Membranoproliferative glomerulonephritis in a child with congenital portosystemic shunt.

Congenital portosystemic shunts (CPSS) are rare congenital vascular anomalies characterized by abnormal connections between the portal vein and systemic circulation, bypassing the liver. They can lead to complications such as recurrent encephalopathy, liver nodules, portopulmonary hypertension, and neurocognitive issues due to hyperammonemia and rarely kidney involvement. Hepatic hemodynamic changes can lead to liver nodules and hepatocellular carcinoma, particularly in extrahepatic shunts. We describe here an 11-year-old girl with type 1 intrahepatic portosystemic shunt with focal nodular hyperplasia in the liver, presenting with nephrotic syndrome that was diagnosed as membranoproliferative glomerulonephritis on kidney biopsy and that responded partially to therapy with immunosuppressants.

Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.

The function of ABC transporters in the body is manifold; such as maintenance of homeostasis, effect on multi-drug resistance and their role in tumor initiation & progression. Evidence pointing towards the direct or indirect role of ABC transporter genes in particular; ABCB1 and ABCG2 in cancer genesis is increasing. However, their role in gallbladder cancer is unexplored. Therefore, we investigated the methylation status and expression pattern of ABCB1 and ABCG2in gallbladder carcinogenesis. The methylation and expression study of ABCB1/MDR1 and ABCG2/BCRP was performed in tumour and normal fresh tissue samples collected from 61 histopathologically diagnosed gallbladder cancer patients. The methylation status was analysed by Methylation-Specific PCR and expression was determined by Real-Time PCR and Immunohistochemistry. Hypomethylation of ABCB1 and ABCG2 was found in 44 (72.13%) and 48 (78.6%) cases, respectively. ABCB1 hypomethylation pattern showed association with female patients (p = 0.040) and GradeII tumors (p = 0.036) while, ABCG2 hypomethylation was more frequent in early tumors (T1-T2). The mRNA expression ofABCB1 and ABCG2 was up-regulated in 33 (54.10%) and 41 (67.21%) patients with fold change of 4.7 and 5.5, respectively. The mRNA expression of both genes showed association with Grade II tumours and the increased fold change of ABCG2 was higher in (T1-T2) depth of invasion (p = 0.02) and Stage I-II disease (p = 0.08). The protein expression on IHC was strongly positive for ABCB1/MDR1and ABCG2/BCRP in 32 (52.46%) and 45 (73.77%) patients, respectively. The protein expression in ABCG2 showed association with patients age > 50 years (p = 0.04) and GradeII differentiation (p = 0.07). Interestingly, the hypomethylation of both the genes showed significant correlation with increased expression. ABCB1/MDR1 and ABCG2/BCRP hypomethylation and overexpression could have a potential role in gallbladder cancer tumorigenesis especially in early stages. The epigenetic change might be a plausible factor for altered gene expression of ABCB1 and ABCG2 in gallbladder cancer.

Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome.

BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay. RESULTS: Apolipoprotein A1 levels of <0.48 µg/mg of creatinine-differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 µg/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 µg/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 µg/mg of creatinine could distinguish SRNS-FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 µg/mg of creatinine differentiated SRNS-FSGS from SRNS-MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %]. CONCLUSIONS: Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive.

Aplasia cutis congenita: a rare case with extensive symmetrically distributed lesions.

Aplasia cutis congenita is a rare developmental disorder of the skin of neonates, usually presenting as a solitary lesion over the scalp. We report an interesting presentation of AC along with the histopathological features in a neonate with extensive lesions over scalp as well as in bilaterally symmetrical areas over trunk and thighs; such symmetrical distributions being rarely reported.

Embryonal tumor with abundant neuropil and true rosettes with melanotic (retinal) differentiation.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

Steroid-resistant nephrotic syndrome associated with steroid sulfatase deficiency-x-linked recessive ichthyosis: a case report and review of literature.

UNLABELLED: Nephrotic syndrome associated with X-linked recessive ichthyosis due to steroid sulfatase deficiency has rarely been reported in English literature. We describe a 4 and a half-year-old boy presenting with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Renal biopsy revealed minimal change disease. As many of the male members of the family also showed similar skin manifestations, genetic analysis was done on the patient, which revealed deletion of the steroid sulfatase (STS) gene spanning both the 3' as well as the 5'ends. The patient was thus diagnosed with SRNS associated with X-linked recessive ichthyosis. He was started on cyclosporine regimen, and remission was achieved in 5 weeks. We speculate that the deficiency of STS resulting in increased cholesterol sulfate accumulation interferes with the integrity of adherens junctions present between glomerular epithelial cells of the slit diaphragm, and this results in proteinuria and nephrotic syndrome. The nephrotic syndrome remitted with a calcineurin inhibitor medication. CONCLUSION: We suggest that the deficiency of STS is another one in an increasing list of genetic causes of podocytopathy and nephrotic syndrome. Remission of proteinuria in such a case may be achieved with immunosuppressive medication.

Chronic Hepatitis B and Nephrotic Syndrome in Children: Treatment Outcomes.

Hepatitis B-related glomerulonephritis (GN) is an uncommon but important cause of renal morbidity in children. While immunosuppressive therapy has been tried along with antivirals for treatment, some children may undergo spontaneous remission or achieve remission with antivirals alone. We retrospectively studied the outcomes of children with nephrotic syndrome (NS) and chronic hepatitis B infection treated at our nephrology clinic over a five years period; seven children were included of which six (86%) presented with NS and one with nephritic syndrome. Renal biopsy (done in 5 children) showed membranous GN in two (40%), membranoproliferative GN in one (20%), and focal segmental glomerulosclerosis in two (40%). Entecavir therapy was started in 6/7(86%) and four (57%) achieved remission after a median period of 2.7 months and achieved hepatitis B e-antigen seroconversion after mean duration of 1.2 years of treatment with entecavir; the remaining achieved remission with immunosuppression with calcineurin inhibitors.

Nephrotic Syndrome with Central Retinal Artery Occlusion: A Unique Presentation.

Childhood nephrotic syndrome is associated with significant morbidity because of recurrent relapses, infections, and episodes of thromboembolism. Thromboembolism in nephrotic syndrome may involve any major blood vessel. Timely recognition of symptoms and early initiation of anticoagulation therapy are important to avoid end-organ damage. We present here a case of a child with steroid-resistant nephrotic syndrome (SRNS) with bilateral central retinal artery occlusion (CRAO), whose vision improved with anticoagulation therapy.

Cytomorphologic spectrum of giant cell tumor of tendon sheath.

OBJECTIVE: To correlate the cytomorphologic spectrum of giant cell tumor of tendon sheath (GCTTS) with clinical and histologic findings and determine key features helpful in preoperative diagnosis. STUDY DESIGN: Retrospective analysis was done on 48 cases diagnosed cytologically over 9 years. Cases were divided into 2 groups: in group 1 cytology and histology were available (12), and in group 2 cytology alone was available (36). Cytomorphologic features were correlated with clinical and histologic findings. RESULTS: Patients ranged in age from 11 to 60 years, with more women. Small joint involvement was seen in all cases except 1, with upper limb involvement in most cases. Recurrence occurred in 3 cases. Aspiration smears in all cases showed high cellularity, multinucleated osteoclastic type of giant cells and stromal cells. Other features seen less frequently were cytoplasmic granules and vacuoles, nuclear grooves, inclusions, budding, focal mild pleomorphism, hemosiderin-laden macrophages and foam cells. Mitosis and necrosis were absent. Cytologic features were classified as constant when present in all cases and variable when present occasionally. CONCLUSION: The constant cytologic features when combined with clinical and radiologic details are sufficiently distinctive of GCTTS. Fine needle aspiration cytology can be used in early, accurate preoperative diagnosis.

Pilocytic Astrocytoma with Adipocytic Differentiation: A Rare Histological Variation.

Lipidization of the low-grade astrocytic tumor is a very rare phenomenon. We report a case of pilocytic astrocytoma with adipocytic differentiation involving the left cerebellar hemisphere and pontis in an 11-year-old boy. Till date, very few such cases have been reported in children. A young boy presented with a clinical picture suggestive of cerebellar dysfunction since 7 months. Imaging revealed a mass lesion involving the left cerebellar hemisphere measuring 4.5×4.1cm. Subtotal excision of the tumor was carried out. Microscopic features were typical of pilocytic astrocytoma but with extensive lipidization of tumor cells. Immunohistochemically, the tumor cells were immunoreactive to glial fibrillary acidic protein, S-100, and immunonegative to p53 and isocitrate dehydrogenase 1. Ki-67 labeling index was 1%. The patient had an uneventful postoperative period and is doing well on follow-up. An extensive review of prior work was carried out to elucidate the clinicopathologic significance of this entity, if any, with special reference to the pediatric age group.

Is thyrogastric disease a potential setting for oncogenesis? Gastric adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated atrophic gastritis in a patient with autoimmune thyroiditis.

Gastric mixed adenoneuroendocrine carcinoma arising from Helicobacter pylori-associated multifocal atrophic gastritis is exceedingly rare. An added association with autoimmune thyroiditis in this case highlighted a complex interplay between Helicobacter, autoimmunity and gastric atrophy. A 55-year-old hypothyroid female presented with hematemesis and a large polypoidal mass in the gastric fundus, suggestive of gastrointestinal stromal tumor on imaging and endoscopy. Histopathology revealed a tumor comprised of nests of monomorphic cells immunopositive for synaptophysin and chromogranin A admixed with malignant glands. Follow-up imaging revealed a heterogeneously enhancing residual gastric body wall. A completion total gastrectomy was performed. Histopathology displayed multifocal atrophic gastritis, occasional Helicobacter and nests of neuroendocrine cells. The patient also had markedly elevated levels of anti-thyroid peroxidase and anti-thyroglobulin. To the best of our knowledge, this is the first case of gastric adenoneuroendocrine carcinoma arising from H. pylori-associated atrophic gastritis, in a patient with autoimmune thyroiditis.

Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome.

Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.

Erythroleukemia: a clinco-hematological review of four cases.

Erythroleukemia is an uncommon disorder in children. Four cases of pediatric erythroleukemia, diagnosed over a period of nine years are presented. The patients presented with pallor, fever and hepatosplenomegaly of recent onset. Peripheral smear examination showed anemia, thrombocytopenia and circulating blasts. The bone marrow displayed erythroid hyperplasia with dysplasia and PAS positive erythroblasts. Myeloid blasts were myeloperoxidase positive and one case showed positivity for non specific esterase, indicating monocytoid differentiation, a poor prognostic feature. Prognosis was poor and follow up period was short.

Combined occurrence of von Willebrand's disease and factor XIII deficiency: a case report.

We report the case of a three year old female child with combined occurrence of von Willebrand's disease and factor XIII deficiency, an extremely rare combination. The patient presented with prolonged bleeding following cuts and wounds. Clot solubility test using 5M urea was positive. Platelet aggregation using ristocetin was reduced, which corrected on adding normal plasma. Aggregation with other agonists was normal. We discuss the clinico- hematological profile of the case. Only one such case has been reported in literature in the past to the best of our knowledge.

Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum.

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

Mutations in the nebulin gene in a child with nemaline (rod) myopathy.

Nemaline myopathy, also called rod myopathy, is a relatively common congenital myopathy and probably second in incidence only to central core disease. The mainstay of diagnosis is histopathology, but detection of the causative mutation is mandatory for determining the mode of inheritance and for prenatal diagnosis. The authors report two siblings with nemaline myopathy caused by mutations in the nebulin gene.

Extensive cutaneous necrosis in a 12-year-old girl: an unusual complication of secondary cold agglutinin syndrome.

Cold agglutinin syndrome (CAS) secondary to infection is rare, usually presenting with anaemia and minor skin changes. A 12-year-old girl with secondary CAS associated with extensive cutaneous necrosis is reported. She presented with fever and multiple necrotic lesions over both cheeks, the tip of nose, ear margins, hands and buttocks, along with pallor, hepatospenomegaly, acrocyanosis and gangrene of the fifth digit of the right hand. She had anaemia, unconjugated hyperbilirubinaemia and a positive direct antiglobulin test owing to cold agglutinins of the IgM type with anti-i specificity and titres of 1:512 at 4°C. Results of bone marrow examination were normal and cryoglobulins were negative. Cold antibodies released even during a brief, self-limited febrile illness can cause widespread cutaneous gangrene. We believe this is the first report in the paediatric age group.