maybe different because your patient is 60 so you probably have more data points, but I did have a few cases where a 30-40 year old was sent to me for "new neutropenia" but then looking back at the 2-3 old "normal" labs, they were all drawn when they were sick or in the ER, etc

 

[gutonc]

Maybe different because your patient is 60 so you probably have more data points, but I did have a few cases where a 30-40 year old was sent to me for "new neutropenia" but then looking back at the 2-3 old "normal" labs, they were all drawn when they were sick or in the ER, etc

Yeah, I see this all the time. If there's one thing that PCPs around here are good at, it's post-hospital f/u. So someone gets hospitalized for whatever (sepsis, GI bleed, etc), sees PCP a day or two after discharge, they look at labs during hospitalization, see high or low whatevers on the CBC and decide they have acute leukemia and need a STAT heme consult.

 

[RainerMaria]

Question, are you guys doing DPD testing prior to 5FU, and if so how do you approach in situations where pt has rapid / late presenting disease where you can't wait the couple of weeks for PGX to come back. I hear Guardant liquid is now including DPD testing but not sure how good the report is in telling you how to dose reduce.

 

[gutonc]

Question, are you guys doing DPD testing prior to 5FU, and if so how do you approach in situations where pt has rapid / late presenting disease where you can't wait the couple of weeks for PGX to come back. I hear Guardant liquid is now including DPD testing but not sure how good the report is in telling you how to dose reduce.

Not really. I just did one the other day for no particular reason other than young and anxious. It was negative and came back in a week. I can't get prior auth for chemo that fast anyway so it's not like it delayed treatment.

My prior institution made it mandatory after a lawsuit that I was named in and then dropped from. The plaintiff eventually settled for $1 and this requirement, as well as mandatory "fluoropyrimidine toxicity education" for everyone in the division.

It's SOC in Europe, but not in the US.

My own personal experience over almost 15 years as an attending is that less than half of the people with significant fluoropyrimidine toxicity have a DPD deficiency. And even if they do, it's easily recognized and managed in the same way you'd do it if you knew about it ahead of time...stop the drug, let the toxicity resolve, restart at 50%.

 

[HemeOncHopeful19]

Tempus has started reflexing DPD/UGT1A1 for all colon cancers… of course it often isn’t back until Cycle #2.

These tests seem more useful for lawyers than physicians tbh. I feel like waiting to get DPD on every single 5FU patient would probably harm more patients than it helps (although the number of each would be extremely small).

 

[ONC2023]

65 year old woman. HgB 10. MCV 90. Ferritin 900, %sat 44. Retic count inappropriately normal at 1.6%. HFE gene testing negative. Remainder of CBC normal - WBC 6, diff normal, platelets 250. Nothing on smear except anemia. Copper, B12, folate, normal. Liver, kidneys normal. No hemolysis. No family history of blood/iron disorders. No obvious source of inflammation/autoimmune conditions.

I am planning on a bone marrow and liver MRI.

I haven’t run across the combination of iron overload and anemia like this - is this a common presentation for patients who have many years of ineffective erythropoiesis?

MDS patients get iron overload from their transfusions of course, I just wasn’t aware it could happen before (assuming this is MDS).

 

[gutonc]

65 year old woman. HgB 10. MCV 90. Ferritin 900, %sat 44. Retic count inappropriately normal at 1.6%. HFE gene testing negative. Remainder of CBC normal - WBC 6, diff normal, platelets 250. Nothing on smear except anemia. Copper, B12, folate, normal. Liver, kidneys normal. No hemolysis. No family history of blood/iron disorders. No obvious source of inflammation/autoimmune conditions.

I am planning on a bone marrow and liver MRI.

I haven’t run across the combination of iron overload and anemia like this - is this a common presentation for patients who have many years of ineffective erythropoiesis?

MDS patients get iron overload from their transfusions of course, I just wasn’t aware it could happen before (assuming this is MDS).

I actually have 2 of these that I'm in the middle of working up ATM. Planning for marrows as well. I haven't seen this combination before either so not helpful to you at all.

 

[bobsmith]

I have a similar case where a patient has been worked up for pseudohypercalcemia (seriously, albumin is high and corrected is normal but they’ve been worked up by 2-3 different MDs for it) with a persistently elevated PTHrP and I have been doing the same thing.

Another bizarre coincidence - I was just asked if I should see a patient with ESRD, normal calcium and mildly elevated PTHrP (sent in the setting of calcium that was high once a few months ago, although subsequently the calcium normalized and ionized calcium is also normal) without any evidence of malignancy clinically.

Anyway, I looked into it and most labs doing PTHrP tests will use a C-terminal assay which can be elevated in pts with CKD; an N-terminal assay will apparently be normal (citation).

Whether I'll be able to actually find a lab that can run this test is another question, but at least I feel like in my patient's case, the ESRD is a decent enough explanation.