Jagdish K. Dhingra

Autofluorescence characteristics of oral mucosa

The fluorescence characteristics of tissues depend upon their biochemical composition and histomorphological architecture, both of which undergo a change during malignant transformation. These changes are detectable as an alteration in the fluorescence spectral profile of the tissues.

Paranasal sinus development: A radiographic study

Objective To demonstrate the development of the paranasal sinuses in a pediatric population by computed tomography scans.

Hereditary Hemorrhagic Telangiectasia: A Review of 76 Cases†

Objectives/Hypothesis Hereditary hemorrhagic telangiectasia has long been viewed as a rare condition. Recent evidence indicates that the disorder is more frequent than previously thought. Recalcitrant epistaxis is a salient feature of this disease, and the otolaryngologist is often called on to make the diagnosis and guide the primary management of patients with hereditary hemorrhagic telangiectasia. Wider recognition of this condition, awareness of the natural history and associated findings, appropriate workup and screening for arteriovenous malformations (lungs, brain, liver), and knowledge of appropriate interventions can help avoid the considerable morbidity associated with hereditary hemorrhagic telangiectasia.

Diagnosis of Head and Neck Precancerous Lesions in an Animal Model Using Fluorescence Spectroscopy

Laser‐induced fluorescence (LIF) of tissues depends on their biochemical and histomorphologic characteristics. LIF spectroscopic properties of 9,10‐dimethyl‐1,2‐benzanthracene (DMBA)‐induced precancerous and early cancerous lesions in a hamster buccal pouch mucosa model were studied. Fluorescence spectra from neoplastic lesions showed a characteristic fluorescence peak in the red region of the visible spectrum centered between 630 and 640 nm when excited with 410‐nm light. Using this as a diagnostic criterion, 45 of 49 lesions studied were correctly diagnosed, including early dysplastic lesions. Follow‐up study of four dysplastic lesions over 2 weeks revealed an increase in red fluorescence intensity. The findings of these experiments suggest that LIF spectroscopy may be a valuable noninvasive technique not only for early diagnosis of head and neck cancer, but also to probe a possible biochemical surrogate biomarker in the follow‐up of suspected lesions.

Slow-release 5-fluorouracil and triamcinolone reduces subglottic stenosis in a rabbit model.

A previous pilot study suggested that a sustained-release conjugate that provided a slow release of 5-fluorouracil and triamcinolone acetonide injected into the tracheal and paratracheal tissues of rabbits at the time of subglottic surgery reduced the formation of subglottic stenosis. Our study was undertaken to confirm the effect. Ten milligrams of the compound suspended in hyaluronic acid was injected at the time of injury via a laryngofissure approach. The results showed that the control group had a mean stenosis of 52%, whereas the treated group had a mean stenosis of 32%. There was a significant difference between the treated and untreated groups (p = 003). It is hoped that this co-drug ultimately can be used in humans to reduce stenosis formation after laryngotracheal surgery and in other forms of otorhinolaryngological surgery.

Perineural invasion in cutaneous squamous cell carcinoma: role of immunohistochemistry, anatomical site, and the high-affinity nerve growth factor receptor TrkA

Perineural invasion (PNI) has been recently added to the American Joint Committee on Cancer cutaneous squamous cell carcinoma (cSCC) staging criteria as a high-risk tumor characteristic and is purportedly more common in cSCCs of the head and neck (H&N). Expression of the high-affinity nerve growth factor receptor TrkA has been shown to be associated with PNI in noncutaneous neoplasms. Given this, we sought to ascertain the incidence of PNI in cSCCs using double immunostaining (DIS) and to investigate PNIs relationship with TrkA and established histopathologic prognosticators. Fifty-seven cSCCs from the H&N and 53 from non-H&N areas were immunohistochemically analyzed for PNI (DIS with S-100 and p63) and TrkA expression. Comparing H&N versus non-H&N areas, using hematoxylin and eosin, PNI was detected in 11% versus 6% cases, respectively, and, using DIS, in 23% versus 15%, respectively, with significant disagreement between both methods (κ = 0.47; P = .002). There was a 2.33-fold increase in PNI detection with DIS compared to hematoxylin and eosin (95% confidence interval, 1.12-4.87; P = .02). TrkA expression was 1.96 times more frequently observed in cSCCs from the H&N compared to those from non-H&N areas (P = .01). Regardless of site, TrkA expression was associated with decreased degree of differentiation (odds ratio, 6.46; P = .0006) and high-risk morphologic variants (odds ratio, 6.53; P = .002) but not significantly associated with PNI (P = .33). Increased PNI detection with DIS underscores the adjunctive utility of immunohistochemistry in microstaging. Significantly more common TrkA expression in cSCCs of the H&N argues in favor of heterogeneity among SCCs from different anatomical sites.

BRAF and Epithelial-Mesenchymal Transition: Lessons From Papillary Thyroid Carcinoma and Primary Cutaneous Melanoma.

The increased prevalence of BRAF mutations in thyroid carcinoma and primary cutaneous melanoma (PCM) hint that dysregulation of BRAF might contribute to the noted association between PCM and thyroid carcinoma. A recent study evaluating the rate of BRAFV600E mutations among patients who had been diagnosed with primary papillary thyroid carcinoma (PTC) and PCM showed that patients with either PCM or PTC were at an increased risk of developing the other as a second primary malignant neoplasm. Furthermore, the authors noted that samples from patients suffering from both malignancies exhibited a higher rate of incidence of the BRAFV600E mutation, compared with patients not suffering from both malignancies. These studies support the hypothesis that the pathogenesis of these 2 malignancies might share a conserved molecular pattern associated with dysregulation of the BRAF protein. One mechanism through which BRAF might contribute to PCM and thyroid carcinoma progression is through induction of epithelial-mesenchymal transition (EMT). Specifically, the Snail/E-cadherin axis has been demonstrated as a pathway dysregulated by BRAF, leading to EMT in both malignancies. Our analysis focuses on the results of these recent investigations, and through a review of select molecules relevant to EMT, looks to provide a context by which to better understand the relevance and role of stromal-parenchymal signaling and the BRAF mutation in the pathogenesis of PTC and PCM.

Office-Based Ultrasound-Guided FNA with Molecular Testing for Thyroid Nodules.

Objective Ultrasound-guided fine-needle aspiration (FNA) biopsy is the primary method of evaluating thyroid nodules. Up to one-third of FNA results are reported to be of “indeterminate” cytology, which carries a 25% malignancy risk. Most of these patients are referred for diagnostic surgery, which results in many unnecessary interventions. We implemented an FNA protocol combining expert thyroid cytopathology and molecular testing of indeterminate lesion in our community practice. This study is a report of the outcomes from this protocol as compared with historical data in the same setting over a similar period. Study Design Case series with planned data collections and retrospective chart reviews. Setting A large community-based practice with multiple satellite offices. Subjects and Methods A total of 264 thyroid nodules (196 patients) were evaluated under the new protocol from January to December 2014, and data were collected in a prospective manner. Historical data for a similar period (2012), obtained by chart review, included 164 nodules (134 patients) biopsied in a hospital setting by a number of radiologists, with cytologic interpretations completed by community-based pathologists. Statistical analyses included χ2 and Fischer’s exact tests. Results Based on the new protocol, the rate of indeterminate lesion diagnosis was reduced from 24% to 10% (P = .006) and the rate of diagnostic surgery from 24% to 6% (P < .001). Of the patients who underwent diagnostic surgery, 58% had evidence of malignancy, as compared with 12% in our previous experience (P = .04). Conclusion Expert cytopathologic analysis combined with molecular testing of indeterminate FNA samples significantly reduced unnecessary operations.