A case of childhood Burkitt's lymphoma with gingival swelling as the first symptom

Annals of Clinical and Medical
Case Reports
Case Report ISSN 2639-8109 Volume 9
Yun-xuan Yang1
, Zhi-yong Zhang2
and Yong-hong Liu1*
1
Department of Oral Medicine, The Second Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, China
2
Department Head Professor, Department of Oral Medicine, The Second Hospital of Hebei Medical University, Hebei Medical Univer-
sity, Shijiazhuang, China
3
Department of Oral Medicine, The Second Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, China
A Case of Childhood Burkitt’s Lymphoma with Gingival Swelling as The First Symptom
*
Corresponding author:
Yong-hong Liu,
Department of Oral Medicine,The Second Hospital
of Hebei Medical University, Hebei Medical Univer-
sity, Shijiazhuang, China, Mobile: +86 13582040748,
E-mail: liuyonghong_sjz@126.com
Received: 02 May 2022
Accepted: 16 May 2022
Published: 21 May 2022
J Short Name: ACMCR
Copyright:
©2022 Yong-hong Liu. This is an open access article
distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, dis-
tribution, and build upon your work non-commercially.
Citation:
Yong-hong Liu, A Case of Childhood Burkitt’s Lympho-
ma with Gingival Swelling as The First Symptom . Ann
Clin Med Case Rep. 2022; V9(4): 1-6
http://www.acmcasereport.com/ 1
Keywords:
Burkitt's lymphoma; Gingival swelling; Diagnose
Abbreviations:
BL: Burkitt's Lymphoma; PET-CT: Positron Emission Tomography-Computed Tomography;
CNCL: China Net-Childhood Lymphoma: KFX: Kangfuxin Liquid: BL/B.AL: BL/Leukemia; EFS: Event-free Survival: PFS: Progression-free Sur-
vival; LDH: Lactate Dehydrogenase
1. Abstract
Burkitt's lymphoma (BL) is a highly infiltrative malignant lym-
phoma caused by germinal B-cell differentiation. There are sev-
eral oral symptoms of BL, including tooth mobility, pain, gingi-
val swelling, maxillofacial swelling and pain, and facial sensory
disturbances. In this paper, we report a case of BL in a 4-year-old
child who initially presented with gingival swelling. The diagno-
sis of BL/leukemia (stage IV) was confirmed by the bone marrow
examination, bone marrow flow cytometry, and B lymphocytoma
mutation gene screening test. After chemotherapy, the general
condition improved, and then there was swelling and pain in the
right cheek. Considering the recurrence of the disease, the patient
died half a year later. This case is characterized by BL with oral
symptoms as the first symptom, emphasizing the important role of
physicians in early detection of systemic disease.
2. Introduction
In 1958, Burkitt's lymphoma (BL) was initially discovered and
named by British surgeon Dennis Burkitt [1]. BL is a highly infil-
trative malignant lymphoma caused by germinal B-cell differenti-
ation. Its development is associated with MYC gene dysregulation,
Epstein-Barr virus infection and falciparum malaria [2]. The clin-
ical manifestations of BL are endemic, sporadic, and immunodefi-
ciency-associated [3]. Endemic BL is more universal in equatorial
Central Africa. More than 95% of endemic BL are associated with
Epstein-Barr virus and falciparum malaria infections. Sporadic
BL, the most common type, accounts for 30% of childhood lym-
phomas with no differences in specific geographical distribution
and climate. It, most commonly manifested as abdominal masses,
such as small intestinal, mesenteric and ovarian masses. Approxi-
mately 25% of sporadic BL could have great impacts on the head
and neck, especially on cervical lymph nodes. Immunodeficien-
cy-associated BL mainly occurs in HIV-infected patients and or-
gan transplant recipients, mainly involving lymph nodes and bone
marrow [4,5,6]. There are several oral symptoms of BL, including
tooth mobility, pain, gingival swelling, maxillofacial swelling and
pain, and facial sensory disturbances. [6]. In this paper, we report a
case of BL in a 4-year-old child who initially presented with gingi-
val swelling. The presentation and treatment of such cases are rare.
The second recurrence of this case also had oral manifestations
of right gingival swelling on the right side of the mouth, and the
prognosis of the case was poor. Under the exclusion of the etiology
of simple periodontal inflammation, if the patient presents with ex-
cessive tooth mobility and severe alveolar bone resorption around
the eruption of permanent teeth, dentists should attach great im-
portance to the examination of the general condition.

Volume 9 Issue 4 -2022 Case Report
3. Case Report
Consent for publication in this report was obtained from the pa-
tient's parents. The patient (male; aging 4-year-old) with a 2-week
history of swelling on the right cheek and swollen gums was di-
agnosed in the Department of Oral Medicine in August 2018 Past
medical history. In January 2018, the patient visited another hospi-
tal due to gingival swelling, and was given "antibiotics" for "acute
periodontal abscess", but the effect was poor. In February 2018, the
patient was admitted to the Department of Pediatric Internal Med-
icine due to persistent low-grade fever. The diagnosis of BL/leu-
kemia (stage IV) was confirmed by the bone marrow examination,
bone marrow flow cytometry, and B lymphocytoma mutation gene
screening test. The condition was improved after anti-infection and
chemotherapy. When the patient suffered from swelling and pain
of the right cheek and gingival swelling and pain of the right lower
posterior tooth again, he visited the Department of Oral Medicine.
After reexamination of Positron emission tomography-computed
tomography (PET-CT), considering the recurrence of the disease,
there was no significant improvement after chemotherapy. The
family gave up treatment, and the patient died half a year later (1).
Clinical examination: A lymph node about 2.5 * 3 cm in size was
palpable in the submandibular region. The throat of the child was
congested with I° tonsillar enlargement. Neurological examination
showed that the right frontal striae became shallower when lift-
ing the eyebrows. The right eyelid could not be completely closed
when closing the eyes. The right nasal striae were shallower when
shrugging the nose. The drumsticks could be drummed, the neck
was soft, and the corneal reflex existed. Dental examination re-
vealed fair oral hygiene and essentially normal occlusal relation-
ship. The buccal lingual gingiva of the lower right first deciduous
molar and the lower right second deciduous molar were red, swol-
len and bright with diffused swelling according to the palpation
(+). The erosive surface was observed on the far middle buccal
side that was covered with a pseudomembrane of the lower right
second deciduous molar. A lingual deviation and detectable peri-
odontal pockets with percussion (+ +) were found, which indicated
the grade Ⅱ loosening (Figure 1). The buccal lingual gingiva of
the lower left second deciduous molar was mild red and swollen
with percussion (-), which indicated the grade I loosening (2).
Auxiliary examination: Laboratory tests showed white blood cells
of 8.69×109
/L (normal range 8-10×109
/L), hemoglobin of 85g/L
(normal range 120-140g/L), platelets of 352×109
/L (normal range
100-300×109
/L), lactate dehydrogenase of 1503 U/L (normal
range 100-300U/L). Examination and analysis of myelogram dis-
played that the lymphocyte system was highly proliferative. The
cells were large and blue with coarse chromatin, nucleoli in some
cells, small cell mass, vacuoles in the nucleus and cytoplasm in
most cells, prolymphocytosis, and prolymphocytosis, considering
the possibility of BL (Figure 2). Bone marrow fluid flow cytom-
etry results: CD45dimCD19 + cells about 18.9%; CD20:96.3%,
Kappa: 86.5%; CD10:56.2%; CD22dim: 44.6%; CD79b: 85.3%;
CD23:96.2%; FMC: 97.7%; CD24:61.5%. It should be reminded
that some abnormal B lymphocytes were found. Genetic screening
for B lymphocytoma mutations: detection of MYC gene p.Y89H,
p.P78T, D236H site mutation. Abdominal ultrasound displayed
several lymph nodes with heterogeneous hypoechogenicity in the
right abdomen. Cerebrospinal fluid cytology revealed multiple het-
erosexual cells, including lymphoma, suggesting involvement of
the central nervous system. PET-CT (February 27th
, 2018, Figure
3): ① Increased diffuse metabolism of the whole-body bone mar-
row. Lymphoma may involve bone, bone marrow, lymph nodes,
pancreas, and both kidneys. ② Significant bone destruction of the
mandible and filling of the surrounding soft tissue shadows. PET-
CT (August 24th
, 2018, Figure 4) reexamination showed that there
was no abnormality in the metabolism of the whole-body bone
marrow, multiple bones, submandibular lymph nodes, pancre-
as, or both kidneys. The right mandible was still hypermetabolic
with visible bone destruction, soft tissue mass formation, unclear
boundary, and heterogeneous density. Panoramic radiography be-
fore treatment (January 1st
, 2018, Figure 5) showed low-density
destruction of the mandibular body, low-density shadows in the
apical region of the lower right second deciduous molar and the
lower left second deciduous molar, and loss of mandibular second
premolars. Panoramic radiography reexamination with chemo-
therapy showed (August 17th
, 2018, Figure 6) that there was root
apical truncating resorption of the lower right second deciduous
molar and bone destruction edge affected tooth germs of the low-
er right first permanent molar and the lower right first premolar,
which led to compression displacement. Compared with before
treatment, the degree of bone destruction around the apical region
of the lower right second deciduous molar and the lower left sec-
ond deciduous molar was improved with increased bone mineral
density.
(3) Diagnosis: 1. BL/leukemia (stage IV) 2. periodontal abscess
(4) Treatment: 1. The child was treated with China Net-Childhood
Lymphoma (CNCL)-HL GroupC regimen. 2. Oral local treatment:
the child was gargled with Kangfuxin liquid (KFX) solution and
treated with gingiva wiping, pseudomembrane washing, 3% hydro-
gen peroxide pericoronal irrigation, and education to maintain oral
hygiene. In addition, after communication with the physician, the
supportive treatment and systemic antibiotics were recommended
to reduce systemic infection and periodontal inflammation.

Figure 1: The buccal lingual gingiva of the lower right first deciduous
molar and the lower right second deciduous molar were diffused swelling.
Lingual deviation of the lower right second deciduous molar.
Figure 2: Increased pro- and prolymphocytes by Myelogram examina-
tion. (Wright Giemsa staining, 10×100).
Figure 3: Systemic increased bone metabolism and bone destruction in
both mandibles by PET-CT.
Figure 4: Increased metabolism in the right mandible with visible bone
destruction and soft tissue formation by PET-CT.
Figure 5: Panoramic radiography (January 1, 2018): low-density destruc-
tion of the mandibular body.
Figure 6: Panoramic radiography (Aug. 17, 2018): there was root apical
truncating resorption of the lower right second deciduous molar and bone
destruction edge affected tooth germs of the lower right first permanent
molar and the lower right first premolar, which led to compression dis-
placement.

4. Discussion
BL has unique clinical and morphological characteristics with rap-
id development, short course of disease, and high degree of malig-
nancy, accounting for 30-50% of pediatric non-Hodgkin's lympho-
ma [7]. BL is extranodal or characterized by leukemia. Due to the
short doubling time of tumor cells, most patients suffer from bone
marrow involvement and progress to leukemia stage (tumor cells >
25%), which is called BL/leukemia (BL/B.AL). BL is mostly char-
acterized by high tumor burden at initial diagnosis and more prom-
inent symptoms of abdominal and maxillofacial tumor masses [8].
Thrombocytopenia is the most common hemogram in patients.
Anemia or leukopenia may occur, and high white blood cell count
may occur in some patients. The varied number of tumor cells may
be seen in the peripheral blood. BL/B.AL is more prevalent in pe-
diatric non-Hodgkin's lymphoma. The diagnosis of BL requires a
comprehensive analysis combined with cytomorphological, im-
munophenotypic and genetic characteristics [9]. Pathological find-
ings are mainly composed of poorly differentiated lymphocytes,
mixed with phagocytic histiocytes with clear cytoplasm, leading
to typical "starry sky" images [10]. On the immunophenotyping,
IgM and B cell-associated antigens (e.g., CDl9, CD20, CD22,
CD79a), CDl0, and BCL-6 were mostly expressed, but CD5, TdT,
and BCL-2 were not expressed [11]. In addition, almost 100% of
Ki-67 was positive, CD45 was highly expressed, and cD34 and
TdT were often negative. These findings were consistent with the
high expression of CD19, CD20, CD10, CD22, and CD79b in this
case. Cytogenetically, the characteristic change is a translocation
of the C-myc gene [12]. In this case, changes in MYC gene locus
were detected in genetic screening. Mutations in the MYC gene
can be found in about 40% of BL. MYC gene is an oncogene en-
coding nuclear protein. MYC gene product, C-myc gene can affect
the protein transcription levels of apoptosis, cell growth, differen-
tiation, and other biological processes. The three c-myc transloca-
tions that often occur in BL accelerate malignant tumor growth by
facilitating cell proliferation [8]. It is interesting to note that the
occurrence of sporadic BL is mostly affected by the relationship
between oncogenes and cancer-suppressor gene mutations. P53
mutation, the most common secondary change in sporadic BL, is
closely related to MYC dysregulation and abnormal activation of
the PI3K-AKT signaling pathway [13]. Mutation of p53 to an on-
cogene is essential for the occurrence and development of BL [14].
In addition, the content of miRNAs was different in BL tumor cells
and lymph node reactive proliferative cells, and miR-155 is cor-
related with poor prognosis in lymphoma and leukemia [15,16].
PET-CT is known with its sensitive, specific and accurate charac-
teristics in localization, which can be used for early diagnosis and
staging of tumors. Due to its prominent role in disease assessment,
it is now widely used in the examination of most lymphoma sub-
types [17]. In this case, the right gingiva swelling was the first
symptom. PET-CT (February 27th
, 2018) showed increased diffuse
metabolism of the whole-body bone marrow with evident bone
destruction of the mandible. After chemotherapy, reexamination
of PET-CT (August 24th
, 2018) exhibited the increased metabolism
of the right mandible and volume of soft tissue mass, and relieved
other parts. Clinically, it is considered that the possibility of recur-
rence was very high. Through the comparison of two PET-CT, it
was found that effective treatment alleviated the bone destruction
of the left mandible, and suppressed the gingival inflammation. In
the right mandible, although the extent of bone destruction was
reduced, the increase of bone metabolism was associated with
soft tissue mass formation. It can be explained that the exposed
periodontal pocket communicated with the outside world is not
conducive to the inhibition of inflammation. In addition, primary
malignant lymphoma of the jaw irregularly destroys the cancellous
bone of the jaw in the early stage, then penetrates the dense bone
to invade the soft tissue, leading to facial swelling. Because the
patient's physical condition was not suitable for tooth extraction
treatment, it is essential to control inflammation and strengthen the
hygienic care of the oral cavity. Chemotherapy is the first choice
for the treatment of BL, which is combined with other therapies,
including monoclonal antibody therapy, immunotherapy, bone
marrow transplantation, surgical treatment, and radiotherapy. Ac-
cording to different types, different stratified chemotherapy reg-
imens have been adopted by major international treatment cen-
ters, and the 5-year event-free survival (EFS) rate has increased
to over 80% [18]. At present, the multi-center cooperative group
treatment regimen adopted in China is the modified protocol CN-
CL-NHL-B-2017 of the internationally accepted basic protocol
LMB89/96. A total of 488 children with mature B-cell lympho-
ma were treated in a multicenter study by the Chinese Children's
Lymphoma Collaborative Group (CNCL) during a 3-year period,
and the overall 2-year progression-free survival (PFS) reached
88.7% [19]. The prognosis of BL is closely related to the type of
disease, the age of patients, tumor size, diagnostic stage, and he-
moglobin level [20]. In this case, there are multiple indicators of
poor prognosis, such as bone marrow and central nervous system
involvement, tumor mass > 10 cm in diameter, abnormal C-myc
gene, and high serum level of lactate dehydrogenase (LDH). With
the wide application of short-course and high-dose chemotherapy
regimens, the prognosis of children with BL has been significantly
improved, but there are still a few children who progress or relapse
during treatment, and the prognosis of children with relapsed and
refractory disease is poor. After high-intensity chemotherapy in
100 children with BL in an Italian center, the recurrence rate was
about 7% [21], close to 8.9% that reported by Beijing Children's
Hospital [22]. At present, relapsed and refractory BL in children
has been improved by rituximab combined with high-intensity
chemotherapy in the first-line treatment at home and abroad [23].
In the future, the treatment of BL will be more inclined to promote
the molecular characteristics of tumorigenesis through molecular
biology, genomics, etc., and targeted immunotherapy is a poten-
tial strategy for relapsed and refractory patients [20]. For children

with malignant tumors, oral conditions should be paid close atten-
tion. Throughout the whole course of treatment, it is imperative
to monitor oral mucosal changes timely and to implement early
intervention and nursing. In addition, strengthening the oral health
education of patients and their families is helpful to prevent and
treat oral problems in patients with cancer and to reduce the risk
of oral infection. Tumor cell infiltration of the disease itself and
drug treatment reduced child's own resistance with the destroyed
tissue structure of oral mucosal cells, reduced salivary secretion,
which is very likely to be secondary to oral infection. Poor oral en-
vironment and oral self-cleaning habits arethe essential factors of
oral infection following chemotherapy in patients with hematolog-
ical malignancies. Kangfuxin liquid (KFX) for traditional Chinese
medicine, the main ingredient is alcohol extract of Periplaneta
americana, containing polyols, sticky sugar amino acid, epidermal
growth factor and other active substances [24]. KFX can effective-
ly shorten the healing time of ulcers and relieve the pain of Oral
ulcer induced by chemotherapy, with no adverse drug reactions.
Cleaning the mouth, protecting the oral mucosa, and keeping the
oral cavity moist are essential to control infection [25].
5. Conclusions
As a unique B-cell tumor, BL develops rapidly. The comprehen-
sive understanding of the disease is conductive to improve the
vigilance and emphasize the important role of physicians in early
detection of systemic disease. For patients with recurrent gingi-
val swelling, the general condition should not be ignored, and the
primary disease should be found as soon as possible to confirm
diagnosis and to refer in time, thereby improving the quality of
life of patients.
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