Publications by authors named "Uma Nahar Saikia"

188 Publications

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy.

Endocr Pract 2021 Jun 13;27(6):614-620. Epub 2020 Dec 13.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India.

Objective: Functional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse.

Methods: Dual-phase Tc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months.

Results: Of the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces.

Conclusion: Hemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. Tc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.
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http://dx.doi.org/10.1016/j.eprac.2020.11.010DOI Listing
June 2021

Diagnostic Dilemma of Cutaneous Tuberculosis: Opening of the Pandora's Box.

Am J Dermatopathol 2021 Jun 2. Epub 2021 Jun 2.

Departments of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India; and Department of Dermatology, Safdarjung Hospital, New Delhi, India.

Abstract: Tuberculosis in all forms, that is, pulmonary (PTB) or extrapulmonary (EPTB), is a universal health problem. Cutaneous tuberculosis (CTb) remains one of the least studied and often under-reported variants of EPTB because of its wide and protean clinical presentation. The diagnosis of CTb remains challenging because of lack of sensitive and specific investigations for its diagnosis. The sensitivity of some of the traditional tests is low because of low concentration of mycobacteria in paucibacillary lesions. Besides it is difficult to distinguish between M. tuberculosis (MTb) and other mycobacterial species in skin biopsies morphologically. Molecular methods may target either MTb DNA or RNA, and serve as promising tools in the diagnosis of various forms of CTb, with high sensitivity and rapidity. This review is focused on diagnostic challenges of CTb and to discuss various methods and newer technologies for diagnosing CTb. This will help the dermatologists and dermatopathologists to elucidate and accurately diagnose CTb from other infectious granulomatous dermatitis for appropriate timely treatment of the patient.
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http://dx.doi.org/10.1097/DAD.0000000000001980DOI Listing
June 2021

GCM2 Silencing in Parathyroid Adenoma is associated with Promoter Hypermethylation and Gain of Methylation on Histone 3.

J Clin Endocrinol Metab 2021 Jun 2. Epub 2021 Jun 2.

Bone and Mineral Research Laboratory, Henry Ford Hospital, Detroit, United States.

Purpose: Glial cells missing 2 (GCM2), a zinc finger-transcription factor, is essentially required for the development of parathyroid glands. We sought to identify if the epigenetic alterations in the GCM2 transcription are involved in the pathogenesis of sporadic parathyroid adenoma. In addition, we examined the association between promoter methylation and histone modifications with disease indices.

Experimental Design: mRNA and protein expression of GCM2 were analyzed by RT-qPCR and immunohistochemistry in 33 adenomatous and 10 control parathyroid tissues. DNA methylation and histone methylation/acetylation of GCM2 promoter were measured by bisulfite sequencing and ChIP-qPCR. Additionally, we investigated the role of epigenetic modifications on GCM2 and DNA methyltransferase 1 (DNMT1) expression in PTH-C1 cells by treating with 5-aza 2'deoxycytidine (DAC) and BRD4770 and assessed for GCM2 mRNA and DNMT1 protein levels.

Results: mRNA and protein expression of GCM2 were lower in sporadic adenomatous than in control parathyroid tissues. This reduction correlated with hypermethylation (P<0.001) and higher H3K9me3 levels in GCM2 promoter (P<0.04) in adenomas. In PTH-C1 cells, DAC treatment resulted in increased GCM2 transcription and decreased DNMT1 protein expression, while cells treated with the BRD4770 showed reduced H3K9me3 levels but a non-significant change in GCM2 transcription.

Conclusion: These findings suggest the concurrent association of promoter hypermethylation and higher H3K9me3 with the repression of GCM2 expression in parathyroid adenomas. Treatment with DAC restored GCM2 expression in PTH-C1 cells. Our results showed a possible epigenetic landscape in the tumorigenesis of parathyroid adenoma and also that DAC may be promising avenues of research for parathyroid adenoma therapeutics.
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http://dx.doi.org/10.1210/clinem/dgab374DOI Listing
June 2021

Immunological response and clinical profile in patients with recurrent dermatophytosis.

Mycoses 2021 May 19. Epub 2021 May 19.

Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host.

Objectives: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis.

Methods: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed.

Results: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17 cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4 cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis.

Conclusions: Reduced IFN-γ , Th1, IL-17 and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.
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http://dx.doi.org/10.1111/myc.13322DOI Listing
May 2021

Enzymatic vitreolysis using reengineered derived collagenase.

Mol Vis 2021 1;27:125-141. Epub 2021 Apr 1.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention. Pharmacological vitrectomy has the potential of avoiding surgical vitrectomy; it is also useful as an adjunct during retinal surgery to induce PVD. Previously studied enzymatic reagents, such as collagenase derived from are nonspecific and potentially toxic. We studied a novel collagenase from (VMC) which remains active (VMA), even after deletion of 51 C-terminal amino acids. To limit the activity of VMA to the vitreous cavity, a fusion construct (inhibitor of hyaluronic acid-VMA [iHA-VMA]) was made in which a 12-mer peptide (iHA, which binds to HA) was fused to the N-terminus of VMA. The construct was evaluated in the context of PVD.

Methods: VMA and iHA-VMA were expressed in purified, and characterized with gelatin zymography, collagen degradation assay, fluorescamine-based assay, and cell-based assays. Two sets of experiments were performed in New Zealand albino rabbits. Group A (n = 10) received iHA-VMA, while group B (n = 5) received the equivalent dose of VMA. In both groups, saline was injected as a control in the contralateral eyes. Animals were monitored with indirect ophthalmoscopy, optical coherence tomography (OCT), and B-scan ultrasonography. Retinal toxicity was assessed with hematoxylin and eosin (H&E) staining of retinal tissue.

Results: The activity of iHA-VMA and VMA was comparable and 65-fold lower than that of collagenase Type IV. In the iHA-VMA group, all the rabbits (n = 10) developed PVD, with complete PVD seen in six animals. No statistically significant histomorphological changes were seen. In the VMA group, four of the five rabbits developed complete PVD; however, retinal morphological changes were seen in two animals.

Conclusions: iHA-VMA displays targeted action confined to the vitreous and shows potential for safe pharmacologic vitreolysis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056467PMC
April 2021

Graft versus host disease localized to striae distensae: An example of locus minoris resistentiae.

Indian J Dermatol Venereol Leprol 2021 [SEASON];87(4):555-557

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.25259/IJDVL_396_20DOI Listing
April 2020

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome.

Endocr Pract 2021 May 15;27(5):471-477. Epub 2020 Dec 15.

Department of Histopathology, PGIMER, Chandigarh, India.

Objective: To examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size.

Methods: This was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma).

Results: CD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005).

Conclusion: Our cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.
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http://dx.doi.org/10.1016/j.eprac.2020.11.014DOI Listing
May 2021

Effects of metformin on experimentally induced acne on rabbit ear.

Exp Dermatol 2021 Jul 13;30(7):966-972. Epub 2021 Apr 13.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre-treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed in dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans.
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http://dx.doi.org/10.1111/exd.14347DOI Listing
July 2021

Oral mycophenolate mofetil in the treatment of acquired dermal macular hyperpigmentation: An open-label pilot study.

Australas J Dermatol 2021 Mar 4. Epub 2021 Mar 4.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Literature on treating acquired dermal macular hyperpigmentation is sparse.

Aims And Objectives: To assess treatment response of mycophenolate mofetil in patients having acquired dermal macular hyperpigmentation.

Material And Methods: In this open-label, pilot study, patients of acquired dermal macular hyperpigmentation affecting at least the face and/or neck were included. Each participant was treated with mycophenolate mofetil 2 g/day for 24 weeks, with a follow-up of 12 weeks. Two aspects of disease severity were measured: activity (appearance of new lesions/extension of existing lesions), and degree of hyperpigmentation (measured using 'dermal pigmentation area and severity index'). Patient satisfaction was assessed on a scale of 0-10.

Results: Forty-three of 46 patients who were prescribed mycophenolate, completed the study (40 females, 6 males; mean disease duration 2.8 ± 1.4 years). Amongst 20 (43.5%) patients with active disease, stability was achieved in 17, after a mean duration of 6.1 ± 2.5 weeks (range 4-12 weeks; median 4; IQR 4 weeks). Mean dermal pigmentation area and severity index at baseline was 18.8 ± 7.1 and decreased to 13.7 ± 6.3 at 24th week (27.5 ± 14.7%; P < 0.001). A significant decreasing trend in dermal pigmentation area and severity index (P < 0.001) was observed, and first significant difference from baseline was noted at the 16th week (P 0.008). Less than 10%, >10-20%, >20%-30%, >30%-40%, >40%-50%, and >50% reduction in dermal pigmentation area and severity index was observed in 8, 5, 4, 15, 10 and 1 patients/patient respectively. The maximum mean grade of pre-treatment dermatoscopic severity was 3 ± 0.7, and decreased to 2.1 ± 0.8 on the face (P < 0.001) and 2.4 ± 0.7 on the neck (P < 0.001) post-treatment. There were 9 (20.1%) non-responders. Self-assessment scores of the rest of the patients fell in the range of moderate/fair improvement (>5 to 7). No significant correlation was seen between patient satisfaction score and degree of reduction in dermal pigmentation area and severity index (r -0.39). Three developed adverse effects (leucopenia, n = 1; transaminitis and hyperbilirubinemia, n = 2) that resolved following discontinuation of mycophenolate.

Conclusion: Mycophenolate mofetil appears to be a promising treatment option in acquired dermal macular hyperpigmentation.
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http://dx.doi.org/10.1111/ajd.13567DOI Listing
March 2021

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry.

Endocr Pract 2021 Jan 27. Epub 2021 Jan 27.

Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients.

Methods: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry.

Results: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations.

Conclusion: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC.
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http://dx.doi.org/10.1016/j.eprac.2021.01.014DOI Listing
January 2021

Bullous lesions in patients with cutaneous lupus erythematosus: A clinicopathologic study.

J Am Acad Dermatol 2021 Jan 7. Epub 2021 Jan 7.

Department of Dermatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.1016/j.jaad.2020.12.060DOI Listing
January 2021

Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population.

Am J Dermatopathol 2021 08;43(8):567-573

Departments of Histopathology.

Background: A definite diagnosis of infectious granulomatous dermatitis (IGD) is difficult for both practicing dermatologists and dermatopathologists due to overlapping clinical and histomorphological features. We aimed to explore the role of multiplex polymerase chain reaction (PCR) for identifying a definite etiological agent for diagnosis and appropriate treatment in IGD in formalin-fixed paraffin-embedded tissue.

Materials And Methods: Sixty-two cases of IGD were included, excluding leprosy. The histochemical stains including Ziehl-Neelsen, periodic acid-Schiff, and Giemsa were performed in all cases. A multiplex PCR was designed for detection of tuberculosis (TB) (IS6110 and mpt64), fungal infections (ITS1, ITS2; ZM1, and ZM3), and leishmaniasis (kDNA). The results of histomorphology, histochemical stains, and multiplex PCR were compared.

Results: Among 62 cases, the sensitivity rate of PCR detection for organisms was 16.7%, 0%, 100%, 72%, 75%, and 66.7% in patients with TB, suggestive of TB, leishmaniasis, fungal infections, and granulomatous dermatitis not otherwise specified and granulomatous dermatitis suggestive of fungus, respectively. The TB PCR using IS6110 primers was negative in all cases; however, PCR using mpt64 primers was positive in 33.33% cases of scrofuloderma. The histochemical stains including Ziehl-Neelsen for acid-fast bacilli, periodic acid-Schiff for fungus, and Giemsa for Leishman-Donovan bodies showed positivity in 11.3%, 43.5%, and 3.2%, respectively.

Conclusion: A multiplex PCR (Mycobacterium tuberculosis, Leishmania, and panfungal) is highly recommended in all cases of IGD where an etiological agent is difficult to establish by skin biopsy and histochemical stains along with a clinicopathological correlation. This will augment in appropriate treatment and will reduce empirical treatment and morbidity in such patients.
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http://dx.doi.org/10.1097/DAD.0000000000001878DOI Listing
August 2021

Clericuzio-type poikiloderma with neutropenia in a patient from India.

Am J Med Genet A 2021 01 27;185(1):278-281. Epub 2020 Oct 27.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

A 9-year-old boy presented for evaluation of variegated skin pigmentation. Palms and soles revealed honeycombed hyperpigmented hyperkeratosis. Irregular, firm, skin coloured nodules suggestive of cutaneous calcification were present on both elbows. Total leucocyte count and absolute neutrophil count were 3720/mm3 and 420/mm3 respectively. The neutropenia was not cyclical. Systematic analysis of the whole exome data revealed a homozygous mutation in USB1 gene; chr16:g.58043892TA>-[1/1]. A final diagnosis of poikiloderma with neutropenia- Clericuzio type (PNC) was made. Naegeli Franceschetti Jadassohn, dermatopathia pigmentosa reticularis, PNC and dyskeratosis congenita, all can present with overlapping cutaneous manifestations. Subtle clinical details like thickened nails, hyperextensible joints, calcinosis cutis, characteristic facies and a preceding erythematopapular rash strongly favor the diagnosis of PNC. The index case highlights two novel findings: obliterated dermatoglyphics and mucin deposition (features not described hitherto in PNC).
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http://dx.doi.org/10.1002/ajmg.a.61943DOI Listing
January 2021

Author Correction: Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion.

Sci Rep 2020 Jul 16;10(1):12083. Epub 2020 Jul 16.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-69093-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363817PMC
July 2020

Lacrimal Sac Actinomycosis: A Masquerade of Lacrimal Sac Malignancy.

Ophthalmic Plast Reconstr Surg 2021 Mar-Apr 01;37(2):e45-e47

Departments of Ophthalmology.

A 60-year-old woman had blood-stained discharge with intermittent hemolacria from the left eye, of 3 months duration. The ophthalmic examination showed a firm, nontender, and immobile mass in the left lacrimal sac region. The sac regurgitation test was positive with purulent blood-stained discharge. Lacrimal punctum and canaliculi of both sides were normal. CT scan of orbits showed a hyperdense lesion in the left lacrimal sac region without bone erosion. A complete dacryocystectomy was performed, and the histopathology revealed actinomycosis of the lacrimal sac. At 14 months of follow-up visit, the patient has no clinical evidence of recurrence.
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http://dx.doi.org/10.1097/IOP.0000000000001737DOI Listing
April 2021

Reduced Calcium Sensing Receptor (CaSR) Expression Is Epigenetically Deregulated in Parathyroid Adenomas.

J Clin Endocrinol Metab 2020 09;105(9)

Bone and Mineral Research Laboratory, Henry Ford Hospital, Detroit, Michigan.

Aim: Reduced calcium sensing receptor (CaSR) expression has been implicated in parathyroid tumorigenesis, but the underlying mechanism remains elusive. Accordingly, we aimed to explore the epigenetic changes (DNA methylation and histone modifications) involved in CaSR regulation in sporadic parathyroid adenomas and correlate epigenetic state with disease indices.

Experimental Design: Forty sporadic parathyroid adenomas and 10 control parathyroid tissues were studied. Real-time quantitative PCR (qPCR) for mRNA and immunohistochemistry for protein expression of CaSR were performed. The methylation status of the CaSR promoter 2 was determined by bisulphite sequencing analysis of sodium bisulphite-converted DNA. To determine the role of histone modifications in the CaSR regulation, chromatin immunoprecipitation-qPCR assay was performed.

Results: Real-time qPCR revealed reduced CaSR mRNA expression with a fold reduction of 0.12 (P < 0.0001) in parathyroid adenomas. Immunohistochemistry revealed reduced protein expression of CaSR in 90% (36/40) of adenomas. The promoter 2 region of CaSR displayed significant hypermethylation in 45% (18/40) of the adenomas compared with the controls (6.7%; 1 of 10) (P < 0.002). Bisulphite sequencing analysis revealed maximum methylated CpG at glial cell missing 2 binding site on the CaSR promoter 2 compared to other CpG sites. The methylation status of CaSR correlated directly with plasma intact parathyroid hormone levels in patients with parathyroid adenoma. With chromatin immunoprecipitation-qPCR analysis, H3K9me3 levels showed increased enrichment by 10-fold in adenomas and correlated with CaSR-mRNA expression (r = 0.61; P < 0.003). Treatment with 5-aza-2'deoxycytidine restored the expression of CaSR in a parathyroid cell line.

Conclusion: Our data suggest that hypermethylation and increased H3K9me3 of the CaSR promoter 2 are involved in silencing CaSR expression in sporadic parathyroid adenoma.
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http://dx.doi.org/10.1210/clinem/dgaa419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500582PMC
September 2020

ACTH increment post total bilateral adrenalectomy for Cushing's disease: a consistent biosignature for predicting Nelson's syndrome.

Pituitary 2020 Oct;23(5):488-497

Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Purpose: Nelson's syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing's disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging.

Methods: All patients (n = 43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (> 2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS.

Results: NS developed in 39.5% (n = 17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥ 4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥ 4 discriminatory features and uncontrolled hypertension had the best overall prediction.

Conclusion: Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.
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http://dx.doi.org/10.1007/s11102-020-01047-xDOI Listing
October 2020

Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion.

Sci Rep 2020 05 19;10(1):8250. Epub 2020 May 19.

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on in vitro, ex-vivo, and in vivo experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.
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http://dx.doi.org/10.1038/s41598-020-64931-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237681PMC
May 2020

Follicular lichen planus pigmentosus in blaschkoid pattern: Superimposed segmental mosaicism.

Indian J Dermatol Venereol Leprol 2020 May-Jun;86(3):305-307

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_680_18DOI Listing
March 2021

Fine-needle aspiration cytology of extra-salivary adenoid cystic carcinoma.

Cytopathology 2020 05 25;31(3):215-222. Epub 2019 Dec 25.

Departments of Cytology, Post Graduate Institute of Medical Education& Research, Chandigarh, India.

Introduction: Adenoid cystic carcinoma (ACC) is a ubiquitous tumour which can occur in several sites of the human body. Commonly, it affects the salivary glands but also can rarely occur in various extra-salivary locations.

Aim: To study the clinical and cytological features of extra-salivary ACC on fine needle aspiration cytology.

Methods: In this paper, we included 27 patients with extra-salivary ACC on fine needle aspiration cytology over a period of 5.5 years. The complete cytomorphological spectrum of extra-salivary ACC was studied.

Results: The mean age of the patients was 50.2 years, with age ranging between 14 and 80 years. Male to female ratio was 1:1.7 with 17 females and 10 males. The most frequent primary site was the orbit, and the most frequent sites of metastasis were liver and lung.

Conclusion: Cytopathologists should be alert about the full range of location as well as the cytological spectrum of extra-salivary ACC for greater precision in diagnosis and prompt treatment.
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http://dx.doi.org/10.1111/cyt.12789DOI Listing
May 2020

Pediatric Parathyroid Carcinoma: A Case Report and Review of the Literature.

J Endocr Soc 2019 Dec 16;3(12):2224-2235. Epub 2019 Sep 16.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Primary hyperparathyroidism (PHPT) is a rare endocrine disease in the pediatric population. Sporadic parathyroid adenomas remain the most common cause of pediatric PHPT. Parathyroid carcinoma (PC) is an extremely rare cause of pediatric PHPT. We report a 16-year-old boy presenting with a nonhealing fragility fracture of the right leg along with florid features of rickets. Examination revealed a neck mass, mimicking a goiter. Biochemical findings were consistent with PHPT. Imaging was suggestive of a right inferior parathyroid mass infiltrating the right lobe of thyroid. The patient underwent surgical excision of the parathyroid mass along with the right lobe of thyroid. Histopathology was suggestive of a PC. He achieved biochemical remission with normalization of serum calcium and parathyroid hormone levels. At follow-up, there was no biochemical or imaging evidence of recurrence or metastasis. Genetic analysis revealed heterozygous germline deletion of . An extensive literature search on PC was conducted, with an emphasis on the pediatric population. Thirteen cases of pediatric PC were identified. The median age of presentation was 13 years; there was no sex predilection. All cases were symptomatic; 31% had a visible neck mass. The median serum calcium and intact parathyroid hormone levels were 14.3 mg/dL and 2000 pg/mL, respectively. All patients underwent surgical excision, with 27% showing metastatic relapse. Our findings indicate that the preoperative features that could point toward a diagnosis of PC in a child with PHPT are a tumor size of >3 cm, thyroid infiltration on imaging, and severe hypercalcemia at presentation.
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http://dx.doi.org/10.1210/js.2019-00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839529PMC
December 2019

Fine needle aspiration cytology of primary and metastatic gastrointestinal stromal tumour.

Cytopathology 2020 03 8;31(2):136-143. Epub 2020 Jan 8.

Department of Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Aim: To explore the cytological spectrum of the gastrointestinal stromal tumour (GIST) including its metastatic sites.

Material And Methods: A total of 42 patients (45 sites) diagnosed with GIST or its metastases on fine needle aspiration cytology were studied over a period of 5 years. May-Grünwald Giemsa- and haematoxylin and eosin-stained smears were reviewed and analysed for the cytomorphological spectrum of GIST.

Results: Primary GIST alone was seen in 24 cases, E-GIST in eight cases and metastasis in 11 cases (one patient showing metastasis at two distinct sites), whereas concurrent primary and metastatic lesions were noted in two cases. Amongst primary sites, the most commonly affected location was stomach (n = 22), followed by ileum (n = 2), duodenum (n = 1) and rectum (n = 1). Extra-GIST was seen in retroperitoneum and pelvis (n = 3 each), omentum and mediastinum (n = 1 each). Fine needle aspiration cytology was done from 11 metastatic sites of GIST which included liver, gall bladder fossa, chest wall, and thigh. The classic spindle cell arrangement was the predominant cytological pattern. About 8.8% cases showed predominant epithelioid cell morphology and 15.5% cases had a mixed cytomorphology comprising of both spindle cell and epithelioid cell patterns. Nuclear pseudoinclusions, perinuclear vacuoles and multinucleation were seen in four cases. Immunocytochemistry on cell-block sections for confirmation was performed in 18 cases and all these cases showed strong c-KIT positivity.

Conclusion: In this largest case series of cytomorphological diagnosis of GIST, we describe the cytomorphology and immunocytochemistry of primary and metastatic GIST. GISTs with predominant epithelioid cell morphology may pose a diagnostic dilemma therefore in all suspected cases of GIST, immunocytochemistry for c-KIT and/or DOG1 should be employed on cell-block preparations to confirm the diagnosis of GIST.
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http://dx.doi.org/10.1111/cyt.12785DOI Listing
March 2020

Artificial neural network model to distinguish pleomorphic adenoma from adenoid cystic carcinoma on fine needle aspiration cytology.

Cytopathology 2020 09 22;31(5):445-450. Epub 2019 Dec 22.

Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: To differentiate pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) on fine needle aspiration cytology (FNAC) is often challenging to cytologists.

Aims: In the present study, we tried to make an artificial neural network (ANN) model from the FNAC smears to differentiate PA from ACC.

Methods: The detailed cytomorphological features were analysed on the FNAC of histopathology proven cases of PA (n = 35) and ACC (n = 33) and enumerated semi-quantitatively by two independent observers. These data were used to make an ANN model to distinguish PA from ACC on FNAC material. We used neuro-intelligence software to build the ANN model. The network architecture was 10-2-1. The heuristic search engine was applied to have this model. We used backpropagation neural network to teach ANN. At least 500 iterations were done to train the model. The efficacy of this ANN model was assessed with the help of the confusion matrix and receiver operating characteristic curve.

Result: The data were separated automatically by the software as a training set (n = 48), validation set (n = 10) and test set (n = 10). The ANN model was able to differentiate every case (10/10) of PA and ACC in the final test set. The area under the receiver operating characteristic curve was 1.

Conclusion: The currently built ANN model is competent to identify PA and ACC cases on FNAC. Additional parameters and new cases can be incorporated into this open-ended ANN model to make it more robust.
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http://dx.doi.org/10.1111/cyt.12784DOI Listing
September 2020

Kikuchi-Fujimoto Disease: An Under Recognized Cause of Fever with Lymphadenopathy.

Indian J Pediatr 2020 01 13;87(1):85. Epub 2019 Sep 13.

Pediatric Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s12098-019-03070-8DOI Listing
January 2020

Neutrophilic emperipolesis in micropapillary carcinoma breast.

Breast J 2020 03 9;26(3):539-540. Epub 2019 Sep 9.

Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/tbj.13563DOI Listing
March 2020

Minimally invasive parathyroid carcinoma-A missing entity between parathyroid adenoma and carcinoma: Scintigraphic and histological features.

Clin Endocrinol (Oxf) 2019 12 3;91(6):842-850. Epub 2019 Oct 3.

Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Purpose: Minimally invasive parathyroid carcinoma (MIPC) is clinically and biochemically comparable with parathyroid adenoma (PA) though histopathologically differ from PA. MIPC is an intermediate of PA and parathyroid carcinoma (PC). In literature, there is no definite criterion to diagnose MIPC. Our aim was to evaluate and characterize the imaging and biochemical parameters with histological characteristics of MIPC.

Methodology: Ten patients with MIPC were recruited from (single centre) Indian PHPT registry (www.indianphptregistry.com) from January 2014 to July 2018. Clinical, biochemical, imaging and histological features of MIPC patients were reviewed.

Results: The mean age of MIPC patients (n = 10; 3 males) was 39.9 ± 11.3 years (range: 17-50). All patients had an elevated preoperative parathyroid hormone (iPTH) level ranging from 427 to 2138 pg/mL (median: 1328). MIBI scan showed intensely avid and enlarged parathyroid tumours in all patients; LIPT in 6, RIPT in 3 and ectopic mediastinal in 1 with mean size of the tumours was 2.8 ± 1.1 cm. The mean of maximum standardized uptake value (SUVmax) of MIPC in F-18 fluorocholine PET/CT was 6.7 ± 1.1 (range 6.0-8.3). The mean tumour weight was 12 ± 9.5 g (range: 1.09-28). All MIPC patients had identified capsular invasion in 80% and vascular invasion in 50% only but there was no local invasion, lymph nodal or distant metastasis. The mean Ki-67 labelling index was 3.2 ± 2.7 (range 1.1-10).

Conclusion: The study concluded that MIPC patients are less aggressive (on the basis of imaging and histopathological findings) and should be differentiated from parathyroid adenoma and carcinoma.
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http://dx.doi.org/10.1111/cen.14088DOI Listing
December 2019

Cutaneous metastasis from solid organ cancer: A histopathological and immunohistochemical study of 74 cases from a tertiary care centre of North India.

Australas J Dermatol 2020 Feb 9;61(1):87-90. Epub 2019 Aug 9.

Department of Histopathology and Dermatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.1111/ajd.13130DOI Listing
February 2020

Verrucous dermatophytosis on photoexposed areas resembling pellagra in acquired immunodeficiency syndrome.

Indian J Dermatol Venereol Leprol 2019 Sep-Oct;85(5):499-502

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_3_19DOI Listing
February 2020

Generalized Lichen Nitidus: A Rare Cutaneous Manifestation of Down's Syndrome.

Skinmed 2019;17(2):141-142. Epub 2019 May 29.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India;

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December 2019

Clinical and pathological characterization of oral mucosal 'lichen planus-like lesions' in patients with pemphigus vulgaris: An observational study.

Indian J Dermatol Venereol Leprol 2020 May-Jun;86(3):278-283

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Lichen planus-like lesions on oral mucosa occasionally occur in Indian patients with pemphigus vulgaris. Its significance, both clinical and pathological, is yet to be elucidated.

Aims And Objectives: To study the clinical and pathological characteristics of clinically apparent oral mucosal lichen planus-like lesions in pemphigus patients and to assess their relation with pemphigus disease activity.

Materials And Methods: A total of 32 patients with pemphigus vulgaris who had oral lichen planus-like lesions were included and classified as 'cases,' and eight diagnosed cases of pemphigus vulgaris without lichenoid 'hue' were included as controls. The biopsy specimens were subjected to routine histopathologic examination, immunohistochemistry with FasL, and caspase-3 and direct immunofluorescence.

Results: On histopathologic examination, the diagnosis of pemphigus vulgaris, lichen planus, 'overlap' and 'nonspecific' were rendered in 19 (59.4%), 4 (12.5%), 5 (15.6%) and 4 (12.5%) cases, respectively. On immunohistochemistry, FasL was positive in epithelial cells in 16 (50%) cases and 4 (12.5%) controls (P = 0.066). Caspase-3 stained positively in 18 (56.2%) cases and 20 (62.5%) controls (P = 0.77). Direct immunofluorescence was positive in 77.8% (21/27) of the cases.

Limitations: Relatively small number of controls is the limitation of this study.

Conclusion: Lichen planus-like lesions in pemphigus should not be labeled as inactive disease or postinflammatory hyperpigmentation. Apoptosis followed by pigment incontinence seems to explain such lesions with 'lichen planus-like appearance' in oral pemphigus vulgaris. Active pemphigus smoulders in a majority of these lesions.
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http://dx.doi.org/10.4103/ijdvl.IJDVL_129_18DOI Listing
November 2020
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