Journal of Pathology and Translational Medicine

Original Article

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified: Bogyeong Han, Sojung Lim, Jeemin Yim, Young Keun Song, Jiwon Koh, Sehui Kim, Cheol Lee, Young A Kim, Yoon Kyung Jeon; J Pathol Transl Med. 2024;58(2):59-71. Published online January 22, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.04

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Abstract PDF Supplementary Material: Background
The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear.
Methods
Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL–not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed.
Results
TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054).
Conclusions
The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Case Studies

Intravascular NK/T-cell lymphoma: a case report and literature review: Ji Min Na, Wookjae Jung, Minhye Kim, Yun-Hong Cheon, Jong Sil Lee, Dae Hyun Song, Jung Wook Yang; J Pathol Transl Med. 2023;57(6):332-336. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.30

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Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Citations

Citations to this article as recorded by

Cutaneous Intravascular Hematolymphoid Entities: A Review
Emily Hatheway Marshall, Bethany Brumbaugh, Allison Holt, Steven T. Chen, Mai P. Hoang
Diagnostics.2024; 14(7): 679. CrossRef

Primary Peripheral Gamma Delta T-Cell Lymphoma of the Central Nervous System: Report of a Case Involving the Intramedullary Spinal Cord and Presenting with Myelopathy: Jeemin Yim, Seung Geun Song, Sehui Kim, Jae Won Choi, Kyu-Chong Lee, Jeong Mo Bae, Yoon Kyung Jeon; J Pathol Transl Med. 2019;53(1):57-61. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.21

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Abstract PDF

Primary central nervous system lymphoma of T-cell origin (T-PCNSL) is rare, and its clinicopathological features remain unclear. Peripheral T-cell lymphoma of γδ T-cell origin is an aggressive lymphoma mainly involving extranodal sites. Here, we report a case of γδ T-PCNSL involving the intramedullary spinal cord and presenting with paraplegia. A 75-year-old Korean woman visited the hospital complaining of back pain and lower extremity weakness. Magnetic resonance imaging revealed multifocal enhancing intramedullary nodular lesions in the thoracic and lumbar spinal cord. An enhancing nodular lesion was observed in the periventricular white matter of the lateral ventricle in the brain. There were no other abnormalities in systemic organs or skin. Laminectomy and tumor removal were performed. The tumor consisted of monomorphic, medium-to-large atypical lymphocytes with pale-to-eosinophilic cytoplasm. Immunohistochemically, the tumor cells were CD3(+), TCRβF1(-), TCRγ(+), CD30(-), CD4(-), CD8(-), CD56(+), TIA1(+), granzyme B(+), and CD103(+). Epstein-Barr virus in situ was negative. This case represents a unique T-PCNSL of γδ T-cell origin involving the spinal cord.

Citations

Citations to this article as recorded by

B-Cell Lymphoma Intramedullary Tumor: Case Report and Systematic Review
Daniel Gregório Gonsalves, Paulo Eduardo Albuquerque Zito Raffa, Gabriela Gerenutti de Sousa, Melissa Esposito Gomes Rigueiral, Iracema Araújo Estevão, Cesar Cozar Pacheco, Roger Thomaz Rotta Medeiros, Paulo Roberto Franceschini, Paulo Henrique Pires de A
Asian Journal of Neurosurgery.2023; 18(02): 231. CrossRef
Primary intramedullary spinal cord lymphoma misdiagnosed as longitudinally extensive transverse myelitis: a case report and literature review
Huizhen Ge, Li Xu, Huajie Gao, Suqiong Ji
BMC Neurology.2023;[Epub] CrossRef
Clinicopathologic and Genetic Features of Primary T-cell Lymphomas of the Central Nervous System
Jeemin Yim, Jiwon Koh, Sehui Kim, Seung Geun Song, Jeong Mo Bae, Hongseok Yun, Ji-Youn Sung, Tae Min Kim, Sung-Hye Park, Yoon Kyung Jeon
American Journal of Surgical Pathology.2022; 46(4): 486. CrossRef
Peripheral T-Cell Lymphomas Involving the Central Nervous System: A Report From the Czech Lymphoma Study Group Registry
Heidi Mocikova, Robert Pytlík, Katerina Benesova, Andrea Janikova, Juraj Duras, Alice Sykorova, Katerina Steinerova, Vit Prochazka, Vit Campr, David Belada, Marek Trneny
Frontiers in Oncology.2022;[Epub] CrossRef

Original Articles

Non-Radioactive Detection of Clonality in Malignant Lymphoid Neoplasms using the Polymerase Chain Reaction.: Chan Kum Park, Chul Woo Kim; Korean J Pathol. 1996;30(4):311-317.

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Abstract PDF: The polymerase chain reaction(PCR) was performed to detect clonal rearrangements of the immunoglobulin heavy chain gene(IgH) or T-cell receptor(TCR) genes in 57 lymphoproliferative diseases including 26 B-cell lymphomas and 23 peripheral T-cell lymphomas(PTCL). Using the IgH primers, monoclonality was detected in 19 out of 22(86.4%) cases of diffuse lymphomas and 2 out of 4(50%) follicular lymphomas, respectively, but not in the 23 PTCL cases. Using the V and J regions of the TCRgamma chain primers, monoclonality was detected in 14 out of the 23(60.9%) PTCL cases. TCR beta chain gene rearrangements were observed in 7 out of the 9 cases which did not show TCRgamma chain gene rearrangements. One non-T non-B acute lymphoblastic leukemia was found to have TCR beta chain gene rearrangements. In conclusion, analysis of Ig and TCR gene rearrangements by using the PCR technique can be used as a useful diagnostic adjunct to establish the clonality of various lymphoproliferative diseases.

EBV in Situ Hybridization Study for Cutaneous T-Cell Lymphomas.: Chan Kum Park, Chang Woo Lee, Jung Dal Lee; Korean J Pathol. 1996;30(8):699-705.

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Abstract PDF: We studied 24 cases of cutaneous T-cell lymphomas and six cases of benign lymphoproliferative diseases of the skin (2 Jessner's lymphocytic infiltration, 2 pseudolymphoma, 2 lymphomatoid papulosis) for the presence of Epstein-Barr Virus(EBV) RNA, using the in situ hybridization(ISH) method. Among the 24 cases of cutaneous T-cell lymphomas (CTCL), 18 cases including 12 cases of mycosis fungoides(MF) were primary CTCL, and the other 6 cases were secondary CTCL. The ISH study demonstrated a positive reaction for EBER probe in 6 out of the 24 cases(25%) of CTCL, and a negative reaction for BHLF nuclear RNA probe in all the cases studied. Double-labelling immunohistochemistry/ISH studies revealed that the EBV positive cells were CD45RO positive and CD20 negative. EBV genome was not demonstrated in any benign lymphoproliferative diseases of the skin. Among the EBER positive cases, none of the 12 cases of MF demonstrated EBER signals, and 6 out of the 12(50%) cases of CTCL were positive for EBER probe. In conclusion, latent infection of EBV may play a role in the development of non-mycosis fungoides T-cell lymphomas involving the skin.

Case Reports

Fine Needle Aspiration Cytological Findings of Angioimmunoblastic T-cell Lymphoma : A Brief Case Report.: Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Chang Suk Kang, Kyo Young Lee; Korean J Cytopathol. 2006;17(2):159-161.

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Abstract PDF: Recently, we experienced a case of Angioimmunoblastic T-cell lymphom (AITL) in a 60-year-old man presented with lymphadenopathy, which is first cytological report in Korea. The cytological features showed a heterogeneous population of small to medium-sized lymphocytes, immunoblasts, and plasma cells. Characteristically, there were also a distinct population of follicular dendritic cells admixed with lymphoid cells, forming the so-called dendritic cell-lymphocyte complexes. Histological features showed the classic morphologic features of AITL. Recognition of the characteristic cytological features can suggest the possibility of AITL.

Ki-1 Positive Extranodal NK/T Cell Lymphoma, Nasal Type, Mistaken as Dermatomyositis: A Case Report and Literature Review.: Hyun Jung Kim, Eunah Shin, Jung Yeon Kim, Kyeongmee Park, Young Jin Yoo, Seung Sook Lee; Korean J Pathol. 2007;41(4):278-283.

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Abstract PDF: We report a case of a 38-year-old male with extranodal NK/T-cell lymphoma, nasal type, showing unusual clinical and pathological features. The patient was admitted for soft tissue swelling and tenderness in both legs. The patient had been treated intermittently 8 months prior for repeated muco-cutaneous ulcers. A muscle biopsy showed medium-sized atypical lymphoid cells with bizarre nuclei and plump cytoplasm, infiltrating to the skeletal muscle fibers with angiocentricity. The immunoresults were Ki-1+, CD56+, cytoplasmic CD3+, with EBV-in situ hybridization +. The patient rapidly deteriorated and died of sepsis and respiratory failure shortly after initiation of low-dose chemotherapy. A careful review of previous biopsies revealed scarce atypical lymphoid cells around vessels with similar immunoprofiles without the presence of Ki-1 positive cells. This case emphasizes that an extranodal NK/T-cell lymphoma may have a dermatomyositis-like diffuse presentation. Ki-1 co-expression can be an unexpected event in a process of the disease course; however, this should be validated with future studies.

Nesal T-cell Lymphoma associated with Hemophagocytic Syndrome: A case report.: Mee Sook Roh, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1994;28(5):541-543.

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Abstract PDF: Peripheral T-cell lymphoma is the generic group given to a family of tumors composed of neoplastic lymphocytes with phenotypic features of peripheral T-cells. Certain peripheral T-cell lymphomas develop a hemophagocytic syndrome that mimics malignant histiocytosis, both clinically and pathologically. We experienced a case of nasal T-cell lymphoma, histologically mimicking malignant histiocytosis in a 40-year-old male. The chief complaints were nasal obstruction and intermittent mild fever. Mild anemia, elevated SGOT and SGPT, polyclonal gammophthy, and moderate hepatomegaly were present. Two weeks later was present an enlarged cervical lymph node. The biopsied nasal mass showed angiocentric and angiodestructive peripheral T-cell lymphoma withextensive necrosis and marked erythrophagocytosis by non-neoplastic histiocytes. Subsequently, cervical lymph node was biopsied, which showed peripheral T-cell ltmphoma with extensive necrosis and erythrophagocytosis as well. The atypical lymphoid cells revealed pan-T(+), but CD4(-) and CD8(-), whereas the reactive histiocytes showed lysozyme(+), immunohistochemistry.

Original Articles

Immunohistochemical Study of Upper Respiratory Tract Malignant Lymphomas with Features of Polymorphic Reticulosis.: Jeong Ja Park, Tae In Park, Young Hyeh Ko, Jung Dal Lee; Korean J Pathol. 1994;28(2):144-148.

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Abstract PDF: Malignant lymphomas of the upper respiratory tract are relatively common in the Orient including Korea. They have a marked clinicopathologic and immunophenotypic diversity. We retrospectively reviewed 20 cases of malignant lymphomas with features of polymorphic reticulosis in the upper respiratory tract. Histopathologic findings consisted of polymorphism of lymphoid cells in 17 cases(85%), angiocentricity in 14 cases(70%), coagulation necrosis in 12 cases(60%), and epitheliotropism in 8 cases(40%). By Working Formulation, 14 cases(70%) were classified as diffuse large cell type, 4 cases(20%) as diffuse mixed small cleaved and large cell type, one case as immunoblastic type, and one case as anaplastic large cell type. On immunostaining, one showed B-cell phenotype and 19 cases showed T-cell phenotype. The B-cell type was histologically diffuse large cell type. From these results, we concluded that polymorphic reticulosis is a type of peripheral T-cell lymphoma with angiocentricity.

A Pathologic Study of Lymphoproliferative Disorders of the Skin.: Yee Jeong Kim, Kwang Gil Lee, Soo Il Chun, Yun Woong Ko; Korean J Pathol. 1991;25(6):551-562.

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Abstract PDF: Forty eight skin biopsies obtained from 24 patients were reviewed, and clinical, histological and immunohistochemical findings were analyzed. Results obtained are as follows: 1) Skin manifestation was plaque, erythroderma, scale and hyperpigmentation in mycosis fungoides, and subcutaneous nodule, mass and ulcerated patch in cutaneous lymphoma. The skin of lymphomatoid papulosis revealed hemorrhagic ulcerated and erythematous papules which healed spontaneously. 2) Histologically, mycosis fungoides showed epidermotropism in most cases. Pautrier's micro-abscesses were present in one-fourth of the cases. Malignant lymphoma was different in histology from mycosis fungoides. As compared with mycosis fungoides, it showed less frequent epidermotropism, more compact and diffuse infiltration of atypical lymphocytes, more often association with ulcer and necrosis, and more frequent mitotic figures. Lymphomatoid papulosis showed striking hemorrhage and edema of the papillary dermis. 3) Based on the results of immunohistochemical study, mycosis fungoides and lymphomatoid papulosis were considered as a T cell proliferative disorder of the skin. According to these findings, lymphoproliferative disorders of the skin occurred predominantly in the elderly and males. Clinical and histopathologic findings overlapped and were similar each other. It was difficult to make a definite diagnosis in early lesions, and a sequential follow up biopsy was required. It is concluded that strict criteria such as marked atypia and clustering of atypical cells are necessary for a histologic diagnosis of malignant lymphoproliferative disorder of the skin.

Immunopathologic Study and Clinical Correlation of Non-Hodgkin's Lymphoma.: Mi Seon Lee, Jin Man Kim, Kwang Sun Suh, Dae Young Kang; Korean J Pathol. 1991;25(5):407-417.

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Abstract: In Korea, the proportion of B-cell and T-cell lymphomas has not yet been clearly estimated. In the present study, we analysed clinicopathologic and immunophenotypic findings in 60 cases of non-Hodgkin's lymphomas(NHL) and in 17 cases of polymorphic reticulosis. Immunohistochemical studies for monoclonal antibodies, such as MB2, UCHL-1, Kappa/Lambda light chains, and IgG/IgM/IgD heavy chains were performed on formaldehyde-fixed paraffin embedded tissue sections. Among 60 cases of NHL, 28 cases(46.7%) expressed B-cell markers, 29 cases(48.3%) T-cell markers, and 3 cases(5.0%) lacked detectable markers, whereas 16 of 17 cases(94.2%) of polymorphic reticulosis reacted with T-cell markers. The mean survival of the 16 cases of T-cell lymphoma group was shorter than that of the lymphoma group positive for B-cell markers.

Ki-1 Positive T-Cell Lymphoma of Bone in a Child.: Hye Seon Ahn, Gil Ro Han, Jin Hee Sohn, Jung Il Suh, Young Hyeh Ko; Korean J Pathol. 1989;23(4):470-475.

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Abstract PDF: Ki-1 monoclonal antibody is a well known marker for Reed-Sternberg cells in Hodgkin's disease, but also occasionally reacts with activated lymphoid cells of either benign or malignant nature. Recently, Ki-1 antibody positive Non-Hodgkin's lymphoma, usually of large cell and/or polymorphous type, has been reported in the lymph nodes, skin, soft tissue, and stomach, but not in the bone. We report a case of multifocal primary bone lymphoma in a seven-year old body involving the left shoulder and right frontal bone, which proved to be a large cell, polymorphous lymphoma, helper T-cell type expressing Ki-1 antigen.

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