Ready. You are wellcome.

2nd line IH will be appended tommorow (S100 etc).

Dear Ugnius,  
 
I looked 3 times at the case, but have still not a good common denominator of all changes seen. Have you performed a cytokeratin stain in order to exclude preexistent thymic remnants, which might explain some of the pecularities seen if we have no better idea?  
 
Obviously there are TDT+ blasts (T? NK? dendritic?) with a cortical/subcortical distribution, but without expression of a marker of cortical thymocytes (CD1a-negative) and a medullar mixed cell population of CD4+/TDT- plasmablastoid cells and s100+ larger cells with some nucear characteristics of Langerhans cells. Would you please stain for Langerin and CD56, CD123, CD163? Are there skin lesions? Are there blasts in the periphery? Has the patient had any history of dermatopathic conditions? Was a bone marrow biopsy perfomed?

Thank you, Alex. Both components CD56(-). I will add PanCK for completteness. I'm sorry: CD123 and Langerin are absent still... Both definite populations are different by HE and IH (I have had an idea of blastic bi- population): espacially TdT/Bcl2/CD45RO and S100.  
The out-patient will be recruited for full evaluation soon.

I see. My problem is that in the middle of the node, the population that conventionally looks like Langerhans cells and that is CD1a and CD4+ expresses s100 only in every 4th cell. This is why I would be happy to see another Langerhans cell marker like Langerin; actually we have the antibody, I will stain it for you if you send me an unstained slide on adhesive glas. I discussed the cases with Sylvia, she convinced me, also based on a literature search, that combinations of Langehans cell neoplasms and lymphomas may exist. I think that she will write a larger comment on that issue.

Alex encouraged me to put here my perspective. Yesterday evening I made a search on Pubmed figuring out that there are already cases discribed with a conincidence of (clonally related)Langerhans cell histiocytosis and T-ALL (PMID: 17874453, PMID: 15925822). Rodig et al. could found also identical NOTCH mutations in these tumors. So these two entities seems to have a link to eachother.  
In our cases here this would fit with a Langerhans cell histocytosis (of course it would be good to have an additional Langerhans cell marker, however, the cytology is pretty convincing)and a component of T-ALL.  
I would recommend to do a comparative clonality analysis of the two compartments. Of course it would also be informative, if the lady has bone marrow involvement and/or peripheral Blasts.

Dear Dr. Mickys, dear Ugnius  
 
Thank you very much for sharing with me this extraordinary case. Additionally to what has been stained in your lab, I extended the panel by LMO2, Langerin as well as our own stainings for CD1a, CD2, CD4, CD7, TDT, S100.  
 
Considering the conventional morphology there is on the one hand a population composed of small immature pro-T lymphocytes (CD7 positive, CD34 positive, TDT positive, at least in our staining CD4 negative). This population expresses in addition LMO2, a feature seen only in neoplastic T lymphoblasts. Considering that population the diagnosis of a pro-T lymphoblastic lymphoma can be established. Importantly such cases with a very immature phenotype, expressing only CD7 but not CD2 have already been reported by Quinatnilla-Martinez et al. in the American Journal of Surgical Pathology 1992, Vol. 16, Page 1075. Importantly, such cases appear to be more commonly associated with Langerhans cell-histiocytosis.  
 
So I come now to the second population, which is one composed of large cells with indented nuclei with nuclear grooves and distinct nucleoli. These cells have abundant cytoplasms with some retraction artifacts and express CD1a, while the lymphoblasts remain CD1a negative. In addition these larger cells are positive for CD4 and S100 but negative for TDT. Langerin is expressed only by a minority of these cells. Considering the morphology and the immunophenotype this population corresponds to "maturing" neoplastic Langerhans cells. Thus, as suggested by you, we are facing here the case of a composite tumour consisting of a pro-T lymphoblastic lymphoma and Langerhans cell-histiocytosis. Such cases have been described (Rodig et al, American Journal of Hematology 2008, Vol. 83, Page 116 and Feldmann et al, Lancet Oncology 2005, Vol. 6, Page 435). Since such a coexistence within the same node hass not been reported I consider this case publicable.  
 
Final diagnosis:  
Lymph node:  
Composite haematolymphoid tumour consisting of a pro-T lymphoblastic lymphoma and Langerhans cell-histiocytosis  
 

Dear Alex. Thank you a lot for all done. The question left: is it possible due to "immaturity" and loss of Langerin of LC propose the version of malignant LC proliferation as LC sarcoma there?

Thank you very much for the further up-work of this very interesting case. I was very curious to hear about the final results, which strengthen the already proposed diagnosis.

Well, considering malignancy in Langerhans cell histiocytosis, WHO suggests overt malignant cytology and high mitotic count of >50/10 HPF; the phenotype does not help. In your case the cytology is worrisome and the mitotic count us 15/10 HPF (0.133mm2), so that the dignity of the LCH (benign/malignant) can not be definitively assessed based on histological criteria alone. At least what has been described in the literature by Quintanilla-Martinez does not seem to indicate a malignant course due to the LCH. What did the staging in this lady show? Are there bone lesions? etc.?

Thank you. By my knoledge only visceral CT (2010 December) was done: generalized lymphadenopathy + splenomegaly + 0.6cm nonspecific nodules (fibrotic?) in the lungs... Treated as acute lymphoblastic...

The case is completted by adding of BM and GASTRIC photos. The patient DOD in ~2013 in other hospital.