UPGRADED CASE RELATED INFO:  
 
12 yo boy with neck lymphadenopathy, a lymph node about 2 x 3 cm taken.  
Smallish abdominal nodes along large vessels (up to 10 mm) and inguinal (up to 11 mm) and several small nodes at the biopsy site (up to 9 mm) are seen on US, CT and MRI.  
There is skin itching with excoriations (legs, mostly). Nothing special in lab tests except high titre of CMV IgG (IgM not elevated) and anti-TPO antibodies with preserved thyroid function. That's all.  
 
Histology shows interfollicular areas infiltrated by T-cells with phenotype CD8+, CD4 partly+, CD1a-, GranB partly+ and very variable Ki67, no CD30. There is no typical paracortical hyperplasia that could be related to CMV, no signs of dermatopathic lymphadenopathy.  
Areas with high proliferation look particularly suspicious.  
 
Thank you in advance!  
 
ADD INS:  
Molecular: no clone detected.  
EBER+ cells absent.  
HISTO: a) Some PTGC like zones appear with focal CD20+ B cell dispersion into interfollicular space;  
b) Voluminous nodular lesion area easilly visible on panoramic HE.  
Interfollicular T population seems to be CD4+CD8+ double, LOM2(-) with high Ki67 index. No T Ag loss. Some CD99+/- fade and CD30+ noise in PTGC areas. Despite visual appearance of "blastoid" T LPD, no definite proof of malignancy...  
We have no NOTCH there.  
A QUALITY (PROBABLY AND DNA) NOT SO OPTIMAL (hyperdehydrated).

ugnius 2018-04-09 15:36	Facing with expanded T zone with elevated CD8 numbers, without prominent atypia or T Ag loss (CD7/CD5/CD2), without CD30+, in pediatric age, I suspend myself on reactive process idea before pushing into T NHL category at the moment (medications? autoimune processes/IBDs/other like this? immunocompetence?). We'll proceed with clonality later on if needed. skin eruptions would be of interest (macro photo by handy? biopsy? eosinophilias in blood?).
tzankov 2018-04-10 08:18	can you add EBER, TdT, CD57 and CD56 stainings? are there any clinical signs of ALPS? FACS of the peripheral T-cells? CD8/Cd4 double+/double-?
SergeyN 2018-04-10 14:22	TdT and CD56 are negative, we don't have CD57 and EBER (EBV antibodies are normal).     There are no clinical signs of ALPD or other PID, his relative and absolute Ly subpopulations are normal; double negative cells are not increased (<5% Ly, up to 10% is considered normal in kids), double positive 0.5%.     CRP, IL6 and LDH were sligtly elevated and normalized in a couple of days in the hospital. There was mild eozinophilia (5.7% / 0.6E9/L) that resolved, too.
SergeyN 2018-04-10 14:44	Sorry, EBV VCA IgM and Chlamydia pneumoniae IgG weakly positive.   total Ig level normal.     There are no focal skin lesions to take biopsy from, inching got much better on anti-histamines.     Trephine will be ready soon, cytology was non-specific, flow showed only inverted T4:T8 ratio.     HIV status pending.
tzankov 2018-04-10 17:02	very strange case...does he take any special medication or has he been given a vaccination recently?
SergeyN 2018-04-10 19:28	No drugs, no vaccination...     The photos don't give the full impression of the interfollicular areas with high mitotic activity, they look like sheets of very young cells. The first thought after HE was partial infiltration by lymphoblastic lymphoma.   But the patient doesn't fit clinically. In addition, the rest of the node is mostly not a typical reaction, but an infiltrate with low Ki67 and transition zones.
tzankov 2018-04-10 20:34	what about LMO2 and NOTCH1 staining?
tzankov 2018-04-10 20:34	what about LMO2 and NOTCH1 staining?
SergeyN 2018-04-10 20:48	Don't have any (
SergeyN 2018-04-13 12:43	Well, bone marrow is ready: mild mature-looking interstitial CD8+, GranB+/- lymphocytosis.
tzankov 2018-04-16 07:45	I will still wait for clonality testing and once again go though his medical files to look for any "strange form" of ALPS. Is there iamging of his thymus? have run a FACS of his T-cells? the high CMV titres may exlpain a CD8 skewed reaction.
SergeyN 2018-04-17 10:03	He has normal T-subsets in blood, double-negative T-cells are within normal range (<10% of total T-cells). Euroflow T2 tube (cytCD3 CD45 CD2 CD117 CD4 CD8 CD7 mCD3) was done on marrow aspirate, there was an inverted T4:T8 ratio, even less DN cells, no phenotypic aberrations.     I can do TCR ab/gd in peripheral DN cells, will it help somehow?     There is no thymic mass, no clinical progression since biopsy, PET including. Ig level normal. No previous immunodeficiency-related history.     HIV negative.     Well, let's hope Ugnius will have some luck with clonality.
ugnius 2018-04-17 10:04	Materials (IH and HE slides) (unfortunatelly a single block) arrives. LMO2, some add ins IH and clonality in progress. In less hyperdehidrated areas infiltrate seems to be MORE BLASTOID (nonreactive) as in blastic leukaemias.   MAYBE WE GOT SOME INFO FROM FLOW CYTOMETRY?
SergeyN 2018-04-17 10:08	The patient is currently at home
SergeyN 2018-04-17 10:12	That's my impression, too ((     At the time of biopsy there were no atypical populations in blood and marrow. Maybe, something will appear at follow-up.
tzankov 2018-04-19 12:22	please keep me updated. NOTCH1 and LMO2 may hepl as suggested:   Appl Immunohistochem Mol Morphol. 2015 Aug;23(7):491-8.   Am J Surg Pathol. 2015 Apr;39(4):565-72.
ugnius 2018-04-30 13:28	Please find MOLECULAR, EBER and NEW scanned photos appended.
ugnius 2018-04-30 13:28	ADD INS:   HISTO: a) Some PTGC like zones appear with focal CD20+ B cell dispersion into interfollicular space;   b) Voluminous nodular lesion area easilly visible on panoramic HE.   Interfollicular T population seems to be CD4+CD8+ double, LOM2(-) with high Ki67 index. No T Ag loss. Some CD99+/- fade and CD30+ noise in PTGC areas. Despite visual appearance of "blastoid" T LPD, no definite proof of malignancy...   We have no NOTCH there.   A QUALITY (PROBABLY AND DNA) NOT SO OPTIMAL (hyperdehydrated).
tzankov 2018-04-30 13:38	Thank you for the updates. Perfect work, Ugnius!   I think that these additional findings further support a reactive/immunologic process (DD ALPS) over malignancy, yet I admitt that the KI67 index in the inerfollicular areas is high, but this may be provoked by a germ or by a developing auto-clone etc.     What is the clniical course like?
ugnius 2018-04-30 13:44	As I know, a kid at home. Just parents nervous a bit. I keep a contact with responsible clinician. I'll ask one more time.
ugnius 2018-04-30 14:19	Of note: a kid was born after IVF procedure from anonymous donor. No clinical signs (on PET scan too) about disease. No signs of immunodeficiency.
SergeyN 2018-04-30 23:17	Currently there is nothing clinically.     Unfortunately, there is no info on his laboratory status at the time of biopsy, it seems no laboratory tests had been performed then.     I shall ask hematologists if there had been something from his family doctor or from a private lab.
ugnius 2018-05-01 11:53	For beeing sure, I've requested ALL BLOCKS from Latvia, cause HE picture variable a bit- at the moment I will scan ALL original HE with some other areas. Just to be sure.
SergeyN 2018-05-01 21:56	Dear Ugnius,     Thank you!   I shall try to get clinical update.
ugnius 2018-05-18 07:57	Last point: I've added some additional pictures and virtual slides (incl thin HE). Some perifocal "spilling" of large immunoblastoid CD20+Pax5+Oct2+ cells (some with lobated nuclei) are seen (not visible in reactive zones with small T lymphos). My idea is HOW NOT TO MISS T/H rich DLBCL like areas of NLP HL... Interestingly Bcl6+ pool is higher than Pax5+, maybe some T cells show Bcl6+?   A CONTRAST of size on CD20 not so prominent as in classic cases of NLP HL, all "immunoblastoids" ar OUTSIDE of follicles, but there we have HYPERHYDRATED slides....
ugnius 2018-05-18 08:05	P.S. And "pale" perifocal T zone very pleomorfic still (on thin section HE). All area of changes seems like VOLUMINOUS/NODULAR lesion in the reactive background (panorami view). NOT LIKE reactive.
tzankov 2018-05-18 12:51	Well, IgD and PD1 (to detect rimming) will be the most important markers to be applied to finally resolve the case. PD1 has been already stained for, please carefully look for rosetting at the HPF and put some additional microphotographs. In my opinion OCT2 much more intesnively stains L&H cells...IgD?
ugnius 2018-05-18 13:22	Thanx. No rimming, faint PD1 (not very well discernible) in interfollicular region, no CD57+ or IgD+ rimming. Some larger ones IgD+ still. PHOTOS will be uploaded and announced additionally. ANYWAY, NOT ENOUGH FEATURES FOR NLP HL.
tzankov 2018-05-18 16:27	agree, at the moment no criteria for lymphoma diagnosis are fulfilled
ugnius 2018-05-18 16:35	IgD and PD1 some photos added. Thank You. "Uncomfortable" unclass case...
SergeyN 2018-05-19 16:06	Dear friends,     Thank you both for the tremendous work!     I shall ask hematologists for clinical update as soon as possible (haven't heard anything about the patient since his discharge).   It seems a careful follow-up should be arranged. If (God forbid) he develops something in future, I shall let you know.
ugnius 2018-05-19 16:49	The report was sent to responsible dr.Zhanna Kovalova. A lot of stains and not too much news... Sounds like     "RARE/UNUSUAL/UNCLASSIFYIBLE CASE:   Atypical reactive lymphadenopathy (polyclonal B/T) with nodular/voluminous T zone hyperplasia with high Ki67 proliferation index, CD4+CD8+ double T population and some PTGC (progressive transformation of germinal centers) features with B immunoblastic reaction.   COMMENT:   Double T (CD4+CD8+) population (rare phenomenon) may arise in infectious/viral settings or in PTGC (or even NLP HL) cases.   High Ki67 proliferation index is worrisome, but T population is still NOT clonal.   Thorough hematological evaluation (immunocompetence? autoimmune diseases? viral infection? Other?) and follow up reccomended (PTGC has some associations with NLP HL risk: it was one of lines of differential diagnosis, but there is not enough features of large "popcorn" cells). Such "abberant" immunoresponse may give rise for another unusual processes/diseases or just be self limited.   At the moment any treatment is needed regarding this pathology.   If any progression signs appears- additional lymph node biopsy/evaluation might be of value.
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