Clinical Case Report Medicine ®

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Marginal zone lymphoma of palatine tonsil

with prominent plasmacytic differentiation
A CARE-compliant article and review of literature
Shuang Ma, MDa, Rachel Jug, MB, BCh, BAOb, Shuai Shen, MSc, Wan-Lin Zhang, MSc,
∗
Hong-Tao Xu, MD, PhDc, Lian-He Yang, MD, PhDc,

Abstract
Rationale: The palatine tonsil is an important component of Waldeyer’s ring and a site commonly involved by lymphoma.
Interestingly, although it is a site of mucosa-associated lymphoid tissue (MALT), primary MALT lymphoma of the palatine tonsil is rare,
especially with prominent plasmacytic differentiation.
Patient concerns: A 59-year-old woman presented to the hospital with a 1-month history of odynophagia. The patient had no
fever or pruritus during this period and she declared no family history of hematolymphoid malignancy.
Diagnosis: Histopathological examination demonstrated effacement of tonsil architecture; normal follicles were replaced by
plasmacytoid tumor cells and small lymphocytes. The tumor cells expanded the marginal zone and infiltrated interfollicular regions, as
well as scattered residual follicles. Immunostaining showed tumor cells positive for cluster of differentiation (CD)20, CD79a, paired
box-5, Mum 1, and B cell lymphoma (Bcl)-2, and negative for CD5, CD 23, cyclin D1, Bcl-6, and CD10. Staining for k and l showed
prominent light chain restriction. The tumor was classified as tonsil MALT lymphoma with prominent plasmacytic differentiation.
Interventions: After the patient was diagnosed with MALT lymphoma with prominent plasmacytic differentiation, she underwent
complete surgical resection and radiotherapy.
Outcomes: There was no recurrence evident at 6-months follow-up.
Lessons: Primary tonsil MALT lymphoma with prominent plasmacytic differentiation is very rare and difficult to distinguish from
other B-cell lymphomas with plasmacytoid morphology, such as follicular lymphoma, lymphoplasmacytic lymphoma, and chronic
lymphocytic leukemia/small lymphocytic lymphoma. Accurate diagnosis of this entity is important in guiding therapy so as to avoid
overtreatment.
Abbreviations: CLL/SLL = chronic lymphocytic leukemia/small lymphocytic lymphoma, DLBCL = diffuse large B-cell lymphoma,
EMP = extramedullary plasmacytoma, FL = follicular lymphoma, MALT = mucosa-associated lymphoid tissue.
Keywords: differential diagnosis, mucosa-associated lymphoid tissue lymphoma, morphology, palatine tonsil, plasmacytic

1. Introduction lymphoid tissue and is exposed to foreign antigens. As with other

lymphoglandular tissues comprising the body’s immune system,
The palatine tonsils are located at the intersection of the digestive
tonsils serve a primary role in helping the body fight infection.
tract and the respiratory tract, where mucosa contains abundant
Most lymphomas found in the palatine tonsils are of the B-cell
type; and, of these, diffuse large B-cell lymphoma (DLBCL)
Editor: N/A.
represents most of the cases, reported to comprise up to 80% in
The study was supported by National Natural Science Foundation of China
(Grant No. 81301930 to L.-H. Yang, Grant No. 81372497 to H.-T. Xu), General
some studies.[1–5] Lymphoma of mucosa-associated lymphoid
project of Education Department of Liaoning Province (Grant No. L2015595 to tissue (MALT) arising from the tonsil is a rare phenomenon.[3,4,6–
8]
L.-H. Yang), and Students’ Innovation and Entrepreneurship Training Program Morphologically, lymphoma cells may be small to medium
(Grant No. 201610159000036 to L.-H. Yang). sized, presenting as small lymphocytes or with a monocytoid
The authors have no conflicts of interest to disclose. appearance. One-third of gastric MALT lymphomas display
a
Department of Neurology, Sheng Jing Hospital of China Medical University, plasmacytic differentiation which is also frequently seen in
Shenyang, Liaoning, b Department of Pathology, Duke University Medical Center, cutaneous and thyroid MALT lymphomas, but very rare in tonsil
Durham, NC, c Department of Pathology, First Affiliated Hospital and College of
MALT lymphomas. To the authors’ knowledge, the current case
Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
∗ is the 2nd report of primary MALT lymphoma with prominent
Correspondence: Lian-He Yang, Department of Pathology, First Affiliated
Hospital and College of Basic Medical Sciences, China Medical University,
plasma cell differentiation affecting the palatine tonsil.
Shenyang 110001, Liaoning, China (e-mail: [email protected]).
Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. 2. Case presentation
This is an open access article distributed under the Creative Commons
Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build A 59-year-old woman presented to the hospital for a 1-month
upon the work, even for commercial purposes, as long as the author is credited history of odynophagia. She did not experience concurrent fever
and the new creations are licensed under the identical terms. or pruritis, nor did she have a personal history of malignancy or
Medicine (2018) 97:2(e9648) other serious illness. The patient had not received any prior
Received: 26 November 2017 / Accepted: 27 December 2017 therapy for lymphoma. She had no family history of tumors
http://dx.doi.org/10.1097/MD.0000000000009648 affecting the lymphatic or hematopoietic systems. Fiberoptic

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laryngoscopic examination and computed tomographic imaging lymphoid follicles and increased interfollicular B cells, including
revealed a left tonsillar lesion. Pathological examination was large plasmacytoid cells (Fig. 2B). Bcl-2 stains interfollicular cells
performed and a diagnosis of primary tonsil MALT lymphoma and mantle zone cells, but is negative in germinal centers
with prominent plasmacytic differentiation was made. (Fig. 2C). Mum-1 is positive in plasmacytoid cells in inter-
follicular or perifollicular areas (Fig. 2D). Pax-5 highlights
lymphoid follicles and increased interfollicular B cells with weak
3. Materials and methods
staining of large plasmacytoid cells. CD3 and CD5 highlight
The resected tumor samples were embedded in paraffin blocks interfollicular T cells; CD10 and Bcl-6 stain for residual follicular
and serially sectioned. Immunohistochemistry was performed centers cells. Ki67 is approximately 10% in the hot area. k stains
using an SP kit (Maixin Biotechnology, Fuzhou, Fujian, China) plasmacytoid cells in interfollicular areas, including many tumor
according to the manufacturer’s instructions. The sections were cells with abundant cytoplasm (Fig. 2E), whereas l stains
incubated overnight at 4°C with the following primary anti- scattered rare plasma cells that appear benign (Fig. 2F), the ratio
bodies: B cell lymphoma (Bcl)-2 (1:200, Dako, Carpinteria, CA), of k/l staining is >10:1. CD138 stains plasmacytoid cells, CD56
Bcl-6 (1:100, Dako), cluster of differentiation (CD)10 (1:100, is partially positve in plasmacytoid cells.
Dako), CD138 (1:100, Dako), CD3 (1:100, Dako), CD20
(1:100, Dako), k (1:100, Dako), l (1:100, Dako), CD56 (1:200,
5. Discussion
Dako), Ki-67 (1:200, Dako), Mum-1 (1:100, Dako), and paired
box (Pax)-5 (1:100, Dako). Immunostaining showing a granular Lymphomas encompass a complex group of malignancies and
brown substance in the appropriate subcellular locations was account for the 2nd commonest group of neoplasms of the head
considered positive. This study was prospectively performed and and neck after squamous cell carcinoma.[9] Non-Hodgkin’s
approved by the institutional Ethics Committees of China lymphoma can involve any region of the head and neck, however,
Medical University and conducted in accordance with the ethical Waldeyer’s ring, nasal cavities, and paranasal sinuses together
guidelines of the Declaration of Helsinki. Written informed account for 90% for all extranodal lymphoma sites in the head and
consent was obtained from the patient for the publication of this neck. Among the aforementioned areas, Waldeyer’s ring (including
case report and accompanying images. tonsil, nasopharynx, and base of tongue) is the most commonly
involved extranodal site. Within the Waldeyer’s ring, more than
50% of lymphomas arise in the palatine tonsil.[1,4,8–15]
4. Results
Most lymphomas involving the tonsil are non-Hodgkin’s type,
4.1. Gross features and approximately 85% are of diffuse large B-cell
type.[4,10,13,14,16–18] Most of non-Hodgkin’s lymphomas in the
Radiologic examination of the neck did not detect lymphade-
tonsil are of B-cell lineage, including DLBCL, follicular
nopathy. Fiberoptic laryngoscopic examination demonstrated a
lymphoma (FL), mantle cell lymphoma, lymphoplasmacytic
bulging left tonsil. Tonsillectomy was performed and the
lymphoma, plasmacytoma, and extranodal MALT lymphoma.
specimen was submitted for pathological examination. The
Interestingly, the occurrence of MALT-type lymphomas in the
tonsil weighed 11 g and measured 3.6  3.0  2.1 cm. The mucosa
tonsils is rare despite the substantial amount of MALT
was pink-red and smooth. The tonsil was serially sectioned to
encountered at this location.[1,8,13,15,18]
reveal a homogeneous pink-tan cut surface.
MALT is characterized by reactive follicles with prominent
marginal zones, infiltration of overlying epithelium by lympho-
4.2. Microscopic features cytes, and the presence of subepithelial plasma cells. In contrast,
Histologically, the luminal surface of normal tonsils is covered with MALT lymphoma can present with proliferation of marginal
a stratified squamous epithelium. Beneath the epithelium, there are zone B cells, composed of morphologically heterogeneous small B
abundant lymphoid follicles with germinal centers similar to those cells including centrocyte-like cells, monocytoid cells, small
seen in lymph nodes. Microscopic examination of our case revealed lymphocytes, and plasma cells. In this case, the tumor cells
marked disruption of the normal tonsil architecture. From low presented predominantly with plasmacytic differentiation. This
magnification, effacement germinal centers were evident with only morphology has been reported in approximately one-third of
scattered residual germinal centers seen (Fig. 1A). Tonsillar tissue gastric MALT lymphomas and is frequently seen in cutaneous
was replaced by eosinophilic plasmacytoid tumor cells. Examina- MALT lymphomas. Surprisingly, MALT lymphomas very rarely
tion of the tumor cells at high magnification showed numerous present with plasmacytic differentiation in the tonsil. To the best
of our knowledge, this is the 2nd case of MALT lymphoma
atypical plasmacytoid cells with a heterogeneous size and shape.
The nuclear contour was irregular yet prominent and the nucleus reported in the English literature which occurred in palatine tonsil
contained a large nucleolus. The cytoplasm exhibited strong and showed predominantly plasmacytic differentiation.
eosinophilic staining (Fig. 1B), scattered large atypical cells could Plasmacytic differentiation is not a specific feature of MALT
be found under high magnification (Fig. 1C and D), the neoplastic lymphoma. When plasmacytic differentiation is identified as a
B-cells assumed an interfollicular growth pattern, plasmacytoid predominant feature, several lymphomas should be considered in
tumor cells invaded and effaced follicles, residual mantle zone formulating a differential diagnosis, including lymphoplasma-
lymphocyte could be found. Marginal zone cells, parafollicular cytic lymphoma (LPL), chronic lymphocytic leukemia/small
cells, and germinal center cells were replaced by plasmacytic tumor lymphocytic lymphoma (CLL/SLL), FL, and extramedullary
cells (Fig. 1E and F). plasmacytoma (EMP).[19–22] LPL is a rare neoplasm of older
patients (50–69 years) with involvement of bone marrow, lymph
node, spleen, and liver. To our best knowledge, LPL occurring in
4.3. Immunophenotypic studies the tonsil as the primary site has not been reported. Most patients
CD20 highlights lymphoid follicles and increased interfollicular B have monoclonal immunoglobin M and Waldenström macro-
cells, as well as scattered large cells (Fig. 2A). CD79a highlights globulinemia with hyperviscosity symptoms, which were not

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Figure 1. (A) Scattered residual normal follicles in the background of serious destruction of normal tonsil architecture (4); (B) normal structure of the tonsil was
replaced by numerous tumor cells which present prominent plasmacytic differential and atypical features (40); (C and D) the plasmacytic tumor cells expand the
marginal zone of the residual follicle and infiltrate into perifollicular region, and the great atypical plasmacytic cells mixed with small population of lymphocyte (40).
(E) (20) and (F) (40) normal structure of follicle was broken by the plasmacytic tumor cells, only scattered germinal center cells could be found under high
magnification.

apparent in our case. Morphologically, LPL is composed of small Morphologically, it is characterized by a proliferation of small
lymphocytes, plasmacytoid lymphocytes, and plasma cells, and round lymphocytes interspersed individually with prolympho-
usually involves the bone marrow, although not uncommonly is cytes and paraimmunoblasts. Tumor cells typically involve nodal
seen in lymph nodes and/or the spleen. Typical features such as or extranodal tissues as a diffuse proliferation with pseudofol-
Dutcher bodies, increased mast cells, and hemosiderin were not licular growth centers, which easily mimic the growth pattern of
identified in our patient. The characteristic immunophenotype MALT lymphoma. Plasmacytic differentiation is rarely found in
includes positive staining for B-cell antigens, and coexpression of CLL/SLL cases, and expression of CD5 and CD23 is useful to
Pax-5 and CD138-positive plasma cells.[23,24] CLL/SLL is distinguish CLL/SLL from MALT lymphoma. FL showing
extremely uncommon in the tonsil, especially at the time of marked plasmacytoid differentiation appears to be extremely
initial presentation of the disease.[9] SLL often presents with rare, making up approximately 3.5% of cases. In such cases, the
leukemia (CLL), although patients may be asymptomatic. growth pattern shows plasmacytic tumor cells infiltrating follicles

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Figure 2. (A) CD20: highlights lymphoid follicles and increased interfollicular plasmacytic tumor cells (20); (B) CD79a highlights lymphoid follicles and increased
interfollicular B cells, including large plasmacytoid cells (20); (C) Bcl-2 highlights staining in large plasmacytoid cells (40); (D) Mum-1 is positive in plasmacytoid
cells in perifollicular areas (40). (E) k stains plasmacytoid cells in interfollicular areas, including many tumor cells with abundant cytoplasm (40); (F) l stains
scattered rare plasma cells that appear benign (40). Bcl = B cell lymphoma, CD = cluster of differentiation.

and interfollicular areas. An extensive workup including immu- uncommon site which could be rarely get involved.[21,22]
nostaining and molecular genetic studies to completely distinguish Histologically, plasmacytomas are composed of mature, imma-
FL with plasmacytoid differentiation from MALT lymphoma. ture, plasmablastic or anaplastic plasma cells. In the current case,
Identification of the small attenuated CD10+/Bcl-2+ neoplastic residual germinal centers and small lymphocytes do not support a
follicles and positive immunoglobulin H/BCL2 fusion by diagnosis of EMP, other morphological feature such as: mott cells/
fluorescence in situ hybridization are important features for morula cells, Russell body, flame cells, Gaucher-like cells/
diagnosing FL in addition to the vast majority also being positive thesaurocytes, cytoplasmic crystals, and Dutcher bodies were
for t (14; 18) resulting in overexpression of the Bcl-2 gene. absent in current case. Immunostaining showing positive expres-
Conversely, negative expression of Bcl-2 excludes the diagnosis of sion for Bcl-2 is also very helpful to exclude the diagnosis of EMP.
FL.[25] EMP occurs outside of the bone marrow is uncommon, Our case presented with tumor cells infiltrating of the marginal
most of these cases involve in the head and neck region (80%), such zone of reactive B-cell follicles and extension into the
as nasopharynx and sinonasal cavities, while tonsil is a very interfollicular region. The tumor cells exhibit prominant

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