Am J Clin Pathol 2010;133:59-69 59
59 DOI: 10.1309/AJCPW64FFBTTPKFN 59
© American Society for Clinical Pathology
Hematopathology / Cutaneous Marginal Zone Lymphoma
Characteristics of Cutaneous Marginal Zone Lymphomas
With Marked Plasmacytic Differentiation and a T Cell–Rich
Julia Turbiner Geyer, MD,1 Judith A. Ferry, MD,1 Janina A. Longtine, MD,2
Thomas J. Flotte, MD,1* Nancy L. Harris, MD,1 and Lawrence R. Zukerberg, MD1
Key Words: Marginal zone lymphoma; Skin; Plasmacytic differentiation; T-cell predominance; IgH rearrangement
A b s t r a c t
Primary cutaneous marginal zone lymphoma
(MZL) is a common B-cell lymphoma of skin and is
characterized by an infiltrate of neoplastic marginal
zone B cells typically within the marginal zones of
reactive lymphoid follicles and the interfollicular
region. However, in our experience, many cases have
underemphasized features such as marked plasmacytic
differentiation and/or a prominent T-cell component,
which may obscure the neoplastic B cells and lead
to misdiagnosis. We wanted to draw attention to
these features and have studied 15 cases of MZL with
marked plasmacytic differentiation, 10 of which had
numerous T cells, some with cytologic atypia, and
few B cells in the interfollicular region. Plasma cells
were monotypic in all cases by in situ hybridization.
By polymerase chain reaction, 6 of 8 T cell–rich cases
had an IGH gene rearrangement, and none were clonal
for T-cell receptor gene. We discuss the terminology,
morphologic features, molecular profile, behavior,
and differential diagnosis of cutaneous MZL.
Primary cutaneous marginal zone B-cell lymphoma
(MZL) is a recently described entity that can present diag-
nostic difficulty. MZL has been historically diagnosed as
“primary cutaneous immunocytoma” or “primary cutaneous
plasmacytoma” if the lesion was considered malignant and
as “lymphocytoma cutis” if the lesion was considered benign.
These terms persist in medical and pathology literature and
contribute to confusion regarding this diagnostic entity.
Primary cutaneous plasmacytoma was first described in the
English literature by Agarwal in 1956.1 A first series of cuta-
neous lymphoplasmacytic lymphomas has been published
by Rijlaarsdam et al2 in 1993 under the name of immunocy-
toma. The term immunocytoma was subsequently used in the
updated Kiel classification and in the European Organization
for Research and Treatment of Cancer (EORTC) Cutaneous
Lymphoma Project Group classification.3,4 At the same time,
similar lesions were being diagnosed as MZL by other groups,
who argued that their morphologic features were analogous
to those of lymphoma of mucosa-associated lymphoid tissue
(MALT) at other extranodal sites and noted that some cases of
cutaneous lymphoma were concurrent with MALT lympho-
mas at extracutaneous sites.5-10 Following consensus meet-
ings of the World Health Organization (WHO) and EORTC,
the term primary cutaneous MZL has been accepted as the
favored diagnostic term, incorporating the entities of primary
cutaneous immunocytoma and primary cutaneous plasmacy-
toma.11,12 This change has been reflected in the latest WHO
classification of skin tumors.13
Primary cutaneous MZL is defined as lymphoma com-
posed of small B cells, including marginal zone (centrocyte-
like) or monocytoid cells, lymphoplasmacytoid cells, and
Upon completion of this activity you will be able to:
• define the current classification criteria for primary cutaneous
marginal zone lymphoma.
• describe the morphologic and immunohistochemical features of
marginal zone lymphoma of skin, including the unusual variants.
• analyze the advantages and pitfalls of molecular clonality testing.
The ASCP is accredited by the Accreditation Council for Continuing
Medical Education to provide continuing medical education for physicians.
The ASCP designates this educational activity for a maximum of 1 AMA PRA
Category 1 Credit ™ per article. This activity qualifies as an American Board
of Pathology Maintenance of Certification Part II Self-Assessment Module.
The authors of this article and the planning committee members and staff
have no relevant financial relationships with commercial interests to disclose.
Questions appear on p 162. Exam is located at www.ascp.org/ajcpcme.
60 Am J Clin Pathol 2010;133:59-69
60 DOI: 10.1309/AJCPW64FFBTTPKFN
© American Society for Clinical Pathology
Geyer et al / Cutaneous Marginal Zone Lymphoma
plasma cells. It is considered to be part of the broad group
of extranodal MALT lymphomas.14 The monotypic lym-
phoplasmacytoid and plasma cells are usually located at
the periphery of the infiltrates, while central areas of the
infiltrates may contain variable numbers of reactive B and
T cells with reactive lymphoid follicles.4 These definitions
allow for a relatively straightforward recognition of classic
cases of cutaneous MZL. However, atypical cases may be
quite challenging for a pathologist owing to their rarity and
the confusing terminology.
We recently encountered an unusual case with a promi-
nent component of monotypic plasma cells, numerous T cells,
and few extrafollicular B cells. We searched our files for pri-
mary cutaneous MZLs with similar features.
Materials and Methods
A computer-assisted search of the pathology files of
the Massachusetts General Hospital, Boston, and review of
identified cases disclosed 15 patients with primary cutaneous
MZL characterized by marked plasmacytic differentiation,
defined as focal solid aggregates of plasma cells occupying
at least one ×20 power field on an excision specimen or a
×40 power field on a small biopsy specimen as determined
by histologic and light chain restriction studies. Lymphomas
were defined as primary if there was no evidence of extracu-
taneous involvement at the time of diagnosis and completion
of initial staging evaluation, based on the WHO-EORTC
The total number of cases diagnosed as primary cutane-
ous MZL was 33. Cases had been classified according to
the criteria of the WHO classification of skin tumors using
a combination of morphologic and immunophenotypic crite-
ria.13 The remaining 18 cases not described in this report were
typical cutaneous MZL as described.11-13 Of 15 cases, 2 were
retrieved from the department of pathology archive and 13
from the consultation files of two of us (J.A.F. and N.L.H.).
Immunohistochemical analysis and in situ hybridiza-
tion were performed on paraffin-embedded tissue as part
of the diagnostic evaluation, including immunostaining for
pan–B and pan–T antigens (CD20, DAKO, Carpinteria,
CA; CD3, Novocastra, Newcastle upon Tyne, England),
CD21 (Novocastra), CD23 (Novocastra), bcl-2 (DAKO),
bcl-6 (DAKO), CD10 (DAKO), CD5 (Novocastra), CD2
(Novocastra), CD4 (Novocastra), CD8 (Novocastra), CD7
(Novocastra), CD138 (Serotec, Raleigh, NC), MUM-1
(DAKO), CD79a (DAKO), and immunoglobulin heavy chains
α (BioGenex, San Ramon, CA), γ (BioGenex), μ (DAKO), δ
(DAKO) and assessment of in situ hybridization for κ and λ
immunoglobulin light chains (Becton Dickinson, Mountain
Based on immunohistochemical analysis of B- and
T-cell markers, cases were further subdivided in 2 groups: a
T cell–rich group (10 cases) with rare extrafollicular B cells
and numerous extrafollicular T cells (B cells < T cells, using
a semiquantitative analysis) and a B cell–rich group (5 cases)
with conspicuous extrafollicular B cells, equal in number or
more frequent than the T cells (B = T or B > T cells).
Cases from the T cell–rich group were analyzed for
immunoglobulin heavy chain (IGH) and T-cell receptor
γ chain (TCR) rearrangements. DNA was isolated from
deparaffinized tissue using QIAGEN QIamp DNA micro
kits (QIAGEN, Valencia, CA). The B- and T-cell clonal-
ity assays were performed using polymerase chain reaction
(PCR) according to the manufacturer’s instructions with
reagents purchased from InVivoScribe Technologies, San
Diego, CA (IgH Gene Clonality Assay and TCRG Gene
Clonality Assay for ABI Fluorescence Detection). The kits
use the primer sequences published by BIOMED-2,15,16 and
had all the necessary reagents except for sample DNA and
Taq polymerase (AmpliTAQ Gold, Applied Biosystems,
Foster City, CA). PCR products were analyzed by capillary
gel electrophoresis (3100xl, Applied Biosystems).
Clinical information was available in all cases through the
pathology report, the electronic medical record, or by contact-
ing the referring physician. Institutional review board approval
was obtained from Partners Healthcare System, Boston.
The clinical features are summarized in ❚Table 1❚.
Overall, 11 patients were men and 4 were women with a
median age of 55 years (range, 20-83 years).
T Cell–Rich Group
There were 8 men and 2 women with a median age of 55
years (range, 20-74 years). All patients had solitary cutaneous
nodules involving the leg (4 cases), trunk (2 cases), shoulder
(2 cases), arm (1 case), and scalp (1 case).
Two patients had a history of lymphoma. Case 1 first
manifested 17 years earlier with a lesion on the left upper arm,
diagnosed at the time as lymphocytoma cutis (original mate-
rial not available for review). Thirteen years later, the patient
had a new skin lesion on the right upper thigh diagnosed as
cutaneous MZL and treated with local radiation. He devel-
oped a recurrence in the right buttocks area 6 months later,
was again treated with electron beam radiation therapy, and is
currently free of disease.
Case 7 first manifested with a solitary scalp lesion 15 years
earlier, diagnosed as “granulomatous mycosis fungoides,”
Am J Clin Pathol 2010;133:59-69 69
69 DOI: 10.1309/AJCPW64FFBTTPKFN 69
© American Society for Clinical Pathology
Hematopathology / Original Article
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