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BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that usually behaves aggressively. After resection, serological surveillance for calcitonin and carcinoembryonic antigen (CEA) is used to prompt a radiographic search for metastatic disease. We report a case of a 65-year-old woman who presented with a large liver metastasis 37 years after she underwent thyroidectomy for organ-confined MTC. Her clinical course over that time showed a smoldering pattern in which she was symptom free until presentation even though her serum calcitonin and CEA concentrations were elevated for 17 years, and a small equivocal radiographic lesion in the liver was detected 10 years prior to presentation. Cytopathology from an ultrasound guided fine needle aspiration of the hepatic lesion was diagnostic for metastatic MTC. This case highlights the ability for smoldering residual MTC to suddenly transform to aggressive biological behavior after a long period of clinical remission. Diagn. Cytopathol. 2015;43:45–48. © 2014 Wiley Periodicals, Inc.

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.

Objective: To determine if focal ‘nuclear atypia’ or ‘microfollicular architecture’ portends a higher risk of malignancy than other subcategories of atypia of undetermined significance (AUS) in thyroid fine-needle aspirations (FNAs). Study Design: The frequencies of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories were calculated from 3,956 thyroid FNAs interpreted over a 26-month period at The Johns Hopkins Hospital after adoption of TBSRTC. TBSRTC criteria were applied strictly. The risk of malignancy, specifically for AUS subcategories, was analyzed by cyto-histo correlation. Results: Of the 133 cases diagnosed as AUS, 32% were found to have stageable carcinoma (not incidental microcarcinoma) on resection. When the subset of AUS with ‘nuclear atypia’ (AUS-N) was separated from other AUS cases, 48% (30/62) of them had stageable carcinoma on resection; of the AUS subset with ‘microfollicular architecture’ (AUS-F), 27% (8/30) were malignant on resection. The ‘suspicious for papillary thyroid carcinoma’ (SPTC) group maintained a higher risk of malignancy versus AUS-N (relative risk, RR 1.57; 95% CI 1.23–1.81). Conclusion: The subcategory of ‘nuclear atypia’ within AUS indicates a higher risk of malignancy than other subcategories of AUS but has a lower risk of malignancy than SPTC does. Thus, it is an important distinction with potential clinical implications.

BACKGROUND Pineal gland lesions are rare, with only a few cytologic descriptions occurring in the literature, according to the authors' knowledge. The current article describes the cytopathologic characteristics of 20 such lesions with discussion of differential diagnoses. METHODS Cytologic material was obtained either by fine-needle aspiration biopsy (FNAB) under stearotactic radiologic guidance or by touch imprinting (TI) at the time of frozen sectioning. The 20 specimens include pineoblastoma (five specimens), pineocytoma (four specimens), astrocytoma (three specimens), germ cell tumor (three specimens), meningioma (one specimen), epidermoid cyst (three specimens), and pineal cyst (one specimen). Smears were stained with Diff-Quik and with Papanicolaou and hematoxylin and eosin stains. In selected specimens, immunoperoxidase (IPOX) stains were performed on cell block sections using synaptophysin, neuron-specific enolase, placental alkaline phosphatase, glial fibrillary acidic protein, leukocyte common antigen, cytokeratins, and human chorionic gonadotropin antibodies. RESULTS Several cytomorphologic characteristics unique to each lesional category with occasional overlapping features were observed. The unique features included the following: small, hyperchromatic, round to oval cells with frequent rosetting (pineocytoma), with a few specimens in addition showing hypercellularity, crowding, mitoses, and necrosis (pineoblastoma); pleomorphic round cells in a fibrillary background (astrocytoma); large polygonal cells with prominent nucleoli and clear cytoplasm (germ cell tumor); spindled fibroblastic cells (meningioma); anucleate squames and mature squamous cells (epidermoid cyst); and small uniform polygonal cells (pineal cyst). When necessary, IPOX studies supported the morphologic diagnoses. CONCLUSIONS FNAB and TI cytology were found to provide a rapid and reliable diagnosis of pineal lesions. This is particularly important when dealing with minute amounts of tissue material. Both techniques appeared to provide equally good cytomorphology on smears. IPOX studies played an important complementary role in difficult cases when performed on cell blocks. Cancer (Cancer Cytopathol) 2005. © 2005 American Cancer Society.

We report the case of a suspicious parotid mass in which molecular determination of loss of heterozygosity (LOH) of chromosome arms 1p and 19q in combination with cytologic and immunohistochemical analysis defined the tumor to be metastatic oligodendroglioma. The patient was a 41-year-old woman who developed a World Health Organization grade II oligodendroglioma in her right frontal lobe at age 32, for which no adjuvant chemo- or radiotherapy was administered. Five years following this diagnosis, radiological assessment revealed a 10-centimeter mass in the tumor bed, suspicious for a recurrence. Resection of this lesion revealed an anaplastic oligodendroglioma (grade III) and adjuvant radiotherapy was given. Eleven months after this surgery the patient presented with a 5.5-cm subcutaneous, non-mobile, non-tender mass in the region of the right parotid gland. Fine needle aspiration (FNA) yielded highly cellular material, morphologically and immunohistochemically suspicious for oligodendroglioma. Molecular analysis of microsatellite loci residing on chromosome arms 1p and 19q was performed using DNA extracted from the patient's recurrent brain oliogdendroglioma and the FNA specimen. This analysis revealed evidence of LOH at all eight of the microsatellite loci tested. The combination of cytologic and molecular findings defined the extracranial tumor to be metastatic oligodendroglioma.

Although cancers metastatic to the thyroid are frequently mentioned in autopsy studies, such a finding is quite rare in routine clinical practice. Metastatic non-small-cell carcinomas to the thyroid may present a diagnostic dilemma, particularly when they share morphological similarities with primary thyroid tumors. Herein, we report a case of metastatic bronchioloalveolar carcinoma that presented as an isolated left thyroid nodule in a 68-year-old woman. The aspirates were cellular and showed numerous papillary-like tissue fragments, elongated nuclei with prominent nuclear grooves, frequent mitoses, and psammoma bodies. The latter features raised the possibility of papillary thyroid carcinoma. However, also seen were three-dimensional tumor nests and acinar-forming fragments. Immunostains (positive for cytokeratin-7 and carcinoembryonic antigen and negative for cytokeratin-20 and thyroglobulin) confirmed the metastatic nature of the carcinoma. In a patient with known primary neoplasm, the differential diagnosis of a thyroid nodule should always include a metastatic lesion along with primary neoplasia.

Objective To analyze the differential diagnosis when keratinized squamous cells are found in a brain aspirate. Study design Twenty cases of brain aspirates with keratinized squamous cells were retrieved (1982-2001). Diagnoses included craniopharyngioma (CP) (n = 11), metastatic squamous cell carcinoma (SCC) (n = 5), epidermoid cyst (EC) (n = 3) and Rathke cleft cyst (RCC) (n = 1). Aspirates were obtained under stereotactic radiologic (CT) guidance. Smears were stained with Diff-Quik or Papanicolaou stain, and cell block sections were stained with hematoxylin and eosin. Radiologic and histopathologic correlation with subsequent resection specimens was performed in selected cases. Results CP showed cellular smears with numerous keratinized squamous cells in a background of degenerated cellular and keratinaceous debris. Also noted were clusters of anucleate squamous cells, multinucleated giant cells, histiocytes, calcified debris and characteristic fragments of basaloid epithelial cells. Metastatic SCC showed single cells and tissue fragments of markedly atypical and focally keratinized cells with enlarged, hyperchromatic nuclei; prominent pleomorphism in a background of necrotic cellular debris and acute inflammatory exudate. EC showed numerous isolated keratinized squamous cells often with prominent keratohyaline granules and occasional parakeratotic cells in a relatively clean background. RCC showed single cells and aggregates of benign-appearing squamous cells admixed with numerous anucleate squames and hemosiderin-laden macrophages. Glandular-type epithelium was present only rarely. Conclusion Squamous cell-containing lesions in the brain present a spectrum of pathologic entities. Although they all display the common morphologic denominator of keratinizing squamous cells, subtle cytomorphologic differences exist in these lesions, permitting an accurate cytopathologic diagnosis. Clinicardiologic features and anatomic location of the tumor in the brain are additionally helpful.

Stereotactic brain fine-needle aspiration (FNA) is a valuable diagnostic modality for evaluating space-occupying central nervous system disorders. Colloid cyst (CC) is a rare nonneoplastic lesion thought to arise from misplaced endodermal tissue in the anterosuperior portion of the third ventricle. This study summarizes cytomorphologic features of CC on FNA along with clinical, radiologic, and histopathologic correlation. Ten cases of CC of the third ventricle diagnosed on FNA were retrospectively reviewed for a period of 12 yr (1989–2000). Material was obtained under stereotactic radiologic guidance. Smears were stained with Diff-Quik and Papanicolaou stains and cell block sections with hematoxylin and eosin. The aspirates showed a characteristic sticky and viscous quality on gross examination. Smears showed abundant, amorphous, proteinaceous material with staining qualities similar to colloid aspirated from thyroid. This included a purplish, filmlike coating of the slide with occasional “cracking” artifact; thick, globular, eosinophilic fragments; and granular, ropelike, and somewhat viscous, mucinous material. Pathognomonic radiating hyphae-like structures were not seen. The cellular components varied from isolated cuboidal/columnar cells to large tissue fragments of glandular-type epithelium with focal ciliated border. Goblet cells were frequently identifiable, as were fragments of collagenous cyst wall. Stereotactic FNA of the CC of the third ventricle is an accurate and cost-effective diagnostic modality. Cytomorphology coupled with the radiologic features is sufficiently unique for the diagnosis of this rare pathologic entity. Diagn. Cytopathol. 2002;27:27–31. © 2002 Wiley-Liss, Inc.

OBJECTIVE To investigate the role of reverse transcriptase polymerase chain reaction (RT-PCR) in determining telomerase catalytic subunit (hTERT) mRNA to assist with the diagnosis of colonic adenocarcinoma (CCA) in colonic brush cytology specimens. STUDY DESIGN Twenty-seven colonic brushes of CCA were obtained. Initial cytologic diagnoses included CCA, suspicious for CCA (SFC), atypical (ATY) and unsatisfactory. The cytologic specimens were reviewed. A homogeneous RT-PCR assay for hTERT mRNA was performed on 27 colonic brushes of CCA and 24 controls (10 negative brushes, 6 resected CCA and 8 benign colonic mucosa from resected specimens). A RT-PCR assay for beta 2-microglobulin was used as an internal control for mRNA quality. RESULTS On review, the initial cytopathologic diagnosis of CCA was confirmed in all 7 cases. In addition, 7 of 19 initially interpreted as SFC and ATY seemed to demonstrate unequivocal cytomorphologic features of malignancy. Telomerase mRNA was more often expressed in CCA than in negative controls in both brush (30%) and resected specimens (57%) (P < .05). Seven cases with hTERT mRNA expression were initially diagnosed as CCA (three), SFC (three) and ATY (one). CONCLUSION CCA may be underdiagnosed in brush cytopathology. The expression of hTERT mRNA may be determined by RT-PCR in brush specimens and may eventually prove to be a useful diagnostic adjunct in the interpretation of inconclusive cases of CCA. Sparse cellularity in brush specimens may result in a relatively low rate of hTERT detection in colonic brushes of CCA; inflammatory changes may contribute to a higher-than-expected rate of hTERT expression in benign colonic epithelium.

Introduction Cytologic screening for urothelial carcinoma is fraught with low sensitivity, a high indeterminate rate, and until recently, poor standardization of terminology. The Johns Hopkins Hospital John K. Frost Cytopathology Laboratory has recently developed and published a template for reporting urine cytopathology; herein, we evaluate its interobserver reproducibility. Materials and methods Two sets of 100 cases each were deidentified; each set was reviewed by 5 of 10 observers in a randomized order at the direction of computerized data collection software that tracked observation time as well as observer classification of the atypia-no atypia, atypia (AUC-US), or atypia suggestive of high-grade urothelial carcinoma (AUC-H). Specific morphologic features were also recorded. Cases were grouped into low-, intermediate-, and high-agreement based on the number of observers who made the assessment. The findings were correlated against clinical outcomes. Results High agreement among observers about the presence or absence of high-grade features was possible in approximately two-thirds of indeterminate urine cases. Time and order did not factor significantly into observer propensity for identifying atypical features or favoring either AUC-US or AUC-H, and cases with high agreement about the presence of high-grade features were more likely to have a malignant follow-up. Furthermore, AUC-H diagnoses based on 2 or more high-grade features had a significantly higher malignancy risk than AUC-US diagnoses did. Conclusions AUC-H is a valid diagnostic category with specific, reproducibly identified features that portend a higher risk of malignancy than the findings of AUC-US.

This chapter presents cytopathologic features of bronchial asthma, sarcoidosis, pulmonary alveolar proteinosis, lipid pneumonia, amyloidosis, and pulmonary infarct. Brief descriptions of the disease and differential diagnosis from other entities with similar morphology are also given.

This chapter has been updated according to the newly proposed classification of lung carcinomas and its application to small biopsies and cytology specimens which provides uniform terminology and criteria for diagnosing subtypes of lung carcinomas, specifically adenocarcinomas and poorly differentiated carcinomas.

Reactive and hyperplastic changes in cytologic specimens, specifically in bronchoscopic and FNA samples, are frequent causes of problems in differential diagnosis. Changes involving bronchial and alveolar epithelium are presented along with differential diagnosis from neoplastic conditions.

Cervical thymic masses are congenital lesions that result from aberrant thymic migration during embryogenesis. Although most of these masses are asymptomatic, they may cause debilitating symptoms secondary to encroachment on adjacent aerodigestive structures. Preoperative diagnosis of ectopic thymic tissue is rare; most cases are clinically misinterpreted as branchial cleft remnants or cystic hygromas. Definitive diagnosis has relied on histopathologic examination in nearly all reported cases. However, the invasiveness of open incisional or excisional biopsy carries the risk of surgical and anesthetic complications. Inadvertent surgical thymectomy may result in cell-mediated immune deficiencies in infants and young children. The utility of fine needle aspiration is gaining wider acceptance in the diagnostic evaluation of neck masses. We describe an infant with an asymptomatic cervical thymic mass diagnosed by fine needle aspiration.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Fine needle aspiration (FNA) is one option for diagnosing GISTs before surgery. This study was designed to evaluate the clinical utility of FNA in the diagnosis of GISTs. STUDY DESIGN: FNAs from 19 GISTs originating in the stomach, small bowel and colon obtained from 1988 to 1998 were studied. Immunocytochemistry was performed on 12 cases. The GISTs were classified as benign, borderline and malignant, according to location, size, mitotic activity and clinical outcome. RESULTS: Benign (three) and borderline (five) GISTs were all spindle cell type; malignant GISTs included five spindle cell type and six epithelioid type. Most smears contained abundant cellular material. Benign and borderline GISTs of spindle cell type tended to have cells arranged in tightly cohesive clusters, while malignant GISTs were more likely to exhibit loosely cohesive groups with many single cells, occasional nuclear pleomorphism, hyperchromasia and irregular nuclear contours. Epithelioid-type GISTs mimicked adenocarcinoma. Mitoses were seldom observed in either type. CD117 (KIT protein product) was demonstrated by immunocytochemistry in 9 cases, CD34 in 11, desmin in 3, S-100 protein in 2 and smooth muscle actin in 6 cases CONCLUSION: FNA can be used to diagnose GISTs as spindle cell and epithelioid types, but cytomorphology alone cannot be used to assess malignant potential. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Care must be taken to differentiate epithelioid-type GISTs from adenocarcinoma.

Objective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case–control study nested in an occupational cohort of tin miners.

OBJECTIVE: To determine if sequencing the KIT gene could facilitate more definitive FNA diagnosis. STUDY DESIGN: Sixteen cases of gastrointestinal stromal/smooth muscle tumor (GIST) in which fine needle aspiration (FNA) was performed (mean age, 67; M/F = 12/4) were studied. DNA was extracted from cytologic preparations from all patients (15 cell blocks, 1 alcohol-fixed smear) and seven subsequent resection specimens. DNA was amplified by polymerase chain reaction, using primers designed to amplify a segment of the KIT gene exon 11 and sequenced on an ABI Prism 377 DNA sequence analyzer (Applied Biosystems, Indianapolis, Indiana, U.S.A.). Immunocytochemical staining for CD 117 (the KIT gene product) was performed on sections from 12 cell blocks and 7 surgical resections. RESULTS: In-frame deletion of exon 11 was detected in eight cases (7 monoalleic, 1 bialleic); a point mutation was found in one case. Mutation was found only in histologically malignant (6 of 10 cases) and borderline GISTs (3 of 4 cases). No mutation was identified in benign tumors. In three cases, scant cellularity or blood precluded sequencing. CD 117 was expressed in 12 of 15 cases. CONCLUSION: Immunocytochemical staining for CD 117 is useful in confirming a cytologic diagnosis of GIST but does not facilitate diagnosis of malignancy. FNA biopsy specimens are suitable for KIT gene sequencing; detection of a KIT mutation favors a malignant diagnosis, though absence of mutation does not preclude malignancy.

Objective Cytopathologic descriptions of thymoma are limited. This study was undertaken to elaborate on the cytomorphologic features along with clinicoradiologic findings of this entity, with special emphasis on the differential diagnosis. Study design Twenty cases of thymoma were retrospectively studied. Material was obtained by fine needle aspiration (FNA). Smears were stained with Diff-Quik and Papanicolaou stain, and cell block sections were stained with hematoxylin and eosin. Immunocytochemical (ICC) studies were done in selected cases using cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, placental alkaline phosphatase, neuron-specific enolase, chromogranin and lymphocytic markers (CD3 and UCHL-1). Results Fourteen thymomas were from the anterior mediastinum; the remaining 6 were invasive or metastatic to the lung (2), pleura (2), liver (1) and abdominal wall (1). The key diagnostic feature was a biphasic population of epithelial cells and lymphocytes in varying proportions. Medullary thymomas showed cohesive, spindled epithelial cells, whereas cortical subtypes displayed more epithelioid epithelial cells singly and in discohesive clusters. All cases of invasive or metastatic thymoma were of the cortical subtype. ICC studies were positive for cytokeratins and epithelial membrane antigen. Conclusion FNA, coupled with clinicoradiologic information and appropriate immunocytochemical studies, is highly accurate in the diagnosis of primary and metastatic thymomas.

The accuracy of using a combination of cytopathologic and histopathologic techniques to diagnose stereotactically guided brain biopsies was investigated in 74 patients. Diagnostic accuracy was assessed by determining whether classification of the biopsies as gliosis, astrocytoma (A), anaplastic astrocytoma (AA), or glioblastoma multiforme (GBM) predicted survival. The utility of on-site evaluation using Diff-Quik-stained crush preparations was also assessed. The patients ranged in age from 5 to 88 years (mean, 55 years) and were followed for over 2 years in most cases. Four cases (5%) were classified as gliosis (G), 7 (9%) as atypical gliosis (AG), 4 (5%) as high-grade mixed oligodendroglioma/ astrocytoma (OA), 11 (15%) as astrocytoma (A), 21 (28%) as anaplastic astrocytoma (AA), and 27 (36%) as glioblastoma multiforme (GBM). Median survival was 11 months in patient with OA, 57 months in patients with A, 10 months in patients with AA, and 5 months in patients with GBM. Diagnosis of Diff-Quik-stained crush preparations made during the biopsy procedure was highly correlated with the final diagnosis and survival. We conclude that the diagnosis of stereotactic brain biopsies using cytopathology with on-site evaluation in combination with histopathological evaluation of needle cores is accurate based on a survival analysis. However, A and G may be difficult to distinguish.

PURPOSE: To examine risk factors and establish a biologic specimen and data bank for the study of early markers of lung cancer. METHODS: We designed a dynamic cohort using an ongoing lung cancer screening program among radon- and arsenic-exposed tin miners in Yunnan China. Through the first four years of the study, 8,346 miners aged 40 years and older with over 10 years of occupational exposure have been enrolled, risk factors have been assessed, annual sputum and chest radiographs have been obtained, and numerous biologic specimens have been collected. RESULTS: A total of 243 new lung cancer cases have been identified through 1995. Radon and arsenic exposures are the predominant risk factors, but lung cancer risk is also associated with chronic bronchitis and silicosis, as well as a number of measures of exposure to tobacco smoke, including early age of first use, duration, and cumulative exposure. Tumor and sputum samples are being examined for early markers of lung cancer. CONCLUSION: A cohort of occupationally-exposed tin miners with an extensive biologic specimen repository has been successfully established to simultaneously study the etiology and early detection of lung cancer.

Background Malacoplakia is an uncommon, peculiar inflammatory disease with few cytologic descriptions. It is seen mostly in the lower urinary tract, with rare occurrences in the lungs. Escherichia coli is the most common underlying etiologic agent, with only a few cases reported with Rhodococcus equi infection. Case A 36-year-old female with AIDS presented with dysphagia, dry cough and fever. Physical examination revealed diffuse bronchi and wheezing. Chest roentgenography showed multiple cavitary lesions bilaterally in the lungs. Fine needle aspiration (FNA) of one of these lesions revealed clusters of granular histiocytes with numerous intracytoplasmic and extracytoplasmic Michaelis-Gutman bodies. Also noted were numerous coccobacillary bacteria, which, on culture, were identified as R equi. Ultrastructural findings are also presented. Conclusion The case illustrates the cytologic findings of malacoplakia in a rare pulmonary lesion associated with R equi infection in an AIDS patient. It reiterates the diagnostic role of FNA in dealing with a nonneoplastic entity for timely and definitive treatment and follow-up.

Pulmonary sequestration is defined as a congenital malformation of abnormal lung tissue that does not communicate with the airway system and that receives blood supply from anomalous arteries. The majority of these sequestrations are encountered in the pediatric population. Surgical excision is the treatment of choice, with excellent prognosis. We studied a case of an extralobar pulmonary sequestration in a young adult, presenting as an intrathoracic mass; it was aspirated twice, final diagnosis being rendered after surgical resection. The cytologic findings and the accompanying diagnostic difficulties to our knowledge have never been reported.

Objectives: The tall cell variant of papillary thyroid carcinoma (TCV-PTC) is an aggressive variant of PTC requiring accurate cytopathologic diagnosis for early aggressive management. Study Design: Twenty-five cases of TCV-PTC in which the tall cells comprised at least 30% of surgically resected tumor were included in the study. The direct smears from a preoperative fine needle aspiration (FNA) and available hematoxylin and eosin cell block sections were reviewed. Ten cases of TCV-PTC were randomly selected and blinded with an equal number of conventional PTC cases. Representative slides were independently reviewed by 7 cytologists. Results: In a majority of the cases, the FNA direct smears were hypercellular and displayed flat monolayer sheets of cells. Tall columnar cells with cytoplasmic tails were seen in 56% of cases. The presence of large polygonal follicular cells with abundant granular oncocytic cytoplasm and distinct cell borders was the most common feature seen in all cases. Seventeen (68%) cases displayed intranuclear pseudoinclusions in cells with abundant granular cytoplasm. A correct diagnosis of TCV-PTC was made in 30-40% of cases by 7 study participants. Conclusions: The correct recognition of TCV-PTC features in preoperative FNA is important for clinical management, and reporting these features in a cytopathology report is suggested.

Background Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. Purpose We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. Methods A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. Results No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). Conclusions Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. Implications While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Microsatellite DNA markers have been widely used as a tool for the detection of loss of heterozygosity and genomic instability in primary tumors. In a blinded study, urine samples from 25 patients with suspicious bladder lesions that had been identified cystoscopically were analyzed by this molecular method and by conventional cytology. Microsatellite changes matching those in the tumor were detected in the urine sediment of 19 of the 20 patients (95 percent) who were diagnosed with bladder cancer, whereas urine cytology detected cancer cells in 9 of 18 (50 percent) of the samples. These results suggest that microsatellite analysis, which in principle can be performed at about one-third the cost of cytology, may be a useful addition to current screening methods for detecting bladder cancer.

BACKGROUND: Cysticercosis is the most common parasitic infection of the central nervous system in the United States. CASE: A case of cerebral cysticercosis radiographically and pathologically mimicked a high grade glioma. A symptomatic solitary cerebral hemispheric lesion in a child, unknown at the time to have been born in Korea and adopted by U.S. residents, was initially evaluated by stereotactically guided needle biopsy and diagnosed as having malignant glioma in accord with the radiographic impression. The subsequently excised mass revealed cysticercus with an exuberant granulomatous inflammation and gliosis surrounding a fibrous-walled cyst. CONCLUSION: In the setting of a solitary parenchymal cyst, the radiographic differential diagnosis of neurocysticercosis often includes a primary neoplasm. However, to our knowledge, this is the first report of cysticercosis's also simulating a brain neoplasm pathologically.

Objectives: Endorectal endoscopic ultrasound (ERUS) allows highly detailed assessment of the rectal wall layers and visualization of the extraluminal structures. Herein, we study the utility of ERUS fine-needle aspiration (FNA) to evaluate perirectal lesions. Study Design: Forty-nine ERUS-FNAs were retrieved from the cytopathology archives of The Johns Hopkins Hospital. The cytology slides, corresponding histology, immunohistochemistry when available, and clinical data were reviewed. Results: The aspirated material showed malignant (n = 24), benign (n = 19), atypical (n = 3), carcinoid tumor (n = 1), and nondiagnostic conditions (n = 2). The past medical history of 36 cases was significant for carcinomas. The primary site of the tumors included colorectal, urinary bladder, prostate, pancreas, gallbladder, ovary, and female lower genital tract. Statistical analysis for endoscopic ultrasonography FNA showed 87% sensitivity, 100% specificity, diagnostic accuracy of 90%, and a positive predictive value of 100% and a negative predictive value of 77%. Conclusion: ERUS-FNA can be utilized for: (1) accurate staging of colorectal adenocarcinomas by evaluation of nodal metastasis, depth of transmural tumor invasion and local tumor spread to perirectal fat, (2) prevention of aggressive surgical intervention in benign conditions, (3) providing diagnostic material for ancillary studies, and (4) evaluation of perirectal lesions with a more accurate method by combining imaging and histology.

Study objective : To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. Design Setting/Participants : Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non-small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen). Interventions : Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up. Measurements and results : Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date. Conclusions : Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue.

Mullerianosis of the urinary bladder is a rare entity characterized by the presence of an admixture of at least two types of mullerian tissue in the muscularis propria of the bladder. We report a case of mullerianosis of the urinary bladder in a 28-year-old nulliparous woman with no history of pelvic surgery or endometriosis, and the diagnosis of mullerianosis was suggested initially in urine cytopathology report. In this study, previously reported cases of mullerianosis of urinary bladder are reviewed, and differential diagnosis of endometrial-like cells in the urine has been discussed. Fewer than 20 cases of mullerianosis of the urinary bladder have been reported in the literature, and only one of these cases had cytological description in a urine specimen. Most of patients were of reproductive age ranging from 28 to 53 years and had no previous history of pelvic surgery or Cesarean section. The clinical presentations frequently were abdominal/pelvic pain and dysuria/hematuria, which may or may not be associated with menstruation. Radiologic study revealed polypoid, mass-like lesion ranging from 1 to 4.5 cm in size, predominantly involving the dome or posterior wall of the bladder. Histological sections showed two or more of the three related benign mullerian glandular epithelial proliferations—endometriosis, endosalpingiosis, and endocervicosis. Most of the patients have good prognosis with medical management. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.

The Fuhrman grading system of renal cell carcinoma (RCC) consists of four grades based on nuclear size/contour and nucleolar conspicuousness. Fuhrman grading of histpathologic material is an independent prognostic parameter for RCC. Although widely used in surgical pathology, Fuhrman grading is not routinely performed on cytologic material. Thirty-three cases of renal fine needle aspirations (FNAs) with histologically proven RCC were retrieved from the cytopathology archives at Johns Hopkins Hospital. Fuhrman grade was determined independently and blindly by three faculty cytopathologists and compared with the Fuhrman grade of the subsequent surgical pathology specimen. The 33 resection specimens had the following Fuhrman grades: 0/33, grade I; 24/33 (73%), grade II; 9/33 (27%), grade III; and 0/33, grade IV. After Fuhrman grading was applied to the FNA material, diagnostic sensitivity was 83% for grade II versus 44% for grade III. The specificity and accuracy were 50 and 75%, respectively, for grade II versus 100% and 84% for grade III. Diagnostic sensitivity for grade II tumors ranged from 38 to 83%, grade III 44-62%. Diagnostic specificity for grade II tumors ranged from 50 to 78%, grade III 80-100%. Accuracy ranged from 48 to 75% for grade II and 75-87% for grade III. Using a two-tier grading model, accuracy improved to 84.2%. In our experience, Fuhrman grading of FNA specimens yielded variable results. There was only moderate agreement between cytopathologists, with an overall tendency to undergrade the tumor when compared with the resection specimen. Averaging the participants' grading and using a two-tier instead of four-tier system improved overall performance.

Four fine-needle aspiration biopsy needles with different tip configurations were used in 133 patients with abdominal lesions. The 20-gauge needles were used in random sequence by several physicians. The specimen from each of the 522 needle passes was evaluated by two cytopathologists for adequacy to render a diagnosis and for the presence of cell block material. The Franseen needle produced a 16% and 9% better yield for diagnostic material than did the cut biopsy and spinal needles (P less than .05), respectively. The Westcott needle was better than the cut biopsy needle by 13%, and the spinal needle produced an 11% better yield than did the cut biopsy needle. Differences did not exist in liver biopsies but were present in pancreatic biopsies. The spinal needle was the least successful in yielding cell block material. Use of the cut biopsy needle resulted in the largest proportion of inadequate specimens, except its yield in cell blocks in the liver was 25% higher than that of the Westcott needle. The authors conclude that not all unusual designs for 20-gauge needle tips render results superior to those of the simple spinal needle.

Eighty consecutive gynecologic specimens obtained with the Cavitron Ultrasonic Surgical Aspirator (CUSA) were evaluated pathologically. Fifty specimens were obtained during intraabdominal tumor debulking and thirty resulted from ablation of lower genital tract lesions. In 98% of intraabdominal specimens and in 93% of patients with a history of lower genital tract lesions, the CUSA material permitted an accurate diagnosis. Although artifacts related to cellular thermal injury were ubiquitous, nearly all cases were interpretable with a combination of cytologic (smear, Cytospin, Millipore filter) and histologic (cell block) preparations. Squamous intraepithelial lesions (SILs) of the lower genital tract were better preserved in cell block preparations, whereas intraabdominal adenocarcinomas were readily diagnosed by both cytologic and histologic techniques. Accurate grading of SILs and exclusion of invasion were difficult in some cell blocks due to the fragmented and superficial nature of the samples. Cytologic preparations of lower genital tract lesions often consisted of thick uninterpretable fragments and degenerated single cells that contributed little to the evaluation of SILs. We conclude that examination of CUSA specimens confirmed the surgical removal of pathologic tissue in 96% of cases, but an exact diagnosis of SILs was not possible in all cases.

BACKGROUND: The objective of this study was to assess the frequency of premalignant and malignant cells in sputum from patients with lung cancer and to measure the dependence of these cells on cancer stage, histologic type, tumor size, and tumor location. METHODS: This analysis included 444 patients with lung cancer. First, all patients were asked to produce sputum spontaneously; then, they underwent sputum induction. Slide preparations of the sputa were screened for the presence of abnormal cells. RESULTS: Of all patients with lung cancer who had produced adequate specimens, 74.6% had sputum that was positive for premalignant or worse cells, whereas 48.7% had sputum that was positive for malignant cells alone. Surprisingly, the presence of premalignant or worse cells in sputum depended only moderately on disease stage (82.9% of stage IV cancers vs 65.9% of stage I cancers), tumor size (78.6% of tumors >2 cm vs 64.7% of tumors ≤2 cm), and location (83.3% of central lesions vs 68% of peripheral lesions) and was found to be independent of histologic tumor type (78.4% of squamous cell carcinomas vs 71.5% of adenocarcinomas, 74.5% of small cell carcinomas, and 75% of large cell carcinomas). CONCLUSIONS: The findings of the current study suggested the important potential of sputum cytology for lung cancer detection and risk assessment across all stages, histologic types, tumor sizes, and locations. However, the high sensitivities in this study were achieved with a level of scrutiny not feasible in the laboratory routine. The diagnostic potential of sputum cytology may be exploited better through the standardization and automation of sputum preparation and analysis. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

This chapter is devoted mostly to lymphomas, presenting their cytopathologic features as well as ancillary techniques to determine their specific type and differential diagnosis from other neoplasms.

Pars plana vitrectomy has been used in cases of ocular toxocariasis to remove vitreous opacities due to chronic inflammation and to relieve vitreoretinal traction causing macular distortion and retinal detachment. To date, the diagnosis of intraocular Toxocara infection in vitrectomy cases has been presumptive, based on characteristic clinical findings, the presence of eosinophils, and corroborative immunodiagnostic tests. The authors report a case in which a vitrectomy for vitreopapillary traction recovered an intact Toxocara canis organism.

Fine-needle aspiration of the prostate has failed to gain widespread acceptance among pathologists more familiar with histologic sections. The authors aspirated 27 freshly excised radical prostatectomy specimens with needles of varying caliber and type and found a 22-gauge Turner needle (Cook Incorporated, Bloomington, IN) which obtained large tissue fragments suitable for cell block preparation as well as high quality cytologic specimens. Thirty men with prostate nodules each had 14-gauge transperineal core biopsy and fine-needle aspiration. In 20 cases, cytologic smears and cell blocks and core biopsies agreed on a diagnosis: 12 benign and eight carcinoma. Of seven cases that were atypical by cytologic smears, five were benign on cell block and core; one was benign on cell block and carcinoma on core; and one was carcinoma on cell block and core. Three cases with scant specimens and diagnoses of carcinoma by cytologic smears were benign on cell blocks and cores: one contained seminal vesicle on review; one had repeat benign biopsies; and one had three microscopic foci of low-grade carcinoma in his radical prostatectomy specimen. This fine-needle aspiration technique provides histologic sections which are especially useful to those gaining experience with cytologic specimens of the prostate. Cases with discordant diagnoses on cell block and cytologic preparations warrant further evaluation.

Tumoral calcium pyrophosphate dihydrate deposition disease (CPPD) is a rare non-neoplastic entity which mimics primary or metastatic soft-tissue or skeletal malignancy. Fewer than a dozen cases have been reported in the literature with only histologic descriptions. We present cytologic findings of a unique case of CPPD in a 73-year-old black female with a history of end-stage renal disease. A fine-needle aspiration (FNA) was done on a 4 x 4-cm neck mass which was clinically thought to be malignant. Cytopathologic examination showed numerous macrophages with markedly distended cytoplasm and containing multiple yellowish-orange, short rhomboid crystals. These were strongly birefringent on polarized microscopy, consistent with CPPD crystals.

BACKGROUND Hepatocellular carcinoma (HCC) is routinely graded histopathologically using a modified Edmondson system (ES). The cytologic grading of HCC has been used predominantly as an adjunct in differential diagnoses (i.e., to help distinguish HCC from other tumors as well as nonneoplastic lesions). However, there are unanswered questions regarding the reliability of the cytologic grading of HCC and its correlation with histologic follow-up. METHODS A total of 106 cases of HCC were identified in the authors' cytopathology files from 1977 to the present. Of these cases, 64 had either a core needle or excisional biopsy sample that was judged to be adequate for histologic grading. From each case smears were graded independently in a blinded fashion by two cytopathologists, and tissue slides were graded by a liver pathologist. The cytopathologists' grading was then adjudicated by considering the histologic diagnosis as the “truth standard”. Finally, after the scores were calculated, a statistical analysis was performed to ascertain the accuracy of the cytopathologic grading. RESULTS The sensitivity for accurate grading was found to be highest for well differentiated (WD) lesions; the specificity was found to be highest for poorly differentiated (PD) HCC for both cytopathologists. Interobserver agreement was highest for WD HCC. WD HCC displayed cohesive fragments, often associated with characteristic vascular/endothelial patterns. In addition, moderately differentiated (MD) HCC demonstrated numerous single cells and atypical naked nuclei, usually with prominent nucleoli. PD HCC displayed loose nests and three-dimensional fragments (often gland-like), pleomorphism, macronucleoli, and focal necrosis. CONCLUSIONS In the authors' experience, the three-tier cytologic grading of HCC was found to be only moderately accurate. The accuracy of cytologic grading was reported to be high for WD/PD HCC and low for MD HCC. The architectural criteria appear to be more useful for WD HCC, whereas marked cellular pleomorphism is specific for PD HCC. The authors propose that a two-tier grading system may be more useful, given the recent studies of HCC recurrence. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

Cancer of the uterine cervix, the sixth most common cancer among women, is still considered a significant health problem, despite declining mortality rates during recent decades. In Baltimore, the age-adjusted mortality rates for cervical cancer are significantly higher than the U.S. average, for both black and white women. Early detection of cervical cancer through screening with the Papanicolaou (Pap) test has been shown to decrease mortality by preventing development of invasive disease, and intervention programs have been developed to increase use of Pap testing. However, the evaluation of those programs is difficult, as self-reports of Pap screening may be inaccurate, and repeated inquiries about Pap tests may influence the behavior being studied. We report in this article a method to use data from cytopathology laboratories to estimate the use of Pap screening by women in a defined population. This approach can be used to evaluate changes in receipt of Pap smears and to provide feedback to intervention programs. [Am J Prev Med 1994;10:235–7]

Approximately 52,300 new cases of carcinoma of the bladder were diagnosed in the United States in 19931. These carcinomas struck primarily older men, who often presented with hematuria or increased frequency of urination. Patients whose cancers are detected in an early, localized stage have a 90 percent chance of surviving at least five years. If the cancer is detected after distant spread of the disease, however, the five-year survival rate drops to 9 percent1. Clearly, techniques for the early detection of carcinoma of the bladder can have a major impact on the outcome of the disease2. Cytologic . . .

To examine the association between pre-diagnostic serum carotenoid levels and lung cancer risk and the effects of alcohol intake on the carotenoid-lung cancer relationship, we conducted a case-control study in an occupational cohort from the Yunnan Tin Corporation in China. During 6 years of follow-up, 339 cases of confirmed lung cancer were diagnosed. Among these cases, those who donated pre-diagnostic blood (n = 108) were eligible for this study. For each case, two individuals alive and free of cancer at the time of case diagnosis, matched on age, sex, and date of blood collection, were selected as controls. Serum beta-carotene (odds ratios (ORs) for tertiles: 1, 1.3, 2.0) and beta-cryptoxanthin (ORs for tertiles: 1, 1.8, 2.9) levels were positively associated with lung cancer risk after adjustment for tobacco use and radon exposure. Among alcohol drinkers, higher serum carotenoid levels were significantly associated with increased lung cancer risk (alpha-carotene OR 2.2, 95% confidence interval (CI) 1.1-4.4, beta-carotene OR 7.6, 95% CI 3.1-18.6, lutein/zeaxanthin OR 2.3, 95% CI 1.2-6.6 and beta-cryptoxanthin OR 7.6, 95% CI 2.7-21.5). Conversely, risk estimates among non-drinkers suggest a possible protective association for higher carotenoid levels.

Monoclonal antibody 703D4 recognizes a 31 kD lung cancer associated antigen (p31) expressed both in resected lung tumor and in sputum cells shed from the bronchial epithelium in advance of clinical cancer [1, 2]. Originally developed by mouse immunization using a whole non-small cell lung cancer (NSCLC) tumor-cell extract, 703D4 recognizes a protein expressed by most NSCLC as well as small cell lung cancer (SCLC) cell lines [1,3]. Recently, the 703D4 antigen has been purified by a seven-step chromatographic procedure, guided by Western blotting [4]. Sequencing of the principal immunostaining protein identified a heterogeneous nuclear ribonucleoprotein-A2 (hnRNP-A2). A splice variant, hnRNP-B1, was identified as a minor copurifying immunoreactive protein. Table 1 presents a summary of the advances in understanding of p31 expression in pulmonary tissues.

The authors evaluate the role of immediate cytologic evaluation (ICE) with fine-needle aspiration biopsy (FNAB) for lung lesions at highest risk for pneumothorax.A prospective randomized study was conducted of 80 patients with lung lesions surrounded by aerated parenchyma undergoing FNAB with and without ICE (47 and 33 patients, respectively). An analysis of needle passes, procedure time, complications, specimen adequacy, diagnostic yield, and accuracy of procedure was made.There was an increased number of needle passes with ICE (or = three passes: 23% [11 biopsies] versus 3% [1 biopsy]; P = 0.01). Fluoroscopic procedures took longer with ICE (median time: 15 versus 9 minutes; P = 0.002) with no difference in complication rates. Specimen adequacy was similar (74% and 64%) and the procedure was diagnostic in 79% (37 biopsies) with ICE and in 70% (33 biopsies) without ICE. There were no significant differences in the sensitivity, specificity, or accuracy of the biopsy.Immediate cytologic evaluation improved results marginally with increased procedure time and needle passes. Immediate cytologic evaluation may be most useful for lesions at lowest risk of complications to assure that a second procedure is not required.

The utility of on-site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on-site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on-site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi-squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation. It is concluded that immediate on-site cytopathological procurement and evaluation of fine needle aspirates of head and neck masses is a valuable practice which assures a higher yield of adequate specimens compared to biopsies taken without immediate evaluation. The technique of immediate on-site evaluation of FNAs is discussed and a cost-benefit analysis of immediate on-site evaluation of FNAs is presented.