H. Stan McGuff

MANAGEMENT OF THE UNKNOWN PRIMARY CARCINOMA: LONG-TERM FOLLOW-UP ON A NEGATIVE PET SCAN AND NEGATIVE PANENDOSCOPY

The unknown primary carcinoma in the head and neck has been estimated to represent up to 7% of all head and neck carcinomas. In an attempt to identify the occult primary tumor the evaluation of this patient population has included a complete head and neck examination, flexible fiberoptic endoscopy, and imaging with CT/MRI. More recently, positron emission tomography (PET) has been advocated as a tool to detect primary tumors.

Nano-bio-chip sensor platform for examination of oral exfoliative cytology

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve ≤0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival. Cancer Prev Res; 3(4); 518–28. ©2010 AACR.

The role of positron emission tomography scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy

Objective: The objective of this study was to determine the sensitivity, specificity, and predictive value of 18‐fluorodeoxyglucose positron emission tomography (PET) in predicting residual cervical metastatic disease in patients with N‐positive necks undergoing curative radiotherapy and chemoradiotherapy for squamous cell carcinoma (SCC) of the upper aerodigestive tract.

Minimally differentiated acute myelogenous leukemia (AML-M0) granulocytic sarcoma presenting in the oral cavity.

Acute myelogenous leukemia with minimal differentiation (AML-M0) is a rare subtype of acute leukemia in which blasts fail to show morphologic differentiation and conventional cytochemical stains and myeloid markers are negative. Acute myelogenous leukemia (AML) presents primarily with peripheral blood and/or bone marrow involvement. Presentation in extramedullary sites, including the head and neck region, is not uncommon. Acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) have had the highest incidence of associated oral infiltrates. We report a case of a 58-year-old gentleman, with no prior history of acute leukemia, presenting with a solitary palatal swelling. Initial morphologic examination favored high-grade non-Hodgkins lymphoma (NHL). Conventional cytochemical and immunohistochemical stains were negative for lymphoid and myeloid markers. Subsequent immunophenotyping via flow cytometry performed on peripheral blood and bone marrow aspirate demonstrated myeloid lineage without lymphoid differentiation, confirming the diagnosis of AML-M0.To our knowledge, this subtype of AML-M0 has not been previously reported involving the oral cavity. With absence of morphologic differentiation, and negative findings on conventional cytochemical and immunohistochemical stains, this subtype of leukemia may be misdiagnosed as non-Hodgkins lymphoma (NHL). Flow cytometry is useful in detecting the myeloid lineage of this leukemia.

Soft tissue response of the rabbit larynx to Gore-Tex implants.

The use of Gore-Tex (expanded polytetrafluoroethylene) for medialization laryngoplasty has recently been described. Clinically, this laryngeal implant has performed well, but no animal studies evaluating the use of this implant in the larynx have been published. This study examines the gross and histologic response of the rabbit larynx to the Gore-Tex implant. Five rabbits underwent bilateral medialization with the Gore Thyroplasty Device. The vocal folds were left innervated and mobile. After 6 months, the rabbits were painlessly sacrificed and the implants were evaluated by gross inspection and histologic examination. No gross changes to the glottis occurred, and the implants were easily removed with gentle traction. A modest inflammatory response with a thin fibrous capsule was present around the implant. Foreign body giant cells were observed at the interface of the implant with the tissue. No migration or extrusion of the implant was observed. These results suggest that Gore-Tex is biocompatible in the rabbit larynx.

Lymphomas of the oral soft tissues are not preferentially associated with latent or replicative Epstein-Barr virus

OBJECTIVES Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. STUDY DESIGN A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. RESULTS Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitts lymphomas. In contrast, Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site of previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. CONCLUSIONS These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status.

Portable oral cancer detection using a miniature confocal imaging probe with a large field of view

We demonstrate a MEMS micromirror enabled handheld confocal imaging probe for portable oral cancer detection, where a comparatively large field of view (FOV) was generated through the programmable Lissajous scanning pattern of the MEMS micromirror. Miniaturized handheld MEMS confocal imaging probe was developed, and further compared with the desktop confocal prototype under clinical setting. For the handheld confocal imaging system, optical design simulations using CODE VR® shows the lateral and axial resolution to be 0.98 µm and 4.2 µm, where experimental values were determined to be 3 µm and 5.8 µm, respectively, with a FOV of 280 µm×300 µm. Fast Lissajous imaging speed up to 2 fps was realized with improved Labview and Java based real-time imaging software. Properties such as 3D imaging through autofocusing and mosaic imaging for extended lateral view (6 mm × 8 mm) were examined for carcinoma real-time pathology. Neoplastic lesion tissues of giant cell fibroma and peripheral ossifying fibroma, the fibroma inside the paraffin box and ex vivo gross tissues were imaged by the bench-top and handheld imaging modalities, and further compared with commercial microscope imaging results. The MEMS scanner-based handheld confocal imaging probe shows great promise as a potential clinical tool for oral cancer diagnosis and treatment.

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials.

OBJECTIVE Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. STUDY DESIGN Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. RESULTS Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. CONCLUSIONS The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis.

Anti-transforming growth factor beta as a treatment for laryngotracheal stenosis in a canine model.

Objectives/Hypothesis: Laryngotracheal stenosis (LTS) represents a significant treatment dilemma faced by otolaryngologists. Recent topical use of Mitomycin C as an adjunctive treatment has proved helpful but does not completely prevent stenosis. Current literature suggests that transforming growth factor beta (TGFB) plays a significant role in the development of subglottic stenosis. We modified an existing canine model to test antitransforming growth factor beta (anti‐TGFB) as a possible treatment for laryngotracheal stenosis.

Pilomatrixoma of the face: A benign skin appendage mimicking squamous cell carcinoma

fi c t A t t r m c t r o n c a ilomatrixomas are benign skin neoplasms orignating from cells of the hair follicle. They are one f the most common causes of superficial head nd neck masses in the pediatric population. Preurgical diagnosis is often difficult, especially in lder patients. Fine-needle aspiration biopsy FNAB) may show keratinaceous material suggesive of carcinoma. The purpose of this report was o present an atypical case of pilomatrixoma in a iddle-age man.