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DLBCL , plasmablastic, MUM1-,focal TdT+, MPO+ (6031)
DLBCL , plasmablastic, MUM1-,focal TdT+, MPO+closed
Subtitle: same case as 177253
Type:
Kidney and lymph node
Sender:
ugnius
2008-06-28 13:46
INCTR - EBMWG Hematopathology Online
This case is created, because IT WAS IMPOSSIBLE to append addition info to REFERALL CASE. Please find all previous discussion in the links below. Thank you. In future it would be usefull to check a box allowding other users to append pictures to the case.  
 
This case is under re-review. Additional material "lymph node" was send additionally.  
MACRO: 1310g 21x12x8cm kidney with 16x8x7 greyish yellow nodule with "capsule" and rudimentary cortical tissue left in periphery.  
KEY FEATURES: 1. "Blastic" appearance of the tumor with "dark" small and large blasts with ovoid, lobated and sligthly irregular/clefted contours (I'm in doubt about plasmablastic origin only). 2. Focal scant TdT and esp MPO positivity. Prominent B cell origin by IH: Pax5+, CD79a+. 3. CD138 reaction is not MEMBRANOUS, but rather cytoplasmic dot like (Golgi).  
FULL IH: LCA+; Pax5+; CD20- (single +); Bcl2+; CD3(-)(single faint +); CD79a+; CD4+; CD138+ 40% (Golgi and membranous); Ig kappa/lambda/M/D+; CD43+; Bcl6/CD10-; Mum1-/+ (faint focal); MPO+; TdT-/+ (single nuclei); CD68-; CD34/CD117-; CD99(+); Vimentin(-)(single groups + <5%); CD15(-); CD56(-); ALK1(-); CD99-/+ (marginal, faint); Myomarkers(-)(desmin/MyoD1/Myogenin); CAM5.2/PanCK(-); CD2/CD8/CD5/CD7(-); Hb/vWF(-); p53(-); CyclinD1(-).  
 
WORKING DIAGNOSIS: High grade tumor, most probably "blastic" lyphoma (BICLONE OR MYELOID?).
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hurwitz
2008-06-29 17:53
The morphology seems to be basically the same as in the previous specimen, plasmablastic differentiation can still be recognized, but it is less pronounced, paradoxically MUM1+ cells can be seen, but CD138 is not as strongly expressed as in the previous specimen.Immunostains are clearly in favour of a B-cell neoplasm. Partial positivity for TdT is an indication of component of precursor cells, which could explain the positive reaction to MPO. Aberrant MPO expression can be seen in lymphoblastic leukemia/lymphoma.  
For comparison stains for TdT and MPO are recommended on the previous biopsy and for Ki67 on the present material.  
It is also important to know if the patient had any therapy in the meantime.
tzankov
2008-06-30 09:03
We should seriously start to critically reconsdier our primary idea, but I am sure that this is a hemato-lymphoid neoplasia (CD45 and CD43+)(did you stain the tumor for the markers, that I recommended: Giemsa, EBER, CD56, Cyclin D1?). I consider the actual Kappa/Lambda expression inconcluisive, probably due to up-take, since there is no evidence of restriction. Myelogenous neoplasia, probaly with t(8;21) with PX5 and CD79a expression DD plasmablastic malignancy would be now my working hypotheses. Is there any evidence of leukemia? Bone marrow? Which colour had the renal tumor on macroscopy? Evidence of immunosuppression? HIV?  
 
I would collect as many as possible clinical and macroscopic data, then stain the slides with Giemsa, PAS, chloracetate-esterase, CD56 and cyclin D1 as well as EBER, and check if there is a t(8;21). All these data should allow correct diagnosis.
ugnius
2008-06-30 09:16
Thank you for comments. Add info: 1. HIV is negative. 2. Leukaemia IH panel is requested. 3. I have not EBER working now (~ after 1 month). 4. Ki67 is high (previous photos).  
The most striking thing is TdT focal positivity. I cannot imagine how to get false positive nuclear stains, but previous case with Burkitt lymphoma with TdT+ was another example.
ugnius
2008-07-01 11:16
Please find add IH and HE attached. MOst interesting thing is scattered faint CD3+ cells, difuse CD4+ positivity. MDSs like picture with serous degeneration and slight CD117+ immature precursor acess (will be appended soon).
ugnius
2008-07-01 16:36
Add: Bcl2+; Hb,vWF(-). Other IH from another block in progress.
anpo
2008-07-02 11:42
Have you stained for CD68? that would be a good marker to differentiate between granulocytic sarcoma with aberrant pax-5/CD79a expression and plasmablastic tumor with aberrant MPO in some cells. I would repeat MPO to be sure if it is specific. CD117 can be seen in plasmablastic tumors, however, CD4 is not characteristic. If TdT is seen only in single cells one can think about granulocytes that may be positive.
ugnius
2008-07-02 11:59
Thanx IH for sure will be repeated. Please find MACRO: 1310g 21x12x8cm kidney with 16x8x7 greyish yellow nodule with "capsule" and rudimentary cortical tissue left in periphery.  
hurwitz
2008-07-02 16:44
Dear Ugnius, I would like to clarify if the images you appended as case ID177253 were taken from additional tissue probes from the original material submmitted under ID177253?  
I fully agree with Anias comment, except for one point, the TdT positivity. Looking at the morphology of the TdT+ cells, which is easy to assess on the high power image of your nice stain, I think that the +cells are in fact tumor cells.  
 
The BMB shows interesting changes as well: The distributîon of hemopoiesis is patchy, and large areas of myelopathy are seen, with the typical mild increase of retuculin fibres. There seems to be slight left shift of myelo- and erythropoiesis. Megakaryocytes appear normal. These changes many be either postchemotherapy changes with regeneration of hemopoiesis or paraneoplastic.I would also recommend stains with CD79a and PAX5 in order to clarify the type of the CD117+ cells on the BMB, immature myeloid cells versus tumor cells.  
 
 
tzankov
2008-07-02 18:53
Since the renal tumor was not greenish, and the only serious argument against lymphoid malignancy are the positivity for MPOX and the vascular adherence/angiotropism (the letter could be observed in DLBCL), I still consider that there are much more arguments for a high grade B-cell lymphoma, than against. I can not find an exact drawer for this particular case, though I would have a speculative explanation for the presence of TdT+ cells, which I would not further comment here. Let's wait for all additional information, though form the clinical point of view this tumor would probably not leave us a lot of time for considerations and discussions.
ugnius
2008-07-02 19:05
Thank you for the comments. Some considerations/comments: 1. In BM CD79a/Pax5+ cells scatered seems to be lympocytes and plasmacytes. Any therapy with exception of steroid prephase was not applied in BM biopsy moment. 2. The tumor parafin blocks are external and low quality (I cannot found cytoplasm in not perfect Giemsa: only naked nuclei). So practically all IH stains are patchy with some exceptions. 3. MPO is focal positive, maybe false pos (polyclone Ab). CD68 is negative. 4. Scattered TdT+ cell phenomenon is strange and still remain unresolved. 5. The cytology and "blue" picture is more closed to blastic tumor of B line, but it seems for me not "plasmablastic" or "immunoblastic" (cleaves and nuclear countour irregularities). 6. CD4+ reaction is possible in ALK1+ DLBCL, but ALK1 is negative on our case. 7. I've requested some stains on 3rd block. By means of therapy (they have get a positive result from steroids only!) this high grade B tumor (DLBCL?) must be treated agressivelly- tomorrow we will discuss wiith clinical team about further tactics. Thank you once more. I'm happy not to be left alone in this complicated situation.
ugnius
2008-07-02 19:08
In added pictures CD99+ and CD138+ (membranous in part) seems to be really positive... Ki67 is patchy distributed (on average 70%, but up to 100% in some areas). P53, CyclinD1 are negative.
hurwitz
2008-07-02 23:32
The CD79a+ cells in the BM are large and have large nucleoli, so are the PAX5+ cells too large for normal lymphocytes as well. I would seriously consider minimal BM involvement. The finding of single scattered tumor cells in the BM is occasionally observed in DLBCL.  
Please do inform us about the decisions in tomorrows clinical conference.
tzankov
2008-07-03 09:41
CD4 can be expressed by plasmablstic DLBCL, see: Tzankov A, Brunhuber T, Gschwendtner A, Brunner A. Incidental oral plasmablastic lymphoma with aberrant expression of CD4 in an elderly HIV-negative patient: how a gingival polyp can cause confusion. Histopathology. 2005 Mar;46(3):348-50.
yethuwin
2008-07-05 07:45
We should also coonsider of intravascular B cell lymphoma  
ugnius
2008-07-06 09:29
Thank you all for discussion. For the treatment purposes this tumor was decided to interpret as high grade DLBCL (with some plasmablastic??? features and atypical imunophenotype). Some questions as nuclear cytology and IH profile (TdT+ (single cells), MPO+ (focal) and esp Mum1 negativity) remains unresolved. Maybe parafin block immunogenity was damaged in tissue processing.
yethuwin
2008-07-08 12:15
interesting case and get alot of knowledge. Thank you for your contribution.
hurwitz
2008-07-10 18:27
Thanks for this difficult case. After a lively discussion of all the different aspects of this tumor I can be closed. Please regard Ugnius' last comment as the final one.  
 
Regarding the unusual IHC profile (TdT+, MUM1- MPO+) I think it is rather due to true aberrant marker expression than to a damage of the block.
ugnius
2008-07-31 16:01
Please find PVR clonality results depicted (ppt file attached).
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Last modified: 2008-06-28 13:46:21