LADOC's Heme case of the week

[LADoc00]

Adult male with approx. 25% circulating immature cells in the PB, subsequently has a marrow that shows 40% immature cells on aspirate and over 70% on the core. Cells are large in size with deeply basophilic cytoplasm and immature chromatin patterns. Patient presented to local dermatologist with skin manifestations.

Okay my attempt to attach jpegs on this have failed (and they looked sweet too, damnit!)
Flow: No increased population in dimCD45/lowSS blast gate, increased population in "myeloid gate" lacking CD16 but strongly expressing CD56, CD13, CD33, HLA-DR. CD34 in this pop. is negative. Interesting this population is also CD4+.

What do you suspect?
What more would you do to confirm this suspicion?

---

Members don't see this ad.

 

[yaah]

What are the skin manifestations? Purpura? Petechiae? "Rash?" Nodules?

 

[LADoc00]

What are the skin manifestations? Purpura? Petechiae? "Rash?" Nodules?

Unkown. The local dermatologist is golfing the remainder of the week and his office is not forwarding calls.

 

[LADoc00]

patient is crashing, about to be transferred to tertiary care and oncologists want to know your impressions..

This is the best I can do for a linkable flow plot, very similar to my case. (do not flow the link the back and cheat please):

Note the difference with this case:

 

[LADoc00]

Looks like some sort of a myelomonocytic entity with a leukemia cutis manifestation. Would like to do cytogenetics and look for inversion(16) etc....

Please let us know...

This paper is what i was thinking about

Leuk Lymphoma. 2000 May;37(5-6):617-21.

matte look at my 2 flow plots. see what you think then. your thought process is good tho.

hint: remember the "blast gate" is empty, no myeloblasts hiding in there.

 

[Path Mama]

NK cell leukemia? LGL leukemia? Microgranular APL? Did the patient have skin nodules?

 

[yaah]

Did you do the NSE, MPO?

 

[LADoc00]

Did you do the NSE, MPO?

What are you thinking?

 

[yaah]

What are you thinking?

That they are monocyte lineage and should all be MPO negative. I haven't really done any flow yet (next few months maybe) so I am a bit ignorant about some of the case aspects thus far.

 

[Path Mama]

I guess I was focusing on the CD56 positive, CD4 positive aspect of the case in thinking they were NK/T-cell lineage, but then CD16 shouldn't be negative, right?.

By morphology, what about an erythroblastic leukemia (basophilic cytoplasm, megaloblastoid chromatin, binucleated cells--or is it "apple core"?)? By flow did you consider the CD71 positive? What about the CD61? If so, how about megakaryocytic leukemia (and am I imagining cytoplasmic blebs?), especially if the glycophorin A is negative?. I think CD34 should be positive in an AML M7, though. Did you do a PAS stain?

Or what about just going back to APL with positive CD64, CD11b, CD33, CD15 and negative CD34? Any FISH or cytogenetics? How does the CD4 fit into all of this? Bilineage?

 

[DrBloodmoney]

My vote is for Blastic NK cell Leukemia/Lymphoma.

The only thing against it is its CD33 positivity. I would get some TCR gene rearrangement studies.

Better tell that guy to buy off the rack

 

[LADoc00]

Answer: FAB M5a, Acute Monoblastic Leukemia

The presence of myeloid antigens CD13 and CD33 on a lymphoid leukemia such as NK/T would be highly unusual. In addition, CD4 although commonly thought as a lymphoid-specific marker, it is also a marker of monocytic differentiation. Also the presence of CD64, CD11b even in the absence of CD14 is a fairly strong indicator of monocytic lineage.

This case illustrates that AML M5 faces the dual challenge of not only being often CD34 negative, but has flow properties which can place it in the myeloid gate rather than the traditional blast gate.

NK/T lymphomas though are in fact N-CAM/CD56 positive are typically CD4 negative. They also express CD2 and CD3 (not positive here) and other markers of lymphoid lineage so you cant have tunnel vision for one single non-specific marker like N-CAM (which is expressed not only on multiple hematolymphoid tumors but also several carcinomas).

You would confirm this hypothesis with an esterase stain like Alpha Naphthyl Butyrate.

The clinical presentation of this is not unusual for monocytic lineage tumors as they have a greater propensity for leukemia cutis.

 

[pathdoc68]

Answer: FAB M5a, Acute Monoblastic Leukemia

The presence of myeloid antigens CD13 and CD33 on a lymphoid leukemia such as NK/T would be highly unusual. In addition, CD4 although commonly thought as a lymphoid-specific marker, it is also a marker of monocytic differentiation. Also the presence of CD64, CD11b even in the absence of CD14 is a fairly strong indicator of monocytic lineage.

This case illustrates that AML M5 faces the dual challenge of not only being often CD34 negative, but has flow properties which can place it in the myeloid gate rather than the traditional blast gate.

NK/T lymphomas though are in fact N-CAM/CD56 positive are typically CD4 negative. They also express CD2 and CD3 (not positive here) and other markers of lymphoid lineage so you cant have tunnel vision for one single non-specific marker like N-CAM (which is expressed not only on multiple hematolymphoid tumors but also several carcinomas).

You would confirm this hypothesis with an esterase stain like Alpha Naphthyl Butyrate.

The clinical presentation of this is not unusual for monocytic lineage tumors as they have a greater propensity for leukemia cutis.

Just a clarification point - I think what the previous poster mentioned or was getting at is Blastic NK cell lymphoma, a specific and unique entity which has an unfortunate WHO designation as this entity is not actually NK cell derived. Rather it is derived from a specialized type of dendritic cell that is CD56 positive. This tumor frequently manifest in the skin and is CD4 positive, hence the synonym CD4(+)/CD56(+) hematodermic neoplasm. This neoplasm also co-expresses CD-123 and has a dismal prognosis. Of course much of the rest of the case would not fit with this diagnosis. I just wanted to contrast this to NK/T cell lymphoma.

 

[LADoc00]

Just a clarification point - I think what the previous poster mentioned or was getting at is Blastic NK cell lymphoma, a specific and unique entity which has an unfortunate WHO designation as this entity is not actually NK cell derived. Rather it is derived from a specialized type of dendritic cell that is CD56 positive. This tumor frequently manifest in the skin and is CD4 positive, hence the synonym CD4(+)/CD56(+) hematodermic neoplasm. This neoplasm also co-expresses CD-123 and has a dismal prognosis. Of course much of the rest of the case would not fit with this diagnosis. I just wanted to contrast this to NK/T cell lymphoma.

Yes, blastic NK is indeed different than NK/T leukemia. CD4/CD56 entity with no EBV association. Definitely in the differential here. I believe the key is tho, blastic NKs are nearly never positive for myeloid markers.

Quoting WHO: "Because of the morphologic similarity...and the fact CD56 maybe expressed in both myeloblastic and precursor T-lymphoblastic leukemia/lymphoma, the diagnosis of blastic NK lymphoma should only be made in the absence of commitment to the T-cell or myeloid lineages. Thus the neoplastic cells should negative for CD3, MPO and CD33.." p215

thanks for clarifying that, though I didnt want to overwhelm our readers with rare esoteric entities.

 

[Sertraline]

Yes, blastic NK is indeed different than NK/T leukemia. CD4/CD56 entity with no EBV association. Definitely in the differential here. I believe the key is tho, blastic NKs are nearly never positive for myeloid markers.

Quoting WHO: "Because of the morphologic similarity...and the fact CD56 maybe expressed in both myeloblastic and precursor T-lymphoblastic leukemia/lymphoma, the diagnosis of blastic NK lymphoma should only be made in the absence of commitment to the T-cell or myeloid lineages. Thus the neoplastic cells should negative for CD3, MPO and CD33.." p215

thanks for clarifying that, though I didnt want to overwhelm our readers with rare esoteric entities.

I think these are now called as either"CD4+/CD56+ hematodermic neoplasm" or "Early plasmacytoid dendritic cell leukemia/lymphoma" due to more recent studies showing derivation from a plasmacytoid dendritic cell precursor.
WHO-EORTC classification of cutaneous lymphomas