Case Report

A case of spontaneous regression of lymphoma in the mandibulargingiva after biopsy

Nobuyuki Kaibuchi, DDS *, Toshihiro Okamoto, DDS, PhD, Toshiyuki Kataoka, DDS,Akira Kumasaka, DDS, Tomohiro Ando, DDS, PhDDepartment of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan

A R T I C L E I N F O

Article history:Received 18 July 2014Revised 1 November 2014Accepted 28 June 2015Available online 3 July 2015

Keywords:Malignant lymphomaSpontaneous regressionOral cavity

A B S T R A C T

We report a case of lymphoma that developed on the mandibular gingiva and spontaneously regressedafter biopsy was performed. The patient was an 87-year-old man who visited our hospital with a com-plaint of gingival swelling in the left mandibular molar region. We observed an elastic, soft, well-demarcated, granuloma-like mass measuring 30 × 25 mm in size and comprising partially whitepseudomembranous areas. We conducted a biopsy, which confirmed a pathologic diagnosis of a diffuselarge B-cell lymphoma. Because of age constraints, the patient was monitored without being adminis-tered aggressive therapy, and the mass disappeared 20 days after biopsy. We then performed a follow-up biopsy, which revealed the absence of tumor cells. There was no recurrence of lymphoma during the2.5-year follow-up period.© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Spontaneous disappearance of malignant tumors is extremelyrare, but it has been reported in cases of hypernephroma, neuro-blastoma, malignant melanoma, breast tumor, and leukemia [1].Cases of spontaneous disappearance of lymphomas have also beenreported, but very few such cases have been reported for high-grade lymphomas of the oral cavity. Here we report the treatmentand case of high-grade lymphoma in the mandibular gingiva thatspontaneously disappeared.

2. Case report

2.1. Patient

An 87-year-old man presented to our hospital with a com-plaint of gingival swelling in the left mandibular molar region.

2.2. Initial examination

The patient was examined at the beginning of January 2007.

2.3. Chief complaint

The patient complained of swelling in the left mandibular gingiva.

2.4. Family history

There is no significant family history that may be related to thepatient’s case.

2.5. Medical history

The patient was undergoing treatment for old cerebral infarc-tion and premature ventricular contraction at the neurology and car-diovascular departments of our hospital. He was on ticlopidine,spironolactone, furosemide, and mecobalamin. The patient did notappear to have suppressed immunity and was not on immunosup-pressant medication.

2.6. History of present illness

At the beginning of January 2007, the patient visited a major uni-versity hospital because of swelling in the left molar region of themandibular gingiva. He was then referred to our department becausehe was regularly visiting the neurology and cardiovascular depart-ments of our hospital for his other conditions.

* Corresponding author. Department of Oral and Maxillofacial Surgery, TokyoWomen’s Medical University, School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo,Japan. Tel.: +81 03 3353 8112 (28338).

E-mail address: nkaibuchi@oms.twmu.ac.jp (N. Kaibuchi).

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3. Presentation

3.1. General findings

The patient had a height of 153 cm, weighed 61 kg, and had abody temperature of 35.7°C. No swelling was found in the cervi-cal, axillary, or inguinal lymph nodes. Night sweat, visceral pain, andmalaise were not observed.

3.2. Intraoral findings

A 30 × 25-mm mass with well-defined borders was identified inthe left molar region of the mandibular gingiva. It was elastic,granuloma-like, and had a partially white pseudomembrane(Figure 1A).

3.3. Panoramic radiographic findings

The remains of a wisdom tooth root were found in the left man-dible (Figure 2).

3.4. Computed tomography (CT) scan findings

A CT scan performed on the patient showed a non-uniform con-trasted mass near the left lower wisdom tooth (Figure 3A).

3.5. Magnetic resonance imaging (MRI) findings

T2-weighted images revealed non-uniform low signals with somehigh signals. T1-weighted images revealed uniform medium signalintensity. Dynamic MRI revealed an increasing trend over time fornon-uniform contrast of the mass soon after its detection (Figure 3B).Lymphoma is a non-uniform mass without rim enhancement.

3.6. Fluorine-18-fluorodeoxyglucose positron emission tomography(FDG-PET) findings

FDG-localized accumulation was noted in the left mandible(maximum standardized uptake values [SUVmax], 6.00). No in-creased accumulations were noted in the neck and other regions(Figure 3C).

3.7. Clinical diagnosis

The patient was diagnosed with cancer on the left mandibulargingiva.

3.8. Treatment and course

The patient was hospitalized at our department from mid-January 2007 to undergo more detailed testing and treatment. Onthe day of admission, for biopsy, partial tissue samples from the an-terior and posterior sides of the tumor were collected with a scalpel.The pathologic diagnosis was diffuse large B-cell lymphoma. Afterbiopsy, azithromycin was administered to prevent infection. Thepatient consulted the hematology department of our hospital, butactive treatment was not conducted in consideration of the pa-tient’s advanced age, and a “wait-and-see” approach was taken.Twenty days after biopsy, the tumor was found to have disap-peared. The lower left wisdom tooth was extracted and anotherbiopsy was performed on the same area. The results of this biopsyrevealed no malignant findings (Figure 1B). The patient was fol-lowed up for 2 years and 6 months until he transferred to anotherhospital, but no relapse was observed. Subsequently, the patient diedfrom other disease.

Figure 1. (A) At the first medical examination, a 30 × 25-mm mass with clear borderswas identified in the left molar region of the mandibular gingiva. (B) Twenty daysafter biopsy, the tumor was found to have disappeared.

Figure 2. Panoramic radiographic findings showed a wisdom tooth root in the leftmandible.

N. Kaibuchi et al. / Oral and Maxillofacial Surgery Cases 1 (2015) 33–3734

3.9. Histopathologic findings

We observed proliferation of hyperchromatic atypical cellswith high nucleus-to-cell (N/C) ratios, accompanied by necrosis.Immunohistochemistry showed the samples to be positive for CD45and negative for the endothelial marker epithelial membraneantigen; the granulocyte marker myeloperoxidase; the T-cell markersCD3, CD5, CD43, and CD45RO; and the B-cell marker CD20. However,some cells that exhibited partially positive findings for CD79a wereobserved. Furthermore, findings indicating that tissue was nega-tive for LMP-1, CD138, cyclinD1, immunoglobulin kappa and lambdachains, and bcl-2, and positive for CD10 suggested a diffuse largeB-cell lymphoma. Also, the MIB-1 index was greater than 95%(Figure 4).

3.10. Histopathologic diagnosis

Histopathologic diagnosis revealed a diffuse large B-celllymphoma.

4. Discussion

Malignant lymphoma primarily involves the neoplastic trans-formation of lymphocytes. It can be classified into extranodal and

intranodal lymphomas according to the primary onset site. Extranodallymphomas comprise a large percentage of lymphomas in theoromandibular region and are often observed in the gingiva, maxillarysinus, and jawbone. In 1967, Burkitt and Kyalwazi were the first toreport the spontaneous disappearance of a malignant lymphoma[2]. Since then, the same phenomenon has been reported in the above-mentioned areas of the oromandibular region. There have been reportsinvolving various tissue types such as B-cell lymphomas, T-cell lym-phomas, Hodgkin’s lymphoma, and mucosa-associated lymphoidtissue, but most of these reports involved low-grade lymphomas,with spontaneous disappearance of high-grade lymphomas beingrelatively rare [3]. According to Gattiker et al., spontaneous disap-pearance of high-grade lymphomas occurred in 18 of 140 patients(12.9%) with nodular lymphoma and 2 of 69 patients (2.9%) withdiffuse lymphoma [4]. As far as we have been able to ascertain fromthe literature, there have been only 11 reported cases of sponta-neous disappearance of lymphomas in the oromandibular region(Table 1). In the above-mentioned cases, the mean age of patientswas 58.2 years (males, 3; females, 7; unknown, 1). Histopathologicfindings indicated that diffuse large B-cell lymphoma was the mostcommon diagnosis, accounting for 5 of 11 patients. A biopsy similarto the present case was performed on 8 of the 11 patients, after whichthe lymphoma was observed to have spontaneously disappeared.

Possible mechanisms for spontaneous disappearance of lym-phoma include immune mediation, tumor suppression by growth

Figure 3. (A) CT findings: A non-uniform contrasted mass was found near the left lower wisdom tooth. (B) T2-weighted MRI images: T2-weighted images revealed non-uniform low signals with some high signals. (C) FDG-PET findings: FDG-localized accumulation was noted in the left mandible (SUVmax, 6.00).

N. Kaibuchi et al. / Oral and Maxillofacial Surgery Cases 1 (2015) 33–37 35

factors or cytokines, induced differentiation, involvement of hor-mones, removal of the carcinogen, tumor necrosis, blocking ofvascularization, psychological factors, apoptosis, and epigeneticmechanisms [14,15]. Moreover, Sakuma et al. reported that becausethe disappearance of lymphoma was clinically and histologically con-firmed after biopsy, tumor immunity may have been activated bylocal infection caused by trauma stimulation or surgical interven-tion [9].

In the present case, because hematoxylin and eosin (H&E) stain-ing revealed disappearance of the follicular structure and diffuse pro-liferation of large cells, while immunohistochemistry showed thatthe tissue was positive for CD45 and negative for MPO, malignantlymphoma was suspected. Cells with an MIB-1 index of 95% orgreater exhibited positive findings, indicating a high-grade malig-nant lymphoma. However, the subsequent clinical course suggested

that it disappeared because of stimulation caused by the biopsy pro-cedure. The patient was followed up for 2 years and 6 monthsbecause he changed hospital. However, a previous study showedthat similar patients should be followed up for longer periods [16].

Conflict of interest

The authors do not have any conflicts of interest to disclose.

References

[1] Papac RJ. Spontaneous regression of cancer. Cancer Treat Rev 1996;22:395–423.

[2] Burkitt DP, Kyalwazi SK. Spontaneous remission of African lymphoma. Br J Cancer1967;21:14–16.

Figure 4. (A) H&E staining (×200); (B) CD45 (×200); (C) CD79a (×200); (D) MIB-1 index (×200) H&E staining showed proliferation of hyperchromatic atypical cells with highN/C ratios, accompanied by necrosis. Immunohistochemistry showed the samples to be positive for CD45 and partially positive for CD79a. Also, the MIB-1 index was greaterthan 95%.

Table 1Reported cases of spontaneous disappearance of lymphomas in the oromandibular region

Case Author Year Age Sex Location Clinical symptoms Histological type Stage Treatment

1 Burkitt and Kyalwazi [2] 1967 4 Female Maxilla Unknown Unknown Unknown Biopsy2 Savarrio et al. [5] 1999 77 Male Soft palate Ulcer, swelling ALCL Unknown Biopsy3 Yamamoto et al. [6] 2003 80 Female Maxilla Ulcer, swelling DLBCL IIE Antibiotics4 Koga et al. [3] 2003 78 Female Maxilla Redness, swelling DLBCL IE Biopsy5 Yokoyama et al. [7] 2003 46 Female Hard palate Swelling MALT I Biopsy6 Heibel et al. [8] 2004 70 Unknown Mandible Ulcer B-cell NHL IAE Biopsy7 Sakuma et al. [9] 2006 70 Female Hard palate Ulcer MALT I Biopsy8 Armstrong et al. [10] 2007 35 Male Maxilla Redness, swelling DLBCL Unknown Biopsy9 Daly et al. [11] 2008 56 Male Maxilla Ulcer, bone exposure T-cell NHL Unknown None

10 Tamas et al. [12] 2011 66 Female Tongue Swelling DLBCL Unknown None11 Brachet et al. [13] 2011 58 Female Hard palate Swelling DLBCL Unknown Biopsy

ALCL, anaplastic large cell lymphoma; DLBCL, diffuse large B-cell lymphoma; MALT, mucosa-associated lymphoid tissue lymphoma; NHL, non-Hodgkin’s lymphoma.

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[3] Koga M, Kusukawa J, Hayabuchi N. Spontaneous regression of extranodal ma-lignant lymphoma occurred in the gingiva. Oral Oncol 2003;39:323–4.

[4] Gattiker HH, Wiltshaw E, Galton DA. Spontaneous regression in non-Hodgkin’slymphoma. Cancer 1980;45:2627–32.

[5] Savarrio L, Gibson J, Dunlop DJ, O’Rourke N, Fitzsimons EJ. Spontaneous re-gression of an anaplastic large cell lymphoma in the oral cavity: first re-ported case and review of the literature. Oral Oncol 1999;35:609–13.

[6] Yamamoto K, Ohgi K, Yasumoto J, Imai Y, Kawakami M, Kirita T. A case of spon-taneous regression of malignant lymphoma of the upper gingiva. J Jpn Soc OralTumor 2003;15:7–12 [in Japanese].

[7] Yokoyama T, Miyazawa K, Otawa M, Kawakubo K, Kuriyama Y, Serizawa H, et al.Spontaneous regression of the hard palate accompanied by Sjogren syn-drome. Jpn J Clin Hematol 2003;44:468–70 [in Japanese].

[8] Heibel H, Knödgen R, Bredenfeld H, Wickenhauser C, Scheer M, Zöller JE. Com-plete spontaneous remission of an aggressive non-Hodgkin’s lymphoma withprimary manifestation in the oral cavity. Leuk Lymphoma 2004;45:171–4.

[9] Sakuma H, Okabe M, Yokoi M, Eimoto T, Inagaki H. Spontaneous regression ofintraoral mucosa-associated lymphoid tissue lymphoma: molecular study ofa case. Pathol Int 2006;56:331–5.

[10] Armstrong R, Bradrick J, Liu YC. Spontaneous regression of an HIV-associatedplasmablastic lymphoma in the oral cavity. J Oral Maxillofac Surg 2007;65:1361–4.

[11] Daly RM, Healy CM, Toner ME, Flint SR. Spontaneous regression of non-Hodgkin’s lymphoma in the oral cavity after incisional biopsy. Br J Oral MaxillofacSurg 2008;46:223–5.

[12] Tamás L, Sári E, Répássy G, Szabó P, Bagdi E, Krenács L, et al. Spontaneous re-mission in localized diffuse large B-cell lymphoma. Pathol Oncol Res 2011;17:779–84.

[13] Brachet P, Deleval L, Chantrain G, Loeb I, Saussez S. Hard palate B cell lymphomawith spontaneous regression. Rev Stomatol Chir Maxillofac 2011;112:180–2.

[14] Papac RJ. Spontaneous regression of cancer: possible mechanisms. In Vivo1998;12:571–8.

[15] Krikorian JG, Portlock CS, Cooney P, Rosenberg SA. Spontaneous regressionof non-Hodgkin’s lymphoma: a report of nine cases. Cancer 1980;46:2093–9.

[16] Wiemik PH. Spontaneous regression of hematologic cancers. Natl Cancer InstMonogr 1976;44:35–8.

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