Desmoplastic hairless hypopigmented naevus: a variant of giant congenital melanocytic naevus.

Desmoplasia has been described in melanoma and Spitz naevus but not in giant congenital melanocytic naevus (GCMN). In melanoma desmoplasia is associated with a better survival. Four paediatric patients with hard, ligneous, progressively hypopigmented and alopecic GCMN were seen among 143 cases of GCMN at the Department of Dermatology of the National Institute of Paediatrics, Mexico City. Clinically, induration was progressive in three patients and regressive in one. Pigmentation was regressive in all. Histopathologically, all four patients showed intense dermal fibrosis, scarce naevus cells, and hypotrophic or absent hair follicles. Follow-up and serial biopsies in three patients documented the progressive nature of fibrosis and naevus cell depletion. No evidence of malignant transformation was found. Naevus cell depletion resulted in pigment loss and may have reduced the risk of malignant transformation. Although the cause of fibrosis is unknown, the possibility of an immune reaction to naevus cells is postulated.

Scleroderma 'en coup de sabre' and progressive facial hemiatrophy. Is it possible to differentiate them?

The aim was to be able to evaluate the diagnosis of two diseases by a consensus of clinical opinion used in the Department of Dermatology of the National Institute of Paediatrics in Mexico City. To differentiate between scleroderma 'en coup de sabre' (SCS) and progressive facial hemiatrophy (PFH), colour slides of 13 patients diagnosed as SCS and nine as PFH were examined by two dermatologists and microscopic slides by two pathologists. In both cases, the slides were randomly presented and no clinical information was given. The clinical and histopathological findings were statistically compared with two-tailed tests and alpha = 0.05. Kappa coefficients were obtained to evaluate the concordance between dermatologists, pathologists, and in terms of the consensus diagnosis. The usefulness of photographic assessment is limited by the inability to palpate the consistency of lesions. The most important clinical feature that differentiated both conditions was cutaneous sclerosis present in eight of 13 patients with SCS and in none of the PFH patients (P < 0.005). Other clinical features more frequently found in SCS were cutaneous hyperpigmentation and alopecia. The more frequent clinical features in PFH were total hemifacial involvement and ocular changes. Statistically significant histopathological features were: connective tissue fibrosis present in all cases with SCS and two of nine patients with PFH (P < 0.0002); adnexal atrophy present in 11 of 13 patients with SCS, and in three of nine with PFH (P < 0.02), and mononuclear cell infiltrates in all patients with SCS cf. six with PFH (P < 0.05). Our results suggest that in most cases it is possible to differentiate SCS from PFH based on clinicopathological findings.

Quantitative study of the infection in brain neurons in human rabies.

Rabies virus is a highly neuronotropic virus that causes encephalomyelitis. Rabies virus infection was studied in neurons in the brain of an 8-year-old girl that died of rabies in Mexico. The extent of the neuronal infection was evaluated quantitatively in neuronal cell types of the brain using histologic staining for Negri bodies and immunoperoxidase staining for rabies virus antigen in the same neurons. Quantitative image analysis was used to compare the amount of infection in five different neuronal cell types, which was expressed as a percentage of neuronal area. Purkinje cells and periaqueductal gray neurons showed the largest percentage area for both Negri bodies and signal for rabies virus antigen. In general, there was a good linear relationship between the area of Negri bodies and the area of signal for rabies virus antigen. Many neurons with rabies virus antigen did not have Negri bodies, however, and some neurons with large antigen signals, especially Purkinje cells and periaqueductal gray neurons, lacked Negri bodies. Formation of Negri bodies is likely influenced by factors that vary in different neuronal cell types.

Liver fibrocystic disease and polydactyly: proposal of a new syndrome.

Liver fibrocystic disease (LFCD), characterized by dilatation of the intrahepatic bile ducts and variable degree of fibrosis, can be present alone or as part of many syndromes, such as Bardet-Biedl syndrome (BBS), Meckel syndrome, Jeune asphyxiating thoracic dysplasia, and Fraser-Jequier-Chen syndrome. We report two cases of LFCD and polydactyly with features similar, but not diagnostic of, BBS. Patient 1 was an 18-month-old boy with mental retardation, polydactyly, chronic renal failure, convergent strabismus, and hepatic fibrosis. Patient 2 was a male neonate with LFCD and polydactyly. Their manifestations could not be diagnosed as any of the previous mentioned entities. Difficulties in the early diagnosis of BBS have been previously reported and this could explain the clinical variability and heterogeneity of manifestations at the time of diagnosis. On the other hand, the existence of liver abnormalities in association with BBS has been previously described, but is rare. Our patients' malformations might represent a new entity where autosomal recessive inheritance is probable, but other patterns cannot be ruled out.

Histopathology of vascular lesions found in Kasabach-Merritt syndrome: review based on 13 cases.

We reviewed the histopathology of 13 cases of Kasabach-Merrit Syndrome (KMS). In 4 (31%) cases the predominant morphology was that of a tufted angioma (TA). Six (46%) cases were Kaposiform hemangioendotheliomas (KHE), and 3 (23%) cases showed an infantile (juvenile) hemangioma only. Immunostaining for CD34 and actin (HHF-35) was helpful in defining these types of hemangiomas. The TA was characterized by a proliferation of endothelial cells positive for CD34 with a minimal component of actin-positive cells. KHE showed a paucity of immunoreactive cells; only the luminal endothelial cells were positive for CD34. In three cases with the morphology of infantile hemangiomas, actin-positive cells outnumbered the CD34-positive cells. Our findings confirm the observation that the underlying vascular lesion in KMS is usually not an infantile hemangioma as was originally thought, but variants of hemangiomas such as TA and KHE (77% of 13 KMS cases). Infantile hemangioma was the phenotypic substrate of KMS in only 3 of 13 cases.

Extraneural organ involvement in human rabies.

Human rabies is a fatal encephalomyelitis. After the development of the central nervous system infection, there is centrifugal spread of the rabies virus to extraneural (systemic) organs. With histochemical staining and localization of rabies virus antigen (RVA) with immunoperoxidase staining, we have examined tissue sections of organs from 14 postmortem pediatric and adult cases of human rabies acquired in Mexico and the People's Republic of China. RVA was found in nerve plexuses in multiple organs, including the gastrointestinal tract. RVA was observed in muscle fibers of the heart, tongue, and larynx. RVA frequently was observed in the adrenal medulla with an associated inflammatory reaction. Minor salivary glands of the tongue contained RVA and major salivary glands showed RVA in plexuses, but not in either acini or ducts. Epithelial cells of the tongue and taste buds were occasionally infected. RVA was observed in hair follicles of the skin and rarely in pancreatic islets. The infection of extraneural organs was sometimes, but not always, associated with an inflammatory reaction. These findings indicate that centrifugal spread of rabies virus to extraneural organs occurs frequently in human rabies.

[Sessions of clinical anatomy in Mexico at the dawn of the 21st century]. / Las sesiones anatomoclínicas en México en los albores del siglo XXI.

The authors present a defense of postmortem clinical anatomy sessions, which contributed enormously to the development of clinical medicine but which today draw little interest in medical studies. Nevertheless, the sessions still provide an unrivalled exercise in diagnosis for medical students and an excellent method of continuing education for practicing professionals. Autopsies make it possible to confirm or correct clinical diagnoses, including those obtained through highly complex technological procedures; they contribute to the discovery of new diseases and other abnormalities; they promote research; they provide reliable statistics on morbidity and mortality; they produce useful genetic information; they facilitate interdisciplinary discussion and knowledge exchange; and they can serve as an indicator of the quality of medical care. The authors recommend reviving the high academic standards of postmortem clinical anatomy sessions and urge professionals in health institutions to contribute as much as possible to the continuation and improvement of these sessions.

Differential expression of p53, c-kit, and CD34 in prepubertal and postpubertal testicular germ cell tumors.

BACKGROUND: The origin of testicular germ cell tumors (TGCTs) in children is poorly understood. There are clear differences between tumors in young children and those in adolescents and adults, which may suggest that they follow different pathways of tumorigenesis. METHODS: Tissue sections from 25 TGCTs (15 from patients age 4 years or younger and 10 from adolescents or adults) were stained immunohistochemically with anti-p53 (DO-1), CD34, and c-kit proto-oncogene protein product. RESULTS: CD34 expression was noted only in 5 prepubertal tumors. Expression of c-kit was observed in 9 of the 15 prepubertal tumors versus 2 of the 10 postpubertal cases. The intensity of expression was equal to that of the adjacent normal tubules in the prepubertal tumors, whereas the intensity was less in the postpubertal tumors. Expression of p53 was strong in 8 of the 10 tumors in adolescents or adults, with a 40-70% positivity, whereas only 6 of 15 prepubertal tumors expressed p53, with < 10% positivity. CONCLUSIONS: CD34 expression in tumors in the group of young children suggests a possible link to teratomas and further provides insight into the fundamental differences between this group and the adolescent/adult group. The expression of c-kit and p53 provides further evidence that c-kit/SCF signaling and p53 play potentially different roles in the initiation and progression of these tumors. Future studies will be required to clarify this issue.

Ependymomas in children express the multidrug resistance gene: immunohistochemical and molecular biologic study.

In view of the poor response of ependymomas to chemotherapy, it may be hypothesized that these tumors have intrinsic drug resistance to some chemotherapeutic agents. The expression of drug resistance may be specific to a single agent or may involve multiple drugs. Among several mechanisms of drug resistance, P-glycoprotein (Pgp) has been the subject of considerable attention in clinical practice. In order to assess the possible participation of Pgp in the chemotherapeutic resistance of ependymomas, 42 biopsy specimens from 35 patients with ependymoma seen at our institutions were studied by immunohistochemistry with two monoclonal antibodies: C219 (Signet) and UIC-2 (Dr. Roninson's gift). In addition, four cases were studied by polymerase chain reaction after reverse transcription to detect transcripts of Pgp. Our results showed that in 35 samples there was a positive reaction for Pgp with both antibodies; two biopsy samples were positive only with C219 and three others with UIC-2; the remaining two samples were negative with both antibodies. Of the four cases studied by RT-PCR, three showed MDR1 transcripts. These results support our hypothesis of Pgp-mediated intrinsic multidrug resistance in these tumors.

A novel mitochondrial DNA point mutation associated with mitochondrial encephalocardiomyopathy.

A novel mitochondrial DNA (mtDNA) mutation at position nt 4320 in the tRNA(Ile) gene was associated with severe encephalopathy in a 7-month-old infant, who died of intractable hypertrophic cardiomyopathy. The mutation was present in heteroplasmic fashion (88%) in muscle and fulfills accepted criteria for pathogenicity. This is the fourth pathogenic mutation identified in this gene, which appears to be a "hotspot" for deleterious mutations affecting the heart. This report adds to the evidence of genetic heterogeneity in hypertrophic cardiomyopathies.

Characterization of a 5025 base pair mitochondrial DNA deletion in Kearns-Sayre syndrome.

We characterized a mitochondrial DNA deletion in a patient with Kearns-Sayre syndrome. Southern blot hybridization showed that 86 to 93% of the mitochondrial genome harbored a 5.0 kb deletion. The percentage of affected genomes is higher than in previously described cases. Direct sequencing of the breakpoint region revealed that the deletion extended 5025 bp from nt 10,050 in the tRNA Gly gene to nt 15,076 in the cytochrome b gene, thus 30% of the total mitochondrial genome was lost by this deletion. A pair of extremely short mirror sequences flanking the mitochondrial DNA breakpoints were identified. These flanking sequences differ from previously published consensus 'hot-spots', known to give rise to deletions in human mitochondrial DNA.

[Causes of death in congenital hypothyroidism. An autopsy study]. / Las causas de muerte por hipotiroidismo congénito. Un estudio realizado en necropsias.

Children with congenital hypothyroidism are prone to die unexpectedly. In order to test this hypothesis, the primary and contributing causes of death were studied in a case series of sixteen consecutive children coming to autopsy. Four patients with absent thyroid died undiagnosed and untreated. The remaining twelve cases had documented hypothyroidism with low T3 and T4 levels. Diagnosis was established after the age of two months. Nine of the sixteen cases died unexpectedly, three while in the hospital and six at home. Autopsy findings suggested bronchoaspiration in five and heart failure in four. The remaining seven cases died under predictable circumstances with serious infections. Children with congenital hypothyroidism with delayed treatment may die unexpectedly as a result of the organic dysfunction caused by their primary disease.

The pathologist's approach to the diagnosis of metabolic disease.

Many inborn errors of metabolism have tissue changes that suggest or indicate a diagnosis on morphologic bases. This emphasizes the involvement of the pathologist in the study of tissues obtained by biopsy as part of the diagnostic workup of cases with clinical evidence suggesting a metabolic disorder. Some of these diseases involve proteins with enzymatic activity with a consequent backlog of precursor metabolites. If these metabolites are insoluble or compartmentalized in cells, they accumulate in tissues. The diagnosis in those cases rests on establishing the nature of the accumulated materials and their topographic distribution. In some storage diseases, the abnormal substance can be identified in the affected tissues by histochemistry or ultrastructure. Another group of inborn disorders of metabolism produce changes in subcellular organelles such as peroxisomes and mitochondria. A third group is expressed by rather unique tissue changes which strongly suggest the diagnosis of metabolic disease.

Ependymomas in children: histologic and DNA-flow cytometric study.

Ependymoma, a common neoplasm in the central nervous system of children, expresses great variability of morphological appearances. Correlation with clinical behavior has been controversial in previous studies. In order to explore the potential value of DNA-flow cytometric analysis in predicting the clinical course of ependymomas in children, we studied 22 patients with this tumor, selected from two large pediatric institutions. In addition, a number of histologic features were reviewed, such as necrosis, mitoses, endothelial proliferation, cellularity, and pleomorphism. DNA analyses of paraffin-embedded tissue from these tumors showed 9 of 17 (53%) with DNA indexes less than 1.16 and 8 of 17 (47%) with DNA indexes above 1.16. Ten of 17 (59%) patients died, 2 (12%) were lost for follow-up, and 5 (29%) are alive. No statistical correlation was found between DNA index, outcome, and histology. In spite of the small sample size, our findings appear to support the general impression that ependymomas are morphologically highly variable tumors of potential aggressiveness without valuable prognostic histologic markers.

Central nervous system tumors in Mexican children.

Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

[Pharyngo-tonsillitis and necrosing submaxillary adenitis caused by Streptococcus pyogenes associated with toxic shock syndrome in children from Mexico City]. / Faringoamigdalitis y adenitis submaxilar necrosante por Streptococcus pyogenes asociado a síndrome de choque tóxico en niños de la ciudad de México.

We report on six previously healthy children between nine months and nine years old, who suffered streptococcal faringoamigdalitis and cervical adenitis with scarlet fever and toxic shock syndrome; four of them died in a fulminant course and two survived. These patients behave similarly to others reported from United States of America, England and Australia, and in similar way these clinical entity could be due to bacterial pyrogenic exotoxins according to the clinical fulminant course.

[The VATER association]. / Asociación VATER.

The clinical, radiologic, and anatomic features of 53 patients with VATER association were reviewed. The vertebral, anorrectal, tracheoesophageal, radial, and renal congenital defects included in the association are similar to those described by other authors. In this report genital anomalies are very frequent and should be included as a diagnostic criteria for this association. Encephalic, facial, and cranial congenital defects are common and can affect prognosis; 17 patients have other malformations patterns, and they can belong to a different group of malformations.