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MedGen UID:
Concept ID:
Neoplastic Process
Synonyms: Germinoblastic Sarcoma; Germinoblastic Sarcomas; Germinoblastoma; Germinoblastomas; Lymphoma, Malignant; Lymphomas; Lymphomas, Malignant; Malignant Lymphoma; Malignant Lymphomas; Reticulolymphosarcoma; Reticulolymphosarcomas; Sarcoma, Germinoblastic; Sarcomas, Germinoblastic
SNOMED CT: Malignant lymphoma (118600007); Reticulolymphosarcoma (188676008); Lymphoma (118600007); Lymphoma (1163043007); Malignant lymphoma (1163043007)
HPO: HP:0002665
Monarch Initiative: MONDO:0005062
Orphanet: ORPHA223735


A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLymphoma
Follow this link to review classifications for Lymphoma in Orphanet.

Conditions with this feature

Ataxia-telangiectasia syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Classic ataxia-telangiectasia (A-T) is characterized by progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma. Individuals with A-T are unusually sensitive to ionizing radiation. Non-classic forms of A-T have included adult-onset A-T and A-T with early-onset dystonia.
Bloom syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. Despite their very small head circumference, most affected individuals have normal intellectual ability. Women may be fertile but often have early menopause, and men tend to be infertile, with only one confirmed case of paternity. Serious medical complications that are more common than in the general population and that also appear at unusually early ages include chronic obstructive pulmonary disease, diabetes mellitus as a result of insulin resistance, and cancer of a wide variety of types and anatomic sites.
Mycosis fungoides
MedGen UID:
Concept ID:
Neoplastic Process
Mycosis fungoides is a malignant T-cell lymphoma of the skin, first reported (and named) by Alibert (1835). Sezary syndrome is a leukemic variant of mycosis fungoides defined by erythroderma with greater than 80% of the skin showing redness, adenopathy and greater than 1,000 circulating Sezary cells/microliter with a CD4+CD26- or CD4+CD7- phenotype. Sezary cells have a type 2 helper T cell cytokine profile. Sezary syndrome has a median overall survival time of only 2.4 years in patients with Sezary cells at a density of greater than 10,000 cells/microliter or 5.4 years in patients with 1,000-10,000 Sezary cells/microliter. Mycosis fungoides and Sezary syndrome are the most common cutaneous T-cell lymphomas. Sezary syndrome can arise de novo or can appear following years of chronic mycosis fungoides. Both are thought to arise from clonal expansion of CD4+ helper T cells responding to chronic antigen stimulation (summary by Wang et al., 2015).
MedGen UID:
Concept ID:
Neoplastic Process
Retinoblastoma is a malignant tumor of the developing retina that occurs in children, usually before age five years. Retinoblastoma develops from cells that have cancer-predisposing variants in both copies of RB1. Retinoblastoma may be unifocal or multifocal. About 60% of affected individuals have unilateral retinoblastoma with a mean age of diagnosis of 24 months; about 40% have bilateral retinoblastoma with a mean age of diagnosis of 15 months. Heritable retinoblastoma is an autosomal dominant susceptibility for retinoblastoma. Individuals with heritable retinoblastoma are also at increased risk of developing non-ocular tumors.
Dubowitz syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Dubowitz syndrome (DS) is a rare multiple congenital syndrome characterized primarly by growth retardation, microcephaly, distinctive facial dysmorphism, cutaneous eczema, a mild to severe intellectual deficit and genital abnormalities.
Metaphyseal chondrodysplasia, McKusick type
MedGen UID:
Concept ID:
Congenital Abnormality
The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (MDWH). Cartilage-hair hypoplasia (CHH). Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family.
Purine-nucleoside phosphorylase deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment (review by Aust et al., 1992).
Microcephaly, normal intelligence and immunodeficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, early growth deficiency that improves with age, recurrent respiratory infections, an increased risk for malignancy (primarily lymphoma), and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Other reported malignancies include solid tumors (e.g., medulloblastoma, glioma, rhabdomyosarcoma).
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
MedGen UID:
Concept ID:
Disease or Syndrome
RUNX1 familial platelet disorder with associated myeloid malignancies (RUNX1-FPDMM) is characterized by prolonged bleeding and/or easy bruising and an increased risk of developing a hematologic malignancy. RUNX1-FPDMM is characterized by thrombocytopenia with normal platelet size; bleeding is often greater than expected due to qualitative platelet dysfunction. Myeloid malignancies are the most common, including acute myelogenous leukemia (and myelodysplastic syndrome. T- and B-cell acute lymphoblastic leukemias and lymphomas have also been reported, as well as skin manifestations (e.g., eczema, psoriasis).
Macroglobulinemia, Waldenstrom, 1
MedGen UID:
Concept ID:
Disease or Syndrome
Waldenstrom macroglobulinemia (WM) is a malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein (review by Vijay and Gertz, 2007). The importance of genetic factors is suggested by the observation of familial clustering of WM (McMaster, 2003). Whereas WM is rare, an asymptomatic elevation of monoclonal IgM protein, termed 'IgM monoclonal gammopathy of undetermined significance' (IgM MGUS) is more common. Patients with IgM MGUS can progress to develop WM, at the rate of 1.5% to 2% per year (Kyle et al., 2003). Genetic Heterogeneity of Waldenstrom Macroglobulinemia A locus for susceptibility to Waldenstrom macroglobulinemia (WM2; 610430) has been mapped to chromosome 4q.
Lymphoblastic leukemia, acute, with lymphomatous features
MedGen UID:
Concept ID:
Neoplastic Process
Celiac disease, susceptibility to, 1
MedGen UID:
Concept ID:
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
Autoimmune lymphoproliferative syndrome type 4
MedGen UID:
Concept ID:
Disease or Syndrome
RAS-associated leukoproliferative disorder is characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia. Laboratory studies show an expansion of lymphocytes due to defective apoptosis, as well as significant autoantibodies. Some patients have recurrent infections, and there may be an increased risk of hematologic malignancy (summary by Oliveira, 2013 and Niemela et al., 2010). The disorder shows significant overlap with autoimmune lymphoproliferative syndrome (ALPS; 601859) and was originally designated ALPS IV.
Immunodeficiency, common variable, 2
MedGen UID:
Concept ID:
Disease or Syndrome
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia
MedGen UID:
Concept ID:
Disease or Syndrome
XMEN is an X-linked recessive immunodeficiency characterized by CD4 (186940) lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation (Li et al., 2011). Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders. Magnesium supplementation may be therapeutic (summary by Li et al., 2014).
Combined immunodeficiency due to LRBA deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Common variable immunodeficiency-8 with autoimmunity is an autosomal recessive disorder of immune dysregulation. Affected individuals have early childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. The presentation and phenotype are highly variable, even within families (summary by Lopez-Herrera et al., 2012 and Alangari et al., 2012). Immunologic findings are also variable and may include decreased B cells, hypogammaglobulinemia, and deficiency of CD4+ T regulatory (Treg) cells (Charbonnier et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Lymphoproliferative syndrome 2
MedGen UID:
Concept ID:
Disease or Syndrome
Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
DDX41-related hematologic malignancy predisposition syndrome
MedGen UID:
Concept ID:
DDX41-associated familial myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) is characterized by an increased risk of myeloid neoplasms, lymphoid neoplasms, adult-onset single- or multiple-lineage cytopenias (including aplastic anemia), and red blood cell macrocytosis. The most common myeloid neoplasms include MDS, AML, and therapy-related myeloid neoplasms. Chronic myelomonocytic leukemia, chronic myeloid leukemia, and myeloproliferative neoplasms are less common. Lymphoid neoplasms include non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.
Lymphoma, non-Hodgkin, familial
MedGen UID:
Concept ID:
Neoplastic Process
Turcot syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, ovary, stomach, small bowel, urinary tract, biliary tract, brain (usually glioblastoma), skin (sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas), pancreas, and prostate. Cancer risks and age of onset vary depending on the associated gene. Several other cancer types have been reported to occur in individuals with Lynch syndrome (e.g., breast, sarcomas, adrenocortical carcinoma). However, the data are not sufficient to demonstrate that the risk of developing these cancers is increased in individuals with Lynch syndrome.
X-linked lymphoproliferative disease due to SH2D1A deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Mismatch repair cancer syndrome 3
MedGen UID:
Concept ID:
Disease or Syndrome
Mismatch repair cancer syndrome-3 (MMRCS3) is an autosomal recessive childhood cancer predisposition syndrome characterized by brain tumors, hematologic malignancy, and gastrointestinal tumors. Multiple cafe-au-lait spots, axillary freckling, and, rarely, Lisch nodules reminiscent of neurofibromatosis type I (NF1; 162200) may be present (Hegde et al., 2005, Ostergaard et al., 2005). Microsatellite instability may be detected in tumor samples (Hegde et al., 2005). For a discussion of genetic heterogeneity of mismatch repair cancer syndrome, see MMRCS1 (276300).
Immunodeficiency 75
MedGen UID:
Concept ID:
Disease or Syndrome
Immunodeficiency-75 with lymphoproliferation (IMD75) is an autosomal recessive immunologic disorder characterized by immunodeficiency, immune dysregulation, and the development of lymphoproliferative disorders, including lymphoma. Affected individuals usually present in infancy with severe and recurrent infections, mainly viral and affecting the respiratory tract. Some patients may have autoimmune cytopenias, anemia, or thrombocytopenia. Patients also develop hepatosplenomegaly, lymphadenopathy, lymphoproliferative disorders, and various types of T- or B-cell lymphomas. Immunologic work-up shows decreased class-switched B cells, impaired B-cell terminal differentiation, and hypo- or hypergammaglobulinemia. There is skewed differentiation and dysregulation of T cells, as well as possibly disrupted hematopoiesis. Additional features include failure to thrive and global developmental delay. The phenotype may be reminiscent of ALPS (601859), including laboratory evidence of impaired Fas-dependent T-cell apoptosis. Although hematopoietic stem cell transplantation may be effective treatment, many patients die in childhood (summary by Stremenova Spegarova et al., 2020).

Professional guidelines


Lewis WD, Lilly S, Jones KL
Am Fam Physician 2020 Jan 1;101(1):34-41. PMID: 31894937
Violeta Filip P, Cuciureanu D, Sorina Diaconu L, Maria Vladareanu A, Silvia Pop C
J Med Life 2018 Jul-Sep;11(3):187-193. doi: 10.25122/jml-2018-0035. PMID: 30364585Free PMC Article
Stefanski AL, Tomiak C, Pleyer U, Dietrich T, Burmester GR, Dörner T
Dtsch Arztebl Int 2017 May 26;114(20):354-361. doi: 10.3238/arztebl.2017.0354. PMID: 28610655Free PMC Article

Recent clinical studies


Nastoupil LJ, Bartlett NL
J Clin Oncol 2023 Feb 1;41(4):903-913. Epub 2022 Dec 12 doi: 10.1200/JCO.22.01848. PMID: 36508700
Jain P, Wang M
Hematol Oncol Clin North Am 2020 Oct;34(5):941-956. Epub 2020 Aug 5 doi: 10.1016/j.hoc.2020.06.009. PMID: 32861288
Olszewska-Szopa M, Wróbel T
Adv Clin Exp Med 2019 Aug;28(8):1119-1124. doi: 10.17219/acem/94068. PMID: 31414733
Maddocks K
Blood 2018 Oct 18;132(16):1647-1656. Epub 2018 Aug 28 doi: 10.1182/blood-2018-03-791392. PMID: 30154113
Matasar MJ, Zelenetz AD
Radiol Clin North Am 2008 Mar;46(2):175-98, vii. doi: 10.1016/j.rcl.2008.03.005. PMID: 18619375


Mozas P, Sorigué M, López-Guillermo A
Med Clin (Barc) 2021 Nov 12;157(9):440-448. Epub 2021 Jun 29 doi: 10.1016/j.medcli.2021.03.041. PMID: 34210513
Sánchez-Romero C, Bologna-Molina R, Paes de Almeida O, Santos-Silva AR, Prado-Ribeiro AC, Brandão TB, Carlos R
Crit Rev Oncol Hematol 2021 Mar;159:103237. Epub 2021 Jan 22 doi: 10.1016/j.critrevonc.2021.103237. PMID: 33493634
Yabe M, Dogan A, Horwitz SM, Moskowitz AJ
Cancer Treat Res 2019;176:99-126. doi: 10.1007/978-3-319-99716-2_5. PMID: 30596215
Maddocks K
Blood 2018 Oct 18;132(16):1647-1656. Epub 2018 Aug 28 doi: 10.1182/blood-2018-03-791392. PMID: 30154113
Ansell SM
Mayo Clin Proc 2015 Aug;90(8):1152-63. doi: 10.1016/j.mayocp.2015.04.025. PMID: 26250731


Eyre TA, Shah NN, Dreyling M, Jurczak W, Wang Y, Cheah CY, Song Y, Gandhi M, Chay C, Sharman J, Andorsky DJ, Messersmith HM, Ruppert AS, Muthig VA, Ito R, Wang ML
Future Oncol 2022 Nov;18(36):3961-3969. Epub 2022 Nov 15 doi: 10.2217/fon-2022-0976. PMID: 36377973
Ryan CE, Davids MS, Hermann R, Shahkarami M, Biondo J, Abhyankar S, Alhasani H, Sharman JP, Mato AR, Roeker LE
Future Oncol 2022 Oct;18(33):3689-3699. Epub 2022 Sep 14 doi: 10.2217/fon-2022-0456. PMID: 36102212
Gauthier J, Gazeau N, Hirayama AV, Hill JA, Wu V, Cearley A, Perkins P, Kirk A, Shadman M, Chow VA, Gopal AK, Hodges Dwinal A, Williamson S, Myers J, Chen A, Nagle S, Hayes-Lattin B, Schachter L, Maloney DG, Turtle CJ, Sorror ML, Maziarz RT
Blood 2022 Jun 30;139(26):3722-3731. doi: 10.1182/blood.2021014497. PMID: 35439295Free PMC Article
Donato EM, Fernández-Zarzoso M, De La Rubia J
Expert Rev Hematol 2017 May;10(5):417-423. Epub 2017 Apr 12 doi: 10.1080/17474086.2017.1313701. PMID: 28359170
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP
J Clin Oncol 1999 Apr;17(4):1244. doi: 10.1200/JCO.1999.17.4.1244. PMID: 10561185


Cerhan JR
Hematol Oncol Clin North Am 2020 Aug;34(4):631-646. Epub 2020 May 5 doi: 10.1016/j.hoc.2020.02.001. PMID: 32586570Free PMC Article
Soteriades ES, Kim J, Christophi CA, Kales SN
Asian Pac J Cancer Prev 2019 Nov 1;20(11):3221-3231. doi: 10.31557/APJCP.2019.20.11.3221. PMID: 31759344Free PMC Article
Olsen TG, Heegaard S
Surv Ophthalmol 2019 Jan-Feb;64(1):45-66. Epub 2018 Aug 23 doi: 10.1016/j.survophthal.2018.08.002. PMID: 30144455
Zaorsky NG, Churilla TM, Egleston BL, Fisher SG, Ridge JA, Horwitz EM, Meyer JE
Ann Oncol 2017 Feb 1;28(2):400-407. doi: 10.1093/annonc/mdw604. PMID: 27831506Free PMC Article
Simon TA, Thompson A, Gandhi KK, Hochberg MC, Suissa S
Arthritis Res Ther 2015 Aug 15;17(1):212. doi: 10.1186/s13075-015-0728-9. PMID: 26271620Free PMC Article

Clinical prediction guides

Bastos-Oreiro M, Ortiz J, Pradillo V, Salas E, Marínez-Laperche C, Muñoz A, Buño I, Diéz-Martin JL, Soria JM, Pascual Izquierdo C
Cancer Med 2021 Nov;10(21):7585-7592. Epub 2021 Oct 1 doi: 10.1002/cam4.4280. PMID: 34598309Free PMC Article
Harkins RA, Chang A, Patel SP, Lee MJ, Goldstein JS, Merdan S, Flowers CR, Koff JL
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Wright CL, Maly JJ, Zhang J, Knopp MV
PET Clin 2017 Jan;12(1):63-82. Epub 2016 Oct 6 doi: 10.1016/j.cpet.2016.08.005. PMID: 27863567
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Fischbach W, Al-Taie O
Best Pract Res Clin Gastroenterol 2010 Feb;24(1):13-7. doi: 10.1016/j.bpg.2009.11.003. PMID: 20206104

Recent systematic reviews

Cook MR, Dorris CS, Makambi KH, Luo Y, Munshi PN, Donato M, Rowley S, Saad A, Goy A, Dunleavy K, Ali A
Blood Adv 2023 Jan 10;7(1):32-39. doi: 10.1182/bloodadvances.2022008525. PMID: 36260735Free PMC Article
Zhong H, Liu S, Wang Y, Xu D, Li M, Zhao Y, Zeng X
Autoimmun Rev 2022 May;21(5):103084. Epub 2022 Mar 24 doi: 10.1016/j.autrev.2022.103084. PMID: 35341972
Rana I, Dahlberg S, Steinmaus C, Zhang L
Lancet Planet Health 2021 Sep;5(9):e633-e643. Epub 2021 Aug 25 doi: 10.1016/S2542-5196(21)00149-2. PMID: 34450064Free PMC Article
Hill HA, Qi X, Jain P, Nomie K, Wang Y, Zhou S, Wang ML
Blood Adv 2020 Jul 14;4(13):2927-2938. doi: 10.1182/bloodadvances.2019001350. PMID: 32598477Free PMC Article
Simon TA, Thompson A, Gandhi KK, Hochberg MC, Suissa S
Arthritis Res Ther 2015 Aug 15;17(1):212. doi: 10.1186/s13075-015-0728-9. PMID: 26271620Free PMC Article

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