- Email: [email protected]
Solitary intraventricular Hodgkin lymphoma post-transplant lymphoproliferative disease (HL-PTLD): Case report
Journal of Clinical Neuroscience 69 (2019) 269–272
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Solitary intraventricular Hodgkin lymphoma post-transplant lymphoproliferative disease (HL-PTLD): Case report Amit Azriel a,b,⇑,1,2, James E. Towner a,c,2, Frank Gaillard d,e, Georgia Box d, TeWhiti Rogers f, Andrew Morokoff a,b a
Department of Neurosurgery, The Royal Melbourne Hospital, Victoria, Australia Department of Surgery, The University of Melbourne, Victoria, Australia Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA d Department of Radiology, The Royal Melbourne Hospital, Parkville, Victoria, Australia e Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Australia f Department of Pathology, The Royal Melbourne Hospital, Victoria, Australia b c
a r t i c l e
i n f o
Article history: Received 10 June 2019 Accepted 6 August 2019
Keywords: Hodgkin lymphoma PTLD CNS Intraventricular tumors
a b s t r a c t Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Immunosuppressed states, including iatrogenic immunosuppression following organ transplantation, are the most significant risk factors for developing primary CNS lymphoma (PCNSL). Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation. PTLD is usually a systemic disease with occasional CNS involvement. The incidence of CNS involvement in PTLD is low, and the majority of these cases tend to be PCNSL. Hodgkin lymphoma PTLD (HL-PTLD) constitutes only a very small percentage of PTLD. We report a rare case of a primary intraventricular CNS classical HL-PTLD in a male patient, 18 years following renal transplantation. The location allowed for safe neurosurgical intervention which resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Reported average rates of secondary CNS involvement among non-Hodgkin lymphoma (NHL) patients are 3–27%, depending on the histologic subtype [1]. Primary CNS lymphoma (PCNSL) is a rare subtype of NHL comprising 2.2% of all CNS tumors [2]. Although the majority of PCNSL are sporadic, with incidence increasing with age, immunosuppressed states, including human immunodeficiency virus infection or iatrogenic immunosuppression following organ transplantation, are the most significant identified risk factors [3,4]. Hodgkin lymphoma (HL) involving the CNS is an even rarer entity than either primary and secondary CNS lymphoma, with a rate of 0.2–0.5% of HL cases [5]. Primary HL of the CNS is more ⇑ Corresponding author at: Department of Neurosurgery, The Royal Melbourne Hospital, City Campus, Grattan Street, Parkville, Victoria 3050, Australia. E-mail address: [email protected] (A. Azriel). 1 Present address: Department of Neurosurgery, Soroka University Medical Center, POB 151, Beer-Sheva, Israel. 2 Amit Azriel and James E Towner contributed equally to this paper.
uncommon yet, with only a few cases previously described in the literature [6]. Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation (SOT) [7]. PTLD is usually a systemic disease with occasional CNS involvement. Intraventricular brain tumors are rare lesions that make up 0.8–1.6% of all intracranial tumors and include tumors involving the septum pellucidum [8,9]. We report an uncommon case of a primary intraventricular CNS classical HL PTLD. 2. Case summary We report a 49-year-old man with a past medical history of renal transplantation on the background of focal segmental glomerulosclerosis 18 years prior to his presentation. His chronic immunosuppression regimen consisted of prednisolone, cyclosporine and mycophenolate mofetil (MMF). The patient initially presented following two weeks of progressively worsening headaches associated with nausea and declining visual acuity. Brain MRI scan demonstrated an isolated intraventricular, vividly enhancing lesion originating in the septum pellucidum with resul-
270
Case Reports / Journal of Clinical Neuroscience 69 (2019) 269–272
Fig. 1. Magnetic Resonance Imaging: FLAIR (A) and T2 (B) showing intermediately low intensity lesion centered on the septum pellucidum. Vivid peripheral, nodular contrast enhancement demonstrated on T1 non-contrast (C) and T1 post gadolinium (D) with high signal on DWI (E) and low ADC values (F), consistent with high cellularity. The tumor showed mildly elevated CBV (G) and MR spectroscopy demonstrated mild elevation of choline and a lipid/lactate peak (H). The lesion had no calcification or hemorrhage. The lateral ventricles are enlarged with transependymal edema consistent with obstruction at the level of the foramen of Munro.
3. Discussion
Fig. 2. Intra-operative photo: right-sided interhemispheric trans-callosal approach. The right lateral ventricle was entered and a septum pellucidum based solid tumor was exposed (arrow).
tant obstructive hydrocephalus (Fig. 1). An uncomplicated interhemispheric transcallosal approach was undertaken (Fig. 2), with subtotal resection of the tumor and subsequent resolution of the increased intracerebral pressure symptoms. Due to short-term memory deficits, the patient was referred for cognitive rehabilitation. The histopathological specimen revealed Reed-Sternberg cells. Immunohistochemical stains were positive for CD20 and CD30, weakly positive for CD15, and positive for Epstein-Barr virus (EBV) encoded RNA chromogenic in-situ hybridization, compatible with a diagnosis of classical Hodgkin lymphoma occurring in the setting of previous SOT (Fig. 3). PET-CT scan showed no extracranial disease and bone marrow aspiration was negative. A chemotherapy regimen of rituximab, methotrexate, procarbazine, vincristine was commenced.
PTLD is a lymphoid proliferation or lymphoma that develops as a consequence of immunosuppression in a transplant recipient, affecting an estimated 1.27–2.12% of transplant patients [10,11]. The incidence of CNS involvement in PTLD is low, with reported rates of 4–15% in large retrospective cohort studies [10–12]. Of the cases of PTLD with CNS involvement, the majority tend to be PCNSL [10,13]. The majority of PTLD, and nearly all CNS PTLD, are a result of Epstein–Barr virus (EBV) infections of B-cells coupled with inadequate T-cell response due to immunosuppression [11,12,14]. HL is a curable malignancy, also with a putative association with Epstein-Barr virus [15]. HL-PTLD constitutes only a very small percentage of PTLDs with a reported frequency of 3–4%, and no reported cases of CNS HL- PTLD [10,11,16]. A retrospective, single-institution study of 6422 transplant patients found the 20-year incidence of PTLD to be 1.7% in SOT [11]. The median time from transplant to PTLD is 4–5.3 years for SOT patients, with cases reported >20 years from transplant [11,13]. Our patient’s presentation 18 years post- transplant is later than the average presentation, but certainly not unheard of. Having a renal SOT has the lowest association of SOT with PTLD, but a history of renal SOT has the highest associated risk of CNS involvement [10–12]. The use of MMF has been found to be associated with developing CNS PTLD. Calcineurin inhibitors such as cyclosporine have conversely been found protective, though not to a strong enough degree to counteract the risk associated with MMF [12]. Patients such as ours, on a regimen of MMF and a calcineurin inhibitor, have 18-fold higher odds of CNS PTLD compared to patients on a calcineurin inhibitor alone [12]. CNS lymphoma occurs 38% of the time in the cerebral hemisphere, which is the most common location [17]. The intraventricular location is more uncommon, representing only 12% of cases [17].
Case Reports / Journal of Clinical Neuroscience 69 (2019) 269–272
(a)
(b)
(c)
(d)
271
Fig. 3. Histopathologic sections: high power field with hematoxylin and eosin (H&E) stain showing dense population of mixed lymphoid cells including scattered large atypical cells with abundant clear cytoplasm (a). Large atypical lymphoid cells with binucleation and prominent nucleoli (Hodgkin cells – arrow) are demonstrated in high power field (b). CD30 positive (c) and EBER-CISH positive Hodgkin cells (d) are also showed.
Traditionally therapy has focused on reduction of immunosuppression as the mainstay of treatment [4]. Various chemotherapy regimens have been utilized, however Rituximab-based therapy has been associated with lower mortality rates [13]. Surgical resection remains controversial, with historical recommendations against it, but emerging evidence that it may be useful to perform a maximal safe resection in order to immediately relieve symptoms from tumor mass effect [18]. Other benefits of tumor resection include more pathologic specimen, faster steroid taper, and theoretical elimination of drug-resistant tumor clones [18]. Reported mortality rates associated with PTLD have historically been high, ranging from 50 to 70% [13]. CNS involvement has been found to be a negative prognostic factor in many studies [13,19]. 3Year progression free survival (PFS) is 57–59% and overall survival (OS) is 49–62% [10,13]. When comparing therapies with Rituximab versus those without, the PFS is 70% and OS 73% compared with 21% and 33%, respectively [13]. 4. Conclusion This case illustrates a very rare CNS variation of a PTLD. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD, are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximabbased chemotherapy regimen.
Disclosure The authors have nothing to disclose. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.08.053. References [1] Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Secondary central nervous system lymphoma. Int J Hematol 2006;84:128–35. [2] Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 2012;14(Suppl 5):v1–v49. [3] Phillips EH, Fox CP, Cwynarski K. Primary CNS lymphoma. Curr Hematol Malig Rep 2014;9:243–53. [4] Rubenstein JL, Gupta NK, Mannis GN, Lamarre AK, Treseler P. How I treat CNS lymphomas. Blood 2013;122:2318–30. [5] Gerstner ER, Abrey LE, Schiff D, Ferreri AJ, Lister A, Montoto S, et al. CNS Hodgkin lymphoma. Blood 2008;112:1658–61. [6] Kresak JL, Nguyen J, Wong K, Davis R. Primary Hodgkin lymphoma of the central nervous system: two case reports and review of the literature. Neuropathology 2013;33:658–62. [7] DeStefano CB, Desai SH, Shenoy AG, Catlett JP. Management of post-transplant lymphoproliferative disorders. Br J Haematol 2018. [8] Agarwal A, Kanekar S. Intraventricular Tumors. Semin Ultrasound CT MR 2016;37:150–8. [9] Schroeder HW. Intraventricular tumors. World Neurosurg 2013;79:S17.e5-9. [10] Dierickx D, Tousseyn T, Sagaert X, Fieuws S, Wlodarska I, Morscio J, et al. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative
272
Case Reports / Journal of Clinical Neuroscience 69 (2019) 272–276
[11]
[12]
[13]
[14]
disorder: incidence, clinicopathological characteristics and prognostic factors. Leuk Lymphoma 2013;54:2433–40. Romero S, Montoro J, Guinot M, Almenar L, Andreu R, Balaguer A, et al. Posttransplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation. Leuk Lymphoma 2018;1–9:1–9. Crane GM, Powell H, Kostadinov R, Rocafort PT, Rifkin DE, Burger PC, et al. Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage. Oncotarget 2015;6:33849–66. Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, et al. Multicenter analysis of 80 solid organ transplantation recipients with posttransplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era. J Clin Oncol 2010;28:1038–46. Krishnamurthy S, Hassan A, Frater JL, Kreisel FH, Paessler ME. Pathologic and clinical features of Hodgkin lymphoma—like posttransplant lymphoproliferative disease. Int J Surg Pathol 2010;18:278–85.
[15] Gobbi PG, Ferreri AJ, Ponzoni M, Levis A. Hodgkin lymphoma. Crit Rev Oncol Hematol 2013;85:216–37. [16] Ranganathan S, Webber S, Ahuja S, Jaffe R. Hodgkin-like post-transplant lymphoproliferative disorder in children: does it differ from post-transplant Hodgkin lymphoma? Pediatr Dev Pathol 2004;7:348–60. [17] Kuker W, Nagele T, Korfel A, Heckl S, Thiel E, Bamberg M, et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005;72:169–77. [18] Carnevale J, Rubenstein JL. The challenge of primary central nervous system lymphoma. Hematol Oncol Clin North Am 2016;30:1293–316. [19] Leblond V, Dhedin N, Mamzer Bruneel MF, Choquet S, Hermine O, Porcher R, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol 2001;19:772–8.
https://doi.org/10.1016/j.jocn.2019.08.053
Rare case of double migration of thoracic intradural schwannoma Krishna Tallapragada a,⇑, Lana Nguyen a, Indika Liyanage a, Mark Sheridan a,b a b
Department of Neurosurgery, Liverpool Hospital, Sydney, NSW, Australia University of NSW, Sydney, NSW, Australia
a r t i c l e
i n f o
Article history: Received 27 July 2019 Accepted 5 August 2019
:
a b s t r a c t Mobile or migratory intradural extramedullary schwannoma have been reported many times in the lumbar levels, however only twice in cervical spine and six times in thoracic spine. Double migration was reported only once. The exact cause of the migration of a schwannoma arising from the nerve sheath of a spinal nerve root is unclear and especially mysterious in cervical and thoracic spine. We report a 49 year old male who presented with multiple sclerosis confirmed on brain MRI and CSF showing oligoclonal bands, with concomitant spinal myelopathy from a thoracic intradural extramedullary lesion. Serial MRIs showed rostral migration of lesion initially from T10 level to T6 and then caudally to T9 level on day of surgery. Intra operatively it was mobile with respirations and disconnected from any neural or vascular attachments. Histopathology confirmed a benign schwannoma with areas of necrosis. This is the rare occurrence of double migration of thoracic intradural schwannoma with possibility of tumor disconnection due to high dose steroid therapy for multiple sclerosis. Ó 2019 Elsevier Ltd. All rights reserved.
1. Background Mobile or migratory intradural spinal schwannomas are very rare, with only 27 individual case reports in literature to date [1]. Other spinal tumors known to migrate are myxopapillary ependymomas and neurenteric cysts [2]. Majority of migrating spinal schwannoma are located in the lumbar or thoracolumbar junction with two reports at cervical spine and six previous reports in the thoracic spine [1,2]. The occurrence of double migration was only reported once before [3]. We report below a 49 year old man with concomitant diagnoses of multiple sclerosis and double migration of thoracic intradural schwannomae.
2. Case A 49 year old male initially presented with acute (2d) left eye monocular vision loss and subacute (2w) gait disturbance. He was of Chinese background, non-smoker, previously employed as a baker. His medical hx included type 2 insulin dependent diabetes with peripheral neuropathy, hypertension, previous hep B infection and left calf schwannoma resection 2 months prior. Neurological examination showed normal upper and lower limb motor ⇑ Corresponding author. E-mail address: [email protected] (K. Tallapragada).
power to all myotomes with no gross sensory deficit. No bowel or bladder dysfunction. Generalised increased reflexes to both upper and lower limbs with positive Babinski reflex bilaterally. Ophthalmology exam showed visual acuity of 6/9 Right eye and 6/60 left eye with marcus gunn pupil. Dilated fundoscopy revealed bilateral optic nerve swelling, severe on left side. Lumbar puncture showed opening pressure of 12 with elevated protein (5.57 g/L) and oligoclonal bands in CSF. MRI brain showed several T2, FLAIR subcortical and periventricular white matter lesions consistent with demyelinating plaques. MRI whole spine demonstrated an incidental intradural extramedullary lesion at T10 (Fig. 1A). The lesion measured 1 1.1 1.7 cm, left anterolateral to the spinal cord at the level of T9/10 disc to mid vertebral body of T10. There was severe cord compression but no signal change at the level of the lesion. Primary diagnosis was optic neuritis and multiple sclerosis needing urgent treatment with intravenous methylprednisolone. The thoracic spinal lesion was radiologically consistent with a spinal schwannoma. Considering there was no cord signal change at the level of the lesion, he was deemed asymptomatic from this lesion and surgery was deferred until improvement from MS. After completing 3 day intravenous methylprednisolone regimen, the patient had rebound deterioration in vision with worsening bilateral optic disc swelling with new retinal hemorrhage and was commenced on plasma exchange with 5 treatments. This was complicated further by a central line related sepsis.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case Reports
Solitary intraventricular Hodgkin lymphoma post-transplant lymphoproliferative disease (HL-PTLD): Case report Amit Azriel a,b,⇑,1,2, James E. Towner a,c,2, Frank Gaillard d,e, Georgia Box d, TeWhiti Rogers f, Andrew Morokoff a,b a
Department of Neurosurgery, The Royal Melbourne Hospital, Victoria, Australia Department of Surgery, The University of Melbourne, Victoria, Australia Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA d Department of Radiology, The Royal Melbourne Hospital, Parkville, Victoria, Australia e Faculty of Medicine, Dentistry, and Health Sciences, The University of Melbourne, Australia f Department of Pathology, The Royal Melbourne Hospital, Victoria, Australia b c
a r t i c l e
i n f o
Article history: Received 10 June 2019 Accepted 6 August 2019
Keywords: Hodgkin lymphoma PTLD CNS Intraventricular tumors
a b s t r a c t Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Immunosuppressed states, including iatrogenic immunosuppression following organ transplantation, are the most significant risk factors for developing primary CNS lymphoma (PCNSL). Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation. PTLD is usually a systemic disease with occasional CNS involvement. The incidence of CNS involvement in PTLD is low, and the majority of these cases tend to be PCNSL. Hodgkin lymphoma PTLD (HL-PTLD) constitutes only a very small percentage of PTLD. We report a rare case of a primary intraventricular CNS classical HL-PTLD in a male patient, 18 years following renal transplantation. The location allowed for safe neurosurgical intervention which resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximab-based chemotherapy regimen. Ó 2019 Elsevier Ltd. All rights reserved.
1. Introduction Lymphomas affecting the central nervous system (CNS), both primarily and secondarily, are uncommon malignancies. Reported average rates of secondary CNS involvement among non-Hodgkin lymphoma (NHL) patients are 3–27%, depending on the histologic subtype [1]. Primary CNS lymphoma (PCNSL) is a rare subtype of NHL comprising 2.2% of all CNS tumors [2]. Although the majority of PCNSL are sporadic, with incidence increasing with age, immunosuppressed states, including human immunodeficiency virus infection or iatrogenic immunosuppression following organ transplantation, are the most significant identified risk factors [3,4]. Hodgkin lymphoma (HL) involving the CNS is an even rarer entity than either primary and secondary CNS lymphoma, with a rate of 0.2–0.5% of HL cases [5]. Primary HL of the CNS is more ⇑ Corresponding author at: Department of Neurosurgery, The Royal Melbourne Hospital, City Campus, Grattan Street, Parkville, Victoria 3050, Australia. E-mail address: [email protected] (A. Azriel). 1 Present address: Department of Neurosurgery, Soroka University Medical Center, POB 151, Beer-Sheva, Israel. 2 Amit Azriel and James E Towner contributed equally to this paper.
uncommon yet, with only a few cases previously described in the literature [6]. Post-transplant lymphoproliferative disease (PTLD) is a well described complication following bone marrow or solid organ transplantation (SOT) [7]. PTLD is usually a systemic disease with occasional CNS involvement. Intraventricular brain tumors are rare lesions that make up 0.8–1.6% of all intracranial tumors and include tumors involving the septum pellucidum [8,9]. We report an uncommon case of a primary intraventricular CNS classical HL PTLD. 2. Case summary We report a 49-year-old man with a past medical history of renal transplantation on the background of focal segmental glomerulosclerosis 18 years prior to his presentation. His chronic immunosuppression regimen consisted of prednisolone, cyclosporine and mycophenolate mofetil (MMF). The patient initially presented following two weeks of progressively worsening headaches associated with nausea and declining visual acuity. Brain MRI scan demonstrated an isolated intraventricular, vividly enhancing lesion originating in the septum pellucidum with resul-
270
Case Reports / Journal of Clinical Neuroscience 69 (2019) 269–272
Fig. 1. Magnetic Resonance Imaging: FLAIR (A) and T2 (B) showing intermediately low intensity lesion centered on the septum pellucidum. Vivid peripheral, nodular contrast enhancement demonstrated on T1 non-contrast (C) and T1 post gadolinium (D) with high signal on DWI (E) and low ADC values (F), consistent with high cellularity. The tumor showed mildly elevated CBV (G) and MR spectroscopy demonstrated mild elevation of choline and a lipid/lactate peak (H). The lesion had no calcification or hemorrhage. The lateral ventricles are enlarged with transependymal edema consistent with obstruction at the level of the foramen of Munro.
3. Discussion
Fig. 2. Intra-operative photo: right-sided interhemispheric trans-callosal approach. The right lateral ventricle was entered and a septum pellucidum based solid tumor was exposed (arrow).
tant obstructive hydrocephalus (Fig. 1). An uncomplicated interhemispheric transcallosal approach was undertaken (Fig. 2), with subtotal resection of the tumor and subsequent resolution of the increased intracerebral pressure symptoms. Due to short-term memory deficits, the patient was referred for cognitive rehabilitation. The histopathological specimen revealed Reed-Sternberg cells. Immunohistochemical stains were positive for CD20 and CD30, weakly positive for CD15, and positive for Epstein-Barr virus (EBV) encoded RNA chromogenic in-situ hybridization, compatible with a diagnosis of classical Hodgkin lymphoma occurring in the setting of previous SOT (Fig. 3). PET-CT scan showed no extracranial disease and bone marrow aspiration was negative. A chemotherapy regimen of rituximab, methotrexate, procarbazine, vincristine was commenced.
PTLD is a lymphoid proliferation or lymphoma that develops as a consequence of immunosuppression in a transplant recipient, affecting an estimated 1.27–2.12% of transplant patients [10,11]. The incidence of CNS involvement in PTLD is low, with reported rates of 4–15% in large retrospective cohort studies [10–12]. Of the cases of PTLD with CNS involvement, the majority tend to be PCNSL [10,13]. The majority of PTLD, and nearly all CNS PTLD, are a result of Epstein–Barr virus (EBV) infections of B-cells coupled with inadequate T-cell response due to immunosuppression [11,12,14]. HL is a curable malignancy, also with a putative association with Epstein-Barr virus [15]. HL-PTLD constitutes only a very small percentage of PTLDs with a reported frequency of 3–4%, and no reported cases of CNS HL- PTLD [10,11,16]. A retrospective, single-institution study of 6422 transplant patients found the 20-year incidence of PTLD to be 1.7% in SOT [11]. The median time from transplant to PTLD is 4–5.3 years for SOT patients, with cases reported >20 years from transplant [11,13]. Our patient’s presentation 18 years post- transplant is later than the average presentation, but certainly not unheard of. Having a renal SOT has the lowest association of SOT with PTLD, but a history of renal SOT has the highest associated risk of CNS involvement [10–12]. The use of MMF has been found to be associated with developing CNS PTLD. Calcineurin inhibitors such as cyclosporine have conversely been found protective, though not to a strong enough degree to counteract the risk associated with MMF [12]. Patients such as ours, on a regimen of MMF and a calcineurin inhibitor, have 18-fold higher odds of CNS PTLD compared to patients on a calcineurin inhibitor alone [12]. CNS lymphoma occurs 38% of the time in the cerebral hemisphere, which is the most common location [17]. The intraventricular location is more uncommon, representing only 12% of cases [17].
Case Reports / Journal of Clinical Neuroscience 69 (2019) 269–272
(a)
(b)
(c)
(d)
271
Fig. 3. Histopathologic sections: high power field with hematoxylin and eosin (H&E) stain showing dense population of mixed lymphoid cells including scattered large atypical cells with abundant clear cytoplasm (a). Large atypical lymphoid cells with binucleation and prominent nucleoli (Hodgkin cells – arrow) are demonstrated in high power field (b). CD30 positive (c) and EBER-CISH positive Hodgkin cells (d) are also showed.
Traditionally therapy has focused on reduction of immunosuppression as the mainstay of treatment [4]. Various chemotherapy regimens have been utilized, however Rituximab-based therapy has been associated with lower mortality rates [13]. Surgical resection remains controversial, with historical recommendations against it, but emerging evidence that it may be useful to perform a maximal safe resection in order to immediately relieve symptoms from tumor mass effect [18]. Other benefits of tumor resection include more pathologic specimen, faster steroid taper, and theoretical elimination of drug-resistant tumor clones [18]. Reported mortality rates associated with PTLD have historically been high, ranging from 50 to 70% [13]. CNS involvement has been found to be a negative prognostic factor in many studies [13,19]. 3Year progression free survival (PFS) is 57–59% and overall survival (OS) is 49–62% [10,13]. When comparing therapies with Rituximab versus those without, the PFS is 70% and OS 73% compared with 21% and 33%, respectively [13]. 4. Conclusion This case illustrates a very rare CNS variation of a PTLD. Both the ventricular location of the PTLD and Hodgkin Lymphoma PTLD, are themselves individually quite rare and have not previously been reported together. The unique location allowed safe neurosurgical intervention which quickly resolved the symptom of elevated intracranial pressure and allowed for induction of a Rituximabbased chemotherapy regimen.
Disclosure The authors have nothing to disclose. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2019.08.053. References [1] Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Secondary central nervous system lymphoma. Int J Hematol 2006;84:128–35. [2] Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 2012;14(Suppl 5):v1–v49. [3] Phillips EH, Fox CP, Cwynarski K. Primary CNS lymphoma. Curr Hematol Malig Rep 2014;9:243–53. [4] Rubenstein JL, Gupta NK, Mannis GN, Lamarre AK, Treseler P. How I treat CNS lymphomas. Blood 2013;122:2318–30. [5] Gerstner ER, Abrey LE, Schiff D, Ferreri AJ, Lister A, Montoto S, et al. CNS Hodgkin lymphoma. Blood 2008;112:1658–61. [6] Kresak JL, Nguyen J, Wong K, Davis R. Primary Hodgkin lymphoma of the central nervous system: two case reports and review of the literature. Neuropathology 2013;33:658–62. [7] DeStefano CB, Desai SH, Shenoy AG, Catlett JP. Management of post-transplant lymphoproliferative disorders. Br J Haematol 2018. [8] Agarwal A, Kanekar S. Intraventricular Tumors. Semin Ultrasound CT MR 2016;37:150–8. [9] Schroeder HW. Intraventricular tumors. World Neurosurg 2013;79:S17.e5-9. [10] Dierickx D, Tousseyn T, Sagaert X, Fieuws S, Wlodarska I, Morscio J, et al. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative
272
Case Reports / Journal of Clinical Neuroscience 69 (2019) 272–276
[11]
[12]
[13]
[14]
disorder: incidence, clinicopathological characteristics and prognostic factors. Leuk Lymphoma 2013;54:2433–40. Romero S, Montoro J, Guinot M, Almenar L, Andreu R, Balaguer A, et al. Posttransplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation. Leuk Lymphoma 2018;1–9:1–9. Crane GM, Powell H, Kostadinov R, Rocafort PT, Rifkin DE, Burger PC, et al. Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage. Oncotarget 2015;6:33849–66. Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, et al. Multicenter analysis of 80 solid organ transplantation recipients with posttransplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era. J Clin Oncol 2010;28:1038–46. Krishnamurthy S, Hassan A, Frater JL, Kreisel FH, Paessler ME. Pathologic and clinical features of Hodgkin lymphoma—like posttransplant lymphoproliferative disease. Int J Surg Pathol 2010;18:278–85.
[15] Gobbi PG, Ferreri AJ, Ponzoni M, Levis A. Hodgkin lymphoma. Crit Rev Oncol Hematol 2013;85:216–37. [16] Ranganathan S, Webber S, Ahuja S, Jaffe R. Hodgkin-like post-transplant lymphoproliferative disorder in children: does it differ from post-transplant Hodgkin lymphoma? Pediatr Dev Pathol 2004;7:348–60. [17] Kuker W, Nagele T, Korfel A, Heckl S, Thiel E, Bamberg M, et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005;72:169–77. [18] Carnevale J, Rubenstein JL. The challenge of primary central nervous system lymphoma. Hematol Oncol Clin North Am 2016;30:1293–316. [19] Leblond V, Dhedin N, Mamzer Bruneel MF, Choquet S, Hermine O, Porcher R, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol 2001;19:772–8.
https://doi.org/10.1016/j.jocn.2019.08.053
Rare case of double migration of thoracic intradural schwannoma Krishna Tallapragada a,⇑, Lana Nguyen a, Indika Liyanage a, Mark Sheridan a,b a b
Department of Neurosurgery, Liverpool Hospital, Sydney, NSW, Australia University of NSW, Sydney, NSW, Australia
a r t i c l e
i n f o
Article history: Received 27 July 2019 Accepted 5 August 2019
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a b s t r a c t Mobile or migratory intradural extramedullary schwannoma have been reported many times in the lumbar levels, however only twice in cervical spine and six times in thoracic spine. Double migration was reported only once. The exact cause of the migration of a schwannoma arising from the nerve sheath of a spinal nerve root is unclear and especially mysterious in cervical and thoracic spine. We report a 49 year old male who presented with multiple sclerosis confirmed on brain MRI and CSF showing oligoclonal bands, with concomitant spinal myelopathy from a thoracic intradural extramedullary lesion. Serial MRIs showed rostral migration of lesion initially from T10 level to T6 and then caudally to T9 level on day of surgery. Intra operatively it was mobile with respirations and disconnected from any neural or vascular attachments. Histopathology confirmed a benign schwannoma with areas of necrosis. This is the rare occurrence of double migration of thoracic intradural schwannoma with possibility of tumor disconnection due to high dose steroid therapy for multiple sclerosis. Ó 2019 Elsevier Ltd. All rights reserved.
1. Background Mobile or migratory intradural spinal schwannomas are very rare, with only 27 individual case reports in literature to date [1]. Other spinal tumors known to migrate are myxopapillary ependymomas and neurenteric cysts [2]. Majority of migrating spinal schwannoma are located in the lumbar or thoracolumbar junction with two reports at cervical spine and six previous reports in the thoracic spine [1,2]. The occurrence of double migration was only reported once before [3]. We report below a 49 year old man with concomitant diagnoses of multiple sclerosis and double migration of thoracic intradural schwannomae.
2. Case A 49 year old male initially presented with acute (2d) left eye monocular vision loss and subacute (2w) gait disturbance. He was of Chinese background, non-smoker, previously employed as a baker. His medical hx included type 2 insulin dependent diabetes with peripheral neuropathy, hypertension, previous hep B infection and left calf schwannoma resection 2 months prior. Neurological examination showed normal upper and lower limb motor ⇑ Corresponding author. E-mail address: [email protected] (K. Tallapragada).
power to all myotomes with no gross sensory deficit. No bowel or bladder dysfunction. Generalised increased reflexes to both upper and lower limbs with positive Babinski reflex bilaterally. Ophthalmology exam showed visual acuity of 6/9 Right eye and 6/60 left eye with marcus gunn pupil. Dilated fundoscopy revealed bilateral optic nerve swelling, severe on left side. Lumbar puncture showed opening pressure of 12 with elevated protein (5.57 g/L) and oligoclonal bands in CSF. MRI brain showed several T2, FLAIR subcortical and periventricular white matter lesions consistent with demyelinating plaques. MRI whole spine demonstrated an incidental intradural extramedullary lesion at T10 (Fig. 1A). The lesion measured 1 1.1 1.7 cm, left anterolateral to the spinal cord at the level of T9/10 disc to mid vertebral body of T10. There was severe cord compression but no signal change at the level of the lesion. Primary diagnosis was optic neuritis and multiple sclerosis needing urgent treatment with intravenous methylprednisolone. The thoracic spinal lesion was radiologically consistent with a spinal schwannoma. Considering there was no cord signal change at the level of the lesion, he was deemed asymptomatic from this lesion and surgery was deferred until improvement from MS. After completing 3 day intravenous methylprednisolone regimen, the patient had rebound deterioration in vision with worsening bilateral optic disc swelling with new retinal hemorrhage and was commenced on plasma exchange with 5 treatments. This was complicated further by a central line related sepsis.