- Department of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia
- Department of Internal Medicine, Division of Haematology, University Hospital Dubrava, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Pathology and Cytology, University Hospital Dubrava, Zagreb, Croatia
- School of Medicine, Catholic University of Croatia, Zagreb, Croatia
- Department of Diagnostic and Interventional Radiology, University Hospital Dubrava, Zagreb, Croatia
- Chair of Medicine of Sports and Exercise, Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia
Correspondence Address:
Petar Marčinković, Department of Neurosurgery, University Hospital Dubrava, Zagreb, Croatia.
DOI:10.25259/SNI_785_2024
Copyright: © 2025 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: Domagoj Dlaka1, Petar Marčinković1, Zdravko Mitrović2,3, Čedna Tomasović-Lončarić4,5, Danijel Cvetko6, Dominik Romić1, Marina Raguž1,5, Darko Chudy1,3, Tonko Marinović1,7. A unique presentation of an osteolytic chronic lymphocytic leukemia/small lymphocytic lymphoma as a helmet-shaped tumor. 28-Mar-2025;16:109
How to cite this URL: Domagoj Dlaka1, Petar Marčinković1, Zdravko Mitrović2,3, Čedna Tomasović-Lončarić4,5, Danijel Cvetko6, Dominik Romić1, Marina Raguž1,5, Darko Chudy1,3, Tonko Marinović1,7. A unique presentation of an osteolytic chronic lymphocytic leukemia/small lymphocytic lymphoma as a helmet-shaped tumor. 28-Mar-2025;16:109. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=13470
Abstract
BackgroundCranial vault lymphomas (CVLs) are rare skull lesions, mostly caused by diffuse large B-cell lymphoma, a subtype of non-Hodgkin lymphoma (NHL). Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) extremely rarely causes cranial vault lesions. Herein, we report a case of a CLL/SLL causing a unique and extensive cranial vault lesion with a striking presentation of a helmet-shaped tumor, whose treatment with ibrutinib led to full bone regeneration.
Case DescriptionA 63-year-old woman was admitted to our hospital for the continuation of treatment of CLL/SLL, which presented with hypercalcemia, generalized lymphadenopathy, and osteolytic lesions of Th10, Th11, and L2 vertebrae. An initial head computed tomography (CT) scan, performed due to psychomotor impairment, showed an extensive CVL. Despite therapy, a control CT scan showed progression of the CVL-shaped like a helmet, destroying the occipital, both parietal and a part of the frontal bone, with the effacement of the external table and somewhat preserved internal table. Successful therapy with ibrutinib led to full bone regeneration.
ConclusionStriking CVL presentations like the extensive permeative dissolution of the whole cranium rarely occur, especially in otherwise indolent types of NHL. Nevertheless, full bone regeneration and recovery are possible with modern treatment options, given adequate analysis is obtained beforehand. In case of a discrepancy between core-needle biopsy or fine-needle aspiration findings and the clinical picture, a surgical biopsy is warranted.
Keywords: Chronic lymphocytic leukemia/small lymphocytic lymphoma, Cranial vault lymphoma, Ibrutinib, Non-Hodgkin lymphoma
INTRODUCTION
Cranial vault tumors are uncommon lesions, usually found incidentally, which encompass roughly 2% of all musculoskeletal tumors.[
CASE DESCRIPTION
A 63-year-old female patient was admitted to our hospital in May 2019 for additional hematological work-up and treatment of CLL, which presented with lymphocytosis, discrete generalized lymphadenopathy, and osteolytic lesions of the Th10, Th11, and L2 vertebrae described on computed tomography (CT) scans of the thorax, abdomen, and pelvis in another hospital. Her general condition was poor due to hypercalcemia. Hypercalcemia was associated with normal phosphate serum levels and slightly elevated alkaline phosphatase but without any evident increase in parathyroid hormone serum levels, leading to the conclusion that hypercalcemia was not caused by disorders of the parathyroid glands but most probably a manifestation of a paraneoplastic syndrome in CLL with additional bone destruction. Soon after bisphosphonate administration, the calcium level normalized; however, she was still psychomotorically impaired. A head CT scan revealed diffuse destruction of the diploic space of the calvaria, alongside internal and external table destruction in certain places [
Figure 1:
Non-contrast head computed tomography (CT) scan. (a) Axial slice showing the destruction of the diploic space (permeating growth pattern) of frontal and both parietal bones; (b) coronal slice, infiltration of the diploic space; (c) sagittal slice, the extent of tumor from the frontal to the occipital bone can be seen; and (d-f) CT scan bone window, axial slices at various levels showing diploic space destruction with mostly preserved internal and external table.
For that reason, she was hospitalized again during August and September of the same year and the control head CT scan showed progression of the destruction of the occipital, both parietal and a part of the frontal bone, where the external table was destroyed by a soft-tissue process that also partially permeated the internal table of the occipital and parietal bones on the right side, forming a sort of “helmet” like CVL [
Figure 2:
Non-contrast head computed tomography (CT) scan. (a) Axial slice, enlargement of the tumor with the effacement of the external table, the internal table is still somewhat preserved; (b and c) coronal slice and sagittal slice, respectively, showing a “helmet” form of the tumor; and (d-f) CT scan bone window, axial slices at various levels showing the destruction of the external table, with somewhat preserved internal table.
This unusual presentation of CLL/SLL with bone tropism prompted us to exclude plasmacytic differentiation of CLL/SLL or Richter transformation to aggressive non-Hodgkin lymphoma (NHL). Bone marrow and lymph node biopsy were repeated, alongside fine-needle aspiration biopsy of the CVL confirming B-cell NHL, CLL immunophenotype, with a low proliferation index (Ki67 positive in 10% of cells). The findings of the fine-needle aspiration biopsy were not consistent with the patient’s clinical picture, as a strong suspicion of an aggressive subclone with a high tropism toward bone existed. Therefore, a neurosurgical procedure was performed in general anesthesia in the form of a piece-meal biopsy of the tumor for histological diagnosis [
Figure 3:
Neurosurgical procedure. (a-c) Axial, coronal, and sagittal slice reconstruction using OsiriX MD program showing the “helmet” CVL (red color); (d) intraoperative appearance of the tumor; and (e and f) non-contrast head computed tomography scan, coronal, and sagittal slice, respectively, showing the site of the operation at the level of the right Kocher’s point.
Histological diagnosis revealed a B-cell non-Hodgkin lymphoma, CLL immunophenotype, but with a higher proliferation rate than expected in indolent lymphoma (Ki67 positive in approximately 40% of cells), confirming an aggressive subclone [
Figure 4:
Histological biopsy findings. (a) Diffuse proliferation of small lymphocytes. Comparison of the size of the nucleus of a small lymphocyte (black arrow) to the nucleus of an endothelial cell (blue arrow), H&E staining, magnification ×400. The immunohistochemical analysis findings were consistent with CLL (b-d). (b) Pax5 nuclear positivity, magnification ×400; (c) CD5 membrane positivity, magnification ×200; (d) CD23 membrane positivity, magnification ×200; (e) CD20 weak membrane positivity due to previous therapy, magnification ×200; and (f) Ki67 nuclear positivity, magnification ×200.
The disease progressed again after 6 months of ibrutinib therapy (March 2020). Interestingly, the non-contrast head CT scan did not visualize the previously described bone destruction except a minimal patch high on the frontoparietal convexity of the skull [
The further course of the disease was complicated by pancytopenia requiring dose-reduction. Three months after venetoclax introduction, sternal bone marrow aspiration for the first time verified the presence of lambda clonal plasma cells along with CLL/SLL cells. The rising monoclonal spike in the serum protein electrophoresis was also observed. Therefore, bortezomib, a proteasome inhibitor routinely used for multiple myeloma, was added to venetoclax. Unfortunately, a month later, the patient died of a stroke. Interestingly, the last CT scan of the head revealed no tumor on the cranial vault.
Figure 5:
Non-contrast head computed tomography (CT) scan. (a and b) Axial slices at different levels showed no previous bone destruction, with clearly visible bone; (c and d) coronal and sagittal slices, respectively, showing no visible tumor; (e and f) CT scan bone window, axial slices at various levels showing well-formed bone with its diploic space, internal and external table.
DISCUSSION
CVL is a rare entity that can be divided into primary and secondary skull lymphomas. Solitary bone lesions are considered primary CVLs, while secondary CVLs are tumors originating from the surrounding tissues such as lymph nodes, organs, or soft tissue and secondarily invading skull bones.[
This case shows a unique presentation of a CVL extending through the whole calvarium, which contrasts the established opinion of a disproportionately small and mild skull destruction, preserved skull contours, and extensive soft-tissue mass observed by neuroradiological imaging (CT, MRI) in CVL patients.[
While most of the CVLs reported by Nitta et al. were diffuse large B-cell lymphomas (DLBCLs), there were only a few mentions of a SLL, which is interchangeably used with CLL.[
Approximately two-thirds of reported primary CVLs were treated surgically, which was especially pronounced in the case of discrete lesions. However, in their meta-analysis, Toyota et al. emphasize that a surgical procedure’s role in CVLs is limited and often brings unnecessary risk, as a core needle biopsy, eventually followed by full-thickness scalp biopsy, suffice in acquiring a final diagnosis. This approach leads to remission at comparable rates, using chemotherapy and radiation while avoiding open surgery.[
Only two cases regarding bone regeneration of a previously affected cranial vault were reported in the literature. In both these cases, the main culprit was DLBCL with intracranial and extracranial involvement, which was successfully treated with chemotherapy with or without radiotherapy.[
Therefore, the current case shows not only a unique, extensive CVL with the destruction of the diploic space (permeating growth pattern) and effacement of the external table of the calvaria but also a dramatic bone regeneration after successful CVL treatment. On its own, it’s not unusual for an osteolytic lymphoma to have a characteristic permeative dissolution, but such an extensive lesion forming a somewhat “helmet” form has not yet been documented. Another specificity of this case is that it was caused by the CLL/SLL, a type of NHL, which is usually indolent but, in this case, had an aggressive subclone with a significant tropism toward the skull bone.
CONCLUSION
Although most CVLs present as an extensive soft-tissue mass with disproportionately mild skull destruction, striking features like extensive permeative dissolution of the whole cranium vault can occur. This impressive neuroradiological finding may be seen even in usually presumed indolent types of lymphomas, like CLL/SLL. Regardless, even such large lesions can be successfully treated, given that adequate analysis is acquired beforehand. In the case of suspicion or inconsistencies between clinical presentation and core-needle biopsy or fine-needle aspiration findings, we believe that a surgical biopsy should suffice. Targeted therapy with Bruton kinase inhibitor in this type of CVL led to bone regeneration. Despite the well-known fact about the lack of potential for generalizing using case reports, we still emphasize the importance of publishing such peculiar cases to characterize unique tumor biology and clonal evolution during treatment with novel agents.
Ethical approval
The Institutional Review Board approval is not required.
Declaration of patient consent
Patient’s consent not required as patients identity is not disclosed or compromised.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation
The author confirms that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Disclaimer
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