The Sensitivity and Specificity of Touch Preparation for Rapid Diagnosis of Invasive Fungal Sinusitis: A Pilot Study.

Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period. Thirteen patients had touch preparation of nasal specimens followed by routine histologic processing; two of these patients underwent 2, and 1 patient had 3 separate debridements, for a total of 17 touch preparations performed. The sensitivity and specificity of touch preparation were calculated by correlating the initial results with the presence of fungal invasion on final pathologic analysis. The sensitivity of touch preparation was 56% (95% confidence interval [CI]: 0.23-0.85), specificity was 100% (95% CI: 0.60-1.00), positive predictive value was 100% (95% CI: 0.46-1.00), and negative predictive value was 67% (95% CI: 0.35-0.89). This procedure may be a useful adjunct in situations requiring rapid diagnosis of invasive fungal sinusitis but should not be used as the sole criteria for determining the need for surgical intervention.

Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported. METHODS: The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC. RESULTS: A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively. CONCLUSIONS: The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: Case report of a rare lesion with novel genetic mutation.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare primary cancer of the thyroid. This tumor is analogous to other primary tumors of the salivary glands, breast, pancreas, and esophagus. We present a case of this rare tumor with characteristic clinical features, ultrasound images, cytopathology, histopathology, and a heretofore undocumented somatic gene mutation. Additionally, we provide a succinct review of the controversial literature for this uncommon lesion.

Mucoepidermoid carcinoma, acinic cell carcinoma, and adenoid cystic carcinoma on fine-needle aspiration biopsy and The Milan System: an international multi-institutional study.

BACKGROUND: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC). MATERIALS AND METHODS: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up. RESULTS: A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa. CONCLUSIONS: The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management.

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs. METHODS: Submandibular gland FNA cytology specimens from 15 international institutions (2013-2017) were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. A correlation with the available histopathologic follow-up was performed, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The case cohort of 734 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 21.4% (0%-50%); nonneoplastic, 24.2% (9.1%-53.6%); AUS, 6.7% (0%-14.3%); benign neoplasm, 18.3% (0%-52.5%); SUMP, 12% (0%-37.7%); SM, 3.5% (0%-12.5%); and malignant, 13.9% (2%-31.3%). The histopathologic follow-up was available for 333 cases (45.4%). The ROMs were as follows: nondiagnostic, 10.6%; nonneoplastic, 7.5%; AUS, 27.6%; benign neoplasm, 3.2%; SUMP, 41.9%; SM, 82.3%; and malignant, 93.6%. CONCLUSIONS: This multi-institutional study shows that the ROM of each MSRSGC category for submandibular gland FNA is similar to that reported for parotid gland FNA, although the reported rates for the different MSRSGC categories were variable across institutions. Thus, the MSRSGC can be reliably applied to submandibular gland FNA.

Evaluating Nonclinical Performance of the Academic Pathologist: A Comprehensive, Scalable, and Flexible System for Leadership Use.

Academic pathologists perform clinical duties, as well as valuable nonclinical activities. Nonclinical activities may consist of research, teaching, and administrative management among many other important tasks. While clinical duties have many clear metrics to measure productivity, like the relative value units of Medicare reimbursement, nonclinical performance is often difficult to measure. Despite the difficulty of evaluating nonclinical activities, nonclinical productivity is used to determine promotion, funding, and inform professional evaluations of performance. In order to better evaluate the important nonclinical performance of academic pathologists, we present an evaluation system for leadership use. This system uses a Microsoft Excel workbook to provide academic pathologist respondents and reviewing leadership a transparent, easy-to-complete system that is both flexible and scalable. This system provides real-time feedback to academic pathologist respondents and a clear executive summary that allows for focused guidance of the respondent. This system may be adapted to fit practices of varying size, measure performance differently based on years of experience, and can work with many different institutional values.

Giant cell tumor of temporomandibular joint presenting as a parotid tumor: Challenges in the accurate subclassification of giant cell tumors in an unusual location.

Fine needle aspiration is frequently used as the initial diagnostic procedure in the work-up of head and neck lesions, including soft tissue masses and salivary gland neoplasms. Giant cell tumors (GCTs), both osseous and extraosseous, are benign tumors that occur, albeit rarely, in the head and neck region. Extraosseous GCTs may be further classified based on their tissue of origin and specific anatomic location. Regardless of location, giant cell tumors are morphologically similar and share cytologic and histologic diagnostic criteria. Evaluation of imaging is therefore essential to the correct classification of these tumors. Accurate diagnosis is crucial since the clinical behavior and treatment is significantly different among the subtypes of GCTs. The case presented herein illustrates the diagnostic dilemma between two uncommon entities in an unusual site: GCT of parotid gland and tenosynovial GCT.

The sensitivity and specificity of touch preparation for rapid diagnosis of invasive fungal sinusitis: A pilot study.

Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period. Thirteen patients had touch preparation of nasal specimens followed by routine histologic processing; 2 of these patients underwent two and 1 patient had three separate debridements, for a total of 17 touch preparations performed. The sensitivity and specificity of touch preparation were calculated by correlating the initial results with the presence of fungal invasion on final pathologic analysis. The sensitivity of touch preparation was 56% (95% confidence interval [CI]: 0.23 to 0.85), specificity was 100% (95% CI: 0.60 to 1.00), positive predictive value was 100% (95% CI: 0.46 to 1.00), and negative predictive value was 67% (95% CI: 0.35 to 0.89). This procedure may be a useful adjunct in situations requiring rapid diagnosis of invasive fungal sinusitis but should not be used as the sole criterion for determining the need for surgical intervention.

GATA3 is a reliable marker for neuroblastoma in limited samples, including FNA Cell Blocks, core biopsies, and touch imprints.

BACKGROUND: Neuroblastomas (NBs) are the most common solid cancer of childhood and infancy; however, in poorly differentiated forms, they present diagnostic challenges. GATA3 has been implicated functionally in NB differentiation, and limited data support its use as an immunohistochemical biomarker for NBs in resection specimens. METHODS: GATA3 was tested retrospectively in 30 consecutive archival NB samples, including archival cytopathology needle cores and cell blocks (n = 6), scant surgical biopsy specimens and 2-mm NB tissue cores (n = 16), and air-dried touch imprints (n = 8) to evaluate the utility of this marker. Immunostaining was performed per the institutional standard, Clinical Laboratory Improvement Amendments-compliant automated staining protocol. GATA3 nuclear staining was scored qualitatively for its intensity and proportion of positivity. RESULTS: All 30 NB specimens showed diffuse nuclear positivity with GATA3. Each sample revealed either strong (n = 26) or moderate nuclear staining (n = 4) in more than 75% of NB cells, regardless of the presence or lack of stromata or necrosis or the degree of differentiation. CONCLUSIONS: GATA3 is a reliable diagnostic marker for NBs not only in scant/limited surgical specimens but also in cytologic samples, including air-dried touch imprints, which have previously been undescribed for this marker. Cancer Cytopathol 2017;125:940-6. © 2017 American Cancer Society.

Unusual paratracheal masses presenting with vocal fold paralysis.

Most paratracheal masses are of thyroid origin. We describe two cases of vocal fold paralysis that were caused by unusual paratracheal masses. In one case, a 35-year-old man was found to have a malignant lymphoma that originated in the mediastinum and extended above the clavicle. The other patient was a 53-year-old man with an enlarged left thyroid lobe, tumor invasion of the adjacent larynx and trachea, and multiple pulmonary nodules all due to adenoid cystic carcinoma. Unusual paratracheal masses presenting with vocal fold paralysis may mimic thyroid malignancies, thereby posing both diagnostic and therapeutic challenges. Fine-needle aspiration cytology is often helpful in making a definitive diagnosis, but incisional biopsy is necessary in some cases.

Cytopathologic features of clear cell papillary renal cell carcinoma: A recently described variant to be considered in the differential diagnosis of clear cell renal epithelial neoplasms.

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a distinctive variant of renal cell carcinoma that has been formally adopted by the new Word Health Organization classification. An emerging consensus has documented its particularly indolent course and emphasized its separation from conventional clear cell renal cell carcinoma (CCRCC) for treatment planning. CCPRCC features in cytologic preparations have not been studied. METHODS: This study retrospectively identified a series of CCPRCCs that had cytology samples before the histopathologic diagnosis and reviewed corresponding cytologic materials, including aspirate smears, cell block materials, touch preparations, and core biopsy samples. The identified clinicopathologic and cytologic features were tabulated. RESULTS: Five cases of CCPRCC with cytopathologic materials were identified from 4 women and 1 man aged 34 to 70 years (2 with end-stage renal disease), and the sampled lesions were 1.8 to 11.0 cm. The original cytopathologic diagnostic considerations ranged from atypical cyst-lining cells to angiomyolipoma to CCRCC and CCPRCC. The aspirate and touch preparation samples showed scant cellularity with scattered sheets and clusters of small, bland epithelial cells (much smaller than admixed renal tubular cells) with optically clear cytoplasm (lacking conspicuous cytoplasmic vacuolization) and small, grade 1 nuclei. The cell block materials and the core biopsy samples showed cyst walls with prominent myomatous stroma lined by low-grade epithelium with optically clear cytoplasm, inverse nuclear polarization, and a characteristic cytokeratin 7-positive/carbonic anhydrase IX-positive phenotype. Three cases were treated with resection, 1 case was treated with ablation, and 1 case was under surveillance. CONCLUSIONS: CCPRCC demonstrates recognizable cytomorphologic features and merits consideration in the cytologic differential diagnosis for kidney lesions. With increasing experience, more conservative management may be contemplated. Cancer Cytopathol 2016;124:565-72. © 2016 American Cancer Society.

Quality control material for the detection of somatic mutations in fixed clinical specimens by next-generation sequencing.

BACKGROUND: Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeq™ Cancer Hotspot Panel v2 (CHP2) assay. METHODS: The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC material was prepared from a mixture of cell lines derived from different cancers, comprising single nucleotide variants and small deletions on actionable genes at different allelic frequencies. RESULTS: The CHP2 assay performed with high precision and sensitivity when custom variant calling pipeline parameters where established. In addition, all expected somatic variants in the QC material were consistently called at variant frequencies ranging from 9.1 % (CV = 11.1 %) to 37.9 % (CV = 2.8 %). CONCLUSIONS: The availability of a reliable and cost-effective QC material is instrumental in assessing the performance of this or any targeted NGS assay that detects somatic variants in fixed solid tumor specimens.

Fine-needle aspiration biopsy of secondary neoplasms of the thyroid gland: a multi-institutional study of 62 cases.

BACKGROUND: Secondary neoplasms of the thyroid gland (SNTGs) are uncommon, and it is important to recognize them in thyroid fine-needle aspiration biopsy (FNAB). METHODS: The authors report a cohort of 62 SNTGs from 7 institutions in the United States and Europe. Patients were identified retrospectively by searching through medical records of the respective institutions. All initial diagnoses were rendered by FNAB. RESULTS: SNTGs represented 0.16% of all thyroid FNABs and were more frequent among women (ratio of women to men, 1.2:1.0). The mean patient age was of 59 years (range, 7-84 years), the mean tumor size was 3 cm (range, 0.9-7 cm), and the mean interval from diagnosis of the primary tumor was 45 months (range, 0-156 months). Eighty-seven percent of SNTGs were diagnosed as malignant by FNAB, and there was a specific SNTG diagnosis in 93% of patients. Immunocytochemistry and flow cytometry, which were used in 30% of patients, were useful ancillary studies. Adenocarcinomas (n = 23; 37%) and squamous cell carcinomas (SCCs) (n = 22; 35.5%) represented the majority of SNTGs, followed by lymphoma (n = 5; 8%), melanoma (n = 5; 8%), adenoid cystic carcinoma (n = 3; 5%), and various sarcomas (n = 3; 5%). Adenocarcinomas originated from the kidney (n = 9; 39%), lung (n = 6; 26%), breast (n = 5; 22%), and colon (n = 3; 13%). SCCs originated mostly from the head and neck (n = 13; 59%), followed by lung (n = 3; 13%), esophagus (n = 3; 14%), and unknown primary sites (n = 3; 14%). CONCLUSIONS: Adenocarcinomas from the kidney, lung, breast, and colon along with SCCs represent the majority of SNTGs. The current results indicate that FNAB is a sensitive and accurate method for diagnosing SNTG; however, diagnostic difficulties can occur. Knowledge of clinical history and the judicious application of ancillary studies can increase the sensitivity and accuracy of FNAB for detecting SNTGs.

Adenoid cystic carcinoma: a pitfall in aspiration cytology of the thyroid.

While adenoid cystic carcinoma is not an uncommon tumor in the salivary glands, its occurrence in the larynx and trachea is rare. Extension of an adenoid cystic carcinoma of the larynx and trachea to the thyroid with manifestation as a thyroid nodule is extremely rare. However, this possibility always should be considered whenever there are cytologic features suggestive of adenoid cystic carcinoma in thyroid aspirates and when there is a history of adenoid cystic carcinoma in the trachea or larynx or in any part of the body.

Isolated plexiform neurofibroma: treatment with three-dimensional conformal radiotherapy.

OBJECTIVES: To present a case of an unusual benign tumor of the tongue treated successfully with radiotherapy. STUDY DESIGN: Case report. METHODS: Retrospective chart review. RESULTS: A 60-year-old man presented with a painful submucosal lesion of the tongue base. Computed tomography showed an infiltrative soft-tissue mass involving the left base of the tongue. Operative biopsy revealed plexiform neurofibroma. Because of the patient's operative risk and the potential morbidity of surgical resection, he was treated with three-dimensional conformal radiotherapy (3DCRT). His treatment was accomplished using a five-field arrangement treating exclusively the mass lesion to a total tumor dose of 60 Gy. After treatment, the patient's tongue pain resolved, and he noted minimal transient xerostomia. Serial follow-up radiographic examinations showed the base of tongue mass to be slightly smaller 4 months after treatment. The most recent follow-up magnetic resonance image reveals a further decrease in size of the mass. The patient is now over 3 years out from treatment. CONCLUSIONS: Solitary plexiform neurofibroma of the tongue base is a rare tumor. These benign neoplasms are usually treated with either observation or surgical excision. This case demonstrates that, when significant symptoms necessitate active management, these lesions may be successfully treated with minimal morbidity using 3DCRT. The ability of this technique to deliver a conformal radiation dose to the tumor volume while sparing the surrounding normal tissues may expand the application of radiotherapy in the treatment of these benign lesions of the head and neck.

Targeting tyrosine kinases in cancer: the converging roles of cytopathology and molecular pathology in the era of genomic medicine.

Because of knowledge gained in the field of cancer biology, clinicians are currently witnessing an explosion of molecular tests as companion diagnostics to targeted therapies against growth factor receptors and their signaling pathways. Such tests are being applied increasingly to cytology specimens as essential components of genomic medicine, because less invasive diagnostic procedures are becoming the norm. The objective of this review was to present an overview of the current and future role of cytopathology in molecular diagnostics, including the adequacy of cytology specimens for such studies. The authors also discuss the critical methodologic aspects of the molecular assays used for the selection of tyrosine kinase treatment for oncology patients.