Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand.

Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16-99 years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1 months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Frequent mutations in HLA and related genes in extranodal NK/T cell lymphomas.

Extranodal NK/T cell lymphomas (ENKTCLs) are aggressive Epstein-Barr virus-associated T/NK neoplasms that predominantly affect Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients by whole-genome (N = 2), whole-exome (N = 16), and targeted sequencing (N = 15). Commonly deregulated gene pathways in ENKTCLs included epigenetic modifiers (58%, 11/19) followed by human leukocyte antigens (HLAs) and related genes including HLA-A, B2M, TAP1, CD274, and PDCD1LG2 (32%, 6/19), and JAK-STAT pathway (26%, 5/19). Conspicuously, loss-of-function mutations in HLA-A were recurrently identified in ENKTCLs (16%, 3/19). HLA protein expression was examined by immunohistochemistry in 16 patients and lower expression was associated with advanced stages at presentation (p = .007). In conclusion, the defective antigen presenting pathway is common and related to disease progression, suggesting immune escape as a pathogenic mechanism of ENKTCLs.

The influence of programmed cell death ligand 2 (PD-L2) expression on survival outcome and tumor microenvironment in diffuse large B cell lymphoma.

The frequency and significance of programmed cell death ligand (PD-L) 2 expression in diffuse large B cell lymphoma (DLBCL) remain undefined. We described the expression pattern of PD-L/PD-1 in 88 DLBCL patients using immunohistochemistry. The association between PD-L expression and clinical characteristics/outcomes were analyzed. PD-L1 and PD-L2 were expressed in 14.8% and 68.2% of DLBCL patients with median positivity on tumor cells of 100% and 90%, respectively. PD-1 on tumor-infiltrating lymphocytes (TILs) was expressed in 12.5% of patients. Interestingly, 45.5% of patients had PD-L2 expressing TILs which were significantly associated with bulky disease (p = .046) and elevated lactate dehydrogenase (p = .048). PD-L1 and/or PD-L2 expression on lymphoma cells was associated with inferior progression-free survival (Hazard ratio [HR] 2.20; 95% Confidence Interval [CI] 1.004-4.84, p = .049) and overall survival (HR 2.27; 95%CI 1.03-4.98, p = .042), using multivariate analysis. In summary, PD-L2 expression on DLBCL is common and, together with PD-L1, were related to poor outcomes.

Lymphoplasmacytic lymphoma with IgA hypergammaglobulinemia and liver involvement.

BACKGROUND: Lymphoplasmacytic lymphoma (LPL) is a low grade lymphoma. Most cases are Waldenstorm macroglobulinemia which has IgM hypergammaglobulinemia. Lymphoplasmacytic lymphoma with IgA hypergammaglobulinemia is less than 5%. Liver involvement was reported in 20%. However this disease has been found to be mostly presented with lymphadenopathy and hypergammaglobulinemia. CASE REPORT: We present a forty-year-old woman with anemia, renal insufficiency and abnormal liver function test. Liver biopsy showed atypical clonal B-cell lymphoproliferation, small cells with prominent plasmacytic differentiation. Serum protein electrophoresis showed monoclonal gammopathy which was IgA. Rituximab, fludarabine and cyclophosphamide were given and resulting in partial response. CONCLUSION: The presentation of LPL can mimic multiple myeloma (anemia, renal failure and monoclonal gammopathy). Definite histological and immunological technique should be done to confirm the diagnosis.

Factors associated with erythropoiesis-stimulating agent hyporesponsiveness anemia in chronic kidney disease patients.

Anemia is one of the most common problems in chronic kidney disease (CKD). Despite comprehensive investigations in several cases, definite causes of anemia frequently remain unknown. Our study aimed to analyze the factors that possibly affect anemia in CKD patients who were referred for hematology consultation. A total of 87 patients were retrospectively included in the cohort. Forty-four cases were excluded, including 30 cases with unavailable intact parathyroid hormone (iPTH) data, 11 cases with bone marrow diseases (8 Pure red cell aplasia, 3 Myelodysplastic syndrome) and 3 cases with thalassemia. In total, 43 patients were analyzed. Patients with high iPTH had a significantly lower Hemoglobin (Hb) level and required a higher dose of erythropoiesis stimulating agents (ESAs) compared with the normal iPTH group (Hb 8.29 vs 9.24 mg/dL, P=0.032 and ESAs dose of 16,352.94 vs. 12,444.44 U/week, P=0.024). Univariate, followed by stepwise multivariate analysis was performed and determined that serum phosphate (PO4) was significantly associated with lower Hb level (P=0.01 and P=0.013, respectively). In addition, Hb level was inversely correlated with iPTH and serum phosphate (PO4) level (r=-0.54, P<0.001 and r=-0.47, P=0.005; respectively). Mineral disequilibrium is an important factor associated with anemia in ESA hyporesponsive CKD. Also, hyperphosphatemia and secondary hyperparathyroidism are significantly correlated with low Hb. As a result, we strongly suggest correction of mineral disequilibrium factors prior to performing bone marrow study.

Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger patients and associated with hemophagocytic lymphohistiocytosis. To clarify the molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole-exome sequencing. All cases were Asians and were phenotypically sporadic with no family history of SPTCL. Consistent with a recent report, germline mutations in HAVCR2, encoding T-cell immunoglobulin mucin 3 (TIM3), were identified in 11 of 13 (85%) cases. All mutated cases were primary SPTCL, whereas the 2 cases without mutation were secondary SPTCL associated with underlying diseases, including viral infection and autoimmune disease. Ten patients harbored homozygous p.Y82C mutations, and 1 showed compound heterozygous mutations (p.Y82C and p.T101I). Both missense mutations altered highly conserved residues located in the extracellular immunoglobulin variable-like domain. According to the Genome Aggregation Database of >138 500 general individuals, both mutations were documented with minor allele frequencies < 0.007, indicating remarkable enrichment of these HAVCR2 alleles in SPTCL. SPTCL cells also harbored somatic mutations (6.2 per patient) that are frequently identified in genes associated with epigenetic regulation and signal transduction. In conclusion, individuals harboring biallelic HAVCR2 (TIM3) germline mutations were highly susceptible to sporadic SPTCL, which was also associated with clonal somatic mutations.

Estrogen receptor beta expression and prognosis of diffuse large B cell lymphoma.

OBJECTIVES: Estrogen receptor beta (ERß)-selective agonists inhibited B cell lymphoma growth in animal models. However, a recent study found that higher ERß expression in tissue from diffuse large B cell lymphoma (DLBCL) patients indicated a poorer survival. This study aimed to determine the ERß expression in DLBCL tissue using immunohistochemistry and correlate with clinical outcomes. METHODS: Diagnostic tissues from newly diagnosed adult DLBCL patients treated with Rituximab-Cyclophosphamide/Doxorubicin/Vincristine/Prednisolone were counted for ERß1-expressing cells. Nodal lymphoma (N = 41) was analyzed separately from extra-nodal DLBCL (N = 31). RESULTS: On immunohistochemistry, ERß1 was expressed in 73.6% of cases with the median expressing cells of 20%. For nodal lymphoma, high ERß expression (≥25%) was associated with poorer event free survival (EFS) independent of the international prognostic index with the adjusted hazard ratio (HR) of 2.49 (95% Confidence interval (CI) 1.03-6.00, P = 0.042). On the contrary, high ERß expression (≥25%) was associated with superior outcomes in extra-nodal DLBCL with the adjusted HR of 0.25 (95% CI 0.09-0.75, P = 0.013) for EFS and adjusted HR of 0.29 (95% CI 0.10-0.85, P = 0.024) for overall survival in multivariate analyses. CONCLUSION: ERß1 protein expression represented opposite prognostic factors in nodal vs. extra-nodal DLBCL.

Cyclosporin in subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of hematologic malignancy characterized by lesions in subcutaneous fat associated with systemic symptoms. The standard treatment of the disease, currently, is not established, but CHOP or CHOP-like regimens are usually given. We report, herein, 4 cases of SPTCL diagnosed by histopathology and immunohistochemistry who were refractory to CHOP and/or ESHAP and/or fludarabine-based regimen, but showed rapid improvement within weeks after oral cyclosporin 4 mg/kg/day. Three sustained complete remission for the durations of 8 - 9 months off-treatments. T-cell receptor gene rearrangement revealed polyclonality in 3 cases and monoclonality in 1 case. Our data suggest the benefit of incorporating cyclosporin into the treatment regimen for SPTCL.

Natural killer cell malignancy associated with Epstein-Barr virus and hemophagocytic syndrome.

Natural killer cell malignancy is a rare and aggressive lymphoid neoplasm encompassing extra-nodal NK/T-cell lymphoma, nasal-type (ENKLN) and aggressive NK-cell lymphoma/leukemia (ANKL). A case of cutaneous ENKLN and a case of ANKL in Thai patients are reported Both patients developed hemophagocytic syndrome and shortly succumbed to death. The cells in cutaneous ENKLN are small to medium in size with minimal cytoplasm, round nuclei, irregular nuclear membrane, andfine chromatin with inconspicuous nucleoli. While that of ANKL are medium to large-sized mononuclear cells with moderate cytoplasm. Their nuclei are elongated to embryo-like with irregularly thickened nuclear membrane, fine chromatin, and small to occasional prominent nucleolus. Ancillary techniques studied on paraffin embedded tissues of both cases demonstrated that the neoplastic cells exhibit cytoplasmic CD3+, CD56+ and cytotoxic granules + by immunohistochemistry, absence of T cell receptor gene rearrangement by PCR, and presence of Epstein-Barr virus mRNA (EBER) transcripts by in situ hybridization. The authors reviewed the literature on natural killer cell neoplasm and compared the clinical characteristics, natural history, and association of Epstein-Barr virus infection with hemophagocytic syndrome.

Necrotizing non-granulomatous lymphadenitis: a clinicopathologic study of 40 Thai patients.

The purpose of this study was to describe the clinicopathological features of 40 cases of necrotizing non-granulomatous lymphadenitis in Thai patients. The clinical features, histomorphology and special stains were evaluated in 40 Thai patients from the pathology records of King Chulalongkorn Memorial Hospital from January 2001 to December 2003 in those diagnosed as having necrotizing non-granulomatous lymphadenitis. Of the 40 patients, 17 cases (42.5%) had Kikuchi-Fujimoto disease (KFD), 8 cases (20%) had tuberculosis (TB) lymphadenitis and 1 case (2.5%) had systemic lupus erythematosus (SLE) with associated lymphadenitis. Fourteen cases (35%) did not have a specific diagnosis due to a lack of follow-up data. KFD most commonly occurs in young women, and is characterized by the presence of coagulative necrosis and karyorrhexis often centered in the paracortex, an absence of neutrophils and plasma cells, proliferation of various cells composed of lymphocytes, histiocytes, immunoblasts and plasmacytoid monocytes and the absence of a granuloma. Tuberculous lymphadenitis usually occurs in women with a mean age of 34.25 years. The lymph nodes reveal extensive coagulative necrosis involving the cortex, paracortex and medulla, proliferation of mixed inflammatory cells, including neutrophils, lymphocytes and plasma cells in the necrotic area and the presence of proliferating histiocytes at the periphery of the necrotic area. The lymph nodes of SLE-associated lymphadenitis reveal large numbers of plasma cells and hematoxylin bodies. We suggest that necrotizing non-granulomatous lymphadenitis is not specific for any disease, but rather a common histologic change found in diseases, such as TB, SLE, and KFD. Further investigation to obtain a definite diagnosis should be done for appropriate treatment.

Polymerase chain reaction for detection of Mycobacterium tuberculosis in papanicolaou-stained fine needle aspirated smears for diagnosis of cervical tuberculous lymphadenitis.

A polymerase chain reaction (PCR) protocol for detecting IS6110 repetitive insertion sequence of Mycobacterium tuberculosis (MTB) was tested on archival Papanicolaou (Pap)-stained fine needle aspirated (FNA) smears from 24 patients with cervical tuberculous lymphadenopathy and 30 negative controls. The protocol involved protease digestion or phenolchloroform extraction, and simple or nested PCR, with PCR amplification of human beta-globin gene for internal control of DNA quality. Sensitivity of 50% and specificity of 100% were obtained. Sensitivity in smears showing necrosis without granuloma was 70% (7/10), whereas it was 36% (5/14) in smears with presence of granuloma. On the other hand, sensitivity of 18% (4/22) was obtained using FNA acid-fast stain, 25% (1/4) for acid-fast stain in histological section, 50% (2/4) for culture, and 100% (8/8) for PCR of fresh specimens. PCR for MTB detection in Papanicolaou-stained slides is a practical and valuable method when no fresh specimen but only Pap-stained smear is available.

RET proto-oncogene expression of papillary thyroid carcinomas in Thai patients.

BACKGROUND: Ret proto-oncogene activation has been found in papillary thyroid carcinoma with different frequencies according to geographic location. The rate of expression ranges from 0-100 percent in the literature. This gene expression has also been studied in many Asian countries but it has never been studied in Thailand. OBJECTIVE: To study the frequency of the RET expression and their roles in predicting prognosis of papillary thyroid carcinoma among Thai patients treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: One hundred and one cases of papillary carcinomas were studied with immunohistochemistry for RET antibodies. All slides with routine staining were reviewed to classify cell variants and record other prognostic parameters such as size, multicentricity, extrathyroid invasion. The clinical data such as age and sex were also included for analyses. RESULTS: Forty-seven of the total 101 cases (46.5%) showed positive RET protein staining. The mean age among patients with RET negative neoplasms was 43.9 years compared with 39.8 years in RET positive group (p = 0.16). The average size of the tumors without RET expression was 2.5 cm, slightly larger than the RET positive tumors (2.1 cm)(p = 0.26). Extrathyroid invasion of the RET-positive tumors was found to be 33.2 percent while the RET negative neoplasms had 38.8 percent of this feature (p = 1). According to AMES score, the RET positive cases had only 11 percent of high-risk tumors, whereas the RET negative group comprised 23.1 percent of high-risk malignancies (p = 0.20). There was no significant difference in RET expression among cell variants (p = 1). CONCLUSION: The study of 101 papillary thyroid carcinomas at the King Chulalongkorn Memorial Hospital disclosed high frequency of RET expression (46.5%) and this is the only data among Thai patients that has ever been documented in the literature. Although, the gene expression in the tumor tends to be associated with good prognostic features but it was not distinct enough to be statistically significant.

Overexpression of c-Myc in primary central nervous system lymphoma of Thais.

BACKGROUND: c-Myc protooncogenes have been implicated in the tumourigenesis of extracerebral lymphomas, however only afew studies on this oncogenic molecule have been available for primary central nervous system lymphoma (PCNSL). OBJECTIVE: To determine the prevalence ofprotein overexpression and gene amplification of c-Myc in PCNSL and to correlate with histological and immunophenotypic subtypes of malignant lymphoma according to WHO classification of tumors of haematopoietic and lymphoid tissue 2001. SETTING: King Chulalongkorn Memorial Hospital, Thailand. DESIGN: Descriptive study. MATERIAL: 25 Thai patients presented between 2001 and 2005. METHOD: The overexpression and amplification of c-Myc in malignant lymphoma were studied by means of immunohistochemistry and chromogenic in situ hybridization (CISH), respectively, in formalin-fixed, paraffin-embedded specimens. The histomorphology and immunohistochemistry were used to subclassify PCNSLs according to WHO classification 2001. RESULTS: Fourteen males and eleven females were recruited. They were between the ages of 21 and 86 years with the mean of 53 years. Eight had documented human immune deficiency virus (HIV) infection. Four of 17 immunocompetent cases overexpressed c-Myc protein without c-Myc gene amplification. No immunocompromised cases showed overexpression of c-Myc protein. All PCNSLs were classified as diffuse large B-cell lymphoma. CONCLUSION: In PCNSL, c-Myc overexpression is notfound immunocompromised (HIV-infected) patients and is found in 23.5% of the immunocompetent individuals without c-Myc gene amplification. All PCNSLs are diffuse large B-cell lymphoma according to WHO classification 2001.

Orbital myeloid sarcoma in adult mimicking nasolacrimal duct obstruction: A case report.

PURPOSE: To describe an orbital myeloid sarcoma in adult presenting with a swollen mass at inferomedial canthal area and epiphora which was misdiagnosed as nasolacrimal duct obstruction. OBSERVATIONS: A 45-year-old male presented with a swollen right lower eyelid around medial canthal area for 2 months with tearing for 6 month-period earlier. Eye examination demonstrated a high tear meniscus, slightly erythematous eyelid with palpable mass closed to the lacrimal sac along the inferior orbital rim. Computed tomography scan depicted infiltrative mass at the inferomedial aspect of right orbit with bony erosion, extended to adjacent paranasal sinuses. An incisional biopsy was performed. Histopathological study revealed soft tissue which was diffusely infiltrated by monotonous medium-sized round cells resembling blasts with lymphoglandular bodies, focally positive myeloperoxidase and negative lymphoid markers. The findings were consistent with myeloid sarcoma. No systemic involvement was found. The patient underwent chemotherapy and radiation without systemic leukemic disease progression. CONCLUSIONS AND IMPORTANCE: Although orbital myeloid sarcoma is rare and difficult to diagnose, it can mimic nasolacrimal duct obstruction. We should consider this condition in our differential diagnosis.

Parvovirus b19 infection in HIV patient with pure red cell aplasia.

Anemia in HIV-infected patients is a common clinical manifestation. We report on a 31-year-old Thai male, who had been HIV positive for 6 years, did not harbor any opportunistic infection, and had been receiving Highly Active Anti Retroviral Therapy (HAART) for one month, and who developed severe anemia. Investigation revealed pure red cell aplasia, suspected secondary to parvovirus B19 infection. This diagnosis was confirmed by the detection of parvovirus B19 DNA in his serum. He received blood transfusions for supportive treatment and continued on HAART to improve his immune status and to resolve the anemia. This case suggests that parvovirus B19 infection should be considered as a possible cause of anemia in HIV-infected individuals.

Extranodal malignant lymphoma of the upper aerodigestive tract: prevalence of Epstien-Barr virus (EBV) infection in King Chulalongkorn Memorial Hospital.

BACKGROUND: High frequency of Epstein-Barr virus (EBV) in the normal mucosa of the upper aerodigestive tract suggests that it may serve as a reservoir for the virus. Malignant lymphomas arising in this site may be associated with EBV. OBJECTIVES: To determine the prevalence of EBV infection in extranodal malignant lymphomas of the upper aerodigestive tract. SETTING: King Chulalongkorn Memorial Hospital, Thailand. DESIGN: Descriptive study. PATIENTS: 42 Thai patients who presented between 1998 and 2003. MATERIAL AND METHOD: The expression of EBV mRNAs (EBERs) of malignant lymphoma was studied by means of in situ hybridization in formalin-fixed, paraffin-embedded specimens. RESULTS: The recruited subjects were 26 males and 16 females, and their age ranged from 3 to 85 years with the mean of 51.43 years, in 4 of them human immune deficiency virus (HIV) infection was documented. Ten of 42 cases (23.81%) expressed EBER transcripts and were extranodal NK/T-cell lymphomas, nasal type (7 cases), plasmablastic lymphomas (2 cases) and diffuse large B-cell lymphoma (1 case). Three of 4 cases (75%) of known HIV-seropositive cases were EBV-positive (2 plasmablastic lymphomas and 1 diffuse large B-cell lymphoma). CONCLUSION: In the upper aerodigestive tract, EBV was present in some but not all malignant lymphoma. It was associated with extranodal NK/T-cell lymphoma, nasal type and B-cell lymphoma arising in HIV-infected patients, but it was not found in B-cell lymphoma arising in immunocompetent patients.

Extranodal malignant lymphoma of the upperaerodigestive tract in King Chulalongkorn Memorial Hospital according to WHO classification.

BACKGROUND: The Working Formulation commonly used to classify NHL in Thailand has been recognized as imperfect for primary extranodal lymphoma, especially in head and neck regions. OBJECTIVE: To study the clinicopathological and immunohistochemical features of extranodal malignant lymphoma of the upper aerodigestive tract according to WHO classification. SETTING: King Chulalongkorn Memorial Hospital. DESIGN: Descriptive study. PATIENTS: 77 Thai patients who presented between 1998 and 2003. METHODS: Routine histology was performed and stained with H&E and immunohistochemistry, and clinical characteristics were recorded. RESULTS: The patients included 42 males and 35 females, with an average age of 53.87 years. Tumor sites were as follows: Waldeyer ring (n = 42, 54.55%), sinonasal areas (n = 19, 24.67%), oral cavity (n = 9, 11.69%), hypopharynx (n = 4, 5.19%), and larynx (n = 3, 3.90%). Immunohistochemically, 57 tumors (74.02%) were of B-cell phenotype and 19 tumors (24.68%) were of T-cell phenotype. According to the WHO classification, 45 cases (58.43%) were large B-cell, 3 (3.90%) were Burkitt, 3 (3.90%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), 4 (5.19%) were follicular lymphoma, 1 (1.30%) was precursor B-lymphoblastic lymphoma, and 1 (1.30%) were mantle cell lymphoma. Among the T-cell lymphomas, 9 (11.69%) were of peripheral T-cell lymphoma, unspecified, 9 (11.69%) were extranodal NK/T cell lymphoma, nasal type, and 1 (1.30%) were anaplastic large-cell lymphomas. In nasal cavity, 8 tumors (42.11%) were extranodal NK/T-cell lymphoma, nasal type, 5 (26.32%) were diffuse large B-cell lymphoma, 4 (21.05%) were peripheral T-cell lymphoma, unclassified, and 1 (5.26%) was Burkitt lymphoma. CONCLUSION: Our data correspond with series from Japan, Hong Kong, and Korea, but there is a significant difference from Western population in T-cell lymphomas of sinonasal area especially extranodal NK/T cell lymphoma of nasal type and peripheral T-cell lymphoma, unspecified which had a higher frequency in Thailand, Japan, Hong Kong, and Korea.

Interobserver variation in classifying lymphomas among hematopathologists.

BACKGROUND: Lymphomas are common malignancies that have various subtypes with many overlapping histologic, immunophenotypic and genetic features. Therefore, discordance in classifying lymphoma among pathologists may be encountered. But this issue is not well characterized. We conducted the present study to demonstrate discordances among Thai hematopathologists as well as to highlight common arguing points for classifying lymphomas. METHODS: The 117 lymphoma cases were randomly retrieved and individually reviewed by 7 hematopathologists, members of the "Thai Hematopathologist Group," without knowing the original diagnoses. The consensus diagnoses were given from a discussion by all members. In each case, the diagnosis from each participant was compared with the consensus diagnosis and classified into 4 categories as follow: 1) concordance, 2) minor discordance, 3) major discordance and 4) serious discordance. RESULTS: There were approximately 11% discordances between original and consensus diagnoses. The average discordances among all pathologists according to minor, major and serious discordances were 10%, 3.5% and 0.3%, respectively. Diffuse large B-cell lymphoma had the least discordance (7%). Small biopsies had been found to increase discordances in some lymphoma subtypes. CONCLUSIONS: The present study reveals some degrees of interobserver variation in classifying of lymphoma by using the 2008 WHO classification among hematopathologists. Some types of lymphomas on small biopsies were found to have a significant higher discordance rate. This study also described some common diagnostic discordances regarded as potential pitfalls in classifying lymphomas. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_162.

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αß, γδ, and αß/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αß or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) ß,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αß, 1% were TCR αß/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αß T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.