70yrs old female 2007 04 26 underwent 2,5cm lymph node biopsy with clin diagnosis "lymphoma".  
HISTORY: In the beginning of 2007: fever and postive blood culture (NOS). AB treatment + steroids. Diagnosis: sepsis. In the moment of LN biopsy: neck lymphadenopathy, blood test normal, ESR and CRB normalized. Ig evaluation was not performed (I've request it now).  
Diagnosis B marginal zone lymphoma was made. Threpine biopsy results: "reactive changes".  
2007 06 06 core biopsy from inquinal lymph node was repeated due to clinical suspition of "transformation to DLBCL".  
HISTO 1 (primary node): 1. B marginaloid monotonous proliferation of "plasmacytoid" B cells with Ig kappa restriction. 2. Some eras seems to be CD3-CD20-: photos No.14-15 (staining?)3. There some CD68+ multinucleated cells with hemophagocytosis. Some dim CD68+ reaction in "marginaloid" population. 4. There are some interstitial CD30+ CD15-CD3-CD20-/+(single +) giant cell accumulations with HL features. 5. The cytology of small lymphos, "marginaloid" cells and giants are demonstrated well in photo No.42.6. There are slingle CD138+ cells in sinus area.  
HISTO 2 (core biopsy LOW QUALITY): 1. T CD3+ population with a little angulated nuclei with some admixture CD20+ cell. 2. High Ki67 activity. 3. The same giant cells CD30+.  
HISTO 3 (core biopsy): 1. Diffuse clear CD3+/Bcl2+ T cell population with some PROMINENT and PALE areas of CD21+ FDC proliferation, "neovascularity", some pleomorphic T (sic!) cells and some faintly CD30+/- andCD15- cells. 2. Residual CD20+ small lymphoid nodules with Mum1+ scattered cells.  
 
MOLECS: 1. PRIMARY node: B monoclonal Ig kapa, polyclonal IgH and TCR beta monoclonal. 3. Last core biopsy: T monoclonal. B was not done (B population is scant).  
 
DIAGNOSIS: 1. LYMPH NODE: B marginal zone lymphoma with prominent plasmacytoid/activated zomponent and HL like giant cells (transformation?) 2. CORE: Atypical T lymphoid proliferation with HL like cells (transformation?). 3. Atypical T lymphoid proliferation (transformation to AILT)???  
 
Thank you for participating.  

SergeyN 2007-06-17 16:04	Just a small comment.     Richter's syndrome with CD30+ Sternberg-like large cell population has been described, we had such case in a B-CLL patient (though the large cell component was much more evident). Do you have CD79a and EBV, by the way?     And another small thing. There really seem to be fields of CD20- plasmacytoid cells in the initial biopsy. Wasn't there IgM paraprotein by chance?
ugnius 2007-06-17 16:44	Hello. dr.Sergey: IgM and IgD is located mainly on the rudiments of small lymphos. CD138+ scatered cells in capsular area.
ugnius 2007-06-17 16:45	The last photos: IgM IgD CD138.
hurwitz 2007-06-17 22:04	The DD includes B-CLL/SLL with RS-like cells, lymphocyte rich classical HL, marginal zone lymphoma and lymphoplasmacytic lymphoma,cannot be exluded but seem less likely. The small cell population is CD20+, positivity for CD23 cannot be appreciated on the low power image (please do add a high power one), but there seem to be some staining in the CD20+ area. To clarify the question of CLL/SLL we need incubations with CD5. Information about the PBC (lymphocytosis?) and if there is generalized lymphadenopathy and/or splenomegaly would be also helpful.   I agree with Sergeys comment about Hodgkin-like transformation of SLL/CLL, which can be EBV associated.   So lets wait for the CD5 stain and the clinical information.   You demonstrated nicely that there are two types of giant cells: CD30 and CD20+/- Hodgkin-like tumor cells and reactive histiocytic giant cells CD68+ with emperipolesis.
ugnius 2007-06-18 10:03	B population in lymph node: CD23- CD5-.
hurwitz 2007-06-18 11:35	Thanks Ugnius, in this case CLL/SLL is out and MZL and lymphoplasmacytic lymphoma in. Actually there cases of lymphoplasmacytic lymphoma with HL-like transformation, I have seen some.
dirnhofer 2007-06-19 12:23	to me, cHl is the most likely dx; is cd15 in the core biopsy also completely negative? please, check for dim expression! bsap would also be helpful. moreover, i m not fully convinced of an underlying b-cell lymphoma at all but of course mzl would be possible (cll can be ruled out). ask for monoclonal m-gradient, bmb, fcm of pb and/or bm etc to demonstrate b-cell lymphoma.
ugnius 2007-06-19 14:00	SOME CLINICAL DETAILS ARE PLACED IN.
ugnius 2007-06-19 17:10	Some new immunos arive. The strange thing, that SOME OF THE marginaloid cells are DOUBLE NEGATIVE CD20-CD3-, but Mum1+ and CD138-. Just recall that we have had strange CD68 positivity in cytoplasm, maybe artifactual. I've requested CD79a to be sure that we deal with B cells. But CD20 negativity???
ugnius 2007-06-19 17:13	CD3/CD20- cells have oval angulated "nonplasmacytic" nuclei and small nucleoli(plasmacytoid T lymphos? Etc.?)
ugnius 2007-06-19 17:35	CD30+ (BROWN) cells are placed in CD20+ (RED) background with some nodularity.
ugnius 2007-06-19 17:58	RS cells: EMA-LCA-Mum1+CD30+CD15-EBV LMP1-; "Marginaloid" CD3-CD20- zone LCA+ weaker than reactive follicular rudiments.
Mueller-Hermelink 2007-06-19 21:00	In my opinion this is a typical case od Marginal Zone B cell lymphoma , probably nodal type , with extreme secretory differentiaqtion . Interestingly the lymphoplasmocytic component is quite often CD 138 negATIVE or only partially positive and CD 79 +, but CD 20 neg.The giant cells are HD-like. If transformation to classic HD is considered the cells should be CD79 neg. , have a typical phenotype and the background found in HD , otherwise I would only mention HD-like cells descriptively. We published 12 cases of HD transformation in Marginalzone B cell Lymphomas ( Zettl. etal 2004(?)
ugnius 2007-06-20 09:14	Thank you, dr.Mueller-Hermelink. CD79a staining and new photos will be appended soon.
tzankov 2007-06-22 08:54	Tzankov: I consider this case (HISTO1) a typical marginal zone lymphoma with scattered blasts and HL-like cells. I would probably check the BSAP and the EBV status in the giant cells, particularly EBNA2, if BSAP is dim and if EBNA2 is negative I would suggest a "Hodkin-like" transformation, if not I woul only mention the resence of these giant cells.   Please add better quality pictures of HISTO2 and some details on the history. Particularly here, on the present pictures I can not rule out HL. Why was HISTO2 performed? Did the patient had any sign of progression? Was this the biopsy on which "transformation" has been suspected?
ugnius 2007-06-22 10:05	Thank you, dr.Tzankov. The next biopsy was done with suspitiion of transformation to DLBCL. The quality of the HE is not optimal. Appologize for that. But the biopsy is infiltrated T cells only with high Ki67 index and with admixture of HL like cells. The question remains about residual B component: maybe it happens due to sampling and WHOLE LYMPH NODE biopsy would be of value.
ugnius 2007-06-24 13:52	THE LAST POINTS/PHOTOS CD79a Pax5: 1. Giant HL like cells seems to be CD79a+Pax5-. 2. The activated plasmacytoid cells are CD20-, but CD79a+ and Pax5-.   Maybe the FINAL sounds like: B marginal zone lymphoma with HL like transformation?   One question left: HOW THE FINAL DGN MUST BE FORMULATED FOR BIOPSY with T population only and giant cells? (CD79a is requested for it).
ugnius 2007-06-24 13:55	NB: some giants are questionably Pax5 -/+ (nuclear)...
ugnius 2007-06-24 14:07	To dr.Tzankov: we have not introduced hybridisation in situ for EBER yet(LMP1 in IH only) and BSAP.
Mueller-Hermelink 2007-06-27 14:09	Just another comment , if HD-like cells are strongly + for CD79a classical HD is very unlikely: CD79a is a BcellReceptor associated protein - Since HD cells usually lack a BCR and this Receptor is combined with the associated proteins at the cell membrane CD 79a should be negative in typical HD.( which is also a good differential diagnosis to EBV associated lymphoproliferative disorders
ugnius 2007-06-27 14:16	Thank you. I'm waiting CD79a on the biopsy. What formulation would be the BEST for this T population with giant HL like calls? We have not B population...
ugnius 2007-06-27 17:59	The last histo-point: unfortunatelly ther was not enough material for Pax5 and CD79a and CD15. We are waiting for PCR from primary node. Giant cells CD30+CD20-/CD3- (maybe due to small population the evaluation is aggravated).
ugnius 2007-06-29 13:13	The last point: PCR: IgH polyclonal; IgK monoclonal. The file is attached. I cannot rule out HL in biopsy. Ig evaluation without any deviations.
SergeyN 2007-07-03 09:39	Another small comment.     To think about Hodgkin here one needs proof, because NHL looks much more logical in this setting. And there is no final proof as long as there are doubts about CD79a (and EBV).     It seems it is a good indication for extirpating the node in question. Besides getting additional material for stainings, it will be possible to exclude a purely topographical artefact of the core biopsy.
Mueller-Hermelink 2007-07-03 18:10	Dr. Hurwitz asked me to make a final comment :   This is a marginal zone lymphoma , probably nodal type , with extreme secretory differentiation and an increased blast content with some HD-like cells. Since CD79 is strongly positive and the adaequate background is lacking I would exclude transformation at that time..Increased blast content is a frequent finding in nodal MZL and usually is still rather indolent clinically. Transformation to DLBCL is diagnosed if there are really sheets of large blast cells and destructive growth pattern, which in this case , at least within the areas available,is not seen.
ugnius 2007-07-04 09:30	Thank you all for all done. SURPRISE: Despite the strong insisting from our side to take intact LN another CORE BIOPSY was taken... Giant cells are not prominent. CD3+ > CD20+ population only. Maybe it's due to dr.Sergey mentioned sampling problem... Photo will be appended soon.
ugnius 2007-07-09 11:32	Dear Collegues, please find materials from the LAST CORE biopsy: 1. Diffuse clear T cell population with some PROMINENT and PALE areas of CD21+ FDC proliferation, "neovascularity", some pleomorphic T (sic!) cells and some faintly CD30+/- andCD15- cells. 2. Residual CD20+ small lymphoid nodules.   The picture is stil indefinite, but maybe an idea of transformation to AILT (not to HL- PRIMARY LYMPH NODE) must be discused? Additionally just recall the second core biopsy with T slightly irregular population and HL like cells.   Unfortunatelly, WHOLE NODE biopsy was not done after pathologist request.   We will try to check T clone from this material.   ]Thank you for comments.
ugnius 2007-07-11 11:24	It seems the larger atypical CD3+ cells show CD4+ immunophenotype. There is some CD68+ cell accumullations in pale CD21+ FDC reach areas. We are waiting for T clonality PCR study.
ugnius 2007-07-13 09:44	Dear Collegues. It seems we have a solution: from materials of last 2 core biopsies we get a TCR beta clone. The file attached. It would be very intereseting to evulate T clonality in PRIMARY node... So the illusion, that in core biopsies T CD4+ population is slightly abnormal becomes true...
ugnius 2007-07-13 09:49	A litle mistake- T monoclonality ppt file contains PCR results from PRIMARY LYMPH NODE too (B07-12549). B07-18811- the last core biopsy. So we have had a BICLONE population (B and T) in primary lymph node with B marginal zone lymphoma combined with uncertain T lymphoma. From last core biopsies the diagnosis AILT of peripheral T lymphoma evolve...   Thank you in advance for new comments.
ugnius 2007-07-13 10:02	Molecular NOTE: from PRIMARY node with marginal B lymphoma B monoclonality is seen in Ig kappa chain. IgH is polyclonal.
tzankov 2007-07-30 10:18	Does the patient fit the clinical criteria of AILT?   Did you perform a PD-1 staining?
ugnius 2007-08-01 14:05	I cannot comment on the clinical picture. PD-1 is unavailable for the moment in our Centre.
ugnius 2008-11-14 10:19	Dear friens, please find EBV hibridisation in situ in 1) PRIMARY node (positive); and 2) the LAST node biopsy after treatment: negative in the tumor cells.
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