Clinical Imaging 39 (2015) 672–676
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Case Reports
Primary leptomeningeal glioblastoma with systemic metastases—case report and review of literature☆,☆☆,★ Girish Bathla a,⁎, Sarika Gupta b, Toshio Moritani a a b
Department of Radiology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA Department of Pathology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
a r t i c l e
i n f o
Article history: Received 5 March 2015 Received in revised form 27 March 2015 Accepted 31 March 2015 Keywords: Glioblastoma Metastases Spine Orbit MRI
a b s t r a c t We present a case of a rare meningeal glioblastoma with extensive systemic metastases, along with a review of the existing literature. The patient presented with headache and visual and sensory symptoms and had a rapidly progressive clinical course despite therapy. The patient went on to develop spinal, orbital, muscular, and cutaneous metastases over a short period. Review of the literature reveals 13 similar previously reported cases, none with a similar presentation. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Primary leptomeningeal astrocytomas (PLAs) are rare glial tumors of meningeal origin that may occur anywhere along the craniospinal axis. More commonly, these present as diffuse meningeal enhancement and mimic metastases or infectious or inflammatory meningitis. The focal form, on the other hand, can mimic a meningioma or a dural metastatic lesion [1]. Systemic metastases are rare, both with intraaxial glial tumors or PLAs [2–4]. We report a case of a primary meningeal glioblastoma (GBM) with extensive systemic metastases, along with a review of imaging findings.
2. Case report A 51-year-old Hispanic male presented to our hospital emergency room with complaints of headache and blurred vision for 3 weeks associated with right-sided parasthesias. There were no associated motor, cranial nerve, or cognitive deficits. There was no history of any fever,
Abbreviations: PLA, primary leptomeningeal astrocytoma; GFAP, glial fibrillary acidic protein; GBM, glioblastoma. ☆ Source of grant: none. ☆☆ Presented at meetings: no. ★ Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. ⁎ Corresponding author. Department of Radiology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Tel.: +1 319 400 1511; fax: +1 319 384 8114. E-mail address: [email protected] (G. Bathla). http://dx.doi.org/10.1016/j.clinimag.2015.03.013 0899-7071/© 2015 Elsevier Inc. All rights reserved.
trauma, or drug abuse leading up to the symptoms. Past medical history and family history were noncontributory. Noncontrast computed tomographic (CT) study revealed presence of a mixed-density extraaxial lesion in the left parafalcine region, minimally extending across the midline. There was no apparent overlying bony destruction. Subsequent magnetic resonance imaging (MRI) redemonstrated a mixed solid–cystic extraaxial left parafalcine lesion with extension across the midline and through the overlying bone into the subcutaneous tissue. Short segment superior sagittal sinus involvement was also seen (Fig. 1a–e). The lesion was felt to represent a metastatic lesion versus an aggressive meningioma. CT of the chest, abdomen, and pelvis was however negative for any primary tumor. The lesion was noted to be extraaxial at surgery, and a gross total resection was performed. Histopathology revealed a moderately pleomorphic meningeal neoplasm with superficial cortical invasion (Fig. 2). Perivascular rosetting, primitive gland formation, and vascular invasion were also noted (Figs. 3 and 4). The tumor was positive for vimentin; weakly positive for glial fibrillary acidic protein (GFAP); and negative for TTF1, CK7, CK20, pankeratin, synaptophysin, chromogranin, myogenin, progesterone receptor, MART1, and CD99. Further staining was positive for SOX2, SOX10, and OLIG-2, supporting a glial origin. A final diagnosis of glioblastoma, adenoid variant, was therefore made. The patient was started on temozolamide and radiation therapy but was subsequently admitted about 6 weeks later with complaints of fever and diffuse back pain. MRI revealed extensive vertebral marrow signal abnormality and enhancement (Fig. 5). Additionally, there were multiple enhancing nodules involving the paraspinal muscles (Fig. 6). Subsequent bone biopsy revealed diffuse marrow tumor infiltration, histopathologically similar to the original glioblastoma (Fig. 7). Extensive
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
673
Fig. 1. (a–e) Sagittal precontrast image (a) reveals dural-based lesion in the left parafalcine region with extension through the overlying bone (black arrows) and a small subcutaneous component (white arrowheads). Axial fluid-attenuated inversion recovery image (b) again reveals left parafalcine tumor (long arrow) with a cystic component (arrowheads) and transcalvarial extension (small arrows). The lesion shows few microhemorrhages on susceptibility-weighted image (c) and foci of restricted diffusion on DW image (d). Postcontrast image (e) demonstrates the heterogeneous enhancement and unilocular cystic component.
infectious workup for the fever was negative, and it was eventually attributed to the tumor. During the same admission, the patient also developed acute left eye chemosis and proptosis. MRI revealed metastatic involvement of the extraocular muscles and left lateral orbital wall, not seen on the initial imaging studies (Fig. 8). The patient was also noted to have a chest wall skin nodule, which again proved to be metastatic on cytological examination. Given the overall poor functional status, rapid tumor progression, and thrombocytopenia from ongoing chemoradiation and marrow infiltration, the patient was felt to be a poor candidate for more aggressive therapy. The patient was offered palliative therapy and chose hospice. The patient subsequently died 3 weeks later.
3. Discussion
Fig. 2. Hematoxylin and eosin (H&E) 2× showing meningeal-based tumor (long arrows) with superficial cortical invasion (arrowheads) associated with reactive gliosis in the cortex (short arrows).
Fig. 3. H&E 40 × illustrating tumor arranged in cords and trabeculae with focal gland formation (arrows). The neoplastic cells show moderate pleomorphism with high nuclear/ cytoplasmic ratio, stippled nuclear chromatin, and occasional central nucleoli.
Primary leptomeningeal astrocytomas, by definition, arise within the meninges, without any attachment to the neural tissue or evidence of primary neoplasm elsewhere within the neuraxis [2,5]. They are thought to arise from heterotropic nests of glial tissue within the meninges, originally described by Wolbach [1,2,6,7]. These may be seen in up to 1% of normal population, but have been noted in up to 25% of those with coexisting central nervous system (CNS) malformations, and often occur over medulla oblongata (57%), spinal cord (20%), pons (15%), midbrain (10.5%), cerebellum (8%), or the cerebral cortex (4%) [2,3,7]. Since these nests may contain oligodendrocytes, ependymal cells,
674
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
Fig. 4. H&E 10× showing a large intravascular tumor embolus (arrowheads).
neurons, choroid plexus, or neuroblasts, the eventual tumor histology may be variable or even mixed [8,9]. Patients most commonly present with headache and seizures [1,2,8]. Other manifestations may include blurry vision, diplopia, sensorimotor deficits, altered mental status, or signs of meningeal irritation [1,8]. In our case, the patient presented with headache and visual and hemisensory symptoms for 3 weeks. Histopathologically, the tumor was negative for epithelial, lymphoid, and meningeal markers. Since the tumor only stained weakly for GFAP, there was considerable confusion initially about its cell of origin. Subsequent positive staining for SOX2, SOX10, and OLIG-2 however eventually confirmed its glial origin. This is in contrast to the previously reported cases, all of which were positive for GFAP. Cellular pleomorphism, high mitotic index, and necrosis were all consistent with high-grade glial tumor. Presence of patchy glandular differentiation prompted a final diagnosis of glioblastoma, adenoid variant. Interestingly, this specific subtype has not been previously described with focal PLAs. Another
peculiar feature in our case was extensive lymphovascular invasion, which again has not been previously described with these tumors and was the possible explanation for extensive systemic disease. Morphologically, PLAs have been divided as focal or diffuse based on the extent of involvement [1,2,8,10]. The diffuse form is more common, with about 50 cases reported in the English literature. The focal form however is extremely rare [1]. An anomaly within the current classification however needs to be recognized. It categorizes regional leptomeningeal involvement as ‘focal glioma,’ giving the erroneous impression of a mass-like lesion. We feel that the term ‘focal glioma’ should only be used in case of a solitary mass. Cases presenting with only leptomeningeal involvement should be further defined as localized
Fig. 5. Postcontrast T1-weighted image (T1WI) through the lumbar spine reveals heterogeneous vertebral marrow involvement and ill-defined paraspinal muscle enhancement.
Fig. 7. H&E 20× illustrating hypocellular bone marrow with necrosis (arrows) and metastatic tumor (arrowheads).
Fig. 6. Axial T1WI postcontrast image through L4 level again demonstrates extensive marrow involvement and enhancing metastatic lesions in the paraspinal muscles (black arrows).
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
Fig. 8. Axial T1WI postcontrast image reveals multiple metastatic lesions involving bilateral extraocular muscles along with involvement of the left lateral orbital wall.
or diffuse, based on whether the involvement is regional or extensive, to help describe the disease extent in a more meaningful manner. The cases previously described as focal gliomas by some authors [11–16] more precisely discuss localized meningeal involvement without any distinct mass and do not strictly reflect a focal pathology. A search for intracranial PLA presenting as a focal mass reveals 13 cases in the English literature [1,2,5–10,17]. Some of the tumors previously described as ‘focal gliomas’ more accurately reflect localized leptomeningeal involvement and were not included in the final analysis for reasons explained above. Including the current case, there have been 14 cases of intracranial PLA presenting as a mass lesion (Table 1). These show a wide age range at presentation (33–78 years), with the mean age being 55 years. Both sexes are affected equally (1:1). The tumor is most frequently supratentorial (85.7%), and most (57.1%) occur over cerebral convexities, as previously reported [6]. Of the 13 cases where the laterality was mentioned, 5 were on the left, 6 on the right, and 2 extended across the midline (including our case). A cystic component was present in
675
about 28% of cases and was frequently multilocular. Underlying parenchymal edema was described in 42% of cases. Of the nine cases where CT was done, the lesion was variably described as hypo- to hyperdense on noncontrast images. Calcification was seen in only two cases. Almost all cases showed moderate postcontrast enhancement. Only seven cases had a prior MR study (including ours), with imaging features described in only four of these cases. Tumors were predominantly T1 hypo- and T2 hyperintense and showed prominent heterogeneous enhancement along with a dural tail. In the present case, few punctate microhemorrhages were noted, consistent with GBM. The cystic component was unilocular and showed T1/T2 prolongation. Additionally, the tumor extended through the superior sagittal sinus and overlying parietal bones into the subcutaneous soft tissues. Extension through the overlying bone is very unusual with GBM and has been previously described only once with PLAs [9]. Subsequently, the patient was also found to have extensive marrow tumor infiltration, in addition to the metastatic lesions in the paraspinal muscles. There was no leptomeningeal involvement. The patient was also noted to have orbital wall and extraocular muscle involvement. Review of the existing literature reveals that systemic metastases are extremely rare, even with intraaxial GBM, with a reported incidence of 0.4%–2% and a median time to diagnosis of about 10 months [3,18]. The bones are the most common site of systemic spread (38%) followed by lymph nodes (37%) and lungs (32%) [3]. Within the focal PLA subgroup, a case of solitary bone metastases and another of cervical lymphnodal metastases have been described, although no reports of extensive systemic metastases exist to the best of our knowledge [2,4]. The proposed pathways for metastatic involvement with astrocytomas include venous invasion through sinuses or dural or bony involvement. It is interesting to note that metastatic disease in the absence of any prior intervention is extremely rare, pointing to the protective role played by the blood–brain barrier [18]. In the previously reported cases of bony and cervical nodal metastases, the patient had undergone surgery previously, and one could argue that the metastases were secondary to breach of blood–brain barrier. In our case, although the metastases occurred after surgery, the patient did have venous, dural, and bony involvement at presentation. In addition, the presence of lymphovascular invasion at microscopy would lead one to speculate that the patient likely had microscopic metastatic spread by the time of presentation.
Table 1 Summary of PLA cases in the English literature presenting as focal mass Age/Sex
Pathology
Site
Maximal dimension
CT findings
MRI findings
Baiely, 1936 Abott, 1955 Horoupian, 1979 Shuangshoti, 1984
39/M 43/F 49/F 49/F
Astrocytoma Astrocytoma Mixed glioma Astrocytoma
Left frontoparietal Right hemisphere Left frontoparietal Right suprasellar and parasellar
NA NA 5 cm 5 cm
NA NA NA NA
Sceats, 1986 Kakita, 1992 Opeskin, 1994
53/F 74/F 59/M
Left CP angle Left parietal Inferior tentorium
2 cm 5 cm 4 cm
Wakabayashi, 2002
33/M
Gr-II astrocytoma GBM Gr-II desmoplastic astrocytoma GBM
NA NA Isodense on NCCT, homogeneous PCE Mildly hyperdense on NCCT with homogeneous PCE Homogenous PCE Homogeneous PCE Posterior fossa tumor
Right temporal convexity
6 cm
T1 hypo, T2 NA. PTE +
72/M
Oligodendroglioma
Right frontal
5 cm
Hyperdense solid component with PCE. Cysts and calcification + Nonhomogeneous PCE, cysts +
72/F
GBM
Anterior falx
4 cm
De Tommasi, 2007 Stavrinou, 2010 Kim, 2013
78/F 53/M 45/M
Left frontoparietal Right temporoparietal Right parafalcine
7 cm 4 cm 7 cm
Present case
51/M
Gr-II astrocytoma GBM Gr-III anaplastic oligoastrocytoma GBM, adenoid variant
Hyperdense on NCCT, homogeneous PCE. Calc + Multicystic, heterogeneous PCE NA Isodense on NCCT
Left parafalcine with small component across midline
6 cm
Hypodense on NCCT
NCCT, noncontrast computed tomography; PCE, postcontrast enhancement; PTE, peritumoral edema.
NA NA Not described
T1 iso, T2 hyper, rim enhancement PCE. PTE + T1 hypo/iso, T2 hyper. PTE + Not described Heterogeneous PCE, dural tail. PTE + T1 hypo, T2 hyper. Heterogeneous PCE. PTE + T1 hypo, T2 hyper, heterogeneous PCE. PTE + involvement of sagittal sinus
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4. Conclusion The authors report an extremely rare case of primary leptomeningeal GBM with extensive systemic metastases and a rapidly fatal disease course. A literature review of similar cases and imaging is also presented. Although rare, a leptomeningeal PLA might be considered in cases of an aggressive extraaxial lesion or localized/diffuse leptomeningeal enhancement, especially if underlying extra-CNS primary/common infectious or inflammatory suspects have been excluded. References [1] Kim YG, Kim EH, Kim SH, Chang JH. Solitary primary leptomeningeal glioma: case report. Brain Tumor Res Treat 2013;1(1):36–41. http://dx.doi.org/10. 14791/btrt.2013.1.1.36. [2] Wakabayashi K, Shimura T, Mizutani N, Koide A, Yamagiwa O, Mori F, et al. Primary intracranial solitary leptomeningeal glioma: a report of 3 cases. Clin Neuropathol 2002;21:206–13. [3] Kalokhe G, Grimm SA, Chandler JP, Helenowski I, Rademaker A, Raizer JJ. Metastatic glioblastoma: case presentations and a review of the literature. J Neuro-Oncol 2012; 107(1):21–7. [4] Goldman JE, Schechter R, Horoupian DS, Noto AC. Astrocytoma arising in the leptomeninges. Arch Pathol Lab Med 1981;105:336. [5] Kakita A, Wakabayashi K, Takahashi H, Ohama E, Ikuta F, Tokiguchi S. Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies. Acta Neuropathol 1992;83:538–42. http://dx.doi.org/10.1007/BF00310033. [6] Opeskin K, Anderson RM, Nye DH. Primary meningeal glioma. Pathology 1994;26: 72–4. http://dx.doi.org/10.1080/00313029400169181.
[7] Sceats DJ, Quisling R, Rhoton AL, Ballinger WE, Ryan P. Primary leptomeningeal glioma mimicking an acoustic neuroma: case report with review of the literature. Neurosurgery 1986;19:649–54. http://dx.doi.org/10.1097/00006123198610000-00027. [8] De Tommasi A, Occhiogrosso G, De Tommasi C, Luzzi S, Cimmino A, Ciappetta P. A polycystic variant of a primary intracranial leptomeningeal astrocytoma: case report and literature review. World J Surg Oncol 2007;5:72. http://dx.doi.org/10.1186/ 1477-7819-5-72. [9] Shuangshoti S, Kasantikul V, Suwanwela N, Suwanwela C. Solitary primary intracranial extracerebral glioma. Case report. J Neurosurg 1984;61:777–81. [10] Stavrinou P, Magras I, Stavrinou LC, Zaraboukas T, Polyzoidis KS, Selviaridis P. Primary extracerebral meningeal glioblastoma: clinical and pathological analysis. Cen Eur Neurosurg 2010;71(1):46–9. [11] Sell M, Mitrovics T, Sander BC. Primary nodular meningeal glioma mimicking metastatic tumor of the cerebellum with diffuse infra- and supratentorial leptomeningeal spread. Clin Neuropathol 2000;19:126–30. [12] Cirak B, Caksen H, Ugras S, Unal O. Primary leptomeningeal astrocytoma in a child. Pediatr Int 2000;42:389–91. http://dx.doi.org/10.1046/j.1442-200x. 2000.01237.x. [13] Ng HK, Poon WS. Primary leptomeningeal astrocytoma. Case report. J Neurosurg 1998;88:586–9. [14] Krief O, Monnier L, Cornu P, Foncin JF, Dormont D, Marsault C. MR of isolated leptomeningeal glioma. AJNR 1994;15:1782–4. [15] Bailey OT, Robitaille Y. Primary diffuse leptomeningeal gliomatosis. Can J Neurol Sci 1985;12:278–81. [16] Sumi SM, Leffman H. Primary intracranial leptomeningeal glioma with persistent hypoglycorrhachia. J Neurol Neurosurg Psychiatry 1968;31:190–4. [17] Horoupian DS, Lax F, Suzuki K. Extracerebral leptomeningeal astrocytoma mimicking a meningioma. Arch Pathol Lab Med 1979;103:676–9. [18] Rajagopalan V, El Kamar FG, Thayaparan R, Grossbard ML. Bone marrow metastases from glioblastoma multiforme—a case report and review of the literature. J Neurooncol 2005;72:157–61.
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
Case Reports
Primary leptomeningeal glioblastoma with systemic metastases—case report and review of literature☆,☆☆,★ Girish Bathla a,⁎, Sarika Gupta b, Toshio Moritani a a b
Department of Radiology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA Department of Pathology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
a r t i c l e
i n f o
Article history: Received 5 March 2015 Received in revised form 27 March 2015 Accepted 31 March 2015 Keywords: Glioblastoma Metastases Spine Orbit MRI
a b s t r a c t We present a case of a rare meningeal glioblastoma with extensive systemic metastases, along with a review of the existing literature. The patient presented with headache and visual and sensory symptoms and had a rapidly progressive clinical course despite therapy. The patient went on to develop spinal, orbital, muscular, and cutaneous metastases over a short period. Review of the literature reveals 13 similar previously reported cases, none with a similar presentation. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Primary leptomeningeal astrocytomas (PLAs) are rare glial tumors of meningeal origin that may occur anywhere along the craniospinal axis. More commonly, these present as diffuse meningeal enhancement and mimic metastases or infectious or inflammatory meningitis. The focal form, on the other hand, can mimic a meningioma or a dural metastatic lesion [1]. Systemic metastases are rare, both with intraaxial glial tumors or PLAs [2–4]. We report a case of a primary meningeal glioblastoma (GBM) with extensive systemic metastases, along with a review of imaging findings.
2. Case report A 51-year-old Hispanic male presented to our hospital emergency room with complaints of headache and blurred vision for 3 weeks associated with right-sided parasthesias. There were no associated motor, cranial nerve, or cognitive deficits. There was no history of any fever,
Abbreviations: PLA, primary leptomeningeal astrocytoma; GFAP, glial fibrillary acidic protein; GBM, glioblastoma. ☆ Source of grant: none. ☆☆ Presented at meetings: no. ★ Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. ⁎ Corresponding author. Department of Radiology, 200 Hawkins Drive, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Tel.: +1 319 400 1511; fax: +1 319 384 8114. E-mail address: [email protected] (G. Bathla). http://dx.doi.org/10.1016/j.clinimag.2015.03.013 0899-7071/© 2015 Elsevier Inc. All rights reserved.
trauma, or drug abuse leading up to the symptoms. Past medical history and family history were noncontributory. Noncontrast computed tomographic (CT) study revealed presence of a mixed-density extraaxial lesion in the left parafalcine region, minimally extending across the midline. There was no apparent overlying bony destruction. Subsequent magnetic resonance imaging (MRI) redemonstrated a mixed solid–cystic extraaxial left parafalcine lesion with extension across the midline and through the overlying bone into the subcutaneous tissue. Short segment superior sagittal sinus involvement was also seen (Fig. 1a–e). The lesion was felt to represent a metastatic lesion versus an aggressive meningioma. CT of the chest, abdomen, and pelvis was however negative for any primary tumor. The lesion was noted to be extraaxial at surgery, and a gross total resection was performed. Histopathology revealed a moderately pleomorphic meningeal neoplasm with superficial cortical invasion (Fig. 2). Perivascular rosetting, primitive gland formation, and vascular invasion were also noted (Figs. 3 and 4). The tumor was positive for vimentin; weakly positive for glial fibrillary acidic protein (GFAP); and negative for TTF1, CK7, CK20, pankeratin, synaptophysin, chromogranin, myogenin, progesterone receptor, MART1, and CD99. Further staining was positive for SOX2, SOX10, and OLIG-2, supporting a glial origin. A final diagnosis of glioblastoma, adenoid variant, was therefore made. The patient was started on temozolamide and radiation therapy but was subsequently admitted about 6 weeks later with complaints of fever and diffuse back pain. MRI revealed extensive vertebral marrow signal abnormality and enhancement (Fig. 5). Additionally, there were multiple enhancing nodules involving the paraspinal muscles (Fig. 6). Subsequent bone biopsy revealed diffuse marrow tumor infiltration, histopathologically similar to the original glioblastoma (Fig. 7). Extensive
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
673
Fig. 1. (a–e) Sagittal precontrast image (a) reveals dural-based lesion in the left parafalcine region with extension through the overlying bone (black arrows) and a small subcutaneous component (white arrowheads). Axial fluid-attenuated inversion recovery image (b) again reveals left parafalcine tumor (long arrow) with a cystic component (arrowheads) and transcalvarial extension (small arrows). The lesion shows few microhemorrhages on susceptibility-weighted image (c) and foci of restricted diffusion on DW image (d). Postcontrast image (e) demonstrates the heterogeneous enhancement and unilocular cystic component.
infectious workup for the fever was negative, and it was eventually attributed to the tumor. During the same admission, the patient also developed acute left eye chemosis and proptosis. MRI revealed metastatic involvement of the extraocular muscles and left lateral orbital wall, not seen on the initial imaging studies (Fig. 8). The patient was also noted to have a chest wall skin nodule, which again proved to be metastatic on cytological examination. Given the overall poor functional status, rapid tumor progression, and thrombocytopenia from ongoing chemoradiation and marrow infiltration, the patient was felt to be a poor candidate for more aggressive therapy. The patient was offered palliative therapy and chose hospice. The patient subsequently died 3 weeks later.
3. Discussion
Fig. 2. Hematoxylin and eosin (H&E) 2× showing meningeal-based tumor (long arrows) with superficial cortical invasion (arrowheads) associated with reactive gliosis in the cortex (short arrows).
Fig. 3. H&E 40 × illustrating tumor arranged in cords and trabeculae with focal gland formation (arrows). The neoplastic cells show moderate pleomorphism with high nuclear/ cytoplasmic ratio, stippled nuclear chromatin, and occasional central nucleoli.
Primary leptomeningeal astrocytomas, by definition, arise within the meninges, without any attachment to the neural tissue or evidence of primary neoplasm elsewhere within the neuraxis [2,5]. They are thought to arise from heterotropic nests of glial tissue within the meninges, originally described by Wolbach [1,2,6,7]. These may be seen in up to 1% of normal population, but have been noted in up to 25% of those with coexisting central nervous system (CNS) malformations, and often occur over medulla oblongata (57%), spinal cord (20%), pons (15%), midbrain (10.5%), cerebellum (8%), or the cerebral cortex (4%) [2,3,7]. Since these nests may contain oligodendrocytes, ependymal cells,
674
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
Fig. 4. H&E 10× showing a large intravascular tumor embolus (arrowheads).
neurons, choroid plexus, or neuroblasts, the eventual tumor histology may be variable or even mixed [8,9]. Patients most commonly present with headache and seizures [1,2,8]. Other manifestations may include blurry vision, diplopia, sensorimotor deficits, altered mental status, or signs of meningeal irritation [1,8]. In our case, the patient presented with headache and visual and hemisensory symptoms for 3 weeks. Histopathologically, the tumor was negative for epithelial, lymphoid, and meningeal markers. Since the tumor only stained weakly for GFAP, there was considerable confusion initially about its cell of origin. Subsequent positive staining for SOX2, SOX10, and OLIG-2 however eventually confirmed its glial origin. This is in contrast to the previously reported cases, all of which were positive for GFAP. Cellular pleomorphism, high mitotic index, and necrosis were all consistent with high-grade glial tumor. Presence of patchy glandular differentiation prompted a final diagnosis of glioblastoma, adenoid variant. Interestingly, this specific subtype has not been previously described with focal PLAs. Another
peculiar feature in our case was extensive lymphovascular invasion, which again has not been previously described with these tumors and was the possible explanation for extensive systemic disease. Morphologically, PLAs have been divided as focal or diffuse based on the extent of involvement [1,2,8,10]. The diffuse form is more common, with about 50 cases reported in the English literature. The focal form however is extremely rare [1]. An anomaly within the current classification however needs to be recognized. It categorizes regional leptomeningeal involvement as ‘focal glioma,’ giving the erroneous impression of a mass-like lesion. We feel that the term ‘focal glioma’ should only be used in case of a solitary mass. Cases presenting with only leptomeningeal involvement should be further defined as localized
Fig. 5. Postcontrast T1-weighted image (T1WI) through the lumbar spine reveals heterogeneous vertebral marrow involvement and ill-defined paraspinal muscle enhancement.
Fig. 7. H&E 20× illustrating hypocellular bone marrow with necrosis (arrows) and metastatic tumor (arrowheads).
Fig. 6. Axial T1WI postcontrast image through L4 level again demonstrates extensive marrow involvement and enhancing metastatic lesions in the paraspinal muscles (black arrows).
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
Fig. 8. Axial T1WI postcontrast image reveals multiple metastatic lesions involving bilateral extraocular muscles along with involvement of the left lateral orbital wall.
or diffuse, based on whether the involvement is regional or extensive, to help describe the disease extent in a more meaningful manner. The cases previously described as focal gliomas by some authors [11–16] more precisely discuss localized meningeal involvement without any distinct mass and do not strictly reflect a focal pathology. A search for intracranial PLA presenting as a focal mass reveals 13 cases in the English literature [1,2,5–10,17]. Some of the tumors previously described as ‘focal gliomas’ more accurately reflect localized leptomeningeal involvement and were not included in the final analysis for reasons explained above. Including the current case, there have been 14 cases of intracranial PLA presenting as a mass lesion (Table 1). These show a wide age range at presentation (33–78 years), with the mean age being 55 years. Both sexes are affected equally (1:1). The tumor is most frequently supratentorial (85.7%), and most (57.1%) occur over cerebral convexities, as previously reported [6]. Of the 13 cases where the laterality was mentioned, 5 were on the left, 6 on the right, and 2 extended across the midline (including our case). A cystic component was present in
675
about 28% of cases and was frequently multilocular. Underlying parenchymal edema was described in 42% of cases. Of the nine cases where CT was done, the lesion was variably described as hypo- to hyperdense on noncontrast images. Calcification was seen in only two cases. Almost all cases showed moderate postcontrast enhancement. Only seven cases had a prior MR study (including ours), with imaging features described in only four of these cases. Tumors were predominantly T1 hypo- and T2 hyperintense and showed prominent heterogeneous enhancement along with a dural tail. In the present case, few punctate microhemorrhages were noted, consistent with GBM. The cystic component was unilocular and showed T1/T2 prolongation. Additionally, the tumor extended through the superior sagittal sinus and overlying parietal bones into the subcutaneous soft tissues. Extension through the overlying bone is very unusual with GBM and has been previously described only once with PLAs [9]. Subsequently, the patient was also found to have extensive marrow tumor infiltration, in addition to the metastatic lesions in the paraspinal muscles. There was no leptomeningeal involvement. The patient was also noted to have orbital wall and extraocular muscle involvement. Review of the existing literature reveals that systemic metastases are extremely rare, even with intraaxial GBM, with a reported incidence of 0.4%–2% and a median time to diagnosis of about 10 months [3,18]. The bones are the most common site of systemic spread (38%) followed by lymph nodes (37%) and lungs (32%) [3]. Within the focal PLA subgroup, a case of solitary bone metastases and another of cervical lymphnodal metastases have been described, although no reports of extensive systemic metastases exist to the best of our knowledge [2,4]. The proposed pathways for metastatic involvement with astrocytomas include venous invasion through sinuses or dural or bony involvement. It is interesting to note that metastatic disease in the absence of any prior intervention is extremely rare, pointing to the protective role played by the blood–brain barrier [18]. In the previously reported cases of bony and cervical nodal metastases, the patient had undergone surgery previously, and one could argue that the metastases were secondary to breach of blood–brain barrier. In our case, although the metastases occurred after surgery, the patient did have venous, dural, and bony involvement at presentation. In addition, the presence of lymphovascular invasion at microscopy would lead one to speculate that the patient likely had microscopic metastatic spread by the time of presentation.
Table 1 Summary of PLA cases in the English literature presenting as focal mass Age/Sex
Pathology
Site
Maximal dimension
CT findings
MRI findings
Baiely, 1936 Abott, 1955 Horoupian, 1979 Shuangshoti, 1984
39/M 43/F 49/F 49/F
Astrocytoma Astrocytoma Mixed glioma Astrocytoma
Left frontoparietal Right hemisphere Left frontoparietal Right suprasellar and parasellar
NA NA 5 cm 5 cm
NA NA NA NA
Sceats, 1986 Kakita, 1992 Opeskin, 1994
53/F 74/F 59/M
Left CP angle Left parietal Inferior tentorium
2 cm 5 cm 4 cm
Wakabayashi, 2002
33/M
Gr-II astrocytoma GBM Gr-II desmoplastic astrocytoma GBM
NA NA Isodense on NCCT, homogeneous PCE Mildly hyperdense on NCCT with homogeneous PCE Homogenous PCE Homogeneous PCE Posterior fossa tumor
Right temporal convexity
6 cm
T1 hypo, T2 NA. PTE +
72/M
Oligodendroglioma
Right frontal
5 cm
Hyperdense solid component with PCE. Cysts and calcification + Nonhomogeneous PCE, cysts +
72/F
GBM
Anterior falx
4 cm
De Tommasi, 2007 Stavrinou, 2010 Kim, 2013
78/F 53/M 45/M
Left frontoparietal Right temporoparietal Right parafalcine
7 cm 4 cm 7 cm
Present case
51/M
Gr-II astrocytoma GBM Gr-III anaplastic oligoastrocytoma GBM, adenoid variant
Hyperdense on NCCT, homogeneous PCE. Calc + Multicystic, heterogeneous PCE NA Isodense on NCCT
Left parafalcine with small component across midline
6 cm
Hypodense on NCCT
NCCT, noncontrast computed tomography; PCE, postcontrast enhancement; PTE, peritumoral edema.
NA NA Not described
T1 iso, T2 hyper, rim enhancement PCE. PTE + T1 hypo/iso, T2 hyper. PTE + Not described Heterogeneous PCE, dural tail. PTE + T1 hypo, T2 hyper. Heterogeneous PCE. PTE + T1 hypo, T2 hyper, heterogeneous PCE. PTE + involvement of sagittal sinus
676
G. Bathla et al. / Clinical Imaging 39 (2015) 672–676
4. Conclusion The authors report an extremely rare case of primary leptomeningeal GBM with extensive systemic metastases and a rapidly fatal disease course. A literature review of similar cases and imaging is also presented. Although rare, a leptomeningeal PLA might be considered in cases of an aggressive extraaxial lesion or localized/diffuse leptomeningeal enhancement, especially if underlying extra-CNS primary/common infectious or inflammatory suspects have been excluded. References [1] Kim YG, Kim EH, Kim SH, Chang JH. Solitary primary leptomeningeal glioma: case report. Brain Tumor Res Treat 2013;1(1):36–41. http://dx.doi.org/10. 14791/btrt.2013.1.1.36. [2] Wakabayashi K, Shimura T, Mizutani N, Koide A, Yamagiwa O, Mori F, et al. Primary intracranial solitary leptomeningeal glioma: a report of 3 cases. Clin Neuropathol 2002;21:206–13. [3] Kalokhe G, Grimm SA, Chandler JP, Helenowski I, Rademaker A, Raizer JJ. Metastatic glioblastoma: case presentations and a review of the literature. J Neuro-Oncol 2012; 107(1):21–7. [4] Goldman JE, Schechter R, Horoupian DS, Noto AC. Astrocytoma arising in the leptomeninges. Arch Pathol Lab Med 1981;105:336. [5] Kakita A, Wakabayashi K, Takahashi H, Ohama E, Ikuta F, Tokiguchi S. Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies. Acta Neuropathol 1992;83:538–42. http://dx.doi.org/10.1007/BF00310033. [6] Opeskin K, Anderson RM, Nye DH. Primary meningeal glioma. Pathology 1994;26: 72–4. http://dx.doi.org/10.1080/00313029400169181.
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