Proliferation index in tuberculous lymphadenitis.

During the pathogenesis of any granuloma, activated macrophages (AMs) are recruited and ex-panded under the influence of the migration inhibition factor. The goal of this study was to determine whether AMs then also proliferate by themselves or not. The proliferation index (PI) of AMs in lymph node biopsies from 40 cases of tuberculous lymphadenitis was evaluated by immunohistochemistry using a monoclonal antibody (MIB-1) to Ki-67. The PI was defined as the percentage of AMs with positive nuclear staining. It ranged from 3.6 - 20.6% (mean = 11.0 ± 4.4) which was slightly lower than that reported in previous studies. Mitotic figures ranged from 0 - 6 per 500 AMs. Multinucleated giant cells ranged from 0 - 6.3 cells per low power field and their PI was exclusively 0%. Areas of caseous necrosis ranged from 5-85% of the total area of the tissue section examined (mean = 61.6 ± 19.8). Mitotic figures, multinucleated giant cells, and areas of caseous necrosis lacked a statistically significant re-lationship to the PI (p > 0.05). In conclusion, AMs in granulomas can proliferate to a limited degree as detected by the mitotic figures and the PI.

A novel mutation of the IL12RB1 gene in a child with nocardiosis, recurrent salmonellosis and neurofibromatosis type I: First case report from Thailand.

Genetic defects of interleukin (IL)-12/23-and interferon (IFN)-γ-mediated immunity can cause in-creased susceptibility to intracellular microbes. Among these defects, a mutation of the gene encoding the IL-12 receptor β1 (IL-12Rβ1) is the most common worldwide. A 12-year old Thai boy with pre-existing neurofibromatosis type 1 (NF1) was evaluated for primary immunodeficiency after a history of tuberculous lymphadenitis, recurrent Salmonella infections and nocardiosis. Flow cytometry of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) revealed a defect in the IL-12Rβ1 surface expression. A genetic study showed a novel nonsense homozygous mutation of the IL12RB1 gene in exon 4 (402C>A), confirming the diagnosis of IL-12Rβ1 deficiency. This is the first case report of a primary IL-12Rβ1 deficiency in Thailand with the interesting finding of a coexisting NF1.

Pitfalls in classifying lymphomas.

BACKGROUND: Although the WHO classification (2001) requires a great deal of morphologic, immunophenotypic, genetic, and clinical features for classifying lymphomas, it is still feasible to misdiagnose under limited resources, especially a limited panel of antibodies used for immunophenotyping. To identify pitfalls in classifying lymphomas among hematopathologist, general pathologists, and pathology residents under this situation. MATERIAL AND METHOD: Newly diagnosed lymphoma cases from 1 July 2002 to 30 June 2003 at Siriraj Hospital were included for two rounds of individually blinded review by a hematopathologist, two general pathologists, and three pathology residents. Final diagnoses were given by consensus. Pitfalls were determined from misdiagnosis, in each case analyzed in terms of frequency. RESULTS: One hundred and four lymphoma cases included 61 diffuse large B-cell lymphoma (DLBCL, 58.6%), 12 MALT lymphoma (11.5%), eight follicular lymphoma (FL, 7.7%), seven classical Hodgkin lymphoma (HL, 6.7%), four unspecified peripheral T-cell lymphoma (PTCL, 3.8%), three Burkitt lymphoma (BL, 2.9%), two subcutaneous panniculitis-like T-cell lymphoma (SPTCL, 1.9%), and seven other uncommon types (1% each). Pitfalls were low infrequency on diagnosis of DLBCL, nodular sclerosis HL, and SPTCL (8% each), but not different among the participants only in DLBCL. Pitfalls in diagnosis of MALT lymphoma, mixed cellularity HL, BL, unspecified PTCL, and FL were 60%, 50%, 33%, 29%, and 24%, respectively. However, considering hematopathologist and non-hematopathologist groups, pitfalls in the former were lower, especially in the uncommon types of lymphoma. CONCLUSION: Pitfalls in classifying lymphomas are common. Interest in hematopathology reduces misdiagnosis in lymphomas other than DLBCL.

Specific immune response and pathological findings in BALB/c mice inoculated with recombinant BCG expressing HIV-1 antigen.

Recombinant BCGs (rBCGs) containing extrachromosomal plasmids with different HIV-1 insert sequences: nef, env (V3J1 and E9Q), gag p17 or whole gag p55 were evaluated for their immunogenicity, safety and persistent infection in BALB/c mice. Animal injected with, rBCG-plJKV3J1, rBCG-pSO gag p17 or rBCG-pSO gag p55 could elicit lymphocyte proliferation as tested by specific HIV-1 peptides or protein antigen. Inoculation with various concentration of rBCG-pSO gag p55 generated satisfactory specific lymphocyte proliferation in dose escalation trials. The rBCG-pSO gag p55 recovered from spleen tissues at different time interval post-inoculation could express the HIV protein as determined by ELISA p24 antigen detection kit. This result indicated that the extrachromosomal plasmid was stable and capable to express Gag protein. It was also demonstrated that rBCGs did not cause serious pathological change in the inoculated animals. The present study suggested the role of BCG as a potential vehicle for using in HIV vaccine development.

Gastrointestinal lymphoma in Thailand: a clinicopathologic analysis of 120 cases at Siriraj Hospital according to WHO classification.

Clinicopathologic information of gastrointestinal (GI) lymphoma in Southeast Asia is lacking. A retrospective analysis of 120 cases of GI lymphoma in Thailand diagnosed at Siriraj Hospital based on WHO classification was performed. All were non-Hodgkin lymphoma (NHL). The peak age was in the sixth and seventh decades; a slight male preponderance was observed. Sites of involvement included stomach (49.2%), intestine (46.7%), and multiple sites (4.2%). There were 104 cases of primary GI lymphoma (86.7%) and 16 cases of secondary GI lymphoma (13.3%). Presenting GI symptoms were more common in the former; while superficial lymphadenopathy and fever were more common in the latter. Mass lesions were observed in both groups (72.1% vs 56.3%). Localized and advanced diseases were found in 68.3% and 31.7% of primary GI lymphomas, respectively. The most common type of lymphoma in both groups was diffuse large B-cell lymphoma. Lymphoepithelial lesions (LEL) were not significantly different between the two groups (58.2% vs 42.9%), but Helicobacterpylori infection was significantly associated with primary gastric lymphoma (p < 0.0001). The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone. GI lymphomas in Thailand are mostly primary B-cell NHL. LEL is not indicative of primary GI lymphoma, but H. pylori infection is closely associated with primary gastric lymphoma. A prospective study to determine the treatment of choice for localized GI lymphoma is needed.

Thrombocytopenic purpura associated with miliary tuberculosis.

The authors report a case of thrombocytopenia associated with miliary tuberculosis. The patient was a 28-year-old woman who was admitted because of massive upper gastrointestinal hemorrhage and acute respiratory failure. Chest radiographs revealed diffuse bilateral reticulonodular infiltration and complete blood count was significant for severe thrombocytopenia. Bone marrow biopsy was performed to investigate the cause of thrombocytopenia and demonstrated multiple tiny caseating granulomas suggesting miliary tuberculosis (TB). She received anti-TB therapy and a short course of steroid with good response. Platelet count returned to normal limit within 10 days. Although isolated thrombocytopenia is uncommon in TB, it is still important to consider TB in the differential diagnosis of thrombocytopenia, particularly in patients with abnormal chest radiographs. Bone marrow examination is very helpful in this situation.

Multicentric Castleman's disease, non-Hodgkin's lymphoma, and Kaposi's sarcoma: a rare simultaneous occurrence.

A rare simultaneous occurrence of multicentric Castleman's disease, non-Hodgkin's lymphoma, and Kaposi's sarcoma was diagnosed in a 70-year-old man who presented with fever, polyarthralgia, weight loss, vascular purpura, anemia, generalized lymphadenopathy, and hepatosplenomegaly. He had no risk of HIV infection and serological tests for HIV were negative twice, but a low number of T-cells and a reversed CD4/CD8 ratio were observed. During hospitalization, he developed Kaposi's sarcoma at the right sole. Lymph node biopsies revealed multicentric Castleman's disease together with a large B-cell lymphoma, which showed monotypic IgM-lambda lymphocytes. To our knowledge, this is the first report in which systemic manifestations of all three diseases occurred simultaneously prior to any specific treatment. The altered immune status and human herpesvirus-8 infection might have played a role in the pathogenesis of this occurrence.

Determination of marrow involvement in non-hodgkin's lymphoma by immunocytochemical studies.

Bone marrow involvement in non-Hodgkin's lymphoma (NHL) alone can raise the clinical stage from I and II (localized disease) to IV (advanced disease). Multiparameter assessment is thus required to detect early marrow involvement (positive marrow) besides the conventional morphologic evaluation of bone marrow biopsy and marrow aspirates. Determination of lymphocyte subsets in the marrow is considered useful if the phenotype of NHL is known. To prove this possibility, we have performed immunocytochemical studies on marrow aspirate smears to determine CD3+ T-cells and CD19+ B-cells by using the alkaline phosphatase-labeled streptavidin-biotin method in 8 cases of NHL with positive marrow (4 B-cell, 4 T-cell NHL), 11 cases of NHL with negative marrow (8 B-cell, 3 T-cell NHL), and 11 cases of controls including Hodgkin's disease (2), acute leukemia (4), SLE (1), anemia (1), inflammatory bowel disease (1), polycythemia vera (1), and Wegener's granulomatosis (1). CD3+ T-cells and CD19+ B-cells were enumerated by counting 500 nucleated marrow cells. The results showed that the mean CD3/CD19 ratios in B-cell NHL and T-cell NHL with positive marrow were 1.8 and 20.5, while those in B-cell NHL and T-cell NHL with negative marrow and in controls were 3.3, 3.1, and 2.6, respectively. Moreover, cytologic difference between CD3+ T-cells and CD19+ B-cells was observed in 1 case of B-cell NHL and 3 cases of T-cell NHL with positive marrow, while such a difference was absent in NHL with negative marrow and in controls except in 1 case of T-cell NHL with negative marrow. Therefore, immunocytochemical studies are helpful to determine marrow involvement in NHL.

Erythrocyte sedimentation rate and plasma viscosity in pulmonary tuberculosis.

Erythrocyte sedimentation rate (ESR) and plasma viscosity (PV) are non-specific indices for screening, diagnosis and follow up to some disease. This prospective study of ESR and PV reports on 21 patients of pulmonary tuberculosis and 45 healthy. The mean and standard deviation of ESR in diseases and healthy were 80.1+35.4 and 11+7 mm/hr compared with PV 2.07+0.17 and 1.69+0.07 mPaS. After three months of complete treatment of pulmonary tuberculosis in six patients, the ESR returned from 69.2+25.9 to 21.3+16.8 mm/hr, the PV returned from 2.08+0.22 to 1.75+0.15 mPaS. Both tests gave good result in supporting diagnosis and follow up, however the PV is probably superior to ESR because of better quality control and precision, longer plasma reservation in room temperature. It is recommended that PV may have a role in clinical practice as well as ESR.