Inverted papilloma presenting as unilateral proptosis: A case report with review of literature

Inverted papilloma is an interesting benign tumour arising from lining epithelium of paranasal sinuses which most commonly involves nasal cavity and paranasal sinuses. However, involvement of orbit and intracranial extension without malignant transformation is very rare. We report a case of extensive inverted papilloma of frontal sinus which primarily presented with proptosis, an uncommon presentation. Ophthalmologic symptoms are rare manifestations of paranasal sinus inverted papilloma without malignant transformation and signify extensive disease with possible intracranial extension.     

Utility of Immunohistochemistry and Immunofluorescence in Determining the Pathogenic Variants of Chronic Granulomatous Disease

Background

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes due to defects in any of the five subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. An initial diagnosis of CGD is made by flow cytometry-based dihydrorhodamine assay or nitro blue tetrazolium test, which is further confirmed by molecular assays. Expression of five subunits of NADPH oxidase components by either flow cytometric or western blot analysis provides clues toward the potential gene targets which are subsequently confirmed by various genetic assays. Immunohistochemistry (IHC) and immunofluorescence (IF) have never been earlier used to determine the expression of different subunits of NADPH oxidase system. We evaluated the utility of IHC and IF in determining the underlying pathogenic variants of CGD.

Materials and Methods

Twelve genetically confirmed cases of CGD, comprising of biopsy specimens (n?=?6), tissue blocks from autopsy cases (n?=?3), and cellblocks of cell pellet prepared from peripheral blood (n?=?4) were included. IHC for p67phox and p47phox subunits and IF for cytochrome b558 were performed.

Results

All 4 cases with pathogenic variation of NCF2 gene showed loss of expression for p67phox subunit. Two cases with pathogenic variation of NCF1 gene showed loss of expression for p47phox subunit. Five cases, except a single case with CYBB gene pathogenic variation, showed loss of expression for cytochrome b558 on IF. Thus, loss of expression consistently matched with the underlying genetic defects assessed by sequencing.

Conclusions

Our results confirm our hypothesis that IHC and IF are two rapid, economical, pathologist-friendly techniques providing pertinent information regarding the underlying pathogenic variants and such immuno-analysis can be easily performed on the tissue.

     

Amyloid goiter: a case of primary thyroid amyloid disease

Amyloid goiter is an atypical presentation of an already rare disease, amyloidosis, which uncommonly comes across in previous review of literature. A patient presented with respiratory distress, which aroused a dilemma on diagnosis because the presentation mimicked that of malignancy. A high index of attentiveness should be kept whenever amyloid deposits are seen on fine needle aspiration cytology, as they are also established in medullary carcinoma. Amyloid deposits have been traced in goiter; however, it was astonishing to observe this condition causing a rapidly growing goiter, large enough to cause respiratory distress. The confirmative diagnosis rested on the histopathology of the specimen.     

Familial Hypercholesterolemia: Cascade Screening in Children and Relatives of the Affected

Objective

Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism characterized by very high low density lipoprotein (LDL) cholesterol since birth, resulting in premature atherosclerosis and coronary artery disease (CAD). Cascade screening of children and family members of proven FH individuals can identify more subjects who have high LDL cholesterol or the family mutation and appropriate intervention can reduce their risk of atherosclerosis and prevent its complications.

Methods

Cascade screening by molecular testing, was carried out in 133 family members, comprising 24 children, of 31 probands with FH having a pathogenic mutation in LDLR/ApoB gene. Lipid profiles were obtained in 44 family members including 11 children.

Results

Of 133 family members tested, 88 (66.1%) were identified to carry the family mutation. Twelve of these were children below 18 y of age and 76 were adults. CAD was present in 15 (11.2%) family members and 63(47.4%) family members, including nine children, were already on Lipid Lowering Therapy.

Conclusions

Cascade screening led to identification of 88 new cases, with a pathogenic mutation, who were at a very high risk of developing premature CAD. The authors identified 12 children with family specific mutation, out of which 9 were initiated on low dose statin therapy. Four homozygous children were treated with high dose statins because of substantially increased risk of CAD. Cascade screening, therefore, proved to be a successful initiative towards primary prevention of CAD in India.

     

Diagnosis and Management of Gaucher Disease in India – Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics

Justification

Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinical manifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD has paucity of information and optimal management guidelines for Indian patients.

Process

Gaucher Disease Task Force was formed under the auspices of the Society for Indian Academy of Medical Genetics. Invited experts from various specialties formulated guidelines for the management of patients with GD. A writing committee was formed and the draft guidelines were circulated by email to all members for comments and inputs. The guidelines were finalized in December 2016 at the annual meeting of the Indian Academy of Medical Genetics.

Objectives

These guidelines are intended to serve as a standard framework for treating physicians and the health care systems for optimal management of Gaucher disease in India and to define unique needs of this patient population.

Recommendations

Manifestations of GD are protean and a high index of suspicion is essential for timely diagnosis. Patients frequently experience diagnostic delays during which severe irreversible complications occur. Leucocyte acid β-glucosidase activity is mandatory for establishing the diagnosis of Gaucher disease; molecular testing can help identify patients at risk of neuronopathic disease. Enzyme replacement therapy for type 1 and type 3 Gaucher disease is the standard of care. Best outcomes are achieved by early initiation of therapy before onset of irreversible complications. However, in setting of progressive neurological symptoms such as seizures and or/neuroregression, ERT is not recommended, as it cannot cross the blood brain barrier. The recommendations herein are for diagnosis, for initiation of therapy, therapeutic goals, monitoring and follow up of patients. We highlight that prevention of recurrence of the disease through genetic counseling and prenatal diagnosis is essential in India, due to uniformly severe phenotypes encountered in our population.

     

Expanding the Phenotype of the Founder South Asian Mutation in the Nuclear Encoding Mitochondrial <Emphasis Type="Italic">RMND1</Emphasis> Gene

Background

Mitochondrial disorders have a wide variability in the phenotype. A 10-mo-old girl presented with a severe phenotype of multisystem involvement due to an uncommon mitochondrial disease. Mutations in the RMND1 gene of nuclear DNA were identified on next generation sequencing. This mutation results in combined oxidative phosphorylation deficiency ?11 (OMIM #614922) of the respiratory chain complex. So far in South Asia, patients of this disorder have been reported only from Pakistan and Bangladesh.

Results

In addition to the features reported in other patients of South Asia with the same mutation at c.1349G>C, index patient from India had hyperaldosteronism, long QT interval but no deafness.

Conclusions

Thus, to conclude, this report emphasizes the diagnostic value of FGF21 assay in this disorder. It extends the phenotype associated with the founder mutation in RMND1 gene in patients from South Asia.