Reactive Polyclonal T-Cell
lymphocytosis mimicking Sezary Syndrome in a patient with Hairy
Cell Leukemia
Gerald G. Wulf,* Harald Schulz,° Christian Hallermann,^
Ekkehard Kunze,° Bernhard Wörmann*
*Abteilung für Hämatologie und
Onkologie,Georg-August-Universität, Göttingen;
°Abteilung für Osteo- und Hämatopatologie,
Georg-August-Universität, Göttingen;
^Universitätshautklinik, Georg-August-Universität,
Göttingen, Germany
Correspondence: Dr.Gerald G.Wulf, Baylor College of Medicine,
Center for Cell and Gene Therapy, One Baylor Plaza, Alkek N1030.
Tel.:713-798-1271.FAX:713-798-1230. E-mail: gwulf@bcm.tmc.edu
In patients with hairy cell leukemia (HCL), skewing of the
T-cell repertoire is frequent, whereas a concurrent Sezary
syndrome is a very rarely event. We here describe an extreme
variant of an oligoclonal T-cell proliferation in reaction to
recurrent HCL mimicking Sezary syndrome. HCL induces a skewing of
the T-cell repertoire via mechanisms yet not well
understood.1,2 Beyond reactive changes, several reports
described cases of secondary T-cell neoplasias, especially Sezary
syndrome, concurrent to or in remission of patients with
HCL.3-6 In this case study, the bone marrow (bm) of an
80-year-old patient was partially replaced by an infiltration with
typical DBA44 positive, T-cell marker negative lymphoma cells
(Figure
1A). Treatment with
2-chlorodes-oxyadenosine (2-CDA) induced complete remission for 41
months, after which the patient presented again with erythema,
pruritus and peripheral blood (PB) lymphocytosis. The PB
lymphocytes exhibited convoluted nuclei resembling Sezary cells,
and the upper corium of the skin was infiltrated by lymphocytes
without clear epidermotropism (Figure
1B,C). A polymerase
chain reaction (PCR) for T-cell receptor (TCR) delta gene
rearrangements showed a polyclonal pattern (Figure
1D), whereas BM
histology revealed a discrete, but unambiguous infiltration by
HCL. The patient received a second course of 2-CDA chemotherapy,
which resolved the symptoms. Since effective therapeutic regimens
of HCL with interferon or 2-CDA were available, secondary T-cell
neoplasias, especially Sezary syndrome, have been reported in
several patients. In three cases, a combination of skin
infiltration and a convoluted-type nuclear morphology of the
lymphocytes in the PB, in one case a PB population of large
granular lymphocytes with lymph node involvement were
described.3-6 In two of these cases, Southern blot
analysis for TCR gene rearrangements established the monoclonal
origin of the T-cell populations.4,6 The
pathophysiological mechanisms involved in this coincidence of HCL
and T-cell neoplasias is currently unkwon. Similar to the reports
above, the combination of lymphocyte morphology and skin symptoms
initially raised the suspicion of a secondary Sezary syndrome in
the propositus. However, the PCR analysis indicated a multiclonal
progeny of the PB lymphocytes, concurrent to a bone marrow
recurrence of the HCL (Figure
1D). A restriction of
HCL recurrence to the BM has been reported for larger cohorts of
patients,7 and might have triggered the polyclonal
T-cell reaction in our case. These polyclonal T-cell reactions
persist for the course of active HCL gradually regress with
successful interferon treatment over a period 2 to 3
years.2 The freedom of symptoms was achieved in the
propositus, suggested a significant effect of 2-CDA on the
dermotropic T cells, either indirectly via induction of HCL
remission or by direct suppressive effects on T cell subsets.
In conclusion, this case report gives the example of a reactive
T-cell lymphocytosis closely mimicking Sezary syndrome in a
patient with bone marrow relapse of HCL. It exemplifies an extreme
variant of reactive T cell changes in HCL and stresses the
importance of bone marrow immunohistology to prove or exclude bone
marrow infiltration by HCL.
