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.

Tumors arising in DNA mismatch repair-deficient mice show a wide variation in mutation frequency as assessed by a transgenic reporter gene.

We reported previously that thymic lymphomas arising in mice lacking the DNA mismatch repair (MMR) gene, Msh2(-/-), exhibited striking elevations in the mutation frequency of a transgenic lacI reporter gene when compared with normal Msh2(-/-) tissues. To investigate whether hypermutation was a feature of all tumors arising in MMR-deficient mice, lacI transgene mutation frequencies were obtained from several different mouse tumors deficient for PMS2 and/or MSH2. While lacI gene hypermutation was again clearly evident in Msh2 +/- ms2(-/-) and Msh2(-/-)Pms2(-/-) thymic lymphomas, three non-thymic MSH2-deficient tumors failed to show lacI gene mutation frequency elevations when compared with a normal tissue of MMR-deficient mice. The elevated mutation frequencies in the lymphoid tumors, and the finding of multiple clustered mutations in lacI genes rescued from these tumors, suggest that they are possibly generated by a lymphoma-specific hypermutational mechanism.

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.

Murine MPS I: insights into the pathogenesis of Hurler syndrome.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease resulting from deficiency of the lysosomal enzyme alpha-L-iduronidase. A murine model which shows complete deficiency in alpha-L-iduronidase activity has been developed and shows phenotypic features similar to severe MPS I in humans. Here we report on the long-term clinical, biochemical, and pathological course of MPS I in mice with emphasis on the skeletal and central nervous system (CNS) manifestations. Affected mice show a progressive clinical course with the development of coarse features, altered growth characteristics and a shortened life span. Progressive lysosomal accumulation is seen in all tissues. Skeletal manifestations represent the earliest clinical finding in MPS I mice with histologic analysis of growth plate and cortical bone revealing evidence that significant early pathology is present. Analysis of the CNS has revealed the novel finding of progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice shows increased levels of GM2 and GM3 gangliosides. This murine model clearly shows phenotypic and pathologic features which mimic those seen in severe human MPS I and should be an invaluable tool for the study of the pathogenesis of generalized storage disorders.

Localized dystrophic periocular calcification: a complication of intralesional corticosteroid therapy for infantile periocular hemangiomas.

Two female infants with eyelid hemangiomas developed prickly, rock-hard, subcutaneous crystals following intralesional corticosteroid injections. In each case, the crystals were isocentered on the injection locus and partly eroded the skin, causing local discomfort and inflammation. This complication occurred after two treatment sessions and presented 8 to 9 months after the second injection. An MRI scan showed subcutaneous calcification in the location of the injected orbital hemangioma in one patient. Histopathologic examination confirmed calcification in areas of degenerate hemangioma. There was no recurrence of either hemangioma or calcium deposition following surgical excision. Localized dystrophic calcification may be a late complication of intralesional corticosteroid therapy of periocular hemangiomas.

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.

'Pilonidal appendicitis' or 'the hair of the dog': an unusual case of foreign body perforation of the appendix.

Perforation is common in the young preschool child who has appendicitis, and can occur as the result of an ingested foreign body. A variety of objects have been incriminated. The present report describes a case in which the appendiceal wall was pierced by a stiff canine hair.

Iatrogenic gastroschisis decreases pulmonary hypoplasia in an ovine congenital diaphragmatic hernia model.

Pulmonary hypoplasia is a major problem in infants with congenital diaphragmatic hernia. Intrauterine reparative procedures are associated with a high complication rate. The development of less complex operations to reduce the degree of fetal lung hypoplasia may improve neonatal survival. Our objective was to investigate the effectiveness of an iatrogenic gastroschisis in reducing fetal pulmonary hypoplasia in a sheep model with an artificially created diaphragmatic hernia. A left-sided diaphragmatic hernia (Bochdalek type) was created at 75 days' gestation in an ovine fetal model during the pseudoglandular phase of lung development. At 110 days' gestational age, a left-sided gastroschisis was created by excising part of the lower abdominal wall and buttressing the opening with a rubber ring. The fetus remained in utero until 135 days' gestation, at which time it was sacrificed for autopsy. Histopathologic and morphometric studies were performed on the lungs. Ten animals had creation of a diaphragmatic hernia. Four underwent the second surgery to create a gastroschisis. One animal completed the entire protocol, 3 fetuses aborted after the second surgery. Autopsy confirmed effective decompression of the herniated abdominal contents from the chest into the amniotic cavity in all 4 cases. The lungs of the animal that completed the protocol were appropriately developed, while those fetuses that died soon after gastroschisis creation had severe pulmonary hypoplasia, mainly involving the left lung. Artificially induced diaphragmatic hernia, in the ovine fetus, causes severe pulmonary hypoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

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.