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Introduction: The Paris System (TPS) has recently been used in classification of urinary tract cytological specimens. Upper urinary tract (UUT) specimens are cytologically challenging. The utility of TPS was investigated in evaluating UUT specimens and its correlation with subsequent histological follow‐up. Method: From 2014 to 2017, 324 cytology cases of UUT from 179 patients were retrieved. Concurrent or subsequent biopsy or resection within a 2‐month period was available in 125 cases from 74 patients. Result: None of the cases with a cytology of low‐grade urothelial neoplasm was found to have a high‐grade urothelial carcinoma (HGUC) on biopsy. Among the 19 atypical urothelial cells (AUC) cytology cases, the histology is heterogeneous (seven benign, one atypia, five low‐grade lesion, and six HGUC). The risk of HGUC for each cytological diagnostic category are 0% for non‐diagnostic/unsatisfactory, 6% for negative for HGUC, 27.3% for AUC, 0% for low‐grade urothelial neoplasm, 48% for suspicious for HGUC and 95% for positive HGUC. When we considered cytology cases with suspicious or positive for HGUC interpretations as positive, the performance of TPS in predicting high grade urothelial carcinoma on histology had values of: 78.6% sensitivity, 86% specificity, 80.5% positive predictive value and 84.5% negative predictive value. Conclusion: More than one‐third of the UUT cytological cases were classified as AUC and approximately 1/15 as suspicious or positive for HGUC. Based on UUT cytology specimens, the risk of malignancy of each cytological diagnostic category of TPS was comparable to those reported in the literature. The use of TPS in evaluating UUT cytology specimens was specific and sensitive in identifying patients with HGUC by histology. [ABSTRACT FROM AUTHOR]

Young pre-menopausal women with breast carcinomas have an overall worse prognosis than older, post-menopausal women. Because histologic grade is a major predictor of tumor behavior and correlates with biomarker expression, we assessed the immunohistochemical expression of epidermal growth factor receptor (EGFR), p185(erbB-2) and Bcl-2, and nuclear accumulation of p53 in breast carcinomas in pre- and post-menopausal women with equivalent histologic grades. This allowed identification of differences in biomarker expression and prognostic significance in pre- and post-menopausal women independent of histologic grade. We investigated 100 infiltrating ductal carcinomas (IDC) in pre-menopausal women, ages 45 years and younger, and 100 IDC in post-menopausal women, ages 65 years and older. The IDC were selected so that the proportions of high and low/moderate grade carcinomas were equal in the pre- and post-menopausal groups. Prognostic utility of biomarker expression in pre- and post-menopausal groups was determined by product limit and multivariate analysis of survival. There were statistically significant differences in cytoplasmic expression of EGFR and Bcl-2 and nuclear accumulation of p53, but not in the expression of p185(erbB-2), in carcinomas of high vs. low histologic grade. There was no difference in the expression of EGFR, p185(erbB-2) or Bcl-2, or in nuclear accumulation of p53 in these IDC from pre- vs. post-menopausal women. Bcl-2 and the nuclear accumulation of p53 were of prognostic significance in our overall study population; however, when assessing pre- and post-menopausal women separately, Bcl-2 and p53 were of prognostic significance only in pre-menopausal, but not post-menopausal women. In summary expression of EGFR and Bcl-2 and nuclear accumulation of p53 were significantly associated with histologic grade, but not with menopausal status. In addition, there were differences in the prognostic effectiveness of these biomarkers in pre- vs. post-menopausal women.

Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA.

Patients with small-cell lung carcinoma (SCLC) rarely present with pleural effusions. Based on morphology alone, recognition of SCLC in effusion cytology may be challenging because of the resemblance of neoplastic cells to lymphocytes. Immunocytochemistry may be helpful in its diagnosis. The objective of this study was to review the morphology and evaluate the use of immunocytochemistry in diagnosing SCLC in pleural fluids. Patients with SCLC who presented with pleural effusions were identified during a 6-yr period. The cytology and medical records were reviewed. Formalin-fixed, paraffin-embedded cell blocks of fluid specimens were immunostained with neuroendocrine markers (chromogranin A and synatophysin), cytokeratin 20 (CK20), and thyroid transcription factor-1 (TTF-1). The latter is a nuclear transcription protein that is expressed in normal respiratory epithelium and also in more than 90% of SCLCs. Of the 256 patients diagnosed with SCLC during the study period, 8 (2.7%) patients (3 females and 4 males, age range from 56-85 yr) also developed pleural effusions. One patient had 2 fluid specimens during the course of their disease, giving a total of 9 specimens. Four specimens had a positive cytologic diagnosis of SCLC, and 2 were initially diagnosed as suspicious for SCLC. The remaining 3 specimens were negative for SCLS. The specimens with a positive or suspicious diagnosis showed single and aggregates of small to medium-sized single cells with a high nuclear:cytoplasmic (N:C) ratio, round to angulated nuclei, and salt-and-pepper chromatin. Nuclear molding was also noted. Five out of 6 (83%) specimens with a positive or suspicious diagnosis of SCLC were positive for both chromogranin A and TTF-1. Synaptophysin was positive in 3 of 6 (50%) positive or suspicious cases. None of the cases were positive for CK20. All cases with a negative cytologic diagnosis were negative for chromogranin A, synatophysin, CK20, and TTF-1. In conclusion, patients with SCLC rarely present with pleural effusions. The cytology of SCLC is characteristic. The use of immunocytochemistry, particularly with antibodies to chromogranin A, TTF-1, and CK 20, aids in the differential diagnosis., (Copyright 2001 Wiley-Liss, Inc.)

Objective: To determine the frequency of atypical glandular cells of undetermined significance (AGUS) for three consecutive calendar years from three different referral sources., Study Design: Cervicovaginal smears with a diagnosis of AGUS were identified from January 1995 through December 1997. The smears were submitted from three different sources: two were city government hospital clinics, one with predominantly African American and Hispanic patients and the other with predominantly Asian and Hispanic patients. The third referral source was private practitioners' offices with predominantly Caucasian patients., Results: A diagnosis of AGUS was made in 707 cases, accounting for 0.56% of all smears examined. This was in contrast to 6,872 smears reported as atypical squamous cells of undetermined significance (ASCUS) (5.4%) and 3,347 reported as squamous intraepithelial lesions (SIL) or above (2.7%). The incidence of AGUS ranged from 0.16% to 1.00% among different patient populations. This difference was also noted in the rate of ASCUS and SIL in the same patient population. There was a steady increase in the rate of AGUS for each referral source during the study period. The overall rate of patients who underwent histologic evaluation and the incidence of biopsy-proven preinvasive and invasive lesions were 62.4% and 23%, respectively. There was no significant difference in the rate of significant lesions after a diagnosis of AGUS during the study period or between the three referral sources., Conclusion: The AGUS rate in our laboratory was low and within the range (0.17-1.83%) reported in the literature. The AGUS rate varies with different patient populations, particularly with the incidence of SIL and age distribution.

Objective: To study the clinical significance of atypical glandular cells of undertermined significance (AGUS) in pregnant and postpartum women., Study Design: We evaluated 35 women who were pregnant (30) or within three months postpartum (5) and had a cytologic diagnosis of AGUS. Twenty-seven (77%) patients had follow-up: 17 (63%) patients underwent colposcopic examination and biopsy, and 10 (37%) had repeat Pap smears. Eight patients were lost to follow-up., Results: Five (29.4%) patients had a squamous intraepithelial lesion (SIL), including three high grade and two low grade, on subsequent biopsy. The remaining (70.6%) patients had benign pathology, which included 5 chronic cervicitis, 4 endocervical and/or endometrial polyps, 2 Arias-Stella reaction and 1 microglandular hyperplasia. Among the patients with repeat Pap smears, two had persistent AGUS/atypical squamous cells of undetermined significance, the remaining cases were within normal limits., Conclusion: Pregnancy-related changes may present with glandular atypia. In addition, about one-third of pregnant and postpartum women with a diagnosis of AGUS had SIL on subsequent biopsy; that rate is similar to that in nonpregnant women. Therefore, pregnant women with a cytologic diagnosis of AGUS should be followed closely.

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), (Copyright 2001 American Cancer Society.)

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., (Copyright 2001 Wiley-Liss, Inc.)

Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings., (Copyright 2000 Wiley-Liss, Inc.)

A substantial percentage of women with a diagnosis of atypical glandular cells of undetermined significance (AGUS) on cervical smears harbor a significant squamous or glandular, preneoplastic or neoplastic lesion on subsequent follow-up. Attempts to subclassify AGUS smears by conventional methods have had mixed results. To determine whether subclassification of AGUS cervical smears using computer-assisted rescreening based on the neural network would improve correlation with subsequent histologic follow-up, 91 cervical smears, conventionally diagnosed as AGUS without concomitant squamous lesions, were subjected to analysis by a computer-assisted automated screening system. Computer-generated images were evaluated by a cytotechnologist without the knowledge of the histologic outcomes. Prior to manual review, each case was classified as either within normal limits, no review required; or abnormal, review required. Based on the degree of abnormality, the latter category was further subclassified into either low probability or high probability of abnormality. The results of the computer-assisted reclassification were then compared with the histologic follow-up of all patients. Thirty-three cases (38.8%) had a significant lesion on histologic follow-up. The lesions included 4 CIN I, 7 CIN II/III, 12 endocervical adenocarcinomas (ACA), and 10 endometrial ACA. Based on computer-generated images, 65% of the smears that were triaged as high probability of abnormality, 11.5% that were triaged as low probability of abnormality, and 10.5% that were triaged as within normal limits had a significant lesion on subsequent follow-up. We conclude that computer-assisted rescreening aids in the triage of AGUS smears and that computer-assisted rescreening based on the neural network or other algorithms may be a useful ancillary tool for subclassifying AGUS cervical smears., (Copyright 2000 Wiley-Liss, Inc.)

Objective: To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions., Study Design: A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996., Results: In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy., Conclusion: Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears.

Background: Fine-needle aspiration (FNA) biopsy of palpable breast masses along with clinical and radiologic findings can provide rapid distinction between benign and malignant lesions. A preoperative determination of invasive or in situ carcinoma assists in the planning of definitive treatment. Previous studies have concentrated on whether cytologic features adequately distinguish invasion, but to the authors' knowledge the predictive value of clinicopathologic correlation has not been investigated. The authors attempted to determine whether a malignant cytologic diagnosis for a palpable breast mass is sufficient for its definitive surgical management as an invasive neoplasm., Methods: The authors reviewed 351 FNAs from palpable breast lesions with a cytologic diagnosis of "adenocarcinoma." The presence of invasive disease was determined by histologic demonstration of invasive carcinoma in the corresponding surgical specimen or by identifying metastatic carcinoma in the absence of another primary source., Results: Three hundred forty-three (97.7%) palpable tumors diagnosed as adenocarcinoma by FNA proved to be invasive adenocarcinoma. The remaining eight tumors contained high grade ductal carcinoma in situ, and two of these contained foci suggestive of microinvasion., Conclusions: A palpable breast mass with an FNA diagnosis of adenocarcinoma usually represents invasive carcinoma. A definitive treatment plan therefore can be planned based on these clinical and FNA findings.

Uterine polypoid adenomyomas, both typical and atypical variants, often arise in the lower uterine segment or endocervical canal as pedunculated polypoid masses that may be accessible for cytologic sampling. However, their cytologic findings have rarely been described in the literature. Two women in their reproductive age presented with abnormal vaginal bleeding. The cervicovaginal smear of the first patient contained sheets and strips of reactive endocervical cells in an inflammatory background. In addition, loose aggregates of spindle-shaped smooth muscle cells were also noted. The findings were consistent with those of a typical polypoid adenomyoma. The cervicovaginal smears of the second patient consisted of tightly packed, crowded clusters of glandular cells which were initially interpreted as atypical glandular cells, suspicious of adenocarcinoma. In retrospect, loose aggregates of smooth muscle stromal cells were noted. Subsequent curettage revealed an atypical polypoid adenomyoma. The cytologic findings of typical polypoid adenomyoma were nonspecific except for the presence of loose aggregates of smooth muscle cells. The cytologic features of an atypical polypoid adenomyoma may mimic that of a neoplastic glandular process. The findings of tightly packed clusters of glandular cells and loose aggregate of bland-appearing smooth muscle cells in premenopausal patients may suggest the diagnosis of atypical polypoid adenomyoma. Diagn. Cytopathol. 2000;22:176-180., (Copyright 2000 Wiley-Liss, Inc.)

Background: Aspirates of thymomas are distinguishable from other lesions and fine-needle aspiration (FNA) is a proven method for investigating mediastinal masses., Methods: Thirty-four cytology specimens of thymomas from 31 patients were examined. Corresponding surgical materials were available in 32 cases. Ten cases were benign and 22 were malignant. Cytologic features of these thymomas were correlated with various histologic classification systems and with biologic behavior. Dual epithelial and lymphoid populations and irregular cohesive tissue fragments of varying proportions of lymphoid and epithelial cells were characteristic of all aspirates., Results: Using the Lattes-Bernatz classification, 10 cases predominately were lymphocytic, 3 cases predominately were epithelial, 3 cases predominately were spindle, 15 cases predominately were mixed, and 1 case was a thymic carcinoma. In the Muller-Hermelink classification, 3 cases were medullary, 12 were mixed, 8 predominately were cortical, 2 were cortical, 6 were well differentiated thymic carcinoma, and 1 was a poorly differentiated thymic carcinoma. In the majority of the cases the epithelial cells were round to oval. Spindle cells and a mixture of round to oval and spindle cells also were observed. No cytologic feature was found to correlate significantly with any classification scheme. Necrosis was present in 5 of the 32 aspirates, most frequently in malignant tumors. Thymomas showing predominately spindle cells frequently were encapsulated. Tumors with predominantly round to oval cells or a mixed population behaved more aggressively than those with spindle cells. Tumors that were well encapsulated and benign clinically tended to possess benign-appearing nuclei. Among the 22 invasive or malignant lesions, 8 exhibited moderate to marked cytologic atypia and 14 showed little or no atypia. No atypia was observed in benign tumors., Conclusions: The presence of cytologic atypia of epithelial cells may be helpful in predicting aggressiveness. However, the absence of atypia and necrosis may not imply a benign course. Correlation with clinical and radiographic findings should be sought.

We report a case of desmoplastic malignant melanoma metastatic to the parotid gland initially evaluated by fine-needle aspiration. The cytologic findings consisted of scattered spindle cells in a background of heterogeneous lymphoid cells. The spindle cells were scant and displayed mild cytologic atypia. In addition, rare stromal fragments were also present. Cytoplasmic pigment and intranuclear cytoplasmic inclusions were not seen. The initial impression was that of a reactive lymph node with fibrosis. In retrospect, rare spindle cells displayed moderate atypia. In addition, the stromal fragments were cellular and contained spindle cells with mild atypia. These cytologic findings along with a known history of malignant melanoma should provide clues to the correct diagnosis of desmoplastic malignant melanoma. Diagn. Cytopathol. 2000;22:97-100., (Copyright 2000 Wiley-Liss, Inc.)

Background: Multilocular thymic cyst with follicular lymphoid hyperplasia is a rare complication in HIV-infected patients, causing pseudotumorous enlargement of the anterior mediastinum. There have been six reported cases, all with only histologic findings. This paper reports another such case and includes perhaps the first cytologic findings on this rare entity., Case: A 35-year-old, HIV-infected male intravenous drug abuser, who complained of worsening central chest discomfort and pain on deep inspiration, was found to have a large, septated anterior mediastinal mass. Computed tomography-guided fine needle aspiration biopsy was performed. The cytologic presentation mimicked that of thymoma, with cystic degeneration and a dual population of epithelial cells and lymphocytes as well as large aggregates of "epithelial" cells intermixed with lymphocytes in a background of macrophages and cyst fluid. Histologic examination of the resected mass revealed a multilocular thymic cyst with follicular lymphoid hyperplasia. HIV-1 core protein p24 was localized immunohistochemically in the dendritic follicular cells of the germinal centers. In retrospect, the quantity of epithelium derived from the cyst lining was too scanty for thymoma, and the presence of plasma cells and lymphohistiocytic aggregates suggested follicular lymphoid hyperplasia., Conclusion: Multilocular thymic cyst with follicular lymphoid hyperplasia should be considered in the differential diagnosis of an anterior mediastinal mass in HIV-infected patients after lymphoma and tuberculosis.

Background: Primary liposarcoma of the breast is an extremely rare lesion. Only two cases describing the aspiration biopsy findings have been reported in the literature. We report the cytologic findings in an additional case, stressing the cytologic clues necessary to distinguish this neoplasm from a primary adenocarcinoma., Case: A 53-year-old female presented to the emergency room with bleeding from a 20-cm, ulcerating mass in the right breast. Four months earlier she had been seen at another institution, where a diagnosis of poorly differentiated carcinoma was made by aspiration biopsy. Computed tomography had been negative for metastatic disease, and the patient refused further evaluation. Aspiration biopsy of the breast mass was repeated at our institution and interpreted as consistent with a poorly differentiated carcinoma. Histologic, immunophenotypic and ultrastructural evaluation of the mastectomy specimen revealed a pleomorphic liposarcoma., Conclusion: With increasing utilization of fine needle aspiration to evaluate breast lesions, it can be anticipated that unusual entities, including liposarcomas, will be encountered increasingly in breast aspirates. Therefore, it is important to consider liposarcoma in the differential diagnosis of aspirates showing isolated spindle and polygonal cells with vacuolated cytoplasm, nuclear scalloping and pleomorphism to avoid a misdiagnosis of carcinoma.

Metastases to the breast from extramammary primary malignancies, including renal adenocarcinoma, are rare. Fine-needle aspiration biopsy (FNA) is a useful, noninvasive, and rapid procedure to evaluate these mammary lesions. This study describes the cytomorphology of 3 cases of renal-cell adenocarcinoma metastatic to the breast. All patients had a prior history of renal-cell adenocarcinoma treated with radical nephrectomy, and they presented with a solitary mammary mass. The cytologic findings showed irregular clusters and dispersed single cells with eccentric nuclei and abundant, vacuolated cytoplasm in a hemorrhagic background. The nuclei were round to oval, with fine granular chromatin and a single, prominent nucleolus. All aspirates were interpreted initially and correctly as consistent with metastatic renal-cell adenocarcinoma. In summary, a cytologic diagnosis of renal-cell adenocarcinoma metastatic to the breast can be made by correlating clinical and cytologic findings. The distinction between metastatic extramammary malignancies to the breast and primary mammary carcinoma is critical to avoid unnecessary surgery and to ensure appropriate chemotherapy or radiation therapy., (Copyright 1999 Wiley-Liss, Inc.)

Fine-needle aspiration (FNA) has been increasingly utilized as a diagnostic tool in evaluating salivary gland masses, primarily to differentiate nonneoplastic from neoplastic lesions. Patients infected with human immunodeficiency virus (HIV) frequently present with salivary gland lesions. In this study, we reviewed the cytology of salivary gland lesions in HIV-infected patients and assessed the value of FNA in the diagnosis of salivary gland lesions in HIV-infected patients. One hundred and three FNAs of salivary gland lesions from 78 HIV-infected patients (63 males and 15 females) were included in our study. The patients' ages ranged from 7-65 yr, with a mean age of 40.9 yr. FNAs were classified into three categories: benign lymphoepithelial lesions (BLL) (77 cases or 74.8%), inflammatory processes (14 cases or 13.6%), including 3 reactive lymphoid hyperplasia, and neoplastic lesions (6 cases or 5.8%). The latter included three malignant lymphomas, a multiple myeloma, a metastatic adenocarcinoma from a lung primary, and a direct extension of basal-cell carcinoma. Six (5.8%) aspirates were nondiagnostic. No false-positive or false-negative cases were noted during follow-up of these patients. In conclusion, FNA is a simple and cost-effective procedure for the diagnosis of HIV-related salivary gland lesions. The majority of these lesions are cystic BLL and can be managed conservatively. Malignant lesions are rarely encountered and are readily recognized by FNA. Diagn. Cytopathol. 1999;21:260-264., (Copyright 1999 Wiley-Liss, Inc.)

Background: The identification of neoplastic cells in synovial fluid is an uncommon occurrence and most often is related to extension of extraarticular tumor into the joint space than to primary neoplasm arising in the joint., Case: In this report the cytologic features of synovial fluid obtained from the right knee of an 18-year-old male with biopsy-proven pigmented villonodular synovitis are described and compared with the features of the concurrent surgical specimen., Conclusion: The cytologic features of pigmented villonodular synovitis in synovial fluid include abundant mononuclear histiocytic cells occurring singly and in papillary clusters, hemosiderin within histiocytes and few multinucleated giant cells.

The bcl-2 gene product inhibits programmed cell death (apoptosis). The expression of this protein has been examined in normal endometrium and found to be cycle dependent with consistent expression in the proliferative phase. In the current report, bcl-2 gene expression was examined in 88 endometrial biopsies that showed 99 histologic patterns ranging from proliferative endometrium to carcinoma. Whereas expression was always detected in 17 samples of proliferative endometrium, eight cases of simple hyperplasia, and five cases of complex hyperplasia, expression was detected in only five (42%) of 12 atypical hyperplasias and in only 27 (47%) of 57 carcinomas. In atypical hyperplasia and carcinoma showing expression, both staining intensity and distribution were less than that seen in their benign counterparts. Three of five biopsies showing both benign endometrium and carcinoma showed positivity in benign but not in malignant glands. In endometrial carcinoma, bcl-2 expression did not correlate with grade, stage, or survival. In addition, in cases of carcinoma, a negative correlation between bcl-2 and p53 expression, which has been reported in other tumors, was not observed in this study. The invariable expression of bcl-2 in proliferative endometrium suggests that this protein may be important for cell survival. Its role in preventing cell death, however, appears to be frequently bypassed in atypical hyperplasia and endometrial carcinoma possibly by other factors impeding programmed cell death. Thus, if an apoptotic pathway usually blocked by bcl-2 expression would not necessarily lead to cell death. Defects in an apoptotic pathway such as the transforming growth factor-beta pathway, which can be blocked by bcl-2, may possibly account for the phenomenon observed in this study.

P-glycoprotein (PGP), which is a product of the multidrug resistance gene (MDR1), is an active transmembrane efflux pump responsible for detoxifying normal cells as well as rendering tumor cells resistant to chemotherapy. It has also been implicated to be expressed by more aggressive cancers. It has not been well described in squamous cell carcinoma of the head and neck. In this investigation, an attempt was made to characterize advanced squamous cell carcinoma of the base of tongue with respect to expression of PGP. Using immunohistochemical techniques two anti-PGP monoclonal antibodies (JSB1 and C494) were used to detect PGP in these lesions, and an attempt was made to correlate levels of PGP staining and various tumor parameters. Usefulness of PGP in predicting survival and time to recurrence was also examined for these advanced lesions. All 33 base of tongue lesions showed staining for PGP with these monoclonal antibodies. This was the first study examining utility of C494 in detecting PGP in squamous cell carcinoma at this site. Increased level of PGP expression was seen in better-differentiated tumors as well as in tumors with diploid DNA. A trend of higher PGP expression and decreased survival emerged. This may represent a true relationship, but inherent heterogeneity of PGP expression within cells cannot be excluded. Both antibodies examined appear to be useful in the investigations of PGP distribution in squamous cell carcinomas of the head and neck sites by immunohistochemical techniques. Prognostic value of the level of PGP expression remains to be seen.

The rare presentation of choriocarcinoma as a cutaneous metastasis in a 23-year-old male is reported. Histological and immunohistochemical analysis of the biopsy material demonstrated two distinct cell populations, syncytiotrophoblasts and cytotrophoblasts, with syncytiotrophoblasts strongly positive for human chorionic gonadotropin antigen. Subsequent clinical evaluation revealed a testicular tumor with metastases to lungs, brain, liver and kidney and increased serum levels of human chorionic gonadotropin. The patient died shortly after diagnosis due to complications of metastatic disease despite chemotherapy.