Diffuse Large B Cell Lymphoma Involving Meckel's Cave Masquerading as Biopsynegative Giant Cell Arteritis

A Case Report

Matthew J. Samec; Andres G. Madrigal; Charlotte H. Rydberg; Matthew J. Koster


J Med Case Reports. 2020;14(57) 

In This Article

Case Description

A 57-year-old white man presented with a 3-month history of new-onset, severe, bi-frontal headaches and a 13.6 kg (30-lb) weight loss. Local emergency room evaluation revealed a negative computed tomography (CT) scan of his head. Laboratory findings included an elevated erythrocyte sedimentation rate (ESR) of 80 mm/hour and C-reactive protein (CRP) of 55.3 mg/L. He was discharged with pain control.

During follow-up with his local primary provider, his headache persisted and bilateral jaw pain and left facial numbness had developed. He was started on prednisone 60 mg/day for presumed GCA with partial improvement in his headache. Bilateral temporal artery biopsies were performed 3 days later and were negative. Prednisone was subsequently discontinued. Two weeks later his headache progressed and right eye horizontal diplopia and perioral numbness developed. Magnetic resonance imaging (MRI) of his brain was performed and interpreted as normal. He was admitted for pulse-dose steroids (1000 mg daily for 3 days) which led to resolution of visual symptoms and was discharged on prednisone 60 mg/day. Tapering below 50 mg/day was unsuccessful due to rising inflammatory markers, symptom progression, and return of diplopia. Severe left hip pain developed for which plain radiographs were obtained but negative for fracture or avascular necrosis.

On referral to our institution he continued to have ongoing headache and left jaw numbness despite 6 weeks of high-dose glucocorticoids (80 mg/day). Left hip pain had worsened to the point of wheelchair dependency. His past medical history was remarkable for atrial fibrillation for which he was receiving warfarin 2 mg/day and diltiazem 240 mg/day. Social history was notable for lack of tobacco or alcohol use and absence of known environmental exposures during his employment as an office manager. Aside from prostate cancer in his father, our patient's family history was negative for other pertinent diagnoses of additional malignancies or autoimmune conditions. Laboratory evaluation noted an ESR 72 mm/hour, CRP 53 mg/L, hemoglobin 11.1 g/dL, leukocytes 5.2 × 109/L and platelets 110 × 109/L, international normalized ratio (INR) 2.3, creatinine 1.04 mg/dL, calcium 11.6 mg/dL, alanine aminotransferase 106 U/L, aspartate aminotransferase 64 U/L, alkaline phosphatase 360 U/L, total bilirubin 1.2 mg/dL, total protein 5.1 g/dL, and albumin 3.4 g/dL. Previously obtained autoimmune serologies were negative for antinuclear and extractable nuclear antigens as well as rheumatoid factor, anti-cyclic citrullinated peptide, myeloperoxidase, and proteinase-3 antibodies.

His vital signs demonstrated a heart rate of 95 beats per minute, blood pressure of 94/44 mm Hg, respiratory rate of 12 per minute, oxygenation saturation of 96%, and weight of 144 kg with body mass index (BMI) of 48.6 kg/m2. An examination was notable for a Cushingoid appearance and morbid obesity. Evaluation of adenopathy and splenomegaly was limited due to body habitus. Pertinent cardiovascular findings included irregularly irregular pulse without murmurs. Upper and lower arterial pulses were normal and symmetric. Common superficial temporal artery palpation was without tenderness or nodularity. Trace pitting edema was noted to the ankle bilaterally. Breath sounds were equal and symmetric without wheezing or rhonchi. Aside from scattered bruising at site of venipuncture, no cutaneous abnormalities were noted. A neurologic examination showed normal speech without language deficits. Visual acuity was 20/20 bilaterally. Cranial nerves 2–12 were assessed and normal except for mild esotropia of his right eye and hypoesthesia to light touch and pinprick over the left mandibular region of the left trigeminal nerve. The remaining dermatomes evaluated showed normal sensation. Reflexes were normal and symmetric throughout and toes were down-going bilaterally. No ataxia was observed. A musculoskeletal examination demonstrated normal range of motion of upper extremities without deficit. Marked pain was noted on passive and active range of motion of his left hip.

Given the persistent headache despite high-dose glucocorticoids and atypical features, alternative etiologies were suspected. The local MRI of his brain was reviewed and evidence of abnormal enhancing soft tissue involving Meckel's cave bilaterally with extension through the foramen ovale was noted (Figure 1a). The differential diagnosis for infiltrative process in Meckel's cave included sarcoidosis as well as primary or secondary neoplastic lesions such as meningioma, nasopharyngeal carcinoma, schwannoma, neurofibroma, and lymphoma.[4,5] The presence of constitutional symptoms and elevated inflammatory markers suggested a secondary process with associated intracranial involvement. As such, positron emission tomography (PET)-CT was obtained. This demonstrated extensive hypermetabolic lesions throughout the axial and appendicular skeleton, including the skull base, as well as fluorodeoxyglucose (FDG)-avid lymph nodes above and below the diaphragm (Figure 1c). MRI of his left hip revealed diffusely abnormal marrow signal suggestive of infiltrative disease. A cervical lymph node biopsy demonstrated evidence of diffuse large B cell lymphoma and staging bone marrow biopsy revealed a hypercellular marrow (90%) with diffuse large B cell lymphoma involving 70% of the total cellularity (Figure 2). Initiation of high-dose methotrexate (3.5 g/m2), rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), hydroxydaunorubicin (50 mg/m2), Oncovin (vincristine; 2 mg), and prednisone (255 mg) (MR-CHOP; 21-day cycle) resulted in interval improvement in his headache and visual symptoms (Figure 1b, d).

Figure 1.

Diffuse large B cell lymphoma involvement on magnetic resonance imaging and positron emission tomography-computed tomography. Magnetic resonance images of brain show: a abnormal enhancement of Meckel's cave bilaterally with extension through the foramen ovale (arrows) before chemotherapy and b decreased soft tissue in Meckel's cave bilaterally (arrows) after chemotherapy. Positron emission tomography-computed tomography scans show: c extensive hypermetabolic lesions throughout the axial and appendicular skeleton, including the skull base, as well as fluorodeoxyglucose-avid lymph nodes above and below the diaphragm before chemotherapy and d marked response of all hypermetabolic lesions after chemotherapy

Figure 2.

Bone marrow involvement by diffuse large B cell lymphoma. Photomicrographs of bone marrow trephine biopsy show: a medium to large neoplastic lymphocytes with nuclear irregularity, dispersed chromatin and variably sized nucleoli and background hematopoietic precursors on hematoxylin and eosin stain, b rare scattered T cells highlighted by CD3 immunohistochemistry, c membranous staining of neoplastic B cells by CD20 immunohistochemistry, and d nuclear staining of neoplastic B cells by PAX5 immunohistochemistry. a–d; × 1000

Ten months after initial diagnosis and 4 months after completion of his sixth cycle of MR-CHOP, our patient re-presented with bilateral lower extremity weakness and PET-CT showed recurrence of disease with evidence of neurolymphomatosis of multiple cervical, thoracic, and sacral nerve roots. Intrathecal cytarabine (50 mg) was given and ibrutinib (140 mg/day) was initiated, resulting in initial findings of improved strength and subsequent decreased nerve root FDG-avidity.