Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2537-2537
CORRESPONDENCE
Large Cell Non-Hodgkin's Lymphoma and Hodgkin's Disease Arising
Synchronously in a Patient With Chronic Lymphocytic Leukemia:
Importance of Immunocytochemistry
 |
LETTER |
To the Editor:
Transformation of chronic lymphocytic leukemia (CLL) into a more
aggressive hematologic malignancy is a well-described phenomenon known
as Richter's syndrome (RS) and has been reported to result in
non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), or multiple myeloma in 3%, 0.5%, and 0.1% of patients,
respectively.1 Although there have been cases of patients
with both de novo HD and high-grade B-cell lymphoma, as well as
sequential HD, follicular NHL, and high-grade B-cell NHL, we have not
been able to identify any patients with HD and NHL concurrently arising
in the setting of CLL.2-4 Here we report the synchronous
occurrence of both diffuse large B-cell NHL and nodular sclerosing HD
in a patient with CLL.
A 51-year-old man with anemia and lymphocytosis was diagnosed with CLL.
His disease did not respond to chlorambucil, but responded well to
fludarabine. A subsequent hemolytic anemia resolved with splenectomy.
Three years after diagnosis, the patient developed night sweats, distal
femur swelling, and ipsilateral inguinal lymphadenopathy. Biopsies of
both posterior iliac crests and of the distal femoral mass were
performed. The bone marrow was 90% cellular largely due to an
infiltrate consisting of large lymphoid cells in a background of small
round lymphocytes. The mass in the distal femur consisted of a subset
of cells containing multiple nuclei and prominent nucleoli with
Reed-Sternberg-like morphology within a background of small round
lymphocytes. The immunocytochemical and morphological findings were
interpreted as showing CD20+, CD15
,
CD30, CD5, CD3 large cell
NHL in the bone marrow; CD15+, CD30+,
Fascin+, CD20 nodular sclerosing HD in the
femoral mass; and a background of CD5+, CD19+,
dim CD20+, CD10 CLL in both biopsy specimens.
The patient was treated with 5 cycles of cyclophosphamide, adriamycin,
vincristine, and prednisone (CHOP), with a dramatic response in his
night sweats and inguinal adenopathy along with normalization of his
bone marrow. However, the mass in his distal femur increased in size
after only a brief response. Repeat biopsy of this area revealed
extensive necrosis with evidence of CLL and a persistent subset of
large malignant-appearing lymphoid cells. Because of this extensive
necrosis, repeat immunocytochemical studies could not differentiate
residual HD from large cell NHL. Radiotherapy to his femur resulted in
local improvement, although subsequent treatment with dexamethasone,
cytosine arabinoside, and cisplatin (DHAP) and then mesna, ifosfamide,
mitoxantrone, and etoposide (MINE) yielded only transient minor
responses. The patient died with progressive lymphoma 11 months after
the recognition of apparent RS, and postmortem examination was not performed.
Based on the observed incidence of NHL and HD in RS patients with CLL,
the likelihood of developing both HD and NHL in the same patient should
be exceedingly rare (0.015%, ie, 3% × 0.5%). With 7,400 new
cases of CLL in the United States each year,5 the estimated
frequency of RS resulting in both HD and NHL in the same patient would
be expected to be, at most, 1 patient per year. The events we report
may be even less likely because the two diseases presented
simultaneously. Unfortunately, the quantity of these samples did not
allow us to definitively confirm clonality between the three
histologies. Because multiple biopsies and pathological evaluations
including detailed immunocytochemistry of each area were required to
establish the diagnosis in our patient, the synchronous occurrence of
NHL and HD might have occurred in previous patients but not been recognized.
Therapy in the rare situations of so called "composite lymphomas"
has traditionally been directed against the more aggressive subtype.6 We treated both of his newly diagnosed lymphomas with CHOP. Initially, he responded well, but ultimately progressed and
died with systemic disease, although faring better than the median
survival of 5 months of RS with NHL.1 Perhaps similar or
even more complex transformations as manifestations of RS will be
identified as clinicians more aggressively evaluate and biopsy patients
with an unexplained change in their disease course and more broadly
apply immunocytochemical techniques. This approach may ultimately lead
to both a clearer understanding of the pathophysiology as well as
improved therapies for this phenomenon.
| |
ACKNOWLEDGMENT |
We thank Dr Marla Fenske for her pathological expertise.
Ajay K. Gopal
Scott M. Schuetze
David G. Maloney
Department of Medicine
Division of Medical Oncology
University of Washington Medical Center
Seattle, WA
Paul L. Weiden
Section of Hematology
The Virginia Mason Medical
Center
Seattle, WA
| |
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