Faculty Bibliography

BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining

INTRODUCTION. Although the cytologic features of Hodgkin disease (HD) has been well described, HD accounts for most of the false-negative fine-needle aspiration (FNA) biopsies of malignant lymphomas. In this study, the authors examined the factors contributing to a false-negative diagnosis of HD. METHODS: Eighty-nine cases from 72 patients (23 females and 49 males) with HD evaluated by FNA were identified between 1990 and 1999. The patients' ages ranged from 5 to 90 years (median, 38 years). Eighty-five FNAs were from lymph nodes, and 4 were from extranodal sites. Histologic correlation was available for all patients. RESULTS: Based on the original cytologic diagnosis, 43 (48.3%) cases had a positive diagnosis of HD, 20 (22.5%) suspicious or atypical diagnosis, 13 (14.6%) a benign diagnosis (false-negative cases), and 10 (11.2%) were nondiagnostic. Three (3.4%) additional cases had a malignant diagnosis other than HD. After review, three false-negative cases were reclassified as HD and seven as atypical lymphoid proliferation. Three of these 10 cases also showed conspicuous collections of histiocytes mimicking poorly formed granulomas. In those 'atypical' cases, only rare Reed-Sternberg (R-S) cells variants were identified. No R-S cells or its variants were identified in the remaining three false-negative cases; subsequent excisional biopsy showed partial involvement of the lymph node by HD in two cases. Among the nondiagnostic cases, nine cases showed considerable fibrosis in the resected lymph node. In addition, six cases were performed without on-site assessment. CONCLUSIONS: The cytologic diagnosis of HD can be challenging when classic R-S cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node by HD, sampling error, and misinterpretation. On-site assessment significantly minimizes the false-negative diagnostic rate. Furthermore, additional material can be obtained for ancillary studies. Cancer (Cancer Cytopathol)

BACKGROUND: Glandular atypia in Papanicolaou (Pap) smears from postmenopausal women is encountered frequently. This finding can be the result of artifactual alterations such as drying artifacts and inflammatory changes or may represent a squamous or glandular, preneoplastic or neoplastic process. Therefore, it is important to determine the clinical implication of a diagnosis of atypical glandular cells of undetermined significance (AGUS) in postmenopausal patients. METHODS: A total of 30,036 Pap smears were obtained from postmenopausal women between 1995 and 1997. Among these smears, 154 (0.51%) had a diagnosis of AGUS. Follow-up was available for 133 patients (86.4%); 110 patients (82.7%) had histologic follow-up (including cervical biopsy, endocervical [EC] curettage, and/or endometrial [EM] biopsy) and 23 patients (17.3%) had repeat smears. RESULTS: Thirty-six of 110 patients (32.7%) were found to have a clinically significant lesion (defined as a preneoplastic or neoplastic, glandular or squamous lesion) on subsequent histologic follow-up. Nineteen patients (53%) had glandular lesions (15 EM adenocarcinoma [ACA] cases, 2 EC ACA cases, 1 EC adenocarcinoma is situ case, and 1 EM hyperplasia case). Seventeen patients (47%) had a squamous intraepithelial lesion (SIL) (6 cases of low-grade SIL, 9 cases of high-grade [HGIL], and 2 cases of squamous cell carcinoma). Among those patients with repeat Pap smears, five patients had persistent AGUS/atypical squamous cells of undetermined significance and one patient had an SIL. CONCLUSIONS: The incidence of AGUS among postmenopausal patients was similar to that of the general population (0.51% vs. 0.56%; P > 0.05). A significant percentage of these patients were found to have a clinically significant lesion on subsequent follow-up. Furthermore, a majority of these lesions were ACA (53%) or HGSIL (26%). The findings of the current study strongly suggest the need for the close follow-up of postmenopausal patients with a diagnosis of AGUS. Cancer (Cancer Cytopathol)

Diagnosis of non-Hodgkin's lymphomas based on cytologic evaluation of fine-needle aspirates and body cavity fluids has gained increasing acceptance. However, the accurate diagnosis and classification of low- and intermediate-grade B-cell lymphomas with a predominant small-cell population still present a diagnostic challenge. In this study, we reviewed the cytology and immunophenotype of 56 cases of low- and intermediate-grade non-Hodgkin's B-cell lymphomas composed of predominantly small cells, with histologic correlation in all cases. These cases consisted of 23 small lymphocytic lymphomas (SLL), 15 follicular center lymphomas (FCL), grade I (small cell predominant), 8 lymphoplasmacytoid lymphomas (LPL), 6 mantle-cell lymphomas (MCL), and 4 marginal zone lymphomas (MZL) including mucosa-associated lymphoid tissue (MALT) lymphoma. Histologic comparison was available in all cases. A cytologic diagnosis of malignant lymphoma was made in 46 (82%) cases. Based on cytomorphology and immunophenotyping of cytologic material, 39 (85%) cases were correctly classified using the Revised European and American Lymphoma classification. In 7 (11%) cases, which included 3 FCLs, 2 MALT lymphomas, and 2 SLLs, the findings were atypical but not diagnostic of lymphoma. There were 3 (5%) false-negative cases. They were 2 SLLs and a FCL. Immunophenotyping done in 4 'atypical' cases was noncontributory. No marker studies were done in the remaining 'atypical' case and all false-negative cases. We conclude that cytology, when used in conjunction with immunophenotyping, can accurately diagnose and in most instances subclassify low- and intermediate-grade B-cell non-Hodgkin's lymphoma with a predominant small-cell population

Tubular adenocarcinoma is an invasive mammary adenocarcinoma associated with an excellent prognosis and a low incidence of axillary metastases. However, identification of tubular adenocarcinoma by fine-needle aspiration (FNA) biopsy has proven difficult. One hundred five patients with documented 'pure' tubular adenocarcinoma were diagnosed at Tisch Hospital from August of 1992 to December of 1998. Twenty-one of these patients had an FNA before excision. We reviewed the smears of these cases and compared them with cases of fibroadenoma and fibrocystic change to identify criteria for diagnosis. Moderately to highly cellular smears with angular cellular clusters with sharp borders and oval cells outlining these clusters, dispersed single cells with minimal atypia, and the absence or paucity of dispersed bare oval nuclei in the background were features that suggest a diagnosis of tubular adenocarcinoma in our study. Attention to these features in combination with appropriate mammographic findings should preclude a false-negative diagnosis in the majority of cases of tubular adenocarcinoma diagnosed by aspiration biopsy. We point to the presence of the peripheral perpendicular cells in the characteristic tubular arrays as an important clue to the diagnosis of tubular adenocarcinoma