Microvessel density and Ki-67 labeling index in esthesioneuroblastoma: is there a prognostic role?

Esthesioneuroblastoma (ENB) is a malignant neuroectodermal tumor. Hyams grading has an established role in its prognostication. The importance of microvessel density (MVD) and Ki-67 labeling index (Ki-67 LI) is well studied in various tumors, but the same remains understated in ENB. The aims of the study were to estimate proliferation index and MVD in ENB and to correlate them with Hyams grade. Twenty-six ENB cases diagnosed over a period of 5 years were included. Hyams grade, MVD, and Ki-67 LI were evaluated for each of them. The cases were categorized as low (Hyams grades 1 and 2) and high (Hyams grades 3 and 4) grades. Microvessel density and Ki-67 LI were correlated with grade. The treatment response was analyzed in different grades. The commonest histologic grade was 4 (42%). The mean Ki-67 LI was 2%, 8.2%, 30.8%, and 40.5% and mean MVD was 81.67/mm(2), 37/mm(2), 24/mm(2), and 25.2/mm(2) in grades 1, 2, 3, and 4, respectively. A statistically significant correlation of grade with Ki-67 LI (P < .001) and MVD (P < .007) was noted. Hyams grade in ENB correlates well with treatment response. Ki-67 LI is an important prognostic factor in ENB. We propose a cutoff of 25% for Ki-67 LI to differentiate low- vs high-grade ENB, but larger studies are needed for validation. Contrary to epithelial tumors, there is a decrease in MVD with increasing grade in ENB.

Role of p40 and cytokeratin 5/6 in the differential diagnosis of sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is an epithelial neoplasm of sinonasal region which does not exhibit a squamous or glandular differentiation. The challenge in diagnosis of this entity is the rarity of the disease, the varying morphology of the tumor which leads to gamut of differential diagnosis and the paucity of consistent immunohistochemical markers except pancytokeratin. Forty-one cases of sinonasal epithelial neoplasm consisting of 11 cases of SNUC and 10 cases each of high-grade (grade 3 and 4) esthesioneuroblastoma, undifferentiated nasopharyngeal carcinoma, and poorly differentiated squamous cell carcinoma of the sinonasal region were analyzed for morphology and immunoexpression of CK5/6 and p40. It was found that SNUC did not exhibit immunohistochemical expression of p40 and CK 5/6, suggesting that these could be useful negative immune markers for diagnosis of SNUC.

A study of Hepatitis A and E virus seropositivity profile amongst young healthy adults in India.

BACKGROUND: Various Serosurveys and studies provide ample evidence of differing perspectives regarding epidemiology of HAV and HEV in India. This study was conducted to assess the seroprevalence of HAV and HEV and its associated factors with an aim to provide inputs to planners regarding requirement of HAV vaccine. METHODS: A multi-centric cross sectional survey amongst 4175 healthy trainees (young adults) was carried out in training centres, selected by multistage random sampling, giving equal representation to all regions of India. Sample size was calculated by taking prevalence of HAV seropositivity amongst adults as 60% and alpha 0.05. RESULTS: Seroprevalence for HAV and HEV was 92.68% (95% CI 91.82, 93.47) and 17.05% (15.90, 18.26), respectively. Logistic regression showed that hand washing without soap, regular close contact with domestic animals, consumption of unpasteurized milk and regular consumption of food outside home were risk factors for HAV (p < 0.05). For HEV, irregular hand washing, consumption of unpasteurized milk and irregular consumption of freshly prepared food were risk factors (p < 0.05). CONCLUSION: High level of immunity against HAV among the healthy young adults clearly demonstrates that vaccination against HAV is not required at present in our country. The large proportion being susceptible to HEV points towards the requirement of preventive strategies in the form of safe drinking water supply, hygiene, sanitation, increasing awareness and behaviour change with respect to personal hygiene especially hand and food hygiene.

Phase 1/2 Study of the Timing and Efficacy of 3 mg Peg-GCSF in Neo/Adjuvant Dose Dense Breast Cancer Treatment Protocols.

Amol PatelBackground Peg-GCSF has similar efficacy at a dose of 60 µg/kg and 100 µg/kg. The conventional 6 mg SC dose was based on the maximum tolerable dose. In Japan, 3.6 mg dose was approved on the basis of dose finding studies. Peg-GCSF is an integral part of dose-dense chemotherapy protocols. Dose finding and scheduling study of peg-GCSF have not been conducted in Indian patients. Materials and Methods We conducted two-center phase 1/2 clinical study addressing the timing and efficacy of peg-GCSF in Indian breast cancer patients (CTRI no: 2021/07/034751). Three groups of timing administration were studied, namely 1, 6, and 24 hours post chemotherapy. The phase 2 part was the expansion of the best timing group. The primary objective was dose density, which was defined as receiving chemotherapy on < 3 days of scheduled date. Adriamycin/epirubicin cyclophosphamide (AC/EC) was administered q2 weeks. The total leucocyte (TLC) and absolute neutrophil (ANC) kinetics were studied. Other outcomes were incidence of grade 4 neutropenia, febrile neutropenia (FN), and requirement of additional doses of G-CSF. Bone pain, fever, and myalgia were studied for adverse effects. Results From November 20 to December 21, 36 patients were enrolled. Patient characteristics are depicted in Table 1. Initially, three patients received the peg-GCSF in each timing group. One patient in each 1-hour and 6 hours needed G-CSF support for maintaining the dose density. The 24-hour group was carried to phase 2 part. Dose density was maintained in 97% of patients. None of the patient in 24-hour group had FN. Also, 4/30 patients had grade 4 neutropenia and required an additional dose of GCSF. Grade 3 or 4 bone pain was not noticed by any of the patients. During the first cycle, the mean ANC (cells/µL) was 5284, 20704, 3010, 6954 on D0, D + 3, D + 7, and D + 13, respectively (Fig. 1A-TLC and 1B-ANC). The mean ANC (cells/µL) rise on D + 3 in cycles 1, 2, 3, 4 was 23810, 29209, 32428,22455, respectively. Conclusion Dose density of AC/EC breast cancer protocol is maintained with peg-GCSF 3 mg. Post chemotherapy 24-hour timing of peg-GCSF administration remains as the standard. A phase 3 trial of 6 mg versus 3 mg is warranted.

Radiation Retinopathy: Detection and Management Strategies.

A gradual shift in trend from primary enucleation to globe salvaging radiation therapy for the management of ocular tumors has resulted in the rise of several post-treatment ocular complications including radiation retinopathy. Radiation retinopathy is a chronic, progressive, and occlusive vasculopathy that can manifest anytime between 1 month to 15 years after starting radiation therapy. The aim of treatment in most of these cases is to prevent further vision loss. Treatment options such as laser photocoagulation, anti-vascular endothelial growth factor and intraviral steroids have been described. However, despite several advances in diagnostic and therapeutic modalities, a significant proportion of eyes with radiation retinopathy eventually go blind. This review summarises some of the clinical features, investigative modalities, and recent therapeutic strategies used in the management of radiation retinopathy.

Microbiological and Antibiotic Sensitivity Profile of Postoperative Endophthalmitis in a Tertiary Eye Care Hospital of North India.

INTRODUCTION: We describe the microbiological profile of postoperative endophthalmitis from northern India and analyse the pattern of antibiotic sensitivity which may have changed due to development of resistance secondary to overuse of antimicrobial drugs. MATERIALS AND METHODS: This is a retrospective study of postoperative endophthalmitis from January 2011 to December 2017 in a tertiary eye hospital of northern India. Any patient developing endophthalmitis within one year of any intraocular procedure was included in the study. According to severity, treatment with a trial of intravitreal antibiotic injections or core vitrectomy was decided. Ocular samples were collected which were either anterior chamber tap or vitreous biopsy and sent for microbiological examination. The samples were stained with Gram's and KOH stain and cultured on chocolate agar, blood agar, brain heart infusion broth and Sabouraud dextrose agar. RESULTS: A total of 545 patients of postoperative endophthalmitis were analysed which showed a male predilection (60.5%) with maximum patients between the age group 50-69 years. 292 patients (53.5%) were culture negative and 253 patients (46.4%) were culture positive. Most common organism identified was Staphylococcus in 73 patients followed by Pseudomonas in 48 patients. Staphylococcus species was most sensitive to vancomycin (97%) followed by amikacin (91%) followed by gentamicin and moxifloxacin (88% each). Pseudomonas was the second most common isolate which showed maximum sensitivity to imipenem (82%) followed by ciprofloxacin(60%). Polymicrobial infection was noted in 23 patients. The most common fungal isolate was aspergillus in 11 patients, followed by fusarium in 10 patients. CONCLUSION: Our study shows that gram positive bacteria are the most common organisms in postoperative endophthalmitis and are most sensitive to vancomycin, followed by gram negative bacteria which show increased sensitivity with imipenem than commonly used antibiotic - ceftazidime.

Necrotic scleral melt and fungal keratitis-a complication of subtenon triamcinolone acetonide injection.

PURPOSE: Subtenon triamcinolone acetonide injection (STAI) is a safe drug delivery method for various ocular conditions. We report two cases of necrotic scleral melt, a rare complication of STAI. METHODS: The first patient received STAI for post-operative inflammation control and developed necrotic scleral melt at the site of STAI with superadded fungal keratitis. The second patient received three STAI for non-necrotizing, non-infectious anterior scleritis and developed scleral necrosis at the site of her last STAI. Noncompliance with medications resulted in the progression of scleral necrosis to a new area. RESULTS: In the first patient, surgical removal of triamcinolone deposit resulted in healing of the scleral melt while the second patient was managed conservatively with corticosteroids and immunosuppressants. CONCLUSION: Scleral melt is a rare complication of STAI; however, an early diagnosis and management of any predisposing factor along with surgical debridement should be considered as a potential critical treatment option to salvage the eye.

Hypermature Intumescent Cataract in Advanced Keratoglobus.

We report a rare case of bilateral keratoglobus with hypermature intumescent cataract in a 55-year-old woman. Clinical examination and corneal topography confirmed generalized corneal bulging and global corneal thinning. A Pentacam® (Oculus Optikgerate, Wetzlar, Germany) demonstrated bilateral diffuse corneal thinning (368 µm in the right eye and 371 µm in the left eye). Phacoemulsification was performed in the right eye after thorough workup and modification of the surgical technique. This case report helps in better understanding of the challenges of cataract surgery and intraocular lens selection in a keratoglobus patient, and stresses the need for both thorough preoperative planning and intraoperative surgical modifications.

Immunohistochemical analysis and correlation of cyclooxygenase-2 expression status with clinicopathological parameters in head and neck squamous cell carcinomas: An Indian perspective.

CONTEXT: Head and neck squamous cell carcinoma (HNSCC) poses a major health problem and despite the advancements in its diagnosis and management the overall survival has not improved significantly. A search for newer diagnostic and prognostic markers along with fresh molecular targets is required for its prevention and cure. AIMS: The study aims to study the expression of cyclooxygenase-2 (COX-2) in HNSCCs and investigate its correlation with the clinicopathological profile of these cases. This study was performed to determine the significance of COX-2 expression in the Indian context. SETTINGS AND DESIGN: This study incorporated 90 cases of HNSCCs; both prospectively and retrospectively in a tertiary care center. MATERIALS AND METHODS: Expression of COX-2 on immunohistochemistry (IHC) was evaluated in correlation with the histological grade, maximum tumor size, tumor depth, nodal status and lymphovascular/perineural invasion (lvi/pni). The study received a waiver from the institutional ethics committee. STATISTICAL ANALYSIS USED: Statistical analysis of the data was done using SPSS software. RESULTS: COX-2 expression was found in 97.8% of the cases. A statistically significant correlation of COX-2 immunopositivity was found with the histological grade, clinical staging (tumor size and nodal status), maximum tumor depth and lvi/pni in our study (P < 0.05). CONCLUSIONS: COX-2 is expressed by most of the cases in this study. Its expression is related to tumor growth, differentiation and aggressiveness and therefore can be used as a good independent prognostic marker in HNSCCs. There is also possible scope of using it for targeted therapy in HNSCCs.

Imaging in a rare case of intramuscular angioleiomyoma around the knee joint.

Angioleiomyoma are rare benign tumors originating from smooth muscles of veins. They are found more commonly in extremities and are seen in subcutaneous tissue. Intramuscular angioleiomyoma is rare and can be confused with hemangioma. Though they do not have any characteristic imaging features but they should be considered in the differential diagnosis due to certain specific imaging findings on MRI which are discussed in this article.

Correlating the treatment outcome with tumor staging, grading, and various treatment modalities in patients with esthesioneuroblastoma.

OBJECTIVE: Although till date no management protocol for esthesioneuroblastoma (ENB) has been standardized due to tumor rarity, still multimodality approach shows better treatment outcomes as compared to surgery alone. The objective of this study was to analyze the clinicopathological spectrum of ENB and to correlate treatment response with tumor staging, histopathological grading, and various treatment modalities. MATERIALS AND METHODS: Twenty-one consecutive patients with biopsy-proven ENB were studied and evaluated for response to treatment in the form of complete tumor resolution. Results were analyzed and correlated with stage and grade of tumor and form of therapy received. RESULTS: There was male preponderance (3.2:1) with age ranging between 7 and 63 years (median of 25 years). Survival rates significantly dropped with increasing tumor stage (63.6% in stages A and B vs. 30% in stages C and D) and grade (100% in Grades 1 and 2 vs. 31.25% in Grades 3 and 4). The recurrence rate was 80% in surgery alone group, which came down to 43.7% if surgery was supplemented with other modalities. In cases where multimodality treatment plan was used, endoscopic procedures fared equally as open surgical procedures. CONCLUSION: Hyam's grade and Kadish stage are important prognostic indicators of treatment outcome, with survival rates dropping with increasing tumor stage and grade. Multimodality treatment protocols have improved the disease outcome, making endoscopic surgery equivalent to radical surgeries regarding result outcomes and giving other advantages such as better cosmesis, less treatment-related morbidities, decreased hospital stay, and better cost-effectiveness.

Rebound inflammation after an intravitreal injection in Vogt-Koyanagi-Harada syndrome.

A 43-year-old male with chronic Vogt-Koyanagi-Harada syndrome (VKH) presented with subfoveal choroidal neovascular membrane (CNVM) in the right eye with no evidence of active inflammation. He underwent intravitreal bevacizumab and dexamethasone injections. Postinjection he developed fresh keratic precipitates and exudative retinal detachment (RD). He received two more bevacizumab injections with oral corticosteroids and immunosuppressants causing resolution of exudative RD with scarred CNVM. We report this case to highlight that intravitreal injection may act as a trigger for rebound inflammation in VKH patients and may require anti-inflammatory drugs to be started even in the absence of an active inflammation.

Syphilitic uveitis misdiagnosed as viral retinitis-a misleading history.

BACKGROUND: Syphilitic uveitis is an infective uveitis and a great mimicker. Misdiagnosis can lead to delay in the specific treatment resulting in deterioration of uveitis and loss of vision. FINDINGS: A 38-year-old unmarried female presented with pain, redness, and blurring of vision in the left eye for the last 5 days. She denied history of any sexual exposure in the past. Anterior segment examination of the right eye was normal and the left eye showed keratic precipitates with anterior chamber cells and iris pigments on anterior lens capsule. Fundus examination of the right eye showed a hyperemic disc with posterior placoid retinochoroiditis and the left eye showed dense vitritis, hyperemic disc, and superficial retinal precipitates. She was misdiagnosed as viral retinitis elsewhere and started on antivirals with oral corticosteroids which resulted in deterioration of uveitis and progression to bilateral involvement. Further systemic investigations confirmed the diagnosis of syphilis and human immunodeficiency virus infection. She was then started on anti-syphilitic and anti-retroviral therapy which resulted in restoration of the vision in one eye. CONCLUSION: Syphilitic uveitis does not occur in primary disease and is common in secondary and early latent phase of syphilis. History given by the patient is often contributory however at times can be misleading. A high clinical suspicion and thorough investigation is necessary for the correct diagnosis and timely intervention in preventing loss of vision.

Epidermal growth factor receptor expression in carcinoma gallbladder: A prospective study in Indian scenario.

AIM: Gallbladder cancer (GBC) is an aggressive disease with poor prognosis and complete surgical resection offering the only cure. Increased epidermal growth factor receptor (EGFR) expression has been noted in various cancers including GBC. Several studies across the world have examined the expression of EGFR in GBC. This study has been done to see the EGFR expression in GBC in Indian context. MATERIALS AND METHODS: Fifty cases of GBC were evaluated histopathologically using hematoxylin and eosin stained sections. Immunohistochemical assessment of EGFR expression was done, and scoring was done as per Kaufman et al. Data were collected, tabulated, and analyzed statistically by SPSS 16.0 version (Chicago, Inc., USA) software. RESULTS: Of 50 cases, 44 revealed EGFR over-expression while 6 were negative. Of the 44 cases, 10 had weak EGFR immunostaining intensity (1+), 26 had moderate (2+), and 8 showed strong EGFR immunostaining (3+). We found that most of the cases showing weak EGFR immunostaining intensity (1+) were well-differentiated tumor (70%) and cases with a strong EGFR immunostaining intensity (3+) were poorly differentiated cases of adenocarcinoma (75%). Moderately differentiated adenocarcinoma showed moderate EGFR immunostaining intensity (2+) in most of the cases (53.8%). CONCLUSION: EGFR is expressed in most of the cases of GBC. In well-differentiated adenocarcinoma, the EGFR expression is less compared to EGFR expression in poorly differentiated tumor, leading to the conclusion that the differentiation of the tumor and EGFR expression is inversely related. Thus, intensity of EGFR expression may correlate with aggressiveness of disease.

Uterine Adenomatoid Tumors: A Study of Five Cases Including Three Cases of the Rare Leiomyoadenomatoid Variant.

OBJECTIVE: Adenomatoid tumor is a benign neoplasm of mesothelial origin encountered most often in the male and female genital tracts. This tumor has a distinct morphology and is characterized by anastomosing and variably sized tubules lined by epithelioid and flattened cells. Only 4 cases of the extremely rare leiomyoadenomatoid variant are on record. We report 5 cases of adenomatoid tumor including 3 cases of leiomyoadenomatoid tumor of the uterus, which is an extremely rare variant of adenomatoid tumor, difficult to recognize on morphology. METHOD: A detailed histopathological review of all the uterine tumor diagnosed as fibroid and adenomatoid tumor over the period of 4 years was done. RESULTS: A total of 5 cases of adenomatoid tumor were documented including 3 cases of leiomyoadenomatoid variant. CONCLUSION: Leiomyoadenomatoid variant of adenomatoid tumor often missed both on imaging and histopathological examination and hence needs to be recognized as a distinct morphological entity.

Margins in skin excision biopsies: principles and guidelines.

Skin biopsies are usually undertaken to confirm a clinical diagnosis, to remove a lesion, and to determine the adequacy of excised tissue margin. A surgical margin is technically defined as the "edge" of the tissue removed. The term is especially pertinent when the tissue excised is suspected of being involved by a malignant process. One of the most important predictive and prognostic factors of a malignant lesion is whether the margins of the resected specimen are involved by the tumor or not. The purpose of this review is to provide an insight into grossing of a skin biopsy specimen with emphasis on techniques and reporting of excision biopsy margins.