Faculty Bibliography

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.

Papillary carcinoma of the breast consists of 3 morphologically distinct established subtypes: encapsulated papillary carcinoma, solid papillary carcinoma, and invasive papillary carcinoma. Papillary carcinoma is one of the special types of breast cancer and, as such, carries a more favorable prognosis. We sought to identify primary breast tumors with tubulopapillary morphology and correlate this finding with predictors of adverse prognosis. We investigated our pathology files for breast tumors exhibiting tubulopapillary features. The dominant morphology consisted of infiltrating gaping tubules with intratubular papillary projections. The study group consisted of 12 cases of papillary carcinoma with tubulopapillary features. A control group of 17 cases of papillary carcinoma were selected consisting of 4 encapsulated papillary carcinomas, 3 solid papillary carcinomas, and 10 invasive papillary carcinomas. The study group showed significantly higher mitotic rate, ki67 proliferation index, nuclear grade 3, lymphovascular invasion, p53 overexpression, unfavorable biomarker signature, and axillary nodal involvement compared to the control group (P = .01, .01, .04, .01, .007, .0001, .03, respectively). Invasive breast carcinomas with tubulopapillary features demonstrate significant correlation with predictors of adverse prognosis compared to ordinary papillary carcinomas. Larger studies with survival analysis are required to confirm aggressiveness in this group of breast cancers.

Core biopsy rapidly replaced fine needle aspiration (FNA) over the past decade in evaluation of diseases of the female breast in many centers in the USA. We continue to heavily utilize FNA for the initial evaluation of breast masses in our institution. In this article, we discuss the cytologic and core biopsy findings in challenging breast lesions such as papillary and mucinous proliferations, fibroepithelial neoplasms, and low grade cancers. We specifically focus on the pitfalls and limitations of both diagnostic modalities in these selected specific lesions. Diagn. Cytopathol. 2011; (c) 2011 Wiley-Liss, Inc

Nuclear expression of the cell cycle inhibitor p27(KIP1) is reduced in a variety of human malignancies, including breast cancer. Loss of nuclear p27(KIP1) during tumor progression, documented by immunohistochemistry (IHC), has been studied for its potential prognostic implication. We examined by IHC the association between nuclear p27(KIP1) expression and hormone receptor status in T1N0M0 breast cancer. PATIENTS AND METHODS: The correlation between nuclear p27(KIP1) expression and estrogen (ER) and progesterone (PR) hormone receptor status was analyzed in 122 human T1N0M0 (68 T1a/b, 54 T1c) breast cancer specimens. All patients were staged as N0 by axillary node dissection. RESULTS: A statistically significant reduction in p27(KIP1) expression was observed as tumor size increased from T1a/b (7%) to T1c (22%). The proportion of tumors with low nuclear p27(KIP1) expression was higher in the ER-negative/PR-negative group compared to the ER-positive/PR-positive group, but this difference was only statistically significant in the T1a/b subgroup (p=0.0007). CONCLUSION: Further investigations into causes of p27(KIP1) deregulation and their relationship to hormone receptor expression in T1N0M0 breast ductal carcinomas are warranted. Such studies may help identify prognostic, as well as predictive, markers of therapy resistance

Endobronchial ultrasonography (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway, including pulmonary and mediastinal lesion. The real time EBUS-guided transbronchial needle aspiration (TBNA) has advanced the diagnostic yield in primary lung pathology and mediastinal lymph node staging of lung carcinoma. Sixty-four patients (36 males, 28 females, ages ranging from 16 to 86 years) with peribronchial lung lesions and mediastinal and/or hilar lymph node lesions underwent EBUS-TBNA. All patients had intraoperative cytological assessment by smears on aspiration samples or touch preparation on needle core biopsies.The cytological final diagnoses were categorized as negative, suspicious/positive, and non-diagnostic. Forty-nine samples were obtained from lymph node lesions and 15 samples were obtained from lung lesions. In cytology specimens, 32 patients had suspicious/positive diagnoses and 32 patients had negative diagnosis. In follow-up histology specimens, 35 patients had malignant diagnoses, including 18 adenocarcinomas, 8 small cell carcinomas, 6 squamous cell carcinomas, 1 metastatic hepatocellular carcinoma, 1 metastatic melanoma, and 1 lymphoma. Twenty-nine patients had negative diagnoses. Sensitivity and specificity were 88.9% and 96.4%, respectively. Positive and negative predictive values were 97.0% and 87.1%, respectively. Diagnostic accuracy was 92.2%. EBUS-TBNA is an efficient and effective technique for diagnosis of intrapulmonary and mediastinal/hilar lymph nodes. It becomes significantly invaluable on clinical management for staging in those patients with lung cancer of other metastatic malignancies. This technique enables us to obtain tissue samples for quick diagnoses beyond central airway with minimal complications. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc

OBJECTIVE: The purpose of our study was to describe the clinical features, imaging characteristics, pathologic findings and outcome of microinvasive ductal carcinoma in situ (DCISM). MATERIALS AND METHODS: The records of 21 women diagnosed with microinvasive ductal carcinoma in situ (DCISM) from November 1993 to September 2006 were retrospectively reviewed. The clinical presentation, imaging and histopathologic features, and clinical follow-up were reviewed. RESULTS: The 21 lesions all occurred in women with a mean age of 56 years (range, 27-79 years). Clinical findings were present in ten (48%): 10 with palpable masses, four with associated nipple discharge. Mean lesion size was 21mm (range, 9-65mm). The lesion size in 62% was 15mm or smaller. Mammographic findings were calcifications only in nine (43%) and an associated or other finding in nine (43%) [mass (n=7), asymmetry (n=1), architectural distortion (n=1)]. Three lesions were mammographically occult. Sonographic findings available in 11 lesions showed a solid hypoechoic mass in 10 cases (eight irregular in shape, one round, one oval). One lesion was not seen on sonography. On histopathologic examination, all lesions were diagnosed as DCISM, with a focus of invasive carcinoma less than or equal to 1mm in diameter within an area of DCIS. Sixteen (76%) lesions were high nuclear grade, four (19%) were intermediate and one was low grade (5%). Sixteen (76%) had the presence of necrosis. Positivity for ER and PR was noted in 75% and 38%. Nodal metastasis was present in one case with axillary lymph node dissection. Mean follow-up time for 16 women was 36 months without evidence of local or systemic recurrence. One patient developed a second primary in the contralateral breast 3 years later. CONCLUSION: The clinical presentation and radiologic appearance of a mass are commonly encountered in DCISM lesions (48% and 57%, respectively), irrespective of lesion size, mimicking findings seen in invasive carcinoma. Despite its potential for nodal metastasis (5% in our series), mean follow-up at 36 months was good with no evidence of local or systemic recurrence at follow-up. Knowledge of these clinical and imaging findings in DCISM lesions may alert the clinician to the possibility of microinvasion and guide appropriate management