Endometrial cancer with congenital uterine anomalies: 3 case reports and a literature review

Background: Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital uterine anomalies associated with endometrial cancer in the past 25 years, to identify similarities and differences in clinicopathologic characteristics and prognosis between endometrial cancer associated with uterine anomalies, and normal uterus. Cases: Case 1 was a 75-year-old gravida 1, para 0, woman with carcinosarcoma (mixed well-differentiated endometrial adenocarcinoma and undifferentiated sarcoma) of the right cavity (grade III, and at least stage II ) of a uterus didelphys. The tumor recurred within 7 months after surgery, salvage radiotherapy was unsuccessful; the patient died 8 months after the surgery. Case 2 was a 63-year-old gravida 5, para 3, woman with a bicornuate uterus and uterus papillary serous carcinoma of the right horn (grade III, stage IIIC). She did not respond to the chemotherapy post surgery and died within 4 months. Case 3 was a 60-year-old gravida 0, para 0, woman with a complete septate uterus and an oblique vaginal septum of the upper region of the vagina with endometrioid adenocarchcinoma of the left cavity (grade II, stage IA). No adjuvant therapy was administered and the patient had recovered 2 y after the surgery. Conclusion: Clinicians should be aware of the coexistence of uterine malignancies and uterine anomalies in patients presenting with persistent abnormal uterine bleeding, but with negative endometrial biopsy or failed in the operation of endometrial biopsy. In such cases, magnetic resonance imaging has an important role in the diagnosis of both malformation and malignancy, and an exploratory laparotomy should be performed to avoid delaying the diagnosis and treatment of cancers.     

Blastic natural killer (NK)-cell lymphoma: report of an unusual CD4 negative case and review of the CD4 negative neoplasms with blastic features in the literature

Blastic Natural Killer (NK)-cell lymphoma is a relatively new entity which has been recently included in the WHO classification. CD4 expression is observed in most cases of blastic NK-cell lymphomas and has been related with skin tropism. We report an unusual CD4 negative blastic NK-cell lymphoma with primary presentation in the skin, subsequent infiltration of the bone marrow and aggressive behavior. It is emphasized that extensive immunophenotyping and EBER RNA in situ hybridization are required in order to establish the diagnosis of blastic NK-cell lymphoma. We also present a review of the literature with respect to the CD4 negative NK-cell lymphomas with blastic morphological features.     

Agranular CD4+/CD56+ cutaneous neoplasm

CD4+ CD56+ cutaneous neoplasm with hematological relapse is a rare malignant disease and has been described recently in the literature as blastic or agranular NK-cell leukemia/lymphoma. The origin of this neoplasm is uncertain. We describe a 75-year-old patient with a primary cutaneous neoplasm CD4+ CD56+ who evolved to leukemic phase despite standard lymphoma chemotherapy. Morphologically, the cells were undifferentiated without granules in the cytoplasm. The immunophenotype showed the expression of CD4, CD56, CD68, CD33, CD7, CD2, CD45RA, and CD38. Histological analysis revealed a cell infiltration mainly located in the dermis. T-cell receptor and immunoglobulin heavy chain genes were in germline configuration. Cytogenetic study showed complex structural abnormalities with a deletion of the chromosome 5 del(5q). The clinical course was aggressive with an early hematological relapse.     

Diagnosis and Management of Primary Nasal Lymphoma of T-Cell or NK-Cell Origin

The primary nasal natural killer cell (NK/T cell) lymphoma is histologically characterized by angiocentricity with invasion of blood vessels and blockage of blood vessels by lymphoma cells, resulting in marked ischemic necrosis of the normal and neoplastic tissues. The cytological appearances of the neoplastic cells are highly variable and accompanied by a mixture of inflammatory cells. On immunophenotyping, the diagnostic features are surface CD3⁻, cytoplasmic CD3 epsilon⁺, and CD56⁺. For the majority of the cases, T-cell receptor gene rearrangement is absent, confirming an NK-cell origin of the tumor cells. Clonal proliferation of Epstein-Barr virus (EBV) is usually present in the tumor cells and is a useful diagnostic marker. Patients commonly present with nasal symptoms: mass, obstruction, or bleeding. The tumor is locally invasive and may infiltrate surrounding tissues and organs, such as the orbits, nasopharynx, oropharynx, and palate. The cranial nerves are sometimes affected. The tumor may also disseminate to skin, gastrointestinal tract, and the testis at the time of progression. Occasionally, other organ sites such as the skin are involved, sparing the nose, and it is then called the nonnasal type. A high index of suspicion is required for the diagnosis of this disease. Because of the small size of the specimen and the necrotic nature of the tumor, biopsy of the nasal tissue may not be easy to interpret. Repeated biopsies are often required. The special stain for EBV in the tumor cells may also be helpful in making the correct diagnosis. Response of primary nasal T-/NK-cell lymphoma to local treatment such as radiotherapy is often not satisfactory. Combined chemotherapy and radiotherapy has been used and appears to be more effective.     

睾丸的原发性NK/T细胞淋巴瘤一例报告及文献复习

Objective： To study the clinical and pathological features of primary NK/T cell lymphoma of testis and to investigate the effective diagnosis and treatment of this disease. Methods： The surgical specimens of a patient with primary NK/T cell lymphoma of the testis were observed by light microscopy, immunohistochemistry and examined by the polymerase chain reaction （PCR） for Epstein-Barr virus （EBV） DNA and T-cell receptor （TCR） gene rearrangement, and the literature were reviewed. Results： The patient presented with left-sided painless testicular enlargement and the lymphoma had a propensity to spread to the contralateral testis, spleen, central nervous system, and so on. The neoplastic cells were positive for CD56, CD45R0 and CD3ε, while the expressions of CD20, CD79α, CD5, Bcl-2 and PLAP were negative. In addition, the EBV DNA was detected in the lymphoma by PCR. And the results of gene rearrangement studies for the y chain of the T-cell receptor were negative. The pathological diagnosis was NK/T cell lymphoma of the left testis. Conclusion： Primary NK/T cell lymphoma of the testis is a rare entity and progressed rapidly. The histopathological, immunohistochemical, EBV examination and TCR gene rearrangement studies should be carried out as soon as possible in order to get the defined diagnosis. Currently, the therapeutic efficacy is poor and the new measures should be investigated to improve the survival rate.     

Primary Testicular NK/T-Cell Lymphoma：A Study of Two Cases and Review of Literature

Primary testicular NK/T-cell lymphoma is an extremely rare entity progressed rapidly. The aim of this study was to examine clinical and pathological features of primary testicular NK/T-cell lymphoma and to investigate the effective diagnosis and prognosis. In this paper, the two cases of primary testicular NK/T-cell lymphoma were observed by light microscopy, immunohistochemistry and examined by in situ hybridization for Epstein-Barr Virus (EBV) DNA and the literatures were reviewed. The two patients respectively present with bilateral and right-side painless testicular enlargement. The morphology of neoplastic cells of case 1 were small to medium, tumor cells of case 2 were small, medium and large mixed. The tumor cells grew diffusely with irregular and distort nuclear, destructed the organizational structure of the normal testis, and damaged blood vessels, meanwhile, coagulation necrosis was exist. Immunohistochemical staining of neoplastic cells showed positive for CD45, CD2, CD56, CD3ɛ (cytoplasm staining pattern), CD45RO and Granzyme B, and negative for CD57, CD20, CD79α, CD30, CK, MPO, TdT, Bcl-2 and PLAP were negative. In addition, the EBV DNA was detected in the lymphoma by In situ hybridization. In conclusion, the expression of CD56, CD3ɛ, and Granzyme B associated proteins and EBV examination by in situ hybridization play a vital role in diagnosis and differential diagnosis of primary testicular NK/T-cell lymphoma.     

CD56+ hematological neoplasms presenting in the skin: a retrospective analysis of 23 new cases and 130 cases from the literature.

BACKGROUND: The aim of this study was to define prognostic parameters and guidelines for diagnosis and treatment for CD56+ hematological neoplasms with first presentation in the skin. PATIENTS AND METHODS: The study group included 153 cases (23 new and 130 from the literature). According to the World Health Organization classification, the group included 15 nasal and 38 nasal-type natural killer (NK)/T-cell lymphomas, 63 blastic NK-cell lymphomas, 14 cutaneous CD30+ lymphoproliferations, 10 cases of myeloid leukemia, six cases of subcutaneous panniculitis-like T-cell lymphoma (SCPLTCL) and seven peripheral T-cell lymphomas, unspecified. RESULTS: In general, these CD56+ hematological neoplasms had a poor prognosis, with only 27% of patients alive after a median follow-up of 12 months. The median survival was 13 months. Nasal and nasal-type NK/T-cell lymphomas and CD56+ SCPLTCL had the worst prognosis, with a median survival of 5, 6 and 5 months, respectively. Only nasal-type NK/T-cell lymphomas presenting with only skin lesions had a somewhat better prognosis (median survival 27 months). In blastic NK-cell lymphomas (median survival 14 months), age 相似文献   

Nasal NK-cell lymphoma followed by relapse in the uterine cervix

We report a case of nasal natural killer (NK)-cell lymphoma in a 51-year-old Japanese woman who showed a later relapse in the uterine cervix. The nasal NK-cell lymphoma regressed after local radiation therapy. Six months after the diagnosis while the patient was being treated with chemotherapy for a subclinical tumor, a mass lesion of the uterine cervix was noticed by follow-up computed tomography. Giemsa-stained vaginal smear showed lymphoid tumor cells with large azurophilic granules, leading to a rapid diagnosis of cervical involvement by NK-cell lymphoma. The chemotherapy regimens were immediately changed, but the patient died 2 months after the relapse with an overall survival of 8 months. This case may be of value in elucidating the biological behavior and natural history of NK-cell lymphoma.     

Primary lymphomas of the cervix and uterus: the University of Pennsylvania's experience and a review of the literature

Primary lymphomas of the cervix and uterus are rare with approximately 150 cases reported in the world literature to date. Appropriate diagnosis is often delayed until the post-operative setting as clinical and radiographic presentations are non-specific. Several sub-types of lymphoma arising primarily in the cervix or uterus have been reported with diffuse large B-Cell lymphoma (DLBCL) being the most frequent. Due to the low incidence of this disease, no randomized clinical trials exist to help guide treatment. This study reports the experience of four patients with primary lymphomas of the uterus and cervix that reflect the heterogeneity of cases reported in the literature to date. The patients had a mean age at diagnosis of 46 (range 35 - 56) and presented with abnormal uterine bleeding. One patient was diagnosed by total abdominal hysterectomy (TAH), two patients were diagnosed by cervical biopsy and one patient was diagnosed by endometrial biopsy. Three patients had DLBCL and one patient had marginal zone lymphoma (MZL). All patients had stage IIE disease. Of the patients with DLBCL, one received chemotherapy followed by TAH and two received TAH followed by chemotherapy. Two of these three patients remain disease-free post-initial therapy with the third now disease-free post-salvage therapy and autologous stem cell transplant. The patient with MZL was treated with TAH alone and remains disease-free. Based on the case series and a review of available literature, primary lymphomas of the uterus or cervix are rare and require an individualized approach to treatment. In general, patients with limited stage disease should be treated with localized and systemic therapy to optimize chances of cure.     

Measurement and cellular sources of the soluble interleukin-2 receptor in primary central nervous system lymphoma

The aims of this study were to determine the diagnostic utility of the serum levels of the soluble interleukin 2 receptor (sIL-2R) as a tumor marker of primary central nervous system lymphoma (PCNSL) and to investigate the cellular source of sIL-2R using immunohistochemical staining. The serum sIL-2R levels of 37 samples from suspected PCNSL patients were measured. There were 13 patients with PCNSL and 24 patients with other diseases such as glioma, metastatic tumor, inflammation, or cerebrovascular disease. The serum sIL-2R levels of the PCNSL cases and other brain diseases were 629.5 ± 586.0 U/ml (mean ± SD; range 189–2220 U/ml) and 408.5 ± 250.7 U/ml (160–837 U/ml), respectively. The serum sIL-2R levels of the two groups overlapped, and hence the difference between them was not significant. sIL-2R is the α subunit of IL-2R. It is also known as CD25, and is cleaved from its position in the cell membrane and released into the blood. CD25 expression was immunohistochemically detected in 7 of 11 PCNSL samples. Confocal laser microscopy revealed that CD25 signals were present in atypical cells and mononuclear cells. We concluded that both lymphoma cells and infiltrating T cells express CD25, which is one of the cellular sources of sIL-2R.     

胃MALT淋巴瘤浸润子宫肌瘤病理及DNA研究

［目的］对胃粘膜相关淋巴组织（ＭＡＬＴ）淋巴瘤浸润子宫平滑肌瘤临床病理、ＤＮＡ倍体进行研究。［方法］标本采用常规石蜡切片、ＨＥ染色及ＡＢＣ法免疫组化染色,并对Ｆｅｕｇｅｌｎ染色切片用细胞影像仪对瘤细胞的ＤＮＡ倍体进行测定。［结果］胃粘膜、粘膜下层、肌层及平滑肌瘤内均可见弥漫多量密集成片的中心细胞样瘤细胞浸润。胃、胃大弯淋巴结淋巴瘤细胞ＤＮＡ质量分布呈单个主峰,瘤细胞ＤＮＡ呈非整倍体。子宫肌瘤细胞ＤＮＡ的质量分布为两个峰,主峰为二倍体,次峰为非整倍体。本例预后不良。［结论］ＭＡＬＴ淋巴瘤浸润子宫肌瘤须与子宫原发性恶性淋巴瘤、慢性淋巴细胞性白血病浸润子宫及子宫内膜间质肉瘤相鉴别。随访结果表明ＤＮＡ指数对于患者预后的判断是一项重要的参考指标。     

Natural killer-cell malignancies: diagnosis and treatment.

Natural killer (NK)-cell malignancies are uncommon diseases. Previously known as polymorphic reticulosis or angiocentric T-cell lymphomas, they are classified by the World Health Organization as NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia. They are prevalent in Asia and South America, but exceptionally rare in western countries. Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with an angioinvasive and angiodestructive pattern. Lymphoma cells are characteristically CD2+, CD56+ and cytoplasmic CD3epsilon+. T-cell receptor gene is germline, and clonal Epstein-Barr virus (EBV) infection is almost invariably. Clinically, they can be divided into nasal, non-nasal, and aggressive lymphoma/leukemia subtypes. Most nasal NK-cell lymphomas present with stage I/II disease, and frontline radiotherapy is the most important key to successful treatment. Many stage I/II patients treated with radiotherapy fail systemically, implying that concomitant chemotherapy may be needed. Chemotherapy is indicated for advanced nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes. However, treatment results are unsatisfactory. High-dose chemotherapy with hematopoietic stem cell transplantation may be beneficial to selected patients. The International Prognostic Index and presentation EBV DNA load is of prognostic significance and may be useful in the stratification of patients for various treatment modalities.     

卵巢子宫内膜样间质肉瘤临床病理观察

目的探讨卵巢子宫内膜样间质肉瘤的发生机制、临床病理特征、诊断与鉴别诊断及预后。方法 对1例卵巢子宫内膜样间质肉瘤进行光镜、免疫组化检测, 并复习有关文献。结果 肿瘤组织由形似增生期子宫内膜间质细胞的小细胞组成, 瘤细胞呈卵圆形或短梭形, 胞浆稀少, 肿瘤细胞呈漩涡状围绕似子宫内膜螺旋小动脉的厚壁小血管。免疫组化示瘤细胞表达Vimentin和CD10, 不表达Calretinin, α-inhibin, H-caldesmon, CD99, CD117, CD34, desmin, SMA and CK(AE1/AE3)。结论 卵巢子宫内膜样间质肉瘤在临床为一惰性生长的恶性肿瘤, 非常罕见。其鉴别诊断主要包括子宫内膜间质肉瘤累及卵巢(直接侵犯或转移)和卵泡膜细胞-纤维瘤。     

Primary gastric mantle cell lymphoma in a patient with long standing history of Crohn's disease

The stomach is the most common site of primary extranodal lymphoma. Virtually all cases are of B-cell lineage, including extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas. While secondary gastric involvement from nodal mantle cell lymphoma (MCL) or in the course of primary intestinal MCL (lymphomatous polyposis) have been described, primary gastric MCL has not been reported so far. A 74-year-old man with a 14 year-history of Crohn's disease was admitted at a general hospital due to epigastric pain refractory to therapy with proton-pump inhibitors. Endoscopy disclosed a large polypoid tumor with an ulcerated surface at the greater curvature of the gastric antrum. Endosonography demonstrated the tumor to be limited to the stomach with only local lymph node involvement. Histology of gastric biopsies revealed a dense atypical lymphoid infiltrate composed of small to medium sized cells with slightly irregular nuclear contours. Immunohistochemichally, the cells were positive for CD20, CD79a, CD43 and cyclin D1, but negative for CD3, CD5 and bcl-6. They stained for IgM and showed lambda-light chain restriction. Fluorescent in situ hybridisation studies showed the presence of the t(11;14) characteristic for MCL. No further evidence of lymphoma was found on extensive clinical staging. Following chemotherapy the patient is disease free at 24 months after diagnosis. This is the first case of a primary localized gastric MCL. The lack of CD5 expression underscores the importance of performing thorough immunohistochemical studies, particularly to exclude MALT lymphoma.     

Positive endometrial cytology associated with primary gastric adenocarcinomas: clinical and cytopathologic findings in 16 patients

Background. Routine endometrial cytology occasionally includes malignant cells of extra-genital origin. We carried out this study to examine both the clinical and the cytopathologic characteristics of patients with positive endometrial cytology associated with gastric cancer. Methods. Sixteen patients whose endometrial smears contained malignant cells derived from gastric adenocarcinoma were studied. The patients' clinical symptoms, clinical courses, and cytologic and pathological findings were analyzed. Results. Among the 16 patients, 5 showed positive endometrial cytology prior to the initial treatment of gastric cancer, but after its diagnosis; 8 patients were being examined for relapse of gastric cancer; and, in the remaining 3 patients, the endometrial cytology led to the diagnosis of gastric cancer. Eleven patients had some clinical signs or symptoms, including abnormal vaginal discharge. Two patients were positive for serum carcinoembryonic antigen (CEA), while carbohydrate antigen (CA)125 was positive in 5 patients. The histological types of the primary gastric lesions were poorly differentiated adenocarcinoma (including signet ring cell adenocarcinoma) in 14 patients, and moderately differentiated tubular adenocarcinoma in 2 patients. Signet ring cells were observed on endometrial cytology in 12 patients. Four patients showed tumor diathesis on the smears. Metastatic lesions in the uterus were histologically confirmed in 5 patients. All 16 patients died as a result of peritoneal carcinomatosis within 12 months of the positive endometrial smears. Conclusion. Examination of routine reproductive tract smears, especially endometrial cytology, presents gynecologists with the opportunity to identify patients with gastric adenocarcinoma cells in the uterus and/or peritoneal cavity. Received: January 5, 2000 / Accepted: April 6, 2000     

Unusual Case of a Sigmoid Mass

Background

Endometrial carcinoma is a relatively common condition which may occur with more than 6,400 new cases diagnosed each year in the UK (Cancer Research UK Statistics http://info.cancerresearchuk.org/cancerstats/types/uterus). It may occur following hysterectomy especially if associated with prolonged hormone replacement therapy.

Case

We report the case of a 63-year-old lady who presented with a tumour in the sigmoid mesentery 13 years after hysterectomy and following 10 years of tamoxifen therapy for a breast carcinoma. This is the first time that endometrial cancer has been reported as a complication of tamoxifen therapy in the absence of a uterus.

Conclusion

We suggest that endometrial carcinoma remains a differential diagnosis of any pelvic or abdominal mass even after hysterectomy, and a history of intake of oestrogen agonists and antagonists needs to be obtained.     

SOHO State of the Art Updates and Next Questions | Challenging Cases in Rare T-Cell Lymphomas

Mature T- and NK-cell neoplasms (MTNKN) collectively represent a rare disorder, representing less than 15% of all non-Hodgkin lymphoma (NHL) cases and qualifying for orphan disease designation by the U.S. Food and Drug Administration (FDA). These consist of 9 families in the fifth revised WHO classification of lymphoid neoplasms, which are made up of over 30 disease subtypes, underscoring the heterogeneity of clinical features, molecular biology, and genetics across this disease group. Moreover, the 5 most common subtypes (peripheral T-cell lymphoma, not otherwise specified; nodal TFH cell lymphoma, angioimmunoblastic type; extranodal NK-cell/T-cell lymphoma; adult T-cell leukemia/lymphoma; and ALK-positive or -negative anaplastic large cell lymphoma) comprise over 75% of MTNKN cases, so other subtypes are exceedingly rare in the context of all NHL diagnoses and consequently often lack consensus on best practices in diagnosis and management. In this review, we discuss the following entities–enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and primary cutaneous ɣδ T-cell lymphoma (PCGD-TCL) – with an emphasis on clinical and diagnostic features and options for management.     

Endometrial carcinoma in a single horn of a bicornuate uterus: A case report

We discuss the diagnosis and the management of endometrial carcinoma in a single horn of bicornuate uterus in a 64-year-old woman as a case report. The case underwent laparoscopic radical hysterectomy and bilateral iliac lymphadenectomy.The gross examination of the uterus revealed a bicornuate uterus with a greater horn of 12?×?9?×?8?cm and a smaller horn of 10?×?3?cm. The cavity of the greater horn showed a neoplastic growth of 10?cm with infiltration of about 1,8 cm of the myometrium from whole thickness of 1.9?cm. while the other horn was free of tumor tissue.The microscopic examination of the uterus revealed G2 endometrioid adenocarcinoma of the endometrium of the greater horn with infiltration of more than 50% of the myometrium.In the presence of bicornuate uterus, a bilateral endometrial biopsy should be performed in order to reduce the risk of delayed or missed diagnosis.The management of a case of bicornuate unicollis uterus with endometrial carcinoma in only one horn is the same as patients with endometrial cancer in single uterus and depends mainly on stage and histological grade of the tumor.The possibility of existence of a separate uterine cavity should always be considered when endometrial cancer is clinically suspected but pathology fails to confirm the diagnosis. This points out the importance of a careful physical examination and radiographic evaluation in such cases.     

Non-Hodgkin's lymphoma of the uterus: apropos of 4 cases and review of the literature]

The primary non hodgkin's lymphoma of the uterus is rare. This rarity explains of one part certain difficulties of the histological diagnosis and on the other hand the absence of a therapeutic strategy clearly established. We report 4 cases of primary non-hodgkin lymphoma of the uterus. Two patients had a cervical location, the two other had corpus location. The average age of our patients is of 59 years (extremes: 54-68). Histological diagnosis was confirmed by biopsy for the cervical location. For the corpus location, it is study of the uterus after hysterectomy which retained the diagnosis of lymphoma. The type of the lymphoma was low grade in two cases and high grade in the two other cases. The disease was limited to the pelvis for all our patients (stage IE according to Ann-Arbor's classification). The treatment consisted of an association of chemotherapy and radiotherapy in both cases of lymphoma of the cervix and in a radical hysterectomy followed by chemotherapy for the two cases of lymphoma of the corpus. Our patients are regularly followed, with an average follow-up of 56 months. Two patients are in disease free, the third patient presented a dissemination of the disease and the fourth patient presented a squamous cell carcinoma of the lung.     

Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological, and genetic features

Nasal natural killer (NK)/T-cell lymphoma (NNKTL) is a clinical illness characterized by progressive unrelenting ulceration and necrosis of the nasal cavity and midline facial tissues. Histological features of the lymphoma include angiocentric and polymorphous lymphoreticular infiltrates, called polymorphic reticulosis. Surface antigens and the NK-cell marker, CD56, as well as pan-T antigen CD2, cytoplasmic CD3 (CD3ɛ), and CD45 are expressed in the lymphoma cells. The origin of the lymphoma is thought to be either NK-cell linkage without T-cell receptor (TCR) rearrangement or γδT-cell linkage with γδTCR rearrangement. Since the authors of this study first demonstrated the presence of Epstein Barr virus (EBV)-DNA and EBV oncogenic proteins in NNKTL, the lymphoma has been classified as one of the EBV-associated malignancies. The NNKTL cells produce interleukin (IL)-9, IL-10, and interferon-γ-inducible protein-10 (IP-10), possibly due to EBV-oncogenic proteins in the lymphoma cells, and such cytokines take an important part in the cell proliferation and invasion, acting in an autocrine manner. Clinically, the serum EBV-DNA copy number is useful as a specific tumor marker and a predictive prognostic factor. Even in early clinical stages, the lymphoma shows poor prognosis caused by the rapid progression of the lesion into distinct organs. Our newly designed arterial infusion chemotherapy, from the superficial temporal artery, in combination with radiotherapy, has shown a favorable outcome in patients with NNKTL. In this article, the clinical, pathological, and virological characteristics of the lymphoma are reviewed, along with a report of our investigations.