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prominent macrophages DD storage disease/microorganisms, reactive lymphocytosis (4084)
prominent macrophages DD storage disease/microorganisms, reactive lymphocytosisclosed
Subtitle: B07-28524		 Type:
bone marrow biopsy		 Sender:
ugnius 		2007-11-12 09:18
INCTR - EBMWG Hematopathology Online
38 yrs old male with hyperglobulinemia (esp. IgM), hepatosplenomegaly underwent threpine biopsy.  
HISTO: The prominenet infiltration of macrofages, focal serous degeneration, architectural abnormalities, erythroid hyperplasia. Definite features of hemophagocytosis are absent. The single mixed B/T (reactive) peritrabecullar follicle is present. Intersticial lymhoid population: CD3+ > CD20+ (reactive).  
CLIN DIAGNOSIS: Waldenstrom disease (LPL)???  
IH: Nothing special. The single CD117+ mastocytes. Ig kappa/lambda monotypic.  
PAS staining (not standard in our BMs) is in progress.  
 
PROPOSAL: Reactive changes: the prominent macrophageal reaction in BM: hemophagocytosis? Virus induced? Etc.?  
 
Thank you fo being 2gether.
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tzankov
2007-11-12 12:24
Considering the clincal history and the peritrabecular location of the nodular (follicular?) B-cell infiltration and the CD38+ cell groups, one should rule out B-cell clonality (kappa, lambda, alpha, my, gamma), partculalry since I have seen a couple of LPL and MZL involving the bone marrow, where T-cell highly outnumbered the B-cells. were there partculalry many mast cells (Giemsa)? were the foamy cells PAS+?
ugnius
2007-11-12 13:00
Thanx. Well, Ig kappa/lambda polytypic; PAS was not done yet (I will proceed); CD117+ mast cells are single. The age 38 is not very typical for LPL. The follicle is typical mixture with reactive architekcture: CD20+ core and CD3/CD43/Bcl2+ rim with CD23+ single cells.
tzankov
2007-11-12 13:18
Of course I would not at all diagnose a LPL, especially if Kappa/Lambda are polytypic (and done, but not mentioned). The accumulation of plasma cells (polytypc), follicles and foamy histocytes should be interpreted within the clinal context, particularly the type of hypergammaglobulinemia (Lupus, chronic viral infection, other autoimmunopathies).
diane.c.farhi
2007-11-12 17:13
This is an unusual case, showing storage histiocytosis, a benign lymphoid follicle, and plasmacytosis. I would consider the possibility of Gaucher disease, which can present in adulthood with hepatosplenomegaly. I don't think the histiocytes are consistent with hemophagocytosis or sinus histiocytosis with massive lymphadenopathy, as no phagocytosis or emperiopolesis is present. The trabecular bone looks thin and sparse for a male of this age, suggesting a long-standing process. I suggest a workup for Gaucher and possibly other storage diseases.
ugnius
2007-11-13 14:26
Please find fine granularity only in these pale histiocytes.
ugnius
2007-11-13 14:29
Giemsa granularity too. 100x air.
hurwitz
2007-11-15 21:38
No question that this is an unusual case. The most striking finding are the large "foamy" macrophages. The added images of Giemsa and Grocott stained sections raise the question of an opportunistic infection(Leishmania or others). Could you please add a high power image (100x)of the Grocott stained section in order to better appreciate the site of the black granularities. An important question is the HIV status of the patient, or if there is any other indication for an immunodeficiency?  
I hate to contradict my friend Diane, but Gaucher seems to me less likely because Gaucher cells have a characteristic " watered silk" appearance, which is not seen in the cytoplasma of these cells.  
I agree with the others that the lymphoid infiltrates are most probably reactive.
diane.c.farhi
2007-11-15 21:55
[comment sent by email]
In response to Nina, I agree that these cells are not typical of
 
Gaucher, per se, but look like storage histiocytes; I should have made
 
myself clearer in my original comment. There are many constitutional and
 
acquired storage histiocytoses, and I think consideration should be
 
given to this possibility
 
ugnius
2007-11-16 15:05
Please find 100x air. I still think, that due to small caliber these granules represent usual debris in macrophages, not parasites/infectious agents.
SergeyN
2007-11-18 18:56
Very strange. Look like toxoplasmosis, SARS or mycobacterium avium associated macrophages, but no evident microorganisms.  
 
I think that theoretically Niemann-Pick type B (adult) should be excluded. There is a range of other extremely rare storage diseases with the similar morphology, but they like NPD type A should be evident in childhood.  
 
Erdheim-Chester disease could be another exotic option (and clinically not very suitable, too).
kunze
2007-11-18 22:07
I've no experience with the appearance of L. donovani in a Grocott stain but I think the Giemsa-stained macrophages are suspicious of a Leishmaniasis.
ffrenchma
2007-11-23 19:14
Clinical presentation: 38 old man, hepatosplenomegaly, hypergammaglobulinemia (polytypic). This is compatible with a leishnaniasis.  
What is the result of blood cell count ? Inflammatory Syndrom ?  
 
Histo: histiocytosis infiltration with reactive lymphocytosis.  
 
- We can exclude Macrophagic Activation Syndrom.  
- Pictures are not typical for Gaucher cells. It semms to be Gaucher-like cells.  
- For leishmania we must clearly see the nucleus and the "kinetocore" of the parasite. We can't see kinetokore on the giemsa. Do you see that on your slides ?  
- If leishmania are not present, a ziehl staining must be performed particularly if the patient is HIV+  
anpo
2007-11-24 21:52
Do you have BM smears from this patient? Leishmania is much easier to diagnose on smears than in the biopsy sections.
hurwitz
2007-11-25 22:11
Thanks Ugnius for the high power images. The information we can gather from those images, is that these are certainly intracellular corpuscules, which is an argument against artefacts. I am not sure, but still I think we cannot exclude the possibility of an intracellular microorganism, such as leishmania. An other more remote option is histoplasmosis, which is rare in Europe, but may occur in HIV+ patients.  
I absolutely agree with Anja that the findings on the aspirate might help to solve the dilemma. Could you please try to find out what has been found on the aspirate and if possible post some images of the aspirate?
hurwitz
2007-11-25 22:22
Considering leishamniasis or histoplasmosis in the DD I must admit that I have never seen such prominent and large histiocytes neither in leishmaniasis nor histoplasmosis.  
In reply to Sergeys suggestion of mycobacterium avium: atypical mycobacteria are long needle shaped and might be recognized on H&E,and certainly on PAS stained sections.
kunze
2007-11-26 13:34
I remember to a visceral Leishmaniasis with similar large histiocytes in a bone marrow biopsy. But I'm not familiar with the appearance of L.donovani in the Grocott stain and would not rule out a fungal infection with a degree of certainty. Is there any possibility to prove a Leishmaniasis by PCR or serology?
ugnius
2007-11-26 18:37
Thank you for shown above still different possibilities. Really I'm not sure that this vesicular "dust" represents the parasites. Sometimes the macrophages display such things (just observation). I will request add data about history (duration of the symptoms, familly anamnesis, etc). All mentioned possibilities was formulated in preliminary report. It seems that all possible was done in this isolated BM biopsy test. Clinical corelation and add evaluation is strongly required.
erber
2007-11-26 19:28
I am of the opinion that the macrophages show features of a primary storage disorder with a reactive lymphoid follicle and plasma cells in the marrow. I do not think this is a primary lymphoid process.  
The family history, a bone marrow aspirate (better morphology of the macrophages) as well as Biochemical analysis (if available somewhere) to determine the precise defect and diagnosis.  
 
ugnius
2007-11-27 11:07
Thank you once more. Unfortunatelly I'm located in totally geographically/admistrativelly separated/isolated/independent pathology center, dealing with all histo materials (except aspirates/ PB) and sometimes the retrieval of add data and insisting to perform add evaluations are complicated enouh. Appologies for that.
hurwitz
2007-12-11 19:37
Following the discussion of the case with many participants I have the difficult task to summarize this case:  
One thing we all agree is that there is no evidence of an infiltrate by low grade lymphoma as stated in the clinical diagnosis.  
But no consensus was reached on the other intriguing finding, the prominent large macrophages containing some "corpuscules". Some thought that they show features of a primary storage disorder suggesting additional clinical data and a work-up for storage disease (Farhi, Erber, Nikulshin) Others favored the option of a parasitic infection, such as leishmaniasis (Hurwitz, Ffrench, Kunze, Porwit), however we did not have enough arguments to prove either option. Therefore this question has to remain unanswered.  
This case in an other example for a fact, repeatedly stressed in this forum: Morphologic findings need integration into a wider clinical and laboratory context for correct and reliable interpretation.  
 
hurwitz
2007-12-16 00:12
I for got to refer to Dr.Kunzes question about PCR for leishmania. Yes there are specific probes in specialized laboratories, usually not in pathology labs, therefore it would be a difficult enterprise to try to perform it on this biopsy.
gmlearmonth
2008-01-10 15:11
DR Hurwwitz, I found this case in the Haematology Group !Thank you for asking my opinion on this patient of 38 years with an appaernt history of B Cell Lymphoma. Has he had treatment for this ? If yes, when. Recently ? or dsistant part ? Do you have a direct blood smear. Or a smear of the trephine biopsy.  
Erythrophagocytosis is observed in many neoplastic syndromes. it is often seen on cytology smears in large lung cancers, folloicular carcinoma of thyroid, hepatocellular carcinoma etc etc.  
I see that one colleague has queationed the hIV status of this patient ? What is the result of this ? Infiltration of the marrow in immunospressed patients has been reported.  
I do not think that the intracytoplasmic parrticles seen on the Giemsa stain are Toxoplasmosis parasites. an outside possibility is an alien organism from, for example a dog/canine bite, in an immmunocompromised patient.  
Thank you for an interesting set of images.
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Last modified: 2007-11-12 09:18:48