[CIS PIDD] [cis-pidd] Lymphoproliferation and massive splenomegaly in CVID

Sun Sep 25 13:51:52 EDT 2016

Dear all,

Thank you for the important suggestions.
The platelet counts for him was 1.3 lakhs (1,30,000/ cu.mm) or 130x10^9/L.
EBV viral loads in this patient was neg (Odd for XLP/ SAP)
No evidence for portal hypertension/ liver disease to explain the
splenomegaly. Splenomegaly is part of the generalized lymphoproliferation.
Double negative T cells were 1.1% (not for ALPS)

Vignesh P
MD Pediatrics,
DM resident in Pediatric Clinical Immunology and Rheumatology (Jan 2015-
Dec 2017),
Allergy Immunology Unit, Advanced Pediatrics Center,
Postgraduate Institute of Medical Education and Research,
Chandigarh, India. 160012.
E mail: vigimmc at gmail.com
Phone no: +91-9592047009, +91-9944547009

On Sun, Sep 25, 2016 at 10:19 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
wrote:

>
> Dr. Vignesh:
>
> Of course, this is outside my field ... but I can't help notice that the
> CD4 + CD8 summation is quite above 100%.  If, indeed, there is a plurality
> of splenic lymphocytes that are CD4+ 8+ double positives, would this not
> point (more strongly) towards a lymphoma?  That, or XLP/SAP/Duncan's.  Do
> you have information if these are all TCR alpha/beta+?
>
> Dr. Sokolic -- I think the platelets are 130,000/mm3.
>
>   - K
>
> Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
> Instructor of Pediatrics (Pediatric Infectious Diseases)
> University of Chicago - Comer Children's Hospital
> 5841 S Maryland Ave, MC 6054, Chicago IL 60637
> Pager:  773-702-6800   x1744
> Fax:  773-702-1196
> Lab phone (Bubeck Wardenburg laboratory): 773-834-6976
>
>
> ________________________________________
> From: CIS-PIDD [cis-pidd at lists.clinimmsoc.org]
> Sent: Sunday, September 25, 2016 11:36 AM
> To: CIS-PIDD
> Subject: RE: [cis-pidd] Lymphoproliferation and massive splenomegaly in
> CVID
>
>                I think that there is some reason to push for a definitive
> diagnosis. If his platelets are in fact 13,000/mcL (? Is that the same as
> 1.3 lakh/cu mm?), he may be OK for bleeding now, but you can anticipate
> that he will need definitive management of splenomegaly in the future. If
> he is symptomatic from his splenomegaly, as I would expect with a spleen
> that big, then that is another reason to try make a definitive diagnosis.
> If he is asymptomatic, there is a little less urgency, but I don’t think
> that he will be stably asymptomatic.
>                I think that there are three diagnostic issues. 1st, does
> he have CVID? He has panhypogammaglobulinemia, does he also have poor
> antibody response? Also, do you have absolute numbers for his lymphocyte
> subsets, and other details about pre-morbid, presenting or current CBCs?
>                Second, is the splenomegaly related to the lymphadenopathy?
> That certainly would be the most parsimonious explanation for the two
> findings, but if the SM is in fact due to portal hypertension of splenic
> vein obstruction, then the differential diagnosis changes. Does he have
> signs of liver disease, hepatomegaly or abnormal portal or splenic vein
> flow on Doppler?
>                Third is the issue of diagnosing the mediastinal
> lymphadenopathy. The FNA is concerning for lymphoid malignancy, but this
> diagnosis is difficult to make on FNA. I would consider getting a core bx
> of a mediastinal LN via mediastinoscopy or interventional radiology.
>                My first concern would be for T-cell lymphoproliferative
> disorder. There is certainly a spectrum of aggressiveness for mature T-cell
> lymphoproliferative disease, but I don’t think that this child can stay
> like this long term. If you are not able to otherwise explain the SM and
> LAN, I think that you will have to subject the patient to splenectomy, in
> which case it might be good to start immunizing him now. Prior to this,
> could consider having LN path reviewed by a hematopathologist with
> particular expertise in lymphoid malignancy.
>                IF the FNA was really mostly T-cells, you could consider
> trying to extract DNA from the aspirated material and assessing for TCR
> restriction, which would also suggest clonality.
>
> --
> Rob Sokolic
> Medical Officer
> Center for Biologics Evaluation and Research
> Office of Cellular, Tissue and Gene Therapies
> U.S. Food and Drug Administration
> Tel: 240-402-5564
> Robert.Sokolic at fda.hhs.gov<mailto:Robert.Sokolic at fda.hhs.gov>
> ______________________________________
> From: CIS-PIDD [mailto:cis-pidd at lists.clinimmsoc.org]
> Sent: Sunday, September 25, 2016 4:31 PM
> To: CIS-PIDD
> Subject: Re: [cis-pidd] Lymphoproliferation and massive splenomegaly in
> CVID
>
> CVID panel for the above patient:
>
> CD3- 93.1% (52- 78%)
> CD20- 1.15% (13- 27%)
> CD19- 2.7% (5- 19%)
> CD56/16- 5.5% (5- 30%)
> CD4- 91.6% (50- 80%)
> CD8- 38.3% (28- 50%)
> Class switched B cells- 11.4% (8- 31%)
> Naive B cells- 52% (42- 82%)
> Marginal zone like B cells- 13.4% (7- 32%)
> Class switched memory B cells- 14.3% (8- 31%)
> Transitional B cells- 6.3% (0.6- 8%)
> Plasmoblasts- 1.7% (0.4- 3%)
> Btk expression in monocytes- percentage expression in case: 71.02%;
> Control: 84.3%
> CD81 expression by flow cytometry in the case- 88.1%
> BAFR expression by flow cytometry in the case- 95.6%
> ICOS expression by flow cytometry- percentage expression in case: 28.2%;
> control: 70.3%
>
> 1. The patient has low B cells and normal class-switched memory B cells.
> Is this seen with the autoimmunity/ lymphoproliferation predominant CVID we
> have in this patient? any other monogenic forms of immuno- dysregulation?
>
> 2. Would anyone use steroids or other kinds of immunosuppression to reduce
> the lymphoproliferation at this point of time?
>
> Thank you very much.
>
> Regards,
> Vignesh P
>
> Vignesh P
> MD Pediatrics,
> DM resident in Pediatric Clinical Immunology and Rheumatology (Jan 2015-
> Dec 2017),
> Allergy Immunology Unit, Advanced Pediatrics Center,
> Postgraduate Institute of Medical Education and Research,
> Chandigarh, India. 160012.
> E mail: vigimmc at gmail.com<mailto:vigimmc at gmail.com>
> Phone no: +91-9592047009, +91-9944547009
> ______________________________________
> On Sun, Sep 25, 2016 at 8:49 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org
> <mailto:cis-pidd at lists.clinimmsoc.org>> wrote:
> Dear all,
>
> We have an 11-year-old male child admitted under our care with the
> diagnosis of CVID. Need opinions and suggestions for some queries we have
> in the management of this child.
>
> He was incidentally detected to have massive splenomegaly (palpable till
> umbilicus) and generalized lymphadenopathy last year. No significant
> infections.
>
> Nov' 15-
> 1. Contrast-enhanced CT chest showed enlarged multiple mediastinal nodes
> with nodular opacities in the right upper lobe and left upper lobe.
> 2. Fine needle aspiration of mediastinal node- intermediate sized atypical
> lymphoid cells that had rim of cytoplasm and round, large nuclei, many
> showing indentations. (? Non-Hodgkin Lymphoma)
> 3. Axillary node biopsy- Reactive lymphoid hyperplasia with paracortical
> T-lymphoid expansion
> 4. IgA- 32 mg/dl (70-400), IgG- 216 mg/dl (700-1600), IgM- <25 (50-180)
> 5. CD3- 84.5%; CD 19- 2.55%
> 6. ESR- 09 mm; CRP- 7.2 mg/L; platelets- 1.3 lakhs/ cu.mm<http://cu.mm/>
>
> Diagnosed as CVID with atypical lymphoproliferation. On regular monthly
> replacement IVIg therapy.
>
> There was no decrease in spleen size till date. Over time, there was a
> progressive right middle lobe collapse/ consolidation. Splenic aspirate
> yielded predominant lymphocytes and lymphoplasmacytic infiltrates.
>
> Specific questions:
>
> There is no progression in spleen size (from Nov'15- Sep'16) and the
> peripheral nodes have actually regressed. Can this be some indolent
> malignancy like hepatosplenic T cell lymphoma? This is thought of as there
> were no features of systemic inflammation (normal ESR and CRP).
>
> Thank you.
> Eagerly awaiting your kind response.
>
> Regards
> Vignesh P
> MD Pediatrics,
> DM resident in Pediatric Clinical Immunology and Rheumatology,
> Allergy Immunology Unit, Advanced Pediatrics Center,
> Postgraduate Institute of Medical Education and Research,
> Chandigarh, India. 160012.
> E mail: vigimmc at gmail.com<mailto:vigimmc at gmail.com>
> Phone no: +91-9592047009, +91-9944547009
>
> ---
>
> You are currently subscribed to cis-pidd as: vigimmc at gmail.com<mailto:
> vigimmc at gmail.com>.
> To unsubscribe click here: http://cts.dundee.net/u?id=104900047.
> fc9f4e54cae45cd032b86c49d3dccf32&n=T&l=cis-pidd&o=3859566
> (It may be necessary to cut and paste the above URL if the line is broken)
> or send a blank email to leave-3859566-104900047.
> fc9f4e54cae45cd032b86c49d3dccf32 at lyris.dundee.net<mailto:lea
> ve-3859566-104900047.fc9f4e54cae45cd032b86c49d3dccf32 at lyris.dundee.net>
> ---
>
> ************************************************************
> ********************
> This e-mail is intended only for the use of the individual or entity to
> which
> it is addressed and may contain information that is privileged and
> confidential.
> If the reader of this e-mail message is not the intended recipient, you are
> hereby notified that any dissemination, distribution or copying of this
> communication is prohibited. If you have received this e-mail in error,
> please
> notify the sender and destroy all copies of the transmittal.
>
> Thank you
> University of Chicago Medicine and Biological Sciences
> ************************************************************
> ********************
>
> ---
> You are currently subscribed to cis-pidd as: vigimmc at gmail.com.
> To unsubscribe click here: http://cts.dundee.net/u?id=104900047.
> fc9f4e54cae45cd032b86c49d3dccf32&n=T&l=cis-pidd&o=3859672
> or send a blank email to leave-3859672-104900047.
> fc9f4e54cae45cd032b86c49d3dccf32 at lyris.dundee.net
>

---
You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://cts.dundee.net/u?id=96396833.5a9591ccd1e327fe6bc4d1543298c482&n=T&l=cis-pidd&o=3859753
or send a blank email to leave-3859753-96396833.5a9591ccd1e327fe6bc4d1543298c482 at lyris.dundee.net
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <https://pairlist7.pair.net/pipermail/pagid/attachments/20160925/918fa221/attachment-0001.html>