Case series of localized nasal NK/T-cell lymphoma treated with preceding intensified local radiation therapy before systemic chemotherapy

Nasal NK/T-cell lymphoma is EB virus-associated aggressive lymphoma, which is more prevalent in Asia. Previously, this lymphoma which was recognized as lethal midline granuloma, commonly presents with midline facial destructive lesions. In early stage I/II disease, radiation therapy exerts a powerful treatment outcome, however, toxic adverse events are indispensable and the tolerability of radiation therapy with chemotherapy has not been fully studied. It is imperative to offer an appropriate treatment for cure of this disease. We report consecutive 4 cases of nasal NK/T-cell lymphoma, which was treated with 56 Gy intensified local radiation therapy followed by systemic chemotherapy. Two cases complicated with grade 3 stomatitis during the treatment course and 3 cases were hospitalized due to the decrease of oral intake. The scheduled radiation chemotherapy was completed and resulted in complete response of disease in all cases. High intensified radiation therapy followed by chemotherapy may be effective for localized nasal NK/T-cell lymphoma.     

Intracranial Nasal Natural Killer/T-cell Lymphoma: Immunopathologically-Confirmed Case and Review of Literature

Summary Advances in immunophenotypic profiling now permit characterization of natural killer/T-cell (NK/T-cell) lymphoma as distinct from other extranodal T- and B-cell Non-Hodgkin’s lymphomas. NK/T-cell lymphoma presents most commonly in the nasal cavity. Disease progression to the central nervous system (CNS) is a rare phenomenon. We present here, to our knowledge, the first immunophenotypically-confirmed case of direct extension of nasal NK/T-cell lymphoma to the brain. In addition, we review the literature with respect to NK/T-cell lymphoma metastasis to the CNS. The overall prevalence of NK/T-cell lymphoma CNS metastasis is less than 3%. Although rare, CNS invasion portends a poor prognosis, emphasizing the importance of early and accurate immunophenotype profiling and the need for novel, aggressive therapy.     

Allogeneic haematopoietic stem cell transplantation as a salvage strategy for relapsed or refractory nasal NK/T-cell lymphoma

Nasal NK/T-cell lymphoma is rare and occurs most frequently in East Asia and Latin America. It is characterized by its aggressive nature and tends to become resistant to chemotherapy and radiotherapy. Autologous haematopoietic stem cell transplantation (auto-HSCT) is often associated with a high relapse rate for the active or disseminated disease. There are limited data about allogeneic haematopoietic stem cell transplantation (allo-HSCT) for relapsed or refractory nasal NK/T-cell lymphoma. In our study, two patients with nasal NK/T-cell lymphoma were successfully treated with allo-HSCT. The first patient was a 31-year-old woman who relapsed after auto-HSCT. Subsequently, HLA-matched allo-HSCT was considered as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/Vm26/Ara-C. Donor lymphocyte infusion was used to reduce the risk of relapse. After allo-HSCT, the tumor in her nasal cavity gradually disappeared. She has been in continuous complete remission (CR) for 3 years. The second patient was a 26-year-old woman diagnosed with stage IIIB advanced nasal NK/T-cell lymphoma who was resistant to combination radiochemotherapy. She underwent HLA-matched allo-HSCT as a salvage treatment. Modified BU/CY conditioning regimens included BU/CY/MeCCNu/Ara-C. She has been in continuous CR for five years. The stem cell source was peripheral blood for both patients, and there was no severe graft-versus-host disease in either patient. Our clinical experience suggests that allo-HSCT with a modified conditioning regimen is a promising treatment for patients with relapsed or refractory nasal NK/T-cell lymphoma.     

Nasal-type NK/T-cell Lymphoma with Palatal Ulcer as the Earliest Clinical Manifestation: A Case Report with Literature Review

Extranodal nasal natural killer (NK)/T-cell lymphoma is a very rare kind of lymphoma, Oral cavity involvement of extranodal natural killer/T-cell lymphoma, nasal type is extremely rare, and its clinicopathologic features are also poorly understood. Recently, we experienced an unusual case of Epstein-Barr virus-associated, extranodal NK/T-cell type with a unhealed palatal ulcer as the earliest clinical feature. It is a challenge for oral medicine specialists to make the early diagnosis for this special type of tumor.     

Radiothérapie des lymphomes NK/T localisés aux fosses nasales

Natural killer (NK)/T-cell lymphoma are part of lymphoproliferative diseases, they are rare in Europe and the United States but relatively common in Asia and South America. Natural killer (NK)/T-cell lymphoma present clinically as destructive lesions of the upper aerodigestive tract with perforation of deep structures of the face, destruction of the palate or an invasion of orbits. Treatment modalities of these lymphomas are still discussed because of the lack of available studies and the rarity of this disease. Radiotherapy provides a rapid control of the disease and is positioned as a major treatment of localized stages of NK/T-cell lymphoma of the nasal cavity. We therefore studied the different forms of radiation therapy in the early stages of nasal NK/T-cell lymphoma.     

L-Asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature

Background: Extranodal natural killer (NK)/T-cell lymphoma,nasal type, and aggressive NK-cell leukemia are highly aggressivediseases with a poor outcome. Patients and methods: We report a multicentric French retrospectivestudy of 15 patients with relapsed, refractory, or disseminateddisease, treated with L-asparaginase-containing regimens inseven French centers. Thirteen patients were in relapse and/orrefractory and 10 patients were at stage IV. Results: All but two of the patients had an objective responseto L-asparaginase-based treatment. Seven patients reached completeremission and only two relapsed. Conclusion: These data, although retrospective, confirm theexcellent activity of L-asparaginase-containing regimens inrefractory extranodal NK/T-cell lymphoma and aggressive NK-cellleukemia. Therefore, L-asparaginase-based regimen should beconsidered as a salvage treatment, especially for patients withdisseminated disease. First-line L-asparaginase combinationtherapy for extranodal NK/T-cell lymphoma and aggressive NK-cellleukemia should be tested in prospective trials. Key words: L-asparaginase, NK/T-cell lymphoma Received for publication July 2, 2008. Accepted for publication July 4, 2008.     

结外鼻型NK/T细胞淋巴瘤30例诊疗分析

目的 探讨结外鼻型NK/T细胞淋巴瘤的临床特征及预后影响因素.方法 对按照WHO淋巴瘤分类标准,经病理确诊的30例结外鼻型NK／T细胞淋巴瘤患者临床特点、长期生存率、预后因素进行分析.结果 30例结外鼻型NK/T细胞淋巴瘤患者,以男性患者居多,中位发病年龄45岁,年轻患者鼻外型较多见,且更易合并噬血细胞综合征.实验室检查发现白细胞、血红蛋白、血小板、丙氨酸氨基转移酶、乳酸脱氢酶、清蛋白常有异常,且在生存组与死亡组之间,血红蛋白下降、血清清蛋白下降程度的差异有统计学意义.死亡患者发病年龄相对较轻,鼻外型多见,更多伴B症状、噬血细胞综合征,国际预后指数（IPI）评分较高,骨髓累及发生率较高,临床分期更晚,实验室检查异常更多.Kaplan-Meier单因素分析显示发病年龄、是否鼻腔来源、有无B症状、有无骨髓累及、是否伴发噬血细胞综合征、IPI评分、临床分期、治疗方法,以及有无白细胞、血红蛋白、血小板、血清乳酸脱氢酶、清蛋白水平异常,有无肝功能损伤等因素,均可影响预后;采用Cox回归模型进行多因素预后分析,显示有无血清LDH升高及有无骨髓累及为影响预后的独立危险因素.结论 结外鼻型NK/T细胞淋巴瘤多见于中年男性,侵袭性高,病初临床表现多样.相比鼻腔NK/T细胞淋巴瘤患者,鼻外型患者发病年龄更轻,实验室异常更明显,更易伴发噬血细胞综合征,更易累及骨髓,预后更差.有无血清LDH升高及有无骨髓累及为影响预后的独立危险因素.     

Natural killer cell lymphoma in the duodenum

We present a case of duodenal non-Hodgkin lymphoma in a 71-year-old woman. Immunohistochemistry characterized the lymphoma cells as CD2(+); surface CD3(-) but cytoplasmic CD3(+); CD7(+); and CD56(+) without a rearrangement of the T-cell receptor gene. Cells had a high N/C ratio and irregular nuclear outlines and lacked azurophilic granules and these features indicated that the lymphoma cells arose from natural killer (NK) cells. She was treated with intensive chemotherapy including pirarubicin, cyclophosphamide, vincristine, and prednisolone, but died three weeks after diagnosis. CD56(+) lymphomas originate from NK or cytotoxic T cells and are designated "extranodal NK/T-cell lymphoma, nasal type" in the WHO classification. Nasal NK cell lymphoma is most common in East Asians and CD56(+) lymphomas usually occur in the nasal area. Extranasal forms such as gastrointestinal lymphomas are very rare and usually carry a poor prognosis. Extranodal NK/T-cell lymphoma, nasal type, is characterized by a broad morphologic spectrum and have variable prognosis. These lymphomas constitute an heterogeneous group, and their subclassification has not yet been established.     

不同治疗方案对鼻、鼻型NK/T细胞淋巴瘤疗效分析

目的：探讨鼻、鼻型NK/T细胞淋巴瘤的临床特征、治疗方法和预后。方法：收集自2004年1月-2010年1月在我院住院治疗的29例鼻、鼻型NK/T细胞淋巴瘤患者临床资料,分析其临床特点、治疗方案及预后。结果：治疗分CHOP方案组及L-ASP组,总有效率分别为56.3%和75.9%（P=0.045）。两组5年OS率和DFS率分别为43.75%、61.54%（P=0.038）及18.8%、46.15%（P=0.009）,具有统计学意义。难治组7例经VDLP方案补救化疗后总有效率为71.3%。B组症状、临床分期及KPS评分可能对患者的生存产生影响。结论：对于临床早期的鼻、鼻腔NK/T细胞淋巴瘤患者,初治时可以选择CHOP方案治疗,而中、晚期病例及CHOP方案治疗无效的病例,选择以左旋门冬酰胺酶为主的联合化疗结合放疗综合治疗可取得较好疗效。     

不同治疗方案对鼻、鼻型NK/T细胞淋巴瘤疗效分析

目的 探讨鼻、鼻型NK/T细胞淋巴瘤的临床特征、治疗方法和预后.方法 收集自2004年1月-2010年1月在我院住院治疗的29例鼻、鼻型NK/T细胞淋巴瘤患者临床资料,分析其临床特点、治疗方案及预后.结果:治疗分CHOP方案组及L-ASP组,总有效率分别为56.3%和75.9%（P=0.045）.两组5年OS率和DFS率分别为43.75%、61.54%（P=0.038）及18.8%、46.15%（P=0.009）,具有统计学意义.难治组7例经VDLP方案补救化疗后总有效率为71.3%.B组症状、临床分期及KPS评分可能对患者的生存产生影响.结论:对于临床早期的鼻、鼻腔NK/T细胞淋巴瘤患者,初治时可以选择CHOP方案治疗,而中、晚期病例及CHOP方案治疗无效的病例,选择以左旋门冬酰胺酶为主的联合化疗结合放疗综合治疗可取得较好疗效.     

Fine needle aspiration cytology of CD56-positive natural killer/T-cell lymphoma of soft tissue

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare form of lymphoma with a predilection for Southeast Asians, including Koreans, and Central and South Americans. It has a high association with Epstein-Barr virus (EBV) and expression of CD56 antigen. In the current study, the authors reviewed the fine needle aspiration (FNA) cytology of NK/T-cell lymphoma involving soft tissue to identify characteristic cytologic features. METHODS: Ten FNAs of soft tissue involvement by histologically documented NK/T-cell lymphoma from eight patients (three nasal primary and five extranasal primary tumors) were included in the retrospective study of a six-year period (1996-2002). Diff-Quik- and Papanicolaou-stained smears were reviewed, as was the biopsy material, including immunohistochemical stains and in situ hybridization studies for EBV. Clinical information was obtained from the patients' medical records. RESULTS: Specimen sources were skin and subcutaneous tissue of the neck (3), arm (3), breast (2), and abdominal wall (1) and soft tissue of the buccal area (1). The smears were moderately to highly cellular in the extensively necrotic background, with an abundance of apoptotic debris. Single, scattered tumor cells had pleomorphic nuclei, coarse chromatin, indistinct or several small nucleoli, and eccentric bluish cytoplasm. Neutrophils were typically rare in most cases except in one case complicated by abscess. CONCLUSIONS: Fine needle aspiration can be a useful adjunct in the diagnosis of the nasal and extranasal NK/T-cell lymphoma. The presence of malignant lymphoid cells in a necrotic background with an abundance of apoptotic bodies is a highly characteristic and consistent finding in FNA of NK/T-cell lymphoma involving soft tissue.     

Treatment outcome of angiocentric T-cell and NK/T-cell lymphoma, nasal type: radiotherapy versus chemoradiotherapy

OBJECTIVE: The purpose of this study was to evaluate the treatment outcome of angiocentric T-cell and natural killer (NK)/T-cell lymphoma, nasal type. METHODS: Between February 1989 and March 2001, 53 patients with newly diagnosed angiocentric T-cell and NK/T-cell lymphoma, nasal type involving the head and neck, were treated with radiation therapy (RT). There were 37 males and 16 females. The median age of the patients was 45 years (range 19-73). Twenty of them were treated with chemoradiotherapy (CRT), while 33 with treated with RT alone. The median follow-up period was 74 months (range 6-173). RESULTS: The 5-year overall survival rate of all patients was 69%. CRT appeared to be inferior to RT alone in terms of 5-year overall survival, though the difference was not statistically significant (59 versus 76%, P = 0.27). CONCLUSIONS: There was no difference in survival between RT and CRT in angiocentric T-cell and NK/T-cell lymphoma, nasal type.     

Partial trisomy of chromosome 13 as a single cytogenetic abnormality in an Italian case of nasal NK/T lymphoma

Extranodal NK/T lymphoma, nasal type, is an uncommon neoplasm that occurs with a higher prevalence among Asian populations and Native American populations of Central and Southern America. In Western countries, this tumor is extremely rare, accounting for less than 1.5% of all non-Hodgkin lymphomas. Cytogenetic analyses have been performed only in a limited number of cases, mainly because of technical problems related to extensive necrosis and the scarcity of clinical samples, and these have shown complex karyotypes with no specific chromosomal translocations. Here, we report the cytogenetic characterization of a clinically aggressive nasal NK/T-cell lymphoma occurring in a 40-year-old Italian male patient, in which the sole chromosome abnormality was a partial trisomy of chromosome?13.     

The clinical study of extranodal natural killer cell lymphoma, nasal type

To analyze the clinical characteristics, treatment of extranodal NK/T-cell lymphoma, nasal type, the term "nasal type" describes in the nasal cavity and also in the extranasal sites. There were 82 patients with nasal NK/T lymphoma (group 1) and 11 patients with extranasal NK/T lymphoma (group 2). In group 1, 4 patients gave up treatment. Five patients received radiotherapy (RT) alone. Fifty-seven patients were treated with combination of chemotherapy and RT. Sixteen patients received chemotherapy alone. Most patients (82.9%) had stage I/II disease and a high frequency (about one-third) of B symptoms. The CR rate was 53.8%. The OS rate was 62.8% (49/78 cases). Three patients died in relation to L-asparaginase. Three patients with late relapses occurred at 10 and 17 years from CR, respectively. In group 2, except that one patient received chemoradiotherapy, 10 patients received chemotherapy. Seven patients died. The OS rate was 36.4%. Our study suggested that nasal and extranasal variants of extranodal NK/T lymphoma, nasal type represented different clinical behavior and prognosis. For comparison, extranasal NK/T lymphoma is more aggressive and higher mortality than nasal NK/T lymphoma.     

An autopsy case of aggressive CD30+ extra-nodal NK/T-cell lymphoma initially manifested with granulomatous myositis

This study reports an autopsy case of a 53 year-old male with rapidly progressive extra-nodal NK/T-cell lymphoma accompanied with unusual clinical and pathologic features. He was initially presented with localized swelling and tenderness in the right lower extremity and the biopsy from the calf muscle was interpreted as granulomatous myositis masquerizing lymphoma. The biopsy from erythematous skin lesion of trunk showed infiltration of medium sized atypical lymphoid cells with relatively plump cytoplasm and immunophenotype of CD30+, CD56+/- and surface CD3-, which lead to the diagnosis of CD30+ anaplastic large cell lymphoma. About 2 months later, nasal obstruction was developed and the nasal biopsy was done. After confirmation of EBV infection, he was finally diagnosed as extra-nodal NK/T-cell lymphoma with peculiar immunophenotype of CD3 dim+ and CD30+. Despite the chemotherapy, he was going rapidly downhill and died of respiratory and multi-organ failure 8 months after the onset of soft tissue lesion. At autopsy, disseminated angiocentric lymphoma was found all over the internal organs including the brain. This case emphasizes that extra-nodal NK/T-cell lymphoma should be considered as a cause of granulomatous myositis and can express CD30 positivity and CD3 weak positivity, which are unusual but rarely predominant feature of NK/T-cell lymphoma.     

造血干细胞移植在鼻型结外NK/T细胞淋巴瘤治疗中的地位

鼻型结外NK/T细胞淋巴瘤（ENKTL）是来源于NK细胞或T细胞的一种侵袭性淋巴瘤,预后较差.文章主要论述造血干细胞移植在该病治疗中的地位.     

Treatment of T-cell non-hodgkin’ lymphoma

Opinion statement T-cell non-Hodgkin’s lymphoma (NHL) represents approximately 10% to 15% of all lympho-mas in Western countries. Patients with T-cell NHL are often treated similarly to patients with intermediate grade B-cell NHL, although many reports have demonstrated lower overall survival rates in patients with T-cell NHL compared to patients with B-cell NHL. Updated classifications have recognized specific clinical and pathologic T-cell entities, such as peripheral T-cell lymphoma, not otherwise characterized, angioimmunoblastic lymphoma, systemic anaplastic T-cell lymphoma, adult T-cell leukemia/lymphoma, subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, and enteropathy-type intestinal T-cell lymphoma. Furthermore, these distinct T-cell NHL subtypes often warrant individual-ized diagnostic and therapeutic strategies, such as the associated cytophagic histiocytic panniculitis and hemophagocytic syndrome with subcutaneous panniculitis-like T-cell lymphoma, the chromosomal translocation t(2;5), leading to the nucleophosmin anaplastic lymphoma kinase fusion protein, viral pathogenesis of Epstein-Barr virus, human T-cell lymphotropic virus type-1 associated with extranodal NK/T-cell lymphoma nasal type and adult T-cell leukemia/lymphoma, respectively, and the role of radiation therapy in extra-nodal NK/T-cell lymphoma nasal type. Other active therapeutic agents in T-cell NHL include purine and pyrimidine antimetabolite agents eg, nucleoside analogues and gemcitabine, respectively), denileukin diftitox, and antinucleoside or retinoic acid with interferon-α combination treatment. The exact role of transplantation in patients with T-cell NHL is unknown, but several case series have documented the feasibility of autologous and allogeneic transplant with reported long-term survival rates similar to transplanted B-cell NHL. Identification of relevant proto-oncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL, such as the nucleophosmin anaplastic lymphoma kinase fusion protein, p53 and retinoblastoma gene, cyclin-dependent kinase inhibitors, histone deacetylation inhibitors, and infectious etiologies (eg, Epstein-Barr virus and Helicobacter pylori), in addition to their interplay with the various regulatory pathways of cell-cycle progression and apoptosis, represent potential candidates for molecular-based therapy. Prospective multi-institution clinical trials are critically important to determine the most effective treatment regimens that will continue to improve cure rates in these aggressive, yet treatable and often curable, diseases.     

Body cavity-based presentation of natural killer cell lymphoma

We describe an unusual case of a 31-year-old Mexican woman who presented with pleural and peritoneal effusions involved by Epstein-Barr virus-positive non-Hodgkin's lymphoma of natural killer (NK)-cell lineage. The patient had no symptoms that could be related to her nasal region, and physical examination and radiologic studies showed no evidence of lymphadenopathy, organomegaly, or other extranodal masses. Thus, this case clinically mimicked body cavity-based lymphoma. Extranodal NK/T-cell lymphoma of nasal type is the current designation for these neoplasms in the recently proposed World Health Organization classification of lymphoid neoplasms. These tumors previously have been referred to many other names, including lethal midline granuloma, midline malignant reticulosis, polymorphic reticulosis, angiocentric immunoproliferative lesion, and angiocentric lymphoma. Nasal-type NK/T-cell lymphomas typically involve the nasal region, but may involve other extranodal sites, such as skin and gastrointestinal tract. The malignant cytologic features and the presence of azurophilic granules within the cell cytoplasm observed in Wright-Giemsa-stained cytocentrifuge preparations led to immunophenotypic and molecular genetic studies that were essential in establishing the correct diagnosis. As demonstrated in the case reported, extranodal NK/T-cell lymphomas of nasal-type can be clinically aggressive and may be associated with paraneoplastic phenomena.     

Extranodal NK/T-cell lymphoma mimicking cellulitis

NK/T-cell lymphoma is difficult to diagnose because there is no characteristic cytology to help the diagnosis in tissue sections, particularly when there is polymorphic cellular infiltration in the early stage of the disease. However, the nasal type of extranodal NK/T-cell lymphoma has a characteristic histologic pattern, which is angiocentric, angioinvasive and angiodestructive. Therefore, many cases of this tumor may show extensive necrosis that mimics infectious process. Furthermore, because the immunosuppressive status of these patients, they may, in fact, have superimposed infections. We are reporting a case that presented as cellulitis and only after careful examination with immunohistochemistry that a correct diagnosis of extranodal NK/T-cell lymphoma, nasal type, was established. Since this lymphoma is incurable and immunophenotyping is instrumental for the diagnosis and prediction of the prognosis, a high index of suspicion for this tumor is needed when an angiocentric lesion is found in the midline of the head and neck region, and a thorough immunohistological study should always be conducted in these cases.