Dilation of the ventriculus terminalis: sonographic findings.

A newborn term male infant was found to have the stigmata of VACTERL syndrome, including cervical and thoracic hemivertebra, partial sacral agenesis, 13 pairs of ribs, high imperforate anus with rectovesical fistula, and tracheoesophageal fistula with proximal esophageal atresia. No open spinal dysraphism or skin dimpling was seen. Ultrasonography of the spinal cord was performed to screen for occult anomalies. The examination revealed a lipoma of the filum terminalis and a low-lying conus medullaris at the L3-L4 level with a large central cystic structure in the terminal cord, which was continuous with the central canal (Fig. 1). This was thought to most likely represent a dilated ventriculus terminalis, and the diagnosis was confirmed on a subsequent MR image (Fig. 2). Fluid in the cyst followed cerebrospinal fluid signal in all sequences. We observed no abnormal signal in the adjacent parenchyma or enhancement associated with the cystic mass. A cranial ultrasonogram did not reveal any intracranial anomalies. The patient demonstrated no neurologic deficits in the lower extremities. Bowel and urinary continence was not assessable in this infant.     

Somatic von hippel-lindau mutation in clear cell papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, α₁-antitrypsin, and α₁-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel—Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.     

Differences in lectin binding of malignant pleural mesothelioma and adenocarcinoma of the lung.

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.     

Mutations of the GREAT gene cause cryptorchidism

In humans, failure of testicular descent (cryptorchidism) is one of the most frequent congenital malformations, affecting 1-3% of newborn boys. The clinical consequences of this abnormality are infertility in adulthood and a significantly increased risk of testicular malignancy. Recently, we described a mouse transgene insertional mutation, crsp, causing high intraabdominal cryptorchidism in homozygous males. A candidate gene Great (G-protein-coupled receptor affecting testis descent), was identified within the transgene integration site. Great encodes a seven-transmembrane receptor with a close similarity to the glycoprotein hormone receptors. The Great gene is highly expressed in the gubernaculum, the ligament that controls testicular movement during development, and therefore may be responsible for mediating hormonal signals that affect testicular descent. Here we show that genetic targeting of the Great gene in mice causes infertile bilateral intraabdominal cryptorchidism. The mutant gubernaculae fail to differentiate, indicating that the Great gene controls their development. Mutation screening of the human GREAT gene was performed using DHPLC analysis of the genomic DNA from 60 cryptorchid patients. Nucleotide variations in GREAT cDNA were found in both the patient and the control populations. A unique missense mutation (T222P) in the ectodomain of the GREAT receptor was identified in one of the patients. This mutant receptor fails to respond to ligand stimulation, implicating the GREAT gene in the etiology in some cases of cryptorchidism in humans.     

Fine-needle aspiration of cystic lesions of the kidney. Morphologic spectrum and diagnostic problems in 41 cases

Although imaging studies show the nature of most cystic lesions of the kidney (RCs), many RCs require fine-needle aspiration (FNA) for accurate diagnosis. Interpretation of the FNAs remains challenging. The FNA specimens of 41 RCs were reviewed and correlated with imaging studies. Final diagnoses for 30 cytologically benign lesions were simple cyst (28), acquired cystic kidney (1), and cystic renal carcinoma (1). The fluid from the benign cysts displayed macrophages, epithelial cells from the cyst lining, tubular cells, neutrophils, and Liesegang rings. Fluid from the acquired cystic kidney and the cystic renal cell carcinoma showed features similar to those of the benign cysts. The 9 cases with "suspicious" cytology included 5 complex cystic lesions displaying rare but atypical epithelial cell clusters, 3 low-grade renal cell carcinomas with many mildly atypical papillary clusters of epithelial cells, and 1 simple benign cyst with many tubular cells. The 2 cytologically malignant lesions were cystic renal cell carcinomas with abundant tumor cells with partially clear cytoplasm and atypical nuclei admixed with abundant macrophages and lymphocytes; 1 case developed in a kidney with acquired cystic disease. Simple cysts remain the most frequently aspirated RCs, but complex cystic lesions are increasingly recognized. Since many RCs are composed of independent loculi, a nonrepresentative sample is a potential problem, and cytologic-radiologic correlation becomes mandatory. The "suspicious" patterns identified in this study should serve as diagnostic guidelines and set the foundation for future validation.     

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.     

A new HLA-B allele, B*1565, identified in three unrelated samples

Anew human leukocyte antigen-B allele, B*1565, has been identified during routine typing of cord blood samples. Subsequently, two individuals from the same family as the first cord blood sample plus two unrelated Australian Bone Marrow Donor Registry samples have been found to carry this novel allele.     

Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma

In southern Vietnam, a four-year-old boy presented with severe diarrhea, followed by seizures, coma, and death. The cerebrospinal fluid contained 1 white cell per cubic millimeter, normal glucose levels, and increased levels of protein (0.81 g per liter). The diagnosis of avian influenza A (H5N1) was established by isolation of the virus from cerebrospinal fluid, fecal, throat, and serum specimens. The patient's nine-year-old sister had died from a similar syndrome two weeks earlier. In both siblings, the clinical diagnosis was acute encephalitis. Neither patient had respiratory symptoms at presentation. These cases suggest that the spectrum of influenza H5N1 is wider than previously thought.     

Pheochromocytoma associated with neuroendocrine carcinoma. A new type of composite pheochromocytoma

The coexistence of pheochromocytoma and other tumor types in a single adrenal gland has been rarely documented. This type of pheochromocytoma is designated "composite" or "mixed," depending on whether the pheochromocytoma and the nonpheochromocytoma components show the same embryologic origin. The nonpheochromocytoma components reported in the composite pheochromocytoma include ganglioneuroma, ganglioneuroblastoma, neuroblastoma, and malignant schwannoma. The components found in the mixed pheochromocytoma include adrenal cortical neoplasms and spindle cell sarcoma. We report a unique case of composite pheochromocytoma in which the nonpheochromocytoma element is a neuroendocrine carcinoma. The histologic and the immunohistochemical profiles of the 2 distinct components of this tumor were typical for those of pheochromocytoma and neuroendocrine carcinoma. This dual differentiation was also supported by ultrastructural findings. This case not only broadens the morphologic spectrum of composite pheochromocytoma but also provides some additional insight into the histogenesis of this rare but fascinating type of tumor.