Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

Kernicterus in a boy with ornithine transcarbamylase deficiency: A case report.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.55 mg/dL). The patient was a full-term male with a family history of two previous male siblings who died as newborns after acute neurologic deterioration. The patient's symptoms began at 24 h of life with lethargy that rapidly progressed to coma upon admission to the neonatal intensive care unit. Although hyperammonemia and hyperbilirubinemia were documented, hemofiltration could not be performed. OTCD diagnosis was biochemically established. Despite nutritional intervention and treatment for hyperammonemia, the patient died on the sixth day of life. At autopsy, external brain examination revealed a marked yellow pigmentation typical of kernicterus that included gray matter, particularly the thalamus and basal ganglia; dentate nuclei of the cerebellum and brain stem gray matter were also affected. Microscopic findings were consistent with the classical description of tissue damage in OTCD, including the presence of Alzheimer type II astrocytes in basal ganglia, necrosis, neuronal loss with spongiform degeneration and macrophage infiltration surrounded by astroglia. This condition may be an important comorbidity in newborns with hyperammonemia.

Intestinal/Peritoneal tuberculosis in children: an analysis of autopsy cases.

Infection by Mycobacterium bovis is not infrequently identified in Mexico. Its relation to nonpasteurized milk products ingestion is well recognized with primary infection usually in the intestinal tract. The term "abdominal tuberculosis" includes peritoneal as well as primary and secondary intestinal tuberculosis. The clinical differentiation of these conditions is difficult. In this work, we reviewed the clinical and pathological features of 24 cases of children dying with tuberculosis in whom autopsy revealed abdominal disease in a referral hospital in Mexico City. We identified 8 cases of primary intestinal tuberculosis, with documentation of M. bovis in 6 of them, and 9 cases of secondary intestinal tuberculosis (primary pulmonary disease), all negative to M. bovis. Seven patients had peritoneal tuberculosis without intestinal lesions and with active pulmonary disease in 4 of them, and of the remaining three, two had mesenteric lymph node involvement suggesting healed intestinal disease. In this approach to abdominal tuberculosis, postmortem analysis was able to differentiate primary from secondary intestinal tuberculosis and to define the nature of peritoneal involvement. This discrimination gives rise to different diagnostic approaches and epidemiological and preventive actions, particularly in countries where tuberculosis is endemic and infection by M. bovis continues to be identified.

Identification of Helicobacter pylori strain cagPAI+ and cagPAI- Antigens by IgG antibodies from sera of experimentally colonized meriones unguiculatus (Mongolian gerbils).

BACKGROUND: Mongolian gerbils that are experimentally infected with Helicobacter pylori develop a chronic inflammation that is similar to natural infections in humans. The aim of this study was to compare the antigens of H. pylori cagPAI+ and cagPAI- strains that are expressed during Meriones unguiculatus colonization. MATERIALS AND METHODS: We identified H. pylori cagPAI+ and cagPAI- strain antigens via Western blotting of samples from Mongolian gerbils that were subjected to unique, mixed, and sequential bacterial infections. RESULTS: The antigens from the J99/CG3 (cagPAI+) strain had a lower molecular weight than the antigens from the 251F/CG3 (cagPAI-) strain. There were fewer identified antigens in the single unique infections compared with the mixed and sequential infections. The number of recognized antigens that had a frequency of recognition >60% was higher for the simultaneous and sequential infection groups compared with the single infection group. A 57-kDa antigen was present in >60% of the samples and four of the five experimental groups. Antigens specific to each bacterial strain were identified; the 190- and 158-kDa antigens appear to be specific for cagPAI-, and the 70-kDa antigen appears to be specific for cagPAI+. CONCLUSIONS: In this study, we identified antigens that are common and specific to the H. pylori cagPAI+ and cagPAI- strains.

Bullous lesions as a manifestation of systemic lupus erythematosus in two Mexican teenagers.

Rarely, systemic lupus erythematosus (SLE) presents with bullous lesions due to severe edema and hydropic degeneration of the basal layer, or as a subepidermal blistering disease. Here, we describe two Mexican teenagers, one with SLE with blisters and another with bullous SLE. We also discuss the mechanisms and clinical implications of lesion formation in patients with SLE and bullae.

Study of simultaneous experimental colonization of Meriones unguiculatus (Mongolian gerbils) by cagPAI+ and cagPAI- strains of Helicobacter pylori.

Helicobacter pylori has a chromosomal pathogenicity island (cagPAI), and the presence or absence of this Island places the microorganism into two types of strains: cagPAI+ which is associated to serious infectious processes, and cagPAI- related to mild to moderate infectious events. Simultaneous colonization by cagPAI+ and cagPAI- strains is frequent and these bacteria can interact among themselves. The aim of this project was to analyze the interaction between cagPAI+ and cagPAI- strains of H. pylori in experimental infection, using the Mongolian gerbil as an experimental animal model. We employed J99 (cagPAI+) and 251F (cagPAI-) strains, and obtained 3 derivate strains in successive isolation from experimentally infected gerbils. By RAPD-PCR we found that cagPAI+ and cagPAI- underwent genetic rearrangement during the gerbil-adaptation process. We identified individual isolates from gerbils, and by in situ hybridization we established that both type of strains were able to colonize the same regions of the host's stomach, and induce a mild to moderate inflammatory process. We studied the competence between cagPAI+ and cagPAI- strains by simultaneous and sequential infections. The study shows that in both colonization experiments, the cagPAI- strains were more efficient than cagPAI+ strains in colonizing the infected host by displacing cagPAI+.

Comparative expression of syndecan-1 and Ki-67 in peripheral and desmoplastic ameloblastomas and ameloblastic carcinoma.

The aims of the present study were to examine whether the pattern of syndecan-1 expression correlates with cellular proliferation index in desmoplastic ameloblastomas (DA), peripheral ameloblastomas (PA) and ameloblastic carcinomas (AC), and to compare with that previously reported for solid (SA) and unicystic (UA) variants of ameloblastoma. Immunohistochemistry was performed for syndecan-1 and Ki-67 in seven ameloblastomas (four DA and three PA) and three AC. Expression of syndecan-1 was related to the histological subtype of tumors and, in the case of malignancy, to lower expression levels observed in AC (22.5%) than in PA (47.5%) or DA (77.5%) (P < 0.05). Syndecan-1 expression correlated inversely with Ki-67 proliferative index: the expression was lower in both types of ameloblastomas (1.5% in DA and 6.4% in PA) than in AC (41.2%; P < 0.05). The present results suggest that the decrease in syndecan-1 expression and increase in the Ki-67 index observed in AC is in accordance with its higher aggressiveness as compared to the rare DA and PA. Interestingly, DA had a lower proliferation index as well as the highest levels of syndecan-1 expression. These data suggest that DA differ from the other types of intraosseous ameloblastomas but more studies are necessary to better understand the role of this protein as a marker in the biological behavior of the epithelial odontogenic neoplasms.

Portopulmonary hypertension in children. A study in pediatric autopsies.

BACKGROUND AND AIMS: The relative frequency and risk factors of portopulmonary hypertension in children have not been defined with precision. The few published reports refer to isolated cases or small series from selected populations. The development of pulmonary hypertension in patients with portal hypertension is seldom suspected or documented during life. The examination of autopsy material can identify these cases because pulmonary hypertension produces characteristic histological changes in the pulmonary vasculature. METHODS: Autopsy cases with evidence of portal hypertension were retrieved. Slides of pulmonary tissue from these cases were examined in search of histopathological changes of hypertensive arteriopathy RESULTS: Seventy six cases of portal hypertension were identified among 7060 autopsies collected between January 1971 and January 2008 (1.07%). Four cases with histopathological evidence of pulmonary hypertension were identified. This represents 5.2% of all cases with portal hypertension. These four patients were females in late childhood or adolescence with idiopathic portal hypertension. Pulmonary hypertension was not diagnosed during their lifetime. CONCLUSIONS: Idiopathic portal hypertension in adolescent girls should be considered a risk factor for the development of portopulmonary hypertension, very likely as a consequence of the functional preservation of hepatic tissue that allows a prolonged survival. An oriented search for early signs of pulmonary hypertension in these patients would appear advisable in order to install timely treatment.

Exogenous lipoid pneumonia superinfected with acid-fast bacilli in infants: a report of nine cases.

Super-infection of an exogenous lipoid pneumonia by nontuberculous mycobacteria has been described in the literature. It produces a distinctive histologic picture with suppurative, noncaseating granulomas surrounding lipid vacuoles containing acid-fast bacilli. Mainly isolated cases have been found, but seldom in children. We describe a series of 9 children with similar histological findings. All our patients were under 1 year of age, malnourished, and with chronic respiratory symptoms. The diagnosis, based on the characteristic histology with acid-fast rods, was established at autopsy in 4 cases, on lobectomy specimens in 4 and by open lung biopsy in 1. Mycobacterium fortuitum-chelonei was cultured in 1 case. Gastro-esophageal reflux was documented in all 4 cases in which it was explored. Aspiration of lipid gastric contents or of oil given as medication can result in exogenous lipoid pneumonia, which in turn becomes super-infected with mycobacteria. Recognition of the distinctive histology permits the diagnosis of this complication.

Experimental induction of heterotopic bone in abdominal implants.

Induction of bone tissue requires three elements: osteoprogenitor cells, osteoinductive factors, and a supporting extracellular matrix. In this study, we report on an experimental model in dogs of heterotopic bone tissue production, based on the integration of these osteo-inductive factors into abdominal implants. The implants consist of either a type I collagen sponge wrapped with periosteum and omentum or a type I collagen sponge embedded with demineralized bone powder, platelet-rich plasma, thrombin, and calcium chloride wrapped with omentum, with or without periosteum. Automated histomorphometric analysis showed an efficient production of trabecular bone, which corresponded to 50-70% of the total tissue composition 4 months after implant formation. High expression of the osteoinductive cytokines transforming growth factor-beta and bone morphogenetic proteins-2 and -4 was shown by immunohistochemistry in macrophages, endothelial cells from neoformed capillaries, osteoblasts, osteoclasts, and the mesenchymal tissue around the bone trabeculae. These approaches are novel and efficient surgical procedures to produce mature trabecular bone that could be used as a potential source of bone tissue for autotransplantation.

Intestinal intussusception associated with adenovirus infection in Mexican children.

Formalin-fixed intestinal tissue specimens from 12 Mexican pediatric patients with intussusception were examined for the presence of adenovirus. Four patients (33%) had detectable adenovirus antigen in epithelial cells as determined by using immunohistochemical analysis. Two of the patients with positive immunohistochemical results had antigens in dendritic and mononuclear inflammatory cells, and 3 patients had positive results for species C adenovirus by in situ hybridization using adenovirus species-specific probes (A-F). A real-time polymerase chain reaction assay specific for species C (nonenteric) adenoviruses was used to confirm immunohistochemical results and to amplify adenovirus DNA for sequencing. A sequence similar to that for adenovirus serotype 1 was found in 1 patient, serotype 2 in another, and serotype 6 in a third; in the fourth patient, the sequence was indeterminate between serotypes 2 and 6. The assays used in this study proved useful for the identification of species C adenoviruses in formalin-fixed specimens from Mexican pediatric patients with intussusception.

Osificación pulmonar idiopática con neumotórax espontáneo recidivante / Idiopathic pulmonary ossification with recidivant spontaneous pneumotorax

La osificación pulmonar idiopática puede ocurrir como depósito de hueso en el intersticio y en los espacios alveolares. La mayoría de los casos publicados han sido hallazgos de necropsia en sujetos viejos con enfermedad pulmonar crónica. Este caso se refiere a un joven con escasa sintomatología y peumotórax espontáneo de repetición, la osificación pulmonar fue diagnosticada por biopsia pulmonar. Las imágenes características de tipo dendriforme se demuestran por TACH

Opportunistic infections in children with AIDS/HIV. A study of twenty five autopsies from the National Institute of Pediatrics in Mexico City

Veinticinco niños que murieron con SIDA/infección por VIH fueron sometidos a estudio postmortem; representan el 1.5 por ciento de las autopsias efectuadas desde enero de 1986 a junio de 1996. incluyen 16 pacientes infectados por vía materna y 6 por transfusión. Solo un caso se infectó por vía sexual y en dos casos se desconoce el mecanismo de infección. La infección materna en los 16 casos de infección vertical fue por transfusión prenatal en 5 transfusión postnatal en 4, sexual en 5 y no se determinó en un caso. La infección secundaria fue la causa de muerte en 23 de los 25 casos. La infección bacteriana estuvo presente en 56 por ciento de los niños infectados por vía materna y en 33 por ciento de los infectados por transfusión. Pseudomonas en 6 casos y Salmonella B en 4 fueron las bacterias mas frecuentes. Los gérmenes oportunistas fueron frecuentes, en especial Histoplasma (4 casos), Citomegalovirus (9 casos) y Herpes/Varicela (5 casos)

Rabies without nwgri bodies: detection of rabies virus at autopsy by immunohistochemistry and in situ hybridization / Rabia sin cuerpos de Negri. Detección del virus rábico en autopsia por inmunohistoquímica y por hibridación in situ

El patólogo puede diagnosticar rabia en autopsia cuando reconoce cuerpos de Negri o si documenta la presencia de antígeno del virus por inmunofluorescencia en tejido fresco o congelado. Técnicas moleculares recientes permiten llegar al diagnóstico en ausencia de estos marcadores. Un muchacho de 13 años fue mordido por un perro rabioso y murió veinte días después a pesar de haber recibido un curso completo de vacuna antirrábica. En la autopsia se encontraron infiltrados inflamatorios en cerebro y médula espinal pero un extenso muestreo no reveló cuerpos de Negri. El cerebro y la médula habían sido fijados en formol y no había tejido fresco para inmunofluorescencia. Se identificó antígeno del virus de la rabia por tinciones con inmunoperoxidasa en cerebelo, hipocampo, bulbo y médula espinal. Se detectó asimismo la presencia de RNA genómico del virus y mRNA de la glicoproteína viral por hibridación in situ usando sonda tritiadas de RNA. En este caso se logró un diagnóstico específico de rabia mediante el uso de métodos de inmunohistoquímica y de hibridación in situ. Estas técnicas pueden ser de utilidad en estudios retrospectivos en material de archivo y particularmente cuando se carece de tejido fresco o congelado para inmunofluorescencia

Las causas de muerte por hipotiroidismo congénito: un estudio realizado en necropsias / Causes of death in congenital hypothyroidism: a postmortem study

Los niños con hipotiroidismo congénito se hallan en riesgo de fallecer en forma inesperada. Con el propósito de probar esta hipótesis, se estudiaron las causas de muerte y las enfermedades concomitantes en 16 necropsias de casos con hipotiroidismo congénito. Cuatro pacientes con atireosis fallecieron sin diagnóstico ni tratamiento. El resto fueron diagnosticados tardíamente(después de los dos meses de edad), por exhibir niveles bajos de T3 y T4. Nueve casos de la serie fallecieron inesperadamente, tres en el hospital y seis en su domicilio. Los hallazgos de la necropsia sugieren broncoaspiración en cinco casos y falla cardíaca en cuatro. Los siete casos restantes fallecieron por complicaciones de índole infecciosa. Se concluye que en el hipotiroidismo congénito diagnosticado y tratado tardíamente, existen trastornos orgánicos sistémicos, que asociados al daño neurológico pueden provocar la muerte. Una atención particular a la función cardíaca y a los trastornos en la deglución, podrían detectar los casos de alto riesgo