- Departments of Neurosurgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
- Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Naoki Nitta, Department of Neurosurgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
DOI:10.25259/SNI_28_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Naoki Nitta1, Suzuko Moritani2, Tadateru Fukami1, Kazuhiko Nozaki1. Characteristics of cranial vault lymphoma from a systematic review of the literature. 03-Jun-2022;13:231
How to cite this URL: Naoki Nitta1, Suzuko Moritani2, Tadateru Fukami1, Kazuhiko Nozaki1. Characteristics of cranial vault lymphoma from a systematic review of the literature. 03-Jun-2022;13:231. Available from: https://surgicalneurologyint.com/surgicalint-articles/11638/
Background: Cranial vault lymphomas are rare and their clinical features are often similar to those of cranial vault meningiomas. The objective of this review was to identify the features helpful for differentiating lymphomas of the cranial vault, from meningiomas which were the most common diagnosis before the definitive pathological diagnosis.
Methods: The inclusion criterion was a histologically proven malignant lymphoma initially appearing in the calvarium. We conducted a literature search of the electronic PubMed and Ichushi-Web databases up to June 1, 2020. Cranial vault lymphoma that was diagnosed after an original diagnosis of lymphoma in a nodal or soft-tissue site was excluded from the study. Descriptive analyses were used to present the patient characteristics.
Results: A total of 111 patients were found in 98 eligible articles. Almost all studies were case reports. The most common symptom was a growing subcutaneous scalp mass (84%) present for a mean duration of 5.9 months before the patient presented for treatment in analyzable cases; this fast growth may distinguish lymphomas from meningiomas. The tumor vascularization was often inconspicuous or poor, unlike well-vascularized meningiomas. A disproportionately small amount of skull destruction compared with the soft-tissue mass was observed in two-thirds of the analyzable cases.
Conclusion: This qualitative systematic review identified several features of cranial vault lymphomas that may be useful in differentiating them from meningiomas, including a rapidly growing subcutaneous scalp mass, poor vascularization, and limited skull destruction relative to the size of the soft-tissue mass.
Keywords: Calvarial lymphoma, Calvarium, Lymphosarcoma, Reticulum cell sarcoma, Skull
Malignant lymphoma of the bone is uncommon and, hence, presents diagnostic and therapeutic problems.[
The inclusion criterion was a histologically proven malignant lymphoma initially appearing in the calvarium. Cranial vault lymphoma that was diagnosed after an original diagnosis of lymphoma in a nodal or soft-tissue site was excluded from the study. Skull base lymphoma and dural lymphoma were also excluded from the study. Articles whose full text was unable to be located were excluded from the study. We excluded systematic and retrospective review articles and case series articles that did not include case-specific data.
Information sources and search strategy
We conducted a literature search of the electronic PubMed and Ichushi-Web databases up to June 1, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We extracted all human reports on cranial vault lymphomas, using the following terms: cranial vault lymphoma; skull lymphoma; calvarial lymphoma; transcalvarial lymphoma; dural lymphoma; and combinations of the variables of lymphoma, lymphosarcoma (an obsolete classification of non-Hodgkin lymphoma), reticulum cell sarcoma (another obsolete classification of non-Hodgkin lymphoma), cranial, vault, skull, and calvarium. The search resulted in 1492 PubMed citations and 391 Ichushi-Web citations, 113 of which were duplicated, resulting in a total of 1770 articles [
Two reviewers (N.N. and T.F.) independently and in duplicate screened, reviewed, and discussed all the selected articles. The full text of all eligible articles was reviewed, and their data extracted and collated. In cases where questions regarding the inclusion of certain articles arose, this was discussed with a third reviewer, K.N.
Data collection process and data items
Data of the eligible works were obtained through careful analysis of the full text by two authors (N.N. and T.F) independently. The senior author, K.N., was available in case of a split decision. Questions arising as to pathological diagnosis were discussed with a pathologist, S.M. We analyzed the clinical and radiological characteristics of the patients, as well as their treatments and survival in these published studies. Specifically, we extracted the following items: age of the patient; sex; clinical symptoms; location of tumors; findings of palpation; skin condition; speed of growth; existence of other lesions; types of treatment; extent of resection; duration of follow-up and outcomes; laboratory data; imaging data of skull X-ray, angiogram, computed tomography (CT), magnetic resonance imaging (MRI), and others; bone images on CT; extra- and intracranial tumor extension on CT and MRI; dural tail and brain invasion on MRI; and histopathological types. Due to the heterogeneity of patient descriptions, some clinical and imaging features were not explicitly reported for each patient. We extracted and reported only unambiguously described data. Data on clinical and imaging features were also extracted from the patient imaging data. Evaluation of publication bias was not feasible because of heterogeneity and because most of the included studies were case reports and case series.
Descriptive analyses were used to present the patient characteristics. Continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed as number and percentage. Because of the limited follow-up data included in each intervention and the lack of standardization of assays and treatments across the many laboratories included in the present review, we were unable to statistically compare the findings on images and the changes in clinical outcomes. All calculations were performed with JMP 13.2.1 (SAS Institute, Inc., Cary, North Carolina, U.S.).
From among the articles found, we selected all studies reporting patients with cranial vault lymphoma (n = 106) without limitation of language and identified additional studies from the reference lists of the articles (n = 3). After discarding duplicate references and publications (n = 2), as well as excluding reports of secondary cranial vault lymphoma, skull base lymphoma, or dural lymphoma (n = 9), we settled on 98 articles for careful review. The number of articles retained at each stage of data acquisition is shown in a PRISMA flowchart [
We found 111 cases of histologically proven malignant lymphomas initially appearing in the cranial vault in the 98 articles and analyzed the data of 111 patients [
The average patient age was 52 ± 20 years (range, 3–85 years) [
Laboratory data were described in 59 cases, with human immunodeficiency virus positivity in 5 cases (8%), elevated lactate dehydrogenase in 6 cases (10%), anemia in 4 cases (7%), increased white blood cell count in 3 cases (5%), elevated erythrocyte sedimentation rate in 2 cases (3%), elevated alkaline phosphatase in 1 case (2%), increased soluble interleukin-2 receptor (sIL2R) in 1 case (2%), and decreased platelets in 1 case (2%) [Table S1]. Findings on plain skull X-ray were described in 38 cases, including osteolytic changes at the tumor site in 29 cases (76%), no change in 6 cases (16%), hyperostosis in 2 cases (5%), and periosteal reaction in 4 cases (11%). A sharp margin of the skull lesion was observed in 6 cases (16%) and an indistinct or irregular margin of the skull lesion in 15 cases (40%). In 12 cases with description of tumor vascularization on angiogram, no or poor tumor vascularization was found in 7 cases (58%). If any vascularization was present, it was mainly derived from the external carotid artery circulation. Among 32 cases with analyzable CT data, the tumor was hyperdense in 25 cases (78%), isodense in 5 cases (16%), and hypodense in 2 cases (6%). Among 42 cases with contrast-enhanced (CE) CT data, the tumor was enhanced well in 37 cases (88%) and slightly in 5 cases (12%). Most tumors were enhanced diffusely, either homogeneously or heterogeneously, whereas some extracranial components showed peripheral enhancement. On MRI, T1-weighted imaging (T1WI) with analyzable data (n = 38) showed a hyper- and isointense tumor in 1 case (3%), isointense tumor in 11 cases (29%), iso- and hypointense tumor in 4 cases (11%), and hypointense tumor in 22 cases (58%). T2-weighted imaging (T2WI) (n = 40) showed a hyperintense tumor in 21 cases (53%), hyper- and isointense tumor in 1 case (3%), isointense tumor in 12 cases (30%), iso- and hypointense tumor in 5 cases (13%), and hypointense tumor in 1 case (3%). CE-T1WI (n = 48) showed an enhancing tumor in 48 cases (100%). The tumors tended to show uptake on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and on bone scintigraphy and gallium scintigraphy, which were also used for the evaluation of lesions outside the cranial vault.
Extra- and intracranial extensions of the tumor were evaluated by CT, MRI, or both in 87 cases [Table S2]; the extracranial extension was much larger than the intracranial extension in 35 cases (40%), both were nearly the same size in 35 cases (40%), the intracranial extension was much larger than the extracranial extension in 16 cases (18%), and there was neither intra- nor extracranial extension in 1 case (1%). Bone changes of the cranial vault due to the tumor were evaluated by CT, MRI, or both in 84 cases. The images showed no skull changes and/or preserved skull contour in 11 cases (13%), osteolytic changes in 68 cases (81%), hyperostosis in 4 cases (5%), and only sclerosis at the lesion in 1 case (1%). In the 68 cases with osteolytic skull changes due to the tumor, the skull was penetrated or dissolved to less than half of the thickness in 26 cases (38%), whereas permeative dissolution with relatively preserved skull contour was observed in 35 cases (51%). Periosteal bone formation was observed in 10 cases (15%). In seven cases, there was no detailed description. A disproportionately small area of cortical destruction of the cranial vault relative to the volume of the extra- or intracranial soft-tissue mass, which we defined as cortical destruction less than one-fifth of the soft-tissue mass in diameter, was observed in 50 cases (67%) on CT, MRI, or both (n = 75). On MRI (n = 57), a dural tail was observed in 42 cases (74%), and invasion of the brain was observed in 15 cases (26%).
Surgery was detailed in 98 cases, of which 45 (46%) involved a biopsy or partial removal and 53 (54%) involved subtotal or gross total removal [
The type of lymphocyte was described in 80 cases: 75 (94%) were B-cell lymphomas and 5 (6%) were T-cell lymphomas [Table S2]. Diffuse large B-cell lymphoma (DLBCL) was the most common, being reported in 34 cases.
To determine the rates of survival, we excluded cases in which the patients died of a cause unrelated to the skull lesion and included cases with follow-up periods of more than 6 months (n = 74) or 1 year (n = 54). In the included cases, 67 (90.5%) and 45 (83.3%) patients were alive at the follow-up of 6 months and 1 year, respectively [
We reviewed the demographic, clinical, and imaging characteristics of cranial vault lymphoma to specify the features that might be helpful for differential diagnosis, especially between lymphomas and meningiomas of the cranial vault.
When a tumor with intra- and extracranial extension sandwiching the skull is seen, meningioma with extracranial extension is often first suspected. In many cases, the subcutaneous scalp mass was firm and nontender, which is also similar to meningioma with extracranial extension. However, in our review, the subcutaneous scalp mass grew very rapidly before the patient presented for treatment, for a mean duration of 5.9 months, which is atypical for meningioma, which is generally slow growing.[
Laboratory data were unremarkable in many cases. Kosugi et al.[
The extracranial component tended to be at least as large as the intracranial component in cranial vault lymphoma. Because meningioma usually originates from the meninges, theoretically, it tends to grow intracranially rather than extracranially. Extracranial-dominant extension might, therefore, also contribute to distinguishing cranial vault lymphoma from meningioma.
However, other findings are unlikely to clarify the diagnosis. For example, the tumors tended to be hyper- to isodense on CT, iso- to hypointense on T1WI, and hyper-to isointense on T2WI, which are nonspecific features of skull tumors. Although a dural tail was observed in many cases, as reported by Xing et al.,[
It has been suggested that lymphoma cells infiltrate the spaces within the diploe and extend along the emissary veins to infiltrate the soft tissues on either side of the bone.[
After histological confirmation of the diagnosis, patients were usually treated with adjuvant chemotherapy, radiotherapy, or both. Although the best treatment for cranial vault lymphoma has not been elucidated because of the paucity of cases and lack of clinical studies, treatments based on those for systemic malignant lymphoma tended to be adopted.
B-cell lymphomas accounted for approximately 94% of the cranial vault lymphomas, whereas T-cell lymphomas roughly accounted for the remaining 6% of cases. Peripheral T-cell lymphomas account for 6–10% of all cases of non-Hodgkin lymphoma[
In analyzable follow-up data, 67 and 45 patients were alive after 6 months (n = 74) and 1 year (n = 54), respectively [
In the present review, we have provided objective data from patients reported in published studies. The difficulty in systematically reviewing the data reported in the literature is the heterogeneity of the data. In particular, almost all reports reviewed for this study were case reports. Because of the limited number and the heterogeneity of described data of preoperative findings and treatments, we could perform only descriptive analyses. Another weakness of the present review resulted from biased reporting in the published studies, with likely underreporting of recent cases in the United States and European countries because of decreased novelty in inverse proportion to the accumulation of reported cases. The data that were more likely to be reported, if present, included findings on MRI and CT. Findings of plain skull X-ray and angiography and long-term follow-up data were less likely to be reported.
The strength of the present review is the comprehensive nature of the literature search. We analyzed cases from all over the world, reported not only in English but also in four non-English languages.
Cranial vault lymphoma is a rare entity among skull tumors. To the best of our knowledge, this is the largest reported pooled database describing cranial vault lymphoma patients. The most common symptom was a rapidly growing subcutaneous scalp mass. The tumor was poorly vascularized on angiography. Skull destruction on images was mild and disproportionately small despite the large size of the extracranial and/or intracranial component in two-thirds of the cases. These features should help to distinguish lymphoma from meningioma.
Patient’s consent not required as patient’s identity is not disclosed or compromised.
There are no conflicts of interest.
The authors thank ELSS, Inc. (https://www.elss.co.jp/ ) for English-language editing of this manuscript.
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