- Email: [email protected]
Small Cell Variant of Anaplastic Lymphoma Kinase–Positive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma
Case Report
Small Cell Variant of Anaplastic Lymphoma KinaseePositive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma Yudai Hirano1, Satoru Miyawaki1, Michiaki Satou2, Kazuki Taoka2, Kazuhiro Toyama2, Masako Ikemura3, Ryo Tanaka1, Shunsaku Takayanagi1, Shota Tanaka1, Hirofumi Nakatomi1, Mineo Kurokawa2, Nobuhito Saito1
Key words Anaplastic large cell lymphoma - Anaplastic lymphoma kinase - CD8 - CD30 - Primary central nervous system lymphoma - Small cell variant -
- BACKGROUND:
Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)epositive ALCL have been reported so far, with no reported cases of a small cell variant.
- CASE
Abbreviations and Acronyms ALCL: Anaplastic large cell lymphoma ALK: Anaplastic lymphoma kinase CD: Cluster of differentiation CNS: Central nervous system CYVE: Cytarabine and etoposide H&E: Hematoxylin and eosin MPV: Methotrexate, procarbazine, and vincristine MRI: Magnetic resonance imaging MTX: Methotrexate PCNSL: Primary central nervous system lymphoma SUVmax: Maximum standardized uptake value 1
2
From the Departments of Neurosurgery, Hematology and Oncology, and 3Pathology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan To whom correspondence should be addressed: Satoru Miyawaki, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2020) 138:169-173. https://doi.org/10.1016/j.wneu.2020.02.171 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2020 Elsevier Inc. All rights reserved.
INTRODUCTION Primary central nervous system lymphoma (PCNSL) is relatively uncommon and accounts for approximately 3% of all brain tumors.1 The most common histologic type of PCNSL is diffuse large B-cell lymphoma, whereas anaplastic lymphoma kinase (ALK)epositive anaplastic large cell lymphoma (ALCL) is less common. ALCL was first described in 19852 and was characterized by the presence of large pleomorphic lymphoid cells expressing cluster of differentiation (CD) 30. The most common genetic alteration of ALCL is the translocation of ALK and NPM
DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE).
- CONCLUSIONS:
In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.
genes.3 The World Health Organization classification of ALCL includes both ALKpositive and -negative types.4 ALK-positive ALCL originating in the central nervous system (CNS) is extremely rare; only a few cases of primary CNS ALCL have been reported,5 most of which have been associated with meningeal lesions. Patients with ALK-positive ALCL exhibit a 5-year survival rate of 75%. Conversely, patients with small cell variants exhibit a much poorer prognosis than those with the common type ALCL in systemic disease. A small cell variant of ALCL originating in the CNS has never been reported. We present, for the first time, to our knowledge, a case of a small cell variant of ALK-positive ALCL originating in the CNS and mimicking a tentorial meningioma.
CASE DESCRIPTION A 26-year-old man with no medical history experienced headache and dizziness,
WORLD NEUROSURGERY 138: 169-173, JUNE 2020
persisting over 3 months, and left homonymous hemianopia, for over 1 month. Computed tomography scan showed a high-density mass, and magnetic resonance imaging revealed a supratentorial extraparenchymal mass measuring 45 28 33 mm that was unevenly enhanced with gadolinium and associated with remarkable edema in the left cerebral hemisphere (Figure 1AeC and E). The tumorebrain parenchyma border was somewhat unclear, and the lesion was considered to be strongly adherent to the brain. The straight sinus was compressed but patent despite apparent tumor invasion (Figure 1F). The mass effect of the tumor caused compression of the ventricles and a slight bias of the median structure to the left. Fluorodeoxyglucose positron emission tomography scan showed a remarkable accumulation of fluorodeoxyglucose in the lesion, with a maximum standardized uptake value (SUVmax) of 21.1 and no abnormal accumulation in the trunk (Figure 1D).
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Figure 1. (A) Preoperative neuroimaging. Preoperative computed tomography scan showing a high-density area. (B) Preoperative T2-weighted magnetic resonance image showing a hyperintense supratentorial mass. (C) The tumor is 45 mm in maximum diameter, with strong but uneven gadolinium enhancement. (D) Fluorodeoxyglucose
Furthermore, cerebral angiography showed that the tumor was not hypervascular and was being supplied by the accessory meningeal artery. The original differential diagnosis included malignant meningioma, hemangiopericytoma, or metastatic brain tumor. However, malignant meningioma was the most likely diagnosis because the tumor was not hypervascular, and no primary tumors were found after a complete body search. An occipital craniotomy was then performed to remove the tumor. Intraoperative findings revealed that the tumor had originated from the dura and invaded the straight sinus. Furthermore, the
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positron emission tomography scans showing remarkable accumulation in the lesion (maximum standardized uptake value 21.1). (E) The cerebral hemisphere around the tumor has remarkable edema. (F) The straight sinus is compressed and possibly invaded by the tumor.
tumoreoccipital lobe border was unclear. The tumor was completely removed by partial subpial dissection of the occipital lobe. The postoperative course was promising with an improvement of the homonymous hemianopia. Postoperative neuroimaging also showed no residual tumor, patency of the straight sinus, and improvement of the brain edema. Hematoxylin and eosin (H&E) staining of the tumor specimen showed the diffuse growth of atypical cells with round enlarged nuclei and eosinophilic cytoplasm (Figure 2A). The nucleoli were clear and varied in size. Immunohistologic examination identified that the atypical
cells were lymphocytic common antigen (þ), mainly CD3 (), CD5 (), CD4 (), CD8 (þ), CD20 (), CD30 (þ), ALK (þ), CD138 (), progesterone receptor (), granzyme B (þ), perforin (þ), T-cell intercellular antigen 1 (þ), and EpsteinBarr virus-encoded RNA in situ hybridization () (Figure 2BeF). Furthermore, the MIB-1epositive rate was more than 90%. H&E staining revealed that the proliferating atypical lymphocytes were not enlarged and were not typical of ALCL (Figure 2A). Therefore, the histologic diagnosis was a small cell variant of ALK-positive ALCL based on the results of immunohistologic staining.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.02.171
CASE REPORT YUDAI HIRANO ET AL.
SMALL CELL VARIANT OF ANAPLASTIC LARGE CELL LYMPHOMA
Figure 2. Histologic features of a small cell variant of anaplastic large cell lymphoma. Hematoxylin and eosin staining showing the diffuse growth of atypical cells with round, enlarged nuclei and eosinophilic cytoplasm. (A) Proliferating atypical lymphocytes are not large and are atypical for anaplastic large cell lymphoma. Original magnification 100. (BeF)
The postoperative course was successful, and the patient was discharged home on foot on the 12th postoperative day. He was admitted to the hematology department for further examination and treatment. A bone marrow biopsy showed no evidence of the presence of atypical cells, which suggested that the lymphoma developed from the CNS. The patient was treated with several biweekly cycles of chemotherapy, including methotrexate (MTX) (3.5 g/m2), procarbazine, and vincristine (MPV) therapy. Whole-body fluorodeoxyglucose positron emission tomography scan performed 1 month postoperatively showed a small area of high accumulation of fluorodeoxyglucose in the pelvis, suggesting tumor metastasis (Figure 3B). Magnetic resonance imaging confirmed the recurrence of the tumor 2 months postoperatively (Figure 3A). Computed tomography scan showed that the lesions on the margin of the excision cavity were enlarged despite 2 courses of MPV therapy. Based on these findings,
Immunohistologic staining showing that the atypical cells are positive for cluster of differentiation (CD) 30 (B), anaplastic lymphoma kinase (C), and CD8 (E), and negative for CD4 (D) and CD20 (F). Original magnifications 400 (scale bar, 50 mm).
cytarabine and etoposide (CYVE) chemotherapy was initiated. During the first course of this treatment, the tumor had reduced in size to under 1 cm,3 and a partial response was observed. At 5 months postoperatively, the partial response has been maintained, and the tumor has not shown any recurrence.
DISCUSSION This case describes a small cell variant of ALK-positive ALCL originating in the dura mimicking meningioma. The differential diagnosis of dural tumors includes hemangiopericytoma, metastatic brain tumor, and non-neoplastic lesions, such as sarcoidosis, tuberculosis, and immunoglobulin G4-related diseases.6 In about 2% of cases, tumors that were originally thought to be meningioma were later identified as something different after the postoperative pathology.7 Therefore, differentiating meningioma from other tumors is often difficult, but 5 imaging
WORLD NEUROSURGERY 138: 169-173, JUNE 2020
features help radiologists distinguish mimics from true meningioma. These include homogeneous T2 hypointensity, homogeneous T2 hyperintensity, osseous destruction adjacent to the mass, leptomeningeal or a pial extension of the tumor, and the absence of dural tail enhancement.8 All of these features are rarely observed in meningioma cases but are common in patients with meningioma mimics. The imaging results in the present case, including homogeneous T2 hypointensity, a pial extension of the tumor, and the absence of a dural tail enhancement, are characteristics that are common for meningioma mimics. ALCL is a subtype of PCNSL which is characterized by the absence of calcification, absence of surrounding bone hardening, lobularity, borderline indistinctness, and marked periedema.6 In addition, CNS lymphoma often shows increased fluorodeoxyglucose uptake in a positron emission tomography scan, and
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SMALL CELL VARIANT OF ANAPLASTIC LARGE CELL LYMPHOMA
Figure 3. Postoperative imaging. (A) Postoperative magnetic resonance image showing the recurrence of the tumor (arrow) in the anterior part of the tentorium cerebelli. (B) Postoperative fluorodeoxyglucose positron emission tomography scan showing new accumulation in the pelvis (arrow) not observed in the preoperative imaging.
the SUVmax of PCNSL is about 6.9e24.8, which is higher than other tumors.9-11 In this case, the SUVmax was 21.1, and the tumor/normal tissue ratio was 2.1, which are characteristics of PCNSL. Considering this case retrospectively, PCNSL should have been suspected preoperatively based on the magnetic resonance imaging findings and the high fluorodeoxyglucose uptake observed in the positron emission tomography scan. The diagnosis of lymphoma requires further molecular analysis to determine the appropriate treatment and prognosis. ALCL was first reported in 19852 and is characterized by the presence of large pleomorphic lymphoid cells that express CD30. ALCL originates from the T-cell (80%) or null-cell (20%) phenotype.3 ALCL is a nodular disease that involves extranodal sites, such as the skin, bone, soft tissue, lungs, and liver,12 but rarely occurs in the CNS. ALCL contains large lymphocytes with abundant cytoplasm and pleomorphic nuclei. In this case, atypical lymphocytes were not large and differed from typical ALCL but were classified as a small cell variant of ALCL because of the ALK expression and CD30 positivity. As previously mentioned, ALCL can be divided into ALK-positive and ALK-negative groups.13 The ALK-positive group is more likely to occur in younger patients, usually develops before age 30 years, and is more common in men. The ALK-negative group carries a more unfavorable prognosis and tends to occur in older patients, with no sex difference.14 The analysis of the
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reported cases of ALK-positive ALCL revealed that this histologic type is usually associated with meningeal lesions rather than common PCNSL. About half of the cases were misdiagnosed as hypertrophic pachymeningitis.5 However, the formation of a meningioma-like large mass, as observed in this case, is extremely rare. The prognosis for patients with ALCL may be worse than common lymphoma.14 On the other hand, the prognosis of ALKpositive ALCL is relatively good. Specifically, the 5-year survival rate for patients with ALK-negative ALCL is 12.5%, whereas the 5-year survival rate for ALK-positive ALCL patients is 75%. ALK positivity, patients under 40 years of age, and chemotherapy of any regimen are associated with the long-term survival for patients with ALCL of the CNS.15 The present patient exhibited all of these favorable prognostic factors, but the tumor recurred from the margin of the resected cavity 2 months postoperatively and metastasized to the pelvis. We speculated that this case may be a small cell variant of ALCL based on the absence of large cells by H&E staining. The small cell variant of ALCL was first reported in 1993,16 accounting for approximately 5%e10% of cases in the systemic disease. Immunohistologic positivity for ALK was observed in all cases of small cell variants.17 Patients with small cell variants of systemic ALK-positive ALCL have an extremely poor prognosis, and this type of tumor follows an aggressive course compared with the common type ALCL.17 This type of tumor has the
potential for dissemination, but the mechanisms contributing to the poor prognosis are unknown. There are few reports of the standard treatment for T-cell lymphomas among PCNSL. High-dose MTX-based regimens are usually used to treat PCNSL. In a previous study, 11 of 17 patients with ALCL who received chemotherapy were treated with MTX-based agents, which was shown to be effective for treatment of ALCL.15 The present patient underwent 2 courses of MPV therapy, but the tumor recurred and showed resistance. After MPV therapy was changed to CYVE therapy, the size of the tumor decreased and showed a good response to the treatment. Therefore, CYVE therapy might be an effective treatment for patients with a small cell variant of primary CNS ALK-positive ALCL. CONCLUSIONS Primary CNS ALK-positive ALCL is very rare, which makes it difficult to diagnose. The case reported here involved a patient with a small cell variant of ALK-positive ALCL originating from the CNS. The small cell variant of primary CNS ALKpositive ALCL may have a poorer prognosis because of the potential for tumor metastasis or resistance to chemotherapy. Based on the findings of this case report, CYVE therapy might be an effective treatment for the small cell variant of primary CNS ALK-positive ALCL. REFERENCES 1. The Committee of Brain Tumor Registry of Japan. Report of Brain Tumor Registry of Japan (19842000). Neurol Med Chir (Tokyo). 2009;49(suppl): PS1-PS25. 2. Stein H, Mason DY, Gerdes J, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66:848-858. 3. Amin HM, Lai R. Pathobiology of ALKþ anaplastic large-cell lymphoma. Blood. 2007;110: 2259-2267. 4. Swerldow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008:312-319. 5. Fujisawa E, Shibayama H, Mitobe F, Katada F, Sato S, Fukutake T. A case of primary central nervous system anaplastic lymphoma kinase
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positive anaplastic large cell lymphoma manifested as a unilateral pachymeningitis. Rinsho Shinkeigaku. 2017;57:705-710 [in Japanese]. 6. Lyndon D, Lansley JA, Evanson J, Krishnan AS. Dural masses: meningiomas and their mimics. Insights Imaging. 2019;10:11. 7. Ghosal N, Dadlani R, Gupta K, Furtado SV, Hegde AS. A clinicopathological study of diagnostically challenging meningioma mimics. J Neurooncol. 2012;106:339-352. 8. Starr CJ, Cha S. Meningioma mimics: five key imaging features to differentiate them from meningiomas. Clin Radiol. 2017;72:722-728. 9. Albano D, Bosio G, Bertoli M, Giubbini R, Bertagna F. 18F-FDG PET/CT in primary brain lymphoma. J Neurooncol. 2018;136:577-583. 10. Yamaguchi S, Hirata K, Kaneko S, et al. Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation. Acta Neurochir (Wien). 2015;157:187-194.
SMALL CELL VARIANT OF ANAPLASTIC LARGE CELL LYMPHOMA
11. Yamaguchi S, Hirata K, Kobayashi H, et al. The diagnostic role of 18F-FDG PET for primary central nervous system lymphoma. Ann Nucl Med. 2014;28: 603-609.
16. Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME. A small-cell-predominant variety of primary Ki-1 (CD30)þ T-cell lymphoma. Am J Surg Pathol. 1993;17:859-868.
12. Karikari IO, Thomas KK, Lagoo A, Cummings TJ, George TM. Primary cerebral ALK-1epositive anaplastic large cell lymphoma in a child. Case report and literature review. Pediatr Neurosurg. 2007;43:516-521.
17. Summers TA, Moncur JT. The small cell variant of anaplastic large cell lymphoma. Arch Pathol Lab Med. 2010;134:1706-1710.
13. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117: 5019-5032. 14. George DH, Scheithauer BW, Aker FV, et al. Primary anaplastic large cell lymphoma of the central nervous system: prognostic effect of ALK-1 expression. Am J Surg Pathol. 2003;27:487-493. 15. Nomura M, Narita Y, Miyakita Y, et al. Clinical presentation of anaplastic large-cell lymphoma in the central nervous system. Mol Clin Oncol. 2013;1: 655-660.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 17 February 2020; accepted 27 February 2020 Citation: World Neurosurg. (2020) 138:169-173. https://doi.org/10.1016/j.wneu.2020.02.171 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2020 Elsevier Inc. All rights reserved.
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Small Cell Variant of Anaplastic Lymphoma KinaseePositive Anaplastic Large Cell Lymphoma of the Dura Mimicking Tentorial Meningioma Yudai Hirano1, Satoru Miyawaki1, Michiaki Satou2, Kazuki Taoka2, Kazuhiro Toyama2, Masako Ikemura3, Ryo Tanaka1, Shunsaku Takayanagi1, Shota Tanaka1, Hirofumi Nakatomi1, Mineo Kurokawa2, Nobuhito Saito1
Key words Anaplastic large cell lymphoma - Anaplastic lymphoma kinase - CD8 - CD30 - Primary central nervous system lymphoma - Small cell variant -
- BACKGROUND:
Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)epositive ALCL have been reported so far, with no reported cases of a small cell variant.
- CASE
Abbreviations and Acronyms ALCL: Anaplastic large cell lymphoma ALK: Anaplastic lymphoma kinase CD: Cluster of differentiation CNS: Central nervous system CYVE: Cytarabine and etoposide H&E: Hematoxylin and eosin MPV: Methotrexate, procarbazine, and vincristine MRI: Magnetic resonance imaging MTX: Methotrexate PCNSL: Primary central nervous system lymphoma SUVmax: Maximum standardized uptake value 1
2
From the Departments of Neurosurgery, Hematology and Oncology, and 3Pathology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan To whom correspondence should be addressed: Satoru Miyawaki, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2020) 138:169-173. https://doi.org/10.1016/j.wneu.2020.02.171 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2020 Elsevier Inc. All rights reserved.
INTRODUCTION Primary central nervous system lymphoma (PCNSL) is relatively uncommon and accounts for approximately 3% of all brain tumors.1 The most common histologic type of PCNSL is diffuse large B-cell lymphoma, whereas anaplastic lymphoma kinase (ALK)epositive anaplastic large cell lymphoma (ALCL) is less common. ALCL was first described in 19852 and was characterized by the presence of large pleomorphic lymphoid cells expressing cluster of differentiation (CD) 30. The most common genetic alteration of ALCL is the translocation of ALK and NPM
DESCRIPTION: A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE).
- CONCLUSIONS:
In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.
genes.3 The World Health Organization classification of ALCL includes both ALKpositive and -negative types.4 ALK-positive ALCL originating in the central nervous system (CNS) is extremely rare; only a few cases of primary CNS ALCL have been reported,5 most of which have been associated with meningeal lesions. Patients with ALK-positive ALCL exhibit a 5-year survival rate of 75%. Conversely, patients with small cell variants exhibit a much poorer prognosis than those with the common type ALCL in systemic disease. A small cell variant of ALCL originating in the CNS has never been reported. We present, for the first time, to our knowledge, a case of a small cell variant of ALK-positive ALCL originating in the CNS and mimicking a tentorial meningioma.
CASE DESCRIPTION A 26-year-old man with no medical history experienced headache and dizziness,
WORLD NEUROSURGERY 138: 169-173, JUNE 2020
persisting over 3 months, and left homonymous hemianopia, for over 1 month. Computed tomography scan showed a high-density mass, and magnetic resonance imaging revealed a supratentorial extraparenchymal mass measuring 45 28 33 mm that was unevenly enhanced with gadolinium and associated with remarkable edema in the left cerebral hemisphere (Figure 1AeC and E). The tumorebrain parenchyma border was somewhat unclear, and the lesion was considered to be strongly adherent to the brain. The straight sinus was compressed but patent despite apparent tumor invasion (Figure 1F). The mass effect of the tumor caused compression of the ventricles and a slight bias of the median structure to the left. Fluorodeoxyglucose positron emission tomography scan showed a remarkable accumulation of fluorodeoxyglucose in the lesion, with a maximum standardized uptake value (SUVmax) of 21.1 and no abnormal accumulation in the trunk (Figure 1D).
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CASE REPORT YUDAI HIRANO ET AL.
SMALL CELL VARIANT OF ANAPLASTIC LARGE CELL LYMPHOMA
Figure 1. (A) Preoperative neuroimaging. Preoperative computed tomography scan showing a high-density area. (B) Preoperative T2-weighted magnetic resonance image showing a hyperintense supratentorial mass. (C) The tumor is 45 mm in maximum diameter, with strong but uneven gadolinium enhancement. (D) Fluorodeoxyglucose
Furthermore, cerebral angiography showed that the tumor was not hypervascular and was being supplied by the accessory meningeal artery. The original differential diagnosis included malignant meningioma, hemangiopericytoma, or metastatic brain tumor. However, malignant meningioma was the most likely diagnosis because the tumor was not hypervascular, and no primary tumors were found after a complete body search. An occipital craniotomy was then performed to remove the tumor. Intraoperative findings revealed that the tumor had originated from the dura and invaded the straight sinus. Furthermore, the
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positron emission tomography scans showing remarkable accumulation in the lesion (maximum standardized uptake value 21.1). (E) The cerebral hemisphere around the tumor has remarkable edema. (F) The straight sinus is compressed and possibly invaded by the tumor.
tumoreoccipital lobe border was unclear. The tumor was completely removed by partial subpial dissection of the occipital lobe. The postoperative course was promising with an improvement of the homonymous hemianopia. Postoperative neuroimaging also showed no residual tumor, patency of the straight sinus, and improvement of the brain edema. Hematoxylin and eosin (H&E) staining of the tumor specimen showed the diffuse growth of atypical cells with round enlarged nuclei and eosinophilic cytoplasm (Figure 2A). The nucleoli were clear and varied in size. Immunohistologic examination identified that the atypical
cells were lymphocytic common antigen (þ), mainly CD3 (), CD5 (), CD4 (), CD8 (þ), CD20 (), CD30 (þ), ALK (þ), CD138 (), progesterone receptor (), granzyme B (þ), perforin (þ), T-cell intercellular antigen 1 (þ), and EpsteinBarr virus-encoded RNA in situ hybridization () (Figure 2BeF). Furthermore, the MIB-1epositive rate was more than 90%. H&E staining revealed that the proliferating atypical lymphocytes were not enlarged and were not typical of ALCL (Figure 2A). Therefore, the histologic diagnosis was a small cell variant of ALK-positive ALCL based on the results of immunohistologic staining.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.02.171
CASE REPORT YUDAI HIRANO ET AL.
SMALL CELL VARIANT OF ANAPLASTIC LARGE CELL LYMPHOMA
Figure 2. Histologic features of a small cell variant of anaplastic large cell lymphoma. Hematoxylin and eosin staining showing the diffuse growth of atypical cells with round, enlarged nuclei and eosinophilic cytoplasm. (A) Proliferating atypical lymphocytes are not large and are atypical for anaplastic large cell lymphoma. Original magnification 100. (BeF)
The postoperative course was successful, and the patient was discharged home on foot on the 12th postoperative day. He was admitted to the hematology department for further examination and treatment. A bone marrow biopsy showed no evidence of the presence of atypical cells, which suggested that the lymphoma developed from the CNS. The patient was treated with several biweekly cycles of chemotherapy, including methotrexate (MTX) (3.5 g/m2), procarbazine, and vincristine (MPV) therapy. Whole-body fluorodeoxyglucose positron emission tomography scan performed 1 month postoperatively showed a small area of high accumulation of fluorodeoxyglucose in the pelvis, suggesting tumor metastasis (Figure 3B). Magnetic resonance imaging confirmed the recurrence of the tumor 2 months postoperatively (Figure 3A). Computed tomography scan showed that the lesions on the margin of the excision cavity were enlarged despite 2 courses of MPV therapy. Based on these findings,
Immunohistologic staining showing that the atypical cells are positive for cluster of differentiation (CD) 30 (B), anaplastic lymphoma kinase (C), and CD8 (E), and negative for CD4 (D) and CD20 (F). Original magnifications 400 (scale bar, 50 mm).
cytarabine and etoposide (CYVE) chemotherapy was initiated. During the first course of this treatment, the tumor had reduced in size to under 1 cm,3 and a partial response was observed. At 5 months postoperatively, the partial response has been maintained, and the tumor has not shown any recurrence.
DISCUSSION This case describes a small cell variant of ALK-positive ALCL originating in the dura mimicking meningioma. The differential diagnosis of dural tumors includes hemangiopericytoma, metastatic brain tumor, and non-neoplastic lesions, such as sarcoidosis, tuberculosis, and immunoglobulin G4-related diseases.6 In about 2% of cases, tumors that were originally thought to be meningioma were later identified as something different after the postoperative pathology.7 Therefore, differentiating meningioma from other tumors is often difficult, but 5 imaging
WORLD NEUROSURGERY 138: 169-173, JUNE 2020
features help radiologists distinguish mimics from true meningioma. These include homogeneous T2 hypointensity, homogeneous T2 hyperintensity, osseous destruction adjacent to the mass, leptomeningeal or a pial extension of the tumor, and the absence of dural tail enhancement.8 All of these features are rarely observed in meningioma cases but are common in patients with meningioma mimics. The imaging results in the present case, including homogeneous T2 hypointensity, a pial extension of the tumor, and the absence of a dural tail enhancement, are characteristics that are common for meningioma mimics. ALCL is a subtype of PCNSL which is characterized by the absence of calcification, absence of surrounding bone hardening, lobularity, borderline indistinctness, and marked periedema.6 In addition, CNS lymphoma often shows increased fluorodeoxyglucose uptake in a positron emission tomography scan, and
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Figure 3. Postoperative imaging. (A) Postoperative magnetic resonance image showing the recurrence of the tumor (arrow) in the anterior part of the tentorium cerebelli. (B) Postoperative fluorodeoxyglucose positron emission tomography scan showing new accumulation in the pelvis (arrow) not observed in the preoperative imaging.
the SUVmax of PCNSL is about 6.9e24.8, which is higher than other tumors.9-11 In this case, the SUVmax was 21.1, and the tumor/normal tissue ratio was 2.1, which are characteristics of PCNSL. Considering this case retrospectively, PCNSL should have been suspected preoperatively based on the magnetic resonance imaging findings and the high fluorodeoxyglucose uptake observed in the positron emission tomography scan. The diagnosis of lymphoma requires further molecular analysis to determine the appropriate treatment and prognosis. ALCL was first reported in 19852 and is characterized by the presence of large pleomorphic lymphoid cells that express CD30. ALCL originates from the T-cell (80%) or null-cell (20%) phenotype.3 ALCL is a nodular disease that involves extranodal sites, such as the skin, bone, soft tissue, lungs, and liver,12 but rarely occurs in the CNS. ALCL contains large lymphocytes with abundant cytoplasm and pleomorphic nuclei. In this case, atypical lymphocytes were not large and differed from typical ALCL but were classified as a small cell variant of ALCL because of the ALK expression and CD30 positivity. As previously mentioned, ALCL can be divided into ALK-positive and ALK-negative groups.13 The ALK-positive group is more likely to occur in younger patients, usually develops before age 30 years, and is more common in men. The ALK-negative group carries a more unfavorable prognosis and tends to occur in older patients, with no sex difference.14 The analysis of the
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reported cases of ALK-positive ALCL revealed that this histologic type is usually associated with meningeal lesions rather than common PCNSL. About half of the cases were misdiagnosed as hypertrophic pachymeningitis.5 However, the formation of a meningioma-like large mass, as observed in this case, is extremely rare. The prognosis for patients with ALCL may be worse than common lymphoma.14 On the other hand, the prognosis of ALKpositive ALCL is relatively good. Specifically, the 5-year survival rate for patients with ALK-negative ALCL is 12.5%, whereas the 5-year survival rate for ALK-positive ALCL patients is 75%. ALK positivity, patients under 40 years of age, and chemotherapy of any regimen are associated with the long-term survival for patients with ALCL of the CNS.15 The present patient exhibited all of these favorable prognostic factors, but the tumor recurred from the margin of the resected cavity 2 months postoperatively and metastasized to the pelvis. We speculated that this case may be a small cell variant of ALCL based on the absence of large cells by H&E staining. The small cell variant of ALCL was first reported in 1993,16 accounting for approximately 5%e10% of cases in the systemic disease. Immunohistologic positivity for ALK was observed in all cases of small cell variants.17 Patients with small cell variants of systemic ALK-positive ALCL have an extremely poor prognosis, and this type of tumor follows an aggressive course compared with the common type ALCL.17 This type of tumor has the
potential for dissemination, but the mechanisms contributing to the poor prognosis are unknown. There are few reports of the standard treatment for T-cell lymphomas among PCNSL. High-dose MTX-based regimens are usually used to treat PCNSL. In a previous study, 11 of 17 patients with ALCL who received chemotherapy were treated with MTX-based agents, which was shown to be effective for treatment of ALCL.15 The present patient underwent 2 courses of MPV therapy, but the tumor recurred and showed resistance. After MPV therapy was changed to CYVE therapy, the size of the tumor decreased and showed a good response to the treatment. Therefore, CYVE therapy might be an effective treatment for patients with a small cell variant of primary CNS ALK-positive ALCL. CONCLUSIONS Primary CNS ALK-positive ALCL is very rare, which makes it difficult to diagnose. The case reported here involved a patient with a small cell variant of ALK-positive ALCL originating from the CNS. The small cell variant of primary CNS ALKpositive ALCL may have a poorer prognosis because of the potential for tumor metastasis or resistance to chemotherapy. Based on the findings of this case report, CYVE therapy might be an effective treatment for the small cell variant of primary CNS ALK-positive ALCL. REFERENCES 1. The Committee of Brain Tumor Registry of Japan. Report of Brain Tumor Registry of Japan (19842000). Neurol Med Chir (Tokyo). 2009;49(suppl): PS1-PS25. 2. Stein H, Mason DY, Gerdes J, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66:848-858. 3. Amin HM, Lai R. Pathobiology of ALKþ anaplastic large-cell lymphoma. Blood. 2007;110: 2259-2267. 4. Swerldow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008:312-319. 5. Fujisawa E, Shibayama H, Mitobe F, Katada F, Sato S, Fukutake T. A case of primary central nervous system anaplastic lymphoma kinase
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 17 February 2020; accepted 27 February 2020 Citation: World Neurosurg. (2020) 138:169-173. https://doi.org/10.1016/j.wneu.2020.02.171 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2020 Elsevier Inc. All rights reserved.
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