Re: Fwd: AW: Clinical case, lymphoma

From: Jeff Miller (jemiller@invivoscribe.com)
Date: Mon Oct 25 1999 - 11:21:47 EST


Dear Sharon,

This is a very interesting discussion and a difficult case. However, I
believe that I be able to provide a rapid, coherent and scientifically
sound approach to diagnosis for this case, and other cases of suspect
monoclonality.

As you know, approximately 90% of follicular lymphomas display a
characteristic bcl2 t(14;18) translocation that can be rapidly and
specifically identified using PCR. Now a PCR-based series of tests have
been developed and validated that simultaneously identify both bcl2
translocations and clonal rearrangements of the B and T cell antigen
receptors. The performance characteristics of Multi-Loci Clonality Testing
were recently peer-reviewed and published [Molecular Diagnosis
4(2):101-117, 1999]. New assays using this advanced technology will be
presented this year at the annual meeting of the Association for Molecular
Pathology (Nov 4-7, St Louis), and the International Society for Laboratory
Hematology Meeting (April 12-16, Banff).

This technology, which uses a PCR-based approach, will identify clonality
and translocations testing as little as 50ng (50 x 10-9g) of genomic DNA,
an amount of material easily obtained from blood, bone marrow, fresh
(aspirate), frozen or formalin-fixed paraffin embedded tissue, or even a
single glass slide.

The monoclonality detection rate, determined in a method comparison study
with Emory University Medical Center, was determined to be 100%, the
sensitivity approximately 1 cell in one hundred normal cells, and the
specificity was determined to be 100%.

One of the major advantages of this approach is that, in addition to
testing for bcl2 translocations, both the immunoglobulin heavy chain gene
and T cell receptor gamma chain genes are tested. Therefore, the technology
identifies cross-lineage clonal rearrangements that are often missed
following lineage assignment and testing for either B cell clonality or T
cell clonality.

I admit a bias for this approach; it is our company's technology.
Turnaround time for the assays is generally one day, and the results can be
posted on our SECURE Internet Client Data Access Site.

Best regards,

Jeffrey Miller



>>From: "Nebe, Thomas C." <thomas.nebe@ikc.ma.uni-heidelberg.de>
>>To: Cytometry Mailing List <cytometry@flowcyt.cyto.purdue.edu>
>>Subject: AW: Clinical case, lymphoma
>>Date: Fri, 22 Oct 1999 14:59:35 +0200
>>MIME-Version: 1.0
>>
>>
>>Dear Sharon,
>>
>>I appreciate the comments from Maryalice and Anna.
>>
>>We had many of these discussions among collgues here in Germany.  For the
>>benefit of the patient and clinician: The way to go is to extirpate the
>>lymph node in total and send it (or pass on) to a reference pathologist who
>>is well trained (belongs to the REAL group).  They hate fine needle biopsies
>>as the architecture of the lymph node gets lost.  Your given immunophenotype
>>(by "feeling", missing morphology and conjugation) does not suggest a CLL
>>and lymphoma diagnosis by flow is a difficult game even including morpholgy
>>and experience. The discussion of your data is complicated by the fact that
>>the missing fluorochrome is crucial: PE gives positive signals eg. for CD25
>>or CD11c while FITC conjugates give negative results.
>>
>>Lymphoma classification and treatment of lymphoma is based upon lymph node
>>pathology.  The extended marker panel you anticipated we use for a while.
>>It helps to exclude B CLL but does not give a safe diagnosis of other B-NHL
>>(except HCL, may be Immunocytoma).  The so called atypical B-CLL has never
>>been defined and even very experienced collegues refused to give a
>>presentation on that subject.
>>
>>SLL from the working formulation is not a well defined clinical entity and
>>therefore did not exist in the KIEL classification.
>>Harald Stein (Berlin, REAL group) just presented at the german hematologist
>>meeting in Jena the new concept of a B1 and B2 CLL, where the latter is CD38
>>positive and forms lymphoma.  (The concept behind is based on B cell
>>development in the lymph node). This provoqued a lively discussion esp.
>>among those who used CD38 in the past.  We also found CD38-FITC surface
>>positive (dim compared to immunocytoma or plasmocytoma) in those CLL
>>patients with spleen and lymph node infiltration (total CLL n=85).  Possibly
>>cytoplasmic staining resolves the controversial issue.
>>I dont want to be bouring but it would be helpful to have a minimum report
>>format (combinations / fluorochrome / surface or cytoplasmic / intensity
>>compared to normal counterparts) when discussing such cases.
>>Best regards
>>Thomas Nebe
>>
>>Dr.med. C. Thomas Nebe
>>Universitaetsklinikum Mannheim
>>Zentrallabor
>>Theodor-Kutzer-Ufer 1-3
>>D-68167 Mannheim
>>Tel.  +49 621 383-3485
>>FAX  +49 621 383-73 3485
>>        +49 621 383-3819
>>e-mail: thomas.nebe@ikc.ma.uni-heidelberg.de
>>
>>Bitte besuchen Sie unsere sehr informativen Webseiten unter
>>http://www.ma.uni-heidelberg.de/inst/ikc/
>>
>>> -----Ursprüngliche Nachricht-----
>>> Von:	Gerhard Nebe-von-Caron
>>>[SMTP:Gerhard.Nebe-von-Caron@unilever.com]
>>> Gesendet am:	Mittwoch, 20. Oktober 1999 16:58
>>> An:	Nebe, Thomas C.
>>> Betreff:	FW: Clinical case, lymphoma
>>>
>>>
>>>
>>> -----Original Message-----
>>> From:	Sharon Vogt [SMTP:svogt@bellsouth.net]
>>> Sent:	Saturday, October 16, 1999 1:14 AM
>>> To:	Cytometry Mailing List
>>> Subject:	Clinical case, lymphoma
>>>
>>>
>>> Hi all,
>>>
>>> We have a clinical case that's interesting to the point of frustration.
>>> Any
>>> comments?
>>>
>>> 53 y male, 3 years ago and now (recurrent) lymphoma, B-cell type.
>>> Phenotype is
>>> similar in both flow cytometric studies:
>>>
>>> CD19+ CD20+ CD22 dim, CD5 dim before, partial now, CD25+, CD23 partial,
>>> CD11c
>>> partial, with kappa light chain restriction. Negative for CD10. We do not
>>> stock
>>> FMC7  (but will soon), CD21 or CD24.
>>>
>>> By morphology and flow (considering dim CD5 as negative), the diagnosis of
>>> follicular center cell lymphoma (noting that 20-30% of these are known not
>>> to
>>> express CD10) was made. None of us are entirely sure of that diagnosis
>>> now, and
>>> there appears to be a tad more CD5 expression (recent specimen was FNA of
>>> cervical node); it was suggested that this may be a mantle cell lymphoma.
>>>
>>> OK, simple enough - immunohistochemical stains bcl-2 and cyclin D1 should
>>> answer
>>> that question. Those are difficult stains to optimize, however, and are
>>> affected
>>> by variations in fixation. In other words, they didn't help much. CD20 nor
>>> kappa
>>> light chain expression is remarkable for staining intensity, but I'd favor
>>> a CLL
>>> based on the rest of the phenotype. The pathologists say small cell, low
>>> grade,
>>> but not really CLL-like and definitely not PLL.
>>>
>>> ?? Thanks for any discussion.
>>>
>>> sharon
>>>
>>> Sharon F. Vogt
>>> svogt@bellsouth.net
>>> Dekalb Medical Center
>>> Atlanta, GA  30033
>>>
>>>
>>>
>>>
>>>  << Datei: ATT01392.ATT >>
>>
>
>
>
>Chris Lena
>Laboratory Technician
>La Jolla Institute For Allergy and Immunology
>phone:(858)678-4536
>fax:(858)678-4595
>cali@liai.org
>http://www.liai.org
>
>               _   _
>              (_)-(_)
>                \"/
>                =V=
>
>


Jeffrey E. Miller, Ph.D.
President & CEO
IVS Technologies, LLC
2915 Avenida Valera
Carlsbad, CA 92009
(760) 431-6705 - Phone
(760) 431-6909 - Fax
(877) 431-6705 - Toll free
jemiller@invivoscribe.com
http://www.invivoscribe.com

La Jolla Institute for Allergy & Immunology
10355 Science Center Drive
San Diego, California 92121
(619) 678-4529 - direct
(619) 678-4595 - Fax



This archive was generated by hypermail 2b29 : Wed Apr 03 2002 - 11:54:09 EST