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Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression. Clin Genet 1993: 44: 287–291. © Munksgaard, 1993 Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.

Objective. To describe the implementation and evaluation of clinical pharmacy services in ambulatory hematology-oncology clinics. Design. A prospective study was conducted to evaluate the impact of the clinical pharmacist in outpatient clinics. Setting. The clinical pharmacist is available to patients and health care professionals for drug consultations in adult hematology-oncology, cancer pain, surgical oncology, pediatric hematology-oncology, and gastrointestinal tumor clinics. The pharmacist also participates in a cancer outreach program in an off-site rural clinic. Interventions. A chart review, pharmacy patient profile review, and patient interview were performed to obtain medication histories. Drug-related problems were identified, resulting in interventions. Patient outcomes were evaluated by follow-up phone calls or by patient interviews on the following clinic visit. Results. A total of 211 interventions were documented within 36 days. The most frequent activity was patient counseling followed by therapeutic recommendations. A majority of the interventions were not related to chemotherapy. The physician acceptance rate was 94.5%. Most of the problems were of high and moderate clinical significance, with positive clinical outcomes after pharmacy interventions. Conclusion. Hematology-oncology clinics provide an excellent opportunity to involve pharmacists. A clinical pharmacist has a significant role in outpatient clinics and can potentially lead to an overall decrease in health care costs and to an improvement of the quality of patient care.

Background Familial adenomatous polyposis (FAP) is a dominantly inherited disorder characterized by the presence of more than 100 adenomatous polyps in the colon and rectum starting in the second decade of life. FAP is associated with extra colonic manifestations, including desmoid tumors. Methods A 2-year-old girl presented with a rapidly enlarging tumor of the forehead and a family history of FAP. The tumor was cultured for cytogenetic studies. A DNA linkage study using flanking and intragenic polymorphisms of the adenomatous polyposis coli (APC) gene was performed to identify the allele loss in the tumor. Germline mutation identification was by single strand conformation polymorphism analysis of exon 15 of the APC gene, with subsequent double stranded sequencing of fragments with conformational changes. A mutation-induced loss of a restriction site was used to confirm allele loss in the tumor. Results Microscopically, the tumor had desmoid features. Cytogenetic analysis of the tumor demonstrated loss of chromosome region 5(q21q22). A truncating adenomatous polyposis coli (APC) gene mutation was identified in the leukocyte DNA from the child and her affected father. Linked DNA markers suggested that the tumor had lost the maternal, wild-type allele. A mutation-induced restriction endonuclease site alteration demonstrated hemizygosity of the mutant sequence in the tumor DNA. Conclusions These findings are compatible with the presence of a "second hit" inactivation of the APC gene and implicate this gene in the pathogenesis of desmoid tumors.

Pseudorheumatoid nodule of childhood is seen uncommonly by pathologists and is thought to be a variant of granuloma annulare. We report a series of 20 patients (13 M, 7 F) age 1 to 17 years. Fourteen lesions arose on the front of the lower limb, and 14 children had numerous lesions at diagnosis. Seven developed some form of recurrence, except for one case occurring at the site of the original lesion. Only one patient had a weakly positive rheumatoid factor, and was the patient with remote recurrence. As a significant number of lesions arose around the foot when the child was beginning to walk or starting to wear shoes, it is suggested that trauma plays a role in the development of some of these lesions.

The Meckel syndrome is an autosomal recessive condition and includes a heterogeneous group of CNS malformations, most frequently occipital encephalocele. We report on 2 sibs and one other unrelated case with Meckel syndrome in whom the CNS anomaly was the Dandy-Walker malformation, an association not previously described. The criteria used to diagnose the Meckel syndrome are also reviewed.

Purpose The purpose of this article is to describe the features, treatment, and risk factors for relapse of children with mature teratoma (MT) and immature teratoma (IT) to assist future treatment plans. Patients and Methods Patients were younger than 16 years of age and referred to the UK Children's Cancer Study Group centers with biopsy-proven extracranial MT and IT and no prior chemotherapy. Complete excision, with the coccyx in sacrococcygeal patients, and follow-up, including serum alpha-fetoprotein monitoring for early detection of malignant yolk sac tumor (YST) recurrence, were recommended. Carboplatin, etoposide, and bleomycin (JEB) were given for YST relapse, whereas relapsed MT and IT were treated at clinicians’ discretion, usually surgically. Pathology was reviewed and treatments, outcome, and prognostic features assessed. Results There were 351 patients, 227 with MT, 124 with IT. Tumor sites were: testis (n = 53), ovary (n = 130), sacrococcygeal region (n = 98), thorax (n = 23), and other (n = 47). Surgical resection was incomplete in 26% of MT and 40% of IT patients; 5-year event-free survival was 92.2% and 85.9%, respectively, and 5-year overall survival was 99% and 95.1%. Poorer outcome occurred with incomplete resection, tumor rupture, nongonadal site (particularly sacrococcygeal), young age, higher stage and grade, and gliomatosis peritonei, but not with cyst fluid aspiration/spillage, tumor enucleation, nodal gliomatosis, or microfoci of YST in the tumor (Heifetz lesions). JEB was effective for YST recurrence, but not for MT or IT. Conclusion Treatment remains primarily surgical, with JEB chemotherapy for YST relapse. No definite response followed JEB for pure MT and IT. Adjuvant chemotherapy after surgery for sacrococcygeal patients is not advocated.

To understand the pathological lesions found in disorders of the endocrine system of the fetus and neonate it is necessary to have a knowledge of the interrelationships which exist within the developing endocrine system and its target tissues. Although the feedback and regulatory mechanisms are similar to those of the adult, the fetal endocrine system has also to incorporate an additional endocrine organ in the placenta, the steroidogenic zone in the adrenal cortex (fetal zone), and a contribution from the central nervous system, which in the fetus is probably capable both of the production of certain tropic hormones and of being a target organ for certain steroid hormones produced by the gonads, adrenal and placenta.

Benign melanocytic lesions in children may give cause for some concern histologically. This is because they represent a specific entity, or they reflect the state of evolution of the lesion or the anatomical location. This latter phenomenon has been poorly documented in children. In this study, we address the problem of atypical features frequently seen in benign nevi from acral sites in a group of patients aged 18 years or less. Twenty-one cases (12 female, 9 male) were identified from the Department of Pathology files during the years 1975–1988. All were Caucasian. Histological examination revealed that 6 cases were congenital and 15 were aquired; of these, 19 cases (90%) had a junctional component and all of these exhibited architecture atypia in the form of either lentiginous proliferation (84%) or confluence of junctional nests (84%). Forty-two percent (8/19) showed a mixture of both. Thirty-seven percent (7/19) exhibited transepidermal elimination of melanocytic nests, with 13/19 (68%) showing single cell infiltration of the epidermis. Atypical size, shape, and location of the junctional nests were present in 10/19 cases (53%). Within this group there appears to be no relationship between the age of the patient and the degree of architectural atypia. Mild cytological atypia was common. This report stresses the importance of anatomic subsite in the assessment of melanocytic lesions in children as well as in adults.

Twenty-one cases of subepidermal calcific nodule are presented. These lesions occur twice as commonly in males compared to females, with the head (particularly the ear), and neck as favored locations. No case was identified correctly clinically and only 1 case had a history of trauma, which appeared unrelated to the lesion. Histologically, there was a variety of appearances, with two-thirds of specimens exhibiting a warty architecture. Younger lesions were composed of large, amorphous, calcific dermal deposits and were frequently associated with epidermal ulceration. The older lesions were not ulcerated and the calcium deposits were in small spherules. There was no evidence of pilomatrixoma or pre-existing nevus. It is hypothesized that subepidermal calcified nodule represents dystrophic calcification secondary to dermal injury-several in our series showed the architectural changes of verruca vulgaris.

A premature male infant is described in whom the presence of coarse facies, diaphragmatic hernia, genital anomalies and Dandy-Walker malformation suggested a diagnosis of Fryns' syndrome. Lymphocyte karyotype revealed a partial trisomy 22, and his mother carried an apparently balanced 11/22 translocation. Three infants have been described recently with features of Fryns' syndrome and various aneuploidies. It is suggested that amplified developmental instability of the midline developmental field may account for some of the phenotypic resemblances between these cases.

Figure 1. Owl's-Eye Cells. The photomicrograph shows a section of kidney taken at autopsy from a three-month-old boy who died of disseminated cytomegalovirus infection contracted in utero. A single periglomerular renal tubule contains large, intranuclear viral inclusion bodies typical of those found in cells infected with cytomegalovirus. Such inclusion bodies are commonly seen at autopsy or in biopsy specimens from the kidneys, lungs, and other organs in cases of congenital or acquired cytomegalovirus infection. (Hematoxylin and eosin, x1920.).

SUMMARY In seventy-eight patients with alopecia areata, the incidence of auto-antibodies to smooth muscle was greater than that in an age and sex matched control population.

The adrenal glands of 12 anencephalic fetuses and 17 norma lfetuses of 11 to 21 weeks' gestation were examined histometrically. The volume of the adrenal gland occupied by the fetal zone in the anecncephalic fetuses was 57.5% compared with 76.5% in normal fetuses. The fetal zone in anecncephaly showed involution in all speciemsn,. which suggests that this invoulution begins well before 20 weeks' gestation.

A significant increase in non-organ specific autoantibodies is demonstrated in 13 per cent of the sera from 202 patients with histologically proven malignancies, as compared with only 4 per cent of sera from 214 age and sex matched control patients. It appears that the incidence of autoantibodies is related to the histological type of the tumour but not to the presence or absence of tumour dissemination. While the control group shows the expected increase in both incidence and titre of autoantibodies with increasing age, the malignant patients show no such pattern, i.e. in cancer patients autoantibodies occur with equal frequency and at similar titres regardless of age. The absence of an age related increase in incidence and titre of non organ specific autoantibodies does not appear to have been reported previously. Our findings lend support to the hypothesis that cancer is associated with a breakdown of immunological surveillance, not only in old but also in young cancer patients. Thus the finding of non organ specific autoantibodies, especially to smooth muscle antigen, in an apparently healthy adult could be considered evidence of such a breakdown, carrying with it an increased risk of neoplasia.

SummaryReactivity of α-fetoprotein with concanavalin A and detection of acetylcholinesterase activity in amniotic fluid were evaluated as secondary tests for fetal neural tube defect in pregnancies with a high or a low risk of such a defect. A retrospective study was done on 72 fluids and a prospective study on selected samples from 342 fluids in all of which total a-fetoprotein had been measured. Both additional tests were useful in discriminating between normal and abnormal outcome in pregnancies with raised total α-fetoprotein.In the prospective series there were four false positive total α-fetoprotein tests and one false positive acetylcholinesterase test in viable pregnancies without fetal abnormality. None of the three tests was falsely negative for fetal neural tube defect.Specific abnormality and other poor pregnancy outcomes were much commoner when amniocentesis followed from high maternal serum α-fetoprotein than any other indication.

The fetotoxicity of cyclosporin A (CsA) was examined in multiparous Sprague-Dawley rats given the drug (25 mg/kg/day) during different phases of gestation, the effects on the outcome of pregnancy being ascertained on day 19. CsA given from days 1 to 7 caused a small but significant reduction in litter size, with no significant increase in the number of resorptions. When the drug was administered from day 8 to 14 there was no significant change in litter size, but a very striking increase in the incidence of resorptions. This fetotoxic effect was also evident but less marked when the drug was witheld until day 15. Reduction in fetal weight was only present in the group given CsA from days 8 to 14. In surviving fetuses the presence of focal decidual necrosis was more frequent in mothers receiving CsA, suggesting a possible mechanism whereby CsA may mediate its fetotoxic effects.

An indirect immunoperoxidase technique was used to investigate the site of prealbumin synthesis in the human fetus from between 8 and 43 weeks. Prealbumin staining was noted in the A cells of the fetal pancreas, both in the primary and secondary generations of the islets of Langerhans, from as early as 12 weeks gestation. Electron microscopy localized the staining to the cytoplasmic secretory granules. Prealbumin was also present in the gastrointestinal mucosa in cells which had a distribution similar to that of argentaffin cells. Positive staining was noted in the lining epithelium of the renal proximal convoluted tubules, but ultrastructural studies indicated that this was probably related to reabsorption, and not to synthesis.

This study is based on the processing of 115 samples of pure chorion. The different types of colony morphology, together with cytogenetic analysis, indicate the predisposition of chorion cells to artefacts of culture. Chorion survives longer than other foetal tissues and can be cultured when those are dead or contaminated (e.g. in macerated foetuses and missed abortions) making it a suitable and popular tissue for cytogenetic purposes. However, our results indicate that it is slow in culture and prone to chromosome variation so that pseudomosaicism frequently arises and may lead to misdiagnosis. We therefore suggest that cytogenetic analysis of spontaneous abortion material is interpreted with caution in cases where chorion is the only tissue cultured, especially when mosaicism is found.

Twelve triploid abortuses were investigated to determine the origin of the additional haploid set and were retrospectively examined for the development of partial hydatidiform mole. Eight out of ten suitable triploids were diagnosed as partial mole. Dispermy was indicated as the cause of triploidy in 6 informative cases of which 3 were also partial moles. However, one diandric triploid had no features of partial mole. The problem of maternal cell contamination in triploids and the difficulty of diagnosing partial moles on pathological grounds alone are discussed.

Over the three years period 1980-1982, 18 256 pregnancies in the Grampian Region of N-E Scotland including the islands of Orkney and Shetland were screened for raised levels of maternal serum alpha fetoprotein (MSAFP) in the second trimester. Thirty six cases of fetal open neural tube defect in singletons were detected (18 anencephaly and 18 spina bifida). Four additional cases of open spina bifida were associated with normal MSAFP levels although two of these were detected by amniotic fluid AFP measurement when amniocentesis was carried out because of previous NTD history. A further three cases of open spina bifida and two of anencephaly occurred in unscreened pregnancies. The MSAFP screening programme alone was thus instrumental in reducing the birth incidence of open neural tube defects by 36 out of 45 cases (80 per cent) in singletons.

The amount of lymphoid tissue in the thyroid gland and thymus at the time of partial thyroidectomy was measured quantitatively with the point-counting technique. The normal pattern of age involution of the thymus was established in patients with non-toxic nodular goitre. In all the patients with thyrotoxicosis the thymus is hyperplastic; after pretreatment with antithyroid drugs, such as carbimazole, the pattern of age involution is similar to that in the control subjects, whereas after propranolol therapy very little age involution is seen. Patients treated with antithyroid drugs show much less lymphoid infiltration of the thyroid gland than those prepared with propranolol.

La presence des globulines lentes α1 et α2 dans la rate des rats normaux est revelee par les techniques immunofluorescentes et immuno-peroxydasiques. En microscopie electronique, les globulines α-lentes semblent se trouver dans les phagosomes. Dans le cas de la globuline α1-lente, le nombre des phagocytes varie avec l'âge du rat. Ils sont presque absents jusqu'a la 18ieme semaine. Par contre le nombre de phagocytes contenant la globuline α2 reste constant.

Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.

2, ~~~~l~~ s, ~~~~i~~~j~~ of products or cl,nception terminated after prenatal investigatacts. It is, however, important to examine by histology all such lesions. Recently we had a case” in which a macerated male fetus of 15 weeks’ gestation presented a paravertebral mass rnacroscopically identical to several artifactual ones we had previously seen. To our surprise, histological examination showed numerous rosette forming neuroblasts (i.e., as in neuroblastoma), and not the disorganized neural and ependymal tissue which is present in the artifactually extruded neural tissue.