Anorectal smear in the diagnosis of anorectal adenocarcinoma.

The purpose of this case report is to point out the diagnostic value of cytologic smears in patients presenting with anorectal complaints, such as bleeding, pain or discomfort, which may suggest a neoplastic lesion. We present a case of a 64-year-old man with a 3 months' history of anal bleeding and pain during defecation. He was diagnosed as having hemorrhoids and a hemorrhoidectomy was performed. The patient developed an anal stricture postoperatively that required operative dilation. He continued to complain about anorectal pain for 2 months and a subsequent rectoscopy revealed the presence of tumor 5 to 7 cm above the dentate line. The tumor was resected laparoscopically and was reported as an adenocarcinoma. Rectal bleeding recurred 18 months postoperatively and a smear was procured from the anorectal mucosal surface for cytologic evaluation. A definitive diagnosis of adenocarcinoma was rendered based on cytologic and histologic examination of the material. To the best of our knowledge, this is the first case report of anorectal adenocarcinoma diagnosed by cytologic smear in the English literature.

Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions.

OBJECTIVE: To study the DNA ploidy pattern of uterine cervical squamous intraepithelial lesions (SILs) and its diagnostic and prognostic significance. METHODS: The study included 31 cases of SIL: 11 low-grade (LSIL) and 20 high-grade (HSIL). Feulgen-pararosaniline staining was performed on previously Papanicolaou-stained smears and a DNA image cytometric study was performed. An internal reference was used to calibrate the samples. RESULTS: All 31 cases of SIL, either LSIL or HSIL, were non-diploid. Of the 11 cases of LSIL, four were tetraploid and seven were aneuploid, whereas, of the 20 cases of HSIL, four were tetraploid and 16 were aneuploid. Stemline aneuploidy was not a significant discriminator between LSIL and HSIL (P=0.32). Based on single-cell analysis, HSIL cases had significantly higher DNA content than LSIL cases (P<0.01). When a mean of 30% or more was used for the 6c-exceeding event (6cEE) value, the sensitivity and specificity to indicate HSIL were 83% and 64%, respectively, with a positive predictive value (PPV) of 81% and negative predictive value (NPV) of 65%. All HSIL cases were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy. In addition, cases which showed recurrence had more DNA content by single-cell analysis than those with an indolent clinical behaviour: P=0.04 and P=0.03 for LSIL and HSIL, respectively. CONCLUSIONS: Image cytometric DNA analysis is a useful technique for diagnostic and prognostic purposes in uterine cervical SIL when appropriate 'c' values are used in single-cell analysis. We propose that a >6c DNA content of 30% is useful as a cut-off level for predicting cases with CIN2+ in DNA image cytometry of cervical smears.

Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer: expression of coxsackie-adenovirus receptor and integrins alphavbeta3 and alphavbeta5.

OBJECTIVE: Ten patients with recurrent ovarian cancer received a combined treatment of optimal tumor debulking, adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (GT), and systemic application of acyclovir or valacyclovir and topotecan. Biopsies were taken at the time of secondary debulking about 1 month after the application of GT and chemotherapy and were analyzed for expression of coxsackie-adenovirus receptor (CAR) and integrins alphavbeta3 and alphavbeta5 with respect to treatment response. METHODS: Treatment modalities and study design have been described recently. Immunohistochemistry was used to visualize expression of CAR and integrins alphavbeta3 and alphavbeta5 in tumor samples taken before and after application of GT. RESULTS: Before GT six of ten patients presented with CAR-positive and four with CAR-negative tumors. After GT all tumors showed CAR expression. Integrin alphavbeta3 was found in all tumors before and after GT. Expression of integrin alphavbeta5 was seen in eight of ten tumor samples before GT and in all samples after GT. CONCLUSION: Despite the importance of CAR and integrin expression for successful adenovirus internalization, other cell surface receptors might be involved in this process. It is too early to decide whether expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells are appropriate additional inclusion criteria for the enrollment of patients in GT trials. Further research is necessary to evaluate the effect of GT plus chemotherapy on CAR and integrin expression.

Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer.

Herpes simplex virus (HSV) thymidine kinase (tk) gene incorporated into adenovirus was delivered intraperitoneally (ip) followed by an antiherpetic prodrug and topotecan in patients with recurrent epithelial ovarian cancer. Tissue response was evaluated. Ten patients underwent secondary debulking with subsequent delivery of ADV-HSV-tk therapy. Two patients each were treated at dose level 1 (2 x 10(10) vector particles = VP), 2 (2 x 10(11) VP), and 3 (2 x 10(12) VP); four patients were treated at dose level 4 (2 x 10(13) VP). Five patients underwent second-look surgery about one month after gene therapy (GT). Treatment response, presence of vector DNA, protein expression of steroid hormone receptors, p53, c-erbB2 and Ki67 protein were analyzed. At second-look, two out of five patients were tumor-free and none of their peritoneal biopsies showed vector DNA. After GT, the vital tumor mass was smaller, desmoplastic reaction had increased, and tumors were less differentiated with an increase of Ki67 expression. There was no change in expression of hormone receptors, p53, or c-erbB2. ADV-HSV-tk GT appears to eliminate cells with higher differentiation first and might induce fibrosis. Dedifferentiation might render residual cells more sensitive to chemotherapy secondary to their subsequent higher mitotic activity.

Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy. STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied. RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified. CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.

Proliferative activity in invasive breast carcinoma: a comprehensive comparison of MIB-1 immunocytochemical staining in aspiration biopsies to image analytic, flow cytometric and histologic parameters.

OBJECTIVE: To use MIB-1 antibody to assess proliferative activity in fine needle aspiration (FNA) samples of invasive breast carcinoma and compare these results to multiple other measures of proliferative activity. STUDY DESIGN: FNA slides from 62 patients with invasive breast carcinoma were subjected to staining with MIB-1. Quantitative MIB-1 values were compared to image analytic proliferative fractions (IPF) obtained from the same FNAs. MIB-1 values were also compared to flow cytometric S-phase fractions (SPF) and S + G2/M-phase fractions (FPF) and to histologic assessment of mitotic count (MC) in resected tumors. RESULTS: MIB-1 values, IPF, SPF, FPF and MC were suitable for evaluation in 55, 53, 50, 50 and 56 cases, respectively. MIB-1 values showed good correlation with IPF in FNAs (correlation coefficient = .57, P <.00001). MIB-1 values also showed correlation with SPF (correlation coefficient =.447, P = .003), FPF (correlation coefficient = .325, P = .023) and MC (correlation coefficient = .402, P = .01) in resected tumors. CONCLUSION: This study supports the use of MIB-1 values obtained from FNA samples for assessment of proliferative activity in invasive breast carcinoma, based on correlation of these values with multiple other parameters of proliferative activity. Assessment of these values can play a role in predicting prognosis and in selecting patients with invasive carcinoma of the breast for preoperative or adjuvant chemotherapy.

Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-year follow-up.

OBJECTIVE: Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor. METHODS: Ten patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal ip flow received delivery of ip ADV. Two patients each were treated on dose level 1 (2 x 10(10) vector particles), dose level 2 (2 x 10(11)), and dose level 3 (2 x 10(12)); four patients were on dose level 4 (2 x 10(13)). Acyclovir and topotecan were started 24 h after vector delivery. Five patients underwent second-look surgery about 4 weeks after application of gene therapy (GT). RESULTS: At the time of the second-look surgery, two out of five patients were free of tumor. Four weeks after GT none of the peritoneal biopsies showed residual vector DNA. Patients pretreated with an average of three different chemotherapeutic drugs and two different chemotherapy regimens had a median overall survival (OS) of 18.5 months. Three patients are still alive 30, 30, and 31 months after GT. CONCLUSION: With the combination of secondary optimal debulking, GT, and topotecan, median OS was about one-third longer than in previously reported second-and third-line trials. Survival was comparable to that of patients of other studies with secondary cytoreductive surgery in combination with chemotherapy.

Should the cytologic diagnosis of "atypical squamous cells of undetermined significance" be qualified? An assessment including comparison between conventional and liquid-based technologies.

BACKGROUND: The diagnosis of atypical squamous cells of undetermined significance (ASCUS) remains an enigma for the treating physician, because it encompasses both benign, reactive, as well as preneoplastic and possibly neoplastic conditions. To address this problem, The Bethesda System recommends qualifying the ASCUS diagnosis. This study analyzes the difference in the follow-up results between the various groups of patients with an ASCUS diagnosis as outlined by the Criteria Committee: favor premalignant (ASCUS-P), favor reactive (ASCUS-R), and unqualified (ASCUS-C). The outcome, based on follow-up biopsies and/or cytologies, for both the conventional Papanicolaou smear (CS) and liquid-based (LB) methodologies is compared. METHODS: The CS and LB biopsies and/or cytologies included 590 patients and 137 patients, respectively, who had an initial diagnosis of ASCUS. The final outcome after subsequent biopsy and cytology within a 1-year period for each methodology was tabulated. Furthermore, the addition of qualifiers for each diagnosis was tabulated for both cytology and biopsy follow-up and compared between CS and LB technologies. RESULTS: For CS, 29 patients (8.6%) were found to have squamous intraepithelial lesions (SIL) on subsequent cytologic smears, and 176 patients (63.7%) had SIL on biopsy follow-up. For LB, these numbers were 17 patients (19.1%) and 56 patients (65.1%), respectively. Regardless of the qualification used in the initial CS biopsy or cytology, over 90% of the subsequent smears resulted in a benign diagnosis. Biopsy outcomes after CS diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 80%, 53%, and 66% of patients, respectively. For LB diagnoses, subsequent smears detected SIL in 33% of patients with a diagnosis of ASCUS-P, 22% of patients with a diagnosis of ASCUS-R, and 12% of patients with a diagnosis of ASCUS-C. Biopsy outcomes after LB diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 68%, 64%, and 66% of patients, respectively. CONCLUSIONS: There appears to be no statistically valid benefit from a clinical point of view in qualifying an ASCUS interpretation by either CS or LB, except for CS evaluation of patients with a diagnosis of ASCUS-P.

Aspiration biopsy of osseous metastasis of retroperitoneal paraganglioma. Report of a case with cytologic features and differential diagnostic considerations.

BACKGROUND: Paragangliomas are uncommon tumors, only 10% of which are malignant, as evidenced by metastatic disease. It is rare for paraganglioma to present with symptomatic osseous metastases. CASE: A retroperitoneal paraganglioma presented in a 52-year-old man as painful metastases in the rib and vertebrae. Fine needle aspiration (FNA) of a lumbar vertebral lesion showed cells arranged singly and in loose clusters with fragile, vacuolated or finely granular cytoplasm, marked anisonucleosis and mitoses. Rare zellballen-type structures and intranuclear inclusions were present. Immunohistochemical studies of a subsequent FNA core biopsy of the retroperitoneal mass showed strong immunoreactivity with chromogranin and negative staining for keratin; that was helpful in differentiating this tumor from others in the differential diagnosis. CONCLUSION: The cytologic diagnosis of paraganglioma is difficult as these tumors exhibit a plethora of features that overlap those of many other neoplasms. The diagnosis can be confirmed with appropriate immunohistochemical studies of corresponding core biopsies.

Accuracy of fine-needle aspiration of thyroid.

CONTEXT: Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. OBJECTIVES: To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.-Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982-1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. RESULTS: The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. CONCLUSIONS: Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.

Renal lymphoma. The diagnostic and therapeutic roles of fine-needle aspiration.

This study focused on 19 patients with renal lymphoma (RL) from whom 20 initial (1 patient with fine-needle aspiration [FNA] specimens of masses in both kidneys) and 1 repeated FNA specimen were obtained. Of the 19 patients, 10 had secondary RL, 8 primary RL, and 1 transplant RL. The FNA samples were studied by smears (all cases), tissues (11), phenotyping by immunostaining (13) or flow cytometry (4), and gene rearrangement (3). The final diagnoses included 1 T-cell lymphoma and 18 B-cell lymphomas. Of the 20 original specimens, 14 were reported as positive for lymphoma, 3 suggestive of lymphoma, 1 positive for transitional cell carcinoma, and 2 unsatisfactory. The follow-up specimen showed reactive changes. Tissue correlation, available in 11 cases, confirmed a positive cytodiagnosis (7), provided a final diagnosis in the cytologically inconclusive cases (3), or revised the misdiagnosis of transitional cell carcinoma from smears (1). The phenotyping elucidated the B vs T lineage of the lymphoma in all tested cases, confirmed the positive cytodiagnosis in 10 cases, confirmed the reactive cytodiagnosis in 1 case, and helped achieve a conclusive diagnosis in 2 cases suggestive of lymphoma. Gene rearrangement studies showed light chain restriction in the 2 tested cases. FNA has an essential role in treatment planning for RL. Although FNA usually is diagnostically conclusive, a high index of suspicion and awareness of atypical or misleading cytomorphologic features are important for a correct interpretation, especially for primary RL. Ancillary testing is essential for the diagnosis in problematic cases and lays the foundation for the differential diagnosis.

Cryptococcal osteomyelitis. Report of a case with aspiration biopsy of a humeral lesion with radiologic features of malignancy.

BACKGROUND: Osteomyelitis due to Cryptococcus neoformans typically exhibits lytic lesions on radiographs. Extensive periosteal reaction is an uncommon feature. CASE: A 68-year-old man presented with pain and swelling in the left elbow. Radiologic studies exhibited a lytic humeral lesion with extensive periosteal reaction, interpreted as a malignant neoplasm. Fine needle aspiration biopsy (FNA) revealed abundant cryptococcal organisms. CONCLUSION: Cryptococcus is an uncommon cause of lytic osseous lesions that may mimic malignant neoplasms. Extensive periosteal reaction may support a radiologic diagnosis of primary osseous malignancy in rare cases. FNA with examination of Diff-Quik-stained slides may be employed for distinguishing cryptococcal osteomyelitis from malignant tumors and for prompt identification of the organisms.

Lymphadenopathy in children and adolescents: role of fine-needle aspiration in management.

This study was undertaken to assess the role of fine-needle aspiration biopsy in the evaluation of palpable peripheral lymphadenopathy in pediatric and adolescent patients. A 15-year experience in aspiration of patients younger than age 21 was reviewed. These cases were taken from four large university hospitals and clinics. Data included clinical information, anatomic site, cytologic diagnosis, and any follow-up surgical excision at these institutions. From a total of 1,302 lymph node fine-needle aspirates, a subset of 106 aspirates from patients 21 years or younger was selected. This group formed the basis for this study, and these aspirates were obtained from 103 patients. Most of these aspirates (88.7%) were from the head and neck; 11 were from sites other than head and neck; and the site was not stated in one case. One hundred and one of the aspirates produced adequate samples, and only five (4.72%) were unsatisfactory. Of the 106 fine-needle aspirates, 88 (83.0%) were diagnosed as negative for malignancy, five (4.7%) were inconclusive, and three (2.8%) were interpreted as suspicious but not diagnostic of malignancy. Five cases (4.7%) were diagnosed as positive for malignancy, including two cases of metastatic papillary carcinoma of the thyroid, two cases of Hodgkin's disease, and a single case of high-grade non-Hodgkin's lymphoma. No false-positive or false-negative diagnoses occurred, excluding the aspirates classified as inconclusive or suspicious but not diagnostic of malignancy (six cases). Results of aspirates from near adolescent and adolescent patients (ages 11-21 years) were compared with those of younger pediatric patients (age < 10 years). Eighty-one (76%) of the 106 aspirates were obtained from the older group. The percentage of unsatisfactory specimens was smaller and the percentage of inconclusive or suspicious or malignant diagnoses was greater in the older group. Fine-needle aspiration biopsy is reliable in the evaluation of palpable peripheral lymphadenopathy. As most fine-needle aspirates in children and adolescents proved to indicate benign reactive conditions that failed to respond to antibiotics rather than proving to be malignant tumors, we advocate a larger role for the fine-needle aspiration biopsy technique in the evaluation of peripheral lymphadenopathy in this age group. Its early use can direct further testing, saving time, expense, and morbidity for the patient and reducing anxiety for the parents.

Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer.

INTRODUCTION: Patients with recurrent ovarian cancer were treated with a replication-deficient recombinant adenovirus containing the herpes simplex virus thymidine kinase gene administered intraperitoneally (i.p.) followed by administration of an anti-herpetic prodrug and topotecan. MATERIALS AND METHODS: A total of 10 patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to < or =0.5 cm residual tumor. Patients with normal i.p. flow received i.p. delivery of adenovirus. Two patients each were treated on dose level 1 (2 x 10(10) vector particles (VP)), dose level 2 (2 x 10(11) VP), and dose level 3 (2 x 10(12) VP); four patients were treated on dose level 4 (2 x 10(13) VP). Acyclovir and topotecan were started 24 hours after vector delivery. RESULTS: No patient treated at any dose level incurred unanticipated toxic effects, and all side effects resolved. The most common adverse event was myelosuppression: grade 3 or 4 thrombocytopenia with grade 2-4 anemia in three patients and grade 3 or 4 neutropenia in eight patients. Three patients developed thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic transaminase/alanine aminotransferase. Temperature elevations that were not associated with detectable infection occurred in two patients. DISCUSSION: I.p. delivery of adenoviral vector with concomitant topotecan chemotherapy was well tolerated without significant lasting toxicities. Side effects were independent of the dose of adenoviral vector.

Thymidine kinase (TK) gene therapy of solid tumors: valacyclovir facilitates outpatient treatment.

BACKGROUND: In a Phase I study replication-deficient adenovirus containing the herpes simplex virus (HSV) thymidine kinase (TK) gene (AdV-HSV-TK) was instilled intraperitoneally in patients with recurrent ovarian cancer. Patients were treated with Acyclovir (ACV) or Valacyclovir (VCV) as enzymatic substrates. The purpose of this study was to compare serum levels of ACV and VCV. PATIENTS AND METHODS: The antiherpetic prodrug and Topotecan (1.0 mg/m2 over 30 minutes each day for 5 days) were started 24 hours after vector application. Eight patients received ACV (15 mg/kg i.v. over one hour every 8 hours for 42 doses), two patients were started on ACV for 5 days and then switched to oral VCV (2 g every 8 hours for a total of 42 doses). Blood samples were obtained 20 minutes prior to each drug. RESULTS: Serum levels of ACV and VCV (converted to ACV) were comparable. CONCLUSIONS: Suicide gene therapy with TK is under investigation in a variety of solid tumors. Replacing ACV by VCV will offer a cost-effective alternative and will significantly reduce duration of hospital stay improving quality of life and facilitating an outpatient gene therapy concept.

Utilization of fine-needle aspiration in the diagnosis of metastatic tumors to the kidney.

Renal masses secondary to metastases are not common. Few comprehensive reviews exist, which consist primarily of autopsy and radiologic reports. The purpose of this study was to review the types and incidences of various neoplasms which metastasize to the kidney and to determine the usefulness of fine-needle aspiration (FNA) in diagnosing them. Two hundred and sixty-one radiologically guided FNAs of renal lesions over a 9-yr period were reviewed. The diagnoses of the 261 renal FNAs were as follows: 136 (52%) were malignant, 111 (43%) were benign, and 14 (5%) were unsatisfactory. Of the 136 positive FNAs, 28 (21%) revealed metastatic tumors. The overall incidence of renal FNAs displaying metastatic tumors was 11%. Among the 28 patients with metastases to the kidney, 23 patients were men and 5 were women, with the mean age being 58 yr. Twenty-five patients (89%) had prior history of a primary malignancy, including lung carcinoma (11 cases, 39%), lymphoma (8 cases, 29%), hepatocellular carcinoma (3 cases, 11%), and one case each of breast, pancreatic, and cervical cancer. In the remaining 3 patients (11%), with metastatic adenocarcinoma (2 cases) and squamous-cell carcinoma (1 case), the primary tumor site remained unknown despite an extensive clinical workup. Overall survival after FNA was poor, with a mean of 9.8 mo. FNA is useful in the diagnosis of masses in the kidney secondary to metastatic disease. This information is of clinical importance, principally in the exclusion of a primary malignancy, but also to avoid unnecessary surgery and to plan for subsequent patient care.

Fine-needle aspiration of renal masses in adults: analysis of results and diagnostic problems in 108 cases.

Fine-needle aspiration (FNA) biopsy of the kidney has a traditionally well-defined role in the diagnosis and treatment of renal lesions. Recent improvements in renal imaging techniques have also brought renal FNA to the forefront, since small and asymptomatic renal masses are increasingly being detected. Before the physician institutes a treatment plan, such lesions usually require a definitive diagnosis that is best provided by FNA. To assess various aspects of renal FNA, including specimen adequacy, questionable cytologic patterns, and diagnostic pitfalls, we retrospectively evaluate our experience with 108 FNA biopsies performed for the evaluation of renal masses in adults. For each case, the smears were reviewed and correlated with tissue sections from cell blocks, surgical specimens, or autopsy material, when available. The cytologic diagnoses were confirmed by cell block (59 cases), nephrectomy or autopsy (35 cases), or clinical follow-up. Of the 108 FNA biopsy samples, 17 showed evidence of blood, soft tissue, necrotic material, glomeruli, or tubular cells and were classified as unsatisfactory. The following diagnostic categories were noted in the 91 satisfactory aspirates: renal abscess (four cases), benign cyst (30 cases), suspicious lesions (11 cases), and malignant lesions (46 cases). In four cases of renal abscess, FNA found abundant clusters of neutrophils. For the 30 cases interpreted on cytologic evidence as benign cysts, the diagnosis was confirmed in 28 cases; the two remaining cases were acquired cystic kidney and cystic renal-cell carcinoma, respectively. Among the 11 suspicious lesions, the final diagnoses were one benign simple cyst, one angiomyolipoma, two multilocular cystic nephromas, two adult polycystic kidneys, one acquired cystic kidney, three cystic papillary renal-cell carcinomas, and one solid renal-cell carcinoma. Cases classified as suspicious shared characteristic cytologic patterns that distinguished them from simple benign cysts and from classic renal-cell carcinoma. Among the 46 malignant lesions, as evidenced on cytologic examination, 27 were renal-cell carcinomas, five were transitional-cell carcinomas, four were lymphomas, one was a small-cell undifferentiated carcinoma, and nine were metastatic carcinomas. False-positive or false-negative cases were not encountered in this category. In conclusion, FNA is an excellent method to diagnose space-occupying lesions of the kidney. For cystic lesions, cytologic-radiographic correlation is needed to avoid misinterpretation. Our study defines a spectrum of suspicious patterns characteristic of a group of renal lesions that are distinct from both benign simple cyst and straightforward renal malignancy.

p53 immunolocalization in cell block preparations of squamous lesions of the neck: an adjunct to fine-needle aspiration diagnosis of malignancy.

OBJECTIVE: Mutations of the p53 tumor suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic abnormalities in human cancers. The purpose of this study was to determine the utility of p53 immunostaining as an adjunct to the diagnosis of malignancy in fine-needle aspirations of squamous lesions of the neck. MATERIALS AND METHODS: Using a monoclonal antibody to the p53 protein and a standard avidin-biotin complex technique, immunostaining was performed on paraffin-embedded cell blocks of 20 cases with the following cytologic diagnoses: (1) metastatic squamous cell carcinoma (SCC) (7 cases); (2) atypical squamous cells, SCC cannot be excluded (7 cases); and (3) cytologic findings consistent with branchial cleft cyst (6 cases). Tissue or clinical follow-up was available in all cases. RESULTS: Five (71%) of 7 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for p53 protein. Tissue follow-up confirmed metastatic SCC in all of these 7 cases. Of the 7 cases with cytologic diagnosis of atypical squamous cells, 2 were negative and 5 (71%) were positive for p53 protein. Subsequent excisional biopsies in these cases revealed metastatic SCC (6 cases) and branchial cleft cyst (1 case). The squamous cells in all 5 cases with cytologic findings consistent with branchial cleft cyst were negative for p53 protein; tissue follow-up confirmed the diagnoses of branchial cleft cyst in 4 cases. In the remaining 2 cases excision was not performed, as the cystic lesion was completely decompressed and, clinically, no recurrences were identified at 14 and 8 months of follow-up. CONCLUSIONS: Our findings suggest that p53 immunostaining is helpful in differentiating benign and malignant squamous lesions. While negative staining for p53 does not exclude malignancy, positive immunostaining may aid in accurate fine-needle aspiration diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the neck.

Fine-needle aspiration of cystic lesions of the kidney. Morphologic spectrum and diagnostic problems in 41 cases.

Although imaging studies show the nature of most cystic lesions of the kidney (RCs), many RCs require fine-needle aspiration (FNA) for accurate diagnosis. Interpretation of the FNAs remains challenging. The FNA specimens of 41 RCs were reviewed and correlated with imaging studies. Final diagnoses for 30 cytologically benign lesions were simple cyst (28), acquired cystic kidney (1), and cystic renal carcinoma (1). The fluid from the benign cysts displayed macrophages, epithelial cells from the cyst lining, tubular cells, neutrophils, and Liesegang rings. Fluid from the acquired cystic kidney and the cystic renal cell carcinoma showed features similar to those of the benign cysts. The 9 cases with "suspicious" cytology included 5 complex cystic lesions displaying rare but atypical epithelial cell clusters, 3 low-grade renal cell carcinomas with many mildly atypical papillary clusters of epithelial cells, and 1 simple benign cyst with many tubular cells. The 2 cytologically malignant lesions were cystic renal cell carcinomas with abundant tumor cells with partially clear cytoplasm and atypical nuclei admixed with abundant macrophages and lymphocytes; 1 case developed in a kidney with acquired cystic disease. Simple cysts remain the most frequently aspirated RCs, but complex cystic lesions are increasingly recognized. Since many RCs are composed of independent loculi, a nonrepresentative sample is a potential problem, and cytologic-radiologic correlation becomes mandatory. The "suspicious" patterns identified in this study should serve as diagnostic guidelines and set the foundation for future validation.