Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.

The National Cancer Institute (NCI) sponsored the NCI Thyroid fine-needle aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters addressing manual and ultrasound guided FNA technique and related issues. Specific topics covered include details regarding aspiration needles, devices, and methods, including the use of core needle biopsy; the pros and cons of anesthesia; the influence of thyroid lesion location, size, and characteristics on technique; the role of ultrasound in the FNA of a palpable thyroid nodule; the advantages and disadvantages of various specialists performing a biopsy; the optimal number of passes and tissue preparation methods; sample adequacy criteria for solid and cystic nodules, and management of adverse reactions from the procedure. (http://thyroidfna.cancer.gov/pages/info/agenda/)

The scheme recommends statements on specimen adequacy followed by the major classification category and then a subclassification and/or comments section. Each of the six main diagnostic categories is associated with an estimated risk of malignancy. Subsequent documents will propose ancillary testing recommendations, techniques for cytologic sampling, indications for cytologic study and postcytologic diagnosis management and follow-up recommendations.

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.

The examination of urine for characteristics of smell, color, and clarity occupied an important place in medicine as practiced by the Egyptians, Babylonians, and Greeks. 1,2 Following the invention of technically useful microscopes, microscopic analysis of the urine was performed for crystals but no real attempt at analysis of the cellular components of urine was made until the mid-19th century. 3 Early descriptions of the cytologic features of urine were published by Hermann Lebert and W.D. Lambl in the mid-19th century. 4 No significant progress in the art and science of urologic cytopathology occurred until the publication by Papanicolaou and Marshall in 1945. 5 The foundations of modern urinary cytology were laid by the pioneering work of Koss and associates, who established a framework for both the cytologic and histologic characterization of papillary and nonpapillary urothelial neoplasia. [5][6][7][8] The criteria for diagnosis and grading established in these studies have remained the basis for modern urinary histopathology and cytology until the recent reevaluation and publication of the WHO classification. 9 -11 Urinary cytology is generally not a screening test for the general population. It has been found useful for surveillance of symptomatic patients and selected populations at increased risk for the development of urothelial carcinoma as a result of smoking or industrial chemical exposure. 5 Of greater importance is the use of urine cytology for the surveillance of patients with known prior urothelial malignancies who have undergone a variety of therapies. [12][13][14] To increase the accuracy and timeliness of early detection of recurrent urothelial carcinoma a variety of nonmorphologic techniques have been developed. [15][16][17][18][19][20][21][22][23] Specimen Types and CollectionSeveral types of urine cytologic specimens are utilized, including: 1) voided or clean-catch urine; 2) catheterized urine; 3) brushings and washings; 4) ileal loop urine specimens; and 5) specimens from ureters with double-J stents. The most inexpensive and widely used specimen for screening is the voided or "clean-catch" urine. 24,25 While of acceptable sensitivity for urothelial lesions of the bladder, it is less sensitive for neoplasms of the ureter and urethra, where directed washing and brushing techniques may be required. 26,27 Bladder washing may be a more appropriate technique when a urothelial malignancy within the bladder is suspected on clinical grounds. When the integrity of the lower Voided Urine SpecimenWhile the first morning voided urine specimen has been traditionally favored for urine analysis, most authorities agree that it is a suboptimal specimen for cytologic evaluation. 28 The integrity of the cellular component of a "first morning" specimen is compromised by the cells' long contact with toxic substances within the urine. Higher quality samples are obtained when specimens are collected after morning voiding and after hydration. A voided urine specimen can be collected at any convenient time ...

Context Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC. Objective The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules. Design, Settings, and Participants Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance. Results The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant. Conclusions GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.

BACKGROUND. Early cytologic detection and treatment of high‐grade squamous intraepithelial lesion (HSIL) is critical to cervical cancer prevention. The term atypical squamous cells (ASC), cannot exclude HSIL (ASC‐H) was introduced in 2001 in the Bethesda System (TBS 2001) to define changes suggestive, but not diagnostic, of HSIL in the absence of unequivocal squamous intraepithelial lesion (SIL). Previous studies showed that women with ASC‐H cytology are at an increased risk of harboring underlying histopathologic HSIL. TBS 2001, however, did not address the significance of finding ASC‐H changes in a background of unequivocal low‐grade SIL (LSIL). There may be a tendency for cytologists to lump these changes with either LSIL or HSIL, depending on their level of comfort. In their laboratory, the authors have referred to these changes as “LSIL, cannot exclude HSIL” (LSIL‐H). METHODS Between July 2001 and July 2003, all Papanicolaou (Pap) tests that were obtained by using the ThinPrep technique were retrieved from the computer data base at the authors' institution. All categories of squamous cell abnormalities, including LSIL‐H, were evaluated for their incidence and follow‐up diagnoses of HSIL and more severe lesions (HSIL +). All patients had a minimum of 2 year follow‐up by biopsy and cytology (range, 2–4 years). RESULTS LSIL‐H comprised 0.15% (n = 194) of all Pap tests (n = 129,911) that were evaluated during the study period. Follow‐up biopsy was available on 59 patients (30.4%), which showed HSIL + in 40.7% of patients. This rate of associated HSIL + differed significantly from that of LSIL (13%; P < .001) and HSIL (74%; P < .001), but was similar to that of ASC‐H (44.6%). CONCLUSIONS The results from this study showed that patients with cytologic diagnoses of LSIL‐H had an intermediate risk of harboring histopathologic HSIL +. This risk was similar to ASC‐H but fell between the low risk associated with ACS‐US and LSIL and the high risk associated with HSIL cytologic diagnoses. The authors believe that LSIL‐H should be considered as a distinct cytologic diagnostic interpretation and should be separated from LSIL and HSIL. Although LSIL‐H does not represent a unique biologic entity, it has clinical usefulness because of its high positive predictive value for HSIL + lesions. Cancer (Cancer Cytopathol) 2006; 108:. © 2006 American Cancer Society.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy.