Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.

INTRODUCTION: Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. METHOD: Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). RESULTS: Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. CONCLUSION: The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

Pharyngocutaneous Fistula Following Primary and Salvage Laryngectomy: Aetiology and Predictive Factors.

Laryngeal cancer treatment is often wrought with challenges, pharyngocutaneous fistula formation (PCF) in patients undergoing either primary or salvage laryngectomy for laryngeal and hypopharyngeal for squamous cell carcinoma is an important one. We aimed to study the factors before and at the surgery that are associated with PCF formation in a South Indian tertiary care hospital. A retrospective chart review of 127 patients who underwent total laryngectomy (TL) between May 2014 and April 2019 at our centre were done. Data was collected, including patient age and gender, comorbidities (Diabetes mellitus, COPD and hypothyroidism), smoking, tumor stage and site, prior tracheostomy, prior radiation, concurrent neck dissection and type of pharyngoplasty, Preoperative hemoglobin and albumin levels, surgical margin status and development of a PCF was also done. Further details specific to the development of a PCF were recorded for that subset of patients including the length of time to fistula, mode of closure, time of closure and modality of management. The overall incidence of PCF was 16.5% (21 of 127 patients), and the median time from TL to the diagnosis of PCF was 6 days (range, 3-20 days). The analysis was done separately for laryngectomies without any pharyngeal reconstruction (112/127 patients). In patients treated with a primary TL, the incidence of PCF was 12.20% (10 of 82) and 26.66% (8 of 30) after salvage TL. Subset analysis for type of pharyngoplasty repair showed 12% (15/127) underwent different types of vascularised/muscular flap for smaller residual pharyngeal mucosa, of which 20% (3/15) developed PCF and one patient developed haematoma needing exploration and re-suturing. The predictive factors for PCF were hypopharynx cancer (P < 0.05), surgical margin positivity (P < 0.0001), female gender (P < 0.05), absence of prior tracheostomy (P < 0.05) and tumor extension into pyriform sinus mucosa (P < 0.05). Preoperative patient factors of gender and site of primary along with histological margin positivity and extension of tumor to the pyriform sinus mucosa were significant risk factors for PCF formation. Pre-Op radiotherapy remains a strong clinical suspicion but not statistically significant.

The Role of Modified Killian's Method in the Evaluation of Hypopharyngeal and Supraglottic Cancers.

Priyanka Schilling AmarObjectives Hypopharyngeal cancer is one of the upper aerodigestive tract malignancies with the poorest prognosis. The aim of this study was to assess the role of modified Killian's (MK) method in routine, outpatient-based flexible laryngoscopy to improve visualization and assess the extent of supraglottic and hypopharyngeal cancers. Materials and Methods An observational study was conducted in a tertiary hospital in India where fifty consecutive patients who presented to the outpatient clinic with suspected hypopharyngeal and supraglottic malignancy underwent a conventional laryngoscopy as well as MK method. The site and extent of the tumor on endoscopy were recorded and the videos were graded independently by two investigators on Murono's scale from 1 to 5. A subset of these patients who underwent direct laryngoscopy under general anesthesia was also scored with the above scale. The scores were compared to check the accuracy of flexible laryngoscopy with the MK method in staging cancer. Statistical Analysis Descriptive statistics were given using mean (standard deviation [SD]) for continuous variables and frequency (percentage) for categorical variables. The difference between the mean scores was analyzed using the paired-t test. The agreement between the scales and the observer, that is, the inter- and intraobserver agreement, was presented with concordance rate and Kappa weighted analysis. Results In this study, the mean scores of the Murono's scale grading of the conventional method, MK method, and direct laryngoscopy were 1.42 (SD: 0.64), 2.94 (SD: 0.95), and 4.30 (SD: 1.49), respectively, which showed significant improvement in scores with MK method. In addition, the subset analysis demonstrated a significant agreement between direct laryngoscopy and MK method. Conclusion The MK method is a good diagnostic test and a valuable adjunct to diagnostic flexible laryngoscopy in the evaluation and staging of hypopharyngeal and supraglottic cancers.

Role of Narrow Band Imaging in Laryngeal Lesions: A Prospective Study from Southern India.

To assess the utility of Narrow Band Imaging (NBI) as a diagnostic tool in evaluating laryngeal pathology in patients presenting with hoarseness. Study design: Prospective cross sectional diagnostic study. Methods: 200 patients with voice change were recruited and laryngeal findings documented with high definition flexible endoscopy with both white light and narrow band light and the representative still images recorded for analysis. The NBI intraepithelial papillary capillary loop (IPCL) patterns was compared with the histopathology report. Of the 200 patients evaluated, 84 lesions were biopsied which included both benign and malignant lesions. The sensitivity obtained was 73.3% [54.1-87.7% with 95% CI] and the specificity was 87% [75.1-94.6% with 95% CI] for detecting malignant lesions. NBI can be considered as a useful diagnostic tool in evaluating laryngeal pathology and can be used to detect early premalignant and malignant lesions.

Role of Human Papilloma Virus in the Aetiology of Sinonasal Cancers.

Sino nasal carcinogenesis is attributed to numerous factors, namely tobacco, alcohol and snuff as the most common. Human Papilloma virus (HPV) has been associated with aetiopathogenesis of malignancies in the upper aerodigestive tract (UADT). The prevalence of HPV in Sino-nasal malignancy (SNM) which is closely related to UADT in location is not known. Hence, this study aims to explore if there is any such association between HPV and Sino nasal malignancies. This study aims to explore the association between HPV and SNM. A prospective case control study using tumour tissue specimens from 40 Sinonasal carcinoma patients and benign nasal tissue specimens from 50 cancer-free controls were conducted. Histopathological analysis and DNA extraction (DNeasy® Tissue kit) and polymerase chain reaction for detection of HPV was done. Positive samples underwent sequencing to detect the HPV serotype and statistical correlation was performed using SPSS software. All 90 patients were tested for HPV and we found that none of the patients had any association with HPV. Sino-Nasal malignancy in the Indian Sub-continent may not be related to HPV primarily.

The Association of Human Papillomavirus in Benign and Malignant Laryngeal Lesions-a Pilot Study.

Various etiological factors have been described in laryngeal carcinogenesis. Tobacco and alcohol play a major role in the development of laryngeal cancers. However, recently there has been an overshadowing of association of human papillomavirus infection in laryngeal cancers. The aim of this study is to assess the prevalence of human papillomavirus (HPV) in malignant laryngeal lesions. This is a case control study. We conducted this study using tumor tissue specimens from 30 laryngeal squamous cell carcinoma patients and benign laryngeal tissue specimens from 30 cancer-free controls. The specimens from the lesion were sent to histopathological analysis as well as DNA extraction (DNeasy® Tissue kit) and polymerase chain reaction for detection of HPV. Positive samples underwent sequencing to detect the HPV serotype. Statistical analysis was performed using SPSS software. All 30 benign laryngeal lesion specimens were negative for the HPV DNA, while 4 of the 30 (7.5%) squamous cell carcinoma lesions were positive. One was HPV 16 and another one HPV 11. Two positive cases were not able to be sequenced probably due to low viral load. Our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be low. Further prospective studies should be conducted with a larger group of patients to confirm the role of HPV in laryngeal cancers especially in treatment response and survival.

Parapharyngeal space pleomorphic adenoma with extensive lipometaplasia - A rare unique pathological entity.

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary gland. Fat-containing tumors encountered in salivary glands are very rare. We had a case of PA of parapharyngeal space and surprisingly the final histopathology showed an unusual finding of lipometapasia. We believe that this is the first case from parapharyngeal space to be reported in the literature. The aim of this report is to discuss the behavior of lipometaplasia in PA with review of literature. Pathological characterization of this rare tumor might help in proper classification and enhance their recognition.

Myoepithelial Tumors of Salivary Gland: A Clinicopathologic and Immunohistochemical Study of 15 Patients with MIB-1 Correlation.

Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological features, immunohistochemical profile and biological behavior are not well characterized and pose a diagnostic challenge. A total of 15 myoepithelial tumors, diagnosed during 2012 and 2019 were subcategorized and correlated with MIB-1 labeling index (LI) and various histological parameters. Immunohistochemical stains for MIB-1 and other antibodies were performed. Statistical analysis was done by chi-square test, Fisher's exact test and Kaplan Meier curve. Nine patients were male and six were female with the median age of 44 years (range 21-83 years). Of the 15 patients, 6 cases were classified as myoepithelioma (ME) and 9 cases as myoepithelial carcinoma (MECA). Parotid gland was the most common site (46.7%) followed by the palate. MEs showed well circumscribed tumor borders whereas MECAs exhibited focal capsular to extensive invasion into adjacent tissues. Epithelioid cell morphology was most common followed by mixed cell morphology. MIB-1 LI was significantly associated with invasive tumor borders, necrosis and high mitosis. Increased frequency of recurrence was noted with high MIB-1 LI, though it was not statistically significant. MIB-1 LI was high in nearly all MECAs with focal capsular to extensive invasion while low in MEs. Myoepithelial tumor with multinodular growth pattern and focal capsular invasion may have an indolent behavior if mitotic activity and MIB-1 LI is low. Early diagnosis and treatment of MECAs significantly improves the patient's survival and prognosis.

Management of the Thyroid Gland in Papillary Carcinoma of the Thyroglossal Cyst: A Case Report.

Carcinoma arising in a thyroglossal cyst is rare. We present a case of anterior neck swelling diagnosed to be thyroglossal cyst clinically which turns out to be a papillary carcinoma arising in thyroglossal cyst. She underwent sistrunk procedure with total thyroidectomy and diseasefree on follow up evaluation. Even though preoperative ultrasonography had shown thyroid nodule, the final histology did not show malignancy. There is a paucity of clear-cut guidelines in the management of the thyroid gland in a thyroglossal cyst carcinoma. In thyroglossal cyst carcinoma cases, we recommend thyroidectomy only when there is a thyroid nodule with high-risk features.

Feasibility of Transoral Approach to Accessory Parotid Tumors.

Tumors of the accessory parotid gland are very rare. Surgical removal of an accessory parotid tumor is usually accomplished by superficial parotidectomy through an external neck incision. However, this procedure inevitably results in a neck scar. In this case, we performed complete excision of a parotid tumor via an endoscopic-assisted transoral approach. Resection of such benign tumors can be achieved with less morbidity by endoscope-assisted surgery with a nerve monitoring system. The field of transoral surgery will continue to expand with technological advancements.

Langerhan's cell Histiocytosis of Sphenoid Sinus causing Vision Loss: A Case Report.

Langerhan's cell histiocytosis is an uncontrolled proliferation of dendritic cells. The involvement of skull base is rare. Variable clinical presentation and multi organ involvement often warrant a multidisciplinary approach for a successful diagnosis. We are reporting a case of 16-year-old male with sphenoid sinus Langerhan's cell histiocytosis which presented as a sudden and painless loss of vision. It is a rare entity in the diagnosis of blindness. Delayed diagnosis and treatment can result in serious complications. The radiological features and management options are discussed with a review of the pertinent literature. Keywords: : blindness; histiocytosis; langerhans-cell; sphenoid sinus.

Hyper-fractionated Intensity Modulated Radiation Therapy (HF-IMRT) in Head and Neck Cancer: The Technical Feasibility and Results of a Short Clinical Series.

Among various altered fractionation schedules, only hyper-fractionation has proven increased local control in head and neck cancers. MARCH (Metanalyses of Hyperfractionated or Accelerated radiotherapy in Head and neck cancer) concluded that hyper-fractionated radiotherapy in head and cancers had a survival benefit. This study attempts to combine the benefits of hyper-fractionation with the tissue sparing qualities of intensity modulated radiotherapy. Three patients with advanced oro-pharyngeal cancers were treated with HF-IMRT (Hyperfractionated-IMRT) (2 oropharynx, 1 hypopharynx). Two phase treatment planning with phase I prescribed to high risk volume (HRV) and intermediate risk volume (IRV), 60Gy in 50 fractions at 1.2Gy per fraction, 2 fractions/day, 6-8 h apart. The low risk volume (LRV) received 55Gy to the 95% volume at 1.1Gy per fraction in the same 50 fractions. In phase II, HRV alone was prescribed 1960cGy in 20 fractions over two weeks. Total dose to HRV was 7960cGy in 7 wk. No concurrent chemotherapy was given. Treatment was completed as planned (<60 days; break of 11 days was due to radiation toxicity). Only one patient had grade III toxicity. All three required diet modifications, an average weight loss of 3 kg and no hospitalization required during treatment. This pilot study shows the feasibility of an effective hyper-fractionation with IMRT for head and neck cancers. A Phase II trial is required to prove its efficacy.

Myoepithelial carcinoma arising in recurrent pleomorphic adenoma in maxillary sinus.

Myoepithelial carcinoma is characterized by nearly exclusive myoepithelial differentiation and evidence of malignancy. It may arise de novo or in preexisting benign tumors including pleomorphic adenoma and benign myoepithelioma. A 39-year-old lady presented with painless progressive swelling on the right cheek and right side of palate. On surgery, there was a mass in right maxillary sinus which was surgically excised and diagnosed on histopathology as pleomorphic adenoma. Subsequently, there were two recurrences. The first recurrence was in the right maxilla after 2 years that was removed surgically and diagnosed as pleomorphic adenoma. One year later, she came with rapidly progressive swelling in bilateral cheeks and face. Intraoperatively, there was a large tumor in both maxillary sinuses with extensive local infiltration. Histologically, it was diagnosed as myoepithelial carcinoma. Carcinoma ex pleomorphic adenoma is usually a high grade malignancy. It occurs most commonly in parotid gland followed by submandibular glands, minor salivary glands and occasionally in sublingual gland. To the best of our knowledge, this is the first case of myoepithelial carcinoma arising in a recurrent pleomorphic adenoma in the maxillary sinus.

Subglottic thyroglossal duct cyst: a rare intralaryngeal presentation.

Thyroglossal duct cysts are common midline neck swellings that can present at any site along their migratory pathway. They are frequently situated just below the hyoid bone. Extension to the subglottic area is very rare; such an unusual presentation can complicate the diagnosis of a thyroglossal duct cyst. We report the case of a 30-year-old man who presented with a subglottic thyroglossal duct cyst and associated laryngeal symptoms. To the best of our knowledge, only 2 similar cases have been previously reported in the literature, both of which occurred in 2-year-old boys. We believe, therefore, that ours is the first reported case of a subglottic thyroglossal duct cyst in an adult. We discuss the clinical presentation, diagnosis, and treatment of our patient, and we summarize the literature on intralaryngeal thyroglossal duct cysts.

Tuberculosis in otorhinolaryngology: clinical presentation and diagnostic challenges.

Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) had Mycobacterium tuberculosis culture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

Angioleiomyoma of the nasal cavity.

Angioleiomyoma is a rare benign tumor in the nasal cavity. There are very few reports in literature. A 34 year old male presented with left sided nasal obstruction and epistaxis. Clinical evaluation revealed a lesion replacing the anterior two-third of the Left inferior turbinate. An endoscopic excision under hypotensive anesthesia was performed. Histopathology confirmed a diagnosis of Angioleiomyoma. The cause and site of origin of angioleiomyomas when they arise from the inferior turbinate remains unclear. We review the literature available on nasal angioleiomyoma. When limited to the nasal cavity endoscopic excision is the treatment of choice.

Mycological profile of fungal sinusitis: An audit of specimens over a 7-year period in a tertiary care hospital in Tamil Nadu.

BACKGROUND: Fungi are being increasingly implicated in the etiopathology of rhinosinusitis. Fungal sinusitis is frequently seen in diabetic or immunocompromised patients, although it has also been reported in immunocompetent individuals. Invasive fungal sinusitis, unless diagnosed early and treated aggressively, has a high mortality rate. AIM: Our aim was to look at the mycological and clinical aspects of fungal sinusitis in a tertiary referral center in Tamil Nadu. DESIGN: This is a retrospective audit conducted on fungal culture positive sinus samples submitted to the Microbiology department from January 2000 to August 2007. Relevant clinical and histopathological details were analysed. RESULTS: A total of 211 culture-positive fungal sinusitis samples were analysed. Of these, 63% had allergic fungal sinusitis and 34% had invasive fungal sinusitis. Aspergillus flavus was the most common causative agent of allergic fungal sinusitis and Rhizopus arrhizus was the most common causative agent of acute invasive sinusitis. A significant proportion of these patients did not have any known predisposing factors. CONCLUSION: In our study, the etiology of fungal sinusitis was different than that of western countries. Allergic fungal sinusitis was the most common type of fungal sinusitis in our community. Aspergillus sp was the most common causative agent in both allergic and chronic invasive forms of the disease.

Chondrosarcoma of the nasal septum.

Chondrosarcoma of the head and neck region are relatively uncommon, arising rarely in the naval septum. The reported cases of nasal septal chondrosarcomas are extensive lesions with involvement of paranasal sinuses, orbit or skull base at the lime of diagnosis. Those limited to the nasal cavity is extremely rare and to date there has been one case report in English language literature. We present a case of chondrosarcoma of the nasal septum with involvement of the nasal cavity alone and no evidence of bony erosion. Initial multiple biopsies showed mature chondromatous areas with no atypia. The patient had wide excision of the tumour. The final biopsy of the excised specimen revealed foci of well-differentiated chondrosarcoma. Wide surgical excision with adequate margins should be considered as the treatment of choice in lesion of nasal septum even if initial biopsies are negative for malignancy. Hence this case report.