FIRST STEP: 80 yrs woman underwent BM biopsy for NHL staging procedure ("NODAL DLBCL"). After routine screen (CD20, CD3, CD138) I've mentioned CD20+/- (dim) small population, different from CD20+++ small reactive lymphos. Pax-5 and CD79a reveal an interstitial infiltrate of lymphocytes (small- medium caliber) with oval and slightly irregular nuclei.  
IH1: CD23-;Bcl6-;CD20-/+;Pax-5/CD79a+: low grade NHL involvement?  
 
2ND STEP: DLBCL was treated with single chemotherapy course (most probably due to patient age and condition).Primary diagnosis of nodal DLBCL was reviewed. The architecture of node was unusual for ordinary DLBCL creating an impression of "histyocytoma". Vague nodules consist of large-medium sized cc like cells and centroblasts with irregular nuclei with slight spindling.  
IH2: LCA+ 100%, CD79a+ 100%, Bcl2+ 100%, PAX5+ 50%, MUM1+ 50%, CD20+(weak) 20%, Ki67+ ~40%, CD10/CyclinD1/CD30/BCL6/CD34/Tdt/CD138-. Some osteoclasts/giants CD79a+, some CD79a-. CD21/CD23 FDC network is absent. Ig kappa++> Ig lambda+.  
 
PROPOSAL: DLBCL in the node, transformed from low grade lymphoma (MzL), spreading in BM???  
QUESTION: THE DEFINITE NOSOLOGY OF NHL?  
NOTE: NUclear details are briliant in reticulin (GSPS) stain.

Mueller-Hermelink 2008-04-13 18:16	This is really a difficult case . Most likely a transformed blastoid MZL with strong secretory differentiation, eqivalent to DLBCL. Giant cells are plasmacells ( Mum 1 +) . Weak CD20 may result either from a first course of chemotherapy ( Rituximab) or downregulation in plasmocytoid differentiation.The cyclin D1 is unusual as some of the plasmocytoid cells appear to be positive . What about CD5?- as blastoid MCL would be a morphological differential diagnosis.
ugnius 2008-04-13 18:24	Than you a lot. Really CyclinD1(-) in the infiltrate and CD5 corespond CD3 (mostly reactive small T cells). Some giant cells seems to be CD68, but another not. Multinucleated cells are CD138-.
ugnius 2008-04-13 18:34	Some irregular cells (small proportion) CD5+: loading photos...
ugnius 2008-04-13 18:41	Some "mononuclear" cells CyclinD1+ clearly positive like in giants cells, but the pattern strictly intersticial and still different from mantle cell CyclinD1+ positivities I've ever seen.
ugnius 2008-04-13 18:53	Add ins are placed in: some giants kappa dim+, CyclinD1+, Mum1+. Others negative. All giants are CD138- (except single plasma cells in periphery of the node).
diane.c.farhi 2008-04-14 17:51	I'm not sure I understand the main question here. My impression is that the lymph node contains a large B-cell lymphoma, probably of follicular origin, with foreign-body type giant cells and focal fat necrosis or other stromal changes. I think that the confusing staining pattern of the giant cells is non-specific and likely due to surface Ig receptors. The bone marrow contains a B-cell lymphoma composed of smaller cells, also probably of follicular origin. This phenomenon (large cells in LN, small cells in BM) is often found in follicular lymphoma.
diane.c.farhi 2008-04-14 18:12	PS. Maybe I'm missing something here? If so, I apologize for not understanding the question very well. Please let me know, and thanks.
diane.c.farhi 2008-04-14 18:12	PS. Maybe I'm missing something here? If so, I apologize for not understanding the question very well. Please let me know, and thanks.
ugnius 2008-04-14 18:28	1. For sure, the nodal NHL satisfy DLBCL criteria, but we have not CD10 and Bcl6.   2. BM infiltration is low grade quality, interstitial in pattern and Bcl6/CD10- too.   3. Rituxi- therapy was not administered yet.   4. Dim CD20+ reaction is not very typical for usual FL. But idea of loosing CD20 due to plasmoid/marginal/activated IH phenotype is very interesting.   5. The giant cell reaction with nodularity and spindling seems for me a little unusual too for NHL.     So maybe academic, but question remains: exact nosology. Thank you for comments.
hurwitz 2008-04-16 18:45	I have not seen anything alike. But I think that Konrad's comment is very valuable. A transformed blastoid MZL is a very good thought. The bone marrow infiltrate consists mostly of small cells, but the high power of the CD20 stain,shows a group of weekly stained large cleaved cells. Could you please try to photograph the equivalent cells stained with CD79a or PAX5?   One of the images of the lymph node biopsy shows large cleaved CD5+ cells, a further argument for MZL.   It might also be worthwhile to stain the BMB with CD5 abd cyclin D1. Are flow cytometry results of the BMB available?   Another puzzling finding are the giant cells. By morphology, their positivity for MUM1 and cyclin D1 they seem to represent tumor cells.
ugnius 2008-04-16 19:21	BM NASDE slide (not optimal quality, but 40x) is apended. In future I will try to sinchronously present virtual HE slide with representing HE pictures for all techno possibilities. I hope we will improve the situation. Because without any doubts reviewing of all slide is more safe and comfortable, tham subjectivelly selected pictures. I will appreciate all recomendations from your side about techno aspects of presentations.
hurwitz 2008-04-16 19:28	Apparently simultaneously with this comment I commented on this problem in an other case and asked for what you are now suggesting. Thanks Ugnius
ugnius 2008-04-17 15:27	The LAST: CD43+; IgM/IgD(-) on the tumor cells.
hurwitz 2008-04-21 18:23	Dear Ugnius, the only thing I can do is to copy the second part of my comment to ID 169300:     My MacBookPro2.2 cannot mange the wonders of modern technology, such as your scanned slides. I cannot open it. It might be a Freudian Error, because as you know I am not sure for whom the sale of these expensive devices if of higher benefit for you or the company.   Please, be so kind and continue to post conventional images until you solved the tricks of high technology!!!!!
ugnius 2008-04-21 18:42	Thank you for comments. For a while "virtual slides" will be out of the access due to technical reasons (we are waiting a new special server will be installed). Maybe 40x files were large enough for reviewing.   In future I will try to duplicate visual/digital info, because the possibility to review all slide is more comfortable and safe than subjectivelly selected focci by my opinion. Anyway I'm impressed how effective is diagnostic help using simple digital photos. We have a lot of scepticism here between pathooogists and around the whorld when talking about TELE consults, but really it works! Thank you a lot. Just for info you may try better organize set of virtual slides- illustrations from International Journal of Surg Path (working very well and fast): http://aperio.nikon-instruments.it/   User: IJSPA Pass: IJSPA
hurwitz 2008-04-21 19:23	Thanks Ugnius, I know about the scepticism about telepathology using digital images, but according to several quality assessments the diagnositc accuracy is high >85%. This applies for histology and cytology, as well as hematologic cytology.
hurwitz 2008-05-09 18:29	Thanks Ugnius for the HE images of the BM sections. They clearly show the heavy interstitial infiltrate by predominantly small lymphoid cells, however occasional large cells are seen as well.This finding is well consistent with BM involvement by low grade lymphoma, with high grade transformation in the lymph node. Do you have a PAS stain of the BM section ? I marked a cell on the NASDE stain with a large nuclear halo, I wonder if this could represent a Dutcher body.   The most plausible DD seems between transformed MZL or transformed MCL. But there still remain several unresolved questions such as the week CD20 expression and the nature of the giant cells.
anpo 2008-05-10 12:59	In the lymph node there is no doubt of DLBC NHL and immunophenotype corresponds best to Activated B-cell (ABC) with strong MUM-1. In my opinion the patient has a bone marrow involvement of her DLBC because there are quite many large B-cells scattered around.The small cells population may be either rest of previous low-grade lymphoma (SC discordant lymphoma when there is low grade in BM and high grade in lymph node) or some reactive infiltrates mixed with high-grade lymphoma involvement. It would help to see T-cells staining and MUM-1 on BM.
franco 2008-05-10 21:04	I find that dr. Porwit comment is very appropriate. No doubt about DLBCL (probably ABC type) in the LN with infiltration of the BM: the only (marginal) problem if the latter is composed by small cells (in this case discordant lymphoma) or large ones.
hurwitz 2008-05-18 20:43	Final diagnosis:   Diffuse large B-cell Lymphoma (probably ABC type) in lymph node   Bone marrow involvement by B-cell lymphoma, large cells and probably a small cell component, possibly representing remnants of a preexisitng low grade lymphoma.
ugnius 2008-05-18 20:52	Thank you a lot.
	» Add comment (Login)