Faculty Bibliography

CONTEXT: - In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. OBJECTIVE: - To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations. DATA SOURCES: - PubMed. CONCLUSIONS: - Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.

PURPOSE/OBJECTIVE:Other studies have shown that levels of carcinoembryonic antigen (CEA) in breast ductal secretions (BDS) differ significantly between breast cancer (BC) patients and healthy individuals, providing direct evidence for CEA in BDS as a promising biomarker for BC. This meta-analysis was designed to assess the potential diagnostic value of CEA in BDS. METHODS:Relevant articles were retrieved from Embase, Pubmed, and the Cochrane Library. Sensitivity, specificity, and diagnostic odds ratio (DOR) of CEA in BDS for diagnosing BC were pooled using random effects models. SROC and the area under the curve (AUC) were used to estimate overall diagnostic performance. RESULTS:This meta-analysis comprised five studies with a total of 340 BC patients and 448 healthy controls. For CEA in BDS, the pooled sensitivity, specificity, and DOR to diagnose BC were 58 % [95 % confidence interval (CI): 52-63 %], 87 % (95 % CI: 84-90 %), and 7.07 (95 % CI: 3.10-16.12), respectively. Moreover, the AUC of CEA in the diagnosis of BC was 0.8570. CONCLUSIONS:CEA in BDS is a promising biomarker in the diagnosis of BC and should be evaluated as a standard screening tool upon verification of our results in a larger study population.

Introduction: The Bethesda System (TBS) uses a two-tiered approach to cervical squamous intraepithelial lesions (SILs). Occasionally, Paps with evident low grade SIL (LSIL) also have some features suggestive but not diagnostic of high grade SIL (HSIL). These Paps in our and other institutions are reported as 'LSIL, Cannot Exclude HSIL' (LSIL-H). LSIL-H has been shown to represent an intermediate risk (between LSIL and HSIL) for harboring a high grade lesion/carcinoma (HGD+) on biopsy. However, TBS 2014 continues to discourage its use to prevent the re-emergence of a threetiered reporting system. We review our experience with LSIL-H and discuss the best approach to report such Paps if the LSIL-H category is abandoned. Materials and Methods: Abnormal Paps were identified between January and June 2014 which had surgical follow-up within six months. Their biopsy outcomes were compared. Statistical analysis was performed using the Fisher's exact test. Results: Table 1 summarizes surgical diagnoses for each abnormal Pap category (total n=571). The differences in detection rates of HGD+ between LSIL and LSIL-H Pap was significant (p=0.000), whereas between LSIL-H and 'Atypical squamous cells, cannot exclude HSIL' (ASC-H) was not (p=0.101). If the LSIL-Hcategory is abandoned and LSIL-Hcases are reported as ASC-H, the rate ofHGD+ for theASC-H categorywould decrease from 55% to 41% (p=0.3). Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7% to 9% (p=0.27). Conclusions: The 'LSIL-H' category indeed detects more HGD+ than LSIL, and fewer HGD+ than ASC-H. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy since management of LSIL Pap depends on multiple factors (age, HPV status, etc). (Table Presented)

BACKGROUND: Chondroid syringoma (CS) is a rare benign adnexal tumor of the skin with a resemblance to pleomorphic adenoma of salivary gland, most commonly involving the head and neck region. In the present literature, reports of the cytologic appearance of CS are scarce as it is rarely encountered by fine needle aspiration (FNA). CASE PRESENTATION: A 67-year-old woman presented with a 1 year history of a 1 cm subcutaneous nodule in the right axilla. FNA biopsy was performed revealing an epithelial-mesenchymal biphasic neoplasm suggesting CS. Surgical excision confirmed the diagnosis and demonstrated extensive ossification, an extremely rare feature, with only seven reported cases, all located on the head. CONCLUSION: CS is a rare benign adnexal tumor of the skin, often overlooked due to its unremarkable clinical presentation. FNA is a reliable tool for the diagnosis of CS and helps guide optimal surgical management. Diagn. Cytopathol. 2016. (c) 2016 Wiley Periodicals, Inc.

Sclerosing hemangioma of the lung is a benign neoplasm with a widely debated histogenesis. It has a polymorphic histomorphology characterized by a biphasic cell population of "surface cells" and "round cells" arranged in four general patterns: Papillary, solid, angiomatous, and sclerotic. This variability in histomorphology makes it difficult to diagnose sclerosing hemangioma by fine needle aspiration (FNA). We present a case of sclerosing hemangioma diagnosed on FNA with immunohistochemistry performed on an accompanied cell block. The clinical presentation, cytomorphology, immunohistochemistry, and differential diagnoses are discussed.

Extraneural ependymomas are rare tumors that occur in sacrococcygeal, pelvic and extra pelvic regions. While sacrococcygeal extraneural ependymomas are equally distributed among males and females, pelvic and extra pelvic ependymomas have been exclusively reported in women, mainly of child bearing age. We present a case of extraneural, pelvic ependymoma that showed clinical response to GnRH therapy with its immunohistochemical and electron microscopic analysis, and an overview of primary extraneural ependymomas based on a review of all such cases published in English literature.

Background Granulomatosis with polyangiitis (GPA) relapse can complicate the differential diagnosis of pulmonary lesions. Case Report A 70-year-old male smoker with GPA and emphysema presented with dyspnea, dry cough, and a right upper lobe pulmonary ground-glass opacity that persisted despite antibiotics. A trans-bronchial biopsy did not reveal active vasculitis, malignancy, or infection. He was treated for presumed GPA relapse based on pulmonary manifestations, renal failure, and elevated PR3-ANCA. Later, hematuria led to the cystoscopic discovery of a bladder wall lesion, which was diagnosed as micropapillary urothelial carcinoma not involving the muscularis propria. The patient developed an increasing pulmonary infiltrate with a new solid component, satellite lesions, and regional lymphadenopathy. A right upper lobe wedge resection showed metastatic urothelial carcinoma. Conclusions The simultaneous presentation of a pulmonary lesion and GPA relapse is a diagnostic challenge. The differential diagnosis should include the rare possibility of metastatic urothelial carcinoma, regardless of how the lesion appears radiographically.

INTRODUCTION: High-risk HPV (hrHPV) testing is now considered standard of care in the detection and management of cervical high-grade squamous intraepithelial lesions (HSIL/CIN 2-3) and their precursors. Recently, there has been concern in the scientific literature and lay media about the lack of data regarding the false-negative rate (FNR) of HPV testing on SurePathTM cytology specimens. This is a critical issue, since guidelines on the management of Pap test abnormalities rely heavily on HPV status. We undertook this study to determine whether HPV testing on SurePathTM specimens is less sensitive compared to reports in the literature for ThinPrep(R). METHODS: We identified women with new diagnoses of CIN 2, CIN 3, and squamous cell carcinoma (SCC) on biopsy or excision in 2009-2013. For each patient, we recorded all SurePathTM cytology and hrHPV HC2 (high-risk HPV Hybrid Capture 2) test results from within 5 years prior to histologic diagnosis. Using the histologic diagnosis as the gold standard, we calculated the sensitivities of cytology and hrHPV HC2 tests for the detection of CIN 2, 3, and SCC. Our findings are based only on women who underwent biopsy or excision after having an abnormal cytology and/or positive HPV result. RESULTS: In our cohort, the sensitivity of testing in the 5 years prior to histologic diagnosis of CIN 2, 3, and SCC (combined as a single group) is 98.4% for SurePathTM cytology, 95.3% for hrHPV HC2, and 100% if both tests are used together. No conclusion can be drawn regarding testing for SCC alone, because there was only one case of SCC. CONCLUSION: Our results show that the false-negative rate of hrHPV HC2 testing on SurePathTM specimens for the detection of CIN 2 and CIN 3 is low and comparable to that of ThinPrep(R) specimens. Diagn. Cytopathol. 2014. (c) 2014 Wiley Periodicals, Inc.