Jos Hille

Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to ones “own” criteria, and then according to the AFIP criteria proposed by Goode et al. 10 Weighted kappa (&kgr;) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15–86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their “own” grading, as expressed by the &kgr; value, ranged from good agreement (&kgr; = 0.79) to poor (&kgr; = 0.27) (average &kgr; = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average &kgr; = 0.61, range 0.38–0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using ones own grading systems (p = 0.0001) but not in applying the AFIP “standardized” grading (p = 0.33). When ones own grading was compared with the AFIP grading, there were 100 pairs of grading “events,” with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading “downgraded” tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

Low-grade salivary duct carcinoma: description of 16 cases.

Low-grade salivary duct carcinoma is a rare neoplasm. We report on 16 patients, with a median age of 64 years. All but one tumor arose from the parotid gland, including one tumor that arose in an intraparotid lymph node; one arose in the submandibular gland. Tumors consist of single to multiple dominant cysts, accompanied by adjacent intraductal proliferation. Cysts are lined by small, multilayered, proliferating, bland ductal cells with finely dispersed chromatin and small nucleoli. Separate, smaller ductal structures are variably filled by proliferating ductal epithelium with cribriform, micropapillary, and solid areas. The overall appearance is very similar to breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Foci of definitive stromal invasion were seen in four tumors. Two tumors demonstrated transition from low- to intermediate- or high-grade cytology, with scattered mitotic figures and focal necrosis. S-100 revealed diffuse strong expression in all 9 cases studied. Myoepithelial markers (calponin) highlighted supportive myoepithelial cells rimming the cystic spaces, confirming the intraductal nature of most, or all, of six tumors studied. Nine tumors studied for Her2-neu antigen were uniformly negative. Follow-up was obtained on 13 of our 16 patients. All patients were disease-free after surgery 6 to 132 months (median 30 months). Low-grade salivary duct carcinoma is a low-grade neoplasm with an excellent prognosis; it may be treated by conservative but complete resection. Its resemblance to atypical breast ductal hyperplasia, or micropapillary/cribriform intraductal carcinoma, distinguishes it from high-grade salivary duct carcinoma, papillocystic acinic cell carcinoma, and cystadenocarcinoma.

Sclerosing Polycystic Adenosis of the Salivary Gland A Report of 16 Cases

Sclerosing polycystic adenosis is a recently described, extremely rare, reactive, sclerosing, inflammatory process somewhat similar to fibrocystic changes and adenosis tumor of the breast. To date, there have been 22 cases described in the literature. Because of the infrequency of this lesion, we describe our combined experience with 16 cases, 1 of which has been previously reported. Thirteen tumors arose in the parotid gland, two involved the submandibular gland, and one arose in the buccal mucosa. There were 9 men and 7 women. Patients ranged in age from 9 to 75 years. Fourteen patients presented with a primary mass. Two were incidental findings in patients with a mixed tumor and an oncocytoma. Tumors ranged in size from 0.3 to 6 cm in greatest dimension. They are typically well circumscribed and are composed of densely sclerotic lobules with prominent cystic change. Hyperplasia of ductal and acinar elements and areas of apocrine-like metaplasia are frequent. Foci with mild ductal epithelial atypia were frequent with >50% of cases demonstrating at least focal areas of duct epithelial hyperplasia with atypia. Follow-up ranged from 1.5 to 40 years. One tumor recurred twice; no patient has developed metastases or died of disease.

Diagnosis and classification of salivary neoplasms : pathologic challenges and relevance to clinical outcomes

MARGARET S. BRANDWEIN, ALFIO FERLITO, PATRICK J. BRADLEY, JOS J. HILLE and ALESSANDRA RINALDO From the Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York, USA, Department of Otolaryngology —Head and Neck Surgery, University of Udine, Udine, Italy, Department of Otorhinolaryngolog y—Head and Neck Surgery, Queen’s Medical Centre, Nottingham , UK and Department of Pathology, University of Western Cape, Cape Town, South Africa

An evaluation of the Shandon Papspin liquid-based oral test using a novel cytologic scoring system.

OBJECTIVES The aim of this study was to evaluate a cost-effective oral liquid-based cytology screening test, Shandon Papspin (PS). STUDY DESIGN We compared the diagnostic accuracy of PS with surgical biopsy in 69 patients. Transepithelial cytology specimens were obtained with the use of cervical cytobrushes. Cytology specimens were graded and scored by using a novel oral cytologic grading and scoring system. RESULTS Histologic diagnosis of dysplasia or malignancy was made in 51/69 cases, and cytology identified 49/51 cases, with a sensitivity of 96% and specificity of 100%. The best cutoff value for distinguishing reactive/mildly dysplastic lesions from high grade/invasive squamous cell carcinoma was determined to be a cytologic score of 3, representing a sensitivity of 95% and specificity of 96%. CONCLUSIONS PS appears to be an accurate and economical test for detection of high-risk dysplasias and cancers, but the real significance of this method will be its diagnostic accuracy in studies focusing strictly on lesions with a low level of clinical concern.

Application of liquid‐based transepithelial flexible brush cytology in the detection of high‐grade laryngeal mucosal lesions

Background The aim of this study was to evaluate the effectiveness of liquid-based transepithelial flexible brush cytology (LBTFBC) in the detection of high-grade laryngeal mucosal lesions. Methods Diagnostic accuracies of LBTFBC and flexible biopsy (FB) were compared with the gold standard of biopsy under general anaesthesia (BUA) in 49 and 46 patients, respectively. Using a flexible laryngoscope, transepithelial cytology and biopsy specimens were obtained with the aid of flexible brushes and biopsy forceps. Cytology specimens were graded and scored using a recently proposed oral cytologic grading and scoring system. Results Cytology showed 97, 29% sensitivity, 100% specificity, 97.9% accuracy, and FB disclosed 77.1% sensitivity, 100% specificity, and 82.2% accuracy when compared with BUA. The best cutoff value for discriminating reactive/mildly dysplastic lesions from high-grade dysplasias/invasive squamous cell carcinomas (SCCs) was determined as a cytologic score of 3, with sensitivity and specificity of 100%. Conclusion LBTFBC is a simple office-based procedure, which in combination with the newly proposed classification scheme appears to be an accurate technique in the detection of high-grade laryngeal mucosal lesions. LBTFBC is more effective than FB owing to the enhanced range of sampling and ease of application. It effectively eliminates the need for general anaesthesia, and thus reducing theatre costs and the number of hospital admissions. LBTFBC is ideal for patients who require regular clinical examinations, where repeated biopsies may lead to significant vocal morbidity. Diagn. Cytopathol. 2015;43:21–27.

The Development of a Novel Oral Cytologic Grading System

While the Bethesda system represents one of the great success stories in cervical cytology, there has been little appetite for the adoption of a universal grading system for oral cytology. This could be explained by the general lack of interest in oral cytology due to a high percentage of false negative diagnoses, a great variation in technical quality and cellularity of oral smears as well as the use of inadequate sampling procedures. The lack of a standardized method for reporting oral cytology adversely affects proper management of patients with oral lesions. The emergence of Liquid-Based Cytology (LBC) with dramatic improvements in technical quality and cellularity of the cytology specimens has provoked a new interest in using this diagnostic modality for suspicious oral mucosal lesions. This chapter describes the adequacy criteria and minimum cellularity specifications of oral cytologic specimens, and proposes an oral cytologic grading system analogous to the Bethesda System for reporting cervical cytology based on LBC techniques. Using this classification, the terminology for reporting results obtained by oral cytology examination of class I and class II oral mucosal lesions is discussed with ample illustrations of the morphologic criteria and diagnostic categories. These include normal, reactive changes, changes including probably atypical reactive/low-grade lesions, low-grade squamous intraepithelial lesions, atypical probably high-grade changes, high-grade squamous intraepithelial lesion and invasive squamous carcinoma. While still at its infancy, this grading system provides a standardised and uniform method of reporting for the practising pathologist. To further validate the newly proposed classification scheme and discover the best cut-off value for distinguishing reactive/low grade lesions from high grade/squamous cell carcinoma, a simple and easy scoring method based on nine cytologic characteristics is proposed. This may well increase the specificity of the oral cytology test in a manner similar to that of the robust Papanicolaou test.

Liquid-based trans-epithelial flexible brush cytology of high-grade laryngeal mucosal lesions

Laryngeal cytology, which was popular in the 1950s and 60s, has lost its appeal due to difficulties in obtaining adequate specimens and frequent false negative results which are often associated with smears of suboptimal quality. Flexible laryngoscope and brushes, and liquid-based cytology (LBC) allow for improved collection and quality of laryngeal mucosal samples. In LBC the cells are optimally fixed and significantly retrieved. The samples are virtually devoid of air drying artefact and obscuring elements such as blood, mucus, necrotic debris and inflammation. The diagnostic accuracies of liquid-based transepithelial flexible brush cytological (LBTEFBC) samples and flexible biopsies (FB) were compared with those of biopsy under general anaesthesia (BUA) in 49 and 46 patients respectively. Cytology specimens were graded and scored using a recently proposed oral cytological grading and scoring system. When compared with BUA, the cytology showed 97% sensitivity and 100% specificity, and FB yielded 77.1% sensitivity and 100% specificity. Reactive/mildly dysplastic lesions can be discriminated from high-grade dysplasias/invasive squamous cell carcinomas with 100% sensitivity and specificity. LBTFBC is a simple, cost-effective, relatively atraumatic office-based procedure, and with the recently proposed classification, it can be accurate in the detection of high-grade laryngeal lesions.

Oral Cytology Techniques

A significant proportion of oral squamous cell carcinomas (OSCC) develop from premalignant lesions. Histological examination of tissue remains the gold standard for diagnosis and identification of pre-malignant and malignant oral lesions, but has many disadvantages. Exfoliative cytology is a simple and noninvasive technique which is based on the concept that malignant cells adhere much less to each other and thus are easier to harvest by scraping or brushing a suspicious tissue surface in a relatively atraumatic way.