Presentation and a 5-year follow-up of a rare case report
1. Introduction:
Lymphomas represent the third most common neoplasm in the head and neck
region arising from the lymphoreticular system. They constitute a group
of neoplasms of varying degrees of malignancy, derived from the basic
cells of lymphoid tissues, lymphocytes, and histiocytes at any stage of
their development [1].
Malignant lymphomas are divided into Hodgkin disease and non-Hodgkin
lymphoma (NHL) [1].
Non-Hodgkin lymphomas (NHLs) account for around 90% of all malignant
lymphomas and Hodgkin lymphomas (HLs) for the remaining 10% [2].
Hodgkin disease typically arises in the lymph nodes and usually occurs
in the cervical and mediastinal nodes. However, NHL often presents as
extranodal disease [3].
Indeed, nearly 25% of NHL occur in extranodal sites, with the skin,
gastrointestinal tract, and central nervous system being the most
commonly affected sites. In the oral cavity, the majority of cases occur
in Waldeyer’s ring, followed by the buccal mucosa, tongue, floor of the
mouth, and retromolar area [4].
Diffuse large B-cell lymphoma (DLBCL) is the most frequently reported
NHL subtype. It is an aggressive, rapidly growing neoplasm of large
lymphoid cells, and it commonly occurs in men older than 50 years
[5]. The manifesting symptoms in the mouth cavity include
nonspecific swelling, non-healing dental extraction wounds, ulceration,
and aposteme. DLBCL may be misdiagnosed as osteomyelitis, periodontosis,
pyogenic granuloma, and as malignant tumors, such as squamous cell
carcinoma [5].
Only few publications have focused on DLBCL in the mouth cavity, leading
to difficulties in diagnosing and understanding the biological
characteristics of this disease, choosing a rational treatment, and
providing an accurate prognosis [4].
The aim of this report was to describe a rare case of a mandibular NHL
mimicking post-extraction complication and to highlight the importance
of early diagnosis in improving the prognosis of the disease.
2. Case report:
A 66-year-old male patient was referred to the dental clinic with a
chief complaint of swelling in the left side mandibular area under the
chin persisting for 60 days, accompanied by left labio-chin
hypoesthesia.
The patient reported having a mobile anterior tooth that was extracted
in a private clinic.
Extraoral examination revealed a solitary swelling on the left side
mandibular area under the chin, measuring about 5 cm of long axis and
extending to the oral floor (Fig. 1).
The swelling surface was smooth.
On palpation, the swelling was not tender; it was firm, non-fluctuant,
and without thrill or pulsation.
Multiple bilateral submandibular lymph nodes were palpable and not
tender. They were firm and fixed to the adjacent tissues. The lymph
nodes of others regions were not palpable.
Intraoral examination revealed a delayed healing at the site of tooth 33
(Fig. 2).
Occlusal radiography and occlusal radiography of the chin revealed
swelling just in the area under the chin without any osseous lesion
(Fig. 3).
Panoramic radiography showed a blurred appearance of the bone at the
site of the extracted tooth (Fig. 4).
Craniofacial CT scan examination revealed an infiltration of the left
lateral mandibular chin soft tissues and the oral floor, associated with
a poorly-limited osteolytic lesion affecting the mandibular crest and
the vestibular bone cortex. The chin foramen was in full osteolytic
lesion. No enhancement of the lesion was noted after injection of
iodinated contrast material (Fig. 5).
Based on these clinical and radiographic findings, a malignant process
was suspected. The patient was therefore immediately referred to the
Department of Maxillofacial Surgery.
A biopsy of the tumor mass on the buccal floor was taken.
The histopathologic examination of the biopsy showed a fibrous adipose
and striated muscular tissue, richly vascularized and crossed by
numerous nerve threads, dissociated by a tumor infiltrate of
lymphomatous appearance, composed of large cells, non-jointed, of
centroblastic type, presenting numerous images of mitosis, enveloping
the vascular and nervous structures and dissociating the striated
muscular fibres. In addition, it presented a rather abundant reactive
lymphocytic population.
The immunohistochemically study carried out on kerosene sections
revealed intense and diffuse labelling of the tumor cells with CD20,
while CD30 was negative (Fig. 6).
Based on these findings, diagnosis of diffuse large B-cell lymphoma
(DLBCL) was made.
The patient was referred to a hematologist-oncologist for evaluation.
Several examinations were performed, including thoracic-
abdominal-pelvic CT scan and bone scintigraphy.
These examinations showed no abdominal-pelvic metastasis; however, left
mandibular hyperfixation was noted at the bone scintigraphy (Fig. 7).
The patient was kept on sequential courses of chemotherapy.
After treatment, the patient completely recovered. Complete tumor
remission was observed, which was confirmed by occlusal radiography and
CT scan. A favorable clinical evolution with total alveolar healing was
noted. Close follow-ups were scheduled, and 5 years after the last cycle
of chemotherapy, no signs of tumor recurrence were noted (Fig. 8).
3. Discussion:
Lymphomas are currently classified based on the clinical features,
morphology, immunophenotyping, and molecular genetics. Over the years,
various schemas have been developed to classify lymphomas [6]. The
most widely used schema is the 2008 World Health Organization (WHO)
classification, which is based on the principles defined in the Revised
European-American Classification of Lymphoid Neoplasms (REAL) [6].
It was updated in 2016 to provide pathologists and hemato-oncologists
with the recent advances in understanding the disease [7].
Lymphomas can be divided into two major entities, namely Hodgkin
lymphoma (HL) and non-Hodgkin lymphoma (NHL). Over 20 different subtypes
of NHL have been classified according to the specific subtype of
lymphoid cells involved [8].
NHLs (Non-Hodgkin Lymphomas) are a heterogenous group of
lymphoproliferative malignancies that are much less predictable than
Hodgkin lymphomas and have a far greater predilection to disseminate to
extranodal locations [1].
The sites for extranodal non-Hodgkin lymphoma are:
1. Waldeyer’s ring (Nasopharynx, palatine tonsils, base of the tongue,
and oropharyngeal wall).
2. The oral cavity (Palate, gingiva, maxilla, and tongue).
3. The salivary glands.
4. Thyroid.
5. Larynx.
6. The nasal cavity.
7. Paranasal sinuses.
8. The skin [1].
In the oral cavity, lymphomas can appear anywhere in the mouth but they
predominate on the hard palate, gingiva, and tongue. The mandible is an
infrequent localization of primary osseous NHL [9].
In the present case, the patient presented with swelling of the area
under the chin extending to the floor of the mouth, leading to a
suspicion of post-extraction complication given the delay in the healing
of the site of tooth 33.
NHLs consist of a group of abnormal proliferation of 2 distinct
lymphocyte types, B or T and their precursor cells [4].
DLBCL represents the most common type of NHLs, accounting for 40% off
all cases. DLBCL is a heterogeneous entity having varied clinical
features, morphology, immunohistochemistry, and prognosis. These
differences should be carefully analyzed in order to ensure successful
management [9].
The median age is 64 years and men are slightly more affected than women
[10].
In their study, Van der Waal et al. published the data of 40 cases of
primary extranodal NHL of the oral cavity. The Median age according to
their study is 59 years (3-88 years) and males are more commonly
affected than females [11].
This coincides with the age and sex of the patient included in this
study who was male at the age of 66 years.
Diagnosis of lymphoma in the jaws is difficult and it is often delayed
for many reasons.
For instance, the clinical and radiographic presentations are not
specific for lymphoma. Clinically, lymphoma may cause vague pain and
discomfort, which might be easily misdiagnosed as periapical lesion
developed from an odontogenic infection [10]. The radiographic
changes in the early stages of the tumor may be subtle and they are
usually detected only late as an ill-defined radiolucency that might
resemble a dental abscess [10].
Conventional radiography of these lesions shows non-defined alveolar
margin, loss of cortical limits, widening of the periodontal space,
irregular radiolucent lesions, and ill-defined borders [12].
Diagnosis of oral lymphomas may therefore be challenging because there
is frequently a low index of clinical suspicion, leading to misdiagnosis
and/or delayed treatment [13]. Oral cavity mass can be a rare
presentation of a number of conditions, including infections, such as
bacterial osteomyelitis, invasive fungal infection and syphilis,
inflammatory diseases, particularly Wegener’s granulomatosis, and
neoplasms, including squamous cell carcinoma and lymphoma [13].
In the present case, standard radiographs (panoramic and occlusal
radiographs) were not conclusive. Only CT scan revealed an osteolytic
lesion with irregular margins at the site of tooth 33, associated with
an infiltration of the soft tissues in the mandibular region under the
chin.
Tumors in the head and neck are easily accessible. Biopsy should
therefore be immediately performed following suspicious findings
[8]. In particular, for NHL with extranodal involvement in the head
and neck occurring at a frequency of 20 to 30%, biopsy should always be
part of the diagnosis in any head and neck lesions, including those in
the oral cavity, major salivary glands, oropharynx, nasopharynx,
paranasal sinus, and larynx [8].
In fact, Diffuse Large B-Cell Lymphoma (DLBCL) is characterized by
diffuse infiltration of medium to large cells with large nucleoli and
abundant cytoplasm, which disrupts and effaces the underlying
architecture of the involved tissue. The cells typically express pan-B
cell antigens, including CD19, CD20, CD22, CD79a, and CD45. The majority
of the cells also express surface immunoglobulin. Approximately 14% of
the cases express CD30, which can portend a favorable prognosis
[14].
In the present case, the cells strongly expressed CD20. They did not
express CD30.
Indeed, CD30 is expressed in various T cell lymphomas and DLBCL. The
expression pattern is variable and in DLBCL, CD30 expression is
associated with prognosis [15].
The standard imaging assessment includes a thoracic, abdominal, and
pelvic computed tomography, with measurement of the lesions that will
serve as the initial reference for the treatment response assessment. A
PET scanner FDG is also necessary to identify the degree of tumoral
extension and to determine the Ann Arbor stage [16].
For our patient, thoracic X-ray, thoracic-abdominal-pelvic CT scan, and
bone scintigraphy were performed. These examinations did not show any
distant lesions.
Our patient was therefore classified as stage IVA according to the Ann
Arbor stage.
Treatment for DLBCL often involves chemotherapy and depending on the
clinical stage and the outcome of the treatment, chemotherapy can be
combined with radiotherapy. However, its response to chemotherapy is not
always satisfactory and if remission is not maintained, the patient is
considered for bone marrow transplantation [5].
The present case was treated with chemotherapy alone and it has so far
shown a satisfactory outcome.
The survival of extra nodal NHL of the head and neck depends on the
extent of the disease, presence or absence of HIV serology status,
histopathology, and Ann Arbor staging. Five-year
survival rate of extranodal NHL of the head and neck was reported by
Pazoki et al. and the medial survival rate for stage IE is 10 years
[17]. Wolvius et al. reported 34 cases of primary extranodal
lymphoma of the oral cavity and the mean survival time was reported to
be 38 months with a mean recurrence-free survival time of 31 months.
According to Slootweg et al., survival of oral NHL varies according to
Ann Arbor stage and it was 70% for those who presented at base line
with stage I disease and 20% for stages II-IV disease [17].
The patient´s follow-up is indispensable because of the disease
recurrence risk which must
not be neglected.
The national Cancer Institute (NCI) recommends that follow-up visits
should include the patient’s history, physical examination for
lymphadenopathy, abdominal masses, organomegaly, complete blood cell
count, and LDH. Additional blood tests and imaging studies may be added
for relevant clinical indications but specific tests cannot be currently
recommended [18].
In the present case, the patient was followed regularly by his
hematologist with clinical, radiological, and biological examinations.
No sign of recurrence was noted over a period of more than 5 years.
4. Conclusion:
Slight clinical symptoms together with clinical and radiological
findings may not be clear enough to provide the dentist with specific
indications.
The clinician should be aware of the possibility of jaw tumors and
should not delay the decision in favor of further radiographic and
histological examinations to avoid tumor progression [19].
Clinicopathologic correlation is therefore crucial to reach the correct
diagnosis in clinically suspicious cases [10].
Figures:
Fig. 1: Extraoral photograph showing left mandibular swelling under the
chin expending inferiorly.
Fig. 2: Intraoral photograph showing delayed healing at the site of
tooth 33 associated with swelling on the floor of the mouth.
Fig. 3: (a) Intraoral occlusal radiography, (b) Extraoral occlusal
radiography of the chin showing swelling of the area under the chin
without any bone lysis.
Fig. 4: Orthopantomogram showing delayed bone healing at the site of
tooth 33 with a poorly-limited appearance of the bone.
Fig. 5: (a) Axial CT, (b) Orthogonal cross section of CT dentascan
showing a poorly-limited osteolytic lesion affecting the mandibular
crest and the vestibular bone cortex, (c) Axial CT without contrast, (d)
Axial CT with contrast showing infiltration of the left lateral
mandibular chin soft tissues and the oral floor without enhancement of
the lesion.
Fig. 6: (a) H and E Stain (Magnification 40X) showing diffuse
infiltration by lymphoid proliferation, (b) H and E Stain (Magnification
200X) showing infiltration of the underlying striated muscle, (c)
Photomicrograph demonstrating tumor positive Immune-Stain of Anti-CD20
Antibody ( Magnification 100X), (d) Photomicrograph demonstrating tumor
negative Immune-Stain of Anti-CD3 Antibody( Magnification 100X).
Fig. 7: Bone scintigraphy showing left mandibular hyperfixation.
Fig. 8: Extraoral and introral photographs showing complete tumor
remission.
References
[1] Singh R, Shaik S, Negi BS, Rajguru JP, Patil PB, Parihar AS,
Sharma U. Non-Hodgkin’s lymphoma: A review. J Family Med Prim Care. 2020
Apr 30;9(4):1834-1840. doi: 10.4103/jfmpc.jfmpc_1037_19. PMID:
32670927; PMCID: PMC7346945.
[2]. Karin Ekström-Smedby (2006) Epidemiology and etiology of
non-Hodgkin lymphoma – a review, Acta Oncologica, 45:3, 258-271. doi:
10.1080/02841860500531682. PMID: 16644568.
[3]. Buchanan A, Kalathingal S, Capes J, Kurago Z. Unusual
presentation of extranodal diffuse large B-cell lymphoma in the head and
neck: description of a case with emphasis on radiographic features and
review of the literature. Dentomaxillofac Radiol. 2015;44(3):20140288.
doi: 10.1259/dmfr.20140288. Epub 2014 Nov 25. PMID: 25421808; PMCID:
PMC4614159.
[4]. Zou H, Yang H, Zou Y, Lei L, Song L. Primary diffuse large
B-cell lymphoma in the maxilla: A case report. Medicine (Baltimore).
2018 May;97(20):e10707. doi: 10.1097/MD.0000000000010707. PMID:
29768336; PMCID: PMC5976336.
[5]. Pereira DL, Fernandes DT, Santos-Silva AR, Vargas PA, de
Almeida OP, Lopes MA. Intraosseous Non-Hodgkin Lymphoma Mimicking a
Periapical Lesion. J Endod. 2015 Oct;41(10):1738-42. doi:
10.1016/j.joen.2015.06.001. Epub 2015 Jul 31. PMID: 26234541.
[6]. Urquhart A, Berg R. Hodgkin’s and non-Hodgkin’s lymphoma of the
head and neck. Laryngoscope. 2001 Sep;111(9):1565-9.
[7]. Hsi ED. 2016 WHO Classification update-What’s new in lymphoid
neoplasms. Int J Lab Hematol. 2017 May;39 Suppl 1:14-22. doi:
10.1097/00005537-200109000-00013. PMID: 11568605.
[8]. Storck K, Brandstetter M, Keller U, Knopf A. Clinical
presentation and characteristics of lymphoma in the head and neck
region. Head Face Med. 2019 Jan 3;15(1):1. doi:
10.1186/s13005-018-0186-0. PMID: 30606206; PMCID: PMC6317257.
[9]. Siqueira JM, Fernandes PM, de Oliveira ACF, Vassallo J, Alves
FA, Jaguar GC. Primary diffuse large B-cell lymphoma of the mandible.
Autops Case Rep. 2019 Aug 22;9(3):e2019109. doi: 10.4322/acr.2019.109.
PMID: 31528626; PMCID: PMC6709649.
[10]. Bugshan A, Kassolis J, Basile J. Primary Diffuse Large B-Cell
Lymphoma of the Mandible: Case Report and Review of the Literature. Case
Rep Oncol. 2015 Oct 24;8(3):451-5. doi: 10.1159/000441469. PMID:
26600778; PMCID: PMC4649735.
[11]. Van der Waal RI, Huigens PC, Van der VP, Van der Waal I.
Characteristics of 40 primary extranodal non‑Hodgkin’s lymphomas of the
oral cavity in perspective of the new WHO classification and the
International Prognostic Index. Int J Oral Maxillofac Surg
2005;34:391‑5. doi: 10.1016/j.ijom.2004.08.009. PMID: 16053848.
[12]. Kolokotronis A, Konstantinou N, Christakis I, Papadimitriou P,
Matiakis A, Zaraboukas T, Antoniades D. Localized B-cell non-Hodgkin’s
lymphoma of oral cavity and maxillofacial region: a clinical study. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Mar;99(3):303-10. doi:
10.1016/j.tripleo.2004.03.028. PMID: 15716836.
[13]. Bhatt VR, Koirala B, Terjanian T. Extranodal natural killer/T
cell lymphoma, nasal type presenting as a palatal perforation and naso
oral fistula. BMJ Case Rep 2011;2011. doi: 10.1136/bcr.11.2010.3511.
PMID: 22707606; PMCID: PMC3063295.
[14]. Liu Y, Barta SK. Diffuse large B-cell lymphoma: 2019 update on
diagnosis, risk stratification, and treatment. Am J Hematol. 2019
May;94(5):604-616. doi: 10.1002/ajh.25460. PMID: 30859597.
[15]. Pierce JM, Mehta A. Diagnostic, prognostic and therapeutic
role of CD30 in lymphoma. Expert Rev Hematol. 2017 Jan;10(1):29-37. doi:
10.1080/17474086.2017.1270202. Epub 2016 Dec 21. PMID: 27927047.
[16]. Haute autorité de la santé. Guide affection longue
durée-Tumeur maligne, affection maligne du tissu lymphatique ou
hématopoïétique, lymphomes non hodgkiniens de l´adulte. Mars 2012.
[17]. Sirsath NT, Lakshmaiah KC, Das U, Lokanatha D, Chennagiri SP,
Ramarao C. Primary extranodal non-Hodgkin’s lymphoma of oral cavity–a
single centre retrospective study. J Cancer Res Ther. 2014
Oct-Dec;10(4):945-50. doi: 10.4103/0973-1482.136024. PMID: 25579534.
[18]. Elis A, Blickstein D, Klein O, Eliav-Ronen R, Manor Y, Lishner
M. Detection of relapse in non-Hodgkin’s lymphoma: role of routine
follow-up studies. Am J Hematol. 2002 Jan;69(1):41-4. doi:
10.1002/ajh.10017. PMID: 11835330.
[19]. Fuessinger MA, Voss P, Metzger MC, Zegpi C, Semper-Hogg W.
Numb Chin as Signal for Malignancy-Primary Intraosseous Diffuse Large
B-Cell Lymphoma of the Mandible. Ann Maxillofac Surg. 2018
Jan-Jun;8(1):143-146. doi: 10.4103/ams.ams_163_17. PMID: 29963443;
PMCID: PMC6018272.