Angiocentric T-cell lymphoma of the pancreas presenting as late-onset diabetes mellitus with diabetic retinopathy.

Pancreatic lymphoma presenting with clinical diabetes mellitus (DM) is rare. We report angiocentric T-cell lymphoma of the pancreas in a 65-year-old Thai woman who presented with progressive deterioration of visual acuity of both eyes. She had diabetic retinopathy (DR) diagnosed only 20 months after the diagnosis of DM at the age of 63. She later developed erythematous rashes, fever, and deterioration of consciousness; she eventually died of shock. A skin biopsy and bone marrow examination revealed angiocentric T-cell lymphoma. At autopsy, the pancreas and both eyes were extensively infiltrated by lymphoma. Widespread involvement of nearly all organs but superficial lymphadenopathy was detected. In contrast to other typical cases of long-standing DM, only mild atherosclerosis was noted, and no DR was found. To the best of our knowledge, this is the first case of lymphoma involving the pancreas and both eyes producing clinical DM and DR.

Malignant carcinoid tumor of the appendix with liver and lung metastasis: report of a case with a high level of serum carcinoembryonic antigen.

We report elevated serum carcinoembryonic antigen (CEA) in a case of malignant carcinoid tumor of the appendix with liver and lung metastasis. A 55-year-old Thai man was found to have multiple nodules in the liver by ultrasonography. Serum CEA was 7,387.9 ng/mL (normal 0-4.1 ng/mL) leading to a clinical impression of colonic carcinoma with liver metastasis. During the investigation, he developed acute abdomen caused by ruptured acute appendicitis. Malignant carcinoid tumor of the appendix, 1 cm in diameter and located proximal to the ruptured acute appendicitis, was identified. The tumor cells showed trabecular or insular growth pattern, some nuclear pleomorphism but typically fine nuclear chromatin, frequent mitoses and focal necrosis. They were immunoreactive for antibody to chromogranin, neuron-specific enolase, CEA, and cytokeratin. Tumor metastases were discovered in the liver, right lung, mediastinal and right supraclavicular lymph nodes. Electron microscopic study demonstrated pleomorphic neurosecretory granules of the midgut type of carcinoid tumor.

Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient.

Clofazimine-induced crystal-storing histiocytosis is a rare but well-recognized condition in the literature. Besides the common reddish discoloration of the skin, clofazimine produces gastrointestinal disturbances-sometimes severe abdominal pain, prompting exploratory laparotomy, because pathologic and radiologic findings can produce diagnostic difficulties if the pathologic changes caused by clofazimine are not recognized. The authors report such a case in a leprosy patient to emphasize the importance of history taking, the radiologic abnormalities of the small intestine, and the pathologic findings in small intestine and lymph node biopsies. Clofazimine crystals are red in the frozen section and exhibit bright-red birefringence. However, they are clear in routinely processed histologic sections because they dissolve in alcohol and organic solvents. They also appear as clear crystal spaces during electron microscopic study, but some osmiophilic bodies can be observed. Histiocytosis caused by clofazimine crystals produces infiltrative lesions in radiologic studies mimicking malignant lymphoma or other infiltrative disorders. Associated plasmacytosis in the histologic sections can simulate lymphoplasmacytic lymphoma or multiple myeloma with crystal-storing histiocytosis. With the knowledge of this rare condition caused by clofazimine, appropriate management to avoid an unnecessary laparotomy is possible.

Specific IgA antibody to Epstein-Barr viral capsid antigen: a better marker for screening nasopharyngeal carcinoma than EBV-DNA detection by polymerase chain reaction.

Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. To assess whether EBV DNA detection by polymerase chain reaction (PCR) or presence of specific serum antibody to viral capsid antigen (VCA) was a better marker for screening NPC, nasopharyngeal tissues and blood samples from 58 NPC patients and 24 non-NPC patients (23 with laryngotracheal stenosis and 1 with chronic tonsillitis) were tested for the presence of EBV DNA and serum specific VCA antibodies, respectively. EBV DNA was detected in 56 (96.5%) of NPC patients and 15 (62.5%) of non-NPC controls, with predominantly EBV type A in both groups. On the other hand, specific VCA IgA antibody was detected in the majority of NPC patients: 52 (89.7%) while only 4 (16.7%) were detected in non-NPC controls. Therefore, specific VCA IgA antibody may serve as a better marker for screening NPC than EBV DNA detected by PCR.

Cross over placebo control trial of dilazep in beta-thalassemia/hemoglobin E patients.

An attempt was made to find better symptomatic treatment for beta-thalassemia/hemoglobin E (beta-thal/Hb E) patients in order to reduce their blood demand. Oral administration of dilazep was prescribed for these patients and a clinical trial was conducted over a 2-year period as a cross over placebo control study. Seventeen beta-thal/Hb E patients were enrolled in the study. All of them received dilazep and placebo for 10 months at different periods of time and were taken care of by the same doctor throughout the study. The blood demand of the same patients during the period of receiving dilazep with the period of receiving placebo, was 1.5 +/- 1.8 U/10 months versus 2.2 +/- 2.6 U/10 months, respectively. Thus dilazep showed a benefit in decreasing the blood demand by about 50% although the results did not reach statistical significance (p = 0.1). There was a statistical difference in hemoglobin concentration of the patients receiving dilazep compared with placebo (p = 0.038). While receiving dilazep the mean +/- SD hemoglobin level was 5.82 +/- 0.8 g/dl, significantly higher than while receiving placebo (5.66 +/- 0.9 g/dl) (p = 0.038). The liver, and renal function tests, and cardiac enzyme levels of the patients showed no significant changes throughout the study. However, one case had a problem with bleeding following tooth extraction whilst receiving dilazep and needed 1 unit of blood transfusion. In conclusion, administration of dilazep to patients with beta-thal/Hb E increased the patients' hemoglobin and reduced their blood demand with few side effects.

Malignant lymphoma in Thailand: changes in the frequency of malignant lymphoma determined from a histopathologic and immunophenotypic analysis of 425 cases at Siriraj Hospital.

BACKGROUND: Analysis of malignant lymphoma in a single institution at different periods of time can determine the changing status of the disease in the region. METHODS: To compare with the large series of 1095 lymphoma cases reported between 1957-1971 at Siriraj Hospital, the largest hospital in Thailand, a similar study was performed through histopathologic evaluation of 425 lymphoma cases diagnosed consecutively at the same institution between August 1993 and October 1995. Phenotypic analysis was performed by paraffin section-immunoperoxidase studies. RESULTS: A striking increase in lymphoma cases was noted from 73 cases/year in the first series to 189 cases/year in the second series (an increase of 158.9%). Lymphoma occurred in all age groups, with a peak incidence at the seventh decade of life. The male to female ratio decreased from 2:1 in 1957-1971 to 1.3:1 in the more recent series. The incidence of Hodgkin's disease (HD) was found to have decreased from 28.9% to 8.5%. There were 36 cases (8.5%) of HD and 389 cases (91.5%) of non-Hodgkin's lymphoma (NHL) reported in the second series. The subtypes of HD included 16 cases of mixed cellularity, 13 cases of nodular sclerosis, 6 cases of lymphocyte depletion, and 1 case of lymphocyte predominance. According to the Working Formulation, the 389 NHL cases included low grade (14.1%), intermediate grade (57.3%), high grade (11.3%), and miscellaneous groups (17.2%). They were classified as small lymphocytic (9.5%), follicular (11.1%), diffuse (50.9%), immunoblastic (4.1%), small noncleaved (4.4%), lymphoblastic (2.8%), anaplastic large cell (9.0%), mycosis fungoides (1.8%), hairy cell leukemia (0.3%), true histiocytic (0.5%), and extramedullary plasmacytoma (1.0%). The immunophenotypes of the 359 NHL cases available for paraffin section-immunoperoxidase studies were B-cell (71.0%), T-cell (24.5%), histiocyte (0.6%), and undetermined phenotypes (3.9%). CONCLUSIONS: The incidence of malignant lymphoma is increasing in Thailand, with a high frequency of intermediate to high grade NHL of B-cell phenotype reported.

Pulmonary dirofilariasis in a patient with multisystem Langerhans cell histiocytosis--the first reported case in Thailand.

Despite a high prevalence of canine dirofilariasis, there is no case of pulmonary dirofilariasis reported from Thailand. We herein report a case of multisystem Langerhans cell histiocytosis who had an incidental pulmonary dirofilariasis found at the time of autopsy as a solitary nodule at the periphery of the right lower lobe. This is the first reported case in Thailand. Association between pulmonary dirofilariasis and Langerhans cell histiocytosis has not been described before in the literature.

Lymph node pathology in patients with a clinical diagnosis of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD): an analysis of 37 cases.

Lymph node pathology was analyzed in 37 patients clinically diagnosed as having angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). Results confirmed AILD in 11 cases and were compatible with AILD in 2 cases. Reactive lymphoid hyperplasia was found in 15 cases, 2 cases had angiofollicular lymphoid hyperplasia or Castleman's disease, atypical lymphoid hyperplasia suggestive of malignant lymphoma was observed in 3 cases, and malignant lymphoma was diagnosed in the remaining 4 cases. The histopathologic features of AILD which differed from reactive lymphoid hyperplasia were effacement of lymph node architecture, vascular arborization, high endothelial venules, and capsular infiltration (p-value < 0.05). Lymphodepletion and PAS-positive interstitial material were occasionally found in both groups (p-value > 0.05). Among the 15 cases with pathology of reactive lymphoid hyperplasia, we identified 8 cases with hyperplastic lymphoid follicles, interfollicular plasmacytosis and hypervascularity which we designated as a hyperimmune reaction. This study emphasizes the necessity of lymph node examination in all patients with a clinical suspicion of AILD.

Detection of thalassemia genes using smeared blood film or leukocytes adhering to polysthylene fibers.

Presently genetic analyses for thalassemia types require relatively large amounts of heparinized blood (5 to 10 ml), and transport as well as degeneration of these sample is a problem in the developing world. We have developed a new method to simplify this procedure and obtain DNAs from small specimens. As experimental materials, thinly smeared blood on a glass slide or blood filtered with and adhered on polysthylene telephtalate (PST) fibers were used. These materials could be safely stored without interfering with DNA extraction for up to 3 months. The slide materials were digested with proteinase K, and DNA was extracted with Tris-EDTA-phenol:chloroform and precipitated with absolute ethanol. The PST specimens were washed with physiologic saline and treated in the same manner as described above. Products were easily amplified by PCR and digested with restriction endonucleases for beta thalassemia typing as well as for HLA-DQA1 gene typing. Results obtained by this method correlated well with previously reported incidences for thalassemia and HLA-DQA1 types in Thailand. This method can be used in the routine laboratory because it allows for stable and biosafe genetic analyses.

Difference in pattern of erythropoietin response between beta-thalassemia/hemoglobin E children and adults.

Thalassemia is one of the most common genetic disorders in Thailand. The thalassemic patients have many pathophysiologic changes secondary to chronic anemia. During these last few years there have been many trials to cure or improve the anemic condition in thalassemia by using various agents, including erythropoietin (EPO). Thus it is very important to understand the EPO response to different degree of anemia in the thalassemic patients. In this study we evaluated the EPO status in 53 beta-thalassemia/HbE patients, from 4-61 years old, by enzyme-linked immunosorbent assay. The results showed that the levels of EPO in beta-thalassemia/HbE patients were much higher than in normal control subjects: mean +/- SE = 527 +/- 183.20 and 3.45 +/- 0.47 mIU/ml respectively. The reverse correlation between the levels of EPO and hematocrit (r = -0.704) was also observed. There was also a tendency to have higher levels of EPO in beta-thal/HbE children than in adults, although this was statistically insignificant. The observed versus predicted levels of EPO (log O/P ratio) showed that most patients had good EPO response to the degree of anemia. However, inappropriate decrease of EPO response was observed in 8/40 adult patients. The EPO levels in these patients were not correlated with any physical or laboratory studies, including kidney function. We thus propose that if EPO is to be considered as one of the alternative treatment to the thalassemic patients, in the future, it may benefit only the patients with low EPO levels.

A double-blind placebo control trial of dilazep in beta-thalassemia/hemoglobin E patients.

Since the obtained results from the pilot study indicated that dilazep which was a membrane stabilizer would be benefit to treatment and prevention of anemia and chronic leg ulcer in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients, the authors had continued the study in a second phase, ie a double blind placebo control trial. Twenty-seven beta-thal/HbE patients were recruited in the study. Eight patients who suffered from chronic leg ulcer were given dilazep. The rest of patients were given dilazep or placebo according to a randomized table. Hence, 16 patients received dilazep and 11 received placebo. When we compared the number of unit of blood transfusion, hemoglobin level, 2-3 DPG and P50 value between the dilazep and placebo groups using unpaired t-test, we found that there were no statistical differences in any of the parameters. However, when we compared the data within the group using paired t-test, there was statistical decrease in blood requirement after treatment in the dilazep group (p < 0.05). Concerning with the treatment of chronic leg ulcer, 3 in 8 patients were completely healed within 3 months, 4 in 8 patients were improved and 1 in 8 patients was not improved. There were complaints of skin itching and mild epigastric pain in placebo group but the liver function tests, kidney function tests and cardiac enzyme did not significantly change during the medication.

The spectrum of multiple myeloma: diagnostic and biological implications.

Myeloma is a common and well-studied hematopoietic neoplasm with an impressive spectrum of clinical, laboratory, and histological findings. To enhance our understanding of the diversity of myeloma, including its earliest forms, the clinical and pathological findings in 145 cases of myeloma were documented and analyzed. Our analysis indicated that myeloma has at least two distinct subtypes: one presenting with bone lesions and a nodular growth pattern and the other presenting with anemia and an infiltrative growth pattern. The relationship of these two forms to plasma cell biology is not clear, although both types appear to arise in the marrow. The criteria used in this study identified 85% of cases overall, with a range of 70% to 100%, depending on clinical presentation. Immunoperoxidase studies are required to establish the diagnosis in patients with early marrow involvement. Myeloma in younger patients appears to be clinically and pathologically similar to myeloma in older patients. Factors such as dysplasia, immunoglobulin type, or leukemic phase were evenly distributed among clinical presentations and did not apparently identify clinicopathological subtypes of myeloma.

Determination of B-cell clonality in paraffin-embedded endoscopic biopsy specimens of abnormal lymphocytic infiltrates and gastrointestinal lymphoma by polymerase chain reaction.

External and seminested polymerase chain reaction techniques were used to determine B-cell clonality in paraffin-embedded biopsy specimens of abnormal lymphocytic infiltrates and malignant lymphomas of the gastrointestinal tract. Using consensus primers for the variable and joining regions, the authors detected clonal immunoglobulin heavy-chain gene rearrangements in five of eight endoscopic biopsy specimens (62.5%) and six of eight resection specimens (75%) of well-characterized B-cell gastrointestinal lymphomas. No clonal rearrangements were detected in 21 negative controls including 7 cases of chronic gastritis and 7 cases of Crohn's disease. In endoscopic biopsy specimens of eight patients with abnormal lymphocytic infiltrates, clonal immunoglobulin heavy-chain gene rearrangement was found in three of six cases (50%) in whom gastrointestinal involvement by lymphoma was subsequently established. Therefore, polymerase chain reaction may be used to demonstrate B-cell clonality in paraffin-embedded endoscopic biopsy specimens of abnormal lymphocytic infiltrates and may circumvent the need for more invasive procedures.

Diagnostic criteria and histologic grading in multiple myeloma: histologic and immunohistologic analysis of 176 cases with clinical correlation.

Diagnostic criteria in myeloma have not been completely standardized or tested for accuracy; furthermore, marrow findings of prognostic value have not been clearly identified. We studied 176 patients with myeloma to determine the relative value of marrow differential, tissue sections, and immunohistology singly or in concert in the diagnosis of myeloma and to correlate morphologic features with prognosis. Controls were patients with benign marrow plasmacytosis. Homogeneous nodules of plasma cells at least 1/2 high-power field and/or monotypic aggregates of plasma cells filling at least one interfatty marrow space correctly identified myeloma in 83.5% of cases, with no false positives. The current numerical criteria of marrow plasmacytosis > or = 10% occurred in 17.1% of the controls, and 39.7% of patients with myeloma had less than 10% marrow plasmacytosis at presentation. Myeloma was graded histologically into categories of none/minimal, moderate, and marked dysplasia on the basis of dysplastic features and mitoses; these categories correlated well with clinical outcome, with median length of survival of 32.9, 25.2, and 12.9 months, respectively (overall median length of survival of 123 patients with myeloma, 29.2 months). Packing of marrow by tumor and mitoses measuring at least 5/high-power field regardless of grade also was associated with a poor prognosis (median lengths of survival, 15.2 and 11 months, respectively). Myeloma may be diagnosed in the great majority of cases by demonstrating homogeneous nodules and/or monotypic aggregates of plasma cells in the marrow. Prognostic features were shown to include marked dysplasia, mitoses, packing of marrow by tumor, and clinical stage.

Detection of clonal immunoglobulin heavy chain gene rearrangements by polymerase chain reaction in scrapings from archival hematoxylin and eosin-stained histologic sections: implications for molecular genetic studies of focal pathologic lesions.

Using a simple scraping technique to obtain DNA directly from archival hematoxylin and eosin-stained slides, we successfully amplified clonal immunoglobulin heavy chain gene rearrangements (IGR) from lymphomatous infiltrates, as small as 1 mm2. The fragments amplified by the polymerase chain reaction (PCR) were identical in size to those from corresponding whole unstained sections freshly cut from the paraffin-embedded blocks. Using this technique, we detected clonal IGR from the scraping of a small lymphomatous nodule in the colon, although no amplified fragments were detected from the whole section. Furthermore, we demonstrated that two morphologically different areas in a case of B-cell lymphoma have identical amplified fragments. It is important that no amplified fragments were detected in scrapings from adjacent nonneoplastic areas. Although DNA recovered from scrapings was partially degraded, fragments as large as 725 base pairs were successfully amplified from a slide stored more than 11 years. This technique thus allows detection of clonal IGR in tissues focally involved by B-cell lymphoma and molecular genetic studies of focal pathologic lesions as an alternative to in situ hybridization or in situ PCR. Finally, this technique can be applied to archival slides when tissue blocks are not available.