Natural Killer–Cell Lymphoma Involving the Gynecologic Tract

2000 ◽  
Vol 124 (10) ◽  
pp. 1510-1513 ◽  
Author(s):  
Paulette Mhawech ◽  
L. Jeffrey Medeiros ◽  
Carlos Bueso-Ramos ◽  
Donna M. Coffey ◽  
Alfredo F. Gei ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Killer Cell ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Gene Rearrangements ◽  
Neoplastic Cells

Abstract Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.

scholarly journals CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3567-3574 ◽  
Author(s):  
Chung-Wu Lin ◽  
Ting-Yun Liu ◽  
Shee-Uan Chen ◽  
Kun-Teng Wang ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Lineage ◽  
Lymphoid Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Gene Rearrangements

AbstractMost lymphoblastic lymphomas (LBLs) are regarded as neoplasms of immature T cells because they express cytoplasmic CD3 and frequently carry T-cell receptor (TCR) gene rearrangements. Immature natural killer (NK) and T cells, however, have a common bipotent T/NK-cell precursor in the thymus, and NK cells also express cytoplasmic CD3. Thus, some LBLs could arise from immature NK cells. Mature NK cells express 2 CD94 transcripts: 1A, induced by interleukin 15 (IL-15), and 1B constitutively. Because immature NK cells require IL-15 for development, CD94 1A transcripts could be a marker of NK-LBL. To test this hypothesis, we used laser capture microdissection to isolate IL-15 receptor α+ lymphoid cells from the thymus and showed that these cells contained CD94 1A transcripts. We then assessed for CD94 transcripts in 21 cases of LBL that were cytoplasmic CD3+, nuclear terminal deoxynucleotidyl transferase positive (TdT+), and CD56-, consistent with either the T-cell or NK-cell lineage. We found that 7 LBLs expressed CD94 1A transcripts without TCR gene rearrangements, suggesting NK-cell lineage. Patients with NK-LBL were younger than patients with T-LBL (15 years versus 33 years; P = .11) and had a better 2-year survival (100% versus 27%; P < .01). These results improve the current classification of LBL and contribute to our understanding of NK-cell differentiation.

Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5631-5637 ◽  
Author(s):  
Kengo Takeuchi ◽  
Masahiro Yokoyama ◽  
Shin Ishizawa ◽  
Yasuhito Terui ◽  
Kimie Nomura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Killer Cell ◽  
Diagnostic Errors ◽  
Cell Receptor ◽  
Clinical Consequences ◽  
Epstein Barr

Abstract Diagnostic errors in distinguishing between malignant and reactive processes can cause serious clinical consequences. We report 10 cases of unrecognized self-limited natural killer–cell proliferation in the stomach, designated as lymphomatoid gastropathy (LyGa). This study included 5 men and 5 women (age, 46-75 years) without any gastric symptoms. Gastroscopy showed elevated lesion(s) (diameter, ∼ 1 cm). Histologically, medium-sized to large atypical cells diffusely infiltrated the lamina propria and, occasionally, the glandular epithelium. The cells were CD2+/−, sCD3−, cCD3+, CD4−, CD5−, CD7+, CD8−, CD16−, CD20−, CD45+, CD56+, CD117−, CD158a−, CD161−, T cell–restricted intracellular antigen-1+, granzyme B+, perforin+, Epstein-Barr early RNA−, T-cell receptor αβ−, and T-cell receptor γδ−. Analysis of the 16 specimens biopsied from 10 patients led to a diagnosis of lymphoma or suspected lymphoma in 11 specimens, gastritis for 1 specimen, adenocarcinoma for 1 specimen, and LyGa or suspected LyGa for 3 specimens. Most lesions underwent self-regression. Three cases relapsed, but none of the patients died. According to conventional histopathologic criteria, LyGa is probably diagnosed as lymphoma, especially as extranodal natural killer/T-cell lymphoma, nasal type. However, LyGa is recognized as a pseudomalignant process because of its clinical characteristics. The concept of LyGa should be well recognized.

scholarly journals Nonnasal Lymphoma Expressing the Natural Killer Cell Marker CD56: A Clinicopathologic Study of 49 Cases of an Uncommon Aggressive Neoplasm

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4501-4513 ◽  
Author(s):  
John K.C. Chan ◽  
V.C. Sin ◽  
K.F. Wong ◽  
C.S. Ng ◽  
William Y.W. Tsang ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Leukemia ◽  
Neoplastic Cells ◽  
Prolymphocytic Leukemia ◽  
Nasal Type ◽  
Nk T Cell

Abstract Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non–B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4− CD3ε+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4− CD56+ CD16− CD57− and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV−. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic γδ T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV−. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Clinical Analysis Of 120 Cases Of Natural Killer/T Cell Lymphoma, Nasal Type By Single Hospital In The North-Western China

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5111-5111
Author(s):  
Rong Liang ◽  
Xie qun Chen ◽  
Zhe Wang ◽  
Bai qin Xian ◽  
qin-Guo guo Yan ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
Primary Site ◽  
Individual Therapy ◽  
T Cell Lymphoma ◽  
Ebv Dna

Abstract Objectives To improve the understanding of extranodal natural killer(NK)/ T cell lymphoma (ENKTCL) with poor prognosis and provide experiential references for individual therapy via a retrospective analysis of the clinical and pathological features. Methods 120 NKTCL cases from April 2007 to Oct 2012 in single center of Northwestern China were retrospectively analyzed on their pathologic diagnosis and clinical manifestations. Pathological examinations were mainly depended on morphology, immunohistochemisty for immunophenotype and In situ hybridizationc for epstein - barr virus (EBV) small encoded RNA£¨EBER£©. Polymerase chain reaction (PCR) for the amount of EBV DNA in whole-blood and T-cell receptor (TCR) gene rearrangement were performed. Chemotherapy and or radiotherapy were the main treatments. Complete remission(CR), 2 year(2y) overall survival (OS) and progressive free survival (PFS) according to clinical characteristics were analyzed. Results The median age of 120 NKTCL cases was 43.19+13.7 years old. 98 primary nasal ENKTCL cases accounted for 81.4%, whose 2y OS and PFS were 88.6% and 69.1% respectively. 22 non-nasal ENKTCL accounted for 18.3%£€whose 2y OS and PFS were 58.8% and 45.5% respectively, which was statistically significant comparing with primary nasal ENKTCL cases. It was found that patients with primary intestinal or Ki67 greater than 80% were dead in first year. Patients with primary liver and intestinal had higher Ki67 than patients with primary nasal. Rate of 2y OS of 43 patients with Ki67 from 60% to 80% was 60% and PFS was 36% as compared to 86.3% of rate of OS and 57.5% for PFS of 30 patients with Ki67 from 30% to 50% and 100% of rate of OS and 78% for PFS of 7 patients with Ki67 less than 30%. Basing on analysis showed that from the cell of origin, it was found that primary site was nasal and 2y OS 100%¡¢PFS 75%£€in 8 cases with CD56+,CD3+ and T-cell receptor (TCR) gene rearrangement, which was statistically significant comparing with CD56- nasal ENKTCL cases. EBER was positive in every case. Among the 13 EBV –DNA samples detected, there were 5 samples with more than 6.1X107 copies/ml with OS 60%. 2y OS and PFS of Patients with normal ferritin ¦Â-microglobulin were longer than that of higher ferritin and ¦Â-microglobuli( P). 2y OS and PFS of 10 cases with I stage who had only radiotherapy was 100% respectively. 47 cases with II-IV stage received only chemotherapy. Their 2y OS and PFS was 100% and 90% respectively for patients with II stage better than that of III and IV stage. 63 cases with treatment of chemotherapy and radiotherapy. Among them, 2y OS and PFS of local nasal and invasion nasal were different. International prognostic index, IPI was good for prognosis for OSºÍPFS. Conclusion£º It was implied that Ki67, CD56, EBER, EBV-DNA and primary site was related with the prognosis of NKTCL. It needs further and more clinical observation and verification to judge if they could be additional markers for prognostication and clinical stratification to be incorporated in clinical individual management algorithms. The chemotherapies containing asparaginase or polyehylene glycol asparaginase are more effective. Autologous stem cell transplantation could make patients long live and pretransplant CR status was a major prognostic factors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Chronic natural killer cell lymphocytosis: a descriptive clinical study

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2721-2725 ◽  
Author(s):  
A Tefferi ◽  
CY Li ◽  
TE Witzig ◽  
MV Dhodapkar ◽  
SH Okuno ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Disease Duration ◽  
Nk Cell ◽  
Receptor Gene ◽  
Killer Cell ◽  
Clinical Manifestations ◽  
Cell Receptor ◽  
Neutropenic Sepsis ◽  
Lgl Leukemia

Abstract We review the clinical manifestations and long-term outlook of patients with chronic natural killer (NK) cell lymphocytosis. After reviewing more than 1,500 peripheral blood lymphoid flow cytometry reports and molecular genetics data from patients with suspected large granular lymphocyte (LGL) proliferation, we identified 10 patients (median age at diagnosis, 60 years; range, 35 to 76 years; male:female ratio, 3:2) with persistent (greater than 6 months) increase in phenotypically determined NK cells (CD3-CD16+). Southern blot analysis performed on 9 patients showed no clonal T-cell receptor gene rearrangements. Disease duration was measured from time of initial recognition of LGL or NK cell excess (greater than 40% of the lymphocyte fraction). Clinical data from these 10 patients were compared with those from 68 patients with T-cell LGL (T-LGL) leukemia. Currently, all patients are alive (median disease duration, 5 years; range, 0.8 to 8 years). Associated disease manifestations included pure red blood cell aplasia, recurrent neutropenia, recurrent neutropenic sepsis, and vasculitic syndromes, all of which were responsive to immunosuppressive therapy. No patient had palpable lymphadenopathy or splenomegaly. Compared with the patients with T-LGL leukemia, patients with chronic NK cell leukemia has similar lymphocyte counts, associated conditions, treatment responses, and survival but had less neutropenia and anemia.

scholarly journals Binding Strength and Dynamics of Invariant Natural Killer Cell T Cell Receptor/CD1d-Glycosphingolipid Interaction on Living Cells by Single Molecule Force Spectroscopy

2011 ◽  
Vol 286 (18) ◽  
pp. 15973-15979 ◽  
Author(s):  
Bianca L. Bozna ◽  
Paolo Polzella ◽  
Christian Rankl ◽  
Rong Zhu ◽  
Mariolina Salio ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Single Molecule ◽  
Killer Cell ◽  
Force Spectroscopy ◽  
Cell Receptor ◽  
Living Cells ◽  
Single Molecule Force Spectroscopy ◽  
Invariant Natural Killer

Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells.

Detection of T-cell receptor γ gene rearrangement in paraffin-embedded T or natural killer/T-cell lymphoma samples using the BIOMED-2 protocol

2014 ◽  
Vol 55 (9) ◽  
pp. 2161-2164 ◽  
Author(s):  
Tomoko Miyata-Takata ◽  
Katsuyoshi Takata ◽  
Sachiko Yamanouchi ◽  
Yasuharu Sato ◽  
Mai Harada ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Killer T Cell ◽  
Natural Killer T
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