Acta Dermato-Venereologica 98-10CompleteContent | Page 11
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CLINICAL REPORT
Paraproteinaemia in Primary Cutaneous Marginal Zone Lymphoma
Verena Gerlinde FRINGS 1 , Kristina RÖDING 1 , Alexander STRATE 2 , Andreas ROSENWALD 3 , Sabine ROTH 3 , Hermann KNEITZ 1 ,
Matthias GOEBELER 1 , Eva GEISSINGER 3 and Marion WOBSER 1
1
Department of Dermatology, Venereology and Allergology, 2 Division of Laboratory Medicine, University Hospital Würzburg, and 3 Institute
of Pathology and Comprehensive Cancer Center Mainfranken, University Würzburg, Würzburg, Germany
Primary cutaneous marginal zone lymphomas (PCMZL)
frequently exhibit lymphoplasmacytoid/plasmacytic
differentiation, implying the capacity to produce mo-
noclonal immunoglobulins. As these paraproteins are
secreted, and thus are measurable in blood and urine,
they may correlate with disease burden and serve as
tumour markers reflecting therapeutic response. This
study retrospectively analysed the records of 23 pa-
tients with PCMZL. During treatment and follow-up,
laboratory tests, including full blood count, lactate
dehydrogenase, serum protein electrophoresis and
turbidimetric analyses, were conducted. Thirty-nine
percent of cases showed a suspicious serum protein
electrophoresis in terms of paraproteinaemia. In 44%
of cases the heavy and light chain restriction in tis-
sue samples correlated with serological findings. Al-
together, 89% of the PCMZL patients with paraprotei-
naemia eventually experienced a relapse, in contrast
to 62% of the group without paraproteinaemia. This
study analysed the incidence and clinical implications
of paraproteinaemia in patients with PCMZL. A clear
correlation was found between paraproteinaemia, tu-
mour relapse and therapeutic intervention.
Key words: lymphoma; immunofixation; monoclonal immu-
noglobulins; monoclonal gammopathy.
Accepted Aug 7, 2018; Epub ahead of print Aug 7, 2018
Acta Derm Venereol 2018; 98: 956–962.
Corr: Verena G. Frings, Department of Dermatology, Venereology and
Allergology, University Hospital Würzburg, Josef-Schneider-Straße 2, DE-
97080 Würzburg, Germany. E-mail: [email protected]
T
he expression and secretion of monoclonal im-
munoglobulins or paraproteins by lymphoma cells
is a well-known phenomenon frequently observed in
various types of B-cell non-Hodgkin’s lymphomas (1).
Lymphoma-derived paraproteins are monoclonal pro-
teins by nature and can be detected as a homogeneous
spike-like peak in a focal region of the gamma-globulin
zone in serum protein electrophoresis (monoclonal
gammopathy). Provided no haematological neoplasm is
diagnosed as the underlying cause of monoclonal gam-
mopathy, this putatively prodromal state before any overt
lymphoma is designated as “monoclonal gammopathy of
undetermined significance” (MGUS). Monoclonal gam-
mopathy has to be clearly separated from polyclonal or
oligoclonal elevation of immunoglobulins in response to,
for example, inflammatory stimuli or chronic illness (2).
doi: 10.2340/00015555-3016
Acta Derm Venereol 2018; 98: 956–962
SIGNIFICANCE
The expression and secretion of monoclonal immunoglo-
bulins or paraproteins by lymphoma cells is a well-known
phenomenon. This study analyses the presence and signi-
ficance of paraprotein expression and secretion in primary
cutaneous marginal zone lymphoma. During treatment and
follow-up, blood and tissue of 23 patients were evaluated
for immunoglobulin expression by immunohistochemistry,
serum protein electrophoresis and turbidimetric analyses.
Concordant paraproteins shown in tissue samples were in
almost all cases also detected in the blood correlating to
the clinical course and tumour relapse. Our data suggest
paraproteinaemia as a tumour marker in primary cuta-
neous marginal zone lymphoma.
Monoclonal immunoglobulins (Ig) can present as
IgM-isotype or as so-called class-switched isotypes,
namely IgG, IgA, or IgE. Class-switched isotypes occur
only after a complex molecular process of recombination
and juxtaposition of the Ig heavy chain gene segment
to rearranged variable segments, mainly in response to
antigen exposure (3). Immunoglobulins expressed on the
cell membrane of lymphoma cells can be visualized by
immunohistochemistry in tumour tissue by routine his-
topathological work-up. Since paraproteins are secreted,
and can thus be detected in blood and urine, they may
serve as tumour markers reflecting therapeutic response.
Their levels are thought to correlate with disease burden
(4). In this respect, elevated monoclonal IgM is a typical
feature of Waldenström’s macroglobulinaemia, defined
as an IgM-restricted lymphoplasmacytic lymphoma
(LPL) with bone marrow involvement and any level of
an IgM monoclonal gammopathy in the blood (5–8).
The WHO classification (9) recommends establishing
the diagnosis of Waldenström’s macroglobulinaemia
after exclusion of plasmacytoid/plasmacytic variants of
other lymphomas. Since IgM paraprotein can also occur
in other B-cell neoplasms such as IgM-expressing nodal
marginal zone lymphomas (5, 10) or any precursatory
MGUS, as mentioned above.
Primary cutaneous B-cell lymphomas (PCBCLs)
encompass distinct entities, including the primary
cutaneous marginal zone lymphoma (PCMZL) (11).
PCMZL, an indolent lymphoma, is the second most
common subtype of PCBCLs and belongs to the hetero-
geneous group of extranodal marginal zone lymphomas
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Journal Compilation © 2018 Acta Dermato-Venereologica.