Thirty-two consecutive patients with mediastinal lesions suggestive of bronchogenic carcinoma underwent transbronchial needle aspiration. Eighteen of 20 patients (90 percent) with proved bronchogenic carcinoma had malignant cytology specimens or tissue fragments. Of 12 patients with normal cytology specimens, six were subsequently proved to have nonneoplastic disease. Transbronchial needle aspiration appears to offer a sensitive and specific alternative to more invasive surgical techniques used in the diagnosis of malignancies with mediastinal involvement.

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.

Solid and papillary epithelial neoplasm of the pancreas (SPENP) is a rare entity, comprising (cid:1) 1% of all pancreatic neoplasms. SPENP was originally described by Franz in 1959. Other synonyms for SPENP include papillary and cystic neoplasm and solid-pseudopapillary tumor of the pancreas. SPENP tends to occur in younger females of non-Caucasian origin. They are typically present in the tail of the pancreas but can occur anywhere in the gland. The tumor is often large (up to 10 cm) at the time of initial diagnosis. The gross appearance is variable with tumors being solid, cystic, or mixed cystic and solid. SPENP often have large areas of necrosis and hemorrhage. Patients typically present with nonspecific abdominal pain and may often be asymptomatic. A 43-yr-old woman presented to her primary physician with nonspecific abdominal pain. An abdominal magnetic resonance imaging (MRI) scan revealed a 4 (cid:2) 3 cm mass in the tail of the pancreas. The mass appeared mostly cystic or necrotic with a small amount of nodular enhancement along the inferior component. There were no other pancreatic lesions and the pancreatic duct was normal. A computerized tomography (CT)-guided FNA was performed. The cytopathologic examination revealed cellular smears with single cells and solid sheet-like fragments of neoplastic epithelium. The most characteristic finding at low magnification was fine and delicate,

Inflammatory pseudotumor (IPT) is a rare space‐occupying lesion of unknown etiology that can mimic malignancy on clinicoradiological and pathological examination. A review of the cytopathology archives at The Johns Hopkins Hospital identified 12 cases from eight patients with histologically proven IPT (lung, seven patients; liver, five patients). There were six men and two women with an age range of 28–84 yr (mean age, 59 yr). Presenting complaints of IPT of the lung included shortness of breath and hemoptysis, and in cases of IPT of the liver complaints included abdominal pain and elevated liver function tests (LFTs). All cases were found to have mass lesions suspicious for a neoplasm on radiographic examination. Cytological specimens consisted of fine‐needle aspiration (FNA; seven specimens) and bronchial brush/wash (five specimens). Diagnostic accuracy of cytology for IPT was low (5/12, 42%). IPT showed hypercellular smears (on FNA) with an admixture of various cell types including inflammatory cells with predominance of plasma cells, fibroblastic proliferation, granulation tissue formation, and atypical‐appearing histiocytes with enlarged nuclei and intranuclear inclusions. Fibroblastic proliferation with mitoses may mimic mesenchymal neoplasms. Cytomorphology is nonspecific and IPT usually is a diagnosis of exclusion. Diagn. Cytopathol. 2004;31:267–270. © 2004 Wiley‐Liss, Inc.

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.

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 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.

We initiated the present study to evaluate the accuracy of a new epithelial biomarker of early lung cancer. We tested the hypothesis that expression of a tumor-associated antigen by exfoliated sputum epithelial cells has greater accuracy (sensitivity and specificity) for the detection of preclinical, localized lung cancer than do routine clinical detection methods. Monoclonal antibody (MAb) 703D4 recognizes heterogeneous nuclear ribonuclear protein (hnRNP) A2/B1. We compared the accuracy of hnRNP up-regulation with cytology and radiographic screening for lung cancer detection in miners who were highly exposed to tobacco smoke, radon, and arsenic in southwestern China. The results showed that MAb 703D4 detection of hnRNP expression by sputum epithelial cells had greater accuracy for the detection of lung cancer than did routine screening methods, particularly for early (localized) disease. Among 57 cases and 76 noncases at the first screening, overall MAb detection of hnRNP was more sensitive (74 versus 21% for cytology and 42% for chest x-ray) but had lower specificity (70 versus 100% for cytology and 90% for chest x-ray) than standard methods. Recognizing hnRNP up-regulation resulted in detection of approximately one-third more early cases than did the combination of X-ray and cytology. Detection of hnRNP A2/B1 expression appears to be a good initial screening test for lung carcinogenesis, as it identified 74% of those who developed subsequent clinical lung cancer. Future studies might separate individuals with high lung cancer risk by MAb detection, confirming the positives with markers having greater specificity (e.g., clinical studies that become positive later in the morphological progression).

The United States lung cancer epidemic has not yet been controlled by present prevention and treatment strategies. Overexpression of a Mr 31,000 protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, had shown promise as a marker of lung cancer. In a pilot study of archived preneoplastic sputum specimens, hnRNP A2/B1 overexpression more accurately detected preclinical lung cancer than standard cytomorphology. In separate, ongoing prospective studies, sputum is collected annually from stage I resected non-small cell lung cancer patients at high risk of developing a second primary lung cancer and Yunnan tin miners at high risk of primary lung cancer. After the first year of follow-up, preclinical detection of lung cancer by routine cytology was compared with hnRNP A2/B1 overexpression as measured by quantitative densitometry of immunostained slides. Up-regulation of hnRNP A2/B1 in sputum specimens accurately predicted the outcome in 32 of 40 primary lung cancer and control patients within 12 months, whereas cytological change suggestive of lung cancer was found in only 1 patient. In the primary lung cancer study, overexpressed hnRNP A2/B1 accurately predicted the outcome in 69 of 94 primary lung cancer and control miners, whereas only 10 with primary lung cancer were diagnosed cytologically. These two prospective studies accurately predicted that 67 and 69% of those with hnRNP A2/B1 up-regulation in their sputum would develop lung cancer in the first year of follow-up, compared with background lung cancer risks of 2.2 and 0.9% (35- and 76-fold increase, respectively). Using sputum cells to monitor hnRNP A2/B1 expression may greatly improve the accuracy of preclinical lung cancer detection.

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. Published by Elsevier Science Inc.

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.

Objective.-Peritoneal washings are routinely performed during gynecologic surgery. The presence or absence of malignant cells in washings helps determine the stage of the malignancy. However, the efficacy of this procedure has not been studied recently.Design.-All intraoperative washings for gynecologic disease at our hospital from 1992 through 1994 (901 cases) were reviewed. Of these, 380 were gynecologic malignancies that were reviewed for changes in staging based on the presence of malignant cells.Results.-Histologically, 380 cases were gynecologic malignancies, 521 benign, 79 nongynecologic, and 25 had no accompanying surgical pathology. Of the malignancies, 125 had a diagnosis of cancer on washings, In 12 cases (3.1%), a change in stage resulted.Conclusions.-ln a small but significant number of cases, malignant cells in the washings changed postoperative staging, impacting therapeutic measures and prognosis for these patients greatly. Peritoneal washings remain a simple yet effective tool in the evaluation and management of gynecologic malignancies.

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.