Skip to main content

Advertisement

SpringerLink
Log in

Primary adrenal lymphoma: a systematic review

  • Review Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Fewer than 200 cases of primary adrenal lymphoma (PAL) have been reported. We have systematically reviewed all 187 cases of PAL reported in the English literature until June 2013, from which we drew the following conclusions: PAL is typically a highly symptomatic and aggressive, metabolically hyperactive, hypovascular, hypoechoic (and heterogeneous on ultrasound), hypodense (with slight to moderate enhancement on computed tomography), high-grade lymphoma, primarily affecting elderly males and presenting with large bilateral adrenal masses. Most cases have adrenal insufficiency, B-symptoms, and elevated lactate dehydrogenase. Hepatosplenomegaly, lymphadenopathy, concurrent or prior immune dysregulation, and bone marrow involvement are uncommon. Epstein–Barr virus positivity is observed in more than half of cases and the disease is disseminated at presentation in 18 % of cases. The two most common WHO 2008-defined PAL subtypes are diffuse large B cell lymphoma (78 %) and peripheral T cell lymphoma (7 %). The prognosis of PAL has improved with the advent of rituximab-containing chemotherapeutic regimens. According to our results, administration of chemotherapy and adrenal insufficiency are significant independent predictors of prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Paling MR, Williamson BR (1983) Adrenal involvement in non-Hodgkin lymphoma. AJR Am J Roentgenol 141:303–305

    Article  PubMed  CAS  Google Scholar 

  2. Rosenberg SA, Diamond HD, Jaslowitz B, Craver LF (1961) Lymphosarcoma: a review of 1269 cases. Med (Baltimore) 40:31–84

    Article  CAS  Google Scholar 

  3. Straus DJ, Filippa DA, Lieberman PH, Koziner B, Thaler HT, Clarkson BD (1983) The non-Hodgkin’s lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969. Cancer 51:101–109

    Article  PubMed  CAS  Google Scholar 

  4. Wang J, Sun NC, Renslo R et al (1998) Clinically silent primary adrenal lymphoma: a case report and review of the literature. Am J Hematol 58:130–136

    Article  PubMed  CAS  Google Scholar 

  5. Wu HC, Shih LY, Chen TC, Chu SH, Tsai CC (1999) A patient with bilateral primary adrenal lymphoma, presenting with fever of unknown origin and achieving long-term disease-free survival after resection and chemotherapy. Ann Hematol 78:289–292

    Article  PubMed  CAS  Google Scholar 

  6. Kumar R, Xiu Y, Mavi A, El-Haddad G, Zhuang H, Alavi A (2005) FDG-PET imaging in primary bilateral adrenal lymphoma: a case report and review of the literature. Clin Nucl Med 30:222–230

    Article  PubMed  Google Scholar 

  7. Ohsawa M, Tomita Y, Hashimoto M, Yasunaga Y, Kanno H, Aozasa K (1996) Malignant lymphoma of the adrenal gland: its possible correlation with Epstein–Barr virus. Mod Pathol 9:534–543

    PubMed  CAS  Google Scholar 

  8. Nakatsuka S, Hongyo T, Syaifudin M, Nomura T, Shingu N, Aozasa K (2002) Mutations of p53, c-kit, K-ras, and beta-catenin gene in non-Hodgkin’s lymphoma of adrenal gland. Jpn J Cancer Res 93:267–274

    Article  PubMed  CAS  Google Scholar 

  9. Al-Fiar FZ, Pantalony D, Shepherd F (1997) Primary bilateral adrenal lymphoma. Leuk Lymphoma 27:543–549

    PubMed  CAS  Google Scholar 

  10. Grigg AP, Connors JM (2003) Primary adrenal lymphoma. Clin Lymphoma 4:154–160

    Article  PubMed  Google Scholar 

  11. Ozimek A, Diebold J, Linke R, Heyn J, Hallfeldt KK, Mussack T (2008) Bilateral primary adrenal non-Hodgkin’s lymphoma—a case report and review of the literature. Eur J Med Res 13:221–228

    PubMed  Google Scholar 

  12. Kim YR, Kim JS, Min YH et al (2012) Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL). J Hematol Oncol 5:49

    Article  PubMed  CAS  Google Scholar 

  13. Kadoch C, Treseler P, Rubenstein JL (2006) Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus 21:E1

    Article  PubMed  Google Scholar 

  14. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO, IARC, Lyon

    Google Scholar 

  15. Hsu CW, Ho CL, Sheu WH, Harn HJ, Chao TY (1999) Adrenal insufficiency caused by primary aggressive non-Hodgkin’s lymphoma of bilateral adrenal glands: report of a case and literature review. Ann Hematol 78:151–154

    Article  PubMed  CAS  Google Scholar 

  16. Mozos A, Ye H, Chuang WY et al (2009) Most primary adrenal lymphomas are diffuse large B-cell lymphomas with non-germinal center B-cell phenotype, BCL6 gene rearrangement and poor prognosis. Mod Pathol 22:1210–1270

    Article  PubMed  CAS  Google Scholar 

  17. Rosenthal FD, Davies MK, Burden AC (1978) Malignant disease presenting as Addison’s disease. Br Med J 1:1591–1592

    Article  PubMed  CAS  Google Scholar 

  18. Redman BG, Pazdur R, Zingas AP, Loredo R (1987) Prospective evaluation of adrenal insufficiency in patients with adrenal metastasis. Cancer 60:103–107

    Article  PubMed  CAS  Google Scholar 

  19. Seidenwurm DJ, Elmer EB, Kaplan LM, Williams EK, Morris DG, Hoffman AR (1984) Metastases to the adrenal glands and the development of Addison’s disease. Cancer 54:552–557

    Article  PubMed  CAS  Google Scholar 

  20. Lam KY, Lo CY (2002) Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 56:95–101

    Article  Google Scholar 

  21. Cedermark BJ, Sjöberg HE (1981) The clinical significance of metastases to the adrenal glands. Surg Gynecol Obstet 152:607–610

    PubMed  CAS  Google Scholar 

  22. Cedermark BJ, Sjöberg HE (1981) Adrenal activity in patients with advanced carcinomas. Surg Gynecol Obstet 152:461–465

    PubMed  CAS  Google Scholar 

  23. Ogo A, Haji M, Ohashi M, Nawata H (1991) Decreased expression of cytochrome P450 17 alpha-hydroxylase mRNA in senescent bovine adrenal gland. Gerontology 37:262–271

    Article  PubMed  CAS  Google Scholar 

  24. Cunningham JJ (1983) Ultrasonic findings in “primary” lymphoma of the adrenal area. J Ultrasound Med 2:467–469

    PubMed  CAS  Google Scholar 

  25. Carroll BA, Ta HN (1980) The ultrasonic appearance of extranodal abdominal lymphoma. Radiology 136:419–425

    PubMed  CAS  Google Scholar 

  26. Falchook FS, Allard JC (1991) CT of primary adrenal lymphoma. J Comput Assist Tomogr 15:1048–1050

    Article  PubMed  CAS  Google Scholar 

  27. Moulton JS, Moulton JS (1988) CT of the adrenal glands. Semin Roentgenol 23:288–303

    Article  PubMed  CAS  Google Scholar 

  28. Guo AC, Cummings TJ, Dash RC, Provenzale JM (2002) Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. Radiology 224:177–183

    Article  PubMed  Google Scholar 

  29. Casola G, Nicolet V, van Sonnenberg E et al (1986) Unsuspected pheochromocytoma: risk of blood-pressure alterations during percutaneous adrenal biopsy. Radiology 159:733–735

    PubMed  CAS  Google Scholar 

  30. Merklin RJ (1966) Suprarenal gland lymphatic drainage. Am J Anat 119:359–374

    Article  PubMed  CAS  Google Scholar 

  31. Freeman C, Berg JW, Cutler SJ (1972) Occurrence and prognosis of extranodal lymphomas. Cancer 29:252–260

    Article  PubMed  CAS  Google Scholar 

  32. López-Guillermo A, Colomo L, Jiménez M et al (2005) Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol 23:2797–2804

    Article  PubMed  Google Scholar 

  33. Hayes JA, Christensen OE (1961) Primary adrenal lymphoma. J Pathol Bacteriol 82:193–194

    Article  PubMed  CAS  Google Scholar 

  34. Dutta P, Bhansali A, Venkatesan R (2005) Primary adrenal lymphoma. Endocrinologist 15:340–342

    Article  Google Scholar 

  35. Osei K, Falko JM, Pacht E, Wall R, Goldberg RF (1983) Primary adrenal insufficiency manifesting as malignant lymphoma. Arch Intern Med 143:1791–1792

    Article  PubMed  CAS  Google Scholar 

  36. Reddy SV, Prabhudesai S, Gnanasekaran B (2011) Origin of primary adrenal lymphoma and predisposing factors for primary adrenal insufficiency in primary adrenal lymphoma. Indian J Endocrinol Metab 15:350–351

    Article  PubMed  Google Scholar 

  37. Ellis RD, Read D (2000) Bilateral adrenal non Hodgkin’s lymphoma with adrenal insufficiency. Postgrad Med J 76:508–509

    Article  PubMed  CAS  Google Scholar 

  38. Sasagawa I, Sadamori N, Itoyama T et al (1995) Primary adrenal lymphoma with chromosomal abnormalities. Acta Haematol 94:156–162

    Article  PubMed  CAS  Google Scholar 

  39. Chai H, Brown RE (2009) Field effect in cancer—an update. Ann Clin Lab Sci 39:331–337

    PubMed  CAS  Google Scholar 

  40. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6:963–968

    Article  PubMed  CAS  Google Scholar 

  41. Robertus JL, Harms G, Blokzijl T, Booman M, de Jong D, van Imhoff G et al (2009) Specific expression of miR-17-5p and miR-127 in testicular and central nervous system diffuse large B-cell lymphoma. Mod Pathol 22:547–555

    Article  PubMed  CAS  Google Scholar 

  42. Cohen JI, Bollard CM, Khanna R, Pittaluga S (2008) Current understanding of the role of Epstein—Barr virus in lymphomagenesis and therapeutic approaches to EBV-associated lymphomas. Leuk Lymphoma 49:27–34

    Article  PubMed  CAS  Google Scholar 

  43. Pratt ZL, Zhang J, Sugden B (2012) The latent membrane protein 1 (LMP1) oncogene of Epstein–Barr virus can simultaneously induce and inhibit apoptosis in B cells. J Virol 86:4380–4393

    Article  PubMed  CAS  Google Scholar 

  44. Ide M, Fukushima N, Hisatomi T et al (2007) Non-germinal cell phenotype and bcl-2 expression in primary adrenal diffuse large B-cell lymphoma. Leuk Lymphoma 48:2244–2246

    Article  PubMed  CAS  Google Scholar 

  45. Hong J, Park S, Park J et al (2011) Evaluation of prognostic values of clinical and histopathologic characteristics in diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy. Leuk Lymphoma 52:1904–1912

    Article  PubMed  CAS  Google Scholar 

  46. Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282

    Article  PubMed  CAS  Google Scholar 

  47. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J et al (2009) A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res 15:5494–5502

    Article  PubMed  CAS  Google Scholar 

  48. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937–1947

    Article  PubMed  Google Scholar 

  49. Eyden B, Chakrabarty B, Hatimy U (2009) Carcinoma versus cytokeratin-positive lymphoma: a case report emphasizing the diagnostic role of electron microscopy. Ultrastruct Pathol 33:33–38

    Article  PubMed  Google Scholar 

  50. Donner LR, Mott FE, Tafur I (2001) Cytokeratin-positive, CD45-negative primary centroblastic lymphoma of the adrenal gland: a potential for a diagnostic pitfall. Arch Pathol Lab Med 125:1104–1106

    PubMed  CAS  Google Scholar 

  51. Gustmann C, Altmannsberger M, Osborn M, Griesser H, Feller AC (1991) Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin’s lymphomas. Am J Pathol 138:1413–1422

    PubMed  CAS  Google Scholar 

  52. Lasota J, Hyjek E, Koo CH, Blonski J, Miettinen M (1996) Cytokeratin-positive large-cell lymphomas of B-cell lineage. A study of five phenotypically unusual cases verified by polymerase chain reaction. Am J Surg Pathol 20:346–354

    Article  PubMed  CAS  Google Scholar 

  53. Rashidi A, Bergeron CW, Fisher SI, Chen IA (2013) Primary adrenal de novo CD5-positive diffuse large B-cell lymphoma. Ann Hematol. doi:10.1007/s00277-013-1690-8

  54. Bourne AE, Bell SW, Wayment RO, Schwartz BF (2009) Primary Hodgkin lymphoma of the adrenal gland: a unique case presentation. Can J Urol 16:4694–4696

    PubMed  Google Scholar 

  55. Kridel R, Dietrich PY (2011) Prevention of CNS relapse in diffuse large B-cell lymphoma. Lancet Oncol 12:1258–1266

    Article  PubMed  Google Scholar 

  56. Villa D, Connors JM, Shenkier TN, Gascoyne RD, Sehn LH, Savage KJ (2010) Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Ann Oncol 21:1046–1052

    Article  PubMed  CAS  Google Scholar 

  57. Boehme V, Zeynalova S, Kloess M et al (2007) Incidence and risk factors of central nervous system recurrence in aggressive lymphoma—a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Ann Oncol 18:149–157

    Article  PubMed  CAS  Google Scholar 

  58. Yoshida S, Morii K, Watanabe M, Saito T (2000) Characteristic features of malignant lymphoma with central nervous system involvement. Surg Neurol 53:163–167

    Article  PubMed  CAS  Google Scholar 

  59. Ferreri AJ, Assanelli A, Crocchiolo R, Ciceri F (2009) Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options. Hematol Oncol 27:61–70

    Article  PubMed  CAS  Google Scholar 

  60. Abe R, Ogawa K, Maruyama Y, Nakamura N, Abe M (2007) Spontaneous regression of diffuse large B-cell lymphoma harbouring Epstein–Barr virus: a case report and review of the literature. J Clin Exp Hematop 47:23–26

    Article  PubMed  Google Scholar 

  61. Coiffier B, Lepage E, Briere J et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242

    Article  PubMed  CAS  Google Scholar 

  62. Zhou L, Peng W, Wang C, Liu X, Shen Y, Zhou K (2012) Primary adrenal lymphoma: radiological; pathological, clinical correlation. Eur J Radiol 81:401–405

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 410, Norfolk, VA, 23507, USA

    Armin Rashidi

  2. Pathology Sciences Medical Group/Sentara Laboratory Services, Norfolk, VA, USA

    Stephen I. Fisher

Authors
  1. Armin Rashidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen I. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Armin Rashidi.

Additional information

ᅟ

While this manuscript was under review, a new case of PAL was published by D'Antonio et al. in BMJ Case Reports (2013). Although complete information about this case is now available in our Online Resource, only parts that were available at the time of preparation of the present article have been included in analysis

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource

This file includes our full database and their corresponding references. (DOCX 110 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rashidi, A., Fisher, S.I. Primary adrenal lymphoma: a systematic review. Ann Hematol 92, 1583–1593 (2013). https://doi.org/10.1007/s00277-013-1812-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1812-3

Keywords

Search

Navigation