Lymphoproliferations at extranodal sites: a morphologically, genetically, and clinically diverse group of neoplasms with overlapping features

  • John R. GoodladEmail author
  • German Ott


The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues represents a list of diseases regarded to be distinct entities, grouped together on the basis of shared morphology, immunophenotype, and genetic features. Clinical characteristics also make an important contribution when it comes to separating specific disease subgroups. For certain lymphomas, origin of disease, particularly at extranodal locations, is increasingly recognized as an important determinant of behavior and outcome. Extranodal presentation of lymphoma is common, with many cases encountered in the skin, stomach, small intestine, and brain, but virtually any organ can be involved [16]. They often represent a diagnostic challenge, encompassing a broad range of histological subtypes harboring a variety of molecular abnormalities and displaying a spectrum of clinical behaviors. Compared with nodal lymphomas displaying similar pathological features, they frequently...



The authors thank all the workshop participants for their case submissions and contributions during the meeting. Without this input, the workshop could not have taken place.

Authors’ contributions

John Goodlad and German Ott conceived, designed, and jointly wrote the commentary.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Both authors declare strict adherence to compliance with ethical standards.


  1. 1.
    Boyer DF, McKelvie PA, de Leval L, Edlefsen KL, Ko YH, Aberman ZA, Kovach AE, Masih A, Nishino HT, Weiss LM, Meeker AK, Nardi V, Palisoc M, Shao L, Pittaluga S, Ferry JA, Harris NL, Sohani AR (2017) Fibrin-associated EBV-positive large B-cell lymphoma: an indolent neoplasm with features distinct from diffuse large B-cell lymphoma associated with chronic inflammation. Am J Surg Pathol 41:299–312CrossRefGoogle Scholar
  2. 2.
    Chapuy B, Roemer MG, Stewart C, Tan Y, Abo RP, Zhang L, Dunford AJ, Meredith DM, Thorner AR, Jordanova ES, Liu G, Feuerhake F, Ducar MD, Illerhaus G, Gusenleitner D, Linden EA, Sun HH, Homer H, Aono M, Pinkus GS, Ligon AH, Ligon KL, Ferry JA, Freeman GJ, van Hummelen P, Golub TR, Getz G, Rodig SJ, de Jong D, Monti S, Shipp MA (2016) Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 127:869–881CrossRefGoogle Scholar
  3. 3.
    Dotlic SPM, King RL, Oschlies I, Ferry J, Calaminici M, Montes-Moreno S, Goodlad JR, Ott G, Traverse-Glehen A (2019) The broad and challenging landscape of extranodal lymphoproliferations. Virchows Archiv.
  4. 4.
    Ettersperger J, Montcuquet N, Malamut G, Guegan N, Lopez-Lastra S, Gayraud S, Reimann C, Vidal E, Cagnard N, Villarese P, Andre-Schmutz I, Gomes Domingues R, Godinho-Silva C, Veiga-Fernandes H, Lhermitte L, Asnafi V, Macintyre E, Cellier C, Beldjord K, Di Santo JP, Cerf-Bensussan N, Meresse B (2016) Interleukin-15-dependent T-cell-like innate intraepithelial lymphocytes develop in the intestine and transform into lymphomas in celiac disease. Immunity 45:610–625. CrossRefPubMedGoogle Scholar
  5. 5.
    Garcia-Herrera A, Calonje E (2017) Cutaneous lymphomas with cytotoxic phenotype. Surg Pathol Clin 10:409–427CrossRefGoogle Scholar
  6. 6.
    Karai LJ, Kadin ME, Hsi ED, Sluzevich JC, Ketterling RP, Knudson RA, Feldman AL (2013) Chromosomal rearrangements of 6p25.3 define a new subtype of lymphomatoid papulosis. Am J Surg Pathol 37:1173–1181. CrossRefPubMedGoogle Scholar
  7. 7.
    King RL GJ, Calaminici M, Dotlic S, Montes-Moreno S, Oschlies I, Ponzoni M, Traverse-Glehen A, Ott G, Ferry JA (2019) Lymphomas arising in immune-privileged sites: insights into biology, diagnosis, and pathogenesis. Virchows Archiv.
  8. 8.
    Matnani R, Ganapathi KA, Lewis SK, Green PH, Alobeid B, Bhagat G (2017) Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update. Hematol Oncol 35:3–16CrossRefGoogle Scholar
  9. 9.
    Moffitt AB, Ondrejka SL, McKinney M, Rempel RE, Goodlad JR, Teh CH, Leppa S, Mannisto S, Kovanen PE, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Iqbal J, Yu J, Naresh K, Villa D, Gascoyne RD, Said J, Czader MB, Chadburn A, Richards KL, Rajagopalan D, Davis NS, Smith EC, Palus BC, Tzeng TJ, Healy JA, Lugar PL, Datta J, Love C, Levy S, Dunson DB, Zhuang Y, Hsi ED, Dave SS (2017) Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med 214:1371–1386. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Montes-Moreno SKR, Oschlies I, Ponzoni M, Goodlad JR, Dotlic S, Traverse-Glehen A, Ott G, Ferry JA, Calaminici M (2019) Update on lymphoproliferative disorders of the gastrointestinal tract: disease spectrum from indolent lymphoproliferations to aggressive lymphomas. Virchows Arch.
  11. 11.
    Onaindia A, Montes-Moreno S, Rodriguez-Pinilla SM, Batlle A, Gonzalez de Villambrosia S, Rodriguez AM, Alegre V, Bermudez GM, Gonzalez-Vela C, Piris MA (2015) Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement exhibit particular histological features. Histopathology 66:846–855. CrossRefPubMedGoogle Scholar
  12. 12.
    Oschlies IKR, Dotlic S, Montes-Moreno S, Ponzoni M, Traverse-Glehen A, Calaminici M, Ferry JA, Ott G, Goodlad JR (2019) The clinico-pathological spectrum of primary cutaneous lymphoma other than mycosis fungoides/Sezary syndrome. Virchows Archiv.
  13. 13.
    Salaverria I, Philipp C, Oschlies I, Kohler CW, Kreuz M, Szczepanowski M, Burkhardt B, Trautmann H, Gesk S, Andrusiewicz M, Berger H, Fey M, Harder L, Hasenclever D, Hummel M, Loeffler M, Mahn F, Martin-Guerrero I, Pellissery S, Pott C, Pfreundschuh M, Reiter A, Richter J, Rosolowski M, Schwaenen C, Stein H, Trumper L, Wessendorf S, Spang R, Kuppers R, Klapper W, Siebert R (2011) Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood 118:139–147. CrossRefPubMedGoogle Scholar
  14. 14.
    Sharma A, Oishi N, Boddicker RL, Hu G, Benson HK, Ketterling RP, Greipp PT, Knutson DL, Kloft-Nelson SM, He R, Eckloff BW, Jen J, Nair AA, Davila JI, Dasari S, Lazaridis KN, Bennani NN, Wu TT, Nowakowski GS, Murray JA, Feldman AL (2018) Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Blood 131:2262–2266. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375–2390. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zucca E (2008) Extranodal lymphoma: a reappraisal. Ann Oncol Off J Eur Soc Med Oncol 19(Suppl 4):iv77–iv80. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of PathologyQueen Elizabeth University HospitalGlasgowScotland
  2. 2.Department of Clinical PathologyRobert-Bosch-KrankenhausStuttgartGermany

Personalised recommendations