Pathologica 4-07.pdf - Pacini Editore

PATHOLOGICA 2007;99:205-213
Patologia del sistema emolinfopoietico
Nodal inflammatory pseudotumour caused
by luetic infection
P. Incardona, F. Facchetti * , M. Ponzoni ** , P. Chiodera ***
2° Servizio Anatomia Patologica, Sp. Civili, Brescia, Italy;
* 1° Servizio Anatomia Patologica, Spedali Civili, Brescia,
Italy; ** Unità di Anatomia Patologica, Istituto Scientifico
“S. Raffaele”, Milano, Italy; *** Servizio di Anatomia
Patologica, Casa di Cura “S. Anna”, Brescia, Italy
Introduction. Inflammatory pseudotumour of lymph nodes
(IPT-LN) represents an unusual cause of lymphadenitis. The
aetiology of IPT-LN is unknown; it has been postulated that
it represents an hyperimmune reaction to different agents.
Since IPT-like changes in extranodal sites can be associated
with Treponema pallidum (TP) infection, we evaluated the
occurrence of TP in a series of 17 nodal and extranodal IPT.
Methods. We retrieved 8 cases of IPT-LN and 9 cases of extranodal
IPT (4 spleen, one each for lung, orbit, gut, skin and
liver); all cases have been analyzed for the presence of TP using
the Warthin-Starry (WS) silver method and an indirect
immunohistochemical (ihc) techniques, applying a monoclonal
antibody recognizing TP (Biocare Medical, Concord,
CA, USA), upon oven heat antigen retrieval in EDTA buffer
(pH 9.0).
Results. Nodal IPT revealed the classical features consisting
of capsular thickening and inflammation (6/8 cases), proliferation
of spindle and endothelial cells, admixed with numerous
plasma cells and variable amounts of neutrophils and
macrophages. Vascular changes of small venules or large
muscular veins were recognized in 5/8 cases. The IPT areas
dissecting the nodal parenchyma were confluent and diffuse
in 2 cases, focal and sometimes (3 cases) limited to small intranodal
nodules in the remaining cases. Unaffected
parenchyma showed lymphoid hyperplasia in 7/8 cases, that
was extremely marked in 5. Microgranulomas were identified
in two cases. The WS and ihc stains revealed numerous
spirillar bacteria in 4/8 cases of IPT-LN but in none of IPTextranodal.
Interestingly, the single distinctive morphological
change constantly associated with TP+ cases was represented
by an extremely pronounced follicular hyperplasia
(FH). TP were identified in the inflamed capsule, within the
IPT areas with a predilection for endothelial cells, and in areas
of monocytoid B cell hyperplasia. However, no single TP
was found within the germinal centers. TP were more easily
detected on immunostained compared to silver stained sections,
allowing the identification of even single bacteria.
Conclusions. This study shows that a significant number of
cases of nodal IPT are caused by TP infection. A spirochetal
aetiology should be suspected in all IPT-LN associated with
pronounced FH, independently from the extent of nodal involvement
by IPT. Since immunohistochemistry has several
advantages compared to WS stain, it should be adopted as the
primary stain for TP detection.
Cord blood cell-transplanted mice as a model
for Epstein-Barr virus infection of the human
immune system. A morphological,
immunophenotypical and molecular study
M. Cocco, C. Bellan, R. Tussiwand * , E. Traggiai * , S. Lazzi,
S. Mannucci, L. Bronz ** , N. Palummo, P. Tosi, A. Lanzavecchia
* , M.G. Manz * , L. Leoncini
Department of Human Pathology and Oncology, Division of
Pathological Anatomy, University of Siena, Italy; * Institute
for Research in Biomedicine, Bellinzona, Switzerland;
** Ospedale “San Giovanni”, Bellinzona, Switzerland
Introduction. Epstein-Barr virus (EBV) infects naïve B
cells, driving them to differentiate into resting memory B
cells via the germinal center reaction 1 . This has been inferred
from parallels with the biology of normal B cells and never
been proved experimentally. Recently a human adaptive immune
system in cord blood cell-transplanted mice has been
demonstrated. We here used this model to better define the
strategy of EBV infection of lymphoid B cells in vivo.
Materials and methods. Reconstitution of a functional immune
system in Rag2-/- -/- γ mice has been previously de-
c
scribed 2 . Bone marrow, spleen, thymus and lymph nodes
were collected from seven EBV infected mice one month after
EBV infection for immunohistochemical and in situ hybridization
analysis on consecutive paraffin-embedded tissue
sections. Molecular analysis of V gene rearrangement has
H
been performed on single cells obtained by Laser Capture
Microdissection. A semi-nested PCR amplification of VH genes was performed by means of the following primers: 5’-
TGG RTC CGM CAG SCY YCN GG-3’ for FRIIA, 5’-TGA
GGA GAC GGT GAC C-3’ for LJH and 5’-GTG ACC AGG
GTN CCT TGG CCC CAG-3’ for VLJH. PCR products were
subsequently sequenced for comparison with germ line sequences
from the ImMunoGeneTics information system ®
(http://imgt.cines.fr) database.
Results. Among the seven cases analyzed, three were characterized
by follicular hyperplasia with a few germinal center
while the others showed a nodular and diffuse lymphoid
proliferation of lymphoid cells with areas of necrosis and no
evidence of germinal centers in the lymphnodes as well as in
the white pulp of the spleen. These findings were consistent
with immunohistochemistry and in situ hybridization analyses,
demonstrating different expressions of latent genes in
EBV-infected B-cells besides varied distributions of CD4 +
and CD8 + T cells in the two groups. Intraclonal diversity was
detected in cases characterized by nodular and diffuse proliferation,
among B cells carrying somatically mutated VH
genes, suggesting an ongoing hypermutation process without
evidence of germinal center reaction.
Conclusion. The here presented data gives evidence of different
strategies of EBV infection in B cells in vivo, probably
corresponding to different conditions of EBV infections in
humans.
References
1 Thorley-Lawson DA, et al. N Engl J Med 2004;350:1328-37.
2 Traggiai E, et al. Science 2004;304:104-7.