Faculty Bibliography

Fine-needle aspiration biopsy (FNAB) of invasive lobular carcinoma (ILC) is associated with notoriously high rates of false negative and equivocal diagnoses. To identify causative factors, we reviewed the cytologic features of presurgical FNAB smears of ILC and correlated the cytologic findings with the number of passes, tumor size, mammographic findings, and the histologic characteristics of the tumor. Smear cellularity, presence of single intact epithelial cells, nuclear size, nuclear atypia, palpability of the tumor, and histologic type of ILC (classic versus nonclassic) were statistically significant in establishing an unequivocally positive diagnosis. We also found that the cytologic cellularity of the lesion does not reflect the actual cellularity of the tumor but instead is an indicator of the architectural arrangement of the neoplastic cells; tumors that form epithelial cell groups, such as in nonclassic ILC, tend to yield more cellular aspirates that are diagnostic for carcinoma. In contrast, classic ILC, in which single neoplastic cells are embedded in fibrous stroma, is more likely to yield a paucicellular smear with subtle atypia and rare single intact epithelial cells. As such, an inconclusive diagnosis in a certain percentage of classic ILC cases may be unavoidable

Invasive carcinoma with osteoclast-like giant cells is an unusual type of mammary adenocarcinoma with few cases reported in the cytology literature. We present the cytologic findings in a case of invasive cribriform carcinoma of the breast containing osteoclast-like giant cells diagnosed by fine-needle aspiration biopsy. The smears displayed three-dimensional cohesive cluster cells of uniform epithelial cells admixed with numerous multinucleated giant cells that morphologically resembled osteoclasts. Core biopsy confirmed the cytologic diagnosis. Immunohistochemical studies indicated that the multinucleated giant cells were of histocytic origin. Knowledge of the bland cytologic pattern and the admixture of giant cells seen in invasive cribriform carcinoma with osteoclast-like giant cells should avoid making a false negative diagnosis on aspiration biopsy

We studied the staining patterns of bronchioloalveolar carcinoma (BAC) with antibodies to cytokeratin (CK) 7, CK20, and thyroid transcription factor-1 (TTF-1) to determine the diagnostic usefulness of this panel in differentiating BAC from metastatic adenocarcinoma in material obtained by fine-needle aspiration biopsy (FNAB) of the lung. We identified 16 cases of BAC. Of these, 6 were mucinous, 4 were nonmucinous, and 6 were mixed with focal mucinous differentiation. Immunohistochemical analysis with antibodies to CK7, CK20, and TTF-1 was performed on cell-block sections. Of the 6 mucinous BACs, 4 (67%) were CK7+, CK20+, and TTF-1-. All 4 nonmucinous BACs were CK7+ and CK20-, and 2 (50%) were TTF-1+. All 6 mixed BACs were diffusely positive for CK7 and focally positive for CK20; 5 (83%) were TTF-1+. Nonmucinous BACs display CK7, CK20, and TTF-1 immunoreactivity similar to conventional pulmonary adenocarcinoma. Mucinous and mixed BACs have an immunohistochemical phenotype that is different from that of conventional pulmonary adenocarcinoma. Knowledge of these staining patterns is crucial for distinguishing mucinous and mixed BACs from metastatic adenocarcinoma involving the lungs

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and 'grooves.' Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma

BACKGROUND: The 2001 Bethesda System recommended qualification of atypical glandular cells (AGC) to indicate the site of origin and separated endocervical adenocarcinoma in situ (AIS) from 'AGC favor neoplastic' as a specific diagnostic category. To the authors' knowledge, the literature evaluating the reproducibility of Papanicolaou (Pap) smear diagnosis of glandular cell abnormalities with emphasis on the cell of origin is limited. The aim of the current study was to investigate whether a variety of benign to neoplastic glandular lesions can be reliably classified on Pap smear with regard to diagnosis and cell of origin. METHODS: Twenty-three conventional Pap smears (CPS) with glandular cellular changes varying from benign to adenocarcinoma (ACA) were reviewed by six observers. They were asked to categorize each smear according to cell of origin (endocervical vs. endometrial) and diagnosis (benign, AGC, or ACA). Kappa statistics were used to evaluate interobserver agreement and correlation of interobserver agreement with experience. RESULTS: There was no consensus among observers for both the origin of the cells and the diagnosis. Interobserver agreement for site was poor (kappa < 0.4) especially in the AGC category. Unanimous agreement for site was reached for 7 of 23 smears (30%). Two of five endocervical AIS were classified as endometrial and another two were classified as benign by four observers. Interobserver agreement was poor in all diagnostic categories (kappa < 0.4) and showed slight correlation with level of experience. Unanimous agreement for diagnosis was reached for only 2 smears (9%). Three of 11 (27%) smears demonstrating preneoplastic/neoplastic processes were diagnosed as benign by 3 observers. Three (25%) benign CPS were diagnosed as ACA by 2 observers. Accurate prediction of the final histologic diagnosis by observers varied from 30% to 87% and did not correlate closely with experience. CONCLUSIONS: Cytologic diagnosis of glandular lesions by CPS was problematic and suffered from significant interobserver subjectivity

OBJECTIVE: To review the cytologic and subsequent histologic findings in intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to evaluate the role of aspiration biopsy (AB) in identifying and grading the disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS who underwent preoperative AB were reviewed. Smears were assessed for cellularity, cellular arrangement (including dissociation, nuclear size and pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases, 22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases were low grade (LG). Cytologic findings of HG DCIS was as follows: high cellularity (22/22), clusters of pleomorphic cells with large nuclei and increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had moderately to highly cellular smears with cohesive, 3-dimensional sheets of uniform, small cells with inconspicuous nucleoli arranged around a central lumen, forming 'punched-out' spaces. Single cells were prominent in 2 of 14 cases. IG DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets with punched-out spaces, abundant single cells, moderate pleomorphism and focal necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however, distinction from invasive carcinoma may not be possible. The cytologic diagnosis of LG DCIS is difficult, and 50% of our cases were called atypical on AB. Recognition of cohesive cellular arrangements with crowding and punched-out spaces is crucial as single cells and prominent atypia are often lacking

The diagnostic category of atypical glandular cells (AGC) in the Bethesda system for the reporting of cervicovaginal cytology has undergone significant modification since its inception in 1988. More than a decade later, this category remains a diagnostic challenge to both clinicians and cytopathologists because of the lack of uniform cytologic criteria, the lack of interobserver agreement in the diagnosis, and the lack of standardized patient management guidelines. This article reviews the current classification of AGC in the Bethesda system, the cytomorphologic features and differential diagnosis, the clinical significance of a diagnosis of AGC, and the clinical management of patients with AGC. This article provides a comprehensive clinicopathologic review of the category of AGC

The 2001 Bethesda System has radically altered the classification of glandular abnormalities. The recognition of the cytologic features of atypical glandular cells on cervicovaginal smears is important because a significant number of patients will be found to have an underlying cancerous or dysplastic lesion of the exocervix, endocervix, or endometrium. The differential diagnosis of AGC on cytology is diverse and accurate classification is necessary because the most appropriate form of follow-up depends on the specific subcategorization of the atypical glandular cells. Because the level of interobserver agreement in the diagnosis of AGC is poor, effective communication between cytopathologists and clinicians is essential to accurately triage these patients. This article should help the cytology practitioner by providing a comprehensive review of the approach to the interpretation, clinical significance, histopathologic correlation, and management of patients who have atypical glandular cells on gynecologic cytology specimens

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FN 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and 'suspicious' for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FN those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia