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

Disclosures

J Med Case Reports. 2020;14(57) 

In This Article

Discussion

This case highlights a notably rare manifestation of metastatic lymphoma presenting with involvement of Meckel's cave, which was initially mischaracterized as biopsy-negative GCA. Awareness of the neurologic features associated with skull base tumors involving Meckel's cave as well as identification of atypical features of elderly-onset headache that should raise suspicion for etiologies other than GCA are needed to educate providers in order to appropriately identify, diagnose, and manage these uncommon presentations that are associated with high morbidity.

Meckel's cave, also known as cavum trigeminale, is a cerebrospinal fluid (CSF)-containing dural pouch in the middle cranial fossa connecting the cavernous sinus to the prepontine cistern of the posterior fossa.[5] This structure contains the Gasserian ganglion of the trigeminal nerve as well as the three postganglionic trigeminal roots: ophthalmic (V1), maxillary (V2), and mandibular (V3).[5] Tumors in Meckel's cave are uncommon but the most frequent neoplasms at this site include trigeminal nerve sheath tumors, schwannomas, meningiomas, neurofibromas, nasopharyngeal carcinoma, and leptomeningeal metastases from solid organ malignancy (renal cell, lung, and breast).[4–7] Metastatic lymphoma involving Meckel's cave is rare with as few as 11 previously reported cases.[8] The most notable features of Meckel's cave involvement include trigeminal neuralgia, facial numbness, and diplopia;[6,9] the latter typically due to sixth nerve palsy resulting from the close proximity of the V1 branch in the cavernous sinus.

MRI is the imaging modality of choice for evaluation of patients with trigeminal neuralgia in which concern of Meckel's cave involvement is suspected and should be performed with T1-weighted and T2-weighted imaging, short-tau inversion recovery, and gadolinium-enhanced T1-images with fat suppression.[5] Radiographic features suggestive of pathology of Meckel's cave include nerve enlargement, enhancement, or trigeminal cistern CSF effacement.[5] Unfortunately if these findings are subtle, particularly if they are symmetrical, they can be overlooked, as occurred initially in the presented case.

Due to its rarity, limited information is present in regards to the best treatment for patients with metastatic lymphoma involving Meckel's cave. Treatment with high-dose methotrexate and whole brain radiation has been used with variable outcomes.[10] Consolidation therapy with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin (vincristine), and prednisone (R-CHOP) has shown benefit in case reports[11] and led to improvement of headache and visual symptoms in our patient when combined with high-dose methotrexate. Relapsing/refractory patients, as observed in our case, may require additional therapies such as single agent ibrutinib, rituximab plus ifosfamide-carboplatin-etoposide (RICE), or chimeric antigen receptor T cell (CAR-T) therapy.[12]

In addition to its rarity, the described case provides a cautionary tale in evaluating patients with headache and inflammatory marker elevation. While classification criteria for GCA include an age at disease onset of ≥ 50 years, new-onset headache, temporal artery abnormality including tenderness to palpation or decreased pulsation, ESR ≥ 50 mm/hour, and an abnormal TAB with characteristic features,[13] the intended use of these criteria is to create homogenous cohorts of patients for research purposes by distinguishing individuals with GCA from other cases with known vasculitis. Currently there are no approved or endorsed diagnostic criteria for GCA. Consequently, classification criteria for GCA are often incorrectly used in routine clinical practice for assistance in diagnosis. Although the described patient met criteria for age, headache, and inflammatory markers, his additional atypical features, including negative temporal artery biopsies, lack of response to high-dose steroids, and presence of trigeminal neuralgia, should raise suspicion for alternative etiologies.

Positive TAB has historically been considered the gold standard for diagnosis of GCA. However, given temporal artery involvement is not uniformly contiguous (that is, skip lesions) it is possible for patients to have classical features of GCA but have a negative biopsy (so-called biopsy-negative GCA). Clinicians should be cautious to exclude other mimicking conditions in this circumstance, particularly if features are atypical. It is noteworthy that among patients with initial suspicion of GCA undergoing TAB, 80% may have an alternative diagnosis.[14] Among a study of 123 patients with a negative TAB who were not diagnosed with GCA, common alternative diagnoses included self-limited disease (23%), isolated polymyalgia rheumatica (18%), stroke or transient ischemic attack (17%), and, less commonly, infection (5%) or malignancy (2%).[14] Furthermore, not all abnormal temporal artery biopsies are due to GCA. In fact, rare but important mimics to consider include perivascular and intravascular lymphoma which may present with vision loss, headache, and increased inflammatory markers; however, pathology shows a strong neoplastic lymphoid infiltrate.[15–18]

Glucocorticoids have been the cornerstone of treatment in patients with GCA. With high-dose glucocorticoids, significant symptomatic improvement can occur within as few as 24–48 hours[19] but may require up to 2 weeks. As such, a presumed diagnosis of GCA should be questioned if a therapeutic trial of high-dose glucocorticoids fails to result in marked clinical improvement in that time frame.[19]

The European League Against Rheumatism (EULAR) recommends early imaging in patients with suspected GCA in capable centers to supplement clinical criteria.[20] For patients with cranial symptoms, evaluation of the temporal arteries by ultrasound or biopsy is prudent, but, if negative, additional imaging should be considered to support a suspected diagnosis of GCA. The use of PET-CT or thoracic magnetic resonance angiography (MRA)/CT angiography (CTA) are particularly helpful to evaluate suspected extracranial large vessel vasculitis but are also useful in identifying potential mimics, as was the circumstance in our case. The authors propose a suggested diagnostic algorithm to assist clinicians in evaluating patients with suspected GCA (Figure 3).

Figure 3.

Algorithm for evaluation of suspected giant cell arteritis based on presentation features. CTA computed tomography angiography, GCA giant cell arteritis, MRA magnetic resonance angiography, MRI magnetic resonance imaging, PET-CT positron emission tomography-computed tomography, TA temporal artery, u/s ultrasound. (Adapted with permission from Koster MJ, Matteson EL, Warrington, KJ. Large-vessel giant cell arteritis: diagnosis, monitoring and management. Rheumatology 2018;57:ii32–ii42)

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