Introduction

Lymphomas are defined as lymphoid cell neoplasms. Traditionally, these are divided into Hodgkin disease and non-Hodgkin lymphoma (NHL). The relative frequency of NHL was 95.4% of malignant lymphoma.1,2  Non-Hodgkin lymphoma affects mostly lymphoid organs, and also affects extranodal sites that do not ordinarily contain lymphoid cells.3  Extranodal lymphomas may vary between the studies with different ethnic groups, comprising 63.3% of NHL cases in Korea.4,5  In a previous study of 2650 cases of extranodal NHL, 1112 (42.0%) cases presented with the disease in the gastrointestinal region.5  The oral cavity involvement in NHL changed from 2.9% in 1998 to 1.9% in 2010 in Korea.1,2 

The most frequent subtype of NHL is diffuse large B-cell lymphoma (DLBCL). It constitutes 25%–30% of adult NHLs in Western countries and 42.7% of NHLs in Korea.5,6  Histologically, DLBCL is a neoplasm of large B lymphoid cells with nuclear size equal to or exceeding normal macrophage nuclei or more than twice the size of a normal lymphocyte that has a diffuse growth pattern.6 

The etiology of DLBCL remains unknown. It usually arises de novo (primary) but can represent progression or transformation (secondary) of a less aggressive lymphoma.6  The immune deficiency is considered a significant risk factor.7  DLBCL more often occurs in Epstein-Barr virus (EBV)-positive elderly patients than those without an overt immunodeficiency.8 

The purpose of this report is to present a case of extranodal DLBCL found in the peri-implant mucosa. Several articles about DLBCL of the oral cavity were reported previously.9,10  To the authors' knowledge, this is the first report of an oral lymphoma in the peri-implant mucosa.

Case Presentation

A 55-year-old man was examined at the Department of Otolaryngology, Seoul St. Mary's hospital in Korea with a complaint of swelling in the left neck region.

Physical examination revealed a nontender hard mass in the left palatine tonsil. On computerized tomography (CT) scan, the left palatine tonsil was enlarged, and multiple lymph nodal enlargements were detected close to the left and right upper internal jugular chains. A biopsy was taken from the mass in the left palatine tonsil.

Histopathologic sections showed diffuse infiltration of large atypical lymphoid cells obliterating lymph node architecture (Figure 1a). On immunostaining, the tumor cells were positive for a B-cell marker (CD20), multiple myeloma oncogene 1 (MUM1), and Bcl-2 (Figure 1b–d), but negative for CD10 (Figure 1e). On hematologic analysis, EBV was detected at a high level in the blood (34 963 copies/mL). The serum lactate dehydrogenase (LDH) level was higher (480 U/L) than normal (250–450 U/L).

Figure 1

Histopathology and immunohistochemical staining of biopsy from neck lymph node. (a) Effacement of nodal architecture with diffuse infiltration of large atypical lymphoid cells (hematoxylin and eosinc; original magnification, ×200 and ×400). Tumor cells were positive for CD20 (b), Bcl-2 (c), and MUM-1 (d), but negative for CD10 (e). Original magnification, ×200, each.

Figure 1

Histopathology and immunohistochemical staining of biopsy from neck lymph node. (a) Effacement of nodal architecture with diffuse infiltration of large atypical lymphoid cells (hematoxylin and eosinc; original magnification, ×200 and ×400). Tumor cells were positive for CD20 (b), Bcl-2 (c), and MUM-1 (d), but negative for CD10 (e). Original magnification, ×200, each.

Prognosis evaluation was performed based on the International Prognostic Index (IPI).11  Five predictors were evaluated: age, serum LDH, sites of involvement, Ann Arbor stage, and Eastern Cooperative Oncology Group performance status (Table 1). The patient was classified as low risk and was expected to have a 73% 5-year survival rate.

Table

Prognosis evaluation by International Prognostic Index*

Prognosis evaluation by International Prognostic Index*
Prognosis evaluation by International Prognostic Index*
*

ECOG indicates The Eastern Cooperative Oncology Group.

Rituximab, cyclophosphamide, hydoroxydaunorubicin, oncovin, and prednisolone therapy was performed 6 times. After chemotherapy, complete resolution of the lymphoma was observed with the 1-, 3-, 6-, 9-, 12-, 15-, and 18-month follow-up CT scans. Enlargement of neck lymph nodes was observed at a 21-month follow-up CT scan, and relapsed DLBCL was diagnosed by needle biopsy of the neck lymph node.

At 23 months, the patient was referred to the Department of Periodontics with a complaint of pain and swelling of the peri-implant mucosa of the lower right second molar implant. Patient's chief complaint was swelling of the peri-implant mucosa and pain when resting. Bleeding on probing and suppuration were observed at the peri-implant mucosa. Clinical evaluation indicated peri-implantitis (Figure 2a). The deepest probing depth was 7 mm. A periapical radiograph showed a crestal bone loss pattern (Figure 2b). A biopsy was performed from the peri-implant mucosa (Figure 3). The patient received additional chemotherapy treatment but did not survive and died 26 months later.

Figure 2

(a) Clinical view indicating bleeding on probing and suppuration were observed at first visit. (b) Periapical radiograph indicating alveolar bone loss around the dental implant.

Figure 2

(a) Clinical view indicating bleeding on probing and suppuration were observed at first visit. (b) Periapical radiograph indicating alveolar bone loss around the dental implant.

Figure 3

Histopathology and immunohistochemical staining of biopsy from peri-implant mucosa. (a) Diffuse infiltration of large atypical lymphoid cells (hematoxylin and eosin; original magnification, ×200 and ×400). Tumor cells were positive for CD20 (b) but negative for CD3(c). Original magnification, ×200, each.

Figure 3

Histopathology and immunohistochemical staining of biopsy from peri-implant mucosa. (a) Diffuse infiltration of large atypical lymphoid cells (hematoxylin and eosin; original magnification, ×200 and ×400). Tumor cells were positive for CD20 (b) but negative for CD3(c). Original magnification, ×200, each.

Discussion

Many studies have focused on oral lymphomas mimicking various oral lesions such as periapical periodontitis,12  periodontal disease,13  gingival swelling,14  dentoalveolar abscess,15  and pericoronitis.16  This report presented DLBCL of peri-implant mucosa, comparable to peri-implantitis.

The peri-implant mucosa has histologic features different from those of the gingiva: composition of connective tissue, the alignment of collagen bundles, and the distribution of vascular structures in the compartment apical of barrier epithelium.17  In contrast, immunologically, the gingiva and the peri-implant mucosa have some common features. When both are healthy, the connective tissues contain small amounts of inflammatory cells. The proportion of T cells is higher than that of B cells.18,19  This feature implies that local immune systems are primarily regulated by T cells in a healthy state. However, in an inflammatory state, B cells dominate among cells in periodontitis and peri-implantitis lesions.20,21  Therefore, metastasis of DLBCL to the peri-implant site could be influenced by continuous B-cell infiltration at the inflammatory peri-implant mucosa.

Peri-implantitis is an inflammatory process of bacterial etiology around an implant, which includes both soft tissue inflammation and progressive loss of supporting bone beyond biologic bone remodeling.21,22  It is generally accepted that changes in the level of the crestal bone in conjunction with bleeding on probing with or without concomitant deepening of peri-implant probing depths are important diagnostic factors.22  Suppuration is a common finding in peri-implantitis sites.22,23  In this report, at the first visit, bleeding on probing with suppuration and crestal bone loss was observed during clinical examination and periapical radiograph. It could have been misdiagnosed as peri-implant disease rather than DLBCL. In consequence of the patients' medical history of lymphoma, a biopsy was performed immediately.

The patient was classified as low risk by IPI. However, in terms of prognosis, the immunophenotype of DLBCL is also important. DLBCL has been subclassified into 3e distinct forms, based on the gene expression profiles: germinal center B-cell like (GCB), activated B-cell like (ABC), and type 3 gene expression (type 3) profiles.24  Generally, the GCB group has a better prognosis than the ABC and type 3 groups.25,26  It is possible to classify DLBCL into the GCB or ABC type using immunohistochemical profiling based on GCB/ABC-related markers (CD10, Bcl-6, and MUM1).27  In addition, Bcl-2 is also strongly related to a poor prognosis of DLBCL.28  In this report, DLBCL was positive for Bcl-2 and subclassified in the ABC group (CD10 negative; MUM1 positive). Therefore, although the patient was classified as low risk by IPI, an adverse prognosis was expected based on immunophenotype.

In conclusion, oral lymphoma should be considered in the differential diagnosis of peri-implantitis. A biopsy and pathologic analysis should be performed, especially in patients with hematologic disease.

Abbreviations

    Abbreviations
     
  • ABC

    activated B cell

  •  
  • CT

    computerized tomography

  •  
  • DLBCL

    diffuse large B-cell lymphoma

  •  
  • EBV

    Epstein-Barr virus

  •  
  • GCB

    germinal center B cell

  •  
  • IPI

    International Prognostic Index

  •  
  • LDH

    lactate dehydrogenase

  •  
  • MUM1

    multiple myeloma oncogene 1

  •  
  • NHL

    non-Hodgkin's lymphoma

Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, Information and Communication Technology, and Future Planning (NRF-2014R1A1A1003106). The authors report no conflicts of interest related to this report.

References

References
1
Kim
JM,
Ko
YH,
Lee
SS,
et al.
WHO classification of malignant lymphomas in Korea: report of the third nationwide study
.
Korean J Pathol
.
2011
;
45
:
254
260
.
2
Ko
YH,
Kim
CW,
Park
CS,
et al.
REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma
.
Cancer
.
1998
;
83
:
806
812
.
3
Wilson
TG,
Wright
JM.
Non-Hodgkin's lymphoma of the gingiva: review of the literature. Report of a case
.
J Periodontol
.
1986
;
57
:
155
158
.
4
Jordan
RC,
Speight
PM.
Extranodal non-Hodgkin's lymphomas of the oral cavity
.
Curr Top Pathol
.
1996
;
90
:
125
146
.
5
Kim
J-M,
Ko
Y-H,
Lee
S-S,
et al.
WHO classification of malignant lymphomas in Korea: report of the third nationwide study
.
Korean J Pathol
.
2011
;
45
:
254
260
.
6
Swerdllow
S,
Campo
E,
Harris
NL.
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
.
Lyon, France
:
IARC Press;
2008
.
7
Flowers
CR,
Sinha
R,
Vose
JM.
Improving outcomes for patients with diffuse large B-cell lymphoma
.
CA Cancer J Clin
.
2010
;
60
:
393
408
.
8
Oyama
T,
Yamamoto
K,
Asano
N,
et al.
Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients
.
Clin Cancer Res
.
2007
;
13
:
5124
5132
.
9
Bulut
E,
Bekcioglu
B,
Gunhan
O,
Sener
I.
Diffuse large B-cell lymphoma with oral manifestations
.
J Craniofac Surg
.
2011
;
22
:
1144
1147
.
10
Sugimoto
KJ,
Shimada
A,
Sakurai
H,
et al.
Primary gingival diffuse large B-cell lymphoma: a case report and a review of the literature
.
Int J Clin Exp Pathol
.
2014
;
7
:
418
424
.
11
The International Non-Hodgkin's Lymphoma Prognostic Factors Project
.
A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project
.
N Engl J Med
.
1993
;
329
:
987
994
.
12
Jessri
M,
AbdulMajeed
AA,
Matias
MA,
Farah
CS.
A case of primary diffuse large B-cell non-Hodgkin's lymphoma misdiagnosed as chronic periapical periodontitis
.
Aust Dent J
.
2013
;
58
:
250
255
.
13
Maxymiw
WG,
Wood
RE,
Lee L.
Primary,
multi-focal, non-Hodgkin's lymphoma of the jaws presenting as periodontal disease in a renal transplant patient
.
Int J Oral Maxillofac Surg
.
1991
;
20
:
69
70
.
14
Urun
Y,
Can
F,
Baris
E,
Akbulut
H,
Utkan
G,
Icli
F.
Primary extranodal non-Hodgkin's lymphoma presenting as painful gingival swelling
.
Exp Oncol
.
2012
;
34
:
134
135
.
15
Ardekian
L,
Peleg
M,
Samet
N,
Givol
N,
Taicher
S.
Burkitt's lymphoma mimicking an acute dentoalveolar abscess
.
J Endod
.
1996
;
22
:
697
698
.
16
Dhanrajani
PJ,
Swaify
GA,
Khateery
SM.
Malignant lymphoma presenting as pericoronitis. A case report
.
Int J Oral Maxillofac Surg
.
1992
;
21
:
295
296
.
17
Lindhe
J,
Lang
NP,
Karring
T.
Clinical Periodontology and Implant Dentistry
.
New York, NY
:
John Wiley & Sons;
2009
.
18
Liljenberg
B,
Gualini
F,
Berglundh
T,
Tonetti
M,
Lindhe
J.
Some characteristics of the ridge mucosa before and after implant installation. A prospective study in humans
.
J Clin Periodontol
.
1996
;
23
:
1008
1013
.
19
Amunulla
A,
Venkatesan
R,
Ramakrishnan
H,
Arun
KV,
Sudarshan
S,
Talwar
A.
Lymphocyte subpopulation in healthy and diseased gingival tissue
.
J Indian Soc Periodontol
.
2008
;
12
:
45
50
.
20
Berglundh
T,
Donati
M,
Zitzmann
N.
B cells in periodontitis: friends or enemies?
Periodontol 2000
.
2007
;
45
:
51
66
.
21
The American Academy of Periodontology
.
Peri-implant mucositis and peri-implantitis: a current understanding of their diagnoses and clinical implications
.
J Periodontol
.
2013
;
84
:
436
443
.
22
Lang
NP,
Berglundh
T,
Working Group 4 of Seventh European Workshop on Periodontology. Periimplant diseases: where are we now? Consensus of the Seventh European Workshop on Periodontology
.
J Clin Periodontol
.
2011
;
38
(
Suppl 11
):
178
181
.
23
Sanz
M,
Chapple
IL,
Working Group 4 of the VEWoP. Clinical research on peri-implant diseases: consensus report of Working Group 4
.
J Clin Periodontol
.
2012
;
39
(
Suppl 12
):
202
206
.
24
Bhattacharyya
I,
Chehal
HK,
Cohen
DM,
Al-Quran
SZ.
Primary diffuse large B-cell lymphoma of the oral cavity: germinal center classification
.
Head Neck Pathol
.
2010
;
4
:
181
191
.
25
Alizadeh
AA,
Eisen
MB,
Davis
RE,
et al.
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
.
Nature
.
2000
;
403
:
503
511
.
26
Rosenwald
A,
Wright
G,
Chan
WC,
et al.
The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma
.
N Engl J Med
.
2002
;
346
:
1937
1947
.
27
Muris
JJ,
Meijer
CJ,
Vos
W,
et al.
Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma
.
J Pathol
.
2006
;
208
:
714
723
.
28
Barrans
SL,
Carter
I,
Owen
RG,
et al.
Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma
.
Blood
.
2002
;
99
:
1136
1143
.