Primary peripheral T-cell lymphoma, not otherwise ... - Springer Link

3 downloads 33 Views 1MB Size Report
Sep 3, 2015 - Primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child. Hiroyuki Momota1,2. • Seiichi Kato3.
Brain Tumor Pathol (2015) 32:281–285 DOI 10.1007/s10014-015-0229-1

CASE REPORT

Primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child Hiroyuki Momota1,2 • Seiichi Kato3 • Masazumi Fujii1 • Takashi Tsujiuchi1 Yoshiyuki Takahashi4 • Seiji Kojima4 • Toshihiko Wakabayashi1



Received: 19 June 2015 / Accepted: 19 August 2015 / Published online: 3 September 2015 Ó The Japan Society of Brain Tumor Pathology 2015

Abstract Primary peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is a rare disease that infrequently involves the central nervous system (CNS), and it is even rarer in pediatric patients. Here, we report of a 13-year-old male with primary CNS PTCL-NOS who exhibited a malignant clinical course with recurrence after radiochemotherapy followed by bone marrow transplantation; he died 43 months after diagnosis. Pathology revealed the proliferation of cytotoxic T-cells and clonal T-cell receptor gene rearrangements. Although the optimal therapy for PTCL remains controversial, intensive radiochemotherapy may be required for some patients. Keywords Peripheral T-cell lymphoma  Central nervous system  Radiochemotherapy  Pediatric

Introduction Peripheral T-cell lymphoma (PTCL) is a rare type of nonHodgkin, mature T-cell lymphoma. PTCL, not otherwise specified (PTCL-NOS), accounts for approximately 30 % of PTCL cases, and represents a heterogeneous patient group [1]. Most patients with PTCL-NOS are adults, and the most involved sites are the peripheral lymph nodes. Although any extranodal tissues may be affected, such as the skin, liver, and bone marrow, the central nervous system (CNS) is rarely involved as the primary site [1–3]. To our knowledge, there is only one report of a pediatric patient with primary PTCL-NOS of the CNS in the English literature [4]. Here, we present a new case of primary CNS PTCL-NOS in a child.

Clinical summary

& Hiroyuki Momota [email protected] 1

Department of Neurosurgery, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan

2

Present Address: Division of Innovative Cancer Therapy, Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

3

Department of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya, Japan

4

Department of Pediatrics, Nagoya University Hospital, Nagoya, Japan

A 13-year-old male developed left upper limb weakness, dysarthria, and headache. He had no other past medical history or familial medical history. A magnetic resonance imaging (MRI) scan of his brain revealed a mass in the right temporal lobe, and he was transferred to our hospital. On admission, laboratory blood examination revealed no apparent abnormalities with respect to the levels of serum lactate dehydrogenase (268 U/L), soluble interleukin-2 receptor (166 U/mL), and antibodies against human T-cell leukemia virus type 1 antigens and Epstein–Barr virus (EBV) antigens (EBV viral capsid antigen-IgM \10, EBV nuclear antigen-IgG \20). Cerebrospinal fluid (CSF) analysis did not reveal any evidence of viral or bacterial infection except for a slight elevation in cell count (21/ 3 mm3) and protein level (72 mg/dL), and CSF cytology was negative. A repeat MRI scan after admission revealed

123

282

Brain Tumor Pathol (2015) 32:281–285

recurrence for approximately 22 months. However, he developed left lower limb weakness, vomiting, and fecal incontinence, and a brain MRI scan revealed multiple enhanced lesions on the brain surface on both sides. Salvage local radiotherapy was administered for a lesion of the medulla oblongata at a whole dose of 20 Gy in 10 fractions, but his symptoms and general condition worsened gradually. Although repeat imaging and laboratory studies during the clinical course did not show any evidence of systemic spread of the disease, he died of respiratory failure 14 months after recurrence i.e. 43 months after the initial diagnosis.

a tumor-like lesion mainly in the right temporal lobe with intratumoral hemorrhage and subarachnoid spread to the temporo-fronto-parietal brain surface (Fig. 1a–c). A fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography image revealed low FDG uptake in the tumor lesion (Fig. 1d). The patient underwent a biopsy of the right frontal lobe via the left fronto-temporal approach. Macroscopically, the lesion was yellowish and adhered to the brain surface, and it was soft, fragile, and hemorrhagic. As the initial pathological diagnosis based on hematoxylin and eosin (H&E) staining indicated the possibility of inflammation, the patient continued to be treated with antiviral and corticosteroid therapies for more 17 days after the biopsy. Further examination revealed no evidence of systemic malignancy. However, the brain lesion enlarged. The final diagnosis was confirmed as a cytotoxic T-cell lymphoproliferative disorder (LPD)/lymphoma, corresponding to PTCL-NOS. As the histopathological examination and clinical course indicated a neoplastic disease, the patient received whole brain radiation therapy (39.6 Gy in 22 fractions) and concomitant chemotherapy with cyclosporine, etoposide, and dexamethasone. After radiochemotherapy, he was further treated with four cycles of a SMILE regimen, which consisted of methotrexate, etoposide, ifosfamide, dexamethasone, and L-asparaginase. Eight months after surgery, he received chemotherapy with intravenous busulfan and melphalan as a conditioning regimen, followed by allogeneic bone marrow transplantation. After these treatments, the patient experienced intellectual disability, hemiparesis of the left upper limb, and renal and adrenal insufficiencies. Follow-up MRI examinations of his brain demonstrated brain atrophy but no evidence of disease

The surgical specimen was fixed with 10 % formalin. Paraffin-embedded 4-lm thick sections were stained with H&E for light microscopy. Immunostaining was routinely performed using monoclonal antibodies against the following antigens: CD3, CD8, CD20, CD30, CD45RO, and ALK (Dako, Santa Fe, CA); CD4, CD5, CD7, CD25, CD27, and CD56 (Novocastra Laboratories, Newcastle, UK); CD16 (MBL, Nagoya, Japan); CD57 (BD Biosciences, San Jose, CA, USA); T-cell receptor (TCR)-b (T Cell Science, Cambridge, MA, USA); TCR-c (Thermo Fisher Scientific, Waltham, MA, USA); granzyme B (Monosan, Uden, The Netherlands); and TIA-1 (Coulter Immunology, Hialeah, FL, USA). The presence of EBV small ribonucleic acids was determined by in situ hybridization (ISH) using Epstein–Barr encoding region (EBER) oligonucleotides on formalin-fixed, paraffin-embedded sections, as reported previously [5]. TCR-c gene

Fig. 1 Preoperative imaging studies of the brain tumor using magnetic resonance imaging (MRI) scans and a fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET). a A cranial T1-weighted MRI scan revealing a well-delineated, hypointense mass with intratumoral hemorrhage in the right temporal lobe

and insula. b A T1-weighted MRI scan with gadolinium contrast showing mild enhancement along the cerebral sulci in the tumor. c A T2-weighted MRI scan showing a mixed intense lesion with minimal peritumoral edema. d An FDG-PET image revealing decreased FDG accumulation around the tumor

123

Methods

Brain Tumor Pathol (2015) 32:281–285

rearrangement was detected using the BIOMED2 polymerase chain reaction (PCR) protocol, as described elsewhere [6].

Pathological findings Histological examination of H&E-stained sections revealed perivascular accumulation of small lymphoid cells (Fig. 2a) with round, oval or occasionally irregular nuclei, often indistinct nucleoli, and scanty cytoplasm (Fig. 2c, d). Some areas showed massive necrosis (Fig. 2b). Immunohistochemically, the lymphoid cells were positive for CD3 (CD4? [ CD8?), CD5, CD7, CD16, CD27, CD45RO, TCR-c, TIA-1, and granzyme B, and they were negative for CD20, CD25, CD30, CD56, CD57, TCR-b, and ALK (Fig. 3a–g). While expression of CD16 indicated differentiation towards natural killer (NK) cells, these lymphocytes exhibited loss of CD56 expression. The expression pattern of TCR-c and TCR-b revealed cd TCR phenotype. The Ki-67 proliferative index was 50 %, and the result for EBER-ISH was negative. Clonal TCR-c gene rearrangement was detected by using PCR (Fig. 3h).

Discussion As the atypia of infiltrating lymphoid cells was not overt in the present case, presumably because of steroid premedication, determining the diagnosis of LPD/lymphoma was difficult. In addition, perivascular accumulation of small lymphocytes suggested the differential diagnosis of vasculitis or lymphomatoid granulomatosis. Infact, there is a case report of an adult patient with lymphomatoid

Fig. 2 Histopathological features of the tumor. a Hematoxylin and eosin staining of a tumor specimen demonstrating perivascular lymphoid infiltrates. b Massive cerebral necrosis in the tumor. c, d High-power view of the section showing perivascular accumulation

283

granulomatosis in the CNS progressing to peripheral T-cell lymphoma [7]. In our case, however, aggressive clinical course during the initial treatment and no glanulomatous lesion in the tumor would be more suggestive to T-cell lymphoma rather than lymphomatoid granulomatosis. The expression pattern of differentiation antigens, TCR gene rearrangement, and EBER-ISH are also useful tools in the diagnosis of primary CNS T/NK-cell neoplasms [4, 8– 13]. In the present case, the expression of CD3, CD4, CD5, CD7, CD8, CD16, CD27, and TCR-c, but negativity for CD25, CD30, CD56, CD57, and TCR-b indicated a particular T-cell phenotype, and the expression of TIA-1 and granzyme B further indicated cytotoxic T-lymphocytes. cd TCR phenotype has been reported to be relatively rare than ab TCR phenotype in PTCL [14]. Clonal TCR gene rearrangements suggested a lymphoproliferative or neoplastic disorder. Although our PCR analysis revealed two peaks, there was a possibility of the biallelic rearrangements. Moreover, ALK expression and EBER-ISH results were both negative in the present case, so ALK-positive anaplastic large-cell lymphoma (ALCL), EBV-positive T-cell LPD, or nasal-type natural killer/T-cell lymphoma were all considered as unlikely diagnoses. In the pediatric population, the most common types of T-cell lymphomas are T-cell lymphoblastic lymphoma and ALCL, while PTCL-NOS comprises only 1 % of nonHodgkin lymphoma cases and CNS involvement in PTCLNOS is rare [3, 15]. In contrast, among primary CNS lymphomas, which account for approximately 5 % of all extranodal lymphomas, T-cell lymphoma represents less than 5 %, and most patients are adults [16, 17]. Although the incidence of PTCL-NOS or primary CNS T-cell lymphoma has been reported to be higher in Asian countries [18–20], primary CNS PTCL-NOS is extremely rare.

of small- to medium-sized lymphocytes with minimal atypia and diffuse lymphoid infiltrate in the perivascular area. Original magnifications: a, b 9100, c 9400, d 9600

123

284

Brain Tumor Pathol (2015) 32:281–285

Fig. 3 Pathological characteristics of the tumor. CD3 (a), CD4 (b), and CD8 (c) staining of a specimen revealing T-cell differentiation of the accumulating cells. d Perivascular lymphoid cells showing CD16 positivity, indicating differentiation of natural killer cells. e Expression of granzyme B indicating a cytotoxic phenotype. f The majority

of lymphoid cells demonstrating expression of T-cell receptor (TCR)c. g Only a few lymphocytes around a vessel displaying TCR-b expression. h Analysis of TCR-c gene rearrangement showing two clear clonal peaks (red arrows). Original magnifications: a–g 9400

Whereas several adult patients with primary CNS PTCL have been reported [8–13], this is the second pediatric case of primary CNS PTCL-NOS in the literature. The prognosis of PTCL-NOS is generally worse compared to that of other non-Hodgkin lymphomas [1, 2], and a high proliferation index (Ki-67 [25 %), a cytotoxic phenotype (expression of TIA-1 or granzyme B), and a cd TCR phenotype have been suggested as poor prognostic factors [1, 14, 21, 22]. In the present case, the Ki-67 index was 50 %, and immunostaining for TIA-1, granzyme B, and TCR-c were positive, indicating an aggressive phenotype. In contrast, there is a report of primary CNS T-cell lymphomas having generally good prognoses [23], or a case of primary CNS PTCL-NOS in children successfully treated by complete resection alone [4]. Although the optimal therapy for PTCL-NOS has not been established because of the rarity of the condition, radiochemotherapyresistant CNS PTCL-NOS as described in the present study does occur, and careful follow-up is recommended even after complete remission.

Acknowledgments This work was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (C) (24590478) to Hiroyuki Momota.

123

Compliance with ethical standards Conflict of interest

The authors report no conflict of interest.

References 1. Weisenburger DD, Savage KJ, Harris NL, Gascoyne RD, Jaffe ES, MacLennan KA, Ru¨diger T, Pileri S, Nakamura S, Nathwani B, Campo E, Berger F, Coiffier B, Kim WS, Holte H, Federico M, Au WY, Tobinai K, Armitage JO, Vose JM, International Peripheral T-cell Lymphoma Project (2011) Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood 117:3402–3408 2. Al Mahmoud R, Weitzman S, Schechter T, Ngan B, Abdelhaleem M, Alexander S (2012) Peripheral T-cell lymphoma in children and adolescents: a single-institution experience. J Pediatr Hematol Oncol 34:611–616 3. Windsor R, Stiller C, Webb D (2008) Peripheral T-cell lymphoma in childhood: population-based experience in the United Kingdom over 20 years. Pediatr Blood Cancer 50:784–787

Brain Tumor Pathol (2015) 32:281–285 4. Lueth M, Stein H, Spors B, Henze G, Driever PH (2012) First case report of a peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child. J Pediatr Hematol Oncol 34:e66–e68 5. Kato S, Takahashi E, Asano N, Tanaka T, Megahed N, Kinoshita T, Nakamura S (2012) Nodal cytotoxic molecule (CM)-positive Epstein–Barr virus (EBV)-associated peripheral T cell lymphoma (PTCL): a clinicopathological study of 26 cases. Histopathology 61:186–199 6. van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcı´a-Sanz R, van Krieken JH, Droese J, Gonza´lez D, Bastard C, White HE, Spaargaren M, Gonza´lez M, Parreira A, Smith JL, Morgan GJ, Kneba M, Macintyre EA (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317 7. Takiyama A, Nishihara H, Tateishi U, Kimura T, Wang L, Marukawa K, Itoh T, Hashino S, Nagashima K, Tanaka S (2008) CNS lymphomatoid granulomatosis with lymph node and bone marrow involvements. Neuropathology 28:640–644 8. Lee DK, Chung CK, Kim HJ, Kim K, Choe G, Moon CW, Kim DY (2002) Multifocal primary CNS T cell lymphoma of the spinal cord. Clin Neuropathol 21:149–155 9. Liu D, Schelper RL, Carter DA, Poiesz BJ, Shrimpton AE, Frankel BM, Hutchison RE (2003) Primary central nervous system cytotoxic/suppressor T-cell lymphoma: report of a unique case and review of the literature. Am J Surg Pathol 27:682–688 10. Demetriades AK, McEvoy AW, Galloway M, Kitchen ND (2003) Peripheral T-cell lymphoma presenting as a solitary vermian mass. Br J Neurosurg 17:473–475 11. Harder A, Dudel C, Anagnostopoulos I, Hummel M, Bru¨ck W (2003) Molecular genetic diagnosis of a primary central nervous system T cell lymphoma. Acta Neuropathol 105:65–68 12. Ogura R, Aoki H, Natsumeda M, Shimizu H, Kobayashi T, Saito T, Takizawa J, Okamoto K, Hasegawa G, Umezu H, Ohshima K, Takahashi H, Fujii Y, Kakita A (2013) Epstein–Barr virus-associated primary central nervous system cytotoxic T-cell lymphoma. Neuropathology 33:436–441 13. Kato Y, Hayashi T, Kawai-Masaoka A, Ichimura T, Sasaki A, Uchino A, Nagamine Y, Tanahashi N (2014) Primary central nervous system cytotoxic T-cell lymphoma mimicking demyelinating disease. Intern Med 53:1197–1200 14. Kato S, Asano N, Miyata-Takata T, Takata K, Elsayed AA, Satou A, Takahashi E, Kinoshita T, Nakamura S (2015) T-cell receptor (TCR) phenotype of nodal Epstein–Barr virus (EBV)-positive

285

15.

16.

17.

18.

19.

20.

21.

22.

23.

cytotoxic T-cell lymphoma (CTL): a clinicopathologic study of 39 cases. Am J Surg Pathol 39:462–471 El-Mallawany NK, Frazer JK, Van Vlierberghe P, Ferrando AA, Perkins S, Lim M, Chu Y, Cairo MS (2012) Pediatric T- and NKcell lymphomas: new biologic insights and treatment strategies. Blood Cancer J 2:e65 Bataille B, Delwail V, Menet E, Vandermarcq P, Ingrand P, Wager M, Guy G, Lapierre F (2000) Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 92:261–266 Ferreri AJ, Reni M, Pasini F, Calderoni A, Tirelli U, Pivnik A, Aondio GM, Ferrarese F, Gomez H, Ponzoni M, Borisch B, Berger F, Chassagne C, Iuzzolino P, Carbone A, Weis J, Pedrinis E, Motta T, Jouvet A, Barbui T, Cavalli F, Blay JY (2002) A multicenter study of treatment of primary CNS lymphoma. Neurology 58:1513–1520 Lymphoma Study Group of Japanese Pathologists (2000) The world health organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Pathol Int 50:696–702 Choi JS, Nam DH, Ko YH, Seo JW, Choi YL, Suh YL, Ree HJ (2003) Primary central nervous system lymphoma in Korea: comparison of B- and T-cell lymphomas. Am J Surg Pathol 27:919–928 Shibamoto Y, Ogino H, Suzuki G, Takemoto M, Araki N, Isobe K, Tsuchida E, Nakamura K, Kenjo M, Suzuki K, Hosono M, Tokumaru S, Ishihara S, Kato E, Ii N, Hayabuchi N (2008) Primary central nervous system lymphoma in Japan: changes in clinical features, treatment, and prognosis during 1985–2004. Neuro Oncol 10:560–568 Asano N, Suzuki R, Kagami Y, Ishida F, Kitamura K, Fukutani H, Morishima Y, Takeuchi K, Nakamura S (2005) Clinicopathologic and prognostic significance of cytotoxic molecule expression in nodal peripheral T-cell lymphoma, unspecified. Am J Surg Pathol 29:1284–1293 Iqbal J, Weisenburger DD, Greiner TC, Vose JM, McKeithan T, Kucuk C, Geng H, Deffenbacher K, Smith L, Dybkaer K, Nakamura S, Seto M, Delabie J, Berger F, Loong F, Au WY, Ko YH, Sng I, Armitage JO, Chan WC (2010) Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. Blood 115:1026–1036 Lim T, Kim SJ, Kim K, Lee JI, Lim do H, Lee DJ, Baek KK, Lee HY, Han B, Uhm JE, Ko YH, Kim WS (2011) Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes. Ann Hematol 90:1391–1398

123