Recurrent Syncope as a Rare Initial Manifestation of Diffuse Large B-Cell Lymphoma in the Cervical Region

Introduction

The incidence of non-Hodgkin lymphoma (NHL) in the United States is approximately 7 cases per 100 000 per year [1]. Diffuse large B-cell lymphoma (DLBCL) accounts for about 25% of all NHL cases worldwide. DLBCL is the most common NHL, followed by follicular lymphoma [2]. Every year, DLBCL is diagnosed in more than 18 000 individuals. DLBCL can be diagnosed at any age, even though it is thought to be a disease mostly affecting older persons, with a median presentation in the 7th decade of life. Individuals suffering from DLBCL may exhibit a wide range of symptoms, ranging from constitutional symptoms like B symptoms (inflammatory effects) to localized effects caused by a rapidly expanding mass. Although it is uncommon, a small number of instances of neck tumors have been documented in which malignancy manifests as syncope. Most of these cases that have been documented thus far were individuals who had recurrent head and neck cancer. Although DLBCL frequently involves the cervical region, syncope from the condition without cardiac involvement has only been documented in a few cases to date [3,4]. In the present case report, we introduce a case of diffuse large B-cell lymphoma, in which the patient presented with frequent positional syncopal events and responded well to treatment with a chemotherapy regimen of rituximab, etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin) (R-EPOCH).

Case Report

A 66-year-old man with a past medical history of hypertension presented to the emergency department (ED) for recurrent syncopal events. The events were reproducible with head lateral flexion. These symptoms did not occur upon position changing or other triggers of syncope such as exercise, deep inspirations, or simply being at rest. Of note, the patient reported the presence of a small mass on the left side of his neck starting 6 weeks before his presentation to the ED, and the patient denied any other symptoms or previous episodes. At the initial presentation, 6 weeks prior, he was treated with antibiotics for presumed cervical lymphadenitis. He did not improve, and the mass rapidly enlarged to reach its current size and started causing syncopal events for 2 weeks prior to being seen by us. In the ED, the patient’s vital signs were stable and unremarkable. A large, firm, left-sided cervical mass was noted on physical examination along with mild tracheal deviation to the right and mild left-sided ptosis. The electrocardiogram (EKG) was unremarkable. A transthoracic echocardiogram (TTE) revealed a normal ejection fraction without valvular abnormalities. During the hospital course the patient’s vital signs were reportedly normal with no evidence of orthostatic changes. Normal telemetry monitoring and echocardiogram ruled out a cardiac etiology for syncope. Neck magnetic resonance imaging (MRI) was attempted but could not be completed due to recurrent positional syncope when the patient attempted a supine position. Computed tomography (CT) of the head without contrast and CT angiogram ruled out any acute intracranial process or large vessel occlusion. However, the CT of the neck, with contrast, showed a 7.5×5.0 cm bulky non-enhanced soft tissue mass involving the left masseter muscle and left retropharyngeal space, encasing the left common carotid artery (Figures 1, 2), and carotid bifurcation leading to proximal left internal carotid artery stenosis, and causing airway displacement to the right. Laboratory evaluation was significant for elevated lactic dehydrogenase (LDH) of 272 U/L (125–220), uric acid of 7.5 mg/dL (3.5–7.2), and phosphate of 4.8 mg/dL (2.3–4.7). His serum calcium was 9 mg/dL, serum magnesium 2.3 mg/dL, blood urea nitrogen 16 mg/dL, creatinine 1 mg/dL, alanine aminotransferase (ALT) 46 U/L, aspartate transaminase (AST) 41 U/L, alkaline phosphatase (ALP) 129 U/L, and total bilirubin 0.6 mg/dL. His international normalized ratio (INR) blood test was 1, and serum glucose was 108 mg/dL, with no other cell count abnormalities. The patient was admitted, the medical oncology department was consulted, and treatment of suspected tumor lysis syndrome was initiated with allopurinol and maintenance intravenous fluid resulting in marked improvement in the uric acid and phosphate levels. The head and neck surgery department was consulted, and a bedside flexible laryngoscope was employed revealing left vocal cord paralysis along with right displacement of the larynx without airway obstruction. Ultrasound-guided biopsy of the neck mass was performed and revealed a large B cell lymphoma, germinal center type, Ki67 90%. Fluorescent-in situ hybridization (FISH) test was negative for double hit/triple hit lymphoma. Positron emission tomography-CT (PET/CT) showed bilateral cervical lymphadenopathy, hepatic involvement (Figure 3), and diffuse abdominal lymph node involvement. Based on the findings above, a diagnosis of stage IV diffuse large B-cell lymphoma was made. Chemotherapy treatment with R-EPOCH for 6 cycles was started in the inpatient setting. After completing his first cycle of R-EPOCH, a repeated CT angiogram of the head and neck at 4 weeks showed marked improvement in the mass’s appearance, with decreased left common carotid narrowing (Figures 4, 5).

Discussion

Depending on the exact cause of the episode, syncope can be categorized as neurologically mediated (reflex), cardiovascular, orthostatic, psychogenic, or idiopathic. Sometimes, it is possible to differentiate between types of syncope based on history and physical examination. Usually, the neurologically mediated reflex is preceded by symptoms of sweating and pallor, following prolonged standing or during emotional and/or physical stress. For syncope secondary to underlying cardiovascular disease, the patient usually has symptoms of exertional shortness of breath or chest pain, or there might be a significant cardiovascular family history including sudden cardiac death. Cardiovascular disease-related syncope needs electrophysiologic workup, including cardiac rhythm monitoring, and might need workup for ischemia. Comparing the blood pressure values in sitting and standing positions could help distinguish orthostatic syncope from other types of syncope, if there is a decrease in systolic blood pressure of more than 20 mm Hg or a decrease in diastolic blood pressure of more than 10 mm Hg within 3 minutes of standing when compared with blood pressure values from the sitting or supine position. Further categorization of each etiology depends on the associated symptoms. Roughly 40% of syncopal episodes have no known cause and are classified as idiopathic. Recurrent syncope is an unusual manifestation of DLBCL, as demonstrated by our case. The patient had syncope episodes that were followed by rapid recoveries with a lack of symptoms in between. A notable element of his clinical presentation was the speed of onset of symptoms. He had an expanding, palpable neck mass 4 weeks before syncope.

Three examples of DLBCL [3,4], 2 cases of primary mediastinal lymphoma [5,6], and 2 cases of Hodgkin’s lymphoma [7,8] presenting as syncope without direct cardiac involvement have been published. The syncope could be attributed to carotid hypersensitivity or carotid sinus syndrome. The incidence of carotid sinus syndrome is 8.8% in patients aged 40 years and older who present with unexplained syncope after initial evaluation [9,10]. Head and neck malignancy has been reported to be the most common malignancy associated with syncope. All previously reported cases had carotid sinus compression or infiltration. In our patient, whose left carotid cavity was surrounded by neck lymphoma, the first symptom was frequent episodes of syncope [10]. The pathophysiology of syncope-related carotid sinus syndrome is multifaceted [11,12]. Carotid baroreceptors are sensitive to mechanical pressure in the bifurcated carotid artery. When a tumor stretches the arterial wall, information is sent via the carotid sinus nerve to the brain stem centers in the caudal nucleus of the solitary tract, where interneurons trigger the efferent pathways to stimulate the parasympathetic system and inhibit the sympathetic system, resulting in a reduction in blood pressure and a decrease in heart rate. Another possible explanation for the origin of our case is syncope as an atypical, paraneoplastic, systemic symptom, as it is known to be a symptom of diffuse large B-cell lymphoma [13]. Syncope has previously been documented as a paraneoplastic neurologic condition in lymphomas, resulting in autonomic failure symptoms [14,15]. Given the size of the mass and the proximity to the carotid arteries, we leaned toward the pressure effect and/or carotid hypersensitivity as the reason for the syncope, feeling that this was a more likely explanation than paraneoplastic syndrome. Therefore, no specific workup regarding the paraneoplastic manifestation was performed. In our case, no syncopal events were reported after starting R-EPOCH. A case report reviewing carotid sinus hypersensitivity of head and neck cancer patients with syncope found that treatment of the cancer improved syncopal symptoms in 13 of 17 patients. In the majority of reported lymphoma cases, the syncope was successfully resolved following therapy for cancer [13]. Syncope may be the first or only symptom of a neck or head malignancy [16].

Conclusions

In conclusion, we provide a case of neck lymphoma with recurrent syncope as the primary symptom, which was effectively treated with immunochemotherapy. As a result, we should be aware of the possibility of an underlying malignancy in individuals with unexplained syncope following an initial assessment. A full medical history, particularly for tumors, as well as a thorough physical examination of the head and neck, should be performed when evaluating a patient with syncope. Treatment of the lymphoma with a specific chemotherapy regimen resulted in the resolution of syncopal events. This supports the close relationship between head and neck lymphoma and syncope.