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\begin{document}

\title{Oropharyngeal Burkitt lymphoma masquerading as oropharyngeal carcinoma
in an adult: A diagnostic challenge}



\author[1]{sudeep kc}%
\author[2]{Himani  Poudyal}%
\affil[1]{Patan Academy of Health Sciences}%
\affil[2]{Dhulikhel Hospital}%


\vspace{-1em}



  
  \date{May 16, 2024}


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\textbf{Oropharyngeal Burkitt lymphoma masquerading as oropharyngeal
carcinoma in an adult: A diagnostic challenge}

\textbf{Dr. Sudeep KC\textsuperscript{1} \textbar{}} \textbf{Dr. Himani
Poudyal\textsuperscript{2}}

\textbf{Department of Radiology, Patan Academy of Health Sciences.
Lalitpur, Nepal}

\textbf{Department of Internal Medicine, Dhulikhel Hospital, Nepal}

\textbf{1 \textbar{} INTRODUCTION}

Burkitt lymphoma (BL) is a non-Hodgkin B-cell lymphoma derived from
germinal center lymphoid B cells; named after Dennis Parsons Burkitt, an
Irish surgeon who first described it as sarcoma of jaws in children from
equatorial Africa in 1958.\textsuperscript{1} Burkitt lymphoma accounts
for 1--5\% of all non-Hodgkin lymphoma cases. It is uncommon in adults
and usually involves the gastrointestinal system, central nervous system
or the head-and-neck region. Sporadic Burkitt's lymphoma is relatively
rare in the head and neck region, accounting for about 25\% of all
cases.\textsuperscript{2} Burkitt's lymphoma is the fastest-growing
tumour in humans, with a cell-doubling time of about 24--48
hours.\textsuperscript{3} The etiology of this tumor is debatable, but
strong evidence implicates Epstein-Barr virus in its
development.\textsuperscript{4} Three distinct forms of Burkitt's
lymphoma have been described; each of them having own clinical and
epidemiological features. Multi-agent chemotherapy is the mainstay of
Burkitt's lymphoma treatment.\textsuperscript{5}

This case report presents the diagnostic challenges encountered in
identifying oropharyngeal Burkitt lymphoma (BL) in a 41- year-old male
who initially presented with mass lesion in oropharynx. Owing to rarity
of BL in the oropharynx, this case underscores the importance of
considering rare malignancies in atypical presentations and highlights
the role of comprehensive diagnostic approaches in clinical management.

\textbf{2 \textbar{} CASE PRESENTATION}

41-year, male, smoker 15 pack year, occasional alcohol drinker, with no
prior co-morbidities and notable previous medical history presented to
the Otolaryngology Clinic with complaints of sore throat and something
stuck in right side of throat for 2 months. He had no history of fever,
night sweats, dysphagia, odynophagia and difficulty in breathing. On
examination of the oral cavity, polypoidal pinkish-white colored tissue
mass lesion was seen in right side of the oropharynx. Rest of the
clinical examination were unremarkable.

\textbf{2.1 METHODS}

\textbf{DIFFERENTIAL DIAGNOSIS:}

On the basis of history and clinical examination, following differential
diagnosis were considered.

Oropharyngeal carcinoma

Lymphoma

\textbf{INVESTIGATIONS:}

\textbf{Imaging Findings:}

In suspicion of oro-pharyngeal malignancy, the patient underwent CE MRI
of neck which showed a homogenously enhancing well circumscribed
lobulated T1 hypointensity and T2 hyper intensity lesion measuring 4.0 x
2.8 x 2.0cm involving the right side of the oropharynx and tonsil(Fig
1). The lesion was causing partial effacement of the right side of
vallecula, without midline extension of the lesion noted. No extension
of the lesion beyond the confinement of oropharynx seen. Diffusion
restriction noted with ADC value of 0.4 x
10\^{}\textsuperscript{-3mm2/sec} on b value of 800. Patient was
counselled about the possibility of malignant lesion and was advised for
biopsy to rule out malignancy. Punch biopsy was done and histopathology
followed by immunochemistry and Interphase fluorescence in situ
hybridization (FISH) confirmed it as case of Burkitt Lymphoma.

Microscopic Findings showed multiple fragments of tissue, partially
lined by non-keratinized stratified squamous epithelium. Sub epithelium
showed infiltration by monotonous population of atypical lymphoid cells.
Those atypical lymphoid cells were intermediate to large in size with
round to ovoid with coarse chromatin, irregular nuclear membrane, scant
cytoplasm. Cytoplasm was scant in amount. Immunohistochemistry showed
atypical lymphoid cells which were diffusely positive for CD45, CD20,
PAX-5, CD10, BCL6 (weak), MUM-1, c-MYC (45\%), while they are negative
for CK (AE1/AE3), CD3, BCL2, Cyclin-D1, CD21 and CD34. Ki67
proliferation index is approximately 90\%.

Thoracic abdominal and pelvic CT scans did not show any distant
extension of the disease. Bone marrow aspiration and biopsy showed
normocellular marrow. The complete blood count was unremarkable. Human
immunodeficiency virus (HIV) serology was negative. Serology testing was
positive for anti-Epstein--Barr virus IgG.

\textbf{Treatment, Outcome and Follow up:}

He was stared on R-Da-EPOCH regimen(Rituximab, etoposide phosphate,
prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and
doxorubicin hydrochloride (hydroxydaunorubicin). CT scan following the
6th cycle showed a complete regression of lesion(figure 2)

\textbf{DISCUSSION}

Lymphoid neoplasm encompasses group of white cell neoplasm varying in
clinical presentation and behavior; \emph{Leukemias} arising in bone
marrow and circulating peripheral blood, \emph{lymphomas} appearing as
tumour masses from lymph nodes or other organs and \emph{plasma cell
dyscrasias} composed predominantly of plasma cells. Sometimes,
distinction between these clinical categories of lymphoid neoplasia is
difficult.\textsuperscript{6}

Lymphomas are divided into two major group; Hodgkin and Non-Hodgkin
lymphoma. The non-Hodgkin lymphomas are further sub-divided into B-cell
and T-cell lymphomas. Burkitt's Lymphoma belongs to peripheral B cell
neoplasm.\textsuperscript{7} There are 3 different types of BL: endemic
(African) form, the sporadic (non-African) form and
immunodeficiency-linked variety. The endemic form, which is the most
prevalent worldwide; affects younger children (4 to 7 years) involving
the head and neck (maxilla and mandible involvement in 58\%).
Concomitant (endemic) malaria (or other infections) impairs immune
competence; allowing sustained B cell proliferation commonly seen in
this variant.\textsuperscript{8} Symptoms include cervical
lymphadenopathy, swelling of the jaw or facial mass, proptosis, teeth
mobility, paresthesia, and pain.\textsuperscript{9} Sporadic Burkitt's
lymphoma (usually seen in European populations) shows gastrointestinal
involvement (56\% of the cases) and is found more often in older
children(male\textgreater{} female). Both endemic and Sporadic Burkitt's
lymphoma rarely arises in the lymph nodes. Immunodeficiency associated
Burkitt lymphoma is frequently seen in AIDS patients and patients on
immunosuppressive drugs following organ transplantation and can be found
in extra-nodal sites; abdomen being common site. Abdominal pain,
vomiting, bowel obstruction and gastrointestinal bleeding constitutes
the usual clinical presentation.\textsuperscript{10}

Manifestations of BL are variable depending on the site of involvement
and the extension toward the adjacent structures. Sometimes, systemic
symptoms such as fever, weight loss, and headache might be
seen.\textsuperscript{11} Rapid progression of symptoms can be seen that
can even reach 24 to 48 hours. \textsuperscript{9} Our patient mainly
presented with sore throat and foreign body sensation in the throat that
was attributed to the oropharyngeal extension. In fact, symptoms in
oropharyngeal BL are not specific to this entity and can delay the
diagnosis, since BL mainly manifests with cervical lymphadenopathy.
Physical examination findings can also be misleading as oropharyngeal BL
typically presents as a polypoid mass resembling other tumorous
condition.\textsuperscript{9}

Although the diagnosis of BL is confirmed pathologically, multimodality
imaging approach imaging plays a critical role throughout the clinical
course from diagnosis to follow up imaging.\textsuperscript{12}According
to the National Comprehensive Cancer Network (NCCN) guidelines, initial
staging should be performed with cervical and abdominal ultrasound, CT
of the chest, abdomen, and pelvis. Depending on the clinical
presentation, contrast-enhanced neck and/or brain MRI may also be
done.\textsuperscript{12} CT scan is a crucial to assess tumor
localization, staging of the disease and post-treatment monitoring.
Currently, Gadolinium enhanced MRI is also the best imaging modality for
confirming oropharyngeal location, extension, its relationship to the
adjacent structures, and follow-up of BL. Compared with CT, MR imaging
can demonstrate homogenously enhancing mass with isointense signal on
T1-weighted images and an iso or hyper-intense signal on T2-weighted
images due to the cellularity and tends to infiltrate surrounding
structures without their destruction, especially in sporadic forms. In
contrast, endemic variants are characterized by osteolytic bone lesion
with destruction of maxilla-facial bones with an enlargement and
invasion of the adjacent structures.\textsuperscript{13} Our patient
also presented as an infiltrating homogenous mass with a hypo-intense
signal on T2-weighted images. However, CT and MRI findings are not
specific to this entity, and their findings can mimic other aggressive
diseases of the oropharynx.

Role of diffusion weighted imaging (DWI) and ADC value in BL is still
under study. Positron emission tomography (PET), when combined with CT,
offers the advantage of combining functional information with anatomic
imaging.\textsuperscript{14}An increasing amount of research is being
done to assess the value of PET/CT in patients with BL and should be
performed if possible, provided it will not delay
treatment.\textsuperscript{12}

Biopsy, immunohistochemistry and genetic analysis are other tests
helpful to get correct diagnosis. All variants of Burkitt lymphoma share
the same morphology and it is almost impossible to differentiate these
three variants on microscopic features alone. They are strongly
associated with translocations involving the \emph{MYC} oncogene on
chromosome 8. Histopathology, BL typically has characteristic starry-sky
pattern. However, immunohistochemistry is a useful method for
identifying particular tumor cells that includes expression of CD20,
CD10, and bcl-6, Ki-67 proliferation rate.\textsuperscript{15}

Bone marrow, Cerebrospinal fluid, Lactate Dehydrogenase Level, HIV and
Epstein-Barr Virus serology may also be required.\textsuperscript{16}EBV
exhibits strong tropism for B cells and infects them, causing them to
proliferate. In our case, the patient had positive antibodies for
Epstein--Barr virus. Virtually all cases of endemic BL carry EBV genome
whereas \textless{} 30\% of sporadic and immunosuppression-associated
variant are associated with this EBV virus. \textsuperscript{17}

The definitive treatment of BL is often based on the patient's age and
the location of tumor. Different modalities such as surgery,
radiotherapy, chemotherapy, and radioimmunotherapy have been used to
treat Burkitt's lymphoma, but systemic chemotherapy is mainstay of
treatment. BL dramatically responds to chemotherapies that includes
cyclophosphamide, vincristine, methotrexate, and prednisone causing
regressions of tumor and often lead to long-term
remission.\textsuperscript{18} Our patient was also placed under complex
chemotherapy resulting in the regression of the mass confirmed on
post-therapeutic imaging.

The role of surgery in BL is still controversial. Surgical treatment is
generally not required unless disease complications require prompt
surgical intervention such as in cases of bowel obstruction, optic nerve
decompression and airway obstruction.\textsuperscript{19}

Prognosis depends on the stage of the disease at presentation, age of
patient, chemotherapy, lactate dehydrogenase levels and the association
with HIV.~Patients who receive an early treatment are associated with
better outcomes in comparison to the delayed treatment which can cause
BL to reach other distant organs.\textsuperscript{20} Patients with
relapsed disease usually present symptomatically and within the first
year after the completion of treatment. Relapsed disease may occur at
the sites of original presentation or remotely. \textsuperscript{12}

\textbf{CONCLUSION}

BL has a very heterogeneous pattern of presentation and clinical course.
The diagnosis can be suspected on CT and MRI, but the confirmation
requires histopathology and immunohistochemistry. Burkitt lymphoma is
high grade tumour however, with aggressive chemotherapy regimens,
majority of the patient can be cured. Delays in diagnosis and treatment
have a significant impact on prognosis. In addition, radiologists need
to identify typical and uncommon sites and presentations in order to
properly guide clinicians considering the urgency of possible therapy.

\textbf{AUTHOR CONTRIBUTIONS}

\textbf{Sudeep KC} :~Conceptualization; Writing -- original draft;
writing -- review and editing.

\textbf{Himani Poudyal} :~Writing -- original draft; writing -- review
and editing.

orcid ID: Sudeep KC \textbf{0000-0002-2826-4855}

\textbf{ACKNOWLEDGEMENTS}

Author would like to thanks to patient who participated in this case
report and collaborative efforts of ENT and hemato-oncology teams.

\textbf{FUNDING} : No funding sources.

\textbf{DATA AVAILABILITY STATEMENT:} The data that support the findings
of this study are available on request from the corresponding author

\textbf{CONFLICT OF INTEREST:} The authors declare that there is no
conflict-of-interest regarding the publication of this paper.

\textbf{ETHICS STATEMENT:} Need for ethics approval waived. Consent from
the patient deemed to be enough.

\textbf{CONSENT:} Written informed consent was obtained from the patient
for publication of this case report and any accompanying images. A copy
of the written consent will be available for review by the editor- in-
chief of this journal if requested

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