Thank you for this highly interesting and rare case. I will try to analyse it: The features of the skin biopsy (2002) are consistent with Langerhans' histiocytosis. The infiltrate is rather uniform, nuclear grooves can be recognized in some nuclei.There are only few lymphocytes in the background. I could not find any eosinophils. The infiltrate in the bone marrow biopsy(03/2005) shows a higher degree of cellular pleomorphism than the 3 years previously performed skin biopsy, and an extensive postivity for CD1a. The spleen, liver and lymphnode specimens examined later the same year exhibit a massive infiltrate by cells with malignant cytologic features most of them S-100+ and focally CD1a+. Focal positivity for CD1a is a feature of langerhans' cell sarcoma.Nuclear grooves can still be recognized in some of the cells. Many giant cells with varying degrees of phagocytosis.  
It seems that the process began as LCH and then gradually progressed to langerhans cell sarcoma with multiorgan involvement. The giant cells might be in part neoplastic, in part reactive. I would rather prefer to think that this in one process than postulating a combination with Rosai-Dorfman's disease.  
Lets wait for the comments of other collegues, since most of us do not have too much experience in such rare cases.

Dear dr.N.Hurwitz, I cannot find any Langerhans' cell CLASSIC component in spleen. CD1a+ cells are single ones. And multiple multinucleated macrofages seems to be reactive. It's strange, that Ki67 expression in lymph node is high enough (the photo is pending). Maybe you know some possibility to VISUALIZE the mononuclear histiocytic neoplastic (???) cells in this infiltrate or to PROVE true malignancy in this case? I can manage S100, CD68 and CD1a only.

In additional pictures "LN cells new" one can see, that CD1a+ single cells are with atypical wrinckled nuclei. Some of CD68+ cells are mononuclear and with some irregularity of nuclei. Some cells show the prominent ampho- nucleoli. For sure, CD68+ multinucleated cells fully obscure these, probably, neoplastic MONONUCLEAR cells with irregular nuclei. But still CD68+ population is > S100 and >>>> CD1a+.

Clin. history in detail: 2003/01: hospitalisation due to extensive maculopapular diffuse rash (from 10 months of age, and was treated for allergy with no effect). Skin biopsy: LCH. Multiple skull bone defects, diffuse skin, lymph node, gum, spleen and liver involvement, mild anemia, elevated ESR. Treatment according DAL-HX 93 protocol group C (Good response). Continuation therapy till 2004/11, because of risk organs involvement.  
2004/12 hospitalisation because of diffuse bone pain, high fever. Peripheral blood/BM aspirate analysis: panhypoplasia. New skull bone defects, enlarged liver and spleen, pancytopenia, elevated ESR. Treatment with cyclophosphamid, etoposid, methotraxate, doxorubicine, corticosteroids. 2005/04: skull bone defects declined. Fever remains with corticosteroids withdrawal. Liver and spleen remain enlarged. Bone marrow biopsy: LCH with hemophagocytosis. Spleen needle biopsy: compatible with LCH. Treatment: ATG, cyclosporine and corticosteroids. Bone marrow smears: panhypoplasia. Fever. He is reliant on blood components transfusion. Very rapid enlargement of spleen (170 mm) and liver.  
2005/09 splenectomy.  

Thank you for the additional images,clearly showing the cellular atypia. I agree that the amount of CD68+ cells is the highest, followed by S-100, and the portion of CD1a+ cells is the lowest. CD68+ are reactive macrophages,but neoplastic LC may express CD68 as well, vice versa macrophages may express S-100. CD1a showed strong positivity in the skin biopsy and the BMB, in spleen and LN there were only sporadic CD1a+ cells, which clearly have atypical features. I am not aware of any other way to visualize the atypical cells in the spleen or LN, except for morphology. I do not have a proper explanation for the small number of CD1a+ cells, except a for short statement in the WHO Classification of Hemopoietic Tumors saying that CD1a+ many be focal in LCS. Does this mean that there is a loss of this antigen? I do not know. I still have the impression that the child is suffering from one disease, which has taken an agressive course,as expressed by extensive multiorgan involvement.  
Do you perform bone marrow transplants in Lithuania? This could be a therapeutic option for this child.  

Dear dr.N.Hurwitz, thank you for comment. It's strange enough, that there were practically no eo's in skin biopsy and in the next biopsies. And the TYPICAL small LH cells with groove nuclei were absent. We have not the material from the bones and e-microscopy for Birbeck granules. One can say maybe it is "Non Langerhans' cell histiocytosis" or "precursor cell histiocytosis"? This child is candidate for BM transplantantion. We do have this possibility in Lithuania.  
It seems the massive giant macrophageal reaction with hemophagocytosis/ emperipolesis and hemosiderin tends to be reactive.

[comment sent by email]
I had the same thought, perhaps we are completely wrong with our
 
diagnosis? Anyway lets hope that BMT will help the child, this is more
 
important than our academic discourse.
 
 

to me, this is an extremely difficult case but well compatible with lch. i do not see the criteria fulfilled for rosai-dorfmann disease or another concomitant process.  
to confirm the dx elmi woul probably be necessary ot at least repeating histochemical and ihc an all blocks in another laboratory.

Dear collegues, thank you for kind opinions. If any lab elsewhere in the whorld would be so kind to make any additional stainings or e-microscopy all material would be sent in a short time. Your help is highly appreciated.

Langerhans' cell histiocytosis is my favourite diagnosis in this case. Although there is a description of an association with Rosai-Dorfman disease (Wang KH, Cheng CJ, Hu CH, Lee WR. Coexistence of localized Langerhans cell histiocytosis and cutaneous Rosai-Dorfman disease.Br J Dermatol. 2002 Oct;147(4):770-4), i think that is not the case. For the definitive assessment of Langerhans cell origin of tumor i would suggest in all specimens the staining with langerin. I know that Dr Fabio Facchetti in Brescia Italy (facchett@med.unibs.it) has the antibody: you could send him unstained slides and ask for the immunostaining.

Dear Collegues: Dr.N.Hurwitz, Dr.S. Dirnhofer, Dr.V.Franco, Thank you for help in this complicated case of malignant LCH/LC sarcoma. It would be great to "see" you in the future cases/discussions.

The case was sent to dr.S.Dirnhofer who kindly accept it for external consultation. Thank you for help.