EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy.

The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus-driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm- and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P = .01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.

Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis.

Previous studies have suggested that macrophages may contribute to acute Leptospira dissemination, as well as having a major role in kidney fibrosis. Our aim was to characterize the role of macrophages and galectin 3 (Gal-3) on the survival, clinical course, bacterial burden, interstitial nephritis, and chronic kidney fibrosis in Leptospira interrogans serovar Copenhageni (LIC)-induced experimental murine leptospirosis. C57BL/6J mice depleted of macrophages by liposome-encapsulated clodronate treatment and infected with LIC presented a higher bacterial burden, had reduced subacute nephritis and enhanced chronic kidney fibrosis relative to untreated, infected mice. Moreover, LIC infection in mice whose Gal-3 was disrupted (Lgals3-/-) had a higher bacterial burden and enhanced subacute nephritis and chronic kidney fibrosis when compared to C57BL/6J wild-type mice. Chronic fibrosis did not correlate with higher transcription levels of TGF-ß1 or IL-13 in the kidneys. Kidney fibrosis was found in chronically infected rats as well as in wild infected rats. On the other hand, human fibroblast cultures exhibited enhanced differentiation to myofibroblasts after treatment with LIC. Our results demonstrate that macrophages and Gal-3 play a critical role in controlling the LIC burden but has a minor role in subsequent fibrosis. Instead, kidney fibrosis was better correlated with bacterial burden. Taken together, our results do not support a role for macrophages to disseminate leptospires during acute infection, nor in chronic kidney fibrosis.

Gliofibroma: Report of Four Cases and Review of the Literature.

Gliofibroma is a relatively rare variant of a mixed glial-fibrous tumor more frequent in children than in adults. It has been reported to appear all along the neuraxis, with predilection for the midline. Its evolution is usually benign, although few examples have shown either multiple sites of involvement or leptomeningeal dissemination. Some authors regard it as part of the desmoplastic astrocytoma spectrum. We report here four examples of this rare condition which exemplify its histological patterns and biological behavior, and provide a review of the literature. Even though this tumor is commonly regarded as heterogeneous and with variable course, our literature review points to a set of clinical and pathological traits that are constant, such as age, location and gross and histological characteristics, as well as a predictable evolution. Currently, this tumor is not included in the WHO Classification of CNS tumors.

Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira.

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden.

Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-ß1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-ß1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

[Cerebral sparganosis in a child: case report]. / Esparganosis cerebral. Presentación de un caso pediátrico.

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Esparganosis cerebral: Presentación de un caso pediátrico / Cerebral sparganosis in a child: Case report

Se presenta el caso de un niño de 8 años con antecedentes de epilepsia en quien el examen anatomopatológico del material extraído de una lesión de 2,5 por 3 cm localizada en la zona corticosubcortical del lóbulo occipital derecho reveló la presencia de un proceso inflamatorio crónico granulomatoso con una larva de Spirometras pp. El paciente nació y vivió varios años en una zona rural de Tarija (Bolivia). Es el primer ejemplo pediátrico de esta infestación parasitaria a nivel cerebral reconocido en la Argentina.

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Esparganosis cerebral: Presentación de un caso pediátrico / Cerebral sparganosis in a child: Case report

Se presenta el caso de un niño de 8 años con antecedentes de epilepsia en quien el examen anatomopatológico del material extraído de una lesión de 2,5 por 3 cm localizada en la zona corticosubcortical del lóbulo occipital derecho reveló la presencia de un proceso inflamatorio crónico granulomatoso con una larva de Spirometras pp. El paciente nació y vivió varios años en una zona rural de Tarija (Bolivia). Es el primer ejemplo pediátrico de esta infestación parasitaria a nivel cerebral reconocido en la Argentina.(AU)

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.(AU)

Esparganosis cerebral. Presentación de un caso pediátrico. / [Cerebral sparganosis in a child: case report].

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Experimental infection with Cryptosporidium parvum IIaA21G1R1 subtype in immunosuppressed mice.

Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. This is the first Cryptosporidium mouse model in which the relationship between infection and apoptosis has been histologically studied at each portion of the gut in order to observe this dynamic in chronic cryptosporidiosis. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection. At proximal jejunum an inverse correlation between infection and apoptosis was observed at days 28 and 35 p.i. Data suggests that jejunum could be an interesting place to carry out further studies on the dynamics of Cryptosporidium infection and apoptosis. Based on these findings, this mouse model was useful to evaluate clinical, parasitological and histological aspects of C. parvum subtype IIaA21G1R1 infection, and it will be an appropriate tool to investigate different aspects of Cryptosporidium infection.

The mucosa beyond the polyps in juvenile polyposis.

Little is known of early histologic changes in the mucosa of the colon aside from the polyps in Juvenile Polyposis. Provided with a surgical specimen of a total colectomy of a 6-year-old boy with this condition, this report describes those changes. The mucosa depicted a peculiar serrated profile of the uppermost part of the crypts due to elongation of them, dilated openings, and scant stroma. Also present were frequent aberrant crypts. Early juvenile polyps presented associated with lympho-glandular sites as distorted and microcystically dilated crypts containing granular and filamentous mucoid material. The findings possibly represent the abnormal cytologic potential of this genetic condition.

Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome: retrospective analysis of 54 children.

Hemorrhagic colitis (HC) is a severe manifestation of the hemolytic uremic syndrome (HUS). We performed a retrospective analysis of patients with HC with the following aims: (1) to characterize the clinicopathologic features; (2) to evaluate mortality rate; (3) to analyze severity of renal and central nervous system (CNS) disease. Patients with HC assisted between 1981-2009 were evaluated and compared with a control group of 137 patients without HC. Among 987 patients with diarrheal prodrome (D) + HUS, 54 (5.5%) presented HC. Clinical findings included abdominal pain (96%), distension (93%), hematochezia (44%), and abdominal mass (11%). Surgery was indicated in 35 patients (65%), and 17 (48.5%) required bowel resection. Transverse and ascending colon were most frequently affected. Macroscopic evaluation showed bowel necrosis (18) and perforation (12). Histologic evaluation (29) showed that 25 (86.2%) had necrosis of the affected segment (transmural in 21). A leukocyte count >20,000/mm(3) and hematocrit >30% were more common in HC patients than in controls (p < 0.001 and p < 0.0001, respectively). Mortality rate was higher in HC patients (33.3%) than in controls (1.4%; p < 0.0001). Dialysis >10 days, seizures, and coma were more frequent in HC patients than in controls (p < 0.0001). In summary, most patients had prominent abdominal findings, and almost 2/3 patients required surgery. Transverse/ascending colon was most affected, and the main histologic finding was transmural necrosis. Higher hematocrit and leukocytosis were frequent. Mortality rate was extremely high, and most had long-lasting anuria and severe neurologic involvement.

Contribución del patólogo en el diagnóstico de enfermedad celíaca. Comentarios sobre recientes avances / The pathologist's role in the diagnosis of celiac disease: recent advances

En la presente revisión se analizan los avances en los criterios y formas de diagnóstico histopatológico de las biopsias de duodeno en pacientes con sospecha de o con enfermedad celíaca diagnosticada. Se realiza especial énfasis en la necesidad de obtener biopsias del bulbo duodenal y utilizar una categorización numérica de la relación vellosidad/cripta(AU)

The present review is intended to analyze the advances in the criteria and classifications of the histopathological findings in patients suspected of or diagnosed with celiac disease. Particular emphasis is placed on duodenal bulb biopsies as well as the use of a numerical system in the determination of the villous/crypt ratio(AU)

Dermatosis congénita vesicular y erosiva con cicatrices reticuladas. Presentación de un caso y revisión de la literatura / Congenital erosive and vesicular dermatosis healing with reticulated supple scarring. A case report and review of the literature

La dermatosis congénita vesicular y erosiva con cicatrices reticuladas es un raro desorden cutáneo de etiología desconocida con lesiones evidentes al nacimiento. Presentamos una niña con esta condición, la cual representa el primer caso diagnosticado en la Argentina, junto a una revisión dela literatura.

Congenital erosive and vesicular dermatosis healing with reticulated, supple scarring is a rare cutaneouscondition of unknown etiology. It presents with patchy or generalized erosion and vesiclesrecognizable at birth, that heal with reticulated scarring. We report a female child with thiscondition, the first recognized in Argentina, together with a review of the literature.

Dermatosis pustular erosiva en el cuero cabelludo de una niña / Erosive pustular dermatosis of the scalp of a girl

La dermatosis pustular erosiva del cuero cabelludo es una erupción pustular idiopática que se ha asociado al trauma físico, quirúrgico o a tratamientos médicos. Se presenta una niña que desarrolla este cuadro como consecuencia del trauma quirúrgico provocado por el drenaje de múltiples abscesos en el cuero cabelludo

Erosive pustular dermatosis of the scalp is characterized by idiopathic pustular eruption often triggered by physical, medical or surgical trauma. We present a girl of 6 years of age that developed this disease as a consequence of surgical trauma after multiple scalp abscesses drainage

Bilateral absence of adrenal glands: a case series that expands the spectrum of associations and highlights the difficulties in prenatal diagnosis.

Adrenal agenesis (AA) defined by the complete absence of development of adrenals is a rare anomaly, which is documented mainly in experimental animals and less frequently in human subjects in the literature. This study was aimed at describing the varied phenotype of this condition in two stillborn and one termination of pregnancy fetuses and two neonates, the associated abnormalities and the difficulties encountered to achieve the prenatal diagnosis. Five cases with AA diagnosed at post-mortem examination were selected and their characteristics were analyzed. The detection of this unusual condition has usually been made as an incidental discovery at post-mortem examination. None of the cases described in this series had been diagnosed at prenatal ultrasonography. Respiratory distress was the commonest clinical presentation in the liveborn. Maternal diabetes was associated with one case. Anomalies of kidneys, lungs, spleen, and blood vessels were associated with two of the cases. No gonadal abnormalities were detected in any of the cases. These cases illustrate the varied clinical presentation of this rare condition and confirm the difficulty in achieving a prenatal diagnosis.

Nodular myofibroblastic mesenchymal dysplasia of the placenta in association with an unusual bone dysplasia.

This case report describes the recognition of nodular and asymmetric perivascular clusters of myofibrolasts-leiomuscular cells in the stroma of immature chorionic villi associated with a fetus delivered at 26 weeks gestation with a peculiar variation of bone dysplasia syndrome and oligohydramnios. Although myofibroblasts are known to exist at these sites, the finding may represent an unusual mesenchymal dysplasia of the placenta perhaps related to the syndrome.

Carcinoma neuroendocrino bien diferenciado (carcinoide) hepático primario / Primary hepatic well differentiated (carcinoid) neuroendocrine carcinoma

Las neoplasias con diferenciación neuroendocrina primitivas del hígado son inusuales. Presentamos el caso de un niño de 12 años con una masa tumoral hepática que en el estudio citológico y de biopsia mostró una proliferación de células pequeñas monomorfas, con aspecto neuroendocrino. La pieza de hepatectomía parcial permitió confirmar el diagnóstico, revelando nidos amplios y cordones de células poligonales de núcleo redondo, sin atipías, y positivas para cromogranina y sinaptofisina. No se encontró lesión primitiva extrahepática. Para el diagnóstico diferencial se tuvo en cuenta además a las siguientes lesiones: hepatoblastoma anaplásico y metástasis de carcinoma con patrón seudoendocrino. La paciente esta viva y bien 8 años después de la cirugía(AU)

Primitive neuroendocrine neoplasms of the liver are rare. We report a case of a hepatic tumour in a 12 year old boy. Both the aspiration cytology and histology of the biopsy specimen revealed a proliferation of small, monomorphous cells with neuroendocrine features. An initial diagnosis of primary hepatic neuroendocrine carcinoma was made and a partial hapatectomy was performed. The diagnosis was confirmed by the histopathology of the surgical specimen which revealed large nests and cords of polygonal cells with round nuclei showing no atypia and which were positive for chromogranin and synaptophysin. No extrahepatic mass was present. Differential diagnosis included anaplastic hepatoblastoma and a metastasis from a carcinoma with pseudoendocrine features. The patient is alive and well 8 years postoperatively(AU)

Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene.

Terminal osseous dysplasia (TOD) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma with onset in female infancy. After performing X-exome capture and sequencing, we identified a mutation at the last nucleotide of exon 31 of the FLNA gene as the most likely cause of the disease. The variant c.5217G>A was found in six unrelated cases (three families and three sporadic cases) and was not found in 400 control X chromosomes, pilot data from the 1000 Genomes Project, or the FLNA gene variant database. In the families, the variant segregated with the disease, and it was transmitted four times from a mildly affected mother to a more seriously affected daughter. We show that, because of nonrandom X chromosome inactivation, the mutant allele was not expressed in patient fibroblasts. RNA expression of the mutant allele was detected only in cultured fibroma cells obtained from 15-year-old surgically removed material. The variant activates a cryptic splice site, removing the last 48 nucleotides from exon 31. At the protein level, this results in a loss of 16 amino acids (p.Val1724_Thr1739del), predicted to remove a sequence at the surface of filamin repeat 15. Our data show that TOD is caused by this single recurrent mutation in the FLNA gene.