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 Study

Unusual biclonal IgA plasma cell myeloma with aberrant expression of high-risk immunophenotypes: first report of a new diagnostic and clinical challenge: Carlos A. Monroig-Rivera, Clara N. Finch Cruz; J Pathol Transl Med. 2023;57(2):132-137. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.02.07

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Abstract PDF: IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.

Original Articles

Neoplastic Stromal Cells of Intracranial Hemangioblastomas Disclose Pericyte-derived Mesenchymal Stromal Cells-like Phenotype.: Yong Han Jung, Jeong Kim, Bo Mi Kim, Eun Kyoung Kim, Mi Seon Kang, Soojin Jung, Young Il Yang, Shin Kwang Khang; Korean J Pathol. 2011;45(6):564-572.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.564

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2 Crossref

Abstract PDF

BACKGROUND
Stromal cells (SCs) of hemangioblastomas (HBs) have been regarded as true neoplastic components, but their ontogeny remains unclear. Convincing evidence suggests that embryonic mesenchymal cells may be the cells of origin of HBs. The aim of the present study was to investigate the immunophenotypic characteristics of neoplastic SCs using a set of markers against endothelial cells (ECs), vascular smooth muscle cells (vSMCs), mesenchymal stromal cells (MSCs), and pericytes.
METHODS
Intracranial HBs (n=46), angiolipoma (n=9), and pyogenic granuloma (n=11) were retrieved and the immunophenotypic profile of SCs was determined by immune stainings.
RESULTS
The MIB-1 labeling index was significantly higher in SCs compared to that of ECs and vSMCs, regardless of the type of lesion. The neoplastic SCs of HBs consistently expressed both MSC and pericyte markers, but did not express markers of ECs and vSMCs. Double immunofluorescent staining demonstrated that the neoplastic SCs of HBs expressing MSC or pericyte markers directly abutted onto the ECs of capillaries/venules.
CONCLUSIONS
The results suggest that the neoplastic SCs of HBs share the immunophenotypic profile and distribution with those of pericyte-derived MSCs. Thus, HBs might originate from a distinctive population of pericyte-derived MSCs in the central nervous system.

Citations

Citations to this article as recorded by

Role of Endothelial-to-Mesenchymal Transition in the Pathogenesis of Central Nervous System Hemangioblastomas
Shigeki Takada, Masato Hojo, Noriyoshi Takebe, Kenji Tanigaki, Susumu Miyamoto
World Neurosurgery.2018; 117: e187. CrossRef
Endogenous Gastric-Resident Mesenchymal Stem Cells Contribute to Formation of Cancer Stroma and Progression of Gastric Cancer
Eun-Kyung Kim, Hye-Jung Kim, Young-Il Yang, Jong Tae Kim, Min-Young Choi, Chang Soo Choi, Kwang-Hee Kim, Jeong-Han Lee, Won-Hee Jang, Soon-Ho Cheong
Korean Journal of Pathology.2013; 47(6): 507. CrossRef

Histopathologic Features and Immunophenotype of 19 Primary Cutaneous Lymphomas.: Hee Sung Kim, Young Hyeh Ko, Howe J Ree; Korean J Pathol. 1999;33(12):1111-1119.

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Abstract PDF: The diagnosis of primary cutaneous lymphoma is based on a combination of clinical, histological, immunophenotypic and genetic criteria. Nineteen cases of primary cutaneous lymphomas were studied for clinicopathologic, immunophenotypic, and genetic features. Seventeen (89%) cases were T cell origin and two cases (11%) were B cell origin. CD30-positive cutaneous lymphoproliferative disorder was the most frequent subtype, occupying 42% (8 cases) of the cases. CD8 was positive in 5 cases consisting of 3 cutaneous T cell lymphomas and 2 anaplastic large cell lymphomas. CD4 was positive in 2 cases of mycosis fungoides and 3 cases of lymphomatoid papulosis. Six (67%) of 9 cases of cutaneous T cell lymphoma were positive for TIA-1. Ten (83%) out of 12 cases showed clonal rearrangements of TCR gamma genes, however, one T/NK cell lymphoma and one anaplastic large cell lymphoma did not. EBV association was detected only in T/NK cell lymphomas among 10 cases examined. In conclusion, our study showed higher proportion of CD30-positive lymphoproliferative disorders and less frequent mycosis fungoides in Korea compared to the incidences in Western countries. Our immunostaining results suggested that mycosis fungoides and lymphomatoid papulosis are CD4-positive T cell origin, however, the remaining primary cutaneous T cell lymphoma is predominantly CD8-positive cytotoxic T cell origin.

Clinicopathologic Characteristics of Replication Error-Positive Gastric Adenocarcinoma in Korean.: Jae Hyuk Lee, Mi Hwa Kim, Wan Sik Lee, Young Jin Kim, Mi Sun Jee, Kwang Min Lee, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2000;34(7):488-493.

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Abstract PDF: The purpose of this study is to obtain the clinicopathological characteristics of replication error-positive (RER ) gastric adenocarcinoma in Korean, and to identify the significance of RER in adenoma stage of gastric carcinogenesis. Microsatellite instability was examined at D2S71, D2S119, D3S1067, D6S87, D11S905, DM, AR, VWF, HPRT, and BAT-26 loci. Frameshift mutation of BAX gene was analyzed in RER tumors. Normal and tumor DNA of 76 cases of gastric carcinoma and 25 cases of adenoma were examined. RER was found in 8 of 76 cases (10.5%), and it was more frequently found in adenocarcinoma of female (17.7%) than those of male (4.8%). The frequency of RER was not different between the histologic types, age of the patient, anatomical location of the carcinoma, and the stage. The RER found in adenoma suggests that RER contributes to the malignant transformation early in the adenoma stage of the gastric carcinogenesis. None of the RER tumors revealed frameshift mutation of the BAX gene.

Expression Pattern of DNA Mismatch Repair Genes in Tumors of Microsatellite Mutator Phenotype.: Jung Jin Kim, Myung Jin Baek, Nam Gyun Kim, Yun Hee Kim, Ji Eun Kim, Hoguen Kim, Chanil Park; Korean J Pathol. 2000;34(9):609-614.

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Abstract PDF: Microsatellite mutator phenotype (MMP) tumors were reported in a subset of gastrointestinal carcinomas. The molecular pathogenesis of MMP tumors shows defects in the DNA mismatch repair genes, and also many germline and somatic mutations were reported in the MMP tumors. However, the detection of genetic defects in the MMP tumors is very difficult, mainly because many genes are included in the DNA mismatch repair genes. This study was undertaken to determine the best strategy for detecting defects in the DNA mismatch repair genes in gastrointestinal carcinomas. One of the effective ways for detecting defects in DNA mismatch repair genes is to screen the MMP tumors and evaluate the products of DNA mismatch repair genes by performing the multiplex RT-PCR method. We have screened the MMP tumors by using 5 microsatellite markers in the 12 cancer cell lines, 120 colon carcinomas and 99 gastric carcinomas and found 6 MMP cell lines, 10 MMP colon cancers, and 9 MMP gastric carcinomas. In addition, we evaluated 6 DNA mismatch repair gene products (hMSH2, hMSH3, hMSH6, hMLH1, hPMS1 and hPMS2) by multiplex RT-PCR analysis and found decreased expression of the DNA mismatch repair genes in 5 (hMSH6 in DLD-1 and HCT-15; hMSH2 in LoVo; hMLH1 and hMSH3 in HCT-116; hMLH1 in SNU-638) out of 6 MMP cell lines. We also found a decreased expression of hMLH1 in 3 out of 10 MMP colon carcinomas, and in 6 out of 9 MMP gastric carcinomas. Our results indicate that the expression analysis of the DNA mismatch repair genes by multiplex RT-PCR method can reduce the number of genes subjected to mutational analysis and is convenient for screening the responsible DNA mismatch repair genes.

Mucin Phenotype and CDX2 Expression as Prognostic Factors in Gastric Carcinomas.: Chan Kwon Jung, Kyo Young Song, Gyeongsin Park, Cho Hyun Park, Myeong Gyu Choi, Young Seon Hong, Kyo Young Lee; Korean J Pathol. 2007;41(3):139-148.

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Abstract PDF: Background
: Mucin phenotypic markers and CDX2 are widely expressed in gastric carcinomas, however, recent studies have produced conflicting results regarding whether the expression patterns of these markers have clinicopathologic significance.
Methods
: We examined samples from 217 gastric carcinoma patients immunohistochemically to determine if the expression of mucin phenotypic markers and CDX2 was correlated with postoperative survival and other clinicopathologic factors.
Results
: All tumors were phenotypically classified as gastric (type G, 81 cases), gastric and intestinal mixed (type GI, 55 cases), intestinal (type I, 43 cases), or unclassified (type U, 38 cases). The occurrence of type G and GI tumors was positively correlated with tumor progression whereas that of type U tumors was negatively correlated with tumor progression. CDX2 expression was correlated with type I tumors. Tumors that expressed MUC5AC or MUC6 had a better prognosis than those that did not. When the relationship between phenotype and prognosis was considered, type GI had the best prognosis, followed by type G, then type U.
Conclusions
: The mucin phenotypic markers may be useful for predicting tumor progression and survival in patients with gastric carcinomas. Additionally, CDX2 may play an important role in gastric carcinogenesis of type I tumors.

Immunohistochemical Study for Ki-1 and EMA Antigens in Large Cell Lymphoma including Anaplastic Large Cell Lymphoma.: Soon Ae Oak, Young Hyeh Ko, Jung Dal Lee; Korean J Pathol. 1994;28(2):135-143.

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Abstract PDF: To evaluate the frequency of EM A and Ki-I antigen expression in the large cell lymphoma and to define the histologic characteristics of Ki-1 positive anaplastic large cell lymphoma, 40 cases of malignant lymphoma, diffuse large cell type were immunostained by Ki-I and EMA monoclonal antibodies. Eight cases of large cell lymphomas expressed EMA, among which 4 cases were positive for Ki-I antibody as well. The positive rate for EMA was much higher in T cell lymphomas than in B cell lymphomas. Among 4 cases of Ki-I positive lymphomas, 2 cases showing membrane staining of Ki-1 with prototypic histologic feature of anaplastic large cell lymphoma were classified as Ki-1 positive anaplastic large cell lymphoma(ALCL). Ki-I positive ALCL were T-cell in one and non-T, non-B cell type in the other, respectively. The remaining 2 cases of Ki-1 positive lymphomas showing cytoplasmic staining were classified as both B-cell centroblastic/centrocytic lymphoma and T-cell pleomorphic large cell lymphoma.

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