63 yrs old Lady with 2005 diagnosed DLBCL (clin. diagnosis was MDS with transformation to AML). After-8 CHOP- treatment 2007 threpine biopsy was done due to hemolysis (progression?): Hb 42g/l; Coombs +; hyperbilirubinemia; Under the Prednisone therapy now.  
SHORT CLIN HISTORY: 2005 10 18: Weakness, dizziness, sweets. Flow: BM lymphocytosis (DLBCL or B marginal zone immunophenotype). Slight hepatomegaly. Blood lymphocytosis 67%. Anemia, thrombocytopenia.  
2006 01 31: subclinical compression fractures of Th8/Th11/Th12.  
2007 06 18: there are any LN, spleen, liver enlargement. Blood: lymphocytosis 40%. BM: lymphocytosis 92.5%.  
HISTO: There is diffuse infiltrate of small, cc like cells with admixture of "blastoid" ones with rudimentary? large cell formed follicle center.  
IH: tumor population: CD20(+++) 100%, CD3/CD5/CD43(-), Bcl2(++/+++) 90%, Bcl6(-) 10% (except FC), CD10/Mum1/CyclinD1/CD30(-), Ig kappa/lambda (-/polytipic), CD23(-)(except large fdc nodule in fc), IgM (+/+++) 100% , IgD(+) 10%. Ki67 ~5% (In FC higher: up to 80% (+++). Prominent intyersticial CD57+ T lympho's. CD21+ FDC network in the LARGE FC and in the INFILTRATED? smaller not vissble in HE follicles. CD138+ polytypic intersticial plasmacytes ~5%.  
 
NOTE: OLD biopsy with darker and clear areas maybe in part due to processing/fixation deficiencies.  
 
PROPOSED DIAGNOSIS: B low grade lymphoma: B marginal zone lymphoma vs FL with extensive marginal differenciation. RETROSPECTIVE (Photo: OLD) biopsy: the same changes.  
 
Thank you for participating and understanding. Appologies, if photos do not represent the same fields or do not represent the definite problem properly.

anpo 2007-07-11 10:42	I agree with your first alternative - GC seems reactive and the cells have "monocytoid" morphology. Does the patient have splenomegaly or enlarged lymph nodes?
ugnius 2007-07-11 12:08	Dear Prof.A.Porwitt, I've append some clin data to description. Shortly: any signs of lymphadenopathy, spleno/hepatomegaly from 2005 (presentation). The lymphocytosis in PB and BM was present only with immunophenotype of DLBCL or B marginal zone lymphoma by flow.
Mueller-Hermelink 2007-07-11 19:44	The cytology of the lymphocytic component is reminiscent of hairy cell leukemia ( I believe that this is also the reason Tthat Ann Porwitt asked for splenomegaly) . Is this definitely excluded?
ugnius 2007-07-12 08:57	The last IH in the panel was HCL, but it's negative. ANXA1 and Co are out of possibilities.
hurwitz 2007-07-24 16:48	Dear Ugnius, sorry for my delayed reaction. I have some dificulties in understanding the time sequence of events. What was the tissue, the first dx of DLBCL, was made on?   What you call old biopsy (separate folder),do you refer to the biopsy performed in 2006? and finally the recent biopsy, was it done in 2007?   The case is rather unusual,therefore we have to try to get the data as exact as possible.
ugnius 2007-07-25 00:00	Dear Prof. Nina. Due to vacation for 2weeks my "add ins" will be late. Appologies. These 2 biopsies were completelly similar histologically. Previous ("OLD", 2005) was diagnosed as DLBCL. Recently I get the new one (2007) and just revise former. 2006 was misstyped. Sorry for that.
hurwitz 2007-07-29 18:27	Thanks Ugnius for the clarification. Both biopsies (2005 and 2007) show identical changes. There is a massive infiltrate by low grade lymphoma in both biopsies. The mmorphology and the immunophenotype of the tumor cells are compatible with marginal zone lymphoma. The extensive presence of reactive germinal centers within the infiltrate is unusual, somewhat reminiscent of residual germinal centres in SMZL.   Infiltrates by hairy cell leukemia seem less likely, still it would be interesting to have the exact results of flow cytometry, in particular CD103, FMC7 and CD25.
tzankov 2007-07-30 10:06	The co-expression of IgM and IgD(stated by you), as well as the presence of "colonized" follicles, "monocytoid" lymphocytes and the negativity for CD5, CD23, follicular markers and Cyclin D1 (expressed in approx. 60% of hairy cell leukemia) as well as the presence of splenomegaly and peripheral lymphocytosis should be considered, in my opinion, as diagnostic of splenic marginal zone lymphoma.     could you show us the lymph node biopsy from 2005, where DLBCL was diagnosed?
tzankov 2007-07-30 12:37	Dr. Hurwitz drew my attention to the fact that the patient has no spleen enlargement. is that correct? nevertheless BM infiltration by MZL (nodal, slenic... extranodal, due to IgD+, less likely) is still my favorite diagnosis.
anpo 2007-08-01 11:35	I think that primary marginal cell lymphomas of the bone marrow with no spleen enlargemant and no lymphadenopathy are not common. Does the patient have monoclonal protein? A variant of immunocytoma or Mb Waldenström could be a differential diagnosis - especially since the patient has haemolytic anaemia. However, some patients with autoimmune haemolytic anaemia can have polyclonal B-cell proliferations in the bone marrow so flow cytometry or PCR on the bone marrow would be of help to see if there is really a monoclonal B-cell population.
ugnius 2007-08-09 09:10	Monoclonal protein is absent.
anpo 2007-08-10 11:23	I have read again the whole discussion but I am still confused - what was the actual phenotype of B-cell population by flow cytometry? there was no clonality by ICH but there was a lymphocytosis in blood and bone marrow and you wrote that it was consistent with B-lymphoma. If it was clearly shown that there is clonal excess of kappa or lambda B-cells in BM I agree with marginal-cell lymphoma and reactive germinal centers. I would not be sure of the previous DLCB diagnosis.
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