Thamathorn Assanasen

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/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 &agr;&bgr; or &ggr;&dgr; 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 &ggr;&dgr; enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) &bgr;,&ggr; and, in cases tested, &dgr; negative (presumptive NK origin); 5% were TCR &ggr;&dgr;+, 3% were TCR &agr;&bgr;+, 1% were TCR &agr;&bgr;/&ggr;&dgr;+, 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 &agr;&bgr; 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 &ggr;&dgr; 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 &ggr;&dgr; EATL.

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.

PCR detection of Mycobacterium tuberculosis in necrotising non-granulomatous lymphadenitis using formalin-fixed paraffin-embedded tissue: a study in Thai patients

Background: Necrotising non-granulomatous lymphadenitis can be observed in several conditions, most notably infection (including tuberculosis, yersiniosis and nocardiasis), Kikuchi–Fujimoto disease and systemic lupus erythematosus. Aims: To evaluate the role of PCR in the detection of Mycobacterium tuberculosis in necrotising non-granulomatous lymphadenitis in Thai patients using formalin-fixed paraffin-embedded tissue. Methods: 35 patient samples showing necrotising non-granulomatous lymphadenitis were subjected to PCR for detection of the IS6110 sequence of M tuberculosis. For comparison, sections were visually assessed for acid-fast bacilli using the Ziehl–Neelsen stain. Results: Among 35 cases of necrotising non-granulomatous lymphadenitis, a conclusive diagnosis could be reached in 23 cases: 15 cases of Kikuchi–Fujimoto disease, 6 of tuberculosis and 2 of systemic lupus erythematosus. Of the 6 cases of tuberculous lymphadenitis, 4 (66.6%) were detected by PCR in formalin-fixed paraffin-embedded tissue samples. PCR was positive in 6/12 of the remaining cases (50%) in which a definitive diagnosis could not be reached by other methods. Conclusion: Using PCR, a significant percentage (28%) of cases of necrotising non-granulomatous lymphadenitis in this study could be attributed to M tuberculosis. PCR for identification of the organism can be extremely helpful in confirming a diagnosis of tuberculosis when Ziehl–Neelsen staining is negative.

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

ABSTRACT Objectives: Estrogen receptor beta (ERβ)-selective agonists inhibited B cell lymphoma growth in animal models. However, a recent study found that higher ERβ expression in tissue from diffuse large B cell lymphoma (DLBCL) patients indicated a poorer survival. This study aimed to determine the ERβ 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 ERβ1-expressing cells. Nodal lymphoma (N = 41) was analyzed separately from extra-nodal DLBCL (N = 31). Results: On immunohistochemistry, ERβ1 was expressed in 73.6% of cases with the median expressing cells of 20%. For nodal lymphoma, high ERβ 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 ERβ 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: ERβ1 protein expression represented opposite prognostic factors in nodal vs. extra-nodal DLBCL.

Significance of MYC/BCL2 Double Expression in Diffuse Large B-cell Lymphomas: A Single-center Observational Preliminary Study of 88 Cases

OBJECTIVES: To study the prevalence of MYC/BCL2 double expression in diffuselarge B-cell lymphomas (DLBCLs) and its prognostic value. MATERIAL AND METHODS: This is a retrospective observational study, which includespatients diagnosed with DLBCLs at King Chulalongkorn Memorial Hospital from 2013 to2014. The slides were reviewed, and MYC and BCL2 immunostains were scored accordingto Revised WHO 2016 Classification. Clinical data were collected from medical records.Patients were divided into two groups: double expression (DE) and non-double expression(NDE). Survivals and hazard ratios (HR) were calculated. RESULTS: Eighty-eight patients were included in the study and 40 (46%) had doubleexpression. The mean age was 60±16 years old; 40.9% were male and 59.1% werefemale. Eight patients were excluded from the survival analysis due to incompleteclinical data. Of the remaining 80 patients, there were 34 (42.5%) DE and 46 (57.5%)NDE. Median overall survival time (OS) and median progression-free survival time(PFS) tended to be lower in the DE group but was not statistically significant (Log-ranktest, p = 0.16). Multivariate analysis identified 4 confounders: sex, cell of origin (COO),risk group and addition of rituximab to the standard treatment. Adjusted HRs of the DEgroup were 1.21 (95%CI 0.63-2.31, p = 0.57) for OS and 1.20 (95%CI 0.63-2.30,p = 0.58) for PFS. In the germinal center subgroup (GCB) of DLBCL, patients with DEhad HRs of 4.33 (95%CI 0.80-23.37, p = 0.08, significance level of p < 0.10) for OS and4.61 (95%CI 0.80-23.37, p = 0.08) for PFS; but, these were not significant in the non-GCBsubgroup. CONCLUSION: MYC/BCL2 double expression (DE) is significantly associated withpoorer prognosis than non-double expression (NDE) among DLBCLs with GCBphenotype. MYC/BCL2 double expression should be reported in the pathologicaldiagnosis of DLBCLs. Keywords: MYC, BCL2, double expression, co-expression, diffuse large B-celllymphoma, prognosis.

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.

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.

Demyelinating patterns of injury in primary central nervous system lymphoma

Background: Primary CNS lymphoma (PCNSL) can be confused clinically and pathologically with primary demyelinating disease such as multiple sclerosis, and glucocorticoids are known to modify the histologic picture of lymphoma. Objectives: To evaluate the axon and myelin patterns of parenchymal brain damage and to correlate the patterns with the preoperative administration of corticosteroids. Methods: Twenty two cases of PCNSL, all diffuse large B-cell lymphoma, were evaluated for patterns of axonal and myelin alteration. Results were correlated with preoperative steroid administration. Results: Nine cases (41%) showed myelin loss with axonal preservation, mimicking a primary demyelinating disorder. Loss of both myelin and axon, resembling infarction, was observed in 13 cases (59%). No cases demonstrated preservation of myelin. No significant correlation was found between the demyelinating disease pattern and preoperative steroid treatment (p = 0.696). Conclusion: In PCNSL, different demyelinating patterns of injury are encountered and the pattern is not influenced by glucocorticoid treatment. Awareness of this situation is important when assessing small brain biopsy specimens where tumor cells may not be readily identified.