30 yrs male was diagnosed skin mycosis fungoides (follicular mucinosis type) in the face skin in Sptember 2009. Previously throid papillary carcinoma pT2 was resected in May 2007. Recently the dext testis was removed due to suspition of malignant tumor.  
HISTO (last episode): prominent necrosis and haemorhages are present. In periphery tubules with interstitial T infiltrate were seen with prominent LARGE B CELL peri- and intra- tubular thropism.  
CLINICALLY: Any signs of systemic disease. Inf parotitis serology NEGATIVE. The lession was strongly unilateral.  
IH: Large cells with tubulothropism: CD20 (+++)/CD79(++) large blastoid cell (IB) up to 30% population with tubulothropism: TdT/CD34(-), Pax5(++)100%, Bcl6(++)10%, CD10/Bcl2(-), Mum1(+/+++) 60%, CD30(++) 20%.  
Ki67 ~80% (in general population ~30%). CD3/CD2(+++) (citopl. r-ja) T lymphos eith irregular/cleaved nuclei up to 70% populiation: Bcl2(++) 80%, TdT(-), CD7/CD5(+++) 70%, CD4(+++) 60% (+++), CD8 40% (+++), GranzymB/Perforin(+)5%, TIA1 30% (+++), EBV LMP1(-), CD56/CD57(+)<5%.  
single CD138+ plazmocitai. Multiple CD68+ macrophages in stroma and within tubules. CONV PHOTOS: Enclosed. VIRTUAL: Enclosed.  
MOLECS: TESTIS: 1st round: B IgH/IgK clonal and T gama clonal, T beta polyclonal (not enough material). 2. Second round: TCR beta clonal, TCR gama ir delta polyclonal, IGH/IGK/IGL polyclonal. The result is ambiguous. SKIN: pending.  
PROPOSAL: B pseudolymphoma, maybe virus induced necrotic-haemorhagic orchitis vs ???.  
QUEST: Incorporation of all findings.  
Thank you for collaboration.

kunze 2009-02-22 14:24	There are serious arguments in favor of an inflammatory finding (pseudolymphoma), in particular a granulomatous orchitis: (1) the granulomatous appearance of the involved tubules with histiocytoid eosinophilic cells (in addition to interstitial aggregates of Leydig-cells which can be found in the VS), (2) the mixed composition of the infiltrate with small to medium-sized B- and T-cells, plasma cells and eosinophils, and (3) the unilaterality.
Mueller-Hermelink 2009-02-22 16:32	Again a difficult case: I believe that the CD3 pos. T cell infiltration is reactive ( no cytological atypias) , you should prove that also by establishing the usual ratio of CD4 /CD8 cells). However , I have difficulties calling the CD20 positive invasion of tubules a reactive process, Maybe it is early testicular large B cell lymphoma. Could you look for a definite phenmotype of these cells( kappa /lambda, Mum1) If these cells are really plasma cell precursors a monotypic light chjain expression would be a strong argument.Do you have a reason for the extensive necrosis: More embedding of the spermatic cord and Epididymis would be interesting.
bvrugt 2009-03-02 13:01	I agree with Prof Kunze and favor an inflammatory process. Despite the dense infiltrate an extensive loss of tubules generally seen in testicular (large cell) lymphomas is not prominent in the presented images. However, because of the necrosis I would investigate the presence / absence of clonality of the B-cell population.
ugnius 2009-03-02 13:24	Thank you. MOLECS: 1st round: B IgH/IgK clonal and T gama clonal, T beta polyclonal (not enough material). 2. Second round: TCR beta clonal, TCR gama ir delta polyclonal, IGH/IGK/IGL polyclonal. The result is ambiguous.
ugnius 2009-03-02 13:24	CD4/CD8 is abou 1,5-2/1.
kunze 2009-03-05 11:52	Apart from the clonality studies the immunohistochemical expression and distribution of light chains would be of interest.
hurwitz 2009-03-05 19:29	It is a very unusual case. Extensive necrosis and hemorrhage are prominent features on low power. Is there any history to explain these changes? Trauma ? infection? Could you see a tumorous mass on macroscopical examination ? On high power, the large CD20+ cells do show a certain degree of atypia, and infiltration into the tubular lumina, still not a convincing argument for lymphoma.   In the absence of unequivocal proof of clonality I would not dare to call this lesion lymphoma. Incubations with Kappa and Lambda light chains might help.
ugnius 2009-03-06 08:15	Comment from our molecs about PCR results: "Discrepant results of the two clonality test rounds could be explained by differences in quantity (i.e. concentration 0,02 ug/ul vs. 1 ug/ul) and quality of the extracted DNA, nevertheless, the same paraffin block was used in both cases. Low DNA amount will result in limited number of targets for PCR which in turn could generate a “clonal-like” picture and false positive interpretation. I suggest the results of the first Clonality test should be treated as “uninterpretable” and therefore must be ignored or dismissed".
anpo 2009-03-08 15:16	I think that one still cannot rule out the possibility for DLCB - the B cells were of activated B-cell phenotype and not of germinal center cell phenotype which is most often in pseudolymphoma. Could you please make a virtual slide of CD20 in HE1? In the virtual slide CD20 there is a dominance of necrosis and it is difficult to evaluate CD20 pattern. However even in this slide there is a sign of rather aggressive infiltration of large CD20+ cells. I assume the DNA for PCR was isolated for the HE1 block. Maybe PCR for IgH should be repeated once more if you got two different results? Also - does the patient have circulating pathological T-cells in blood? that happens in paths with cutaneous T-cell lymphomas and can explain the positive TCR pcr.
torlakovic 2009-03-17 19:25	I agree with most what was already said. I would only want to add and additional consideration. Even though the site is not perfect, an extranodal disease with T-cell predominance, in a young male, and extensive, infarct-like necrosis evokes the possibility of a lymphomatoid granulomatosis. I wonder if the skin lesion also had some B-cells that are EBER+. LMP1 is not good for EBV demonstration since it will not be positive in latency type 1. You need to do EBER.
ugnius 2009-03-18 10:02	Thank you. LYG udea was discussed, but really there are very rare reports on that in extracutaneous or extrapulmonic localisations. EBER was negative.
ugnius 2009-03-18 10:02	Please find kappa/lambda without restriction and add CD20 vurtual slides.
ugnius 2009-03-18 10:36	COMMENT 2 FROM MOLEC'S LAB (M.Stoškus): Clonality test of this case (B09-2959) was performed twice. The results of the first analysis round were not valid as too low DNA quantity was available for the clonality test. The second round revealed a valid result with a clonal TCRB V-J1/2 rearrangement in the polyclonal background. All other regions (IGH, IGK, IGL, TCRG, TCRD) tested were polyclonal.     Clonality analysis of the microdissected skin biopsy failed due to insufficient material for the clonality test.
tzankov 2009-03-20 15:48	In deed a very difficult case. I agree with all what has been previously said. The unilaterlity, withot signs of sytemic disease and the inflitration of the tubules by CD20+ B-cells with "immunoblastoid" morphology and lacking germinal center phenotype is worrying. Clonality analyes are obviously inconclusive. FISH analyses to rule out IgH breaks or other recurrent chromosmal abnormalities e.g. BCL6 gains etc. might help to solidify the diagnosis. How ist the follow-up? Has the patient "prophylactically" being staged? What do the clinicians think?
ugnius 2009-03-20 16:00	After viral orchitis idea (it was not confirmed serologically) the version of reactive state was choosen. The patient is still under supervision. I've asked info about clinical news.
tzankov 2009-03-23 16:14	A final conclusion can not be drawn in this particular case, since malignancy, especially DLBCL, can not be completely ruled out at that time. Because additional examinations (e.g. IgH, BCL6, BCL2 or c-MYC FISH) would probably be very difficult to be performed due to obstacles in identification of the relevant cells and the clinicians have been informed on the diagnostic uncertainty to perform a close follow-up, the case can be closed for the moment as "lymphoid testicular proliferation of uncertain significance". Any follow-up data are welcome.
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