scholarly journals Intraepithelial Lymphocytosis of the Resection Margin in the Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5317-5317
Author(s):  
Mi Hwa Heo ◽  
Hye Ra Jung ◽  
Young Rok Do ◽  
Jung-Sook Ha ◽  
Hyera Kim ◽  
...  

Abstract Background: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a disease involving the intestine and is often diagnosed in surgically resected specimens. The disease prognosis of MEITL is fatal because of rapid recurrence and leakage after excision. Recently, in microscopic finding of MEITL, intraepithelial lymphocytosis in mucosa that were grossly intact has been reported. In this study, we evaluated the intraepithelial lymphocytosis of the resection margin to determine the reason for the early recurrence or leakage in MEITL. Materials and Methods: We reviewed the medical records of all patients who were diagnosed with small intestine lymphoma from January 1995 to June 2018 at our medical center. We analyzed a tissue array from 8 patients diagnosed with MEITL. The expression of CD3, CD5, and CD8 were analyzed by immunohistochemistry. Results: A total of 8 cases of small intestine lymphoma were collected in this period. There were three men (37.5%) and five women (mean age 55 years). Two patients died without initiation of chemotherapy. Six patients received chemotherapy after resection of MEITL (4 patients received CHOP regimens, 2 patients received ProMACE-CyBOM regimens), but five patients died within 6 months (mean survival time 4.1 months, range 0.3-12.1 months). Only one patient survived for 5 years. On gross examination, the distance to the resection margin was 7.58 cm (3.8-14.0 cm) on average. Microscopic examination revealed intraepithelial lymphocytosis at least of one of the resected margins in all case. Immunohistochemical staining for CD3, CD5, and CD8 was performed on the resection margins. As a result, severe intraepithelial lymphocytosis accompanied by aberrant loss of CD5 was observed in 6 cases (75%). Conclusion: In the MEITL, an intraepithelial lymphocytosis accompanied by aberrant CD5 loss is frequently observed in the resection margin, even if the resection margin is grossly intact, and there is no clear microscopic involvement of the lymphoma especially on low power. This fact is thought to be related to the early recurrence or leakage of MEITL at the surgical site. Disclosures No relevant conflicts of interest to declare.

2012 ◽  
Vol 45 (7) ◽  
pp. 758-765
Author(s):  
Satoshi Nomura ◽  
Takeshi Shioya ◽  
Tetsuo Shibuya ◽  
Yosimasa Watanabe ◽  
Kotaro Nanbu ◽  
...  

2011 ◽  
Vol 19 (21) ◽  
pp. 2301
Author(s):  
Dong-Jie Yang ◽  
Zhe-Qiang Wei ◽  
Qing Mao ◽  
Qiu-Lan Xu ◽  
Xiao-Xing Feng

2014 ◽  
Vol 75 (8) ◽  
pp. 2229-2233
Author(s):  
Chie SAKIMURA ◽  
Masahiro KOMOTO ◽  
Yukie GO ◽  
Eiji AKO ◽  
Shigeki FUJITA ◽  
...  

2012 ◽  
Vol 53 (8) ◽  
pp. 1623-1624 ◽  
Author(s):  
Yasuo Kakugawa ◽  
Soushi Terasaka ◽  
Takashi Watanabe ◽  
Shu Tanaka ◽  
Hirokazu Taniguchi ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3662-3662
Author(s):  
Pier Paolo Piccaluga ◽  
Antonio De Leo ◽  
Maura Rossi ◽  
Maria Antonella Laginestra ◽  
maria Rosaria Sapienza ◽  
...  

Abstract Abstract 3662 The differential diagnosis among the commonest peripheral T-cell lymphomas (PTCLs) (i.e. PTCL not otherwise specified, NOS; angioimmunoblastic T-cell lymphoma, AITL; and anaplastic large cell lymphoma, ALCL) is difficult, the morphologic and phenotypic features being largely overlapping. Noteworthy, recent international studies indicated significant differences in their clinical behavior as well as concerning the presence of potential therapeutic targets. We performed whole genome gene expression profiling (GEP) of PTCLs aiming to identify molecular signatures able to improve their diagnosis. We studied 95 PTCLs, including 73 PTCLs/NOS, 12 ALCLs (6 ALK+ and 6 ALK-), and 10 AITLs. All tissue samples were formalin-fixed and paraffin embedded (FFPE). GEP was performed by Illumina Whole Genome DASL Assay. First, we documented the efficiency of GEP from FFPE tissues by comparing the mRNA levels and the presence of the corresponding protein, including expressed (i.e. CD3) and not expressed (i.e. BCL10) molecules. Secondly, we tried to discriminate different PTCLs basing on their GEPs. By dividing a training (N=47) and a test set (N=48), we found 2 signatures able to differentiate PTCL/NOS vs. AITL and PTCL/NOS vs. ALCL ALK-. Specifically, in the test set the sensitivity (ST) and specificity (SP) of the assays were 100% – 80% (PTCL/NOS vs. AITL) and 100% – 100% (PTCL/NOS vs. ALK- ALCL) (Table 1). Accordingly, the positive (PPV) and negative (NPV) predicting values for the identification of PTCL/NOS were 0.92 and 1 (vs. AITL) and 1 and 1 (vs. ALK- ALCL) (Table 1).Table 1.Accuracy of GEP based signature in differentiating PTCL subtypesSTSPPPVNPVTraining setPTCL/NOS vs. AITL100%80%0.921PTCL/NOS vs. ALK-ALCL100%100%11Test setPTCL/NOS vs. AITL92.50%100%10.77PTCL/NOS vs. ALK-ALCL92.50%100%10.67Validation setPTCL/NOS vs. AITL85%86%0.920.76PTCL/NOS vs. ALK-ALCL96%73%0.960.73 Interestingly, the identified genes represented relevant functional pathways differentially regulated in the 3 tumour types, including protein kinase cascade, proliferation, and cell cycle. When applied to the test set of cases, the assay correctly classified 37/40 PTCLs/NOS (92.5%), 5/5 AITLs, and 3/3 ALK- ALCLs. Finally, we tested our signatures on 133 independent PTCL cases (including 78 PTCL/NOS, 43 AITL, and 12 ALK- ALCL) for which GEP data were available on the GEO database and were originally obtained from fresh/frozen tissues. Interestingly, we could efficiently recognize PTCL/NOS cases vs. AITLs (ST, 85%; SP 86%; PPV 0.92; NPV 0.76) and vs. ALK- ALCLs (ST 96%; SP 73%; PPV 0.96; NPV 0.73). In conclusion, we successfully generated for the first time GEP from routinary FFPE PTCL samples, identifying molecular signatures potentially useful for the clinical practice and, specifically, for the differential diagnosis of PTCL types. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3238-3238
Author(s):  
Robert S. Ohgami ◽  
Shuchun Chun ◽  
Jane Ohgami ◽  
James L. Zehnder ◽  
Matthew Van de Rijn ◽  
...  

Abstract Abstract 3238 A central dogma of human immunology is that proliferation of immature T-cells, and their development after release from the bone marrow, occurs in the central thymus. Recently, we identified several patients with aberrant polyclonal immature TdT+ precursor T-cell populations in extra-thymic lymphoid tissues. Here we demonstrate that immature precursor T-cell populations, with a cortical thymocyte phenotype, in fact, are expanded in extra-thymic lymphoid tissues of patients with Castleman disease (P < 0.001; n = 29), and angioimmunoblastic T-cell lymphoma (P = < 0.001; n =31) and increased in cases of Castleman disease in association with follicular dendritic cell sarcoma (Figures 1 and 2). Analysis of the proliferation marker, MiB-1, and the morphologic presence of mitoses reveal that these populations are undergoing extra-thymic proliferation and expansion, arguing against simple release from the central thymus and sequestration in these extra-thymic organs. Finally, these populations of immature T-cells are not associated with a particular anatomic site (i.e. neck or mediastinum). These findings challenge the dogma that proliferation of immature human T-cell populations occurs nearly exclusively in the central thymus and demonstrates that stimulation and significant proliferation of extra-thymic immature T-cells does, and can occur in a subset of patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3006-3006 ◽  
Author(s):  
Tokuhira Michihide ◽  
Kimura Yuhta ◽  
Takahashi Yasuyuki ◽  
Tomikawa Tatsuki ◽  
Morihiko Sagawa ◽  
...  

Abstract Background Recent studies have investigated the pathogenesis of the class of conditions known as “other iatrogenic immunodeficiency-associated lymphoproliferative diseases” (OIIA-LPDs), particularly in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is a potent cause of LPDs, and withdrawal of MTX can result in spontaneous regression of LPD, which suggests that this drug plays an important role in the tumorigenesis of LPDs. In addition, an impaired immunity against Epstein-Barr virus (EBV) has been obserbed in RA patients. A number of reports describe LPD regression in patients with OIIA-LPDs-RA, but its precise etiology and pathogenesis remain unclear. Furthermore, the phenomenon of relapse/regrowth of LPDs after initial regression has not been well documented. This study retrospectively analyzed the clinicopathological features of OIIA-LPDs-RA patients to determine the influence of EBV infection on regression/relapse of the disease. Methods & Results Data were collected from 35 patients with RA who developed LPD and who were treated at our institute between 1998 and 2013. All patients had received treatment with MTX. The diagnosis of RA was made according to the American College of Rheumatology criteria. Based on immunohistochemistry performed on paraffin-embedded tissue sections, diagnoses were as follows: diffuse large B cell lymphoma (DLBCL; n=14), Hodgkin lymphoma (HL; n=7), follicular lymphoma (FL; n=4), mucosal-associated lymphoid tissue (MALT; n=3), Hodgkin-like lymphoma (HL-like; n=3), T-cell lymphoma (n=3), polymorphic LPD (P-LPD; n=2) according to the 4th WHO classification. Regarding EBV infection, 16 patients (44%) were positive. Patients with FL, MALT, and T-cell lymphoma were negative for EBV, except for one patient with T-cell lymphoma. In contrast, EBV infection positivity was prevalent in patients with DLBCL, HL, HL-like and P-LPD (46%, 100%, 100%, and 50%, respectively). Although HL indicated a specific phenotype, such as positivity for CD15 and CD30 (83%, and 100%, respectively), and rarely expressed CD20, OCT2 or BOB1 (0%, 14%, 14%, respectively), the phenotypes of HL-like and P-LPD were supposedly intermediate between DLBCL and HL. The phenotypes of FL, MALT, and T-cell lymphoma were the same as those of de novo cases. LPD regression was observed in 23 (66%) of 35 patients, which is more common than that seen in previous reports. Although LPD regression was not documented in patients with T-cell lymphoma, it did occur in all patients with HL, HL-like and P-LPD. In addition, the incidence of regression among patients with DLBCL, FL and MALT was 46%, 75% and 33%, respectively. The relationship between EBV infection and LPD regression among patients with HL, DLBCL, HL-like and P-LPD was statistically significant (p=0.048, Fisher's exact test). Of 23 patients with regression, 13 patients (56%) subsequently showed relapse/regrowth, and the incidence of this phenomenon was relatively high in patients with HL, HL-like and P-LPD (100%, 67%, and 50%, respectively), whereas a lower incidence was seen in patients with DLBCL, FL, and MALT (7%, 33%, and 0%, respectively). Summary/Conclusions LPD regression was relatively common (66%) in patients with OIIA-LPDs-RA, particularly in patients with B cell phenotypes. There was a significant relationship between LPDs and EBV infection in patients with HL, DLBCL and HL-like, suggesting that underlying EBV infection might influence the immunosuppressant effect of MTX against EBV in those phenotypes. Further, LPD relapse/regrowth was common in patients with HL, HL-like and P-LPD and was unlikely in patients with DLBCL. Further studies would be of benefit to investigate the underlying molecular mechanism of regression/relapse of LPD after withdrawal of MTX. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4148-4148
Author(s):  
Wei Xu ◽  
Jin-Hua Liang ◽  
Li Wang ◽  
Lei Fan ◽  
Hua-Yuan Zhu ◽  
...  

Abstract Objective: Determine efficacy and safety of PEMD (pegaspargase, etoposide, methotrexate, dexamethasone) in persons with newly-diagnosed advanced-stage extra-nodal NK/T-cell lymphoma. Subjects and methods: Twenty-seven consecutive subjects with newly-diagnosed advanced-stage (stage III-IV) extra-nodal NK/T-cell lymphoma were prospectively studied from July, 2010 to August, 2015. All subjects received PEMD (methotrexate, 3.0 g/m2 IV over 6 h on day 1, etoposide, 100 mg/m2 IV on days 2-4, dexamethasone, 40 mg IV on days 1-4 and pegaspargase, 2500 U/m2 IM on day 2). Courses were given every 3 week. Primary co-endpoints were response and survival. Secondary endpoints were proportion of subjects completing planned therapy (4 to 6 cycles of PEMD regimen) and frequencies of adverse events. Results: Median age was 46 y (range, 17-73 y). There were 21 males (78%). Nine subjects (33%) had non-nasal NK/T-cell lymphoma including 5 of the skin involvement, 1 of the testis involvement, 1 of the muscle involvement and 2 of the gastrointestinal tract involvement. Thirteen subjects (48%) had elevated serum LDH levels. Eleven subjects (41%) had higher level of EBV-DNA in blood (>5000 copies/mL). Twenty-one subjects (78%) had B-symptoms and 13 (48%) had an IPI score of 3-5. Subjects received a median of 4 courses of PEMD (range, 1-6). Median follow-up is 48 mo (range, 13-74 mo). Three patients had early death (within 3 mo after the diagnosis). Overall response rate (ORR) was 74% (95%CI 54%-89%) in the 27 subjects with advanced-stage disease including complete response (CR)/unconfirmed CR (CRu) in 12 (44% [95%CI 26%-65%]) and a partial response (PR) in 8 (30% [95%CI 14%-50%]). Four-year progression-free survival (PFS) was 44% (95%CI 25%-63%) and overall survival (OS) 51% (95%CI 32%-70%) (Figure 1). PFS and OS were not correlated between nasal and non-nasal types of ENKTL. There was no treatment-related death or serious allergic reactions. The most common grade-3/-4 hematologic complication was neutropenia (37% [95%CI 19%-58%]). The most common non-hematologic complications were infection (16% [95%CI 4%-34%]) and hypo-fibrinogenemia (12% [95%CI 2%-29%]). Conclusion: PEMD is effective and safe in persons with newly-diagnosed advanced-stage extra-nodal NK/T-cell lymphoma. Figure 1. PFS and OS for all the patients (N=27). Figure 1. PFS and OS for all the patients (N=27). Disclosures No relevant conflicts of interest to declare.


Surgery Today ◽  
2006 ◽  
Vol 36 (5) ◽  
pp. 474-477 ◽  
Author(s):  
Yoshio Deguchi ◽  
Kazuhiko Yoshimatsu ◽  
Shungo Endo

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