61 yrs male underwent lymph node biopsy due to neck lymphadenopathy, weight loss and fever.  
Clinical diagnosis: HL.  
HISTO: On the slides: focal septation and "granulomatous" necrosis with sincytial growth, focal sinus spread, focal L and H picture.  
IH: GIANT CELLS: CD30+ 100%; CD15+ 15%; EMA+ 60%; GranzymB/Perforin+ 80%, TIA1+ 60%; CD4+ 80%; LCA-/+?; ALK1(-), Bcl6(+/-) 40% (weak), CD43+ 20%, CyclinD1/CD20/CD3/CD79a/CD2/CD5/CD7(-), EBV LMP1(-), Pax5-.  
 
PROPOSED DIAGNOSIS: cHL (MC?) with cytotoxic phenotype and ALCL like (sinus) spread.  
QUEST: 1. Septation and nodularity: NS grade II possibility? 2. CD4+ cytotox + phenotype?  
 
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tzankov 2009-02-16 10:42	An ALK and a PAX5 and an LMP-1/EBER stains as well as, when possible, MUM1 and Cyclin E stains are absolutely needed for proper diagnosis. "Simple" morphology is in favor of cHL, but ALKOMA or other T-NHL should be excluded.
ugnius 2009-02-16 18:52	Please find expand immunophenotype: ALK1/EBV LMP1(-) as well as negative all T markers. LCA and CD4 are doubtfull +, but cytotox molecules are surpprisingly +...
tzankov 2009-02-17 13:42	morphology, CD30 and CD15 are still in favor of cHL; there are reported cases of cHL with cytotoxic phenotype, I have also seen some routine cases, therefore TIA1, Granzyme CD4 would not play a matter, EMA is little bit more complicated, thus there are still some phenotypic difficulties/inconsistencies. was PAX5 completely negative? please perform MUM1 and cyclin E stains.
anpo 2009-02-18 11:50	I would favor the anaplastic large cell lymphoma ALK-1 negative - mostly due to the growth pattern, sinusoidal growth and positivity for cytotoxic enzymes. Also, Pax5 should be positive in HL.
hurwitz 2009-02-18 20:42	I share Anias opinion, there are many arguments in favour of anaplastic large cell lymphoma ALK1-, such as the morphology of the tumor cells and their sinusoidal spread. Tumor cells are CD45+, CD4+ with cytotoxic phenotype, EMA+, CD15 expression may be observed in a proportion of tumor cells in ALCL as well.
ugnius 2009-02-21 17:39	Thank you for urgent comments. PCR clonality testing shows any definite result: TCR G may be clonal, but polyclonal phoning too strong (no formal confirmation of clonality).   TCR B without rearr.   TCR D polyclonal.   IGH, IGK, IGL polyclonal.
anpo 2009-02-22 12:19	Ig TCR G may be clonal this further supports the ALC diagnosis.
ugnius 2009-02-22 13:05	Thank you. One more question: recently our molec's lab get a laser microdissection technique. I hope it would be benefitial on isolating small tumor cell pools in reactive background for clonality studies, but they have some doubts about low quantity of DNR from single cells. Your comments and experience on this topic would be appreciated. Thank you for comments on that.
ugnius 2009-02-22 15:46	Some cells CyclinD1+, solid areas (-).
SergeyN 2009-02-22 22:23	EMA, though non-specific, is more in favour of ALCL, too. Looking forward to microdissection results.
tzankov 2009-02-23 09:46	The expression of cyclin D1 is in my opinion (see. Tzankov et al. 2003, J Pathol) in favor of cHL... please perfom a MUM1 stain. My experianec with microdissection is that you need at least 200 Hodgkin and Reed-Sternber cells (-like cells) to get reliable results.
anpo 2009-03-09 11:19	MUM-1 cannot be differentiating between cHL and ALK-1 neg. ALC - there are T-cell NHL positive for MUM-1. In this case the PAX5 should be the most important one (if it works properly). Microdissection studies are not easy....
torlakovic 2009-03-17 17:28	I wonder if you did CD30 on the slide with the least malignant cells. I could hardly find any malignant cells in areas that were CD30-negative. I mention this because ALK1-neg ALTCL is uniformly CD30-pos, which actually seems to be the case here, too. Many features favor ALCL (localization of cells, uniform staining for CD30, the overall immunophenotype (the only exception is CD15, but rare to even moderate number of CD15 does not rule out ALCL), and also cytological features because I could convince myself that "hallmark" cells are indeed present.
ugnius 2009-03-30 15:14	Appologies for delay: giant cells seems to be Mum1+ at leasy 70% and Pax5 (-).
tzankov 2009-03-30 16:03	Considering all evidences and the arguments of Dr. Porwit and Dr. Torlakovich, meanwhile I also think that the "pro"-s for an ALK- ALCL are more than those for cHL with a cytotoxic phenotype.
tzankov 2009-03-30 16:10	This difficult case can be closed now. Considering all molecular details and the above comments, a consensus on the proper classification of this lymphoma as an ALK-negative anaplastic large T-/0-cell lymphoma can be met.     Thanks to all participants for their comments.
ugnius 2009-06-01 17:48	Please find BOB1 and Oct2, kindly stained in dr.S.Dirnhofer's Institute, Basel. A lot of thanx.
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