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To study the proteomics of papillary thyroid carcinoma (PTC), and to detect the differential expression of proteins compared to normal thyroid (NT) tissue.Protein extracts of papillary thyroid carcinoma and normal thyroid tissues from 10 patients were separated by proteomics technique and identified using Image Master software. The selected differential proteins were sent to Proteomics Research Center of Chinese Academy of Medical Sciences for mass-spectrometry identification.The basic 2-dimensional electrophoresis (2-DE) images of PTC and NT were obtained, and four potential differential expression spots were selected for mass-spectrometry identification. Among them, annexin I, peroxiredoxin I, mitochondrial aconitase were up-regulated while carbonic anhydrase I was down-regulated.Proteomics may provide a new direction to study PTC, by identifying some tumor-specific markers, leading to elucidation of the mechanism of tumorigenesis and identification of therapeutic targets.

To analyze the clinical characters and prognosis of postpartum choriocarcinoma.Retrospective analysis of 103 patients diagnosed with postpartum choriocarcinoma in Peking Union Medical College Hospital between 1985 and 2005 was performed.In a total of 103 cases of postpartum choriocarcinoma treated with multiagent cytotoxic chemotherapy and combined modality therapy, 92 patients (89.3%) achieved a complete remission while 2 patients had a partial remission, and 9 patients died. Regarding 25 cases with chemorefractory choriocarcinoma and 4 relapsed cases, 18 and 3 cases achieved a complete remission respectively. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system, 17 cases were at FIGO stage I, 8 cases at stage II, 56 cases at stage III, and 22 cases at stage IV. Complete remission was achieved in 100%, 8/8, 95% and 64% respectively. Thirty-five cases in low risk group had FIGO scoresor = 6, and all achieved a complete remission. Of 68 cases in high risk group with FIGO scoresor = 7, 57 (84%) of them obtained a complete remission. There were significant differences in the two groups (P0.05).Postpartum choriocarcinoma could have an increasing probability of cure with early diagnosis and the use of modern multiagent cytotoxic chemotherapy and combined modality therapy.

To analyze the clinical and pathologic characteristics of placental site trophoblastic tumor (PSTT) cases and to discuss the diagnosis, treatment and prognosis of PSTT.The clinical and pathologic data on 11 patients with PSTT at Peking Union Medical College Hospital (PUMCH) from 2000 to 2005 were analyzed retrospectively using SPSS 11.0 software (Chicago, Illinois).Between 2000 and 2005, 635 patients with gestational trophoblastic neoplasms were treated at PUMCH, 11 with PSTT (1.73%). The mean age was 36 years. The antecedent pregnancy was molar in 5 cases (45.5%), full-term delivery in 4 cases (36.4%) and missed abortion in 2 cases (18.2%). The mean interval from the antecedent pregnancy to diagnosis was 16 months. The most common presentations were vaginal bleeding (72.7%) and amenorrhea (63.6%). All patients were pathologically diagnosed, in most cases with human placental lactogen immunohistochemical stain. Chemotherapy and hysterectomy were performed on all patients. Nine complete remissions and 1 partial remission were attained after therapy.Pathologic diagnosis of PSTT was the gold standard. Multidrug chemotherapy combined with hysterectomy was effective in metastasis cases. (J Re

Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P

Primary thyroid lymphomas (PTLs) are closely correlated with the autoimmune reaction of thyroid. However, the molecular mechanisms of PTLs are still unclear. It is really necessary to improve the ability to differentiate between benign and malignant PTLs along with the introduction of some new molecular biology methods. The diagnosis and prognosis of PTLs depend on their histological features, pathological classification, and clinical stages. Customized therapy of PTLs becomes possible with the further advances in lymphoma's pathological classification, clinical stages, and international prognosis index standard.

To determine the parental origin of the genome in the molar pregnancies of two familes with familial recurrent hydatidiform mole (FRHM) and to investigate whether the gene responsible for FRHM is likely to be located within the 19q13.4 region in these familes.The features of complete hydatidiform mole (CHM) were confirmed by pathological examination. DNA of CHM was prepared from sections of formalin-fixed paraffin-embedded blocks of molar tissue following laser capture microdissection. The polymerace chain reaction was used to amplify microsatellite polymorphisms in DNA from the patients, their husbands and the captured molar tissue. Parental contributions to the molar tissue were determined using ABI 310 GeneScan software. Genotyping and haplotype analysis of the candidate region on 19q13.4 was performed for members of both families using 25 microsatellite markers.One CHM from each family was identified as a biparental complete hydatidiform mole. All patients were heterozygous for most of the markers in the chromosome region of interest. In addition the two affected sisters in one of the families had different genotypes for the 19q13.4 region, suggesting that mutations in a different locus might be responsible for the disorder in this family.The location of the gene responsible for FRHM is unlikely to be located in the 19q13.4 chromosomal region in these two families suggesting that FRHM shows genetic heterogeneity.

To study the immunoglobulin gene rearrangement patterns in Hashimoto's thyroiditis (HT) and primary thyroid lymphoma (PTL), and to analyze the relationship between the two diseases.Formalin-fixed and paraffin-embedded tissues of 11 cases of PTL and 38 cases of HT as well as their clinical data, were retrieved. The latter group was further subcategorized into classic HT and suspicious PTL. Gene rearrangement studies for immunoglobulin heavy chains and light chains were carried out by polymerase chain reaction (PCR) using VH, FR3A and FR3kappa primers.There was an increasing trend in immunoglobulin gene rearrangement rate for classic HT (10.7%), suspicious PTL (40.0%) and PTL (72.7%) groups. In general, a female predilection was observed. This sex predilection however was less obvious in the PTL group. There was no relationship between serum antibody (both thyroglobulin and thyroid peroxidase) titers and gene rearrangement patterns.HT and PTL show morphologic overlaps and may not be clearly distinguished on the basis of light microscopy alone. PCR-based immunoglobulin gene rearrangement study may be helpful in the detection of cases with early lymphomatous transformation of HT.

To determine the characteristics of anatomical distribution of pelvic endometriosis and the correlation between visual and histologic findings of endometriosis at laparoscopy.A prospective study of 62 patients undergoing laparoscopy for the pelvic pain, infertility and/or pelvic masses was carried out. All lesions with the diagnosis of endometriosis laparoscopically were excised and examined pathologically. Normal-appearing peritoneal biopsies were obtained randomly. All lesions were identified by anatomical site and color of the foci. The positive predictive value (PPV), sensitivity, negative predictive value (NPV), and specificity were determined for visually identified endometriosis versus the histologic findings.Totally, 219 peritoneal endometriotic lesions, 54 normal peritoneal biopsies, and 71 ovarian endometriotic cysts were obtained. Peritoneal lesions tended to locate in posterior part of the pelvis (80.8%, 177/219) and in left (58.0%, 127/219) with most in black (39.2%). The PPV was 67.6%; sensitivity, 93.7%; NPV, 81.4%; and specificity, 38.3% for visual versus histologic diagnosis of peritoneal endometriosis. Lesions in black or from sacral ligaments were confirmed histologically in 94.2% and 84.7% respectively, and 80.3% (57/71) of ovarian endometriotic cysts diagnosed by laparoscopy were confirmed histologically with 43.6% in the left, 27.3% in the right; and 29.1% (16/55) in both sides of the ovary. In addition, 18.5% (10/54) of normal-appearing peritoneal biopsy were identified as endometriosis by pathological examination. Laparoscopy was confirmed to be in 100% diagnostic accordance with pathology for patients with endometriosis.Our study showed asymmetrical distribution of pelvic endometriosis. Peritoneal lesions in black or from sacral ligament are more likely to be histologically confirmed, and microscopic lesions are not a rare phenomenon of endometriosis.

To study the clinicopathologic features of osteomalacia or rickets-associated mesenchymal tumors.The clinical and pathologic findings of 10 cases of osteomalacia or rickets-associated mesenchymal tumors were evaluated. Hematoxylin and eosin stain, immunohistochemistry and histochemistry were performed on the archival paraffin sections.Amongst the 10 patients studied, 6 were males and 4 were females. Their age at the time of operation ranged from 28 to 69 years ( mean = 45.6 years). A history of long-standing bone pain, arthralgia, limitation in movement, hypophosphatemia and hyperphosphaturia was present in all cases. The duration of symptoms ranged from 2 to 27 years (mean = 9.6 years). The tumor size ranged from 1 to 7 cm (mean size = 3.52 cm). Microscopically, the tumors were composed of various mesenchymal cells, including spindled fibroblast-like cells, adipocytes, chondroid cells and mucinous cells. The background was rich in blood vessels. In 8 of the 10 cases, there was also dystrophic calcification in an unusual flocculent or "grungy" pattern. Peripheral woven bone shell formation was noted in 2 cases and non-urate crystal deposition in 2 cases. Mitotic figures were rare in 9 cases. In 1 of the 10 cases however, mitotic figures and bizarre cells were commonly encountered. On immunohistochemical study, the tumor cells were all positive for vimentin. There was focal positivity for smooth muscle actin and CD34 in 5 and 3 cases respectively. The staining for desmin, S-100 and AE1/AE3 was negative. Ki-67 proliferation index was less than 4% in 8 cases and 30% in 1 case. Alcian blue-positive mucinous matrix and mucinous degeneration around vessels were noted in 8 cases.Most of the osteomalacia or rickets-associated tumors are either benign or low-grade malignant mesenchymal tumors. They can be mistaken as other neoplasms due to the morphologic heterogeneity present. Thorough understanding of the associated clinical features and laboratory investigation results is helpful in arriving at the correct diagnosis.

To investigate the clinical and pathological characteristics, treatment measures and prognosis of pseudomyxoma peritonei (PMP).The clinical records and follow-up data of the patients with PMP were retrospectively analyzed. Survival analysis (Kaplan-Meier method and Cox regression) was used to investigate the prognosis.Thirty-three patients (twenty-two women, eleven men) have a median interval between onset and definite diagnosis of 12 months with an average age of 50. The main clinical presentation includes bloating, abdominal mass and abdominal distention. A delay in diagnosis is common and many patients are labeled as other diseases (84.8%). Positive results were often found in the assistant examinations such as erythrocyte sedimentation rate, gastrointestinal tumor markers (carcinoembryonic antigen, carcinomatous antigen 19-9 and so on), imaging (B ultrasound and computer tomography) and abdominal paracentesis which was usually unsuccessful. The most frequently practiced approach is debulking surgery with the main assistant means of chemotherapy which was lack of the uniform rationale. Benign type of pathological samples accounts for 66.7% of all, while mid-type 21.2% and malignant 12.1%. The general median survival time is 70 months with a follow-up rate of 79%. The pathological type and chemotherapy are main factors which influence the cumulative survival rate (P0.05). Up to the end of 2004, sixteen patients died of various complications, multiple organ failure and severe infection, while ten patients survival and seven patients lost.PMP is a rare condition of borderline malignancy with its unique clinical and pathological characteristics. Gastrointestinal tumor markers, imaging and abdominal paracentesis are very important to the diagnosis. The existing treatment measures need to be improved further. The pathological type and chemotherapy are main factors which influence the prognosis.

To investigate surgical treatment results and clinical pathological specifics in the treatment of non-functional islet cell tumor.To perform retrospective analysis of 78 cases of non-functional islet cell tumor treated at Peking Union Medical College Hospital from July 1968 through January 2005, and summarize clinical symptoms and signs, primary diagnosis before surgery, surgical treatment, pathologic specifics and immuno-histological analysis.Of 78 cases, 27 cases (34.6%) was found in physical examinations, the most common symptoms was upper abdominal pain and upper abdominal discomfort, 30.7% (24 cases) and 26.9% (21 cases) respectively; the most common sign being abdominal masses 35.9% (28 cases). B-us and CT are most commonly used forms of preoperative examination, with positive rates being 98.6% (71/72), 100% (53/53) respectively. Operative mortality was 1.28%, Radical surgery of malignant cases with 5 year survival rate 75% (9/12). Immuno-histological examinations showed that tumors with multi peptide linked hormones 78.6% (55/70), a larger number of positive examinations of neuron specific enolase and chromaffin, 91.4% (32/35) and 79.4% (27/34) respectively. Insulin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide and gastrin positive rates are 64.6% (42/65), 47.5% (22/53), 45.8% (22/48), 37.5% (21/56), 23.9% (11/46) and 22.6% (7/31).Non-functional islet cell tumor lack specificity, Bus and CT are primary examination methods, immuno-histological analysis indicates various different hormones, but lacks the presence of related clinical symptoms. Surgery is an effective form of treatment in the treatment of non-functional islet cell tumor, even with distal metastasis, immediate surgical removal and treatment, extend prognosis.

BACKGROUND: Familial recurrent hydatidiform mole is an extremely rare autosomal recessive condition in which affected individuals have a predisposition to molar pregnancies that are diploid but biparental, rather than androgenetic, in origin. A gene for this condition has been previously mapped to a 1.1 Mb region of chromosome 19q13.4. However, investigation of further families is needed to refine the location of the specific gene(s) involved. METHODS: We have recently identified two novel Chinese families in which four affected women had recurrent pregnancy loss including 14 complete hydatidiform moles (CHM). Fluorescent microsatellite genotyping was used to determine the origin of CHM in both families. Using a panel of polymorphic microsatellite markers, genotyping and haplotype analysis of the 19q13.4 chromosomal region was performed in both families. RESULTS: Genotyping of CHM from affected individuals confirmed their biparental origin and diagnosis of familial recurrent hydatidiform mole in both families. However, no significant homozygosity for the 19q13.4 candidate region was found in affected members of either family. CONCLUSION: Genotyping and haplotype analysis has shown that a mutation in 19q13.4 is unlikely to be responsible for recurrent CHM in the two Chinese families investigated and provides further evidence to support the hypothesis that, although extremely rare, this condition shows genetic heterogeneity.

To analyze the clinical characteristics of nonfunctioning pheochromocytoma, and to evaluate the efficacy of 131I-metaiodobenzylguanidine (MIBG) scan in the diagnosis and perioperative treatment of nonfunctioning pheochromocytoma.The clinical data of 14 patients with nonfunctioning pheochromocytoma were analyzed retrospectively. Plasma free corticoid, renin, aldosterone, and urine catecholamines levels were estimated. B-mode ultrasonography, computed tomography scan, thoracic X-ray and 131I-MIBG were used.All patients with nonfunctioning pheochromocytoma had no hypertension and the tumors were found incidentally. The 24 hours urine catecholamines levels in 80% (8/10) patients were normal. The positive rate of 131-MIBG was 80% (8/10) and the specificity was 100%. All patients underwent surgical operation of tumor resection. No preoperative volume expansion was given to all patients. All tumors were resected completely, and no death accident happened. There was no recurrence and metastasis after operation by long-term follow-up.131I-MIBG scan is the first choice technique for the diagnosis of nonfunctioning pheochromocytoma. Blood volume expansion is unnecessary before resection of pheochromocytoma.

To determine the expression status of survivin gene in pancreatic carcinoma.Expression of survivin gene was evaluated by immunohistochemistry, Western Blot and RT-PCR in 59 cases of pancreatic carcinoma along with their corresponding adjacent benign tissues, 11 cases of chronic pancreatitis, and 7 pancreatic carcinoma cell lines.The positive expression rate of survivin in pancreatic carcinoma was 72.8% (43/59). There was no relationship between the expression of survivin and tumor stage and differentiation. No expression of survivin was detected in benign tissue adjacent to the tumors as well as in samples of chronic pancreatitis. All 7 pancreatic carcinoma cell lines showed a positive expression of survivin mRNA and protein.The expression of survivin appears to be tumor specific to some extent in our pancreatic carcinoma samples. Survivin may be an ideal target for therapy against pancreatic carcinoma.

A large number of data derived from molecular analyses support the hypothesis that human cancer is a genetic disease and a distinct subset of genes have been found to be genetically changed in most tumors. Molecular alterations in pancreatic cancer include: (1) oncogenes such as K-ras, c-myc, c-fos, and c-erbB-2; (2) tumor suppressor genes such as p53, p16, DPC4/SMAD4, and DCC; and (3) growth factors such as EGF, FGF, HGF, PDGF, VEGF, TGF-beta. Genetic alterations of K-ras and p53 are common in human pancreatic cancer, but the occurrence of pancreatic cancer is a multi-step phenomenon in which the accumulation of genetic changes is extremely important.

Background. Uterine leiomyoma with lymphoid infiltration is a rare disease that simulates malignant lymphoma with only nine cases reported to date. We describe the first case of uterine adenomyoma with lymphoid infiltration simulating lymphoma. Case. The specimen resected from a 30-year-old Chinese woman was a well-defined firm nodule measuring 5 × 5.5 × 5.5 cm. The cut surface was similar to that of adenomyoma, which contained dark brown spots and a cyst. Microscopically, the tumor comprised smooth muscle cells intermixed with many lymphocytes. Many lymphoid follicles were present, just locating beside one side of thin-walled blood vessels and protruding into the vessels. Endometrial-type glands and stroma were visible in the tumor. Conclusion. We describe the first case of uterine adenomyoma with lymphoid infiltration simulating lymphoma.

To analyze the clinical characteristics and treatment of hematogenous disseminated tuberculosis.Twenty-seven cases of hematogenous disseminated tuberculosis diagnosed by autopsy from 1961 to 2000 were retrospectively analyzed.Among these patients the disease was acute in 22 cases (including 3 non-reactive) and chronic in 5. Twenty cases (74%) were misdiagnosed before death, most of which were due to concomitant with or misdiagnosed as connective tissue disease, hematological disease or tumor. 63% of the cases had long-term use of corticosteroids or repeated chemotherapy. Most cases showed atypical clinical manifestations and chest X-ray lesions. The positive rate of tuberculin skin test and sputum for smear were low. Autopsy showed that all cases had active lung tuberculosis and the major extra-pulmonary organs involved were liver, spleen and lymph nodes.Unaware of the risk for tuberculosis among immune compromised patients was the main reason for misdiagnosis and corticosteroid abuse was common. Physician should be alert to the occurrence of hematogenous disseminated tuberculosis, especially in immune compromised patients with long-term fever and systemic injury. Direct smear and cultural examination as well as newer diagnostic approaches with sputum and tissue may be useful for a rapid and correct diagnosis.

To demonstrate the alterations of DPC4/SMAD4/MADH4 gene in paraffin-embedded tissues of pancreatic carcinomas.Forty-six cases of resected specimens containing carcinomatous tissue and normal pancreatic tissue were analysed for possible DPC4 gene mutations by polymerase chain reaction (PCR)and single-strand conformation polymorphism (SSCP). The DNA sequencing technique was applied to determine the patterns of gene mutation in the PCR-SSCP positive cases. Fifty-six cases of pancreatic carcinoma along with the specimens corresponding normal pancreatic tissues were studied by in situ hybridization (ISH) and immunohistochemistry (IHC) techniques for gene expression in mRNA and protein level.The homozygous deletion rate of exon 1, 2, 3, 4, 8, 11 of DPC4 gene in pancreatic carcinoma was 28.26%, while the mutation rate of DPC4 gene was 21.74%. In these tumors, there were 3 cases of nonsense mutation, 5 cases of missense mutation, 1 case of deletion and missense mutation, 1 case of insertion mutation. Positive rates of SMAD4 in carcinomatous tissues detected by the ISH and IHC were 53.57% and 58.93% respectively, whereas they were 91.07% and 89.29% in the matched normal tissue respectively. There were significant difference between cancer and normal tissue (P0.05). Thrity-two cases were positive of DPC4/SMAD4 with all methods mentioned above, the coincident rate was 87.50% (28/32). The coincidence between gene detection and ISH of SMAD4 was 87.50%, and it was 96.88% between gene detection and IHC of SMAD4. Of all 56 cases, the coincidence of the positive rates of SMAD4 detected by ISH and IHC was 91.07%. No significant difference among the positive rates of DPC4/SMAD4 as detected by the three different techniques (P0.05).The main mechanisms of inactivation of DPC4 gene in pancreatic carcinoma are homozygous deletion and mutation. The product of DPC4 expression is significantly decreased in cancer group compared with the normal tissues. As a tumor suppressor gene, DPC4 alteration is an important molecular event in pancreatic carcinoma, and probably plays a crucial role in cancer development and progression.

Ting Gui,1,* Huimin Bai,1,* Jianfang Zeng,1 Zhaoji Zhong,1 Dongyan Cao,1 Quancai Cui,2 Jie Chen,2 Jiaxin Yang,1 Keng Shen11Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China *These authors contributed equally to this work Purpose: To investigate tumor heterogeneity in the recurrence of epithelial ovarian cancer demonstrated by polycomb group (PcG) proteins. Methods: Tissue microarrays containing matched primary and recurrent ovarian tumors from the same patients were constructed for detection of PcG protein expression. Survival analyses of clinicopathological parameters and expression of PcG proteins were performed on progression-free survival (PFS) and overall survival (OS) of patients. Genetic and epigenetic heterogeneity was explored in aspects of gene copy number and microRNA (miRNA) profiling. Results: PcG proteins were heterogeneously expressed in primary versus recurrent tumors (P

OBJECTIVE: It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Based on the identification of tumor suppressor gene HRPT2/CDC73 and its association with hereditary and sporadic PC, screening of gene mutations and detection of parafibromin immunoreactivity have been suggested as diagnostic instruments of PC in Whites. There is little information about HRPT2/CDC73 mutations and its corresponding protein expression in patients with sporadic PC in Chinese population, and the long-term follow-up data is scarce. METHODS: Paraffin-embedded tissues were obtained from 13 patients with PC, 13 patients with parathyroid adenoma (PA) and 7 patients with parathyroid hyperplasia(PH), and 6 normal parathyroid (NP) tissues as controls. Peripheral blood from 11 patients with PC was collected. PCR products using Genomic DNA extracted from tumor tissues or blood as template was sequenced for HRPT2/CDC73 gene. Expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis. RESULTS: Six mutations in 6 of 13 patients with PC were identified, with three being novel. Four of them were germ-line mutations. Patients with mutations were susceptible to recurrence of the PC. Complete (8/13, 61.5%) or partial (5/13, 38.5%) loss of parafibromin expression was observed in PC tissues. All of tissue samples from normal parathyroid or benign parathyroid tumors displayed positive immunostaining of parafibromin except one adenoma. CONCLUSIONS: The present study supplies information on the mutations and protein expression of HRPT2/CDC73 gene and phenotypes of parathyroid carcinoma in Chinese population. And the expanded mutation database of this gene may benefit patients in the diagnosis and treatment of this disease.

The pathophysiological, biochemical, histological, ultrastructural, and immunohistochemical characters of a case of malignant pancreatic islet cell tumor with watery diarrhea syndrome were carefully investigated. Four hormones or mediators--somatostatin (SST), vasoactive intestinal peptide (VIP), serotonin, and prostaglandin E--were markedly elevated in the circulation. The diagnosis was further confirmed by exploratory laparotomy and autopsy. The contents of SST and VIP in tumor tissues were very high. Gel chromatography of tumor extract revealed single peaks for both SST and VIP. Immunohistochemical studies of tumor tissues showed numerous immunoreactive cells to anti-SST, moderate amount of VIP-positive cells, and a few hCG-, insulin-, and glucagon-positive cells. In conclusion, this is an unusual case of Verner-Morrison syndrome in which three kinds of bioactive hormones or mediators were simultaneously secreted; peptides, amine, and prostaglandin.

One hundred twenty-seven insulinomas from 95 cases (1 malignant and 94 benign) were studied pathologically. Thirty-six tumors (35 cases) were examined by electron microscopy. Typical beta-cell secretory granules of crystalloid-form cores and/or atypical secretory granules were discerned in all tumors examined. A new type of secretory granule, with high electron-dense crystalloid-form cores and moderate electron-dense granular substance filling the space between the core and the limiting membrane, were observed in two cases. Among 68 insulinomas (67 cases) subjected to immunocytochemical investigations with ten peptide hormones (insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, motilin, secretin, vasoactive intestinal polypeptide (VIP), gastric inhibitory polypeptide (GIP), and neurotensin), 42 were found to be multihormonal, varying from two to four peptides secreted. The hormones contained were insulin, glucagon, PP, somatostatin, and gastrin in different combinations. One patient had hyperinsulinemia and hypergastrinemia concurrently, and two islet tumors were excised at an interval of 10 months. Both electron microscopy and immunocytochemistry confirmed the presence of beta- and alpha-cells in the first tumor, whereas the second tumor revealed only G-cells by electron microscopy, and G- and beta-cells on immunocytochemical staining. The morphologic and immunocytochemical characteristics of the insulinomas in this series are discussed.