Navigating an unexpected diagnosis - experience of a tertiary referral centre with two cases of intraplacental choriocarcinoma.

Intraplacental choriocarcinoma is a rare tumour, with approximately 62 reported cases. It may manifest as a spectrum of disease ranging from an incidental lesion diagnosed on routine placental examination to disseminated maternal and/or neonatal disease. In this case series, we presented two rare cases of intraplacental choriocarcinoma with extremely varied clinical presentations. The extremely varied clinical presentations of both patients described in the case series complicated the process of arriving at the diagnosis. In both cases, subsequent investigations showed no maternal or neonatal metastasis, and maternal serum beta-hCG levels downtrended with conservative management. We aim to highlight the importance of performing a detailed physical examination and evaluation of the patient and multidisciplinary management with oncology opinion. A detailed examination of the placenta should also be considered when faced with obstetric complications so that early diagnosis and the required management can be executed in a prompt fashion.

Effect of long-term omeprazole treatment on antral G and D cells in children.

BACKGROUND: Long-term omeprazole therapy is associated with hypergastrinemia. In the antrum, gastrin secretion from G cells is inhibited in a paracrine manner by somatostatin secreted from D cells. Omeprazole may alter the ratio of G to D cells; however, there are limited data concerning such an effect in humans and none in children. The authors studied the effect of long-term omeprazole therapy on antral G- and D-cell numbers in children. METHODS: Six children received omeprazole for 4 to 7 years for erosive reflux esophagitis. Endoscopic antral biopsy specimens obtained at baseline and at 1, 4, and 7 years of omeprazole administration were immunostained to assess G and D cell numbers per antral gland. The G- and D-cell numbers were also assessed in an age-matched control group consisting of 24 healthy children from six different age groups. RESULTS: The mean G-cell number per unit area showed a significant increase at 4 years (85 +/- 5.7 years) and at 7 years (89 +/- 6.8 years) on omeprazole compared with baseline (56 +/- 4.8 years) ( P < 0.01). D-cell numbers did not change. The ratio of G to D cells increased progressively, and the change from baseline was significant at 7 years taking omeprazole ( P < 0.02). In the control group, G- and D-cell numbers did not differ significantly within the six age groups. CONCLUSIONS: Long-term omeprazole therapy is associated with a significant increase in G-cell numbers and in the ratio of G to D cells in children. These changes reflect the effect of omeprazole because there was no change in these parameters in the age-matched control group.

Grade and stage in chronic hepatitis.

The liver biopsy is essential to the investigation and management of chronic liver disease. The pathologist provides an etiologic diagnosis, reports the grade of disease activity and stage of fibrosis, and comments on any response to therapy. Recent progress in our understanding of chronic hepatitis, its causes, prognosis, and therapy, has influenced the revision of its nomenclature and classification. The use of a descriptive or numerical scoring system allows the pathologist to provide reproducible, clinically relevant information in the surgical pathology report.

Gonadal pathology in triploidy.

There are numerous reports describing the pathology of the fetus and placenta in triploidy. Although gonadal pathology is described in many of these reports, consistent changes have not been noted nor is it clear whether genital ambiguity can be considered part of the triploid phenotype. We present a case of triploidy of probable diandric origin, in which there were dysgenetic gonads with abnormal seminiferous tubules, nodules of undifferentiated stroma, and focal absence of the tunica albuginea. As this finding was distinctly unusual in our experience of triploid gonadal pathology, we reviewed the gonadal histology in 51 fetal and infant triploids examined in our autopsy/embryopathology laboratory. The gonads were compared to age-matched normal controls to determine if there was a specific gonadal pathology associated with triploidy and if there was any correlation of this pathology with parental origin of the triploidy. Our review of the triploid gonads indicated that while minor, nonspecific changes were not uncommon, overtly dysgenetic gonads, as observed in the index case, are rare.

Spectrum of gastritis in celiac disease in childhood.

Celiac disease (CD) may cause changes throughout the gastrointestinal tract. The pathology is best described in the distal duodenum and jejunum. It is also associated with lymphocytic gastritis (LG) and varioliform gastritis in adults and children, but the histologic spectrum in the gastric biopsy and the clinical implications are undefined. In this report we relate our experience with the clinical, endoscopic, and histologic changes in gastric biopsies in CD in childhood. Slides (hematoxylin and eosin stained) were reviewed from 33 celiac children, 5 having had more than 1 gastric biopsy during a 7-year period. Gastric intraepithelial lymphocyte (IEL) counts were compared with those of 10 histologically normal controls (normal range, 1-7 IEL/100 antral or body epithelial cells) and 10 nonceliac chronic gastritis (CG) biopsies without H. pylori (normal range, 1-19 IEL/100 antral cells), noting changes in the epithelium and lamina propria (LP). LG was present in 29/33 initial biopsy sets. Fifteen of 29 showed LG/CG. The IEL number was greater in LG/CG than in LG only (27.2 +/- 9.3, n = 14 vs. 18.6 +/- 13.4, n = 15 in the antrum; 23.5 +/- 2.8, n = 4 vs. 13.0 +/- 8.4 in the body). In CD the difference between these mean values and those of normal and nonceliac CG controls was statistically significant. In CG/LG the inflammatory infiltrate was predominantly diffuse/superficial in the LP; mucin depletion was noted in 11/15. The IELs were in the LG/CG range in two CG controls. The IELs were normal at follow-up in five cases. There were no statistically significant differences between the groups with respect to clinical parameters or gastric endoscopic findings. No child had varioliform gastritis. We conclude that in CD children, the stomach is endoscopically unremarkable but may show LG, or LG/CG with or without mucin depletion, or occasionally appear normal. Gastric histology returned to normal with gluten withdrawal. Normal gastric histology is not typical, but does not exclude CD.

Biliary atresia and cytomegalovirus infection: a DNA study.

The cause of extrahepatic biliary atresia (EHBA) is undetermined in most instances, but an infectious agent is widely suspected. Cytomegalovirus (CMV) infection has been associated with intrahepatic bile duct destruction and paucity, raising the question of its role in EHBA. We identified 12 children in the past 5 years with biliary atresia and examined the bile duct biopsy. These showed acute/chronic inflammation and epithelial degeneration. CMV inclusions were not identified. We used in situ hybridization and the polymerase chain reaction (PCR) for CMV-DNA on formalin-fixed, paraffin-embedded tissue. All samples showed the presence of amplifiable DNA using beta-globin primers. No biopsy tissue showed CMV DNA using specific probes and primers. The absence of demonstrable CMV DNA by in situ hybridization and PCR in EHBA biopsies implies that it is unlikely that this virus has any major role in the pathogenesis of this condition.

Histopathologic approach to metabolic liver disease: Part 2.

In this, part 2 of the histopathologic approach to the diagnosis of metabolic disease of the liver, the steatotic, cirrhotic, and neoplastic groups are addressed. See the previous issue, Volume 1, Number 3, of Pediatric and Developmental Pathology for part 1 [1]. The perspective concludes with a tabulated assessment of the likelihood of diagnostic ascertainment.

Epstein-Barr virus in non-Hodgkin's lymphomas and lymphoid tissue in children.

In developed countries the majority of adolescent children show serological evidence of past Epstein-Barr virus (EBV) infection. This virus is associated with non-Hodgkin's lymphomas in immunocompromised children, but the relationship of EBV DNA to these tumors in children without documented immunodeficiency has not been investigated by the polymerase chain reaction (PCR). We used a PCR method with primers from the Bam W and Bam HI regions to study non-Hodgkin's lymphomas in children, with tonsillar tissue of age-matched children as controls for the presence of EBV DNA. Six of the 20 tonsils were positive using the Bam W primers; another four showed this DNA with Bam HI primers. EBV DNA was detected in only one tumor (a lymphoblastic lymphoma) by both primer sets. The demonstration of EBV DNA in the tonsils reflects past infections and the incidence is in accordance with that expected from serologic epidemiological studies. The absence of demonstrable EBV DNA in 19 lymphomas suggests that this virus is of little consequence in the pathogenesis of non-Hodgkin's lymphomas in children who are not known to be immunocompromised. The lymphoblastic lymphoma had a mixed cell population, and the virus was not necessarily related to the malignancy.

An analysis of lymph node DNA for possible bacterial agents of cat-scratch disease.

Recent investigations have implicated Afipia felis and Rochalimaea henselae as possible agents of cat-scratch disease (CSD). We studied lymph nodes with necrotizing granulomas characteristic of CSD for A. felis and R. henselae DNA so that the relationship of these organisms to lymph nodes with necrotizing granulomas of unknown etiology might be better defined. We examined formalin-fixed, paraffin-embedded lymph node biopsies with necrotizing granulomas suggestive of CSD from 28 children obtained over the last 10 years. None had identifiable bacteria, fungi, or acid-fast organisms on routine staining. Pleomorphic bacillary structures consistent with the CSD bacillus were seen with the Steiner stain in 17 cases. We performed the polymerase chain reaction (PCR) on the extracted lymph node DNA with DNA primers for these organisms after demonstrating the presence of amplifiable DNA with c-K-Ras primers. R. henselae was identified in two samples. A. felis DNA was found in just one specimen. These putative CSD bacteria are infrequently associated with necrotizing granulomas using standard PCR techniques. It is possible that some of the patients did not have clinical CSD. The preservation of DNA or numbers of bacteria in the extracted sections may be inadequate for demonstration by DNA amplification methods. These bacilli may be responsible for a small proportion of these characteristic lesions of unknown etiology, or the typical CSD histology, including the presence of pleomorphic bacillary structures, may be nonspecific.

Reliability of histological criteria in glycogen storage disease of the liver.

The histological criteria for the diagnosis of the hepatic glycogen storage diseases (GSDs) are well recognized. However, some biopsies do not have the characteristic features peculiar to their type and not all biopsies with GSD changes are confirmed by enzyme analysis. We reviewed the liver biopsies of 59 patients with clinically suspected GSD. The enzyme defects in 31 of 40 patients with GSD morphology were demonstrated by enzyme analysis. We describe the history and histology of the 9 patients with GSD morphology not confirmed by enzyme analysis, present the diagnoses of the 19 patients shown not to have a GSD, and evaluate the reliability of the morphological criteria used to distinguish the types of hepatic GSD. In this study the predictive value of a biopsy with GSD changes was 90%. Mosaicism, the most sensitive criterion in the diagnosis of GSD, is not type-specific. Fibrosis does not reliably distinguish between the GSD types and although nuclear hyperglycogenation and lipid are characteristic of type I GSD, these features are not diagnostic of any particular enzyme deficiency. The lack of morphological specificity implies that a complete enzyme analysis be performed on each biopsy. A normal enzyme analysis does not exclude a GSD and careful long-term follow-up may be necessary.

Fatal group A streptococcal meningitis and toxic shock-like syndrome: case report.

A previously healthy 8-year-old girl presented with flu-like symptoms, developed toxic shock-like syndrome, and died within 48 hours. At autopsy she was found to have purulent meningitis. The group A beta-hemolytic streptococcus isolated from her CSF was a member of clone ET 2. This strain produced a variant form of streptococcal pyrogenic exotoxin A (SPEA 2) that has recently been associated with widespread toxic shock-like syndrome.

Intussusception of the appendix. A report of four cases and review of the literature.

The clinical and pathologic features of four cases of intussusception of the appendix are reported and the literature is reviewed. All patients had vague abdominal symptoms. The diagnosis of intussusception of the appendix was not made preoperatively in any of these cases. All four patients were females who ranged from 37 to 70 years of age (mean age, 46 years). Examination of the surgical specimens showed tow appendixes that had completely inverted, one with a polyp attached at the base of the appendix forming the intussusceptum and the other with inversion of the appendiceal tip. Three cases were associated with endometriosis and one with a tubulovillous adenoma. Radiologically and endoscopically, the intussuscepted appendix may mimic a neoplastic lesion. Since intussusception may be caused by both benign and malignant conditions, appropriate management will depend on the associated cause.

Apatite determination and distribution in an early stage of gallbladder calcification.

This study is concerned with the nature and distribution of mineral in the gallbladder of a patient with chronic cholecystitis. Light and electron microscopic imaging revealed the mineral to be in the epithelial cells of the mucosa and fibroblasts of the submucosa. In the epithelial cells at the early stages of deposition, mineral was located in the nuclei and throughout the cytoplasm in association with interdigitating cell processes and apical microvilli but was absent in mitochondria. Elemental and electron diffraction analyses indicated the mineral inclusions to be apatite in nature.