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

Sun Sep 25 12:49:55 EDT 2016

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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