Nasopharyngeal diffuse large b-cell lymphoma in a teenage presenting with cavernous sinus syndrome: A case report

Abstract

Primary lymphoma of the nasopharynx is uncommon and is more commonly seen as an association with other primary pathologies. Nasopharyngeal lymphoma is an aggressive tumor and can affect all age groups but is more commonly seen in middle-aged and older individuals. Majority of these tumors belong to the non-Hodgkin’s group. Cavernous sinus syndrome (CSS) is a rare but severe complication indicating advanced aggressive stage of disease with direct extension of tumor into the cavernous sinus. Our patient is a young teenage 18-years old presented to emergency department with the symptoms of left jaw pain (4 months), facial swelling (1 month), bilateral nasal obstruction, dysphagia (1 month), visual loss in left eye and proptosis (1 week) along with weight loss. Magnetic resonance imaging (MRI) face and neck with contrast performed immediately revealed a nasopharyngeal mass with extension of disease into the left cavernous sinus encasing cavernous part of the left internal carotid artery (ICA), involvement of the left orbital apex, optic chiasm and pituitary gland. Histopathology later confirmed diffuse large B cell lymphoma (DLBCL). Laboratory investigations were unremarkable except for an elevated ESR. The patient underwent multidisciplinary management with combined chemotherapy and radiotherapy, demonstrating an excellent response on follow-up MRI and PET-CT, and was discharged with appropriate follow-up instructions. This case highlights early recognition with MRI and histopathological confirmation enables timely chemotherapy, improving outcomes and reducing the risk of permanent neurological sequelae.

Introduction

Head and neck lymphomas are most commonly non-Hodgkin lymphomas; predominantly these are B-cell lymphomas. Diffuse large B cell lymphoma (DLBCL) is a highly aggressive B-cell NHL. Primary nasopharyngeal lymphoma (NPL) is still a very rare entity [1] and accounts for 1% of head and neck cancers; only few cases on involvement of the sinonasal tract have been reported [2,3]. Peak age incidence is also an important factor and usually tends to be around fifty to sixty years of age [4], making this case interesting in this aspect as well. Primary nasopharyngeal DLBCL in teenagers is however uncommon presenting with non-specific symptoms such as nasal obstruction, mouth breathing or facial swelling [2]. Cavernous sinus syndrome (CSS) is a rare and aggressive initial presentation for lymphoma, typically characterized by compression of the cavernous sinus along with involvement of its nerves and encasement of internal carotid artery (ICA), leading to ophthalmoplegia, ptosis, proptosis and even visual loss [5,6]. Timely recognition is very vital as these aggressive tumors often respond well to prompt chemotherapy [7,8].

Case presentation

Our case is an 18 year-old teenager presented to emergency department with complains of left jaw pain (4 months), facial swelling (1 month), bilateral nasal obstruction, dysphagia (1 month), visual loss in left eye and proptosis (1 week) along with weight loss. On clinical examination, patient looked malnourished tolerating liquids only with left eye ptosis, ipsilateral palate mass, left parotid area swelling and left cervical lymphadenopathy. Computed tomography paranasal sinuses (CT PNS) performed elsewhere revealed a large left nasopharyngeal mass extending into the left middle cranial fossa with left cavernous sinus compression and further left nasal obstruction. Biopsy of the mass confirmed the diagnosis DLBCL (Fig. 1). Urgently patient was admitted and initial workup done including baseline laboratory investigations and virology were within normal limits. Patient was immediately started on steroids, proton pump inhibitors and xanthine oxidase inhibitors (allopurinol).

Fig. 1.

(A) Lymphoid neoplasm composed of large tumor cells arranged in sheets in a discohesive fashion with scattered lymphocytes in the background. Tumor cells have rounded vesicular nuclei, conspicuous nucleoli, and an appreciable amount of cytoplasm. Numerous mitoses are seen (40x). (B) CD20 Positive (10x). (C) BCL2 Positive (10x). (D) Ki 67 80 Percent proliferation index (10x).

Urgent MRI brain, face and neck along with CECT chest abdomen pelvis (pre chemo) was performed. MRI face and neck and paranasal sinuses (Figs. 2 & 3) revealed a large ill-defined mass showing T1 low and T2/FLAIR heterogenous signals with heterogenous post contrast enhancement, involving nasopharynx, oropharynx and deep neck spaces on the left side, extending caudally into the ipsilateral para-pharyngeal, infratemporal fossa, masticator space and carotid space. Superior extension to bilateral cavernous sinus with involvement of clivus, sella and medial wall of left orbit, further extending to left orbital apex and optic chiasma level. Baseline CECT CAP showed an ill-defined hypodense splenic mass abutting pancreatic tail (Fig. 4A) along with nodal disease above and below diaphragm.

Fig. 2.

MRI face and neck; axial sections (A) T2WI heterogeneously hyperintense mass involving left para pharyngeal, masticator and carotid space with mass effect and contralateral shift of oropharynx. (B) Coronal section; post contrast heterogeneous enhancement is seen. Superiorly the mass extends into the left cavernous sinus with encasement of cavernous part of internal carotid artery (red arrow). Enlarged ipsilateral cervical necrotic level II lymph node (orange arrow). Axial sections showing diffusion restriction in terms of high DWI (C) signals with corresponding low ADC (D) signals, hypointense on T1WI (E) showing heterogenous post contrast enhancement (F).

Fig. 3.

(A & B) Post contrast MRI brain axial sections showing involvement of bilateral cavernous sinus by the mass (yellow arrow left cavernous sinus; orange arrow right cavernous sinus). (C) Post contrast MRI brain axial section shows post contrast enhancement along left orbital apex (blue arrow) suggesting its involvement. (D) MRI face and neck coronal section demonstrates the heterogeneous post contrast enhancement involving left parapharyngeal, infratemporal fossa, masticator space and carotid space with mass effect, further there is encasement of left hemi-mandible ramus (green arrow) which is involved by the mass.

Fig. 4.

(A) Baseline CECT scan abdomen; axial section shows large ill-defined splenic hypodensity suggestive of disease involvement. (B & C) Post chemo PET CT scan shows complete metabolic response of splenic lesion with residual non avid hypodensity.

Patient was discussed in multidisciplinary meeting and clinically staged as 4BX. Further management was planned as follows: intrathecal RCHOP (Rituximab, Cyclophosphamide, Doxorubicin [hydroxydaunorubicin], Vincristine [Oncovin], and Prednisone), then MATRIX (Methotrexate [high-dose], Ara-C [cytarabine], Thiotepa and Rituximab [a targeted monoclonal antibody]); alternate with R-ICE (Rituximab, Ifosfamide, Carboplatin and Etoposide); radiotherapy (XRT) to nasopharyngeal mass + whole brain XRT. Patient was kept on Surveillance and follow up MRI brain, face and neck (Fig. 5) showed excellent treatment response with complete resolution. Post treatment PET CT scan (Figs. 4B & C) revealed complete metabolic resolution of splenic lesion with residual non avid hypodensity.

Fig. 5.

Post chemo MRI brain axial sections FLAIR (A), T2WI (B), post contrast axial (C) and Coronal (D) sections showing good treatment response with near complete resolution of disease process.

Discussion

Non-Hodgkin lymphoma is the most common type found in the head and neck; predominantly these are B-cell lymphomas. DLBCL is a highly aggressive B-cell NHL. Primary nasopharyngeal lymphoma (NPL) is still a very rare entity and few cases on involvement of the sinonasal tract have been reported [2,3]. Literature shows the peak age incidence to be around fifth to sixth decade of life [4], however our case presents an interesting scenario of teenage patient. Nasopharyngeal masses are often misdiagnosed in teenagers initially as infectious mononucleosis or benign adenoid hypertrophy leading to delayed treatment [7].

Further, adding to the rarity of this case is the presentation with cavernous sinus syndrome as a primary manifestation of lymphoma [5]. Cavernous sinus syndrome is a constellation of symptoms and signs resulting as a complication to involvement of cavernous sinus. It suggests advanced aggressive disease involving multiple cranial nerves leading to neuropathies, and in some cases additional vascular features may be seen. The most common presentation would be Ophthalmoplegia (involvement of III/IV/VI cranial nerves), facial loss of sensations (trigeminal nerve involved) or Horner's syndrome due to involvement of Oculosympathetic fibers. In young age group, some cases have been reported where orbital symptoms like unilateral ophthalmoplegia have preceded systemic symptoms [6]. Other aggressive lymphomas like Burkitt lymphoma, can also present with involvement of cavernous sinus [9]. Presenting cavernous sinus syndrome signifies advanced stage of disease and requires urgent intervention [10].

Nasopharyngeal masses tend to involve cavernous sinus due to its anatomical location and close proximity to skull base, affecting the traversing cranial nerves [10] and cavernous part of internal carotid artery [3]. In teenagers, chronic headaches, visual problems, nasal blockade or new-onset neurological deficits should prompt urgent imaging [7]. MRI is the modality of choice for evaluating the extent of cavernous sinus involvement and disease status [11]. On MRI, cavernous sinus lymphoma typically demonstrates iso- to hypointense T2 signal, diffusion restriction due to high cellularity, and intense post-contrast enhancement [12]. Computed Tomography Angiography/Computed Tomography Venography (CTA/CTV) and Magnetic Resonance Angiography/Magnetic Resonance Venography (MRA/MRV) may provide complementary assessment of the cavernous internal carotid artery and cavernous venous structures, particularly when vascular involvement, thrombosis, aneurysm, or carotid-cavernous fistula is suspected [12,13].

Diagnosis relies on histopathology showing dense infiltration of atypical large tumor cells resembling centroblasts [14] and Immunohistochemistry, where markers such as CD20, BCL2 and BCL6 are crucial for identifying B-cell lineage [2,14]. DLBCL and Burkitt-like lymphomas have some similar clinical features, however, DLBCL is less likely to involve the bone marrow at presentation [8]. Management includes planning an intensive multidrug chemotherapy regimen such as R-CHOP: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [2] after a multidisciplinary approach. Multidrug chemotherapy regimen seems to have improved survival rates and prognosis if administered promptly [2,7]. Multidrug chemotherapy can be administered Intravenously or in some cases Intrathecal route is preferred, depending upon the recommended MDT management plan. Radiotherapy is also given in some cases; again, the decision must be made based on variable factors including imaging, disease burden, and treatment response via a multidisciplinary approach.

Conclusion

Nasopharyngeal DLBCL presenting with cavernous sinus syndrome in a teenager is indeed a rare but critical clinical entity. Clinicians must be vigilant in showing a high index of suspicion when a young patient presents with sinonasal symptoms along with cranial nerve palsies. Immediate cross-sectional imaging, MRI being superior in such cases, along with histopathology is certainly beneficial for early diagnosis and a crucial step to start life-saving chemotherapy, hence preventing permanent neurological sequelae.

Author contributions

FA, KS, and AU conceived and designed the case report. MJT and FA were responsible for data collection and acquisition of data. FA, MJT, NN and AU performed the literature review and wrote the manuscript. SA, AU, and KS reviewed and critically revised the manuscript. All authors have approved the final manuscript.

Patient consent

Written informed consent was obtained from the patient.