1Division of Oncology, Hanoi Medical College, Hanoi, Vietnam; 2Division of Head and Neck Radiation Oncology, Vietnam Nationwide Most cancers Hospital, Hanoi, Vietnam; 3Middle of Pathology and Molecular Biology, Vietnam Nationwide Most cancers Hospital, Hanoi, Vietnam
Correspondence: Dang Nguyen Van
Division of Oncology, Hanoi Medical College, 01 Ton That Tung Road, Dong Da District, Hanoi, 10000, Vietnam
Tel +84 94 2727 899
E-mail [email protected]; [email protected]
Background: Major central nervous system (CNS) lymphoma is an unusual non-Hodgkin illness restricted to the CNS, and most circumstances are diffuse giant B-cell lymphomas. Different pathologies, together with lymphoplasmacytic lymphoma (LPL), are exceedingly uncommon and poorly understood. The medical presentation of major CNS LPL is various. It relies on the unique website and the tumor’s extension. There may be at present no consensus on a therapy technique for this unusual manifestation. To our information, no beforehand revealed case was efficiently handled with radiation remedy alone.
Case Presentation: We current right here a case of major CNS LPL. A 46-year-old, beforehand wholesome girl was introduced with a worsening headache and decrease extremity numbness. Multifocal enhanced plenty had been detected in an MRI with biopsy outcomes in line with LPL. An entire staging workup was carried out with no proof of systemic illness. The affected person obtained external-beam radiotherapy alone and had a whole remission. After 2 years of follow-up, she stays disease-free.
Conclusion: Radiation alone is a promising therapy possibility for major CNS lymphoplasmacytic lymphoma.
Lymphoplasmacytic lymphoma is a low-grade, B-cell neoplasm composed of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that usually contain the bone marrow and it’s related to an immunoglobulin M (IgM) gammopathy.1 The analysis of LPL is principally based mostly on the histological analysis of concerned tissue, normally bone marrow or lymph nodes. Though the overwhelming majority of LPL circumstances are Waldenström macroglobulinemia (WM), there are some exceptions not glad with the analysis of WM.1 They embody tumors producing different immunoglobulins, mixed immunoglobulins, blended cryoglobulins, gamma heavy chains, or non-gammopathy illness.2 Major CNS lymphoma is an unusual variant of non-Hodgkin lymphoma that includes the mind, leptomeninges, spinal wire, or eyes with out systemic involvement. In literature, just a few circumstances identified with LPL within the setting of major CNS lymphoma have been reported. The present therapy technique isn’t constant because of the rarity and restricted information of this entity.
A forty-six-year-old feminine was introduced to the emergency division of our hospital with a two-month-headache and progressive numbness of her proper leg. She additionally complained of nausea and dizziness 2 weeks earlier than admission. The affected person’s medical and household historical past revealed no significance. On admission, the affected person appeared excitable with a Glasgow Coma Scale (GCS) of 14 (E:4; V:4; M:6); different important indicators had been of their regular ranges. In a normal examination, no lymphadenopathy or organomegaly was discovered. A neurological examination revealed numbness in her proper decrease limb with no motor dysfunction, cranial neuropathy, or indicators of elevated intracranial strain. Nonetheless, magnetic resonance imaging (MRI) of her mind confirmed multifocal lesions scattered throughout the left occipital and parietal lobes; the biggest one measured 16 mm in its transverse dimension. These lesions demonstrated a hypointense sign on the T1W sequence, a hyperintense sign on FLAIR, and no irregular diffusion restriction on DWI photographs (Figure 1). In addition they revealed rim enhancement following gadolinium distinction injection.
Determine 1 Contrasted mind MRI revealed enhanced plenty within the occipital and parietal lobes (arrow).
Concern for mind metastases prompted additional diagnostic procedures, together with thoracic and stomach distinction CT, lumbar and thoracic backbone MRI, endoscopy of the gastrointestinal tract and ENT, however they recognized no abnormalities. The affected person then underwent a surgical biopsy with two samples resected from the 2 largest plenty within the left occipital lobe. Microscopically, the lesions had been composed of small lymphocytes and neoplasm cells with plasma cell morphological options. The immunohistochemical (IMH) take a look at confirmed tumor cells are optimistic for CD79a, CD138, CD38, and MUM-1, however detrimental for CD3 and CD20 (Figure 2). These microscopic and IMH findings had been in line with lymphoplasmacytic lymphoma. Quantitative dedication of the serum globulin take a look at confirmed a rise in IgE at 740 IU/mL; different globulin ranges had been of their regular ranges (IgG 1206 mg/dL, IgM 155 mg/dL, IgA 220 mg/dL, Free Kappa 12.2 mg/L, Free Lambda 12.5 mg/L). Her serum protein electrophoresis and serum immunoelectrophoresis assessments recognized no monoclonal gammopathy. Bone marrow biopsy and cerebrospinal fluid (CSF) evaluation detected no cancerous involvement. Items of the proof above confirmed the analysis of stage I major CNS LPL, based on the Arbor-Cotswold staging system for lymphomas.
Determine 2 Immunohistochemistry outcomes: (A) CD79a (+); (B) CD138 (+); (C) CD3 (-); (D) GFAP (-).
Because the illness was confined to her mind and she or he denied each chemotherapy strategy, we determined to deal with her with whole-brain radiation at a 32 Gy dose (20 fractions of 1,6 Gy per faction). She additionally obtained a mixture of dexamethasone throughout radiation remedy. Her headache was relieved after 2 weeks, and the left-foot numbness often solely after therapy. Two years after irradiation, medical examination and imaging workup revealed no neurological deficits or recurrences.
Lymphoplasmacytic lymphoma is an unusual number of non-Hodgkin lymphoma composed of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. It accounts for about lower than 1% of hematologic malignancies and is even rarer in Asia, with an incidence of 0.31–0.43 circumstances per million.3 Waldenström macroglobulinemia (WM), the most typical subset of LPL, is featured by an elevated serum stage of monoclonal immunoglobulin M and bone marrow involvement.4
Major CNS lymphoma is a really uncommon subgroup of extranodal non-Hodgkin lymphoma that’s confined to the mind parenchyma, leptomeninges, the attention or spinal wire and has no proof of extra-CNS involvement. Its medical expression are usually not particular and range by website of involvement, together with focal neurologic deficits, neuropsychiatric signs, indicators of elevated intracranial strain, and seizures. As a result of lack of particular signs, a definitive analysis of major CNS lymphoma requires a pathological evaluation of the concerned tissue. Some circumstances could be identified by the histopathological analysis of a vitreous biopsy or by a CSF evaluation. Diffuse giant B-cell lymphoma causes most circumstances of major CNS lymphoma, whereas in uncommon circumstances, different entities corresponding to T-cell, lymphoplasmacytic lymphoma and Burkitt’s lymphoma are encountered. Major CNS LPL medical options and optimum therapy stay poorly understood because of the rarity of circumstances and the issue of analysis.
Within the literature, we discovered not more than 30 circumstances of major CNS LPL revealed (through a PubMed seek for “major CNS” and “lymphoplasmacytic lymphoma” in case stories). We introduced right here 9 circumstances with detailed affected person data (Table 1); the opposite circumstances reported are listed within the references.5–7
Desk 1 Comparability of Medical Options of Documented Case Experiences
LPL, like different major CNS lymphomas, can manifest within the mind, meninges, or spinal wire, however no eye involvement has been reported. Nonetheless, mind parenchyma is the most typical major website (Table 1). Its medical expression are atypical and range by website of involvement, together with focal neurologic deficits, neuropsychiatric signs, indicators of elevated intracranial strain, or seizures. Intracranial plenty are normally detected by a head and neck MRI.9 As well as, different laboratory evaluation instruments corresponding to Positron Emission Tomography Scan (PET-CT), blood immunoglobulin assessments and bone marrow biopsy are carried out to detect different website involvement and exclude WM standards. Pathological analysis of tissue, which is important for confirming LPL analysis, usually demonstrates infiltration by small lymphocytes, plasmacytoid lymphocytes, and plasma cells with intranuclear inclusion (Russell our bodies) in some reported circumstances.8 The everyday immunophenotype of LPL contains expression of CD19, CD22, CD20, CD38, and CD79a and the detrimental T-cell marker CD3, BCL. Due to restricted options clinically and pathologically, LPL must be approached as a analysis of exclusion.
A serious differential analysis of major CNS LPL is Bing-Neel syndrome (BNS). Fintelman et al proposed proscribing the definition of BNS to sufferers with beforehand confirmed WM and CNS indicators not as a consequence of hyperviscosity or lymphocyte transformation.16 Minnema et al 2017 have offered pointers for the analysis, therapy, and response standards for Bing-Neel syndrome. It emphasizes the position of cerebral spinal fluid evaluation with multiparameter circulation cytometry in establishing B-cell clonality, protein electrophoresis and MRI of the mind and spinal wire.17 Nonetheless, bone marrow involvement and IgM monoclonal paraprotein are important standards for WM, however they had been omitted in our case, so the analysis of major CNS LPL was established. Additionally it is famous that Bing-Neel syndrome could be identified with out fulfilling WM diagnostic standards.18
There may be nonetheless no consensus guideline for optimum therapy for sufferers with major CNS LPL. The chosen therapies in reported circumstances included tumor resection, chemotherapy, radiation remedy, and focused remedy. The reviewed case with the very best final result is a 50-year-old affected person identified with a mass on the T4 stage of the spinal wire. She was handled by full surgical resection solely (corpectomy) and lived with out neurological sequelae and had no relapse after 51 months. Apparently, within the therapy of major CNS lymphoma, nearly all of which is DLBCL, surgical procedure has a restricted position as a result of the first CNS lymphoma nature tends to be systemic reasonably than localized. To this point, high-dose intravenous methotrexate (MTX) is the best agent in opposition to major CNS lymphoma. In distinction, different mixed regimens utilized in treating systemic lymphoma are both ineffective or insupportable.
Radiation remedy was used as a single-modality routine to deal with major CNS lymphoma within the ‘70s.19 These days, radiation remedy performs a restricted position in major CNS lymphoma and is simply used as a consolidation modality after induction of MTX or as a salvage therapy after illness recurrence or persistence. Nonetheless, major CNS lymphoma is a radiosensitive illness, with over 90% of sufferers reaching a response and signs relieved in 84%.20 For sufferers who’re unsuitable or unwilling to interact in chemotherapy, whole-brain radiation is a suitable various, regardless of the upper threat of illness development and late neurotoxicity. Since low-grade B-cell lymphomas, together with LPL, have a greater prognosis than diffuse giant B-cell lymphoma, radiation remedy alone can be a promising pathway, moreover chemotherapy and surgical resection. One of many late toxicity of whole-brain radiation remedy is injury to the hippocampus. Nonetheless, with the development of radiotherapy strategies right this moment, it’s attainable to attenuate the late toxicity of whole-brain radiation remedy.21 Additional investigation and randomized trials needs to be executed to substantiate the impact and validate the optimum radiotherapy dose.
Major CNS lymphoplasmacytic lymphoma is an unusual number of non-Hodgkin lymphoma similar to the Bing – Neel syndrome. The definitive analysis is principally based mostly on pathology and immunohistochemistry. At the moment, the therapy technique isn’t uniform however individualized relying on every case. We report a medical case of a affected person with major CNS lymphoplasmacytic lymphoma, and was handled with radiation remedy alone. We propose that radiotherapy could also be an encouraging technique for this illness.
CNS, central nervous system; LPL, lymphoplasmacytic lymphoma; WM, Waldenström macroglobulinemia; IMH, immunohistochemical; CSF, cerebrospinal fluid; BNS, Bing-Neel syndrome; MTX, methotrexate.
Knowledge Sharing Assertion
The datasets used within the present research can be found upon affordable request from the corresponding creator.
Ethics Approval and Knowledgeable Consent
The research was permitted by our analysis committee, Hanoi Medical College, Hanoi, Vietnam and Vietnam Nationwide Most cancers Hospital, Hanoi, Vietnam.
Consent for Publication
The publication of this research has been consented to by the affected person.
All authors contributed to knowledge evaluation, drafting or revising the article, gave closing approval of the model to be revealed, agreed to the submitted journal, and comply with be accountable for all facets of the work.
There isn’t a funding to report.
The authors report no conflicts of curiosity on this work.
1. Naderi N, Yang DT. Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia. Arch Pathol Lab Med. 2013;137(4):580–585. doi:10.5858/arpa.2012-0034-RS
2. Marzia Varettoni, Emanuela Boveri, Silvia Zibellini, et al. Medical and molecular traits of lymphoplasmacytic lymphoma not related to an IgM monoclonal protein: A multicentric research of the Rete Ematologica Lombarda (REL) community. Am J Hematol. 2019;94(11):1193-1199. doi: 10.1002/ajh.25600
3. Iwanaga M, Chiang C-J, Soda M, et al. Incidence of lymphoplasmacytic lymphoma/Waldenström’s macroglobulinaemia in Japan and Taiwan population-based most cancers registries, 1996–2003. Int J Most cancers. 2014;134(1):174–180. doi:10.1002/ijc.28343
4. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.
5. Jahnke Okay, Korfel A, O’Neill BP, et al. Worldwide research on low-grade major central nervous system lymphoma. Ann Neurol. 2006;59(5):755–762. doi:10.1002/ana.20804
6. Bogdahn U, Bogdahn S, Mertens HG, et al. Major non-Hodgkin’s lymphomas of the CNS. Acta Neurol Scand. 1986;73(6):602–614. doi:10.1111/j.1600-0404.1986.tb04607.x
7. Shenkier TN. Uncommon variants of major central nervous system lymphoma. Hematol Oncol Clin North Am. 2005;19(4):651–664. doi:10.1016/j.hoc.2005.05.001
8. Abbi KKS, Muzaffar M, Gaudin D, et al. Major CNS lymphoplasmacytic lymphoma: a case report and evaluation of literature. Hematol Oncol Stem Cell Ther. 2013;6(2):76–78. doi:10.1016/j.hemonc.2013.06.002
9. Yan C, Kong X, Yang L, et al. An unusual case of lymphoplasmacytic lymphoma in cerebellopontine angle area. Medication (Baltimore). 2016;95(34):e4627. doi:10.1097/MD.0000000000004627
10. Layden BT, Dubner S, Toft DJ, et al. Major CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus. Pituitary. 2011;14(2):194–197. doi:10.1007/s11102-008-0166-7
11. Ikeda T, Hara Okay, Yamanaka T, et al. [A case of primary central nervous system malignant lymphoma developing from the optic chiasma and hypothalamus]. Rinsho Shinkeigaku. 2006;46(7):475–479. Japanese.
12. Lim T, Kim SJ, Kim Okay, et al. Major CNS lymphoma aside from DLBCL: a descriptive evaluation of medical options and therapy outcomes. Ann Hematol. 2011;90(12):1391–1398. doi:10.1007/s00277-011-1225-0
13. Braks E, Urbach H, Pels H, et al. Major central nervous system immunocytoma: MRI and spectroscopy. Neuroradiology. 2000;42:738–741. doi:10.1007/s002340000392
14. Carrasco CA, Rojas ZD, Chiorino R, et al. Major pituitary lymphoma in immunocompetent affected person: diagnostic issues and extended follow-up. Pituitary. 2012;15(1):93–96. doi:10.1007/s11102-010-0219-6
15. Kanavaros P, Mikol J, Nemeth J, et al. Stereotactic biopsy analysis of major non-Hodgkin’s lymphoma of the central nervous system: a histological and immunohistochemical research. Pathol Res Pract. 1990;186(4):459–466. doi:10.1016/S0344-0338(11)80464-4
16. Fintelmann F, Forghani R, Schaefer PW, et al. Bing-Neel syndrome revisited. Clin Lymphoma Myeloma. 2009;9(1):104–106. doi:10.3816/CLM.2009.n.028
17. Minnema MC, Kimby E, D’Sa S. Guideline for the analysis, therapy and response standards for Bing-Neel syndrome. Haematologica. 2017;102(1):43–51. doi:10.3324/haematol.2016.147728
18. Grainger BT, Issa S. Bing-Neel syndrome presenting as remoted CNS lymphoplasmacytic lymphoma: a case report and evaluation of the literature. J Clin Neurosci. 2019;71:277–280.
19. Henry JM, Heffner RR, Dillard SH, et al. Major malignant lymphomas of the central nervous system. Most cancers. 1974;34(4):1293–1302. doi:10.1002/1097-0142(197410)34:4<1293::AID-CNCR2820340441>3.0.CO;2-P
20. Kwak Y-Okay, Choi B-O, Choi KH, et al. Radiotherapy in its place therapy possibility for major central nervous system lymphoma sufferers who’re noncandidates for chemotherapy. Oncotarget. 2017;8(63):106858–106865. doi:10.18632/oncotarget.22427
21. Kazda T, Pospíšil P, Doleželová H, et al. Entire mind radiotherapy: penalties for personalised medication. Rep Pract Oncol Radiother. 2013;18(3):133–138. doi:10.1016/j.rpor.2013.03.002