Pongsak Wannakrairot

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.

Difference in neuropathogenetic mechanisms in human furious and paralytic rabies

Whereas paralysis is the hallmark for paralytic rabies, the precise pathological basis of paralysis is not known. It is unclear whether weakness results from involvement of anterior horn cells or of motor nerve fibers. There is also no conclusive data on the cause of the neuropathic pain which occurs at the bitten region, although it has been presumed to be related to sensory ganglionopathy. In this study, six laboratory-proven rabies patients (three paralytic and three furious) were assessed clinically and electrophysiologically. Our data suggests that peripheral nerve dysfunction, most likely demyelination, contributes to the weakness in paralytic rabies. In furious rabies, progressive focal denervation, starting at the bitten segment, was evident even in the absence of demonstrable weakness and the electrophysiologic study suggested anterior horn cell dysfunction. In two paralytic and one furious rabies patients who had severe paresthesias as a prodrome, electrophysiologic studies suggested dorsal root ganglionopathy. Postmortem studies in two paralytic and one furious rabies patients, who had local neuropathic pain, showed severe dorsal root ganglionitis. Intense inflammation of the spinal nerve roots was observed more in paralytic rabies patients. Inflammation was mainly noted in the spinal cord segment corresponding to the bite in all cases; however, central chromatolysis of the anterior horn cells could be demonstrated only in furious rabies patient. We conclude that differential sites of neural involvement and possibly different neuropathogenetic mechanisms may explain the clinical diversity in human rabies.

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.

A retrospective analysis of immunohistochemical staining in identification of poorly differentiated round cell and spindle cell tumors — results, reagents and costs

Summary Immunohistochemistry has rapidly established a significant role in diagnostic pathology. We use immunohistochemistry as an adjunct to morphological diagnosis and employ a “panel approach” to the classification of poorly differentiated tumors. This retrospective analysis was conducted to examine the efficacy of such an approach, using, as an example, the two most common categories of poorly differentiated tumors, namely, the poorly differentiated round cell tumors and spindle cell tumors. Five hundred and fifty‐seven consecutive cases of such tumors, collected over a two‐yr period, had been subjected to immuno‐histochemical staining because specific or definitive categorization of the tumor was not possible on the basis of the examination of hematoxylin and eosin stained sections. The clinical history, gross and microscopic findings, as well as the results of immunohistochemical stains were analyzed. Immunohistochemistry allowed a definitive diagnosis to be assigned in 420 cases (75.4%). It was particularly useful in identifying malignant melanoma of both epithelioid and spindle types and distinguished between melanoma, lymphoma and poorly differentiated carcinoma in 126 cases of such lesions occurring in adult lymph nodes. It was also useful in identifying tumors in small biopsies where poor cytomorphological preservation or small size precluded accurate categorization. The application of appropriately chosen panels of antibodies tailored to a narrow list of differential diagnoses helped to identify myogenous, vascular, nerve sheath and fibrocystic lesions among the group of spindle cell tumors. Immunohistochemistry provided definitive diagnoses in 70% of round cell tumors and 92% of spindle cell tumors. Immunostaining was also useful in determining the source of metastatic carcinomas, particularly those of prostate, breast, thyroid and germ cell origin, all of which are “treatable” malignancies. Immunostaining provided contributory but non‐diagnostic information in 71 cases (12.8%). While most of these were confirmed to be metastatic carcinoma, their primary source remained undetermined because of the currently limited repertoire of tissue‐associated markers. Immunohistochemistry was not contributory in 66 instances (11.8%) and the major reason for this was the suboptimal preservation of tissue antigens, especially in consultation material. Various combinations of a total of 48 antibodies were employed to produce the diagnostic information. For the 557 cases examined, a total of 2,352 sections were stained at an average cost of about

The morphological spectrum of lymphadenopathy in HIV infected patients.

71 per case inclusive of

Apoptosis is a major cause of so-called “caseous necrosis” in mycobacterial granulomas in HIV-infected patients

5.00 for staining reagents. We conclude that the efficacy and cost of this important adjunct to morphological diagnosis is largely dependent on two factors, viz, optimal preservation of tissue antigens and the experience and knowledge of the characteristics of the antibodies to allow the selection of appropriate reagents for the separation of a narrow list of differential diagnoses developed from morphological examination.

Eosinophil Count in Nasal Mucosa Is More Suitable than the Number of ICAM-1-Positive Nasal Epithelial Cells to Evaluate the Severity of House Dust Mite-Sensitive Allergic Rhinitis: A Clinical Correlation Study

Aims: To study the histological spectrum of lymphadenopathy in human immunodeficiency virus (HIV) infected Thai patients. Methods: Lymph nodes from 55 HIV infected patients were accessioned over a 19 month period in two pathology laboratories in Bangkok, Thailand. These were examined with H&E, Ziehl‐Neelsen, periodic acid‐Schiff (PAS), PAS with diastase (PAS/D), Gram and methenamine stains. Results: Six reaction patterns were observed: (1) classic necrotising granulomas (30 cases); (2) extensive necrosis with minimal granulomatous response (5 cases); (3) sarcoid‐like non‐necrotising granulomas (5 cases); (4) foamy macrophage or pseudo‐Gaucher cell response (5 cases); (5) inflammatory pseudotumour‐like proliferation (3 cases); and (6) non‐specific lymphoid hyperplasia (7 cases). Myriads of intracellular, long, slender acid‐fast bacilli were found in those cases with the pseudo‐Gaucher cell and inflammatory pseudotumour‐like response, while variable numbers of bacilli were identified in those cases with non‐necrotising sarcoid‐like granulomas. Few scattered acid‐fast bacilli were found in five cases with necrotising granulomas. In one case, yeast‐like organisms in keeping with Cryptococcus were identified. No organisms were identified in the cases showing lymphoid hyperplasia, extensive necrosis and minimal granulomatous response, and in the remaining cases of classic necrotising granulomas. Conclusions: The wide spectrum of histological changes in HIV‐associated lymphadenomegaly requires recognition, particularly as the majority were associated with acid‐fast organisms, mostly in keeping with the morphological features of Mycobacterium avium–M. intracellulare complex that was distinctively stained by Grocott methenamine‐silver, Gram and PAS stains. The histological changes mimic those of infarction and other infective lymphadenitis, sarcoidosis, Whipples disease, inflammatory pseudotumour and spindle cell neoplasms.

High frequency of BCL2 translocation in Thai patients with follicular lymphomas.

Aim: To demonstrate that so-called “caseous necrosis” is the result of apoptosis and investigate the association of B and T cells, and macrophages with the granulomas and their relationship to some apoptosis-related proteins. Methods: Cervical lymph node biopsy specimens from 55 HIV-infected Thai patients with caseating granulomas, confluent caseating granulomas, sarcoid-like granulomas, foamy macrophage response, pseudo-inflammatory tumour response or non-specific lymphoid hyperplasia were examined histologically and for apoptosis by immunostaining for caspase 3 and TUNEL. Classic tuberculoid caseating granulomas in cervical lymph node and lungs from non-HIV-infected patients were also stained with caspase 3. Results: All areas of caseous necrosis frequently displayed extensive apoptosis that readily accounted for the so-called “necrosis”. Small foci of apoptosis were present in the other reaction patterns and fibrotic granulomas often showed residual apoptosis. The extent of apoptosis was inversely related to the numbers of identifiable acid-fast bacilli; all epithelioid macrophages revealed strong immunoexpression of the pro-apoptotic proteins Bax and Fas, whereas the anti-apoptotic protein Bcl-2 was not present. Apoptosis occurred in CD68+ macrophages and CD3+ CD8+ T cells; all nodes were deficient of CD4+ cells. CD8+ T cells were intimately related to the apoptotic foci, suggesting a role in the process, particularly in the absence of CD4+ cells. In non-HIV-infected cases, similar extensive apoptosis was confirmed with caspase 3. Conclusions: So-called “caseous necrosis” is shown for the first time to be the result of apoptosis. In the absence of CD4+ cells the findings negate many of the postulated mechanisms of apoptosis in the murine model and have implications for the treatment of mycobacterial infections.

The social network index and its relation to later-life depression among the elderly aged ≥80 years in Northern Thailand

Background: House dust mite (HDM)-sensitive allergic rhinitis is a perennial rhinitis with persistent nasal inflammation. Currently, there are no reliable parameters to monitor the severity of perennial allergic rhinitis. The purpose of this study was to evaluate correlations between clinical and laboratory parameters in patients with HDM-sensitive allergic rhinitis. Methods: We measured nasal symptoms, did the Dermatophagoides pteronyssinus (Der P) skin prick test (SPT), evaluated the Der P allergen nasal challenge threshold, and laboratory parameters [(1) inflammatory cell count from nasal mucosal scraping specimens: eosinophils and neutrophils and (2) immunocytochemistry: ICAM-1 expression on nasal epithelial cells] in 20 cases of HDM-sensitive allergic rhinitis and performed correlation tests between all parameters. Results: The wheal diameter induced by Der P SPT was significantly correlated with the Der P allergen nasal challenge threshold (p = 0.001). The number of eosinophils from nasal mucosal scrapping specimens was correlated with the ICAM-1 expression on nasal epithelial cells (p = 0.039), the number of neutrophils from nasal mucosal scrapping specimens (p = 0.001), and nasal stuffiness (p = 0.037) but did not correlate with total nasal symptom scores. Conclusion: Clinical symptoms of HDM-sensitive allergic rhinitis showed a poor correlation with inflammatory parameters. The eosinophil count in nasal mucosa is correlated with ICAM-1 expression and more suitable than ICAM-1 levels to evaluate the severity of HDM-sensitive allergic rhinitis. This study also supports the role of the SPT in the diagnosis of nasal allergy to HDM.

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

Follicular lymphoma is characterized by chromosomal translocation involvingBCL2 and immunoglobulin heavy chain genes (IgH). That the incidence of follicular lymphoma and the previously reported frequency ofBCL2 translocation are lower in Asians than in Caucasians implies a different molecular pathology. The study ofBCL2 rearrangement will yield deeper insights into the pathogenesis of follicular lymphomas and into clinical applications of molecular diagnosis for Asian follicular lymphoma patients.BCL2 /IgH translocation was analyzed in paraffin-embedded tissues from follicular lymphoma patients by using polymerase chain reaction (PCR) analysis of the major breakpoint region (MBR), the intermediate cluster region (ICR), and the minor cluster region. In addition, fluorescence in situ hybridization (FISH) analysis with split-signalBCL2 probes was performed. PCR analysis revealedBCL2 rearrangement in 12 (23.5%) of 51 cases (10 MBR and 2 ICR breakpoints).This frequency is lower than the frequencies reported from Western countries (40%–60%). DNA sequencing of the breakpoints revealed nucleotide insertions suggesting V(D)J recombination-mediated mechanisms. On the other hand, FISH analysis revealed 11 (84.6%) of 13 cases with positive signals forBCL2 translocation. Our results suggest thatBCL2 translocation is essential for the pathogenesis of follicular lymphoma in Thai patients. In addition, the data demonstrate the low sensitivity of the PCR for diagnostic testing and suggest that split-signal FISH is the method of choice.