Primary central nervous system lymphoma MRI

Primary central nervous system lymphoma MRI

Reported signal characteristics include:

T1

Typically hypointense to grey matter

T1 C+ (Gd)

typical high-grade tumours show intense homogeneous enhancement while low-grade tumours have absent to moderate enhancement

Peripheral ring enhancement may be seen in immunocompromised patients (HIV/AIDS)

T2

Variable

Majority are iso to hypointense to grey matter

Isointense: 33%

Hypointense: 20% 9 – when present this is a helpful distinguishing feature

Hyperintense: 15-47%, more common in tumours with necrosis

DWI/ADC

Restricted diffusion with ADC values lower than normal brain, typically between 400 and 600 x 10-6 mm2/s (lower than high-grade gliomas and metastases)

A number of studies have suggested that the lower the ADC values of the tumour the poorer the response to tumour and higher likelihood of recurrence

AADC is particularly useful in assessing response to chemotherapy, with increases in ADC values to above those of normal brain predictive of complete response

MR spectroscopy

Large choline peak

Reversed choline/creatinine ratio

Markedly decreased NAA

Lactate peak may also be seen

MR perfusion

Only modest if any increase in rCBV (much less marked than in high-grade gliomas, where angiogenesis is a prominent feature).

Volume

Precise volumetric assessment of brain tumors is relevant for treatment planning and monitoring. However, manual segmentations are time-consuming and impeded by intra- and inter rater variabilities.

To investigate the performance of a deep learning model (DLM) to automatically detect and segment primary central nervous system lymphoma (PCNSL) on clinical MRI.

Study type: Retrospective.

Population: Sixty-nine scans (at initial and/or follow-up imaging) from 43 patients with PCNSL referred for clinical MRI tumor assessment.

Field strength/sequence: T1 weighted image -/T2 weighted image, T1 -weighted contrast-enhanced (T1 CE), and FLAIR at 1.0, 1.5, and 3.0T from different vendors and study centers.

Fully automated voxelwise segmentation of tumor components was performed using a 3D convolutional neural network (DeepMedic) trained on gliomas (n = 220). DLM segmentations were compared to manual segmentations performed in a 3D voxelwise manner by two readers (radiologist and neurosurgeon; consensus reading) from T1 CE and FLAIR, which served as the reference standard.

Statistical tests: Dice similarity coefficient (DSC) for comparison of spatial overlap with the reference standard, Pearson’s correlation coefficient ® to assess the relationship between volumetric measurements of segmentations, and Wilcoxon rank-sum test for comparison of DSCs obtained in initial and follow-up imaging.

The DLM detected 66 of 69 PCNSL, representing a sensitivity of 95.7%. Compared to the reference standard, DLM achieved good spatial overlap for total tumor volume (TTV, union of tumor volume in T1 CE and FLAIR; average size 77.16 ± 62.4 cm3 , median DSC: 0.76) and tumor core (contrast enhancing tumor in T1 CE; average size: 11.67 ± 13.88 cm3 , median DSC: 0.73). High volumetric correlation between automated and manual segmentations was observed (TTV: r = 0.88, P < 0.0001; core: r = 0.86, P < 0.0001). Performance of automated segmentations was comparable between pretreatment and follow-up scans without significant differences (TTV: P = 0.242, core: P = 0.177).

Data conclusion: In clinical MRI scans, a DLM initially trained on gliomas provides segmentation of PCNSL comparable to manual segmentation, despite its complex and multifaceted appearance. Segmentation performance was high in both initial and follow-up scans, suggesting its potential for application in longitudinal tumor imaging.

Level of evidence: 3 TECHNICAL EFFICACY STAGE: 2 1).

1)

Pennig L, Hoyer UCI, Goertz L, et al. Primary Central Nervous System Lymphoma: Clinical Evaluation of Automated Segmentation on Multiparametric MRI Using Deep Learning [published online ahead of print, 2020 Jul 13]. J Magn Reson Imaging. 2020;e27288. doi:10.1002/jmri.27288

Meckel’s cave primary lymphoma

Meckel’s cave primary lymphoma

Diagnosis

The diagnosis of lymphoma should be considered for lesions affecting Meckel’s cave in high-risk immunocompromised patients. The presence of an apparent dural tail in an otherwise typical schwannoma is the distinguishing characteristic of a lymphoma. The absence of hyperostosis helps differentiate it from a meningioma 1).

Treatment

The preferred surgical strategy is biopsy for diagnosis and then radiotherapy and chemotherapy rather than major cranial base surgery for total resection. 2).

Management of lesions involving Meckel’s cave can represent a challenge for neurosurgeons, because of the deep-seated location and the surrounding complex neurovascular structures. Very small lesions arising from MC are generally asymptomatic and radiological follow-up with head MRI and PET-CT is sufficient to control these lesions. In rare cases, the rapid increase in the size of lesions and the alteration of the neurologic status make early histological characterization mandatory in the plethora of lesions arising from Meckel’s cave; a very small percentage is represented by central nervous system lymphomas. Primary diffuse large B cell lymphoma is the most commonly found. Aggressive surgery, in case of suspicious Meckel’s cave lesions, is strongly discouraged because this procedure may increase the risk of postoperative deficit and provides no survival benefit compared with biopsy alone 3).

Outcome

Extra-axial primary CNS lymphoma, considered rare, mainly arises in the white matter of the brain. Though the tumor responds well to radiation and chemotherapy, the prognosis of primary CNS lymphoma remains poor.

Its prognosis appears to be identical to that of other intracranial lymphomas 4)

Case reports

The aim of a paper of Paglia et a. was to report a very rare case of primary Meckel’s cave diffuse large B-cell lymphoma (only seven cases were described in the literature) and standardize an operative algorithm to avoid the risks of an incorrect surgical conduct 5).


A 65-year-old man was examined at another hospital for unilateral facial pain. Carbamazepine was prescribed, but his symptoms did not improve. Magnetic resonance imaging (MRI) revealed swelling of the trigeminal nerve and a mass lesion in Meckel’s cave. The patient was referred to our hospital at this point. Gadolinium-enhanced MRI and F18-Fluorodeoxyglucose-position emission tomography suggested a likely malignant tumour and a biopsy was performed. Histopathological examination showed diffuse a large B cell lymphoma. The patient was treated with high-dose methotrexate (HD-MTX) and radiotherapy. Despite responding well to initial treatment, the patient relapsed, with lymphoma observed throughout the body. He died of pneumonia 18 months after the initial diagnosis. Facial pain is a symptom that is commonly managed in general practice. If symptoms do not improve, repeated imaging studies, including contrast MRI, is warranted. This is the first reported case of primary neurolymphomatosis (NL) of the trigeminal nerve associated with facial pain alone. Furthermore, HD-MTX and radiotherapy may be considered for the management of primary NL of a cranial nerve 6).


Ang et al. described an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel’s cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms 7).


A 52-year-old man with a history of malignant lymphoma of the cecum presented with lancinating facial pain in the left. Magnetic resonance imaging (MRI) revealed a tumor in the Meckel’s cave extending along the trigeminal nerve. The tumor was partially removed via left retrosigmoid lateral suboccipital craniotomy. Histological examination showed findings consistent with diffuse large B cell lymphoma, which was later confirmed to be metastatic lesion from the cecal lesion. Postoperative chemotherapy with cyclophosphamide, high dose, cytarabine, steroid (dexamethasone), etoposide, and rituximab (CHASER) followed by whole brain irradiation (30 Gy) resulted in complete remission. Although facial pain persisted, the patient’s general condition remained favorable and he did not experience recurrence over the 51-month follow-up period. Histological confirmation and awareness of malignant lymphoma are very important to determine the therapeutic strategy and to avoid misdiagnosis or delayed diagnosis. Long-term survival of patients with metastatic malignant lymphoma in the Meckel’s cave extending along the trigeminal nerve was very rare. In addition, metastatic malignant lymphoma in the extra-axial and peripheral nervous tissue might be different from primary central nervous system lymphoma in the white matter, since the efficacy of chemotherapeutic agents against malignant lymphomas in the extra-axial regions is not attenuated by the blood brain barrier. 8).


Kinoshita et al. reported a case of primary lymphoma of Meckel’s cave mimicking a trigeminal schwannoma radiographically, which achieved complete remission through use of rapid high-dose MTX therapy and radiation therapy.

The patient, a 55-year-old Japanese male, presented left trigeminal neuralgia. Magnetic resonance imaging (MRI) revealed a mass lesion in the left side of Meckel’s cave, with extension into the cerebellopontine angle and the infratemporal fossa through the foramen ovale, suggesting trigeminal schwannoma. However, the patient suffered radiologically inexplicable progressive cranial nerve palsy, which suggested malignant disease. MRI and CSF disclosed malignant tumor dissemination; biopsy revealed malignant lymphoma. The treatment, composed of the rapid infusion of high-dose MTX and whole brain and spine radiation, resulted in complete remission.

This case, which included atypical presentation of malignant lymphoma, illustrates the importance of including malignant lymphoma in the differential diagnosis of CP-angle and Meckel’s cave tumor. The results also confirmed the usefulness of combined rapid high-dose MTX therapy and radiation. 9).


Wakamoto et al. reported a rare primary intracranial malignant lymphoma that spread along the trigeminal nerve through the skull base foramen. The patient was a 50-year-old woman, who was diagnosed as having a primary intracranial malignant lymphoma in the right temporal lobe and had undergone an operation and radiation 5 years previously. The tumor was reduced in size and no recurrent tumor could be detected for 5 years. The patient complained of left face swelling and CT scan revealed a large mass in the pterygopalatine fossa. MRI revealed the recurrent tumor in the left Meckel’s cave with extension into the cavernous sinus. The tumor extended through the foramen ovale into the pterygopalatine fossa, through the superior orbital fissure into the orbital cavity and through the infraorbital fossa into the face subcutaneously. Biopsy of the subcutaneous tumor was carried out and the pathological diagnosis was malignant lymphoma, B cell type, which was identical with the initial tumor. MRI revealed the enlarged trigeminal nerve and 3D-CT revealed the enlargement of the infraorbital fossa and the foramen ovale. We suspected that primary intracranial malignant lymphoma had recurred in the left Meckel’s cave and the tumor had spread along with the peripheral three divisions of the trigeminal nerve. Perineural spreading along the trigeminal nerve passing through the skull base in patients with nasopharyngeal carcinoma is not rare, but this rarely occurs in the case of intracranial tumors 10).


Abdel Aziz et al. reported a case of primary lymphoma of Meckel’s cave. The ability of lymphoma to mimic a trigeminal schwannoma, both clinically and radiographically, resulted in misdiagnosis and flawed surgical strategy. They discussed the characteristics of a Meckel’s cave lymphoma on magnetic resonance images, the predisposing medical conditions that should cause the neurosurgeon to add lymphoma to the normal differential diagnosis, and appropriate management strategies.

A 40-year-old African-American woman presented with a 5-month history of progressive facial numbness and pain in all three divisions of the left trigeminal nerve. Magnetic resonance imaging revealed a mass in the left side of Meckel’s cave, with extension into the lateral compartment of the cavernous sinus, without encasement of the internal carotid artery, through the foramen rotundum into the posterior aspect of the maxillary sinus, and through the foramen ovale into the pterygopalatine fossa. The diagnosis, based on clinical history and radiographic imaging, was schwannoma of Meckel’s cave. The patient had a history of systemic lupus erythematosus that had been treated with intermittent steroid therapy.

The surgical approach selected was a frontotemporal craniotomy with orbitozygomatic osteotomy and anterior petrosectomy. The lesion was totally excised, although the gross intraoperative appearance of the lesion was inconsistent with the preoperative diagnosis, and the pathological examination was unable to establish a histological diagnosis on the basis of frozen sections. Histological diagnosis was confirmed on permanent section after surgery as B-cell lymphoma. Evaluation for other primary sites produced negative results. The patient was then treated with cyclophosphamide (Cytotoxan; Bristol-Myers Oncology, Princeton, NJ), doxorubicin (Adriamycin; Pharmacia & Upjohn, Kalamazoo, MI), vincristine, and prednisone chemotherapy every 3 weeks for six cycles and then by radiation therapy to the affected area.

The diagnosis of lymphoma should be considered for lesions affecting Meckel’s cave in high-risk immunocompromised patients. The presence of an apparent dural tail in an otherwise typical schwannoma is the distinguishing characteristic of a lymphoma. The absence of hyperostosis helps differentiate it from a meningioma. At this point, the preferred surgical strategy is biopsy for diagnosis and then radiotherapy and chemotherapy rather than major cranial base surgery for total resection. 11).

Artico et al. presented a rare case of Meckel’s cavity lymphoma. Only two other cases of identical localization were presented in the literature. The symptoms consisted of sensorimotor impairment of the Vth nerve associated with slight exophthalmos. C.T. scan showed a hyperdense lesion in Meckel’s cavity. After total surgical removal, histological analysis diagnosed a B-lymphocyte non-Hodgkin’s lymphoma. The patient received both radiotherapy and chemotherapy and at one year follow up, the clinical course was good. The lesion had no clinical or radiological specificity. Its prognosis appears to be identical to that of other intracranial lymphomas 12)

References

1) , 2) , 11)

Abdel Aziz KM, van Loveren HR. Primary lymphoma of Meckel’s cave mimicking trigeminal schwannoma: case report. Neurosurgery. 1999 Apr;44(4):859-62; discussion 862-3. PubMed PMID: 10201312.
3) , 5)

Paglia F, di Norcia V, D’Angelo L, Berra LV, Santoro A. A rare case of Meckel’s cave primary lymphoma: a case report and elaboration of the diagnostic algorithm. Acta Neurol Belg. 2020 Jan 25. doi: 10.1007/s13760-020-01281-x. [Epub ahead of print] PubMed PMID: 31983037.
4) , 12)

Artico M, Salvati M, Raco A, Innocenzi G, Delfini R. [Primary Meckel’s cave lymphoma. A case and review of the literature]. Neurochirurgie. 1992;38(6):368-71. Review. French. PubMed PMID: 1306893.
6)

Sato H, Hiroshima S, Anei R, Kamada K. Primary neurolymphomatosis of the trigeminal nerve. Br J Neurosurg. 2019 Feb 11:1-4. doi: 10.1080/02688697.2019.1568391. [Epub ahead of print] PubMed PMID: 30741017.
7)

Ang JW, Khanna A, Walcott BP, Kahle KT, Eskandar EN. Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge. J Clin Neurosci. 2015 Jul;22(7):1188-90. doi: 10.1016/j.jocn.2015.01.018. Epub 2015 Apr 10. PubMed PMID: 25865026; PubMed Central PMCID: PMC4457609.
8)

Tanaka T, Kato N, Itoh K, Hasegawa Y. Long-term survival of diffuse large B cell lymphoma of the trigeminal region extending to the Meckel’s cave treated by CHASER therapy: case report. Neurol Med Chir (Tokyo). 2014;54(8):677-80. Epub 2013 Dec 5. PubMed PMID: 24305022; PubMed Central PMCID: PMC4533500.
9)

Kinoshita M, Izumoto S, Oshino S, Nonaka M, Moriuchi S, Maruno M, Yoshimine T. Primary malignant lymphoma of the trigeminal region treated with rapid infusion of high-dose MTX and radiation: case report and review of the literature. Surg Neurol. 2003 Oct;60(4):343-8; discussion 348. Review. PubMed PMID: 14505860.
10)

Wakamoto H, Miyazaki H, Tomita H, Ishiyama N. [Perineural spreading along the trigeminal nerve in a patient with primary intracranial malignant lymphoma: a case report]. No Shinkei Geka. 2000 May;28(5):471-6. Japanese. PubMed PMID: 10806633.

Primary central nervous system lymphoma diagnosis

Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates.


In a retrospective study of patients with Primary central nervous system lymphoma (PCNSL) treated between January 2001 and December 2011 at the Navy General Hospital (Beijing). All included patients were pathologically diagnosed with PCNSL. Specimens were obtained by stereotactic biopsy and diagnosed by pathological examination. Serological panel had to be negative for HIV.

Out of the 118 patients, 73 (61.9%) were male and 45 (38.1%) were female. Median age was 54 (range 11-83) years. All patients had B cell lymphoma. The lesions showed slightly hyperdense shadows on computed tomography (CT) images, and mostly hyperintense T1 and iso- or hyperintense T2 signals on magnetic resonance imaging (MRI). Most lesions showed patchy enhancement after enhanced scanning, and some had the characteristic “butterfly sign” on enhanced MRI. The magnetic resonance spectroscopy of PCNSL manifested as increased Cho peak, moderately decreased NAA peak, and slightly decreased Cr peak. Positron emission tomography indicated high metabolism of 18F-FDG in PCNSL lesions.

MRI is important in the diagnosis of PCNSL. Understanding the imaging features of PCNSL will help improve its diagnosis in clinics 1).


van Westrhenen et al., performed a systematic review literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2).

They evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty-five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs -21, -19b, and -92a, RNU2-1f, CXCL13, interleukins -6, -8, and -10, soluble interleukin-2-receptor, soluble CD19, soluble CD27, tumour necrosis factor-alfa, beta-2-microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA-21 soluble CD27, and beta-2-microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL13, beta 2 microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice 2).

Radiographic features

The most helpful imaging pattern presents mainly in untreated non-immunocompromised patients is of a CT hyperdense avidly enhancing mass, with MRI T1 hypointense, T2 iso- to hypointense, vivid homogeneous gadolinium-enhancing lesion/s with restricted diffusion, subependymal extension, and crossing of the corpus callosum. Unfortunately, this pattern is not always present.

Typically PCNSL are supratentorial (75-85%) and appear as a mass or multiple masses (11-50%) that are usually in contact with the subarachnoid/ependymal surfaces. Crossing the corpus callosum is not infrequently seen. Enhancement on both CT and MRI is pronounced and usually homogeneous. Even with larger lesions, there is little mass effect for size and limited surrounding vasogenic oedema.

Low-grade tumours differ from the more common high-grade PCNSL in several ways:

Deep locations and spinal involvement is more common

Contrast enhancement is absent, irregular or only mild

Disseminated meningeal/intraventricular disease is uncommon, it is seen in ~5% (range 1-7%) of cases at presentation and usually in high-grade cases.

It should be noted that in patients who are immunocompromised (typically HIV/AIDS or post-transplant) appearances are more heterogeneous, including central non-enhancement/necrosis and haemorrhage, although the latter is still uncommon

CT

Most lesions are hyperattenuating (70%) 3

Shows enhancement

Haemorrhage is distinctly uncommon

There are often multiple lesions in patients with HIV/AIDS

MRI

Scintigraphy

Thallium 201

Shows increased uptake

C11 Methionine PET

Shows increased uptake 3).

Flow cytometry

Flow cytometry has a high specificity and can confirm the diagnosis of a lymphoma significantly faster than immunohistochemistry. This allows for rapid initiation of treatment in this highly aggressive tumor. However, since its sensitivity is less than 100%, van der Meulen et al., recommend to perform histology plus immunohistochemistry in parallel to flow cytometry 4).

References

1)

Cheng G, Zhang J. Imaging features (CT, MRI, MRS, and PET/CT) of primary central nervous system lymphoma in immunocompetent patients. Neurol Sci. 2018 Dec 22. doi: 10.1007/s10072-018-3669-7. [Epub ahead of print] PubMed PMID: 30580380.
2)

van Westrhenen A, Smidt LCA, Seute T, Nierkens S, Stork ACJ, Minnema MC, Snijders TJ. Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review. Br J Haematol. 2018 May 29. doi: 10.1111/bjh.15410. [Epub ahead of print] PubMed PMID: 29808930.
4)

van der Meulen M, Bromberg JEC, Lam KH, Dammers R, Langerak AW, Doorduijn JK, Kros JM, van den Bent MJ, van der Velden VHJ. Flow cytometry shows added value in diagnosing lymphoma in brain biopsies. Cytometry B Clin Cytom. 2018 May 10. doi: 10.1002/cyto.b.21641. [Epub ahead of print] PubMed PMID: 29747221.
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