Primary Cutaneous T-Cell–Rich B-Cell Lymphoma:
Clinically Distinct from Its Nodal Counterpart?
Shiyong Li, Constance A. Griffin, Risa B. Mann, Michael J. Borowitz
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
The cases of two patients with Stage IE primary
cutaneous T-cell–rich B-cell lymphoma (TCRBCL)
are described. In both, the lesion showed a dense
infiltrate by numerous small T lymphocytes with
scattered histiocytes and large atypical B-lymphoid
cells. Polymerase chain reaction assays demon-
strated that the B cells were monoclonal, with im-
gene were observed. Both patients were disease-free
at 4 months and at 5 years after therapy, respec-
tively. Although rare, primary cutaneous T-cell–rich
B-cell lymphoma appears to have a better prognosis
than its nodal counterpart, with or without skin
KEY WORDS: gene rearrangement, skin, T-cell–rich
Mod Pathol 2001;14(1):10–13
T-cell–rich B-cell lymphoma (TCRBCL) was initially
proposed in 1988 to describe a B-cell lymphopro-
liferative disorder in which the majority of the cells
are reactive T lymphocytes, with the large neoplas-
tic B cells accounting for ?15% of the overall infil-
trating lymphoid cells (1). It is a rare entity,
accounting for approximately 1–2% of all non-
Hodgkin’s lymphomas, and is generally believed to
be a subtype of diffuse large B-cell lymphoma in the
Revised European-American Lymphoma classifica-
tion and the upcoming World Health Organization
classification. A variant form of TCRBCL, histiocyte-
rich B-cell lymphoma, was described by Delabie et
al. (2); it is characterized by a prominent reactive
histiocytic infiltrate. The neoplastic B cells are
clonal based on results from immunohistochemical
and/or immunoglobulin heavy-chain gene rear-
TCRBCL has both nodal and extranodal presenta-
tion. Nodal TCRBCL with or without cutaneous in-
volvement is an aggressive lymphoma that often pre-
sents as Stage IV disease, with frequent bone marrow
involvement, and requires systemic chemotherapy
counterparts, particularly the primary cutaneous one,
is unclear for several reasons. First, primary cutane-
ous TCRBCL is so rare that only a handful of cases
have been reported in the literature (6–13). Second,
TCRBCL in general is frequently misdiagnosed as
pseudolymphoma, pleomorphic peripheral T-cell
lymphoma, or lymphocyte-predominant Hodgkin’s
lymphoma (1, 3, 5, 8). In this report, we describe two
cases of primary cutaneous TCRBCL and review the
The first patient was a 51-year-old white man with
no relevant medical history who presented to an out-
side plastic surgeon for a small lesion on the upper lip
near the base of the right naris. The lesion was noted
by the patient to have grown slowly during the last
several months. He was feeling fine without fever,
night sweat, weight loss, or other symptoms. At phys-
ical examination, the lesion was ?1 cm in maximal
dimension. No other skin lesions were observed.
There was no evidence of peripheral lymphadenopa-
carcinoma and was excised.
Histologically, the lesion showed a dense poly-
morphous lymphohistiocytic infiltrate in the der-
mis and subcutaneous adipose tissue. The majority
of the cells were small and mature appearing, with
a few admixed large, atypical cells (Fig. 1, A–B). The
epidermis was unremarkable. By immunoperoxi-
dase staining, the small lymphocytes, which ac-
counted for more than 90% of the lymphocytes,
were CD3?T cells, whereas the scattered, large,
atypical lymphocytes were CD20?B cells (Fig. 2,
Copyright © 2001 by The United States and Canadian Academy of
VOL. 14, NO. 1, P. 10, 2001 Printed in the U.S.A.
Date of acceptance:
Address reprint requests to: Michael J. Borowitz, M.D., Ph.D., Department
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A–B). Immunostains for kappa and lambda light
chains were noncontributory, and in situ hybridiza-
tion for Epstein-Barr virus mRNA was negative. A
polymerase chain reaction assay using degenerate
consensus primers to amplify across the variable
and joining region junction of the immunoglobulin
heavy-chain gene generated a distinct product (Fig.
3A), demonstrating that the small number of large,
atypical B cells were clonal. The T cells showed no
evidence of clonal rearrangement of their T-cell
receptor gamma gene by polymerase chain reaction
assay (data not shown).
Subsequent chest and abdominal computed to-
mography scans showed no evidence of visceral
lymphadenopathy. A bone marrow biopsy was neg-
ative for lymphoma involvement. Complete blood
count and other chemical analyses including lac-
tate dehydrogenase level were within normal range.
A diagnosis of Stage IE T-cell–rich B-cell lymphoma
arising from the upper lip was made. The patient
received three cycles of cyclophosphamide, doxo-
rubicin, vincristine, and prednisolone plus involved
field radiation (3600 cGy). He is symptom- and
disease-free 4 months after treatment.
The second patient was a 62-year-old white man
who presented to an outside hospital in March 1994
with a subcutaneous nodule in his scalp. No other
cutaneous lesions or lymphadenopathy were noted
during physical examination.
The histologic appearance of the scalp lesion was
similar to that seen in the first patient (not shown).
A PCR assay for the immunoglobulin heavy-chain
gene revealed a single prominent product (Fig. 3B),
demonstrating the monoclonal nature of the large
transformed B cells in this lesion. There was no
evidence of clonal T-cell receptor gamma gene re-
arrangement. Extensive staging at the time of lym-
phoma diagnosis failed to reveal visceral lymphad-
enopathy or bone marrow involvement. After
excision, the patient received radiation therapy to
the involved field in the scalp (a total of 5940 cGy).
In December 1995, a repeat bone marrow biopsy
demonstrated a normocellular marrow with focal
granulomatous reaction. A liver biopsy at the same
time showed a similar granulomatous process. In
both biopsy specimens, organisms morphologically
compatible with Histoplasma capsulatum were
identified by special silver staining. It was thought
that in both liver and bone marrow, the granulomas
were secondary to disseminated histoplasmosis,
and the patient was treated accordingly. Multiple
follow-up bone marrow biopsies and magnetic res-
onance–imaging examinations thereafter showed
no evidence of systemic lymphoma. He is disease-
free 5 and a half years after the initial diagnosis of
Stage IE primary cutaneous TCRBCL.
Primary cutaneous TCRBCL is a rare lymphoma.
Until now, only 16 cases (including the ones we
have described here) have been described in the
literature (Table 1). Most patients were men (M:F ?
13:3). Their ages ranged from 30 to 87 years, with an
average age of 57.6 years at the time of lymphoma
diagnosis. In the majority of cases, the lesion was
FIGURE 1. A, Low-power view of the dermis showing a diffusely
dense lymphocytic infiltrate (hematoxylin and eosin, 100?). B, High-
power view of the dermal infiltrate showing a predominance of small
lymphocytes with scattered large, atypical lymphoid cells.
FIGURE 2. Immunoperoxidase staining showing that the large,
atypical lymphoid cells are CD20?B cells (A, 400?), whereas the
background small lymphocytes are CD3?T lymphocytes (B, 400?).
FIGURE 3. Detection of clonal immunoglobulin heavy-chain gene
rearrangement by polymerase chain reaction using consensus primers
for the variable (5?-ACA-GGG-C(C/T)(G/C)-TGT-ATT-ACT-GTG-3?) and
the joining (5?-GTG-ACC-AGG-GTN-CCT-TGG-CCC-CAG-3?) regions of
the gene. Arrow (A) and arrowhead (B) indicate the clonally rearranged
products amplified from DNAs of the first and the second patients’ skin
Primary Cutaneous T-Cell–Rich B-Cell Lymphoma (S. Li et al.)11
located in the head, arms, or trunk. Most patients
had Stage IE disease with lesions confined to the
skin. The treatment modalities varied from no
treatment to combined radiation therapy and che-
motherapy. Except for two patients who died of
diseases unrelated to their primary cutaneous
TCRBCL, all the remaining patients were alive and
well within the period of follow-up.
Histologically, the lymphoid infiltrate in the skin is
composed of a mixture of small lymphocytes, some
with irregular nuclear contours, epithelioid histio-
cytes, plasma cells, and sparse individual large lym-
phoid cells accounting for ?15% of the infiltrating
cells. The epidermis is usually spared. The large atyp-
ical lymphoid cells sometimes have clear cytoplasm
and multilobated nuclei. But typical Reed-Sternberg
cells are not seen. Frequently, prominent vascular
proliferation is present. The histologic appearance
mimics that seen in pleomorphic peripheral T-cell
lymphoma or Hodgkin’s lymphoma, but the large
atypical lymphoid cells are positive for B-cell markers,
whereas the background small lymphocytes are reac-
tive T cells on immunohistochemical stain, and the
large B cells are always negative for CD15 and CD30.
be more difficult to distinguish histologically, though
cutaneous involvement by this disease is exceedingly
rare. In addition, the clonality of the large B cells can
usually be demonstrated by immunohistochemical
staining for immunoglobulin light-chain protein
and/or molecular genetic study for rearrangement of
the immunoglobulin heavy-chain gene.
Numerous studies have documented that pri-
mary cutaneous lymphomas often have different
clinicopathologic features compared with primary
nodal lymphoma of the same histologic subtype,
with or without secondary skin involvement. For
example, primary cutaneous CD30?anaplastic
large-cell lymphoma lacks epithelial membrane an-
tigen expression and shows no evidence of Epstein-
Barr virus infection. The t(2;5) translocation and the
resultant expression of anaplastic lymphoma ki-
nase are consistently absent in primary cutaneous
CD30?anaplastic large-cell lymphoma. In noncu-
taneous CD30?anaplastic large-cell lymphoma,
cases expressing anaplastic lymphoma kinase have
a better prognosis than those not expressing ana-
plastic lymphoma kinase. However, primary cuta-
neous CD30?anaplastic large-cell lymphoma has
an excellent prognosis, with an estimated 5-year
survival of ?90% (14, 15). Therefore, correct diag-
nosis and appropriate staging of primary cutaneous
lymphomas are essential to avoid unnecessarily ag-
Although the histologic appearance of primary
cutaneous TCRBCL is similar to its nodal counter-
part, the clinical behavior is drastically different.
Nodal TCRBCL with or without secondary skin in-
volvement usually presents as advanced-stage dis-
ease, with frequent bone marrow involvement and
splenomegaly. Despite aggressive treatment with
combination chemotherapy, the overall survival
rate at 3 years in general is ?50% (3–5). The re-
ported cases of primary cutaneous TCRBCL appear
to have a better prognosis. Although the follow-up
was relatively short (from 2 months to 13 years,
with an average of about 2 years; Table 1), most
patients were alive and well without disease during
that time. Only two patients died of unrelated dis-
eases, one with residual lymphoma and one with-
out residual lymphoma. Interestingly, primary cu-
taneous diffuse large B-cell lymphoma reported by
Yang et al. (16) also had an excellent prognosis.
Nodal TCRBCL and diffuse large B-cell lymphoma
are considered to represent a spectrum of disease.
It may be that primary cutaneous TCRBCL and
primary cutaneous diffuse large B-cell lymphoma
TABLE 1. Summary of the Reported Cases of Primary Cutaneous TCRBCL
References Age (Year)/Sex LocationStage TreatmentFollow-Up
Osborne et al. (6)
Arai et al. (7)
Krishnan et al. (8)
Died of AIDS with disease/8 months
Dommann et al. (9)
Take et al. (10) 74/MNeck IE Died of pneumonia without disease/
Sander et al. (11)41/F
Dunphy et al. (13)
Chemo, chemotherapy; BM, bone marrow; RT, radiation therapy; AW, alive and well.
represent a spectrum of disease, with both showing
better outcome than their systemic counterparts.
The massive T-cell infiltration in TCRBCL is
probably related to the cytokine milieu of the tu-
mor, such as interleukin-4 (17). It has also been
hypothesized that Epstein-Barr virus might partic-
ipate in the pathogenesis of the B-cell lymphoma,
with a corresponding T-cell reaction (18, 19). How-
ever, evidence of Epstein-Barr virus infection has
only been documented in a few cases of nodal
TCRBCL and in only one case of primary cutaneous
TCRBCL (8). In both cases described here, there
was no evidence of Epstein-Barr virus infection.
Although the pathogenesis is not completely under-
stood, it has been suggested that the neoplastic B
cells are germinal center B cells in origin (20).
In conclusion, the unusual good prognosis of pri-
mary cutaneous TCRBCL compared with its nodal
counterpart is exactly analogous to what has been
seen with other types of histologically aggressive
lymphomas, including CD30?anaplastic large-cell
lymphoma and diffuse large B-cell lymphoma.
Though more cases need to be studied to further
characterize this entity, if true, our findings further
support the notion that the skin is a special site of
involvement for lymphomas of many types and that
the usual adverse histologic features may not nec-
essarily predict poor outcome in cutaneous lesions.
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