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

Sun Sep 25 14:02:24 EDT 2016

The child had undergone following procedures for ruling out underlying NHL
and the slides were reviewed by experienced hematopathologists here in our
Institute
1. Transbronchial ultrasound guided mediastinal node aspiration once (Nov'
15)- suggestive of atypical lymphoproliferation ? NHL, however,
immunohistochemistry not suggestive of malignancy
2. Axillary node biopsy under general anaesthesia (Nov' 15)- Reactive
hyperplasia
3. Ultrasound guided splenic aspirate (Sep' 16)- Lymphoplasmocytic
aggregates, no granulomas.

Over time, there was no increase in the size of the mediastinal node or of
his spleen (at least in past 9 months). Peripheral adenopathies (axillary
and inguinal) have regressed over time. Could this still be a lymphoma?

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 11:21 PM, Vignesh Pandiarajan <vigimmc at gmail.com>
wrote:

> 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
>>
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