nach oben

Erschienen in:

13.01.2016 | Original Article

Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of “germinotropic” lymphoproliferative disorder

verfasst von: Luisa Lorenzi, Silvia Lonardi, Murad H. M. Essatari, Vilma Pellegrini, Simona Fisogni, Anna Gazzola, Claudio Agostinelli, William Vermi, Giuseppe Rossi, Giovannino Massarelli, Stefano A. Pileri, Fabio Facchetti

Erschienen in: Virchows Archiv | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Germinotropic lymphoproliferative disorders were previously described as localized disorders associated with coinfection by human herpes virus 8 and Epstein-Barr virus and characterized by good clinical outcome. We report the clinical, morphological, phenotypical, and molecular features of three cases of a hitherto unreported variant of Epstein-Barr virus (EBV)-positive, human herpes virus 8 (HHV8)-negative large B cell lymphoma with exclusive intrafollicular localization. All cases occurred in elderly individuals (63, 77, and 65 years old; one male, two females) without obvious immunedeficiency, who presented with high stage disease. Lymph nodes showed an effaced nodular architecture with abnormal B follicles colonized by EBV+ large, pleomorphic atypical cells, including Reed-Sternberg-like cells, showing an activated B cell phenotype (CD10-FOXP1-Bcl6-IRF4+ or CD10-FOXP1+Bcl6+IRF4+) and intense expression of CD30. No monoclonal light-chain restriction was detected by immunohistochemistry or in situ hybridization, and IGH rearrangement was polyclonal; notably, EBV clonality was detectable in one case. Lymphoma cells in all cases showed diffuse expression of the c-Myc protein, while Bcl2 was dim or negative; moreover, the strong expression of phosphorylated-STAT3 in tumor cell nuclei suggested activation of the JAK-STAT pathway. FISH analysis was performed in two cases and showed no translocations of BCL2, BCL6, MYC, and PAX5 genes. Response to treatment was poor in 2/3 patients: one died after 18 months, one is alive with disease after 12 months. The intrafollicular EBV-positive large B cell lymphoma expands the spectrum of EBV-associated lymphoproliferative disorders in immunocompetent individuals.

Nur mit Berechtigung zugänglich

Suster S (1992) Large cell lymphoma of the mediastinum with marked tropism for germinal centers. Cancer 69(12):2910–2916CrossRefPubMed

Du MQ, Diss TC, Liu H, Ye H, Hamoudi RA, Cabecadas J, Dong HY, Harris NL, Chan JK, Rees JW, Dogan A, Isaacson PG (2002) KSHV- and EBV-associated germinotropic lymphoproliferative disorder. Blood 100(9):3415–3418CrossRefPubMed

D'Antonio A, Boscaino A, Addesso M, Piris MA, Nappi O (2007) KSHV- and EBV-associated germinotropic lymphoproliferative disorder: a rare lymphoproliferative disease of HIV patient with plasmablastic morphology, indolent course and favourable response to therapy. Leuk Lymphoma 48(7):1444–1447CrossRefPubMed

Oh J, Yoon H, Shin DK, Jang MJ, Kim GI, Chong SY, Oh D (2012) A case of successful management of HHV-8(+), EBV(+) germinotropic lymphoproliferative disorder (GLD). Int J Hematol 95(1):107–111CrossRefPubMed

Courville EL, Sohani AR, Hasserjian RP, Zukerberg LR, Harris NL, Ferry JA (2014) Diverse clinicopathologic features in human herpesvirus 8-associated lymphomas lead to diagnostic problems. Am J Clin Pathol 142(6):816–829CrossRefPubMed

Papoudou-Bai A, Hatzimichael E, Kyriazopoulou L, Briasoulis E, Kanavaros P (2015) Rare variants in the spectrum of human herpesvirus 8/Epstein-Barr virus-copositive lymphoproliferations. Hum Pathol 46(10):1566–1571CrossRefPubMed

Vermi W, Lonardi S, Morassi M, Rossini C, Tardanico R, Venturini M, Sala R, Tincani A, Poliani PL, Calzavara-Pinton PG, Cerroni L, Santoro A, Facchetti F (2009) Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage. Immunobiology 214(9–10):877–886CrossRefPubMed

van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcia-Sanz R, van Krieken JH, Droese J, Gonzalez D, Bastard C, White HE, Spaargaren M, Gonzalez 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(12):2257–2317CrossRefPubMed

Gutierrez MI, Spangler G, Kingma D, Raffeld M, Guerrero I, Misad O, Jaffe ES, Magrath IT, Bhatia K (1998) Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the EBNA-1 gene. Blood 92(2):600–606PubMed

10.

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282CrossRefPubMed

11.

Visco C, Li Y, Xu-Monette ZY, Miranda RN, Green TM, Li Y, Tzankov A, Wen W, Liu WM, Kahl BS, d'Amore ES, Montes-Moreno S, Dybkaer K, Chiu A, Tam W, Orazi A, Zu Y, Bhagat G, Winter JN, Wang HY, O'Neill S, Dunphy CH, Hsi ED, Zhao XF, Go RS, Choi WW, Zhou F, Czader M, Tong J, Zhao X, van Krieken JH, Huang Q, Ai W, Etzell J, Ponzoni M, Ferreri AJ, Piris MA, Moller MB, Bueso-Ramos CE, Medeiros LJ, Wu L, Young KH (2012) Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia 26(9):2103–2113CrossRefPubMedPubMedCentral

12.

Dirmeier U, Hoffmann R, Kilger E, Schultheiss U, Briseno C, Gires O, Kieser A, Eick D, Sugden B, Hammerschmidt W (2005) Latent membrane protein 1 of Epstein-Barr virus coordinately regulates proliferation with control of apoptosis. Oncogene 24(10):1711–1717CrossRefPubMed

13.

Shin DY, Kim A, Kang HJ, Park S, Kim DW, Lee SS (2015) Histone deacetylase inhibitor romidepsin induces efficient tumor cell lysis via selective down-regulation of LMP1 and c-myc expression in EBV-positive diffuse large B-cell lymphoma. Cancer Lett 364(2):89–97CrossRefPubMed

14.

Kiuchi N, Nakajima K, Ichiba M, Fukada T, Narimatsu M, Mizuno K, Hibi M, Hirano T (1999) STAT3 is required for the gp130-mediated full activation of the c-myc gene. J Exp Med 189(1):63–73CrossRefPubMedPubMedCentral

15.

Cyster JG, Ansel KM, Reif K, Ekland EH, Hyman PL, Tang HL, Luther SA, Ngo VN (2000) Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev 176:181–193CrossRefPubMed

16.

Muller G, Hopken UE, Lipp M (2003) The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Immunol Rev 195:117–135CrossRefPubMed

17.

Montes-Moreno S, Odqvist L, Diaz-Perez JA, Lopez AB, de Villambrosia SG, Mazorra F, Castillo ME, Lopez M, Pajares R, Garcia JF, Mollejo M, Camacho FI, Ruiz-Marcellan C, Adrados M, Ortiz N, Franco R, Ortiz-Hidalgo C, Suarez-Gauthier A, Young KH, Piris MA (2012) EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol 25(7):968–982CrossRefPubMed

18.

Ok CY, Li L, Xu-Monette ZY, Visco C, Tzankov A, Manyam GC, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Chen J, Richards KL, Hsi ED, Choi WW, van Krieken JH, Huh J, Ai W, Ponzoni M, Ferreri AJ, Farnen JP, Moller MB, Bueso-Ramos CE, Miranda RN, Winter JN, Piris MA, Medeiros LJ, Young KH (2014) Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries. Clin Cancer Res 20(9):2338–2349CrossRefPubMedPubMedCentral

19.

Bromberg J, Darnell JE Jr (2000) The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19(21):2468–2473CrossRefPubMed

20.

Lam LT, Wright G, Davis RE, Lenz G, Farinha P, Dang L, Chan JW, Rosenwald A, Gascoyne RD, Staudt LM (2008) Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma. Blood 111(7):3701–3713CrossRefPubMedPubMedCentral

21.

Ding BB, Yu JJ, Yu RY, Mendez LM, Shaknovich R, Zhang Y, Cattoretti G, Ye BH (2008) Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood 111(3):1515–1523CrossRefPubMedPubMedCentral

22.

Kato H, Karube K, Yamamoto K, Takizawa J, Tsuzuki S, Yatabe Y, Kanda T, Katayama M, Ozawa Y, Ishitsuka K, Okamoto M, Kinoshita T, Ohshima K, Nakamura S, Morishima Y, Seto M (2014) Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways. Cancer Sci 105(5):537–544CrossRefPubMedPubMedCentral

23.

Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R (2001) Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A 98(13):7319–7324CrossRefPubMedPubMedCentral

24.

Ok CY, Chen J, Xu-Monette ZY, Tzankov A, Manyam GC, Li L, Visco C, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WW, van Krieken JH, Huh J, Zhao X, Ponzoni M, Ferreri AJ, Bertoni F, Farnen JP, Moller MB, Piris MA, Winter JN, Medeiros LJ, Young KH (2014) Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma. Clin Cancer Res 20(19):5113–5123CrossRefPubMedPubMedCentral

25.

Taddesse-Heath L, Meloni-Ehrig A, Scheerle J, Kelly JC, Jaffe ES (2010) Plasmablastic lymphoma with MYC translocation: evidence for a common pathway in the generation of plasmablastic features. Mod Pathol 23(7):991–999CrossRefPubMed

26.

Valera A, Balague O, Colomo L, Martinez A, Delabie J, Taddesse-Heath L, Jaffe ES, Campo E (2010) IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol 34(11):1686–1694PubMedPubMedCentral

27.

Gebauer N, Gebauer J, Hardel TT, Bernard V, Biersack H, Lehnert H, Rades D, Feller AC, Thorns C (2015) Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly. Leuk Lymphoma 56(4):1100–1106CrossRefPubMed

28.

Hoeller S, Tzankov A, Pileri SA, Went P, Dirnhofer S (2010) Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations. Hum Pathol 41(3):352–357CrossRefPubMed

29.

Uccini S, Al-Jadiry MF, Scarpino S, Ferraro D, Alsaadawi AR, Al-Darraji AF, Moleti ML, Testi AM, Al-Hadad SA, Ruco L (2015) Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly. Hum Pathol 46(5):716–724CrossRefPubMed

30.

Vaghefi P, Martin A, Prevot S, Charlotte F, Camilleri-Broet S, Barli E, Davi F, Gabarre J, Raphael M, Poirel HA (2006) Genomic imbalances in AIDS-related lymphomas: relation with tumoral Epstein-Barr virus status. Aids 20(18):2285–2291CrossRefPubMed

31.

Capello D, Scandurra M, Poretti G, Rancoita PM, Mian M, Gloghini A, Deambrogi C, Martini M, Rossi D, Greiner TC, Chan WC, Ponzoni M, Moreno SM, Piris MA, Canzonieri V, Spina M, Tirelli U, Inghirami G, Rinaldi A, Zucca E, Favera RD, Cavalli F, Larocca LM, Kwee I, Carbone A, Gaidano G, Bertoni F (2009) Genome wide DNA-profiling of HIV-related B-cell lymphomas. Br J Haematol 148(2):245–255CrossRefPubMed

32.

Rinaldi A, Kwee I, Poretti G, Mensah A, Pruneri G, Capello D, Rossi D, Zucca E, Ponzoni M, Catapano C, Tibiletti MG, Paulli M, Gaidano G, Bertoni F (2006) Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas. Br J Haematol 134(1):27–36CrossRefPubMed

33.

Huppmann AR, Nicolae A, Slack GW, Pittaluga S, Davies-Hill T, Ferry JA, Harris NL, Jaffe ES, Hasserjian RP (2014) EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults. Am J Surg Pathol 38(3):316–324CrossRefPubMedPubMedCentral

34.

Lorenzi L, Lonardi S, Petrilli G, Tanda F, Bella M, Laurino L, Rossi G, Facchetti F (2012) Folliculocentric B-cell-rich follicular dendritic cells sarcoma: a hitherto unreported morphological variant mimicking lymphoproliferative disorders. Hum Pathol 43(2):209–215CrossRefPubMed

35.

Dojcinov SD, Venkataraman G, Pittaluga S, Wlodarska I, Schrager JA, Raffeld M, Hills RK, Jaffe ES (2011) Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma. Blood 117(18):4726–4735CrossRefPubMedPubMedCentral

36.

Kojima M, Nakamura S, Shimizu K, Iijima M, Murayama K, Ohno Y, Itoh H, Sakata N, Masawa N (2005) Reactive lymphoid hyperplasia of the lymph nodes with giant follicles: a clinicopathologic study of 14 Japanese cases, with special reference to Epstein-Barr virus infection. Int J Surg Pathol 13(3):267–272CrossRefPubMed

37.

De la Hera Magallanes AI, Montes-Moreno S, Hernandez SG, Hernandez-Leon CN, Lopez M, Pajares R, Pinilla SM, Piris MA (2011) Early phase of Epstein-Barr virus (EBV)-positive diffuse large B cell lymphoma of the elderly mimicking EBV-positive reactive follicular hyperplasia. Histopathology 59(3):571–575CrossRefPubMed

38.

van der Horst M, Hardwick A, Rahilly M, Goodlad JR (2015) Epstein-Barr virus-positive primary cutaneous follicle center lymphoma; an age related phenomenon? Virchows Arch 467(1):111–117CrossRefPubMed

Titel: Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of “germinotropic” lymphoproliferative disorder
verfasst von: Luisa Lorenzi
Silvia Lonardi
Murad H. M. Essatari
Vilma Pellegrini
Simona Fisogni
Anna Gazzola
Claudio Agostinelli
William Vermi
Giuseppe Rossi
Giovannino Massarelli
Stefano A. Pileri
Fabio Facchetti
Publikationsdatum: 13.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 4/2016
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-015-1902-9

Springer Medizin

Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of “germinotropic” lymphoproliferative disorder

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2016

Prognostic significance of tumor regression in lymph nodes after neoadjuvant therapy for rectal carcinoma

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma

Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term

Application of the 2013 ASCO/CAP guideline and the SISH technique for HER2 testing of breast cancer selects more patients for anti-HER2 treatment

Doing more with less: fluorescence in situ hybridization and gene sequencing assays can be reliably performed on archival stained tumor tissue sections

The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie