79 yrs old woman with 0,5year duration of symptoms: itching, dark coloured skin (from birth after patient's words) with papular eruption and excoriations (buttocks, hands, abdomen, inguinal skin). Peripheral (neck, axillary up to 3cm) and visceral(1,5cm paraaortic) lymphadenopathy. Eosinophilia in BM aspirate. LDH 1121 U/L. Any lymphocytosis in the blood.  
HISTO:  
1. NODE BIOPSY (inguinal): Dermatopathic/LCH like picture with binary S100/CD1a (dark and light) population and minimal CD3 convoluted cell component. FE deposition is absent.  
2. SKIN BIOPSY (inguinal): Linear CD3+ CD4+ infiltrate with minimal epidermothropism and convolutions.  
3. BM BIOPSY: Single CD3+ convoluted cells and CD117+ mastocyte reaction (single spindle cells) in slight fibrotic background.  
 
PROPOSAL: 1. NODE: LCH vs MYCOSIS FUNGOIDES/SEZARY S. spread in lymph node with lch/dermatopathic lymphadenopathy like reaction.  
2. SKIN: Minimal mycosis fungoides 3. BM: REACTIVE CHANGES vs minimal mycosis fungoides ???  
DIFFERENTIAL: Thank you for continous support/education.  

hurwitz 2008-06-23 19:42	Let's start with the skin,the infiltrate is well consistent with MF. The expanded paracortical areas of the LN seem to contain two populations which are closely intermingled, one morphologically and immunophenotypically consisitent with LCH, and another minor population of CD3+ atypical lymphoid cells, some of which are CD30+. These changes are suggestive of LN involvement by MF with evidence of large cell transformation, CD30+ and concomitant LCH. The association between LPD and LCH is well documented, in most cases it seems to represent a reactive polyclonal process   {PMID: 16360413}.   The BMB contains scattered large CD3+ cells, arising suspicion of a minimal BM involvement which has to be confirmed by clonality analysis. The single scattered mast cells are reactive.   The LN and BM involvement should be confirmed by a clonality analysis prove TCR rearrangement.
hurwitz 2008-06-23 19:54	Of course it would also help to know the exact localization of the skin lesions
schulze 2008-06-23 21:24	A dermatopathologist, I agree with you, the skin infiltrate is well consistent with MF, eczema stage.
k.naresh 2008-06-23 21:33	Skin: The morphological features are compatible with Mycosis fungoides. I would however, like to know the distribution of lesions and CD4:CD8 ratio of the infiltrate, and would perform T-cell clonality studies.     Lymph node: Florid reactive Langerhans cell and dendritic cell expansions are known to occur and the findings presented would be consistent with it. This appears to be a reactive process. Eosinophils are notably absent in the lymph node images. In addition, there is an atypical T-cell infiltrate and this would be compatible with skin lesion, once the clonality studies are performed on the skin lesion.     Bone marrow: I would refrain from over-interpreting the scanty T-cell infiltrate.
diane.c.farhi 2008-06-24 01:30	I agree with the statements above, with a few reservations. The skin lesions show relatively little epidermotropism and a somewhat scanty dermal infiltrate. I would feel better about the dx of MF with high-power H&E or hematoxylin only (such as a negative control for immunostains) images showing atypical lymphoid cells and mitoses, not obscured by positive immunostaining, but I defer to the other discussants on this point. The node does look like LCH, but what about the possibility of dermatopathic lymphadenopathy? The node also shows atypical cells, mitoses, and CD30+ cells, and may be involved by MF; again, I would like to see high-power images of the atypical cells not obscured by immunostaining. The bone marrow shows surprising fibrosis; I don't know what this means. I think the marrow should also be stained for Langerhans cells. This is an interesting case; perhaps the pt should be worked up for other evidence of LCH. There are very few reports in the literature of MF+LCH, the best being the one Nina has already referenced. It might be worth putting this one into the literature as well.
tzankov 2008-06-25 16:35	I would favor, late (therefore predominantly non-epideriotropic) MF in the skin, dermatopathic LA with MF infiltration in the lymph node (with increased amounts of CD30+ large cells) and reactive BM changes.
SergeyN 2008-06-25 21:39	There is CD1a infiltrate in the skin, too, and CD1a+ cells seem to be morphologically similar to the lymph node population. Just to be sure, I would second the ideas to stain bone marrow for S100/CD1a and lymph node for melanin/iron.     By the way, 79 is a very uncommon age for LCH, another reason to be careful. Systemic manifestations in this case, including rather disseminated lymph nodes remains unexplained. Do we face a disseminated MF with limited local process?
hurwitz 2008-06-26 15:56	Thank you for mentioning dermatopathic lymphadenopathy with involvement by MF in the DD. I think there is little doubt that the lymph node is involved by MF, possibly with large cell transformation CD30+. As said before clonality anylysis of the LN and BM is recommended for confirmation.   However, I do not recall having ever seen a dermatopathic lymphadenitis with such a prominent langerhans' cell reaction. Reactive LCH cam be local and does not necessarily imply a disseminated process.   Regarding Sergeys comment, the CD1a+ staining in the skin, represents the normal langerhans' cell population in the skin.
tzankov 2008-06-26 16:09	I have seen for several times such Langerhans cell hyperlasia in dermatopathic conditions and in patients with cutaneuos T-NHL. Indeed, one can anticipate that Langerhans cell hpyerplasia in the lymph nodes should be much more commonly seen in reactive conditions than in disseminated LCH, since disseminated LCH is an extremly rare disorder, but dermatopathic conditions are not.
hurwitz 2008-06-27 17:25	I would suggest simple old fashioned stains for fe and melanin to show the "dermatopathic" component.
torlakovic 2008-06-28 00:07	I agree that skin looks like MF. I think that the lymph node is involved by MF (LN2 or LN3 pattern with small vs. large clusters of atypical cells, which is not entirely clear from the images; favor LN3) and shows exaggerated dermatopathic response (dermatopathic lymphadenopathy - DL). The main differential with LCH should be resolved histologically. LCH in the lymph nodes is usually sinusoidal primarily and than paracortical, while DL is primarily paracortical and is expected in LN involved by MF. Also, there is no eosinophilia in the LN. Langerhans cells associated with MF can/usually have immature phenotype and I wonder if what we see here as a variation of CD1a expression is due to that fact combined with activation of Langerhans cells when they migrate in the LN. I just have not seen that many cases of MF with exaggerated DL to pay attention to this fact.   The bone marrow eosinophilia can be seen in patients with MF and it does not correlate with clinical stage. In this case, there are suspicious atypical cells in the BM and molecular study may help.
ugnius 2008-06-28 10:09	Thank you. Please find some clinical data above. PCR will be requested. Mycosis fungoides diagnosis, as preliminary, from LN and SKIN is stated at the moment. Appologies for problematic visualisation of single "cerebriform" cells. Apperio scaner is under repair so there is only limited possibilities to depict the histo picture in detail via digital shots.
hurwitz 2008-06-28 13:48	Thanks Emina for the suggestion that the obvious difference in staining intensity of th Langerhans' cells might be related to their maturation.   We shall wait for the PCR results promised by Ugnius, before closing this case.
ugnius 2008-07-31 17:25	Please find T polyclonal results from node and skin...
hurwitz 2008-08-01 17:47	Regarding the skin, I doubt that the failure to demonstrate a clonal T receptor rearrangement does affect the original diagnosis. As for the result on the lymph node, it means that no lymph node involvement can be proven by PCR, but it is not excluded.
torlakovic 2008-08-07 23:04	The sensitivity of the similar PCR test is our institution is about 90% (meaning <100%). That said, I would re-evaluate the case with dermatologist. Also, findings in the skin biopsy seem to be compatible with MF, but we are actually looking into frozen images of various magnification, which is suboptimal. There is only one image that shows intraepidermal component without spongiosis and possibly atypical lymphocytes. While the lymph node clearly demonstrates dermatopathic lymphadenopathy, the evidence for the presence of atypical lymphoid cells should be assessed in the first place by morphology and by the CD3 staining. The findings in your images appear compatible with involved LN, but you need to evaluated again yourself to see if you indeed are convinced that there are atypical cells. Showing 40X images rather than 60X or 100X may be better for estimating cell size and possible atypical in this case, because if the cells are "too close", they will look more atypical. Alternatively, you may want to ask for a new skin biopsy to confirm the diagnosis.
ugnius 2008-08-08 09:16	Thank you. I will inform you about follow up of the case.
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