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Joflaher/sandbox
Other nameslymphoepithelioid cell variant of the peripheral T-cell lymphoma not otherwise specified
SpecialtyOncology
Usual onsetAdults
TreatmentChemotherapy
Prognosisguarded
FrequencyRare

Lennert lymphoma, previously also termed lymphoepithelioid lymphoma or lymphoepithelioid variant of peripheral T-cell lymphoma,[1] is a rare type of T-cell lymphoma.[2] It was first characterized by Karl Lennert in 1952 as a variant of Hodgkin lymphoma based on the presence of cells resembling the Reed–Sternberg cells that typify Hodgkin lymphoma.[2][3] However, later studies concluded that these cells are not Reed-Sternberg cells and that Lennert lymphoma is not a variant of Hodgkin lymphoma. It is now considered to be a lymphoepithelioid cell variant of the peripheral T-cell lymphoma not otherwise specified group of lymphomas.[4]

The criteria used for diagnosing Lennert lymphomas has varied between different studies.[4][5][6]

Clinical presentation

In a review study of 26 patients (i.e., 5 men and 11 women, median age 72 years, range from 44 to 90 years) diagnosed with Lennert lymphoma: a) 7 presented with B symptoms (i.e., fever, night sweats, and/or unintentional weight loss); b) 8 presented with or later acquired cancer cells in their bone marrow, blood, skin, liver, lung, bone, and/or subcutaneous tissue in addition to their lymph nodes; c) 6 presented with hepatosplenomegaly (i.e., enlargement of both the liver and spleen); d) 5 had a 2 or 3 score on the ECOG/WHO/Zubrod questionnaire (i.e., they stayed in bed some or most of the day) at presentation; and e) 16 had a 3 or 4 on the International Prognostic Index (i.e., they had a projected 5 year survival of 43% or less) at presentation.[7] A later study[8] of 10 patients (9 males, 1 female; mean age of 48.7, range 22–67 years) reported that: 6 were stages III (i.e., occurring in many lymphatic tissues) or IV (i.e., invading non-lymphatic tissue); 3 had bulky disease; 4 had a mediastinal mass; and 1 had bone marrow involvement. A 2009 review reported on one patient and 11 previously reported patients with Lennert lymphomas that invaded their skin. The skin lesions were asymptomatic, non-ulcerated, and red to violet papules, nodules, or small plaques on the trunk and extremities.[1] In a more recent recent report, one patient with Lennert lymphoma had symptomatic skin lesions: the patient skin patches on the nape of the neck, back, and buttocks itched and felt warm, On microscopic examination, these skin patches were infiltrated with Lennert lymphoma cells.[9] Another recent study reported that a 65 year old patient had a painless subcutaneous soft tissue Lennert lymphoma on his forehead but no evidence that it had invaded the nearby bone or skin surface nor that it was present in his lymph nodes, It was suggested that this Lennert lymphoma originated in the subcutaneous soft tissue rather than lymphatic system.[4]

Follicular helper T cell bearing lymphoma

In the review study of 26 patients with Lennert lymphoma, 15 had cells that expressed one or more of the three proteins expressed by follicular helper T cells viz., PD-1, CXCL13, and CD10. These patients had a more severe form of Lennert lymphoma as defined by there survival times: the percentage of patients surviving 52 months after the diagnosis in the 15 patients with tumor cells that one or more of these marker proteins was 35%, i.e., 5 patients, while it was 73%, i.e., 8, of the 11 patients that lacked tumor cells with one or more of these maker proteins. This difference was statistically significant (P=0.011) based on the log-rank testing and Kaplan–Meier estimator for the survival curves of the two patient groups.[7] It should be noted, however, that other studies suggest that these follicular helper T cell-bearing lymphomas are best defined as follicular helper T-cell lymphomas[8] or angioimmunoblastic T cell lymphoma[10] rather than Lennert lymphomas.

Human T-cell lymphotropic virus type 1

Globally, the number of individuals infected with the human T-cell lymphotropic virus type 1 is estimated to be 5-10 million.[11] These individuals reside principally in this virus's endemic areas, i.e., Japan (mainly the islands of Kyushu and Shikoku), sub-Saharan Africa, South America, the Caribbean area, Iran, Romania, and Melanesia.[12] This virus causes adult T-cell leukemia/lymphoma, tropical spastic paraparesis, and various inflammatory disorders such as uveitis and dermatitis.[11] Clinically and histopathologically, T-cell leukemia/lymphoma mimics and is therefore misdiagnosed as other types of T-cell neoplasms including Lennert lymphoma.[13] One large study suggested that in diagnosing Lennert lymphomas test be conducted to test for the presence of the human T-cell lymphotropic virus type 1, particularly in individuals living in or from this virus's endemic areas.[12]

Epstein-Barr virus

The Epstein-Barr virus infects about 95% of the world's population. It initially causes infectious mononucleosis, non-specific symptoms, or no symptoms but nonetheless enters a latency period in its hosts and thereafter may become active in causing wide range of lymphoproliferative diseases termed Epstein–Barr virus–associated lymphoproliferative diseases[14] as well as various other diseases (see The role of EBV in disease). An early study reported that 11 of 15 patients expressed Epstein-Barr virus DNA in their Lennert lymphoma tissues.[15] Other studies have reported that this virus is less prevalent in Lennert lymphomas. For example, more recent studies have reported that 8 of 26 patients,[7] 4 of 13 patients,[13] and none of 6 patients[16] expressed the products made by the Epstein-Barr virus in their Lennert lymphoma tissues. Studies suggest that although Epstein-Barr virus-infected cells are frequently present in Lennert lymphoma cells, this virus is probably not directly involved in the development of this lymphoma.[15] or that the presence of this virus is associated with a more severe form of Lennert lymphoma. [17]


An analysis of 5 Lennert lymphomas taken from 4 patients found that only the CD4-positive T cells had a significant rate of cell proliferation (i.e., were growing and multiplying). Our results strongly suggest that Lennert's lymphoma is a CD4-positive T cell lymphomaPMID: 2943330

Histopathology

The microscopic examination of Lennert lymphoma tissues commonly shows numerous granulomas containing aggregates of epithelioid histiocytes (i.e., epithelioid cells that express histiocyte antigens[2]) intermingled with T cells (i.e., a subtype of lymphocytes).[7] However, some cases of Lennert lymphomas consist of: a) epithelioid histiocytes intermingled with small, similarly appearing, lymphoid cells but without distinct granuloma or b) abundant histiocytic clusters and medium to large atypical lymphoid cells. In one study, more than 90% of the T cells in the Lennert lymphoma tissues expressed C3.[2] In the study of 26 patients with Lennert lymphomas, all 26 had CD3-expressing cells, 24 had CD4-expressing cells, and 5 had CD8-expressing cells.[7] CD3 is a protein complex and part of the T cell receptor found on T cells, CD4 is a membrane glycoprotein receptor expressed on helper T-cells; and CD8 is a transmembrane glycoprotein co-receptor for the T-cell receptor on T cells.[2][4][7][18][19] A study of four patients co-authored by Karl Lennert found that the T4-expressing lymphocytes but not other the other cells types in the Lennert lymphoma tissues of four patients were rapidly proliferating (i.e., rapidly growing and multiplying) based on their levels of the cell proliferation marker Ki-67) and also had some cancerous morphological features. The study suggested that, although further studies are needed, the T4-expressing cells may be the cancer cells in Lennert lymphomas.[2]

Cytogenetics

Lennert lymphoma tissue samples from 15 patients were cultured and the chromosomes in metaphase were analyzed using a standard G banding protocol. The tissues of 7 patients exhibited a normal karyotype, i.e., a normal appearing and complete set of chromosome. However, eight patients' Lennert lymphoma tissues had cytogenetic karyotype abnormalities: two had trisomy of chromosome 7 plus an extra X chromosome, one had trisomies of chromosome 3 and chromosome 5, one had trisomies of chromosome 3 and chromosome 7 plus an additional X chromosome, one had trisomy of chromosome 3, and three had additions and/or deletions to parts of multiply chromosomes.[7] An analysis of pre-selected genes found 455 genes that expressed different levels these genes' RNA or protein products in the tumor tissues of Lennert lymphoma versus the group of non-Lennert peripheral T-cell lymphoma not otherwise specified tumor tissues: 385 of these products were more highly express in Lennert lymphoma than the group of non-Lennert peripheral T-cell lymphoma not otherwise specified tumor tissues. These findings, if confirmed in other studies would be extremely helpful in making the diagnosis of Lennert lymphoma.[8]

Diagnosis

Currently, LL is diagnosed only based on morphology and immunohistochemical characteristicsCite error: A <ref> tag is missing the closing </ref> (see the help page).

The small lymphoid cells were positive for CD3, CD4, and CD5 and were negative for CD20, CD8, and CD10 (Figure 2B). The Ki-67 proliferative index was 60% in t[18]

epithelioid cells expressing histiocyte antigens and large numbers of T cells CD8 + lymphocytes More than 90% of the T cells expressed the T cell antigens CD3, CD5, and CD2, and the majority of lymphoid cells (>80%) expressed CD4, whereas three of the four samples were composed of less than 10% CD8-positive cells .[2]

In our case the cytologic findings were similar to those found in other peripheral T-cell lymphomas [20]

Prognosis

See also

References

  1. ^ a b Summers TA, Rush W, Aguilera N, Lupton G (October 2009). "Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature". Journal of Cutaneous Pathology. 36 Suppl 1: 25–30. doi:10.1111/j.1600-0560.2008.01203.x. PMID 19775391.
  2. ^ a b c d e f g Feller AC, Griesser GH, Mak TW, Lennert K (September 1986). "Lymphoepithelioid lymphoma (Lennert's lymphoma) is a monoclonal proliferation of helper/inducer T cells". Blood. 68 (3): 663–7. PMID 2943330.
  3. ^ Lennert K: Zur Histologischen Diagnose der Lymphogranulomatose. Frankfurt, FRG, Habil-Schrift, 1952
  4. ^ a b c d Yin Y, Liu H, Luo M, Yu G, Yin W, Li P (February 2023). "Primary extranodal soft tissue Lennert lymphoma (lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified): a case report and review of the literature". Diagnostic Pathology. 18 (1): 12. doi:10.1186/s13000-023-01297-w. PMC 9896693. PMID 36737805.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Kitamura A, Yamashita Y, Sato Y, Hasegawa Y, Kojima H, Nagasawa T, Mori N (October 2005). "Aggressive Lennert's lymphoma: report of three cases in comparison to non-aggressive Lennert's lymphoma". Pathology International. 55 (10): 626–31. doi:10.1111/j.1440-1827.2005.01880.x. PMID 16185292.
  6. ^ Hartmann S, Agostinelli C, Klapper W, Korkolopoulou P, Koch K, Marafioti T, Piccaluga PP, Patsouris E, Pileri S, Hansmann ML (December 2011). "Revising the historical collection of epithelioid cell-rich lymphomas of the Kiel Lymph Node Registry: what is Lennert's lymphoma nowadays?". Histopathology. 59 (6): 1173–82. doi:10.1111/j.1365-2559.2011.04069.x. PMID 22175897.
  7. ^ a b c d e f g Kurita D, Miyoshi H, Yoshida N, Sasaki Y, Kato S, Niino D, Sugita Y, Hatta Y, Takei M, Makishima M, Ohshima K (September 2016). "A Clinicopathologic Study of Lennert Lymphoma and Possible Prognostic Factors: The Importance of Follicular Helper T-cell Markers and the Association With Angioimmunoblastic T-cell Lymphoma". The American Journal of Surgical Pathology. 40 (9): 1249–60. doi:10.1097/PAS.0000000000000694. PMID 27428734.
  8. ^ a b c Etebari M, Navari M, Agostinelli C, Visani A, Peron C, Iqbal J, Inghirami G, Piccaluga PP (2019). "Transcriptional Analysis of Lennert Lymphoma Reveals a Unique Profile and Identifies Novel Therapeutic Targets". Frontiers in Genetics. 10: 780. doi:10.3389/fgene.2019.00780. PMC 6748072. PMID 31552092.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ Kim JH, Lee SK, Kim HY, Uh JA, Lee JH, Kim MS, Lee UH (February 2022). "Rare Case of Double-Positive CD4/CD8 Immunophenotype in Lennert Lymphoma With Cutaneous Involvement: A Case Report". The American Journal of Dermatopathology. 44 (2): 121–125. doi:10.1097/DAD.0000000000002011. PMID 34816803.
  10. ^ Zhan HQ, Li XQ, Zhu XZ, Lu HF, Zhou XY, Chen Y (April 2011). "Expression of follicular helper T cell markers in nodal peripheral T cell lymphomas: a tissue microarray analysis of 162 cases". Journal of Clinical Pathology. 64 (4): 319–24. doi:10.1136/jcp.2010.084459. PMID 21330314.
  11. ^ a b Seighali N, Shafiee A, Rafiee MA, Aminzade D, Mozhgani SH (May 2023). "Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies". BMC Infectious Diseases. 23 (1): 320. doi:10.1186/s12879-023-08289-7. PMC 10173209. PMID 37170214.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ a b Khanlari M, Ramos JC, Sanchez SP, Cho-Vega JH, Amador A, Campuzano-Zuluaga G, Vega F, Chapman JR (July 2018). "Adult T-cell leukemia/lymphoma can be indistinguishable from other more common T-cell lymphomas. The University of Miami experience with a large cohort of cases". Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 31 (7): 1046–1063. doi:10.1038/s41379-018-0037-3. PMC 6931282. PMID 29449683.
  13. ^ a b Weisenburger DD, Savage KJ, Harris NL, Gascoyne RD, Jaffe ES, MacLennan KA, Rüdiger T, Pileri S, Nakamura S, Nathwani B, Campo E, Berger F, Coiffier B, Kim WS, Holte H, Federico M, Au WY, Tobinai K, Armitage JO, Vose JM (March 2011). "Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project". Blood. 117 (12): 3402–8. doi:10.1182/blood-2010-09-310342. PMID 21270441.
  14. ^ Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein–Barr virus–associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408. S2CID 47010934.
  15. ^ a b Anagnostopoulos I, Hummel M, Tiemann M, Korbjuhn P, Parwaresch MR, Stein H (October 1994). "Frequent presence of latent Epstein-Barr virus infection in lymphoepithelioid cell lymphoma (Lennert's lymphoma)". Histopathology. 25 (4): 331–7. doi:10.1111/j.1365-2559.1994.tb01351.x. PMID 7835838.
  16. ^ Jeon YK (July 2016). "Clinicopathological analysis of a case series of peripheral T-cell lymphomas, not otherwise specified, of lymphoepithelioid variant (Lennert's lymphoma). A Central European single-center study-reply". Human Pathology. 53: 194–5. doi:10.1016/j.humpath.2015.12.034. PMID 27016487.
  17. ^ Gafencu GA, Selicean SE, Petrushev B, Cucuianu A, Dima D, Frinc I, Irimie A, Pileczki V, Berindan-Neagoe I, Berce C, Buiga R, Tomuleasa C (July 2016). "Clinicopathological analysis of a case series of peripheral T-cell lymphomas, not otherwise specified, of lymphoepithelioid variant (Lennert's lymphoma). A Central European single-center study". Human Pathology. 53: 192–4. doi:10.1016/j.humpath.2015.12.033. PMID 27016488.
  18. ^ a b Cho U, Park G, Kim JA, Im S (February 2021). "Lymphoepithelioid variant of peripheral T cell lymphoma (Lennert lymphoma): Cytologic and histologic features". Diagnostic Cytopathology. 49 (2): 322–324. doi:10.1002/dc.24552. PMID 32745376.
  19. ^ Savage KJ, Ferreri AJ, Zinzani PL, Pileri SA (September 2011). "Peripheral T-cell lymphoma--not otherwise specified". Critical Reviews in Oncology/hematology. 79 (3): 321–9. doi:10.1016/j.critrevonc.2010.07.007. PMID 20702104.
  20. ^ Vaíllo Vinagre A, Gutiérrez Martín A, Pérez Barrios A, Alberti Masgrau N, Ruiz Liso JM (2004). "Lymphoepithelioid cell lymphoma (Lennert's lymphoma). Report of a case with fine needle aspiration cytology". Acta Cytologica. 48 (2): 234–8. doi:10.1159/000326323. PMID 15085759.
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