Limin Gao

Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.

Hydroa vacciniforme-like lymphoma of an adult: a case report with review of the literature

Hydroa vacciniforme-like lymphoma (HVL) is a rare type of Epstein-Barr virus (EBV)-positive lymphoma of cytotoxic T-cell or natural killer cell origin that mainly affect children, characterized by a vesicopapular skin eruption that clinically resemble hydroa vacciniforme (HV). In current study, we report an adult patient with the tumor. The patient presented similar morphologic, immunophenotypic and genotypic changes of the disease with that occurred in children, whereas clinically, he showed a prolonged clinical course without hepatosplenomegaly or generalized lymphadenopathy. Whether there are some differences in biologic behavior between children and adults still remains unknown and it is necessary to collect more data to observe and to investigate in the future.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7644172219178472

Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases Using the WHO (2008) Classification in a Single Institution

The gastrointestinal tract (GIT) is the most common anatomic site of extranodal non-Hodgkin lymphoma (NHL) involvement. The classification criteria of lymphoma have changed in recent decades, and few large-sample studies regarding subtype analysis of lymphoma have been performed in this site. Aim: Therefore, the present study was conducted to analyze the histological subtype distribution of the GIT. Method: All patients in a single institution with a diagnosis of primary NHL in the GIT were enrolled between January 2007 and April 2014. The patients were categorized according to the WHO (2008) classification of tumors of hematopoietic and lymphoid tissue. Result: A total of 1,010 eligible cases diagnosed as NHL were collected in this study. The male:female ratio was 1.7:1 and the median age was 55 years. The percent of patients with lymphoma involvement in the stomach was 52% (n = 522), and the remaining 48% (n = 484) had intestinal tract involvement. Histologically, diffuse large B cell lymphoma (DLBCL) was the most common subtype in all of the GIT lymphoma cases, and was also the most common subtype in cases involving the stomach (78%) and the intestinal tract (53%). The incidence of DLBCL and mucosa-associated lymphoid tissue lymphoma in the stomach was significantly higher than the incident in the intestinal tract (p < 0.01). T and NK cell lymphoma was significantly more common in the intestinal tract than in the stomach (p < 0.01). Extranodal NK/T cell lymphoma nasal type (ENKTL-N) was the most common subtype of T and NK cell lineage lymphoma in GIT and was also the second most common intestinal tract-involved lymphoma. Conclusion: DLBCL was the most frequent lymphoma in the stomach and in the intestinal tract. T and NK cell lineage lymphoma had a higher occurrence in the intestinal tract than in the stomach. ENKTL-N was the most frequent subtype of lymphoma derived from NK/T cell lineage, and was the second most common lymphoma among all intestinal tract lymphomas.

High Frequency of Bone Marrow Involvement in Intravascular Large B-Cell Lymphoma: A Clinicopathological Study of 13 Cases in China.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL.

Clinicopathological study of pulmonary extranodal nature killer/T-cell lymphoma, nasal type and literature review

OBJECTIVES Malignant tumors of the lung are predominantly derived from epithelial tissue, such as squamous cell carcinoma and adenocarcinoma, while pulmonary lymphatic and hematopoietic tumor is relatively rare. Extranodal NK/T-cell lymphoma (ENKTL), nasal type, originates in nasal and extra-nasal sites anatomically. This distinct non-Hodgkin lymphoma is endemic and is characterized by a highly aggressive clinical course and dismal survival outcome. Extra-nasal ENKTL, especially pulmonary ENKTL, is rare compared with nasal type ENKTL and has received relatively little attention. Therefore, this study was conducted to assess the clinicopathological features of pulmonary ENKTL and to promote awareness of this malignancy. MATERIALS AND METHODS All cases of ENKTL, nasal type diagnosed from January 2008 to June 2014 in our institution were collected, and those with pulmonary involvement were selected for further study. The eligible cases were analyzed retrospectively: medical recordings, imaging manifestations, pathological features, immunophenotypes, EBER1/2 hybridizations in situ and other related literatures were reviewed. RESULTS AND CONCLUSIONS A total of 1105 cases were diagnosed as ENKTL, nasal type, in this period, and 8 cases (7.2‰) had lung involvement. Seven cases had core biopsy, and for 1 case, a resected tissue specimen was available. The group was composed of 6 men and 2 women (gender ratio 3:1) with ages ranging from 19 to 44 (average age of 33.5) years. In this group, 2 cases were secondary and 5 cases were primary. The clinical symptoms and computed tomography (CT) manifestations were nonspecific. Histologically, the neoplasms presented angiocentric and angiodestructive growth patterns with different degrees of inflammatory response and necrosis. The neoplastic cell sizes were heterogeneous with spectra of small to large or mixed-composition types. For the immunophenotypes, all cases were positive for CD3ɛ and cytotoxic granule (granzyme B or TIA-1). The positive ratios of CD56 and CD30 were 6/8 and 4/5 respectively. All 8 cases showed positive in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER). TCR-γ gene rearrangement was tested in 4 cases, and only 1 of these cases was monoclonal. Laboratory testing demonstrated that the whole blood was decreased while the average level of LDH was elevated. Six bone marrow biopsy specimens were negative and showed no neoplastic cells infiltration. For treatment, 4 individuals accepted chemotherapy and 1 patient underwent localized tumor resection surgery. The follow-up information was available for 6 patients, 1 of whom was alive and the other 5 cases survived shortly between 20 days and 4 months. ENKTL, nasal type of lung is very rare, and the diagnosis is challenging due to nonspecific clinical symptoms and imaging results. The diagnosis of pulmonary ENKTL should be based on comprehensive clinical, imaging, histopathological and molecular examination. More effective treatment strategies are required for this disease.

Primary Central Nervous System Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Colliding with Meningioma

BACKGROUND Collision tumors are defined as coexistence of 2 histologically different neoplasms occurring in the same anatomic location. Such co-occurrence of tumors in the brain is uncommon. To our knowledge, meningioma colliding with extranodal natural killer/T-cell lymphoma has not been described previously. CASE DESCRIPTION A 50-year-old man presented with a 1-year history of progressive memory decline and 2 weeks of drowsiness, bradykinesia, and aphasia. Magnetic resonance imaging revealed a heterogeneously enhanced mass beside the left frontal cerebral falx resulting in midline shift. The left frontal lobe mass was resected. Pathologic examination showed the tumor consisted of whorled spindle cells and diffuse medium-sized lymphoid cells. The spindle cells were positive for epithelial membrane antigen and negative for S-100. The lymphoid cells expressed CD3ε, CD56, TIA-1, and granzyme B. Epstein-Barr virus encoded small RNAs were detected by in situ hybridization. No monoclonal T-cell receptor gamma gene rearrangement was detected. Four weeks after surgery, the patient was treated with polychemotherapy and intrathecal methotrexate, but he died 2 months later. CONCLUSIONS This is the first report of a unique brain collision tumor consisting of a meningioma and an extranodal natural killer/T-cell lymphoma. Diagnosis depends on histopathology. Awareness of this entity is important to distinguish it from other intracranial tumors.

CD30 expression and survival in extranodal NK/T-cell lymphoma: a systematic review and meta-analysis

Background The paradoxical reports about the prognostic value of the CD30 expression in extranodal NK/T-cell lymphoma (ENKTL) have restricted its further applications in clinical practice. To identify the common effects and the variation, we conducted this systematic review and meta-analysis. Methods PubMed, MEDLINE, Embase, and Web of Science were searched between January 1975 and 31 January 2017. The pooled hazard ratio was used to estimate the effect of the CD30 expression on overall survival. Bias was assessed by prespecified criteria referring to Reporting Recommendations for Tumor Marker Prognostic Studies and Newcastle-Ottawa Scale. Results Ten retrospective cohort studies with 310 patients are included. CD30 is associated with better overall survival significantly (HR 0.71, 95% CI 0.51 to 0.99, I2 = 0%). A greater effect is observed among studies including participants predominant in regional involvement (HR 0.31, 95%CI 0.13 to 0.76, I2 = 0%) compared with those in systemic involvement. Conclusions This study indicates that the CD30 expression is significantly associated with better prognosis in ENKTL, especially for patients with regional lymphoma involvement.

Epstein-Barr virus positive peripheral T cell lymphoma with novel variants in STAT5B of a pediatric patient: a case report

BackgroundEpstein-Barr virus positive peripheral T cell lymphoma (EBV + PTCL) is a rare type of lymphoproliferative disorder which is always present in late adulthood. However, pediatric EBV + PTCL is extremely rare and always present with lymphadenopathy. Additionally, gene detection was not performed in all of these pediatric patients.Case presentationWe report an EBV + PTCL in a 9-year-old child with initial symptom of subcutaneous masses without lymph node involvement. Histologically, the neoplastic cells were centroblastoid with round or oval nuclei, slightly condensed chromatin and median eosinophilic inconspicuous nucleoli. Immunohistochemically, all neoplastic cells were positive for CD8, GranzymeB and TIA-1. Two novel variants (S420Y and E623K) were detected in STAT5B.ConclusionTo the best of our knowledge, this is the first case of EBV + PTCL with STAT5B variants of a pediatric patient presented as extranodal lesions.