Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

Diagnosis of dihydropyrimidinase deficiency in a Chinese boy with dihydropyrimidinuria.

Dihydropyrimidinase deficiency is an autosomal recessive inborn error of metabolism characterised by the presence of dihydropyrimidinuria. Its clinical presentation is variable and has also been reported in asymptomatic subjects. We report the first case of dihydropyrimidinase deficiency in Hong Kong, which is also the first reported in a Chinese subject. The patient was a 32-month-old boy who presented with language development delay. Biochemical analysis confirmed markedly increased urinary excretion of dihydrouracil and dihydrothymine, whilst DNA testing confirmed that the patient was compound heterozygous for two missense mutations, one known (p.R302Q) and the other was novel (p.N16K).

Helicobacter pylori-negative duodenal ulcer.

UNLABELLED: PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.

Ulcer risk factors: interactions between Helicobacter pylori infection, nonsteroidal use, and age.

PURPOSE: To evaluate the influence of Helicobacter pylori, nonsteroidal anti-inflammatory drug (NSAID) use, tobacco and alcohol use, age, gender, ethnic group, and the indication for endoscopy on the frequency of gastric and duodenal ulcers in patients referred for upper endoscopy. PATIENTS AND METHODS: One thousand eighty-eight consecutive patients without prior antrectomy or active bleeding at endoscopy who were able to provide a history were interviewed prior to endoscopy, and antral biopsies were performed for H. pylori at endoscopy. Variables were tested for univariate association with duodenal or gastric ulcer and those variables with p < 0.25 were included in the logistic regression model building. RESULTS: One hundred seven patients had duodenal ulcer, 97 had gastric ulcers, and 5 had both. Significant risk factors in the final model for duodenal ulcer were H. pylori, history of previous ulcer, male gender, bleeding, and pain at presentation (p < 0.001), whereas alcohol was associated with a decreased risk (p = 0.026). H. pylori presence (p = 0.011), aspirin use (p = 0.009), and bleeding (p = 0.012) were associated with gastric ulcer in the final model; esophageal symptoms were associated with decreased risk of gastric ulcer (p = 0.003). NSAID use was associated with gastric ulcers only in those over 55 (p < 0.05), especially whites, and in nonwhites without prior ulcer. There was no interaction between H. pylori and NSAIDs. CONCLUSIONS: H. pylori was associated with an increased risk of duodenal and gastric ulcers. Aspirin increases the risk for gastric ulcer in patients of all ages, whereas nonaspirin, nonsteroidal use increases the risk for gastric ulcers to varying degrees in patients over age 55, depending on race and history of ulcer.

Intravenous leiomyoblastoma.

A unique case of leiomyoblastoma involving the veins and venules of the skin and subcutaneous space is reported. There was no evidence of recurrence or metastasis 1 1/2 years after excision.

Hepatocellular adenoma of the placenta.

A unique primary placental tumor, designated "hepatocellular adenoma of the placenta," is reported. The tumor was composed of cells resembling fetal hepatocytes. The hepatocellular nature of the tumor cells was supported by ultrastructural and immunohistochemical findings. Histogenetically, this tumor most likely represents a highly specialized monodermal teratoma.

Clear cell myeloma.

We report a case of clear cell myeloma misinterpreted at initial biopsy as liposarcoma. The patient had lytic skeletal lesions and monoclonal IgA, kappa, serum immunoglobulin. The tumor cells contained cytoplasmic vacuoles that produced a clear histologic appearance. The light-microscopic and ultrastructural findings are compared with those of other cases of lymphoplasmacytic disorders with prominent cytoplasmic inclusions.

Hemangiomas with localized nodular proliferation of the liver. A suggestion on the pathogenesis of focal nodular hyperplasia.

Multiple cavernous hemangiomas circumscribed by focal regenerative nodules of hepatocytes were incidental findings at the autopsy of two elderly men. Neither patient was on steroids or had venous thrombosis. The lesions were not typical for other nodular proliferations of the liver, such as focal nodular hyperplasia, nodular regenerative hyperplasia, or liver cell adenoma, and they have not been previously reported. We also explore the roles of vascular malformation, oral contraceptives, and thrombosis in the pathogenesis of localized nodular proliferation of the liver.

Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells.

Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the scrotum, one from the penis, and one from the nose) and one histologic "simulant" (from skin of the nose) were studied. The lesions were solitary, raised, or polypoid with cup-shaped craters filled with parakeratotic cells that blended into keratinocytes of an acanthotic and papillomatous epidermis. There was a neutrophilic infiltrate of varying intensity between plump parakeratotic cells and keratinocytes, near the surface of the epidermis. Aggregates of foam cells were present in the papillary dermis, which was highly vascular. A plasma cell predominant infiltrate was seen at the base in a bandlike fashion. Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case. The foam cells were weakly positive for cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac 387 immunostain showed focal weak staining in foam cells. We postulate that a cascade of events pursue after initial keratinocytic damage attracting neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by dermal dendrocytes, eventually leading to the ultimate manifestation of the lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on our findings, we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated squamoproliferative lesion and that the foam cells, a histologic hallmark of the lesion, are most likely derived from dermal dendritic cells.

Diversion colitis: a clinicopathologic study of 21 cases.

Inflammation occurring in a defunctionalized portion of bowel, following either ileostomy or colostomy, has long been recognized by endoscopists. However, little has been written about this entity, particularly the histopathologic changes. Glotzer et al in 1981 described 10 cases, and coined the term "diversion colitis". We studied 21 patients without previous history of inflammatory bowel disease who, for reasons including perforated diverticulitis, carcinoma, or trauma, had loop colostomies or Hartmann's procedure performed. Many of these patients became symptomatic with complaints related to the defunctionalized bowel, including rectal discomfort, pain, discharge, and bleeding. Nineteen patients had endoscopic examinations, which revealed a variety of findings including mucous plugs, friability, petechia, erythema, ulcers, exudate, and nodules or polyps. All except one case had tissue from the excluded portions of bowel available for pathologic examination. Most displayed nonspecific changes with mild-to-moderate lymphoplasmacytic infiltrates in the lamina propria, mild architectural alterations of the crypts, and slight decrease in crypt numbers. Ulceration, cryptitis, and crypt abscesses simulating ulcerative colitis were uncommon findings and were observed almost exclusively in more severe cases. Granulomas were observed in two cases, raising the possibility of Crohn's disease.

Immunohistochemical characterization of atypical fibroxanthoma and dermatofibrosarcoma protuberans.

Atypical fibroxanthoma (AFX) and dermatofibrosarcoma protuberans (DFSP) have generated undue interest regarding their histogenesis, biological behavior, and differentiation from other forms of spindle cell tumors of the skin, including spindle cell squamous carcinomas and desmoplastic melanomas. To identify characteristic immunophenotypes, 12 AFXs and 15 DFSPs were examined with a panel of antibodies against cytokeratin; vimentin; desmin; proteolytic enzymes (alpha-1-antitrypsin and alpha-1-antichymotrypsin); melanoma-associated antigens defined by HMB-45, HMB-50, and NKI/C3; muscle-specific actin (HHF-35); and S-100 protein. The staining patterns of these two tumors were nearly identical. All cases tested negative for cytokeratin, desmin, and S-100 protein and strongly positive for vimentin. Six (50%) AFXs and 12 (80%) DFSPs tested focally positive for muscle-specific actin. None of the cases were reactive with melanoma antibodies HMB-45 and HMB-50; NKI/C3 strongly stained 26 of 27 tumors. Compared to HMB-45 and HMB-50, NKI/C3 cross-reacted with nonmelanocytic neoplasms. Two AFXs stained for alpha-1-antitrypsin and alpha-1-antichymotrypsin. This study confirms (1) the immunophenotypic similarity of AFX and DFSP, (2) the presence of myofibroblastic differentiation in both tumors, as reflected by HHF-35 staining, and (3) that AFX and DFSP are easily distinguished from spindle cell squamous carcinoma and desmoplastic melanoma by the absence of cytokeratin, HMB-45, and HMB-50 staining.

Ki-67 and proliferating cell nuclear antigen tumor proliferative indices in DNA diploid colorectal adenocarcinomas. Correlation with histopathologic characteristics and cell cycle analysis with two-color DNA flow cytometry.

The prognostic significance of tumor proliferative activity (TPA) in colorectal adenocarcinomas (CA) determined by proliferating cell nuclear antigen (PCNA) and Ki-67 staining is not well defined. Previous investigations of TPA using Ki-67 immunohistologic studies and flow cytometric (FCM) analysis have found no correlation with conventional histopathologic parameters. To better define the relationship of these various TPA measurements in CA, the authors selected 46 tumors with diploid DNA content previously analyzed by two-color DNA FCM analysis of fresh specimens to more effectively assess actual S-phase fractions (SPFs) from cytokeratin-gated DNA histograms for comparison with the following: (1) immunohistologic Ki-67 and PCNA tumor proliferation indices (TPIs); and (2) conventional histopathologic observations of prognostic import. These data show no significant correlation coefficient between Ki-67 or PCNA TPIs and SPFs derived from FCM analysis; however, the DNA diploid tumor subset categorized as having a greater than median SPF value had a significantly higher mean Ki-67 but not PCNA proliferation index. There was no correlation of any measure of proliferation with any of the eight histopathologic features of known prognostic significance.

Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome.

Morphologic studies of gastric stromal tumors (GSTs) indicate that mitotic counts (MCs) and tumor size are major discriminants predictive of biologic behavior. The authors evaluated the tumor proliferation of GSTs with anti-proliferating cell nuclear antigen (PCNA; DAKO clone PC10, DAKO Corporation, Carpinteria, CA) for correlation with MCs, histologic cell type, and clinical outcome. Fifty-eight tumors ranging from 1.5 to 45 cm in size were selected for clinicopathologic assessment. Mitotic activity was counted per 50 high-power fields (MC). For this study, combined parameters of MC and tumor size were used to categorize tumors into three groups: (1) benign: MC less than 5, tumor smaller than 5 cm; (2) borderline: MC less than 5, tumor larger than 5 cm; and (3) malignant: MC greater than 5, tumor any size. The PCNA tumor proliferation index (TPI) was assessed from evaluation of 200 tumor cells per case and expressed as the percentage of cells with positive results. Clinical follow-up was available in 45 cases. None of the 19 benign or 16 borderline tumors recurred or metastasized, whereas 7 of 10 malignant tumors metastasized and 1 of 10 recurred. The mean PCNA TPI values among benign (11.2%), borderline (16%), and malignant (34.5%) tumors were significantly different (P = 0.0002, Kruskal-Wallis test). When the pathologic tumor categories were compared, the mean TPI of benign tumors was significantly different from that of borderline tumors (P = 0.0306, Kruskal-Wallis), and the TPI of borderline tumors was different from that of the malignant tumors (P = 0.0060, Kruskal-Wallis test). The Spearman rank correlation showed a significant relationship between the MC and PCNA TPI (P = 0.0003, r = 0.4543). Logistic regression analysis showed that the TPI, independent of MC and size, contributed significantly (P = 0.00295) to the prediction of outcome. In the malignant group, the mean TPI for malignant tumors with metastases (43.6%) was significantly different (P = 0.0411, Kruskal-Wallis test) from that of malignant tumors without metastases (including the case with probable recurrence) (11.83%). No correlation was found when PCNA TPIs for epithelioid GCTs were compared with those of spindle cell GSTs.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.

Small intestinal stromal tumors: a clinicopathologic study of 20 cases with immunohistochemical assessment of cell differentiation and the prognostic role of proliferation antigens.

Small intestinal stromal tumors (SISTs), similar to their gastric counterpart, are complex because of their divergent cellular differentiation and because of the difficulty in accurately predicting their clinical outcome. We studied a series of 22 SISTs from 20 patients to characterize lineage and investigate prognostic morphologic parameters and possible histologic and immunohistochemical differences from gastric stromal tumors (GSTs) and to determine the potential prognostic value of proliferation markers. Cases were categorized into the three following groups based on mitotic count (MC) per 50 high-power fields and tumor size: (1) benign, n = 6 (< 5 MC, < 5 cm); (2) borderline, n = 6 (< 5 MC, > or = 5 cm); and (3) malignant, n = 10 (> or = 5 MC, any size). For the formalin-fixed, paraffin-embedded tissue sections, an immunohistochemical panel was used to characterize differentiation toward myogenic cells (pan-muscle specific actin [HHF-35], alpha-smooth muscle actin, and desmin), Schwann cells (S-100 protein), enteric glial (glial fibrillary acidic protein), and nerve cells (neurofilament). Cellular proliferative activity was assessed immunohistochemically using monoclonal antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67 antigen (MIB-1) and a tumor proliferation index (TPI) was obtained as the percentage of positive-staining tumor nuclei. Clinical follow-up revealed that none of the benign tumors progressed (mean follow-up, 96 months). Half of the patients with borderline tumors were dead of disease (mean, 50.7 months), while 8 of 9 patients with a malignant tumor died of disease (mean, 24.6 months). By Cox Proportional Hazard Regression analysis, mitotic count, tumor size, and cellularity significantly predicted survival. PCNA, MIB-1, tumor necrosis, and atypia were not significant predictors of survival. All tumors stained with vimentin; 17 (77%) and 13 (59%) of the tumors showed immunoreactivity with muscle-specific actin markers (HHF-35) and alpha-smooth muscle actin, respectively. Only 1 tumor stained with desmin, and none stained with S-100 protein, neurofilament, or glial fibrillary acidic protein. Immunophenotypic characteristics did not differ among the 3 groups. The TPI for PCNA and MIB-1 significantly differed between benign and malignant tumors and between borderline and malignant tumors, but it failed to separate the benign and borderline groups. Compared with 52 cases of GST previously reported by us using the same criteria and antibody panel, these tumors were histologically and immunohistochemically indistinguishable. However, none of the 18 borderline GSTs progressed, while 3 of 6 patients with a borderline SIST died of the disease. Based on this series of 22 SISTs, we conclude the following: (1) MC, size, and cellularity are the best predictors of clinical outcome in SIST. (2) The majority of SISTs show smooth muscle differentiation based on their immunoreactivity with HHF-35 and alpha-smooth muscle actin). (3) The TPI for PCNA and MIB-1 correlated with MC but failed to predict survival for individual cases. (4) SISTs and GSTs are morphologically and immunohistochemically similar; however, SISTs seem to have greater malignant potential than GSTs of similar size.

Benign childhood epilepsy with centrotemporal spikes: a study of 50 Chinese children.

In order to collect local data for children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS), we conducted a retrospective study of 50 Chinese children (32 males and 18 females) with BECTS diagnosed in two regional hospitals in Hong Kong from 1995 to 1998. Their peak age of onset was 7 years (range 3-13 years) and a male predominance was observed. Seven patients (14%) had a past history of febrile convulsions and five cases (10%) had a family history of epilepsy. The presentation was protean, but most of them had infrequent, short, nocturnal generalised seizures. The EEG spike foci were most frequently found in mid-temporal regions, followed by centrotemporal regions. Fourteen percent of children did not require anti-epileptic drug treatment. For those who were treated, they were easily controlled on a low dose of carbamazepine (median dosage of 12.75 mg/kg per day) or sodium valproate (median dosage of 20 mg/kg per day). Our study suggested a generally good prognosis for BECTS. No risk factors of frequent seizure recurrence could be identified.

Primary tracheal neurilemoma: report of a case with ultrastructural examination.

A case of tracheal neurilemoma that was removed by segmental tracheal resection was studied. Only seven other cases of benign neurogenic tracheal tumor (three neurofibromas and four neurilemomas) were found in the literature. Failure to consider this rare tracheal tumor as a cause of respiratory distress has frequently resulted in delay of its recognition.

Retrorectal cystic hamartoma: report of 5 cases with malignancy arising in 2.

BACKGROUND: Retrorectal cystic hamartomas, or tailgut cysts, are rare congenital lesions that typically present as presacral masses. These lesions are frequently clinically unrecognized and misdiagnosed. Malignant change is extremely rare. Only 10 additional cases with associated malignancy were recovered from the literature. We describe the clinicopathologic features of 5 cases, including 2 cases with malignant transformation. RESULTS: All patients were women (age range, 36-69 years). The most common symptoms were pain with defecation and rectal bleeding. One patient was asymptomatic. All lesions presented as multicystic presacral masses and all were surgically resected. The lesions varied in size from approximately 2 to 12 cm (average, 9.5 cm) and overall had similar histology composed of a variety of epithelial linings (stratified squamous, transitional, and simple or ciliated pseudostratified columnar). Skin adnexa, neural elements, and heterologous mesenchymal tissue, discriminators between retrorectal cystic hamartoma and teratoma, were not identified. Arising in association with the cysts was a focus of adenocarcinoma in one case and a neuroendocrine carcinoma in another. CONCLUSIONS: The clinical diagnoses in our cases were often delayed, which in part may be due to unfamiliarity with this entity. The main diagnostic difficulty is distinction from presacral mature cystic teratomas and rectal duplication cysts. Tailgut cysts require complete surgical excisions to prevent future recurrences and to preclude possible malignant transformation. Meticulous gross examination and adequate sampling are important to document the exact nature of these cysts and to rule out possible coexisting malignancies, which may be focal.

Pathologic findings in adrenoleukodystrophy heterozygotes.

Two women, heterozygous for X-linked adrenoleukodystrophy, contained striated adrenocortical cells without inflammation and central nervous system demyelinative lesions. Only one was symptomatic neurologically; neither exhibited hypoadrenalism. These findings further document the variability of adrenoleukodystrophy heterozygotes and provide evidence that the major pathologic differences between hemizygote and heterozygote are quantitative in nature.

Accumulation of biopolymers in activated sludge biomass.

In this study, activated sludge bacteria from a conventional wastewater treatment process were induced to accumulate polyhydroxyalkanoates (PHAs) under different carbon-nitrogen (C:N) ratios. As the C:N ratio increased from 20 to 140, specific polymer yield increased to a maximum of 0.38 g of polymer/g of dry cell mass while specific growth yield decreased. The highest overall polymer production yield of 0.11 g of polymer/g of carbonaceous substrate consumed was achieved using a C:N ratio of 100. Moreover, the composition of polymer accumulated was dependent on the valeric acid content in the feed. Copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] was produced in the presence of valeric acid. The 3-hydroxyvalerate (3HV) mole fraction in the copolymer was linearly related to valeric content in the feed, which reached a maximum of 54% when valeric acid was used as sole carbon source. When the 3HV U in the polymer increased from 0-54 mol%, the melting temperature decreased from 178 degrees to 99 degrees C. Thus, the composition, and hence the mechanical properties, of the copolymer produced from activated sludge can be controlled by adjusting the mole fraction of valeric acid in the feed medium.