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NLP- HL CD15+ (3062)
NLP- HL CD15+closed
Subtitle: B07-10534
Type:
HEMATO
Sender:
ugnius
2007-04-19 12:50
INCTR - EBMWG Hematopathology Online
CONSULTATION CASE/ EXTERNAL PARAFIN BLOCKS/ LOW QUALITY.  
HISTORY:49 yrs old male with lymphadenopathy in the neck slowly growing for 2 yrs. Any B symptoms are present. Lymph node biopsy (5,3cm) was performed.  
HISTO: Nodular and diffuse LH infiltrate with scattered giant cells with lobulated nuclei. Multifocal central "clearing" in nodules (floret like).  
IMMUNO: atypical lobated/iregularly nucleated cells with large nucleoli in "floret" nodules: CD30-CD15+EMA+CD20+ Bcl2-Mum1-Bc6+; There are identical scattered cells in diffuse histyocyte reach areas, but CD15-/+CD30-EMA-CD20+. CD21+ prominent FDC network in the nodules, but CD23+ only single groups of FDC. CD57 accentuation in the nodules with peritumoral rosetting.  
SCHEME: Blue- rudimentary follicles, dotted blue- tumor nodules, pink- diffuse histyocyte reach areas.  
QUEST: NLP HL with CD20+CD30-CD15 immunophenotype? Why tumor cells in the diffuse areas are slightly IH different: CD15/EMA loosing (TcrB transformation possibility? Underfixation/underprocessing in eosinophilic/diffuse areas?).  
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hurwitz
2007-04-22 19:56
The differential diagnosis is between NLPHL and cHL, lymphocyte predominant.CD15 expression is usually not observed in NLPHL, but it may occur and does not exclude the diagnosis. Most features favour the diagnosis of NPLHL, for the nodular part.  
For the diffuse part you describe a change in immunophenotype, which is difficult to follow on the images, since not all images are labelled from where they were taken, nodular or diffuse areas.I would be gratefull for adding the missing labelling and then try to reassess the case.
hurwitz
2007-04-22 22:15
I am afraid I did not express myself clearly in the previous comment. The question regarding the diffuse areas is: is it part of the NLPHL, or cHL, or beginning transformation into TCRBCL?  
Anyway lets see what others have to propose.
anpo
2007-04-23 00:31
I think that this case may be one of the sc grey zone lymphomas - it has morphological and IHC features of NLP HL (especially very clear CD57+ rosettes) but also positivity for CD15 and EMA and some clusters of large CD20+ cells. I have not seen any case of NLP HL strongly positive for CD15 and could not find really any good example in literature. Are there are sheets of CD20+ cells that would suggest transformation? I agree with Nina that the morphology and IHC of these diffuse areas are somewhat difficult to evaluate.  
I attach a publication that describes CD20/CD15+ grey zone NHL/HL but these were different due to mediastinal presentation and CD30 weak positivity.
attachment: CD15_NHL.pdf
aorazi
2007-04-23 00:44
Interesting case. The morphologic features are consistent with a nodular lymphocyte predominant HD. I would not be concerned for the the presence of "diffuse" areas. These seem to have the same cytological composition of the nodular ones. The presence in NLP-HD of areas resembling TCRBCL has been reported. This finding, however, seems to be devoid of clinical meaning (see Boudova et al. Blood. 2003 Nov 15;102(10):3753-8. Epub 2003 Jul 24). In conclusion, I believe hat this is NLP-HD. CD15 expression in NLP-HD ia actually not that uncommon and can occurr in 10% of the cases.
SergeyN
2007-04-23 09:30
Dear Ugnius, in our case (see "progressively transformed GC's (109451)") a bit peculiar LPHL was followed by a B-cell NHL within a month. So it is possible that atypia could be sometimes a mark of evolving transformation.  
 
So have the patient followed, it could be the final proof. Otherwise it looks like LP.
kremer
2007-04-23 12:54
I fully agree with Attilio, and think its a NLPHL, rather than two lymphomas (NLPHL and TCRBCL) since the nodular and diffuse part are phenotypically similar. Is CD30 staining certainly negative ?
ugnius
2007-04-23 13:37
Dear collegues and friends. A lot of thanx for your comments and a lot of appologies for difficulties with understanding of photos. The well known problem is how to represent all lession with the kaleidoscope of the 10x-40x pictures. Th subjectivity does remain...  
The diffuse areas seems to be similar to nodular ones (cellularity, giant cells, CD15+EMA+ CD20+cells) with exception of LOWER IH reactions (EMA and CD15).  
With great pleassure I will repeat some photos if you need.  
CD30 is faintly positive only in medium perifollicular cells.  
The question is: are there some additional conventional or IH methods which I miss to exclude THsr DLBCL? The PCR for IgH will be arranged routinelly.
ugnius
2007-04-23 13:44
Some remarks on the file names: NODULAR and DIFFUSE are appended to all photos.
torlakovic
2007-04-24 06:30
I agree that this is a case of NLPHL in nodular and "diffuse" areas. The neoplastic cells may be CD15+, which would be OK in rare case of NLPHL, but also one must admit that it is becoming more difficult to interpret CD15 results nowadays when the sensitivity of the test is such that some histiocytic and dendritic cells, which may be rather large, also turn strongly positive. For the sake of discussion only, cHL is kind of excluded by absence of CD30 expression and by strong expression of all other markers already mentioned (CD20,Bcl-6,CD45,etc.), but Oct-2 and PU.1 may have been confirmatory if done. Also, if you would really need more evidence, which I do not think you need, EBV would never be expressed in NLPHL and in my experience, it has been present in good number of lymphocyte rich cHL. The real question is about diffuse areas. They are not so extensively illustrated, but I think it is very likely that these are a slight variation of the same because the immunophenotype changes slightly when the cells do not home to GC environment anyway. If there are not sheets of large B-cells or total loss of small B-cells, or other striking background changes, I would not consider any other diagnosis.
ugnius
2007-04-24 09:06
Thank you once more. Really the distribution of the similar tumor cells (like in nodules) is similar in diffuse areas. Oct2 and BOB.1 are still absent in our centre.
Mueller-Hermelink
2007-04-27 12:06
There are very good comments that I all agree. I just want to add two short comments:  
1.) I have seen incidental coexpression of CD15 in NLPHD L&H cells, however, as a focal and inconsistent feature which did not change the outcome ( within the study of Boudova et al). The very consistent expression here is unusual.  
2.) The amount of proliferation in the diffuse areas is very high and to my view not explained by the amount of large B cells( but this is really not easy to be judged from the submitted photos) and also the expression of CD 68 in the diffuse areas is very high and unusual. Can a myeloid proliferation be excluded?  
In summary , the NLPHD is an agreed diagnosis and the features shown do not signalize a form of transformation to DLBCL, but a review of proliferating cell types in the diffuse areas would be interesting.
hurwitz
2007-06-30 23:49
The main point of interest in this case is the combination of nodular and diffuse areas in an NLPHL, raising the question of the nature of the diffuse areas, either part of the same process or transformation?  
Most commentators felt that there are no real morphologic and immunophenotypical differences between diffuse and nodular areas,meaning that both are part of the same process, which lead to the diagnosis of NLPHL with diffuse areas.  
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Last modified: 2007-04-19 12:50:22