Abstract
This chapter discusses the clinical, radiologic, histopathologic, and relevant cytogenetic and molecular alterations of reactive and malignant mediastinal lymphoproliferative disorders. All these entities comprise a significant proportion of cases seen by clinicians, radiologists, and pathologists, particularly those specialized in thoracic or hematologic diseases. Clinically, these lesions manifest as mediastinal lymphadenopathy or a mediastinal mass with or without disease elsewhere, and the clinical and radiologic suspicion is usually that of malignancy. A biopsy (fine needle aspiration, core biopsy, video-assisted thoracoscopy, mediastinoscopy, or excisional biopsy) is required to establish a diagnosis and the modality of this procedure depends on the location of a lesion within the mediastinum. Benign or reactive conditions discussed here include sarcoidosis, other granulomatous lymphadenitis with a known etiology, Castleman disease, IgG4-related disease/sclerosing mediastinitis, and the histiocytic disorders Langerhans cell histiocytosis and Rosai-Dorfman disease. For some of these lesions, morphology and a limited panel of ancillary studies are sufficient to establish a diagnosis. However, for some others clinico-radiologic and laboratory correlation (cultures, PCR, serology) are required to render a complete diagnostic interpretation. Malignant mediastinal hematolymphoid disorders discussed here include common and rare neoplasms at this location such as classic Hodgkin lymphoma, non-Hodgkin lymphomas (T-lymphoblastic leukemia/lymphoma, diffuse large B-cell lymphoma, primary mediastinal [thymic] large B-cell lymphoma, mediastinal gray zone lymphoma, T-cell lymphomas), myeloid sarcoma, and follicular dendritic cell (FDC) sarcoma. In contrast to reactive conditions, each of these malignant disorders has a particular clinic-radiologic presentation and tends to present with chest pain, dyspnea, cough, effusions, and superior vena cava syndrome if there is bulky disease. Along with proper morphologic evaluation, the diagnosis of these neoplasms requires the use of ≥1 ancillary studies to arrive at the correct diagnosis, and nowadays most cases require cytogenetics, fluorescence in situ hybridization, and/or molecular analyses to identify potential prognostic or predictive markers.
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References
Scadding JG. The eponymy of sarcoidosis. J R Soc Med. 1981;74:147–57.
Eishi Y. Etiologic aspect of sarcoidosis as an allergic endogenous infection caused by Propionibacterium acnes. Biomed Res Int. 2013;2013:935289.
Eishi Y. Etiologic link between sarcoidosis and Propionibacterium acnes. Respir Invest. 2013;51:56–68.
Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153–65.
Narula N, Iannuzzi M. Sarcoidosis: pitfalls and challenging mimickers. Front Med (Lausanne). 2020;7:594275.
Asano S. Granulomatous lymphadenitis. J Clin Exp Hematop. 2012;52:1–16.
Fontanilla JM, Barnes A, von Reyn CF. Current diagnosis and management of peripheral tuberculous lymphadenitis. Clin Infect Dis. 2011;53:555–62.
Crothers JW, Laga AC, Solomon IH. Clinical performance of mycobacterial immunohistochemistry in anatomic pathology specimens. Am J Clin Pathol. 2021;155:97–105.
Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer. 1956;9:822–30.
Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer. 1972;29:670–83.
Lin O, Frizzera G. Angiomyoid and follicular dendritic cell proliferative lesions in Castleman’s disease of hyaline-vascular type: a study of 10 cases. Am J Surg Pathol. 1997;21:1295–306.
Ohgami RS, Zhao S, Ohgami JK, et al. TdT+ T-lymphoblastic populations are increased in Castleman disease, in Castleman disease in association with follicular dendritic cell tumors, and in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol. 2012;36:1619–28.
Ohgami RS, Arber DA, Zehnder JL, Natkunam Y, Warnke RA. Indolent T-lymphoblastic proliferation (iT-LBP): a review of clinical and pathologic features and distinction from malignant T-lymphoblastic lymphoma. Adv Anat Pathol. 2013;20:137–40.
Nathwani BN, Kansal R, Yiakoumis X, Pangalis GA. Indolent T-lymphoblastic proliferation: a name with specific meaning—reply. Hum Pathol. 2015;46:1786–7.
Sun X, Chang KC, Abruzzo LV, Lai R, Younes A, Jones D. Epidermal growth factor receptor expression in follicular dendritic cells: a shared feature of follicular dendritic cell sarcoma and Castleman’s disease. Hum Pathol. 2003;34:835–40.
Iwaki N, Fajgenbaum DC, Nabel CS, et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol. 2016;91:220–6.
Dispenzieri A. POEMS syndrome: 2017 Update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92:814–29.
Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129:1646–57.
Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol. 2012;29:226–34.
Dozois RR, Bernatz PE, Woolner LB, Andersen HA. Sclerosing mediastinitis involving major bronchi. Mayo Clin Proc. 1968;43:557–69.
Afrin LB. Sclerosing mediastinitis and mast cell activation syndrome. Pathol Res Pract. 2012;208:181–5.
Gorospe L, Ayala-Carbonero AM, Fernandez-Mendez MA, et al. Idiopathic fibrosing mediastinitis: spectrum of imaging findings with emphasis on its association with IgG4-related disease. Clin Imaging. 2015;39:993–9.
Jain N, Chauhan U, Puri SK, Agrawal S, Garg L. Fibrosing mediastinitis: when to suspect and how to evaluate? BJR Case Rep. 2016;2:20150274.
Kang DW, Canzian M, Beyruti R, Jatene FB. Sclerosing mediastinitis in the differential diagnosis of mediastinal tumors. J Bras Pneumol. 2006;32:78–83.
Masunaga A, Ishibashi F, Koh E, Oide T, Sekine Y, Hiroshima K. Possible relationship between fibrosis of IgG4-related thymitis and the profibrotic cytokines, transforming growth factor beta 1, interleukin 1 beta and interferon gamma: a case report. Diagn Pathol. 2018;13:6.
Peebles RS, Carpenter CT, Dupont WD, Loyd JE. Mediastinal fibrosis is associated with human leukocyte antigen-A2. Chest. 2000;117:482–5.
D’Agaro T, Bittolo T, Bravin V, et al. NOTCH1 mutational status in chronic lymphocytic leukaemia: clinical relevance of subclonal mutations and mutation types. Br J Haematol. 2018;182(4):597–602.
Worrell JA, Donnelly EF, Martin JB, Bastarache JA, Loyd JE. Computed tomography and the idiopathic form of proliferative fibrosing mediastinitis. J Thorac Imaging. 2007;22:235–40.
Lindholm KE, de Groot P, Moran CA. Fibrosing/sclerosing lesions of the mediastinum: a review. Adv Anat Pathol. 2019;26(4):235–40.
Rossi GM, Emmi G, Corradi D, et al. Idiopathic mediastinal fibrosis: a systemic immune-mediated disorder. A case series and a review of the literature. Clin Rev Allergy Immunol. 2017;52:446–59.
Chen JL, Osborne BM, Butler JJ. Residual fibrous masses in treated Hodgkin’s disease. Cancer. 1987;60:407–13.
Engleman P, Liebow AA, Gmelich J, Friedman PJ. Pulmonary hyalinizing granuloma. Am Rev Respir Dis. 1977;115:997–1008.
Flieder DB, Suster S, Moran CA. Idiopathic fibroinflammatory (fibrosing/sclerosing) lesions of the mediastinum: a study of 30 cases with emphasis on morphologic heterogeneity. Mod Pathol. 1999;12:257–64.
Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.
Coppes-Zantinga A, Egeler RM. The Langerhans cell histiocytosis X files revealed. Br J Haematol. 2002;116:3–9.
Breathnach AS, Gross M, Basset F, Nezelof C. Freeze-fracture replication of X-granules in cells of cutaneous lesions of histiocytosis-X. Br J Dermatol. 1973;89:571–85.
Nezelof C, Basset F, Rousseau MF. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine. 1973;18:365–71.
Langerhans P. Ueber die Nerven der Menschlichen Haut. Virchow Arch [B]. 1868;44:325–37.
Birbeck MS, Breathnach AS, Everall JD. An electron microscopy study of basal melanocytes and high-level clear cell (Langerhans cells) in vitiligo. J Invest Dermatol. 1961;75:51–64.
Willman CL, Busque L, Griffith BB, et al. Langerhans’-cell histiocytosis (histiocytosis X)—a clonal proliferative disease. N Engl J Med. 1994;331:154–60.
Yu RC, Chu C, Buluwela L, Chu AC. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet. 1994;343:767–8.
Badalian-Very G, Vergilio JA, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 2010;116:1919–23.
Capper D, Preusser M, Habel A, et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 2011;122:11–9.
Berres ML, Merad M, Allen CE. Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X? Br J Haematol. 2015;169:3–13.
Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124:3007–15.
Nelson DS, van Halteren A, Quispel WT, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer. 2015;54:361–8.
Chakraborty R, Burke TM, Hampton OA, et al. Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis. Blood. 2016;128:2533–7.
Egeler RM, Katewa S, Leenen PJ, et al. Langerhans cell histiocytosis is a neoplasm and consequently its recurrence is a relapse: In memory of Bob Arceci. Pediatr Blood Cancer. 2016;63:1704–12.
Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672–81.
Haroche J, Charlotte F, Arnaud L, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120:2700–3.
Alayed K, Medeiros LJ, Patel KP, et al. BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases. Hum Pathol. 2016;52:61–7.
Nicholson HS, Egeler RM, Nesbit ME. The epidemiology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998;12:379–84.
Abramson SJ, Berdon WE, Reilly BJ, Kuhn JP. Cavitation of anterior mediastinal masses in children with histiocytosis-X. Report of four cases with radiographic, pathologic findings and clinical follow up. Pediatr Radiol. 1987;17:10–4.
Ducassou S, Seyrig F, Thomas C, et al. Thymus and mediastinal node involvement in childhood Langerhans cell histiocytosis: long-term follow-up from the French national cohort. Pediatr Blood Cancer. 2013;60:1759–65.
Fahrner R, Hoksch B, Gugger M, Schmid RA. Langerhans cell histiocytosis as differential diagnosis of a mediastinal tumor. Eur J Cardiothorac Surg. 2008;33:516–7.
Khadilkar UN, Rao AT, Sahoo KK, Pai MR. Langerhans cell histiocytosis of mediastinal node. Indian J Pediatr. 2008;75:294–6.
Mogul M, Hartman G, Donaldson S, et al. Langerhans’ cell histiocytosis presenting with the superior vena cava syndrome: a case report. Med Pediatr Oncol. 1993;21:456–9.
Odagiri K, Nishihira K, Hatekeyama S, Kobayashi K. Anterior mediastinal masses with calcifications on CT in children with histiocytosis-X (Langerhans cell histiocytosis). Report of two cases. Pediatr Radiol. 1991;21:550–1.
Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev. 2010;36:354–9.
Donadieu J, Bernard F, van Noesel M, et al. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015;126:1415–23.
Haroche J, Cohen-Aubart F, Emile JF, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013;121:1495–500.
Edelweiss M, Medeiros LJ, Suster S, Moran CA. Lymph node involvement by Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical study of 20 cases. Hum Pathol. 2007;38:1463–9.
Garces S, Yin CC, Miranda RN, et al. Clinical, histopathologic, and immunoarchitectural features of dermatopathic lymphadenopathy: an update. Mod Pathol. 2020;33:1104–21.
Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol. 1969;87:63–70.
Foucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. Arch Otolaryngol. 1978;104:687–93.
Foucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. An analysis of 14 deaths occurring in a patient registry. Cancer. 1984;54:1834–40.
Foucar E, Rosai J, Dorfman RF, Eyman JM. Immunologic abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy. Am J Clin Pathol. 1984;82:515–25.
Levine PH, Jahan N, Murari P, Manak M, Jaffe ES. Detection of human herpesvirus 6 in tissues involved by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). J Infect Dis. 1992;166:291–5.
Mehraein Y, Wagner M, Remberger K, et al. Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations. J Clin Pathol. 2006;59:1320–6.
Ortonne N, Fillet AM, Kosuge H, Bagot M, Frances C, Wechsler J. Cutaneous Destombes-Rosai-Dorfman disease: absence of detection of HHV-6 and HHV-8 in skin. J Cutan Pathol. 2002;29:113–8.
Tsang WY, Yip TT, Chan JK. The Rosai-Dorfman disease histiocytes are not infected by Epstein-Barr virus. Histopathology. 1994;25:88–90.
Liu L, Perry AM, Cao W, et al. Relationship between Rosai-Dorfman disease and IgG4-related disease: study of 32 cases. Am J Clin Pathol. 2013;140:395–402.
Zhang X, Hyjek E, Vardiman J. A subset of Rosai-Dorfman disease exhibits features of IgG4-related disease. Am J Clin Pathol. 2013;139:622–32.
Menon MP, Evbuomwan MO, Rosai J, Jaffe ES, Pittaluga S. A subset of Rosai-Dorfman disease cases show increased IgG4-positive plasma cells: another red herring or a true association with IgG4-related disease? Histopathology. 2014;64:455–9.
Marsh WL Jr, McCarrick JP, Harlan DM. Sinus histiocytosis with massive lymphadenopathy. Occurrence in identical twins with retroperitoneal disease. Arch Pathol Lab Med. 1988;112:298–301.
Morgan NV, Morris MR, Cangul H, et al. Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease. PLoS Genet. 2010;6:e1000833.
Rossbach HC, Dalence C, Wynn T, Tebbi C. Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness. Pediatr Blood Cancer. 2006;47:629–32.
Garces S, Medeiros LJ, Patel KP, et al. Mutually exclusive recurrent KRAS and MAP2K1 mutations in Rosai-Dorfman disease. Mod Pathol. 2017;30(10):1367–77.
Matter MS, Bihl M, Juskevicius D, Tzankov A. Is Rosai-Dorfman disease a reactve process? Detection of a MAP2K1 L115V mutation in a case of Rosai-Dorfman disease. Virchows Arch. 2017;471(4):545–7.
Jacobsen E, Shanmugam V, Jagannathan J. Rosai-Dorfman disease with activating KRAS mutation—response to Cobimetinib. N Engl J Med. 2017;377:2398–9.
Costa AL, Silva NO, Motta MP, Athanazio RA, Athanazio DA, Athanazio PR. Soft tissue Rosai-Dorfman disease of the posterior mediastinum. J Bras Pneumol. 2009;35:717–20.
Cunha BA, Durie N, Selbs E, Pherez F. Fever of unknown origin (FUO) due to Rosai-Dorfman disease with mediastinal adenopathy mimicking lymphoma: diagnostic importance of elevated serum ferritin levels and polyclonal gammopathy. Heart Lung. 2009;38:83–8.
Dalia S, Sagatys E, Sokol L, Kubal T. Rosai-Dorfman disease: tumor biology, clinical features, pathology, and treatment. Cancer Control. 2014;21:322–7.
Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: a pseudolymphomatous benign disorder. Analysis of 34 cases. Cancer. 1972;30:1174–88.
Overholtzer M, Brugge JS. The cell biology of cell-in-cell structures. Nat Rev Mol Cell Biol. 2008;9:796–809.
Rastogi V, Sharma R, Misra SR, Yadav L, Sharma V. Emperipolesis—a review. J Clin Diagn Res. 2014;8:ZM01-2.
Bonetti F, Chilosi M, Menestrina F, et al. Immunohistological analysis of Rosai-Dorfman histiocytosis. A disease of S-100 + CD1-histiocytes. Virchows Arch A Pathol Anat Histopathol. 1987;411:129–35.
Emile JF, Charlotte F, Amoura Z, Haroche J. BRAF mutations in Erdheim-Chester disease. J Clin Oncol. 2013;31:398.
Ozkaya N, Rosenblum MK, Durham BH, et al. The histopathology of Erdheim-Chester disease: a comprehensive review of a molecularly characterized cohort. Mod Pathol. 2018;31:581–97.
Temes R, Allen N, Chavez T, Crowell R, Key C, Wernly J. Primary mediastinal malignancies in children: report of 22 patients and comparison to 197 adults. Oncologist. 2000;5:179–84.
Temes R, Chavez T, Mapel D, et al. Primary mediastinal malignancies: findings in 219 patients. West J Med. 1999;170:161–6.
Macchiarini P, Ostertag H. Uncommon primary mediastinal tumours. Lancet Oncol. 2004;5:107–18.
Strickler JG, Kurtin PJ. Mediastinal lymphoma. Semin Diagn Pathol. 1991;8:2–13.
Klapper W, Jaffe E, Gaulard P, et al. Primary mediastinal large B-cell lymphoma. In: Travis W, Brambilla E, Burke A, Marx A, Nicholson A, editors. WHO classification of tumors of the lung, pleura, thymus and heart. 4th ed. Lyon: IARC; 2015. p. 267–9.
Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (“Groupe d’Etude des Lymphomes de l’Adulte”) study. Am J Surg Pathol. 1996;20:877–88.
Dunleavy K. Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies. Hematol Am Soc Hematol Educ Program. 2017;2017:298–303.
Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med. 2003;198:851–62.
Savage KJ, Al-Rajhi N, Voss N, et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol. 2006;17:123–30.
Lichtenstein AK, Levine A, Taylor CR, et al. Primary mediastinal lymphoma in adults. Am J Med. 1980;68:509–14.
Miller JB, Variakojis D, Bitran JD, et al. Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction. Cancer. 1981;47:748–56.
Moller P, Lammler B, Eberlein-Gonska M, et al. Primary mediastinal clear cell lymphoma of B-cell type. Virchows Arch A Pathol Anat Histopathol. 1986;409:79–92.
Moller P, Moldenhauer G, Momburg F, et al. Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation. Blood. 1987;69:1087–95.
Nakagawa A, Nakamura S, Koshikawa T, et al. Clinicopathologic study of primary mediastinal non-lymphoblastic non-Hodgkin’s lymphomas among the Japanese. Acta Pathol Jpn. 1993;43:44–54.
Perrone T, Frizzera G, Rosai J. Mediastinal diffuse large-cell lymphoma with sclerosis. A clinicopathologic study of 60 cases. Am J Surg Pathol. 1986;10:176–91.
Davis RE, Dorfman RF, Warnke RA. Primary large-cell lymphoma of the thymus: a diffuse B-cell neoplasm presenting as primary mediastinal lymphoma. Hum Pathol. 1990;21:1262–8.
Lamarre L, Jacobson JO, Aisenberg AC, Harris NL. Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases. Am J Surg Pathol. 1989;13:730–9.
Menestrina F, Chilosi M, Bonetti F, et al. Mediastinal large-cell lymphoma of B-type, with sclerosis: histopathological and immunohistochemical study of eight cases. Histopathology. 1986;10:589–600.
Yousem SA, Weiss LM, Warnke RA. Primary mediastinal non-Hodgkin’s lymphomas: a morphologic and immunologic study of 19 cases. Am J Clin Pathol. 1985;83:676–80.
Hofmann WJ, Momburg F, Moller P. Thymic medullary cells expressing B lymphocyte antigens. Hum Pathol. 1988;19:1280–7.
Hofmann WJ, Momburg F, Moller P, Otto HF. Intra- and extrathymic B cells in physiologic and pathologic conditions. Immunohistochemical study on normal thymus and lymphofollicular hyperplasia of the thymus. Virchows Arch A Pathol Anat Histopathol. 1988;412:431–42.
Isaacson PG, Norton AJ, Addis BJ. The human thymus contains a novel population of B lymphocytes. Lancet. 1987;2:1488–91.
Calaminici M, Piper K, Lee AM, Norton AJ. CD23 expression in mediastinal large B-cell lymphomas. Histopathology. 2004;45:619–24.
Fend F, Nachbaur D, Oberwasserlechner F, Kreczy A, Huber H, Muller-Hermelink HK. Phenotype and topography of human thymic B cells. An immunohistologic study. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;60:381–8.
Colby TV, Yousem SA. Pulmonary lymphoid neoplasms. Semin Diagn Pathol. 1985;2:183–96.
Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368:1408–16.
Shimosato Y, Mukai K. Atlas of tumor pathology. Tumors of the mediastinum. 3rd ed. Washington: Armed Forces Institute of Pathology; 1995.
Pileri SA, Gaidano G, Zinzani PL, et al. Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins. Am J Pathol. 2003;162:243–53.
de Leval L, Ferry JA, Falini B, Shipp M, Harris NL. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol. 2001;25:1277–82.
Hoeller S, Zihler D, Zlobec I, et al. BOB.1, CD79a and cyclin E are the most appropriate markers to discriminate classical Hodgkin’s lymphoma from primary mediastinal large B-cell lymphoma. Histopathology. 2010;56:217–28.
Higgins JP, Warnke RA. CD30 expression is common in mediastinal large B-cell lymphoma. Am J Clin Pathol. 1999;112:241–7.
Copie-Bergman C, Plonquet A, Alonso MA, et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol. 2002;15:1172–80.
Gentry M, Bodo J, Durkin L, Hsi ED. Performance of a commercially available MAL antibody in the diagnosis of primary mediastinal large B-cell lymphoma. Am J Surg Pathol. 2017;41:189–94.
Bledsoe JR, Redd RA, Hasserjian RP, et al. The immunophenotypic spectrum of primary mediastinal large B-cell lymphoma reveals prognostic biomarkers associated with outcome. Am J Hematol. 2016;91:E436–41.
Pelland K, Mathews S, Kamath A, et al. Dendritic cell markers and PD-L1 are expressed in mediastinal gray zone lymphoma. Appl Immunohistochem Mol Morphol. 2018;26:e101–e6.
Tanaka Y, Maeshima AM, Nomoto J, et al. Expression pattern of PD-L1 and PD-L2 in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and gray zone lymphoma. Eur J Haematol. 2018;100:511–7.
Shi M, Roemer MG, Chapuy B, et al. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol. 2014;38:1715–23.
De Mello CA, De Andrade VP, De Lima VC, Carvalho AL, Soares FA. Prognostic impact of MUM1 expression by immunohistochemistry on primary mediastinal large B-cell lymphoma. Leuk Lymphoma. 2011;52:1495–503.
Lees C, Keane C, Gandhi MK, Gunawardana J. Biology and therapy of primary mediastinal B-cell lymphoma: current status and future directions. Br J Haematol. 2019;185:25–41.
Guiter C, Dusanter-Fourt I, Copie-Bergman C, et al. Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma. Blood. 2004;104:543–9.
Menter T, Tzankov A. Genetic alterations of 9p24 in lymphomas and their impact for cancer (immuno-)therapy. Virchows Arch. 2019;474:497–509.
Mottok A, Woolcock B, Chan FC, et al. Genomic alterations in CIITA are frequent in primary mediastinal large B cell lymphoma and are associated with diminished MHC class II expression. Cell Rep. 2015;13:1418–31.
Twa DD, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014;123:2062–5.
Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med. 2009;206:981–9.
Mansouri L, Noerenberg D, Young E, et al. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. Blood. 2016;128:2666–70.
Tsang P, Cesarman E, Chadburn A, Liu YF, Knowles DM. Molecular characterization of primary mediastinal B cell lymphoma. Am J Pathol. 1996;148:2017–25.
Suster S, Moran CA. Pleomorphic large cell lymphomas of the mediastinum. Am J Surg Pathol. 1996;20:224–32.
Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–82.
Klui PM, Harris NL, Stein H, et al. High-grade B-cell lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumors of the hematopoietic and lymphoid tissues. Lyon: IARC; 2017. p. 335–41.
Sehn LH, Salles G. Diffuse large B-cell lymphoma. N Engl J Med. 2021;384:842–58.
Traverse-Glehen A, Pittaluga S, Gaulard P, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin’s lymphoma and mediastinal large B-cell lymphoma. Am J Surg Pathol. 2005;29:1411–21.
García JF, Mollejo M, Fraga M, et al. Large B-cell lymphoma with Hodgkin’s features. Histopathology. 2005;47:101–10.
Jaffe ES, Stein H, Swerdlow SH, Campo E, Pileri SA, Harris NL. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumors of hematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 267–8.
Jaffe ES, Stein H, Swerdlow SH, Campo E, Pileri S, Harris NL. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumors of hematopoietic and lymphoid tissues (revised 4th edition). Lyon: IARC; 2017. p. 342–4.
Schurch CM, Federmann B, Quintanilla-Martinez L, Fend F. Tumor heterogeneity in lymphomas: a different breed. Pathobiology. 2018;85:130–45.
Wilson WH, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014;124:1563–9.
Evens AM, Kanakry JA, Sehn LH, et al. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort. Am J Hematol. 2015;90:778–83.
Grant C, Dunleavy K, Eberle FC, Pittaluga S, Wilson WH, Jaffe ES. Primary mediastinal large B-cell lymphoma, classic Hodgkin lymphoma presenting in the mediastinum, and mediastinal gray zone lymphoma: what is the oncologist to do? Curr Hematol Malig Rep. 2011;6:157–63.
Sarkozy C, Molina T, Ghesquieres H, et al. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association. Haematologica. 2017;102:150–9.
Sarkozy C, Copie-Bergmand C, Damotte D, et al. Gray-zone lymphoma between cHL and large B-cell lymphoma: a histopathologic series from the LYSA. Am J Surg Pathol. 2019;43(3):341–51.
O’Malley DP, Fedoriw Y, Weiss LM. Distinguishing classical Hodgkin lymphoma, gray zone lymphoma, and large B-cell lymphoma: a proposed scoring system. Appl Immunohistochem Mol Morphol. 2016;24:535–40.
Pilichowska M, Pittaluga S, Ferry JA, et al. Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL. Blood Adv. 2017;1:2600–9.
Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer. 1983;52:1410–6.
Isaacson PG, Chan JK, Tang C, Addis BJ. Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus. A thymic lymphoma mimicking myoepithelial sialadenitis. Am J Surg Pathol. 1990;14:342–51.
Takagi N, Nakamura S, Yamamoto K, et al. Malignant lymphoma of mucosa-associated lymphoid tissue arising in the thymus of a patient with Sjogren’s syndrome. A morphologic, phenotypic, and genotypic study. Cancer. 1992;69:1347–55.
Weissferdt A, Moran CA. Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: a clinicopathologic and immunohistochemical study of 4 cases. Am J Clin Pathol. 2012;138:816–22.
Porubsky S, Popovic ZV, Badve S, et al. Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: strong association with lymphomas and non-myasthenic autoimmune diseases. Cancers (Basel). 2021;13.
Go H, Cho HJ, Paik JH, et al. Thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a clinicopathological and genetic analysis of six cases. Leuk Lymphoma. 2011;52:2276–83.
Lorsbach RB, Pinkus GS, Shahsafaei A, Dorfman DM. Primary marginal zone lymphoma of the thymus. Am J Clin Pathol. 2000;113:784–91.
Sakamoto T, Yamashita K, Mizumoto C, et al. MALT lymphoma of the thymus with Sjogren’s syndrome: biphasic changes in serological abnormalities over a 4-year period following thymectomy. Int J Hematol. 2009;89:709–13.
Shimizu K, Yoshida J, Kakegawa S, et al. Primary thymic mucosa-associated lymphoid tissue lymphoma: diagnostic tips. J Thorac Oncol. 2010;5:117–21.
Weissferdt A, Moran CA. Primary MALT-type lymphoma of the thymus: a clinicopathological and immunohistochemical study of six cases. Lung. 2011;189:461–6.
Giroux Leprieur E, Antoine M, Gounant V, Copie-Bergman C, Lavole A, Milleron B. [Association between thymic MALT lymphoma and Sjogren’s syndrome]. Rev Pneumol Clin. 2009;65:108–12.
Kurabayashi A, Iguchi M, Matsumoto M, Hiroi M, Kume M, Furihata M. Thymic mucosa-associated lymphoid tissue lymphoma with immunoglobulin-storing histiocytosis in Sjogren’s syndrome. Pathol Int. 2010;60:125–30.
Shimizu K, Ishii G, Nagai K, et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the thymus: report of four cases. Jpn J Clin Oncol. 2005;35:412–6.
Muramatsu T, Tanaka Y, Higure R, Iizuka M, Hata H, Shiono M. Thymic and pulmonary mucosa-associated lymphoid tissue lymphomas. Ann Thorac Surg. 2013;95:e69–70.
Nagasaka T, Lai R, Harada T, et al. Coexisting thymic and gastric lymphomas of mucosa-associated lymphoid tissues in a patient with Sjogren syndrome. Arch Pathol Lab Med. 2000;124:770–3.
Sunohara M, Hara K, Osamura K, et al. Mucosa associated lymphoid tissue (MALT) lymphoma of the thymus with trisomy 18. Intern Med. 2009;48:2025–32.
Yamanaka S, Uekusa T, Tajiri M. [Mucosa-associated lymphoid tissue lymphoma in the thymus with multiple amyloid nodules in the both lungs]. Kyobu Geka. 2010;63:392–5.
Balakrishna JP, Jaffe ES. Crystal-storing histiocytosis associated with thymic extranodal marginal zone lymphoma. Blood. 2017;130:1683.
Inagaki H, Chan JK, Ng JW, et al. Primary thymic extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue type exhibits distinctive clinicopathological and molecular features. Am J Pathol. 2002;160:1435–43.
Kominato S, Nakayama T, Sato F, et al. Characterization of chromosomal aberrations in thymic MALT lymphoma. Pathol Int. 2012;62:93–8.
Ortonne N, Copie-Bergman C, Remy P, et al. Mucosa-associated lymphoid tissue lymphoma of the thymus: a case report with no evidence of MALT1 rearrangement. Virchows Arch. 2005;446:189–93.
Harigae H, Ichinohasama R, Miura I, et al. Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly 46,X,dup(X)(p11p22). Cancer Genet Cytogenet. 2002;133:142–7.
Momoi A, Nagai K, Isahai N, Sakai T, Ohshima K, Aoki S. Thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with 8q24 abnormality. Intern Med. 2016;55:799–803.
Yoshida M, Okabe M, Eimoto T, et al. Immunoglobulin VH genes in thymic MALT lymphoma are biased toward a restricted repertoire and are frequently unmutated. J Pathol. 2006;208:415–22.
Takino H, Li C, Yamada S, et al. Thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a gene methylation study. Leuk Lymphoma. 2013;54:1742–6.
Ganesh M, Sankar NS, Jagannathan R. Extramedullary plasmacytoma presenting as upper back pain. J R Soc Promot Health. 2000;120:262–5.
Jacob JJ, John M, Thomas M, Thomas N, Nair A. Plasmacytoma mimicking mediastinal parathyroid tumour in a patient with primary hyperparathyroidism. Asian J Surg. 2007;30:147–50.
Lee SY, Kim JH, Shin JS, et al. A case of extramedullary plasmacytoma arising from the posterior mediastinum. Korean J Intern Med. 2005;20:173–6.
Miyazaki T, Kohno S, Sakamoto A, et al. A rare case of extramedullary plasmacytoma in the mediastinum. Intern Med. 1992;31:1363–5.
Moran CA, Suster S, Fishback NF, Koss MN. Extramedullary plasmacytomas presenting as mediastinal masses: clinicopathologic study of two cases preceding the onset of multiple myeloma. Mod Pathol. 1995;8:257–9.
Raci-Wetherbee E, Dincer HE. IgG myeloma presenting as a large mediastinal mass and pleural effusion. J Bronchology Interv Pulmonol. 2012;19:65–7.
Salem KZ, Nishihori T, Kharfan-Dabaja MA, Horna P, Alsina M. Primary plasmacytoma involving mediastinal lymph nodes: A diagnostic mimicry of primary mediastinal lymphoma. Hematol Oncol Stem Cell Ther. 2016;9:26–9.
Bink K, Haralambieva E, Kremer M, et al. Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics. Haematologica. 2008;93:623–6.
Bassan R, Maino E, Cortelazzo S. Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment. Eur J Haematol. 2016;96:447–60.
Cortelazzo S, Ferreri A, Hoelzer D, Ponzoni M. Lymphoblastic lymphoma. Crit Rev Oncol Hematol. 2017;113:304–17.
Maeshima AM, Taniguchi H, Suzuki T, et al. Distribution of malignant lymphomas in the anterior mediastinum: a single-institution study of 76 cases in Japan, 1997-2016. Int J Hematol. 2017;106:675–80.
Waldron JA Jr, Dohring EJ, Farber LR. Primary large cell lymphomas of the mediastinum: an analysis of 20 cases. Semin Diagn Pathol. 1985;2:281–95.
Boucheix C, Diebold J, Bernadou A, et al. Lymphoblastic lymphoma/leukemia with convoluted nuclei: the question of its relation to the T-cell lineage studied in 13 patients. Cancer. 1980;45:1569–77.
Navas Palacios JJ, Valdes MD, Pallares MA, Gomez de Salazar MD, Garcia MA. Lymphoblastic lymphoma/leukemia of T-cell origin: ultrastructural, cytochemical, and immunologic features of ten cases. Cancer. 1981;48:1982–91.
Stein H, Petersen N, Gaedicke G, Lennert K, Landbeck G. Lymphoblastic lymphoma of convoluted or acid phosphatase type-a tumor of T precursor cells. Int J Cancer. 1976;17:292–5.
Donlon JA, Jaffe ES, Braylan RC. Terminal deoxynucleotidyl transferase activity in malignant lymphomas. N Engl J Med. 1977;297:461–4.
Borowitz MJ, Falletta JM. Leukemias and lymphomas of thymic differentiation. Clin Lab Med. 1988;8:119–34.
Braziel RM, Keneklis T, Donlon JA, et al. Terminal deoxynucleotidyl transferase in non-Hodgkin’s lymphoma. Am J Clin Pathol. 1983;80:655–9.
Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84:1361–92.
Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008.
Dong M, Zhang X, Yang Z, et al. Patients over 40 years old with precursor T-cell lymphoblastic lymphoma have different prognostic factors comparing to the youngers. Sci Rep. 2018;8:1088.
Jin X, Zhao HF, Yu Y, et al. Analysis of clinical characteristics and prognostic factors of primary mediastinal T-cell lymphoblastic lymphoma. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21:377–82.
Borowitz MJ, Chan JKC, Bene M-C, Arber DA. T-lymphoblastic leukemia/lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumors of hematopoietic and lymphoid tissue. Revised 4th edition. Lyon: IARC; 2017. p. 209–12.
Abruzzo LV, Jaffe ES, Cotelingam JD, Whang-Peng J, Del Duca V, Jr., Medeiros LJ. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol. 1992;16:236–45.
Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010;41:461–76.
Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN. Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015;144:377–92.
Vega F, Medeiros LJ, Davuluri R, Cromwell CC, Alkan S, Abruzzo LV. t(8;13)-positive bilineal lymphomas: report of 6 cases. Am J Surg Pathol. 2008;32:14–20.
Jain N, Lamb AV, O’Brien S, et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood. 2016;127:1863–9.
Chisholm KM, Krishnan C, Heerema-McKenney A, Natkunam Y. Immunohistochemical profile of MYC protein in pediatric small round blue cell tumors. Pediatr Dev Pathol. 2017;20:213–23.
Boddu P, Thakral B, Alhuraiji A, et al. Distinguishing thymoma from T-lymphoblastic leukaemia/lymphoma: a case-based evaluation. J Clin Pathol. 2019;72(3):251–7.
Adam P, Hakroush S, Hofmann I, Reidenbach S, Marx A, Strobel P. Thymoma with loss of keratin expression (and giant cells): a potential diagnostic pitfall. Virchows Arch. 2014;465:313–20.
Bhaker P, Das A, Rajwanshi A, et al. Precursor T-lymphoblastic lymphoma: Speedy diagnosis in FNA and effusion cytology by morphology, immunochemistry, and flow cytometry. Cancer Cytopathol. 2015;123:557–65.
Gorczyca W, Tugulea S, Liu Z, Li X, Wong JY, Weisberger J. Flow cytometry in the diagnosis of mediastinal tumors with emphasis on differentiating thymocytes from precursor T-lymphoblastic lymphoma/leukemia. Leuk Lymphoma. 2004;45:529–38.
Ward N, Baqai J, Zehnpfennig A, Fine N, Huang J, Smith MD. Bcl-2 maturation pattern in T-cells distinguishes thymic neoplasm/hyperplasia, T-lymphoblastic lymphoma, and reactive lymph nodes. Cytometry B Clin Cytom. 2018;94:444–50.
Siegert E, Weissbach G, Fischer R, Lauterbach I. Non-Hodgkin lymphoma (NHL) as a second neoplasm occurring after neuroblastoma treatment. Med Pediatr Oncol. 1998;30:18–21.
Sekimizu M, Sunami S, Nakazawa A, et al. Chromosome abnormalities in advanced stage T-cell lymphoblastic lymphoma of children and adolescents: a report from Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) and review of the literature. Br J Haematol. 2011;154:612–7.
Krieger D, Moericke A, Oschlies I, et al. Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia. Haematologica. 2010;95:158–62.
Bongiovanni D, Saccomani V, Piovan E. Aberrant signaling pathways in T-cell acute lymphoblastic leukemia. Int J Mol Sci. 2017;18.
Baleydier F, Decouvelaere AV, Bergeron J, et al. T cell receptor genotyping and HOXA/TLX1 expression define three T lymphoblastic lymphoma subsets which might affect clinical outcome. Clin Cancer Res. 2008;14:692–700.
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;66:848–58.
Bullrich F, Morris SW, Hummel M, Pileri S, Stein H, Croce CM. Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res. 1994;54:2873–7.
Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263:1281–4.
Shiota M, Fujimoto J, Takenaga M, et al. Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood. 1994;84:3648–52.
Shiota M, Nakamura S, Ichinohasama R, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood. 1995;86:1954–60.
Gonin J, Kadiri H, Bensaci S, et al. Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20. Virchows Arch. 2007;450:355–8.
Sevilla DW, Choi JK, Gong JZ. Mediastinal adenopathy, lung infiltrates, and hemophagocytosis: unusual manifestation of pediatric anaplastic large cell lymphoma: report of two cases. Am J Clin Pathol. 2007;127:458–64.
Makiguchi N, Ohsaki Y, Fujiuchi S, et al. Ki-1-positive anaplastic large-cell lymphoma with mediastinal involvement. Nihon Kyobu Shikkan Gakkai Zasshi. 1997;35:660–4.
Kayao J, Tamaru J, Wakita H, et al. Anaplastic large cell lymphoma of the mediastinum diagnosed by transbronchial scratch cytology. A case report. Acta Cytol. 2002;46:405–11.
Xing X, Feldman AL. Anaplastic large cell lymphomas: ALK positive, ALK negative, and primary cutaneous. Adv Anat Pathol. 2015;22:29–49.
Parrilla Castellar ER, Jaffe ES, Said JW, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124:1473–80.
Hodgkin T. On some morbid appearances of the absorbent glands and spleen. Med Chir Trans (London). 1832;17:68–114.
Wilks S. Cases of enlargement of the lymphatic glands and spleen, (or Hodgkin’s disease), with remarks. Guy’s Hospital Rep. 1865;11:56–67.
Ortiz-Hidalgo C. A short history of Hodgkin’s disease and Burkitt’s lymphoma. Am J Clin Pathol. 1994;101:S27–33.
Sternberg C. Über eine eigenartige unter dem Bilde der Pseudoleukämie Verlaufende Tuberculose des lymphatischen Apparates. Ztschz Heilk. 1898;19:21–90.
Reed DM. On the pathological changes in Hodgkin’s disease, with especial reference to its relation to tuberculosis. Johns Hopkins Hosp Rep. 1902;10:133–96.
Kanzler H, Kuppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin’s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med. 1996;184:1495–505.
Kuppers R, Kanzler H, Hansmann ML, Rajewsky K. Immunoglobulin V genes in Reed-Sternberg cells. N Engl J Med. 1996;334:404. Author reply 5–6
Kuppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A. 1994;91:10962–6.
Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66:443–59.
Hutchison GB. International symposium on Hodgkin’s disease. Session 6. Survival data and prognosis. Criteria of cure: statistical considerations. Natl Cancer Inst Monogr. 1973;36:561–5.
Shimkin MB. Hodgkin’s disease; mortality in the United States, 1921-1951; race, sex and age distribution; comparison with leukemia. Blood. 1955;10:1214–27.
Shimkin MB, Oppermann KC, Bostick WL, Low-Beer BV. Hodgkin’s disease: an analysis of frequency, distribution and mortality at the University of California Hospital 1914-1951. Ann Intern Med. 1955;42:136–53.
al-Naaman YD, al-Ani MS, al-Omeri MM. Primary mediastinal tumours. Thorax. 1974;29:475–81.
Benjamin SP, McCormack LJ, Effler DB, Groves LK. Primary lymphatic tumors of the mediastinum. Cancer. 1972;30:708–12.
Eberle FC, Mani H, Jaffe ES. Histopathology of Hodgkin’s lymphoma. Cancer J. 2009;15:129–37.
Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7:1630–6.
Bonadonna G. Historical review of Hodgkin’s disease. Br J Haematol. 2000;110:504–11.
Diehl V, Thomas RK, Re D. Part II: Hodgkin’s lymphoma—diagnosis and treatment. Lancet Oncol. 2004;5:19–26.
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–9.
Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016;34(31):3733–9.
Hoppe RT, Advani RH, Ai WZ, et al. Hodgkin lymphoma, version 2.2015. J Natl Compr Canc Netw. 2015;13:554–86.
Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34:2690–7.
O’Malley DP, Dogan A, Fedoriw Y, Medeiros LJ, Ok CY, Salama ME. American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol. 2019;39:105–10.
Carbone A, Gloghini A, Aldinucci D, Gattei V, Dalla-Favera R, Gaidano G. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin’s disease. Br J Haematol. 2002;117:366–72.
Pileri SA, Ascani S, Leoncini L, et al. Hodgkin’s lymphoma: the pathologist’s viewpoint. J Clin Pathol. 2002;55:162–76.
Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM. Programmed death ligand 1 is expressed by non-Hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17:4232–44.
Paydas S, Bağır E, Seydaoglu G, Ercolak V, Ergin M. Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma. Ann Hematol. 2015;94:1545–52.
Xie W, Medeiros LJ, Li S, Yin CC, Khoury JD, Xu J. PD-1/PD-L1 pathway and its blockade in patients with classic Hodgkin lymphoma and non-Hodgkin large-cell lymphomas. Curr Hematol Malig Rep. 2020;15:372–81.
Pallesen G, Hamilton-Dutoit SJ, Rowe M, Young LS. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin’s disease. Lancet. 1991;337:320–2.
Uccini S, Monardo F, Ruco LP, et al. High frequency of Epstein-Barr virus genome in HIV-positive patients with Hodgkin’s disease. Lancet. 1989;1:1458.
Weiss LM, Movahed LA, Warnke RA, Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin’s disease. N Engl J Med. 1989;320:502–6.
Harris JA, Jain S, Ren Q, Zarineh A, Liu C, Ibrahim S. CD163 versus CD68 in tumor associated macrophages of classical Hodgkin lymphoma. Diagn Pathol. 2012;7:12.
Gomez-Gelvez JC, Smith LB. Reed-Sternberg-like cells in non-Hodgkin lymphomas. Arch Pathol Lab Med. 2015;139:1205–10.
Etienne B, Guillaud PH, Loire R, Coiffier B, Berger F, Cordier JF. Aggressive primary mediastinal non-Hodgkin’s lymphomas: a study of 29 cases. Eur Respir J. 1999;13:1133–8.
Lam S, Rizkalla K, Hsia CC. Mediastinal choriocarcinoma masquerading as relapsed Hodgkin lymphoma. Case Rep Oncol. 2011;4:512–6.
Re D, Muschen M, Ahmadi T, et al. Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells. Cancer Res. 2001;61:2080–4.
Thomas RK, Re D, Wolf J, Diehl V. Part I: Hodgkin’s lymphoma—molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol. 2004;5:11–8.
Schwering I, Bräuninger A, Klein U, et al. Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood. 2003;101:1505–12.
Chan WC. The Reed-Sternberg cell in classical Hodgkin’s disease. Hematol Oncol. 2001;19:1–17.
Kuppers R, Hansmann ML. The Hodgkin and Reed/Sternberg cell. Int J Biochem Cell Biol. 2005;37:511–7.
Stein HS, Hummel M. Hodgkin’s disease: biology and origin of Hodgkin and Reed-Sternberg cells. Cancer Treat Rev. 1999;25:161–8.
Hinz M, Lemke P, Anagnostopoulos I, et al. Nuclear factor kappaB-dependent gene expression profiling of Hodgkin’s disease tumor cells, pathogenetic significance, and link to constitutive signal transducer and activator of transcription 5a activity. J Exp Med. 2002;196:605–17.
Hinz M, Löser P, Mathas S, Krappmann D, Dörken B, Scheidereit C. Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood. 2001;97:2798–807.
Skinnider BF, Elia AJ, Gascoyne RD, et al. Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood. 2002;99:618–26.
Farrell K, Jarrett RF. The molecular pathogenesis of Hodgkin lymphoma. Histopathology. 2011;58:15–25.
Weniger MA, Melzner I, Menz CK, et al. Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. Oncogene. 2006;25:2679–84.
Savage KJ, Monti S, Kutok JL, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood. 2003;102:3871–9.
Gunawardana J, Chan FC, Telenius A, et al. Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nat Genet. 2014;46:329–35.
Rengstl B, Rieger MA, Newrzela S. On the origin of giant cells in Hodgkin lymphoma. Commun Integr Biol. 2014;7:e28602.
Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging—do we need contrast-enhanced CT? Radiology. 2004;232:823–9.
Bruzzi JF, Macapinlac H, Tsimberidou AM, et al. Detection of Richter’s transformation of chronic lymphocytic leukemia by PET/CT. J Nucl Med. 2006;47:1267–73.
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.
Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32:3048–58.
Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol. 2011;29:1844–54.
Cheson BD. Staging and response assessment in lymphomas: the new Lugano classification. Chin Clin Oncol. 2015;4.
Shah HJ, Keraliya AR, Jagannathan JP, Tirumani SH, Lele VR, DiPiro PJ. Diffuse large B-cell lymphoma in the era of precision oncology: how imaging is helpful. Korean J Radiol. 2017;18:54–70.
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–68.
Hare SS, Souza CA, Bain G, et al. The radiological spectrum of pulmonary lymphoproliferative disease. Br J Radiol. 2012;85:848–64.
William J, Variakojis D, Yeldandi A, Raparia K. Lymphoproliferative neoplasms of the lung: a review. Arch Pathol Lab Med. 2013;137:382–91.
Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J. 2002;20:750–62.
van der Kolk LE, Grillo-Lopez AJ, Baars JW, Hack CE, van Oers MH. Complement activation plays a key role in the side-effects of rituximab treatment. Br J Haematol. 2001;115:807–11.
Sauter CS, Matasar MJ, Meikle J, et al. Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma. Blood. 2015;125:2579–81.
Broccoli A, Zinzani PL. The unique biology and treatment of primary mediastinal B-cell lymphoma. Best Pract Res Clin Haematol. 2018;31:241–50.
Jacobson JO, Aisenberg AC, Lamarre L, et al. Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer. 1988;62:1893–8.
Pfau D, Smith DA, Beck R, et al. Primary mediastinal large B-cell lymphoma: a review for radiologists. AJR Am J Roentgenol. 2019;213:W194–210.
Kocurek A, Malkowski B, Giza A, Jurczak W. Primary mediastinal B-cell lymphoma—metabolic and anatomical features in 18FDG-PET/CT and response to therapy. Contemp Oncol (Pozn). 2016;20:297–301.
Lekovic D, Miljic P, Mihaljevic B. Increased risk of venous thromboembolism in patients with primary mediastinal large B-cell lymphoma. Thromb Res. 2010;126:477–80.
Shaffer K, Smith D, Kirn D, et al. Primary mediastinal large-B-cell lymphoma: radiologic findings at presentation. AJR Am J Roentgenol. 1996;167:425–30.
Hill M, Cunningham D, MacVicar D, et al. Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma. J Clin Oncol. 1993;11:2273–8.
Barrington SF, Kluge R. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas. Eur J Nucl Med Mol Imaging. 2017;44:97–110.
Martelli M, Ceriani L, Zucca E, et al. [18F]fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol. 2014;32:1769–75.
Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest. 1997;112:511–22.
Pina-Oviedo S, Moran CA. Primary mediastinal classical Hodgkin lymphoma. Adv Anat Pathol. 2016;23:285–309.
Tateishi U, Muller NL, Johkoh T, et al. Primary mediastinal lymphoma: characteristic features of the various histological subtypes on CT. J Comput Assist Tomogr. 2004;28:782–9.
Rios A, Torres J, Roca MJ, Galindo PJ, Alonso JL, Parrilla P. [Primary thymic lymphomas]. Rev Clin Esp. 2006;206:326–31.
Tsang RW, Hodgson DC, Crump M. Hodgkin’s lymphoma. Curr Probl Cancer. 2006;30:107–58.
Inaoka T, Takahashi K, Mineta M, et al. Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging. Radiology. 2007;243:869–76.
Takahashi K, Inaoka T, Murakami N, et al. Characterization of the normal and hyperplastic thymus on chemical-shift MR imaging. AJR Am J Roentgenol. 2003;180:1265–9.
D’Angio M, Paesano P, Quattrocchi L, et al. Mediastinal isolated myeloid sarcoma: a single-institution experience. Leuk Lymphoma. 2015;56:539–41.
Gogia A, Sharma A, Chopra A, Kumar R. Mediastinal granulocytic sarcoma: poor risk AML? J Indian Med Assoc. 2013;111:562.
Howell DL, Abramowsky CR. Granulocytic sarcoma presenting as a large mediastinal mass with acute spinal cord compression in a non-leukemic child. Pediatr Blood Cancer. 2005;44:527.
Lee JM, Song HN, Kang Y, et al. Isolated mediastinal myeloid sarcoma successfully treated with chemoradiotherapy followed by unrelated allogeneic stem cell transplantation. Intern Med. 2011;50:3003–7.
Lee MJ, Grogan L, Meehan S, Breatnach E. Pleural granulocytic sarcoma: CT characteristics. Clin Radiol. 1991;43:57–9.
Liu HW, Wong KL, Chan TY, Lau CC, Liang R. Superior vena cava syndrome: a rare presenting feature of acute myeloid leukemia. Acta Haematol. 1988;79:213–6.
Makis W, Hickeson M, Derbekyan V. Myeloid sarcoma presenting as an anterior mediastinal mass invading the pericardium: Serial Imaging With F-18 FDG PET/CT. Clin Nucl Med. 2010;35:706–9.
McCluggage WG, Boyd HK, Jones FG, Mayne EE, Bharucha H. Mediastinal granulocytic sarcoma: a report of two cases. Arch Pathol Lab Med. 1998;122:545–7.
Naesens L, Devos H, Nollet F, Michaux L, Selleslag D. Mediastinal myeloid sarcoma with TP53 mutation preceding acute myeloid leukemia with a PICALM-MLLT10 fusion gene. Acta Haematol. 2018;140:97–104.
Ramasamy K, Lim Z, Pagliuca A, Devereux S, Ho AY, Mufti GJ. Acute myeloid leukaemia presenting with mediastinal myeloid sarcoma: report of three cases and review of literature. Leuk Lymphoma. 2007;48:290–4.
Ravandi-Kashani F, Cortes J, Giles FJ. Myelodysplasia presenting as granulocytic sarcoma of mediastinum causing superior vena cava syndrome. Leuk Lymphoma. 2000;36:631–7.
Rege K, Powles R, Norton J, et al. An unusual presentation of acute myeloid leukaemia with pericardial and pleural effusions due to granulocytic sarcoma. Leuk Lymphoma. 1993;11:305–7.
Sahu KK, Tyagi R, Law AD, et al. Myeloid sarcoma: an unusual case of mediastinal mass and malignant pleural effusion with review of literature. Indian J Hematol Blood Transfus. 2015;31:466–71.
Suemitsu R, Fukuyama S, Ondo K, Ueda H. Resection of mediastinal granulocytic sarcoma triggered the rapid progression of acute myeloid leukemia. Ann Thorac Cardiovasc Surg. 2008;14:181–3.
Takahashi H, Koh K, Kato M, Kishimoto H, Oguma E, Hanada R. Acute myeloid leukemia with mediastinal myeloid sarcoma refractory to acute myeloid leukemia therapy but responsive to L-asparaginase. Int J Hematol. 2012;96:136–40.
Toback A, Hasbrouck DJ, Blaustein J, Ershler WB. Granulocytic sarcoma of the anterior mediastinum. Am J Med Sci. 1985;290:206–8.
Tsai MH, Yang CP, Chung HT, Shih LY. Acute myeloid leukemia in a young girl presenting with mediastinal granulocytic sarcoma invading pericardium and causing superior vena cava syndrome. J Pediatr Hematol Oncol. 2009;31:980–2.
Tufekci O, Yilmaz S, Erdem M, Baysal B, Oren H. Isolated mediastinal myeloid sarcoma after NPM1 positive acute myeloid leukemia. Turk J Haematol. 2019;36(4):285–6.
Wong WS, Loong F, Ooi GC, Tse TC, Chim CS. Primary granulocytic sarcoma of the mediastinum. Leuk Lymphoma. 2004;45:1931–3.
Miettinen M, Wang ZF, Paetau A, et al. ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. Am J Surg Pathol. 2011;35:432–41.
Fang L, Cui Y, Mi Y, et al. Somatic ASXL1 p.R693X mutation identified by next generation sequencing in isolated myeloid sarcoma involving the mediastinum. Curr Med Res Opin. 2020;36:1003–7.
Heesters BA, Myers RC, Carroll MC. Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol. 2014;14:495–504.
Nossal GJ, Ada GL, Austin CM. Antigens in immunity. Iv. cellular localization of 125-I- and 131-I-labelled flagella in lymph nodes. Aust J Exp Biol Med Sci. 1964;42:311–30.
Nossal GJ, Abbot A, Mitchell J, Lummus Z. Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles. J Exp Med. 1968;127:277–90.
Monda L, Warnke R, Rosai J. A primary lymph node malignancy with features suggestive of dendritic reticulum cell differentiation. A report of 4 cases. Am J Pathol. 1986;122:562–72.
Aguzzi A, Kranich J, Krautler NJ. Follicular dendritic cells: origin, phenotype, and function in health and disease. Trends Immunol. 2014;35:105–13.
Perkins SM, Shinohara ET. Interdigitating and follicular dendritic cell sarcomas: a SEER analysis. Am J Clin Oncol. 2013;36:395–8.
Chan JK, Fletcher CD, Nayler SJ, Cooper K. Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized. Cancer. 1997;79:294–313.
Chan JKC. Proliferative lesions of follicular dendritic cells: an overview, including a detailed account of follicular dendritic cell sarcoma, a neoplasm with many faces and uncommon etiologic associations. Adv Anat Pathol. 1997;4:387–411.
Perez-Ordonez B, Erlandson RA, Rosai J. Follicular dendritic cell tumor: report of 13 additional cases of a distinctive entity. Am J Surg Pathol. 1996;20:944–55.
Hu J, Dong D, Jiang Z, Hu H. Clinicopathological characteristics of mediastinal follicular dendritic cell sarcoma: report of three cases. J Cardiothorac Surg. 2016;11:56.
Lee BE, Korst RJ, Taskin M. Right pneumonectomy for resection of a posterior mediastinal follicular dendritic cell sarcoma arising from Castleman’s disease. Ann Thorac Surg. 2014;97:e101–3.
Purkait S, Mallick S, Joshi PP, et al. Retroperitoneal and mediastinal follicular dendritic cell sarcoma: report of 3 cases with review of literature. Hematol Oncol. 2017;35:374–9.
Viola P, Vroobel KM, Devaraj A, et al. Follicular dendritic cell tumour/sarcoma: a commonly misdiagnosed tumour in the thorax. Histopathology. 2016;69:752–61.
Wu YL, Wu F, Xu CP, et al. Mediastinal follicular dendritic cell sarcoma: a rare, potentially under-recognized, and often misdiagnosed disease. Diagn Pathol. 2019;14:5.
Chan AC, Chan KW, Chan JK, Au WY, Ho WK, Ng WM. Development of follicular dendritic cell sarcoma in hyaline-vascular Castleman’s disease of the nasopharynx: tracing its evolution by sequential biopsies. Histopathology. 2001;38:510–8.
Facchetti F, Lorenzi L. Follicular dendritic cells and related sarcoma. Semin Diagn Pathol. 2016;33:262–76.
Vermi W, Lonardi S, Bosisio D, et al. Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma. J Pathol. 2008;216:356–64.
Xie Q, Chen L, Fu K, et al. Podoplanin (d2-40): a new immunohistochemical marker for reactive follicular dendritic cells and follicular dendritic cell sarcomas. Int J Clin Exp Pathol. 2008;1:276–84.
Xu J, Sun HH, Fletcher CD, et al. Expression of programmed cell death 1 ligands (PD-L1 and PD-L2) in histiocytic and dendritic cell disorders. Am J Surg Pathol. 2016;40:443–53.
Griffin GK, Sholl LM, Lindeman NI, Fletcher CD, Hornick JL. Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-kappaB regulatory genes. Mod Pathol. 2016;29:67–74.
Andersen EF, Paxton CN, O’Malley DP, et al. Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology. Mod Pathol. 2017;30(9):1321–34.
Go H, Jeon YK, Huh J, et al. Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology. 2014;65:261–72.
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Pina-Oviedo, S., Strange, C.D. (2023). Mediastinal Lymphoproliferative Disorders. In: Moran, C.A., Truong, M.T., de Groot, P.M. (eds) The Thorax. Springer, Cham. https://doi.org/10.1007/978-3-031-21040-2_8
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