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Follicular hyperplasia

MedGen UID:
863170
Concept ID:
C4014733
Finding
HPO: HP:0002729

Definition

Lymphadenopathy (enlargement of lymph nodes) owing to hyperplasia of follicular (germinal) centers. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFollicular hyperplasia

Conditions with this feature

Autoimmune lymphoproliferative syndrome type 1
MedGen UID:
231300
Concept ID:
C1328840
Disease or Syndrome
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.
Autoimmune lymphoproliferative syndrome type 2A
MedGen UID:
349065
Concept ID:
C1858968
Disease or Syndrome
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.
Autoimmune lymphoproliferative syndrome type 4
MedGen UID:
382434
Concept ID:
C2674723
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:
461704
Concept ID:
C3150354
Disease or Syndrome
Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
MedGen UID:
816258
Concept ID:
C3809928
Disease or Syndrome
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
STING-associated vasculopathy with onset in infancy
MedGen UID:
863159
Concept ID:
C4014722
Disease or Syndrome
STING-associated vasculopathy with onset in infancy is an autoinflammatory vasculopathy causing severe skin lesions, particularly affecting the face, ears, nose, and digits, and resulting in ulceration, eschar formation, necrosis, and, in some cases, amputation. Many patients have interstitial lung disease. Tissue biopsy and laboratory findings show a hyperinflammatory state, with evidence of increased beta-interferon (IFNB1; 147640) signaling (summary by Liu et al., 2014).
Immunodeficiency 75
MedGen UID:
1741014
Concept ID:
C5436860
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).
Immunodeficiency 82 with systemic inflammation
MedGen UID:
1781752
Concept ID:
C5543581
Disease or Syndrome
Immunodeficiency-82 with systemic inflammation (IMD82) is a complex autosomal dominant immunologic disorder characterized by recurrent infections with various organisms, as well as noninfectious inflammation manifest as lymphocytic organ infiltration with gastritis, colitis, and lung, liver, CNS, or skin disease. One of the more common features is inflammation of the stomach and bowel. Most patients develop symptoms in infancy or early childhood; the severity is variable. There may be accompanying fever, elevated white blood cell count, decreased B cells, hypogammaglobulinemia, increased C-reactive protein (CRP; 123260), and a generalized hyperinflammatory state. Immunologic workup shows variable B- and T-cell abnormalities such as skewed subgroups. Patients have a propensity for the development of lymphoma, usually in adulthood. At the molecular level, the disorder results from a gain-of-function mutation that leads to constitutive and enhanced activation of the intracellular inflammatory signaling pathway. Treatment with SYK inhibitors rescued human cell abnormalities and resulted in clinical improvement in mice (Wang et al., 2021).
Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
MedGen UID:
1801342
Concept ID:
C5676971
Disease or Syndrome
Immunodeficiency-99 with hypogammaglobulinemia and autoimmune cytopenias (IMD99) is an autosomal recessive immunologic disorder characterized by the onset of recurrent sinopulmonary infections in early childhood. Laboratory studies reveal hypogammaglobulinemia with decreased memory B cells that show impaired class-switch recombination (CSR) and decreased somatic hypermutation (SHM). Due to abnormal antibody production and impaired self-tolerance, patients may develop autoimmune cytopenias, such as thrombocytopenia, or autoimmune features, such as vitiligo. There are also defects in the T-cell compartment (Kuhny et al., 2020).

Professional guidelines

PubMed

Sanges S, Germain N, Vignes S, Séguy D, Stabler S, Etienne N, Terriou L, Launay D, Hachulla É, Huglo D, Dubucquoi S, Labalette M, Lefèvre G
J Clin Immunol 2022 Oct;42(7):1461-1472. Epub 2022 Jun 23 doi: 10.1007/s10875-022-01299-1. PMID: 35737255
Wick MR, O'Malley DP
Semin Diagn Pathol 2018 Jan;35(1):61-66. Epub 2017 Nov 11 doi: 10.1053/j.semdp.2017.11.006. PMID: 29157939
Kabir SI, Kabir SA, Richards R, Ahmed J, MacFie J
Int J Surg 2014 Oct;12(10):1088-92. Epub 2014 Aug 20 doi: 10.1016/j.ijsu.2014.08.350. PMID: 25150021

Recent clinical studies

Etiology

Gerber TS, Porubsky S
Histopathology 2024 Jan;84(1):183-195. Epub 2023 Nov 21 doi: 10.1111/his.15088. PMID: 37988262
Bansod S, Vaideeswar P, Ravat S, Panandikar G
Indian J Pathol Microbiol 2022 Jan-Mar;65(1):129-132. doi: 10.4103/IJPM.IJPM_935_20. PMID: 35074977
Menon D, Katzberg H, Barnett C, Pal P, Bezjak A, Keshavjee S, Bril V
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Aguilera N, Gru AA
Semin Diagn Pathol 2018 Jul;35(4):236-246. Epub 2018 Mar 3 doi: 10.1053/j.semdp.2018.02.001. PMID: 29615296
Carling T, Udelsman R
Thyroid 2005 Jun;15(6):583-7. doi: 10.1089/thy.2005.15.583. PMID: 16029125

Diagnosis

Cheuk W, Bledsoe JR
Semin Diagn Pathol 2024 Mar;41(2):108-115. Epub 2024 Jan 5 doi: 10.1053/j.semdp.2024.01.003. PMID: 38228439
Suster D, Ronen N, Pierce DC, Suster S
Mod Pathol 2023 Aug;36(8):100207. Epub 2023 May 5 doi: 10.1016/j.modpat.2023.100207. PMID: 37149223
Faraz M, Rosado FGN
Clin Lab Med 2021 Sep;41(3):433-451. Epub 2021 Jul 2 doi: 10.1016/j.cll.2021.04.001. PMID: 34304774
Weiss LM, O'Malley D
Mod Pathol 2013 Jan;26 Suppl 1:S88-96. doi: 10.1038/modpathol.2012.176. PMID: 23281438
Asano S
J Clin Exp Hematop 2012;52(1):1-16. doi: 10.3960/jslrt.52.1. PMID: 22706525

Therapy

Wong CS, Buckner CM, Lage SL, Pei L, Assis FL, Dahlstrom EW, Anzick SL, Virtaneva K, Rupert A, Davis JL, Zhou T, Laidlaw E, Manion M, Galindo F, Anderson M, Seamon CA, Sneller MC, Lisco A, Deleage C, Pittaluga S, Moir S, Sereti I
Front Immunol 2021;12:752782. Epub 2021 Dec 1 doi: 10.3389/fimmu.2021.752782. PMID: 34938286Free PMC Article
Aguilera N, Gru AA
Semin Diagn Pathol 2018 Jul;35(4):236-246. Epub 2018 Mar 3 doi: 10.1053/j.semdp.2018.02.001. PMID: 29615296
Truffault F, de Montpreville V, Eymard B, Sharshar T, Le Panse R, Berrih-Aknin S
Clin Rev Allergy Immunol 2017 Feb;52(1):108-124. doi: 10.1007/s12016-016-8558-3. PMID: 27273086
Kabir SI, Kabir SA, Richards R, Ahmed J, MacFie J
Int J Surg 2014 Oct;12(10):1088-92. Epub 2014 Aug 20 doi: 10.1016/j.ijsu.2014.08.350. PMID: 25150021
Jancic SA, Stosic BZ
Vitam Horm 2014;94:391-425. doi: 10.1016/B978-0-12-800095-3.00014-6. PMID: 24388198

Prognosis

Budginaite E, Kloft M, van Kuijk SMJ, Canao PA, Kooreman LFS, Pennings AJ, Magee DR, Woodruff HC, Grabsch HI
Gastric Cancer 2023 Nov;26(6):847-862. Epub 2023 Sep 30 doi: 10.1007/s10120-023-01426-w. PMID: 37776394Free PMC Article
Zhuang S, Chen X, Chen W, Li C, Wang T, Lin Q, Wang D
Acta Otolaryngol 2022 Mar-Apr;142(3-4):357-362. Epub 2022 Apr 5 doi: 10.1080/00016489.2022.2055139. PMID: 35382684
Menon D, Katzberg H, Barnett C, Pal P, Bezjak A, Keshavjee S, Bril V
Muscle Nerve 2021 Jun;63(6):868-873. Epub 2021 Mar 16 doi: 10.1002/mus.27220. PMID: 33675078
Asano S
J Clin Exp Hematop 2012;52(1):1-16. doi: 10.3960/jslrt.52.1. PMID: 22706525
Agrawal R, Wang J
Arch Pathol Lab Med 2009 Jan;133(1):142-6. doi: 10.5858/133.1.142. PMID: 19123728

Clinical prediction guides

Menon D, Katzberg H, Barnett C, Pal P, Bezjak A, Keshavjee S, Bril V
Muscle Nerve 2021 Jun;63(6):868-873. Epub 2021 Mar 16 doi: 10.1002/mus.27220. PMID: 33675078
Krüger-Genge A, Tondera C, Hauser S, Braune S, Görs J, Roch T, Klopfleisch R, Neffe AT, Lendlein A, Pietzsch J, Jung F
Clin Hemorheol Microcirc 2021;77(3):335-350. doi: 10.3233/CH-201028. PMID: 33337355
Agostinelli C, Akarca AU, Ramsay A, Rizvi H, Rodriguez-Justo M, Pomplun S, Proctor I, Sabattini E, Linch D, Daw S, Pittaluga S, Pileri SA, Jaffe ES, Quintanilla-Martinez L, Marafioti T
Virchows Arch 2019 Dec;475(6):771-779. Epub 2019 Nov 4 doi: 10.1007/s00428-019-02681-y. PMID: 31686194Free PMC Article
Berrih-Aknin S, Le Panse R
J Autoimmun 2014 Aug;52:90-100. Epub 2014 Jan 3 doi: 10.1016/j.jaut.2013.12.011. PMID: 24389034
Asano S
J Clin Exp Hematop 2012;52(1):1-16. doi: 10.3960/jslrt.52.1. PMID: 22706525

Recent systematic reviews

Budginaite E, Kloft M, van Kuijk SMJ, Canao PA, Kooreman LFS, Pennings AJ, Magee DR, Woodruff HC, Grabsch HI
Gastric Cancer 2023 Nov;26(6):847-862. Epub 2023 Sep 30 doi: 10.1007/s10120-023-01426-w. PMID: 37776394Free PMC Article

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