Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and Berliner Blau reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.     

Cantú syndrome: report of nine new cases and expansion of the clinical phenotype

Cantú syndrome, a rare disorder of congenital hypertrichosis, characteristic facial anomalies, cardiomegaly, and osteochondrodysplasia was first described in 1982 by Cantú. Twenty-three cases of Cantú syndrome have been reported to date. The pathogenesis of this rare autosomal dominant condition is unknown. We describe 10 patients with Cantú syndrome (9 new cases and the long-term follow-up of a 10th case reported by Robertson in 1999) comparing the phenotype with that of the previously reported cases. We describe how the distinctive facial appearance evolves with time and report several new findings including recurrent infections with low immunoglobulin levels and gastric bleeding in some of our patients. The cardiac manifestations include patent ductus arteriosus, septal hypertrophy, pulmonary hypertension, and pericardial effusions. They may follow a benign course, but of the 10 cases we report, 4 patients required surgical closure of the patent ductus arteriosus and 1 patient a pericardectomy. Long-term follow-up of these patients has shown reassuring neuro-developmental outcome and the emergence of a behavior phenotype including obsessive traits and anxiety.     

Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?

The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view (‘pros’ and ‘cons’), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.     

Enterovirus determination in cases with a diagnosis of the Guillain-Barré syndrome by using the acid-concentration technic

The purpose of this work was to detect enteroviruses in feces by an acid concentration technique (ACT). Fifty-eight samples from children less than 5 years age with diagnosis of Guillain-Barré syndrome (GBS) were analyzed using the routine technique and ACT. Nine positive samples with the routine technique were used as controls. Nine control samples and 22 additional (31 cases) non-polio enteroviruses were isolated and identified with the ACT (53%). Thus, 38% more isolates were obtained by ACT. Isolation was more successful in the RD cellular line (59%) than in Hep-2c (41%). In most cases most titers (71%) obtained were low. ACT improved the detection of enteroviruses but because it is very expensive and laborious, it should be used in the case of laboratories that analyze multiple samples, for special cases such as with autopsy cases and when results are compatible to poliovirus using the routine technique and only in samples obtained during the first 15 days of symptomatology.     

β-Radiation of the fetal fluid in man

Summary It was experimentally proved that the activity of -radiation of the fetal fluid is different depending upo the sex of the embryo.Thus, radiation activity of the fluid in which a fetus of the female sex (Table 1) was developing, was found to be significantly higher than that of the fluid in which a fetus of the male sex was developing (Table 2).Submitted by Active Member of the Academy of Medical Sciences USSR Professor L.V. Gromashevsky     

Anophthalmia,intracerebral cysts,and cleft lip/palate: Expansion of the phenotype in oculocerebrocutaneous syndrome?

We report on a patient with multiple congenital anomalies including anophthalmia, cleft lip and palate, and central nervous system anomalies similar to the case reported by Leichtman et al. [1994: Am J Med Genet 50:39–41] and to oculocerebrocutaneous (Delleman) syndrome. Although the two cases and those with oculocerobrocutaneous syndrome may represent separate but overlapping entities, our patient and the case described by Leichtman et al. [1994: Am J Med Genet 50:39–41] may represent a more severe form of oculocerebrocutaneous syndrome. Am. J. Med. Genet. 68:39–42, 1997 © 1997 Wiley-Liss, Inc.     

Does geographical location influence the phenotype of Fabry disease in women in Europe?

Barba‐Romero M‐Á, Deegan P, Giugliani R, Hughes D. Does geographical location influence the phenotype of Fabry disease in women in Europe? This study examines the relationship between phenotype and geographical location of patients with Fabry disease in Europe. Data were taken from patients enrolled in the Fabry Outcome Survey (FOS), as of October 2007. A modified version of the Mainz Severity Score Index (FOS‐MSSI) was used to classify patients according to the severity of disease. European patients were grouped depending on country of residence (northern or southern European countries). Results are presented from 762 patients enrolled in FOS in Europe (357 men and 405 women); 66% lived in northern and 34% in southern countries. Median age at onset of symptoms of Fabry disease was similar in both sexes. No differences in disease severity were seen among men, according to place of residence; however, women living in northern countries had higher severity scores (p < 0.001) than those in southern countries. In men and women, FOS‐MSSI scores increased with age, irrespective of place of residence. The results suggest that expression of different phenotypic features in Fabry disease in women living in Europe may be influenced by extra‐genetic or epigenetic factors. These factors might be related to dietary or environmental influences that differ according to the patient's country of residence.     

What is expected from the pathologist in the diagnosis of viral hepatitis?

The clinician expects from the pathologist a clinically relevant diagnosis on the basis of liver biopsy interpretation. Today, a liver biopsy, as invasive procedure, is only justified when a significant benefit for the patient can be expected particularly with respect to the clinical management. Consequently, liver biopsy is usually not required in uncomplicated acute viral hepatitis. It is, however, an important diagnostic tool in chronic hepatitis and in transplanted liver to confirm the clinical diagnosis and to assess stage and grade of necroinflammation, treatment efficiency, and concurrent diseases. The diagnosis of liver disease is based on teamwork between clinician and pathologist. Evaluation of the biopsy in the clinical context requires clinical information and appropriate size and handling of the biopsy specimen. Aim of this review is the discussion of morphologic features of acute and chronic viral hepatitis with regard to their clinical relevance.     

Expanding the phenotype of 12q21 deletions: A role of BTG1 in speech development?

We report on a female individual with feeding difficulties, constipation, poor overall growth, periventricular lesions resembling gliosis in brain MRI, recurrent otitis media with palsy of facial nerve, distinct facial features, and pronounced delay in speech development. The latter was the most prominent feature. Molecular karyotyping revealed a heterozygous de novo deletion of 4.353 Mb at chromosome 12q21.33q22. This report expands the number of described individuals with heterozygous deletions at 12q21.33, their clinical spectrum and highlights the clinical variability, even in individuals with deletion of the same genes. Furthermore, our findings indicate a role of BTG1 (OMIM *109580) in speech development.     

Significance of isolated vasculitis in the gynecological tract: what clinicians do with the pathologic diagnosis of vasculitis?

Vasculitides includes a heterogeneous group of disorders with the common histologic findings of vascular wall inflammation. Systemic or localized disease (eg, renal vasculitis) has serious consequences. The incidence of isolated gynecologic vasculitis diagnosed on pathology specimens and its significance is little known. We performed a 20 year retrospective review including 53 cases with vasculitis diagnosis affecting the female genital tract identified in pathology reports. None had prior symptoms or were diagnosed with generalized vasculitis, while one patient had prior diagnosis of fibromyalgia. Most patients presented with abnormal bleeding and were treated for conditions unrelated to vasculitis. The different types of vasculitis were: predominantly lymphocytic (nonspecific) 30 cases, necrotizing 17 cases and granulomatous 6 cases. Only 2 patients had additional serologic tests. None of the patients with isolated gynecologic vasculitis received corticosteroids or additional treatment related to the vasculitis. None of the patients developed systemic vasculitis at follow-up (2 months-19.5 years; mean, 5.5 years). Isolated gynecologic vasculitis diagnosed on pathology slides is rarely associated with systemic vasculitis. Potential isolated gynecologic vasculitis causes include: previous surgical interventions and vascular inflammation secondary to local neoplasm. In almost all cases, clinicians did not perform a thorough laboratory analysis to exclude systemic vasculitis and therapy was not required in any case, suggesting minimal clinical significance.     

PTEN immunohistochemistry in endometrial hyperplasia: which are the optimal criteria for the diagnosis of precancer?

Guidelines recommend protein phosphatase and tensin homolog (PTEN) immunohistochemistry for differentiating between benign endometrial hyperplasia (BEH) and atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). However, it is unclear when PTEN expression should be defined as ‘lost’ and thus suggestive of AEH/EIN. We aimed to determine the optimal immunohistochemical criteria to define PTEN loss in endometrial hyperplasia, through a systematic review and meta‐analysis of diagnostic accuracy. Electronic databases were searched for studies assessing immunohistochemical expression of PTEN in both BEH and AEH/EIN specimens. PTEN status (‘loss’ or ‘presence’) was the index test; histological diagnosis (‘AEH/EIN’ or ‘BEH’) was the reference standard. Accuracy was quantified based on the area under the curve (AUC) on summary receiver operating characteristic (SROC) curves, for several different thresholds of PTEN expression. Eighteen studies with 1362 hyperplasias were included. Six different criteria to define PTEN loss were assessed. Low diagnostic accuracy was found for complete loss of expression (AUC = 0.71), presence of any null gland (AUC = 0.63), positive cells <10% (AUC = 0.64), positive cells <50% (AUC = 0.71) and moderate‐to‐null intensity (AUC = 0.64). Barely moderate diagnostic accuracy was only found for the subjective criterion ‘weak‐to‐null intensity’ (AUC = 0.78). Therefore, the clinical usefulness of PTEN immunohistochemistry in this field should be further investigated.     

Amplification of the Xq28 FRAXE repeats: Extreme phenotype variability?

We report on a new case of FRAXE mutation identified through the screening of a population of FRAXA-negative mentally retarded individuals. The index case, a 4-year-old boy with distinct minor anomalies and mental retardation with severe verbal impairment, his older brother, referred to as normal, and the mother have undergone careful clinical and molecular evaluation. The molecular defect, characterized by standard Southern blot analysis, is represented by a hypermethylated “full mutation” in the 2 boys and by a unique, altered, presumably unmethylated, band in the mother, which is interpreted as a “premutation.” The cytogenetic analysis failed to detect a folate-sensitive Xq27-28 fragile site in either “fully mutated” individual. The phenotype and intellectual performance of the 15-year-old brother of the propositus appeared completely normal. Our propositus shares some traits with previously described FRAXE-mutated subjects, suggesting an association with the Xq28 molecular defect; nevertheless, we find it difficult to reconcile the molecular identity and phenotypic difference in these mutated members of the same family. This could be a case of extreme phenotypic variability or a result of a more complicated molecular mechanism. © 1996 Wiley-Liss, Inc.     

Choanal atresia: the result of maternal thyrotoxicosis or fetal carbimazole?

We present the fourth published case of a child affected with choanal atresia following maternal treatment with carbimazole. The mother was receiving her highest dose of carbimazole at the crucial period for development of the choanae, between days 35 and 38.     

Pericellular lacunae in the diagnosis of metastatic carcinoma in effusions: Is this a useful sign?

The presence of pericellular lacunae has been cited as a useful criterion in distinguishing between benign and malignant effusions from body cavities. This study assessed the presence of pericellular lacunae in 75 specimens of malignant and 38 specimens of benign effusions. In a large number of cases, lacunae could not be assessed reliably because of technical and artifactual reasons. Pericellular lacunae were detected around the majority of the cell clusters in only 4 of the malignant and 2 of the benign cases. In our material, peri-cellular lacunae were not a useful criterion for the diagnosis of malignancy in body cavity fluids. Diagn Cytopathol 1996;15:193–196. © 1996 Wiley-Liss, Inc.