primary

Primary central nervous system ALK-negative anaplastic large cell lymphoma

Primary central nervous system ALK-negative anaplastic large cell lymphoma

see also Primary central nervous system ALK-positive anaplastic large cell lymphoma

Primary central nervous system anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is an extremely rare type of primary central nervous system lymphoma (PCNSL).

Outcome

There are only nine cases reported in the literature to date, most of which have an overall survival time of no more than 8 months. Yuan et al. reported such a rare case that has a good outcome with the longest survival time and performed a literature review 1).

George et al. reported four new cases of primary central nervous system ALCL from the Mayo Clinic and incorporated additional data from five previously published cases. ALK-1 expression was determined in all nine tumors. Patient age was 4-66 years (mean 29 years) with a bimodal distribution: 6 < or = 22 years, 3 > or = 50 years. Six were female. Tumors were mostly supratentorial, five were multifocal, and seven had involvement of dura or leptomeninges. Seven tumors were T cells, two were null cells, and five of nine were ALK-1 immunopositive. Total mortality was six of nine. Three patients, 4-18 years of age (mean 13 years), were alive at 4.8-6.1 years postdiagnosis; these tumors were all ALK-positive. Five patients, 13-66 years of age (mean 43 years), died of tumor 4 days to 11 weeks postdiagnosis; four of five of these tumors were ALK-negative. One 10-year-old child with an ALK-positive tumor died of sepsis, but in remission. The central nervous system ALCL is aggressive. The study suggests that a better outcome may be associated with young age and ALK-1 positivity, prognostic parameters similar to systemic ALCL 2).

A review demonstrated that ALK-negative ALCL exhibits a poor prognosis and is very often fatal. The majority of ALK-negative patients were treated with radiotherapy or supportive care, due to their older age or poor PS. As ALK-negative ALCL tends to occur in older individuals, similar to PCNSL and DLBCL, chemoradiotherapy including HD-MTX should be initiated earlier.

In conclusion, findings indicate that the prognosis of ALCL of the CNS is correlated with ALK positivity and patient age of <40 years. Chemoradiotherapy with MTX is recommended as the standard treatment for ALCL. However, additional multicenter studies including large numbers of cases are required 3).

Case reports

A 19-year-old male patient was admitted to the hospital complaining of dizziness. CT and MRI imaging showed a heterogeneous enhanced lesion in the left parieto-occipital lobe and the leptomeninges of the occipital lobe and the cerebellum. The lesion was resected and confirmed to be ALK-negative ALCL by pathological examination. Then, the patient received 10 cycles of chemotherapy with high-dose methotrexate (HD-MTX) and whole brain radiotherapy. The patient recovered well and was regularly followed up. He was free of symptoms without recurrence on imaging examination 3 years later. ALCL is a rare type of PCNSL. HD-MTX combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify the biological characteristics of this rare type of PCNSL 4).

1) , 4)

Yuan C, Duan H, Wang Y, Zhang J, Ou J, Wang W, Zhang M. Primary central nervous system ALK-negative anaplastic large cell lymphoma: a case report and literature review. Ann Palliat Med. 2021 Jul 1:apm-21-557. doi: 10.21037/apm-21-557. Epub ahead of print. PMID: 34263607.
2)

George DH, Scheithauer BW, Aker FV, Kurtin PJ, Burger PC, Cameselle-Teijeiro J, McLendon RE, Parisi JE, Paulus W, Roggendorf W, Sotelo C. Primary anaplastic large cell lymphoma of the central nervous system: prognostic effect of ALK-1 expression. Am J Surg Pathol. 2003 Apr;27(4):487-93. doi: 10.1097/00000478-200304000-00008. PMID: 12657933.
3)

Nomura M, Narita Y, Miyakita Y, Ohno M, Fukushima S, Maruyama T, Muragaki Y, Shibui S. Clinical presentation of anaplastic large-cell lymphoma in the central nervous system. Mol Clin Oncol. 2013 Jul;1(4):655-660. doi: 10.3892/mco.2013.110. Epub 2013 Apr 30. PMID: 24649224; PMCID: PMC3915681.

Primary Central Nervous System Angiosarcoma

Primary Central Nervous System Angiosarcoma

Angiosarcoma is an infrequent tumor among sarcomas, especially presenting as a primary tumor within the central nervous system, which can lead to rapid neurological deterioration and death in few months.

Literature review

Mena et al. reported in 1991 eight patients with primary angiosarcoma of the central nervous system these included five males and three females ranging in age from 2 weeks to 72 years (mean 38 years). Of the eight neoplasms, six were located in the cerebral hemispheres and one was in the meninges; the site was unknown in the other. All patients underwent surgical resection. Five of the eight patients died, four within 4 months after surgery and one after 30 months. Two of the remaining three patients were 17 and 27 years old at the time of diagnosis and were alive at follow-up review 39 and 102 months after surgery, respectively. One patient was lost to follow-up monitoring. Microscopically, all eight tumors demonstrated a well-differentiated pattern with irregular vascular channels and intraluminal papillae; in addition, four showed poorly differentiated solid areas. Immunohistochemical staining of neoplastic cells to factor VIII-related antigen and Ulex europaeus agglutinin I was performed in five tumors and was focally positive in four. No correlation could be shown between the histological features and the growth and biological behavior of the tumors 1)

Case reports

Valera-Melé et al. presented a 41-year old man with a right frontal enhancing hemorrhagic lesion. Surgery was performed with histopathological findings suggesting a primary central nervous system angiosarcoma. He was discharged uneventfully and received adjuvant chemotherapy and radiotherapy. At 5 months, the follow-up MRI showed two lesions with an acute subdural hematoma, suggesting a relapse. Surgery was again conducted finding tumoral membranes attached to the internal layer of the dura mater around the right hemisphere. The patient died a few days later due to the recurrence of the subdural hematoma. This case report illustrates a rare and lethal complication of an unusual tumor. The literature reviewed shows that gross-total resection with adjuvant radiotherapy seems to be the best treatment of choice 2).

Gao M, Li P, Tan C, Liu J, Tie X, Pang C, Guo Z, Lin Y. Primary Central Nervous System Angiosarcoma. World Neurosurg. 2019 Dec;132:41-46. doi: 10.1016/j.wneu.2019.08.128. Epub 2019 Aug 27. PubMed PMID: 31470162 3).

report a case of intracranial angiosarcoma in a Caucasian male and present a review of the imaging features in the recent literature. The tumor mostly presents as a well-demarcated, heterogeneous, moderately to strongly enhancing lesion with signs of intratumoral bleeding and surrounding vasogenic edema. The differential imaging features of common hemorrhagic intracranial tumors are discussed 4).

Two cases of primary angiosarcoma of the brain are well characterized by imaging, histopathology, and immunohistochemistry. Case 1: The first patient was a 35-year-old woman who developed exophthalmos. Subtotal resection of a left extra-axial retro-orbital mass was performed.

Case 2: our second patient was a 47-year-old man who presented with acute visual loss, word-finding difficulty, and subtle memory loss. A heterogeneously-enhancing left sphenoid wing mass was removed. We also review the literature aiming at developing a rational approach to diagnosis and treatment, given the rarity of this entity.

Gross total resection is the standard of care for primary angiosarcoma of the brain. Adjuvant radiation and chemotherapy are playing increasingly recognized roles in the therapy of these rare tumors 5).

References

1)

Mena H, Ribas JL, Enzinger FM, Parisi JE. Primary angiosarcoma of the central nervous system. Study of eight cases and review of the literature. J Neurosurg. 1991 Jul;75(1):73-6. doi: 10.3171/jns.1991.75.1.0073. PMID: 2045922.
2)

Valera-Melé M, Darriba Allés JV, Ruiz Juretschke F, Sola Vendrell E, Hernández Poveda JM, Montalvo Afonso A, Casitas Hernando V, García Leal R. Primary central nervous system angiosarcoma with recurrent acute subdural hematoma. Neurocirugia (Astur). 2021 Mar 22:S1130-1473(21)00027-0. English, Spanish. doi: 10.1016/j.neucir.2021.02.002. Epub ahead of print. PMID: 33766476.
3)

Gao M, Li P, Tan C, Liu J, Tie X, Pang C, Guo Z, Lin Y. Primary Central Nervous System Angiosarcoma. World Neurosurg. 2019 Dec;132:41-46. doi: 10.1016/j.wneu.2019.08.128. Epub 2019 Aug 27. PubMed PMID: 31470162.
4)

Jerjir N, Lambert J, Vanwalleghem L, Casselman J. Primary Angiosarcoma of the Central Nervous System: Case Report and Review of the Imaging Features. J Belg Soc Radiol. 2016 Oct 10;100(1):82. doi: 10.5334/jbr-btr.1087. PMID: 30151480; PMCID: PMC6100495.
5)

Hackney JR, Palmer CA, Riley KO, Cure JK, Fathallah-Shaykh HM, Nabors LB. Primary central nervous system angiosarcoma: two case reports. J Med Case Rep. 2012 Aug 21;6:251. doi: 10.1186/1752-1947-6-251. PMID: 22909122; PMCID: PMC3459733.

Primary dystonia

Primary dystonia

Primary dystonia is a neurological disease with the characteristics of abnormal, involuntary twisting and turning movements, which greatly affects life quality of patients.

Primary dystonia is suspected when the dystonia is the only sign and there is no identifiable cause or structural abnormality in the central nervous system.

Etiology

Primary Dystonia Etiology.

Pathophysiology

The dystonia pathophysiology is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperintense signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare.

Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients.

There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients <25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group.

BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear 1).

Treatment

Pallidal Deep Brain Stimulation is the primary surgical treatment for dystonia 2). The response is better for primary dystonias, e.g. tardive dystonias than for secondary dystonias such as postanoxic, postencephalitic, perinatal, and post-stroke dystonia 3) (other targets need to be assessed). For primary dystonias, the globus pallidus internus (GPi) is the most common primary target. Good results have also been reported with STN DBS. Dyskinetic cerebral palsy in children may also be treated with pallidal stimulation 4).

Treatments for dystonia consist of oral medications, botulinum neurotoxin injections, physical therapy and surgeries. For medication-refractory dystonia, surgeries, especially deep brain stimulation (DBS), are the optimal option.

Treatment response is better for primary dystonias than for secondary dystonias. 5).

Case series

A strategy based on targeted gene panel sequencing identifies possibly pathogenic variants in fewer than 20% of cases in the early-onset and familial form of dystonia. By using Whole Exome Sequencing (WES), Wirth et al. aimed to identify the missing genetic causes in dystonic patients without a diagnosis despite gene panel sequencing.

WES was applied to DNA samples from 32 patients with early-onset or familial dystonia investigated by sequencing of a 127 movement disorders-associated gene panel. Dystonia was described according to the familial history, body distribution, evolution pattern, age of onset, associated symptoms and associated movement disorders. Rate of diagnoses was evaluated for each clinical feature.

They identified causative variants for 11 patients from 9 families in CTNNB1, SUCLG1, NUS1, CNTNAP1, KCNB1, RELN, GNAO1, HIBCH, ADCK3 genes, yielding an overall diagnostic rate of 34.4%. Diagnostic yield was higher in complex dystonia compared to non-complex dystonia (66.7%-5.9%; p < 0.002), especially in patients showing intellectual disability compared to the patients without intellectual disability (87.5%-16.7%; p < 0.002).

This approach suggests WES as an efficient tool to improve the diagnostic yield after gene panel sequencing in dystonia. Larger study are warranted to confirm a potential genetic overlap between neurodevelopmental diseases and dystonia 6).

Case reports

A 13-year-old boy suffering from extremely severe primary dystonia, with a BFMDRS-M score of 118 and a TWSTRS-S score of 29. The examination of 173 genes including DYT failed to identify any abnormality. He responded ineffectively to medications. After both bilateral subthalamic nucleus DBS and unilateral Vim-Vo thalamotomy (combined thalamic lesion in ventralis intermedius nucleus and ventralis oralis nucleus), his movement disorder improved dramatically. Four months and seven months after the operation, the scores of two rating scales sharply decreased. And potential brain structural changes were reflected in sensorimotor-related cortical thickness, surface area and gray matter volume from MRI, which revealed a valid method to evaluate surgical effect on the brain with enough patients.

DBS and thalamotomy is potentially an effective combination of treatments for severe medication-refractory dystonia 7).

References

1)

Bai X, Vajkoczy P, Faust K. Morphological Abnormalities in the Basal Ganglia of Dystonia Patients. Stereotact Funct Neurosurg. 2021 Jan 20:1-12. doi: 10.1159/000512599. Epub ahead of print. PMID: 33472209.
2) , 3)

Awan NR, Lozano A, Hamani C. Deep brain stimulation: current and future perspectives. Neurosurg Focus. 2009; 27. DOI: 10.3171/2009.4.FOCUS0982
4)

Keen JR, Przekop A, Olaya JE, et al. Deep brain sti- mulation for the treatment of childhood dystonic cerebral palsy. J Neurosurg Pediatr. 2014; 14: 585–593
5)

Awan NR, Lozano A, Hamani C. Deep brain stimulation: current and future perspectives. Neurosurg Focus. 2009 Jul;27(1):E2. doi: 10.3171/2009.4.FOCUS0982. Review. PubMed PMID: 19569890.
6)

Wirth T, Tranchant C, Drouot N, Keren B, Mignot C, Cif L, Lefaucheur R, Lion-François L, Méneret A, Gras D, Roze E, Laroche C, Burbaud P, Bannier S, Lagha-Boukbiza O, Spitz MA, Laugel V, Bereau M, Ollivier E, Nitschke P, Doummar D, Rudolf G, Anheim M, Chelly J. Increased diagnostic yield in complex dystonia through exome sequencing. Parkinsonism Relat Disord. 2020 Apr 20;74:50-56. doi: 10.1016/j.parkreldis.2020.04.003. [Epub ahead of print] PubMed PMID: 32334381.
7)

Lin H, Cai XD, Zhang DD, Liu JL, Li WP. Both DBS and Thalamotomy in a 13-year-old Patient with Primary Dystonia: A Case Report. World Neurosurg. 2018 Jun 8. pii: S1878-8750(18)31202-6. doi: 10.1016/j.wneu.2018.05.248. [Epub ahead of print] PubMed PMID: 29890276.

Methotrexate for Primary central nervous system lymphoma

In neurooncology and onco-hematology, intraventricular injection of chemotherapeutic agents (most typically, methotrexate) is an inevitable part of many protocols for treating patients with malignant tumors of the CNS, neuroleukemia, CNS lymphomas and some other disorders.

High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL 1).

MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy 2).

The addition of intraventricular MTX (rather than just intrathecal via LP) delivered through a Ommaya reservoir (6 doses of 12 mg twice a week, with IV leucovorin rescue) may result in even better survival 3)

In the event of an intrathecal MTX overdose (OD), interventions recommended 4) :

ODs of up to 85 mg can be well tolerated with little sequelae; immediate LP with drainage of CSF can remove a substantial portion of the drug (removing 15 ml of CSF can eliminate ≈ 20–30% of the MTX within 2 hrs of OD). This can be followed by ventriculolumbar perfusion over several hours using 240 ml of warmed isotonic preservative-free saline entering through the ventricular reservoir and exiting through a External lumbar cerebrospinal fluid drainage. For major OD of > 500 mg, add intrathecal administration of 2,000 U of carboxypeptidase G2 (an enzyme that inactivates MTX). In cases of MTX OD, systemic toxicity should be prevented by treating with IV dexamethasone and IV (not IT) leucovorin.

Therapeutic Outcomes and Toxicity of High-Dose Methotrexate-Based Chemotherapy for Elderly Patients with Primary Central Nervous System Lymphoma: A Report on Six Cases. 5).

A study provides Class III evidence that in immunocompetent patients with primary CNS lymphomas (PCNSLs), high-dose methotrexate (HD-MTX) plus rituximab compared with HD-MTX alone improves complete response (CR) and overall survival rates 6).

Case series

Yoon et al. presented the experiences with high-dose methotrexate (HD-MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival.

PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD-MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy.

A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty-six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty-one patients with recurrence or progression following HD-MTX underwent second-line treatment. Progression-free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression-free survival and overall survival (P < 0.05).

MTX-monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non-CR responders to induction chemotherapy 7).

A single-institution retrospective analysis was performed for 12 patients with newly diagnosed PCNSL treated with combined high-dose methotrexate (HD-MTX) and RTX. MTX was administered biweekly at 8 g/m2/dose until a complete response (CR) was achieved or for a maximum of eight doses. RTX was provided for a total of eight weekly doses at 375 mg/m2/dose. Following a median of 11 cycles of MTX, the radiographic overall response rate was 91% and the CR rate was 58%. A CR was achieved after a median 6 cycles of MTX. The median progression-free survival time was 22 months and the median overall survival time has not yet been attained. These results compare favorably to single-agent HD-MTX and suggest a role for immunochemotherapy in the treatment of PCNSL 8).

Zhu et al. studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. They identified 31 patients diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survivals were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL 9).

References

1) , 9)

Zhu JJ, Gerstner ER, Engler DA, Mrugala MM, Nugent W, Nierenberg K, Hochberg FH, Betensky RA, Batchelor TT. High-dose methotrexate for elderly patients with primary CNS lymphoma. Neuro Oncol. 2009 Apr;11(2):211-5. doi: 10.1215/15228517-2008-067. Epub 2008 Aug 29. PMID: 18757775; PMCID: PMC2718993.
2) , 7)

Yoon WS, Park JS, Kim YI, Chung DS, Jeun SS, Hong YK, Yang SH. High-dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15-year multicenter experience. Asia Pac J Clin Oncol. 2020 Sep 25. doi: 10.1111/ajco.13427. Epub ahead of print. PMID: 32978898.
3)

DeAngelis LM, Yahalom J, Thaler HT, Kher U. Com- bined Modality Therapy for Primary CNS Lympho- mas.JClinOncol.1992;10:635–643
4)

O’Marcaigh AS, Johnson CM, Smithson WA, et al. Successful Treatment of Intrathecal Methotrexate Overdose by Using Ventriculolumbar Perfusion and Intrathecal Instillation of Carboxypeptidase G2. Mayo Clin Proc. 1996; 71:161–165
5)

Tempaku A, Takahashi Y, Kamada H. Therapeutic Outcomes and Toxicity of High-Dose Methotrexate-Based Chemotherapy for Elderly Patients with Primary Central Nervous System Lymphoma: A Report on Six Cases. Acta Haematol. 2019 May 21:1-2. doi: 10.1159/000499100. [Epub ahead of print] PubMed PMID: 31112947.
6)

Holdhoff M, Ambady P, Abdelaziz A, Sarai G, Bonekamp D, Blakeley J, Grossman SA, Ye X. High-dose methotrexate with or without Rituximab in newly diagnosed primary CNS lymphoma. Neurology. 2014 Jul 15;83(3):235-9. doi: 10.1212/WNL.0000000000000593. Epub 2014 Jun 13. PubMed PMID: 24928128; PubMed Central PMCID: PMC4117362.
8)

Ly KI, Crew LL, Graham CA, Mrugala MM. Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience. Oncol Lett. 2016 May;11(5):3471-3476. doi: 10.3892/ol.2016.4393. Epub 2016 Mar 30. PMID: 27123138; PMCID: PMC4840907.

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 Intracranial Solitary Fibrous Tumor

Primary Intracranial Solitary Fibrous Tumor

Intracranial solitary fibrous tumors (ISFTs) are rare mesenchymal neoplasms originating in the meninges and constitute a heterogeneous group of rare spindle-cell tumors that include benign and malignant neoplasms of which hemangiopericytoma is nowadays considered a cellular phenotypic variant. ISFT usually shows benign or indolent clinical behavior 1).

Primary Intracranial Solitary Fibrous Tumor (SFT) involving the central nervous system (CNS) was first reported in 1996 by Carneiro et al, who described 7 cases of meningeal SFT that could be distinguished from fibrous meningioma on morphologic and immunohistochemical grounds 2).

Since then, more than 60 cases of CNS SFT including the meninges and the spinal cord have been described in the pertinent literature.

For its rarity and resemblance to other more common brain tumors, such as meningioma and hemangiopericytomas, intracranial SFT (ISFT) is often poorly recognized and remains a diagnostic challenge.

Although there are no pathognomonic imaging findings, some imaging features, such as the “black-and-white mixed” pattern on T2-weighted images and marked heterogeneous enhancement, might be helpful in the diagnosis of intracranial solitary fibrous tumor

A 62-year-old man with headache and memory disturbance for 2 years. A, Noncontrast CT shows a heterogenous hyperattenuated multilobulated tumor in left middle cranial fossa. B, Contrast-enhanced CT, intense but inhomogeneous contrast enhancement is noted. C, T1-weighted axial MR image, a large lobulated mass is seen in the left paraclinoid portion to the tentorium. D, T2-weighted axial MR image reveals 2 different signal intensity portions of the mass, hyposignal intensity and hypersignal intensity to gray matter. E and F, Gadolinium-enhanced T1-weighted axial and coronal MR images show marked and heterogenous enhancement. The tumor is partially implanted on the surface of the tentorium (arrows). Memory disturbance might be because of the mass effect on the limbic system. G, Selective injection of the left internal carotid artery (capillary phase); the tumor is supplied at its periphery by pial branches. H, Selective injection of the left external carotid artery; there is tumor blushing with dysplastic dilation of the tumor vessels. There is no demonstrable significant arteriovenous shunt or early venous drainage. 3).

Case reports

Yamaguchi et al. reported a very rare case of intracranial SFT in a 55-year-old woman who presented with gait disturbance and numbness in bilateral upper limbs from three months prior to visiting the hospital. Head MRI revealed a homogeneously enhancing mass lesion located primarily in the fourth ventricle extending into the spinal canal and left foramen of Luschka, with a maximum diameter of 60 mm. Notably, this tumor presented spontaneous partial regression during waiting planned surgery without therapy, including chemotherapy and radiotherapy. This patient underwent a midline suboccipital craniotomy and resection of the tumor. Interestingly, there was no attachment to the dura mater of the posterior cranial fossa and the lesion was only attached to the dorsal part of the medulla oblongata.

Although the location of the SFT in the fourth ventricle is rare, SFT should be considered as one of the differential diagnosis of fourth ventricle tumors. In addition, this case indicates that SFT in the fourth ventricle may regress on occasion spontaneously without a precisely known cause for this spontaneous partial regression 4).

Torazawa et al., encountered a case of small solitary fibrous tumor in the optic canal causing rapid visual deterioration. The radiographic findings of pre-operative imaging studies were compatible with those of meningioma; however, unlike meningioma, bleeding from the tumor was very profuse during the operation. The endoscopic transnasal approach was effective for handling the highly vascularized tumor in this delicate region, and gross total removal was achieved with postoperative gradual improvement in his visual function. Nevertheless, the tumor recurred after six months, and re-resection was performed with using the same surgical corridor, followed by adjuvant radiotherapy.

Endoscopic transnasal surgery is a valuable option for aggressive lesions in the optic canal. Although the efficacy of radiotherapy for SFT remains controversial, it should be considered when the tumor shows progressive features 5).

A 63-year-old female patient who had confused mentality, without other neurological deficit. The brain MRI showed an ovoid mass in the right frontal lobe. The tumor was surgically removed grossly and totally, and the pathologic diagnosis was SFT. At 55 months after the surgery, the tumor recurred at the primary site and at an adjacent area. A second operation was thus done, and the tumor was again surgically removed grossly and totally. The pathologic diagnosis was the same as the previous, but the Ki-67 index was elevated. Ten months later, two small recurring tumors in the right frontal skull base were found in the follow-up MRI. It was decided that radiation therapy be done, and MRI was done again 3 months later. In the follow-up MRI, the size of the recurring mass was found to have decreased, and the patient did not manifest any significant symptom. Follow-up will again be done 18 months after the second surgery 6).

References

1)

Aljohani HT, Chaussemy D, Proust F, Chibbaro S. Intracranial solitary fibrous tumor/hemangiopericytoma: Report of two cases and literature review. Int J Health Sci (Qassim). 2017 Jul-Sep;11(3):69-70. PubMed PMID: 28936155; PubMed Central PMCID: PMC5604277.
2)

Carneiro SS, Scheithauer BW, Nascimento AG, Hirose T, Davis DH. Solitary fibrous tumor of the meninges: a lesion distinct from fibrous meningioma. A clinicopathologic and immunohistochemical study. Am J Clin Pathol. 1996 Aug;106(2):217-24. PubMed PMID: 8712177.
3)

Weon YC, Kim EY, Kim HJ, Byun HS, Park K, Kim JH. Intracranial solitary fibrous tumors: imaging findings in 6 consecutive patients. AJNR Am J Neuroradiol. 2007 Sep;28(8):1466-9. PubMed PMID: 17846192.
4)

Yamaguchi J, Motomura K, Ohka F, Aoki K, Tanahashi K, Hirano M, Nishikawa T, Shimizu H, Wakabayashi T, Natsume A. Spontaneous tumor regression of intracranial solitary fibrous tumor originating from the medulla oblongata: A case report and literature review. World Neurosurg. 2019 Jul 18. pii: S1878-8750(19)31958-8. doi: 10.1016/j.wneu.2019.07.052. [Epub ahead of print] PubMed PMID: 31326640.
5)

Torazawa S, Shin M, Hasegawa H, Otani R, Ueki K, Saito N. Endoscopic transnasal resection of solitary fibrous tumor in the optic canal. World Neurosurg. 2018 May 16. pii: S1878-8750(18)31003-9. doi: 10.1016/j.wneu.2018.05.050. [Epub ahead of print] PubMed PMID: 29777894.
6)

Kim JH, Yang KH, Yoon PH, Kie JH. Solitary Fibrous Tumor of Central Nervous System: A Case Report. Brain Tumor Res Treat. 2015 Oct;3(2):127-31. doi: 10.14791/btrt.2015.3.2.127. Epub 2015 Oct 30. PubMed PMID: 26605270; PubMed Central PMCID: PMC4656890.

Factors Related to the Primary Discectomy in Recurrent Lumbar Disc Herniation

Factors Related to the Primary Discectomy in Recurrent Lumbar Disc Herniation

The degree of disc removal did not influence the outcome or complication rate in Fountas et al., clinical series 1)

For Carragee et al., the more aggressive removal of remaining intervertebral disc material may decrease the risk of reherniation, but the overall outcome was less satisfactory, especially during the first year after surgery 2).

McGirt et al., found that larger annulus defects and smaller percentage of disc removed during primary surgery, rather than absolute volume as reported in previous studies, were associated with an increased risk of recurrent lumbar disc herniation while more aggressive removal contributed to accelerated disc height loss 3).

A systematic review of the literature suggests that conservative discectomy may result in shorter operative time, quicker return to work, and a decreased incidence of long-term recurrent low back pain but with an increased incidence of recurrent disc herniation. Prospective randomized trails are needed to firmly assess this possible benefit. 4).

The question remains how to balance the desire for maintaining disc height with minimizing the risk for reherniation 5).

References

 
1) 
Fountas KN, Kapsalaki EZ, Feltes CH, et al. Correlation of the amount of disc removed in a lumbar microdiscectomy with long-term outcome. Spine (Phila Pa 1976). 2004;29:2521–2526.
2) 
Carragee EJ, Spinnickie AO, Alamin TF, Paragioudakis S. A prospective controlled study of limited versus subtotal posterior discectomy: short-term outcomes in patients with herniated lumber intervertebral discs and large posterior anular defect. Spine (Phila Pa 1976). 2006;31:653–657.
3) 
McGirt MJ, Eustacchio S, Varga P, et al. A prospective cohort study of close interval computed tomography and magnetic resonance imaging after primary lumbar discectomy: factors associated with recurrent disc herniation and disc height loss. Spine (Phila Pa 1976). 2009;34:2044–2051.
4) 
Walters WC, 3rd, McGirt MJ. An evidence-based review of the literature on the consequences of conservative versus aggressive discectomy for the treatment of primary disc herniation with radiculopathy. Spine J. 2009;9:240–257.
5) 
Shepard N, Cho W. Recurrent Lumbar Disc Herniation: A Review. Global Spine J. 2019 Apr;9(2):202-209. doi: 10.1177/2192568217745063. Epub 2017 Dec 18. Review. PubMed PMID: 30984501; PubMed Central PMCID: PMC6448208.

Primary intraosseous meningioma classification

Primary intraosseous meningioma classification

Lang et al. 1) classified primary intraosseous meningioma into 3 types in order to prevent any confusion: purely extra-calvarial (type I), purely calvarial (type II), and calvarial with extracalvarial extension (type III).

Intraosseous lipomatous meningioma 2)

Osteolytic intraosseous meningiomas are the rarest and very few cases have been reported. Given that many of these may develop signs of malignancy, early histological confirmation is important in order to ensure appropriate treatment.

Type III intraosseous meningioma

Type III intraosseous meningioma is a very rare type of meningioma with extracranial extension.

Su et al., reported a case of type IIIC intraosseous meningioma with invasion of the superior sagittal sinus and skull periosteum. A 67-year-old woman was admitted due to a mass on the left frontoparietal region for 4 years. Magnetic resonance imaging showed a skull tumor with invasion of the superior sagittal sinus. After partial resection of the tumor, pathological and immunohistochemistry revealed that the epithelial meningioma derived from skull involved the skull periosteum. There was no enlargement of residual parasagittal tumor after 1 year of follow-up. The intraosseous meningioma in the present case was a rare benign tumor with good prognosis after surgery 3).

A 78-year-old female with a slowly growing hard mass in the left parietal bone was admitted. Neurological findings were normal. Plain skull radiograph showed a 6 x 6 cm hyperostotic lesion in the left parietal bone. Bone window CT scan showed thickening and hyperostosis in the same area. MRI using Gd-DTPA showed heterogeneous enhancement of the intraosseous mass, and homogenous enhancement of the dura matter. And angiogram showed a tumor stain fed by the bilateral superficial temporal artery and the It-occipital artery. The tumor and the underlying dura mater were totally removed. Preoperative diagnosis was an osteogenic tumor, but histological examination revealed a transitional meningioma. We discussed the development and the classification of an ectopic meningioma and the mechanism of hyperostosis. We should be aware of the existence of intraosseous menigiomas mimicking osteogenic tumors 4).

References

1)

Lang FF, Macdonald OK, Fuller GN, DeMonte F: Primary extradural meningiomas: A report on nine cases and review of literature from the era of computerized tomography scanning. J Neurosurg 93(6):940-950, 2000
2)

Kim L, Huang C, Morey AL, Winder MJ. Intraosseous lipomatous meningioma. Case Rep Neurol Med. 2015;2015:482140. doi: 10.1155/2015/482140. Epub 2015 Jan 26. PubMed PMID: 25688309; PubMed Central PMCID: PMC4321083.
3)

Su J, Ba Y, Liang S, Liu H. Type III Intraosseous Meningioma Invading Superior Sagittal Sinus and Skull Periosteum. J Craniofac Surg. 2019 Mar 27. doi: 10.1097/SCS.0000000000005525. [Epub ahead of print] PubMed PMID: 30939563.
4)

Nanto M, Tsuji N, Miki J, Tanaka S, Uematsu Y, Itakura T. [A case of intraosseous meningioma with extracranial progression having difficulty in making a preoperative diagnosis]. No Shinkei Geka. 2005 Jan;33(1):51-6. Japanese. PubMed PMID: 15678869.

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

see Primary central nervous system lymphoma 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.
3)

https://radiopaedia.org/articles/primary-cns-lymphoma
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.