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Background: The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.Methods: During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.Results: All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.Conclusions: Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. [ABSTRACT FROM AUTHOR]

The Chornobyl (Chernobyl) accident in 1986 exposed many individuals to radioactive iodines, chiefly (131)I, the effects of which on benign thyroid diseases are largely unknown. To investigate the risk of follicular adenoma in relation to radiation dose after Chornobyl, the authors analyzed the baseline data from a prospective screening cohort study of those exposed as children or adolescents. A stratified random sample was selected from all individuals who were younger than 18 years, had thyroid radioactivity measurements taken within 2 months after the accident, and resided in the three heavily contaminated areas in Ukraine. This analysis is based on the 23 cases diagnosed in 12,504 subjects for whom personal history of thyroid diseases was known. The dose-response relation was linear with an excess relative risk of 2.07 per gray (95% confidence interval: 0.28, 10.31). The risk was significantly higher in women compared with men, with no clear modifying effects of age at exposure. In conclusion, persons exposed to radioactive iodines as children and adolescents have an increased risk of follicular adenoma, though it is smaller than the risk of thyroid cancer in the same cohort. Compared with results from other studies, this estimate is somewhat smaller, but confidence intervals overlap, suggesting compatibility. [ABSTRACT FROM AUTHOR]

Introduction: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure., Methods: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose., Results: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00-23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10-0.29 Gy compared to a dose of 0.00-0.09 Gy and decreased at doses of 0.3-24 Gy (p value for linear trend = 0.99)., Conclusions: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure., (© 2024 S. Karger AG, Basel.)

PAX8 is a nuclear transcription factor with limited expression in normal and neoplastic tissues in a cell lineage-dependent manner. PAX8 has been detected in embryonic Müllerian ducts, human fallopian tubes, and ovarian carcinomas. However, little is known about its expression in other areas of the female genital tract. In this study, we used immunohistochemistry (IHC) to examine PAX8 expression in the normal uterine corpus and cervix, malignant tumors arising from these sites, and malignant effusions. We reported here that PAX8 was also detected in endometrial epithelial cells and endocervical glands, with a lower expression level in the latter, but not in the stromal cells of these areas. All endometrial carcinomas (N = 52) were positive for PAX8, whereas endocervical adenocarcinomas (N = 5) and uterine leiomyosarcomas (N = 3) were negative for PAX8. PAX8 was detected in 70% (22/31) and 68.8% (11/16) of metastatic carcinomas of the ovary and endometrium in serous effusions, respectively. No PAX8 was detected in carcinomas of nongynecologic origin or noncarcinomas (N = 71) in serous effusions except in one renal-cell carcinoma and one carcinoma of unknown primary in a woman. In addition, papillary serous carcinomas of the peritoneum (N = 10) were diffusely positive for PAX8, implying a Müllerian origin similar to malignant tumors in the female genital tract. Our findings suggest that PAX8 is an additional IHC marker for carcinomas of Müllerian origin hence we recommend including PAX8 for evaluation of malignant serous effusions in women, especially when tumors of Müllerian origin are in the differential diagnosis., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers., Objective: To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study., Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models., Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size., Conclusions: I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

Objective: Over time, the histology of papillary thyroid cancers detected in a repeatedly screened population exposed to radiation at Chornobyl (Chernobyl) has shifted from a more aggressive subtype toward less aggressive subtypes. This change may reflect biologic behavior but could also be influenced by the detectability of different subtypes. The study objective was to identify whether there is any relationship between the conspicuity of sonographically detected papillary cancers and histologic subtype., Materials and Methods: Sonographic images of 84 papillary cancers occurring in young people exposed to radiation at Chornobyl were each given a conspicuity score using a subjective 1-5 scale by four independent expert readers blinded to histologic subtype. The effects of tumor subtype, tumor encapsulation, reader, machine type, and nodule size on sonographic conspicuity were determined using analysis of variance and Spearman correlations., Results: Cancer subtype was related to sonographic conspicuity (p < 0.01). The relatively aggressive solid subtype of papillary carcinoma was more conspicuous than the papillary, follicular, and mixed subtypes (p < 0.05). The other subtypes did not differ significantly from each other in conspicuity. Conspicuity was not significantly related to nodule size, degree of encapsulation, age and sex of the subject, or machine type. Although the mean conspicuity score for each reader differed significantly, reliability of conspicuity judgments across readers was fair., Conclusion: In subjects exposed to radiation from the Chornobyl accident, the solid subtype of papillary carcinoma appears to be more conspicuous on sonography than the other subtypes. Therefore, the change in subtype observed over time in this repeatedly screened population may be influenced by differences in nodule conspicuity.

Urine cytology is a sensitive and specific method in detecting urothelial carcinoma of the urinary bladder, particularly the high-grade ones. However, the cytologic features of nonneoplastic lesions of the lower urinary tract, including nephrogenic adenoma, are nonspecific and may cause false positive diagnosis. Recent evidence has demonstrated that nephrogenic adenoma is a true "nephrogenic" lesion derived from the exfoliated and implanted renal tubular cells in the urinary tract. This has promoted the use of immunostaining of renal transcription factor PAX2 in tissue biopsies to differentiate nephrogenic adenoma from the common malignant tumors of the lower urinary tract. We report here that PAX2 immunostaining can also be used in urine cytology specimen to identify nephrogenic adenoma. Combination of PAX2 immunostaining and cytologic analysis may increase the accuracy in identifying this benign lesion in urine cytology specimen and therefore reduce unnecessary repeat cystoscopy and biopsy procedures. This may be a cost effective follow- up method for patients with an established diagnosis of nephrogenic adenoma.

Background: The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening., Methods: From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv., Results: Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group., Conclusions: Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (>30% solid structure). Small carcinomas (

Background: The Chornobyl accident in 1986 exposed thousands of people to radioactive iodine isotopes, particularly (131)I; this exposure was followed by a large increase in thyroid cancer among those exposed as children and adolescents, particularly in Belarus, the Russian Federation, and Ukraine. Here we report the results of the first cohort study of thyroid cancer among those exposed as children and adolescents following the Chornobyl accident., Methods: A cohort of 32 385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model., Results: Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998-2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate (P<.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval [CI] = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant., Conclusion: Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population.

Epithelioid hemangioendothelioma (EHE) is an uncommon vascular tumor with biological behavior intermediate between hemangioma and angiosarcoma. It rarely occurs in the oral cavity. We report a case of an 81-yr-old woman with a 2-mo history of a 2 x 2 cm2 submucosal buccal mass. Fine needle aspiration (FNA) smears were paucicellular and showed mainly single atypical large epithelioid cells in a bloody background. The atypical cells had abundant dense cytoplasm, some with fine vacuoles. Occasionally, cells with large cytoplasmic lumina were seen. Cytology preparations from fresh tissue received for frozen section revealed numerous neoplastic cells with large intracytoplasmic lumina, some of which contained red blood cells. In addition, cells with distinct intranuclear inclusions were present. Histologic sections and immunohistochemical stains confirmed the diagnosis of EHE. Although the histologic features of EHE are well recognized, reports of FNA cytology findings are sparsely existent in the literature as several case reports. The characteristic cytological features of EHE are reviewed in this report. We believe that the diagnosis of this rare tumor can be suggested when an adequate FNA specimen is obtained., (2006 Wiley-Liss, Inc.)

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

Background: The head and neck region is one of the most common locations of rhabdomyosarcoma. Salivary gland involvement is usually secondary to advanced disease, and presentation as a primary salivary gland tumor is very rare., Methods: Three cases of rhabdomyosarcoma presenting as parotid masses, in 2 boys (ages 3 and 7 years) and a girl (age 5 years), were retrieved from the files of 2 institutions., Results: The three patients presented with parotid gland enlargement. Clinically, the enlargements appeared to be inflammatory, and they were treated unsuccessfully with antibiotics. Fine-needle aspiration biopsy (FNAB) was performed on all three patients. The cytologic features varied from one case to another; one case had features of a small round cell tumor, another was composed of a monomorphic population of spindle cells in a metachromatic stroma, and the third case was composed mostly of spindle cells with moderate cellular pleomorphism. Immunohistochemical studies performed in two of the cases confirmed the diagnosis of rhabdomyosarcoma, and ultrastructural studies were confirmatory in the other case. The patients are alive; 2 of them have had no evidence of disease after 6 and 9 years of follow-up, and the third, the most recent patient, has just finished adjuvant chemotherapy., Conclusions: With the increased use of FNAB for the evaluation of salivary gland masses in children, the authors believe that it is important to recognize the occurrence of rhabdomyosarcoma in this location. Immunohistochemical studies have proved helpful in differentiating rhabdomyosarcoma from other parotid gland tumors and can be readily done on cytologic preparations.

A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.

Adenovirus (ADV) is increasingly recognized as a cause of morbidity and mortality in transplant recipients, but ADV pneumonitis has rarely been reported after lung transplantation. The few reported instances of ADV pneumonitis occurred mostly in children immediately after lung transplantation suggesting "primary" infection. We report a fatal case of ADV pneumonitis occurring in an adult, 4 years after unilateral lung transplantation, in whom the premortem diagnosis was not determined. Autopsy revealed severe necrotizing bronchitis, bronchiolitis, and interstitial pneumonitis. Characteristic smudgy intranuclear inclusions, immunohistochemistry for viral protein, in situ hybridization for viral genome, and postmortem lung cultures established ADV as the etiologic agent. ADV can cause fatal, occult respiratory infection in adult lung transplant recipients, remote from transplant surgery.

To determine the origin and nature of mucinlike material in fine-needle aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied breast FNA smears from four patients. All smears contained epithelial cells floating in a mucinlike background, which raised suspicion for mucinous (colloid) carcinoma. Mucicarmine stain was performed on one smear from each case. Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid-Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on selected tissue sections. Correlation of the cytologic and histologic findings of each lesion was performed. The mucinlike background in all four FNA smears stained strongly with mucicarmine. Corresponding biopsy specimens revealed pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma in the fourth. Each lesion in cases 1 to 3 was associated closely with fibrocystic changes. In case 4, cystic changes were located within the fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to 50% of normal lobule and duct contents stained with mucicarmine, indicating that the cyst contents were the most probable source of mucin in the FNA smears. The presence of pools of mucicarmine-positive material in FNA smears of the breast is not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can arise from benign cystic changes as well as from normal lobules and ducts.

Objective: To compare the relative strengths of two factors involved in making an accurate differentiation between functional and epithelial ovarian cysts, along with their combination: (1) the cytologist's level of experience in interpreting ovarian cytology, (2) the use of the tumor markers carcinoembryonic antigen (CEA) and CA-125 in cyst fluid, and (3) a combination of (1) and (2)., Study Design: Papanicolaou-stained sediments from fluid aspirated from 31 resected ovarian cysts (6 functional and 25 epithelial) were blindly and independently evaluated by five pathologists with varying experience in ovarian cytology. Cyst fluid supernatant was used for CEA, enzyme-linked immunosorbent assay, and CA-125 radioimmunoassay; CEA levels > 5 ng/mL or CA-125 > 5,000 U/mL were considered elevated. Cysts were categorized cytologically and histologically as functional or epithelial and by tumor markers as "neither elevated" or "either or both elevated" (EBE)., Results: The agreement of histologic diagnosis with each pathologist's cytologic diagnosis ranged from 53% to 84% (53%, 71%, 83%, 82%, 84%), corresponding to increasing level of experience. The percentage of agreement with EBE was 77%, whereas combined experienced pathologist's diagnosis and EBE was 87%. Kappa equaled .45 for experienced cytopathologist's diagnosis or EBE alone. Kappa equaled .53 when the pathologist or EBE diagnosed an epithelial cyst, indicating results unlikely to occur by chance., Conclusion: The distinction of functional from epithelial ovarian cysts is best achieved by combining measurement of the tumor markers CEA and CA-125 with a high level of cytopathology experience.

The Orphan Annie-eyed clear nucleus, defined as a large, optically clear nucleus, devoid of chromatin strands, with sharp chromatin rim, is a more specific feature than are nuclear grooves or intranuclear cytoplasmic inclusions in papillary thyroid carcinoma. In addition, this characteristic nuclear feature is detectable at low magnification. Although these clear nuclei are routinely seen in paraffin sections, they are inconspicuously seen in conventionally processed touch-imprints and fine-needle aspiration (FNA) smears. Among our two institutions, there have been 148 thyroid cases processed by Ultrafast Papanicolaou stain (UFP), including 43 papillary carcinomas, 38 cellular follicular lesions, and 67 cases of nodular hyperplasia. We observed clear nuclei in all of the cases of UFP-processed FNA and intraoperative smears of papillary carcinoma but not of other thyroid lesions. The clear nuclei are most evident in tumor cells with direct contact to the glass slide and are not seen in tumor cells soaked in cystic fluid. UFP is a valuable way to detect Orphan Annie-eyed clear nuclei of papillary thyroid carcinoma early in the diagnostic evaluation, either at immediate on-site evaluation of FNA or at intraoperative consultation and before the availability of permanent sections.

Enterogenous cyst is a benign lesion derived from misplaced endodermal epithelium. We report the aspiration cytology findings of an orbital cyst from a 32-year-old woman. The smears contain benign-appearing cuboidal glandular cells with focal mucinous features. Carcinoembryonic antigen level in the cyst fluid was markedly elevated. These findings are consistent with recurrence of the enterogenous cyst initially diagnosed 7 years earlier.

Using fluoroscopic guidance, polyethylene biliary stents are replaced endoscopically or percutaneously when bile duct stenosis recurs. To improve the sensitivity of conventional biliary cytology, we examined cells recovered from removed stents. Biliary stents removed endoscopically from each of 11 patients were rinsed with saline; next, the rinse was centrifuged and the sediment smeared and Papanicolaou stained. Three patients with choledocholithiasis had biliary stent replacement cytology (BSRC) to exclude a neoplastic etiology. Eight patients with clinicoradiologic evidence of hepatobiliary or pancreatic carcinoma had BSRCs performed for pathologic documentation of carcinoma. BSRC from six of eight patients with clinicoradiologically malignant biliary strictures contained malignant cells, predominantly in loose clusters, but also singly (sensitivity 75%, specificity 100%; positive predictive value 75%, negative predicative value 60%). Reparative epithelial atypia was also present in all cases. BSRC from two patients with clinicoradiological evidence of carcinoma of the biliary region and from three with choledocholithiasis contained only bile pigment, leukocytes, and benign epithelial cells. The sampling of cells which have accumulated on, or in biliary stents, improves the sensitivity of biliary cytology. This is most applicable when 1) a patient is inoperable, 2) tissue biopsy is neither feasible nor diagnostic, 3) prior brush, suction, percutaneous, or endoscopic needle aspiration cytology is inconclusive, and 4) permanent metal stent is needed.

Cytologic evaluation of second trimester amniotic fluid (AF) is a rapid, inexpensive adjunct to prenatal diagnosis of open neural tube defects (ONTDs). Our goal was to determine whether the neural-appearing cells and/or large foamy macrophages in the AF of anencephalics are indeed of neural and/or glial origin. In two second trimester patients with elevated serum alpha-fetoprotein (AFP) and polyhydramnios, fetal sonogram studies showed anencephaly; amniocentesis was performed for AF-AFP, cytogenetic, and cytologic studies. AF sediment smears were initially Papanicolaou-stained; next, the same smears were immunoperoxidase (IP)-stained for glial fibrillary acidic protein (GFAP). If GFAP negative, slides were restained for synaptophysin (SYN) and neuron-specific enolase (NSE). Both AFs contained small neural-appearing cells (5-10 microns) singly and in clusters, with dense, round, homogeneous nuclei, an occasional nucleolus, and scant cytoplasmic rim. These were GFAP negative and SYN and NSE positive; the large vacuolated, lipid-laden macrophages (20-40 microns) were negative for all three IP stains. In conclusion, positive IP staining for SYN and NSE supports the morphologic impression that small dark cells in AF are of neural origin, while negative IP staining of large foamy macrophages suggests nonneural, nonglial origin.

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy.

We present and discuss major current theories about the developmental natural history of the anencephalic human fetus. We confirm previous observations made using transvaginal ultrasonography of exencephalic fetuses which were later imaged and/or delivered as anencephalic fetuses. We explore the possibility of proving the theory of the slowly rubbed-off exposed brain tissue by cytologic examination and special staining of aspirated cells in amniotic fluid. Three fetuses with a typical sonographic picture of exencephaly at 13-15 postmenstrual weeks underwent amniocentesis. The aspirated fluid contained pathognomonic neural cells. The same fetuses later showed the characteristic sonographic and postabortion picture of anencephaly. Our results support the theory that exencephaly is the forerunner of anencephaly.

Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure.

Purpose: To heighten awareness of colonic tuberculosis (TB) as a once rare disease that is undergoing a resurgence in the United States., Methods: Report of a case of isolated sigmoid tuberculosis with a brief literature review of the topic., Results: TB can no longer be considered a rare disease in the United States because, in part, of the acquired immunodeficiency syndrome epidemic and because, in part, of increased immigration and lack of containment. The signs and symptoms of colonic TB are nonspecific; therefore, a high index of suspicion must be maintained. Only 20 percent of patients will have associated active pulmonary TB. Colonoscopy with multiple biopsies at ulcer margins should be performed for diagnosis. Tissue should be sent for routine histology and culture and smeared for direct visualization of acid-fast bacilli. If colonic TB is suspected, empiric treatment is warranted, despite negative histology, smear, and culture results. Patients will usually show a dramatic response in one to two weeks. Treatment is solely medical, and all patients should receive a full course of antituberculous chemotherapy. Exploratory laparotomy is necessary if diagnosis is in doubt, when there is concern about a neoplasm, or for complications including perforation, obstruction, hemorrhage, or fistulization., Conclusion: An increased awareness of intestinal TB coupled with familiarity of the pathophysiology, diagnostic methods, and treatment should increase the number of cases correctly diagnosed preoperatively and, therefore, improve the outcome of patients with this disease.

Carbon-laden macrophages in bronchoalveolar lavage have been noted to be associated with a history of crack smoking. We report herein the finding of carbon-laden macrophages in four cytological preparations of pleural fluid from two crack smokers. The etiology of the two patients' pleural effusions differed; neither had a bronchopleural fistula. Patient 1 had AIDS, Pneumocystis carinii pneumonia, and Kaposi's sarcoma of the right lung with an associated bilateral pleural effusion. Patient 2 was HIV seropositive, had pulmonary tuberculosis, hepatitis A, B, and C, cardiomyopathy, pulmonary embolism, and bilateral pleural effusions, the latter of which were probably due to cardio-pulmonary dysfunction. An additional two crack smokers with pleural effusions due to malignancy, one primary pulmonary adenocarcinoma and the other metastatic melanoma, did not have carbon-like material in their pleural fluid cytology. We hypothesize that intracellular accumulation of carbonaceous material in the lung parenchyma and pleural space occurs when normal clearance mechanisms are overwhelmed.

Large biopsy needles (18 and 19 gauge) have been reported to yield high-quality tissue cores for reliable histologic diagnosis. In our institution, image-directed percutaneous biopsy specimens obtained with these needles are processed routinely for simultaneous cytologic and histologic analysis. For the present study, we reviewed our experience with 82 such biopsies of the thoracoabdominal region. We examined the value of cytologic analysis as a supplement to histologic analysis of such biopsies in terms of diagnostic yield and sensitivity for detecting malignancy. Among the 82 specimens, material was adequate for histologic diagnoses in 70 (85%) and for cytologic diagnosis in 63 (77%). Combining the histologic and cytologic results increased the diagnostic yield to 93% (76 of 82 specimens). Forty-eight lesions were diagnosed as malignant by either one or both means of analysis. While histologic analysis produced 44 of the 48 positive results (92%), cytologic analysis produced 33 (66%) (P < .05, McNemar's test). Because tissue fragments were selected preferentially for histologic processing, histologic evaluation was more valuable than cytologic evaluation in achieving definitive diagnoses of malignancy. In spite of this bias in preparation technique, malignancy was diagnosed by cytologic analysis alone in 4 of the 48 positive cases (8%). We conclude that the combined approach of histologic and cytologic examination of large-gauge core needle biopsy specimens maximizes the diagnostic yield and sensitivity for detecting malignancy.

An athletic patient presented with a nontraumatic peroneal neuropathy that failed to resolve after a period of rest. A magnetic resonance image (MRI) showed a multilobulated mass in the course of the common peroneal nerve consistent with a plexiform neurofibroma. Surgical exploration revealed a mass, which coursed from the midthigh to the fibular neck, that was intimately involved with the fibers of the nerve bundle and had cystic degeneration with vesicles along its length. The authors recommend MRI as highly accurate in diagnosing unusual causes of peroneal neuropathy.

It is increasingly common for cytology laboratories to receive ovarian, adnexal and pelvic cyst fluids obtained via sonographically directed aspiration and laparoscopic techniques, especially from women who are desirous of preserving fertility or who are undergoing in vitro fertilization (IVF). Accurate characterization of such cysts is a worthwhile goal, given the superior prognosis for ovarian carcinomas that are diagnosed at an early stage. In an effort to improve upon the false-negative diagnosis rate associated with cytology, we evaluated DNA ploidy as a possible adjunctive criterion. We examined 55 benign, 3 borderline and 6 malignant aspirates received by our cytopathology laboratory; 35 were aspirated directly from the patient from clinically and ultrasonographically benign cysts, and 29 were aspirated from surgically removed benign (20) and malignant (9) cysts. Adjunctive DNA ploidy and cell cycle analysis was performed using the Cell Analysis Systems CAS-200 on Feulgen-stained cytologic smears of the 64 cyst fluids. Adequate material for DNA analysis was obtained from 33/35 in situ aspirated cysts and from 19/29 surgical specimen cysts. Forty-seven of 52 cytologically benign cysts were diploid. Of the 5 nondiploid benign cysts, 3 were follicle cysts (2 from hormonally stimulated IVF patients and 1 from a postpartum patient), and 1 was a benign cystic teratoma. Their nondiploid DNA pattern or tetraploidy may be due to a high proliferative index. The fifth nondiploid benign aspirate was from a resected benign epithelium-lined cyst; its DNA histogram contained a conspicuous tetraploid population. All 9 malignant cysts were cytologically malignant. Of the 3 borderline cysts, 1 was nondiploid, and 2 were diploid. All 6 fully malignant cysts were nondiploid; 2 of them were tetraploid. Based on our results, we conclude that DNA ploidy analysis of cells derived from ovarian and adnexal cyst aspirates is feasible (in 95% of cases) and relatively specific (90%) and has a relatively high negative predictive value (92%). The results are not sufficiently predictive of the histology of the lesion to warrant therapeutic intervention based on ploidy alone (sensitivity of nondiploid results, 78%; positive predictive value of nondiploid results, 58%). Nondiploidy should suggest consideration, but is not conclusive, of a malignancy diagnosis. There may even be prognostic implications to the ploidy pattern, particularly in borderline tumors, in which nondiploidy portends a poor prognosis.

Purpose: To report on a vitreous specimen in a 53-year-old patient with unilateral choroiditis and vitritis of unknown cause., Methods: Cytologic examination of a vitreous aspirate stained by the Papanicolaou method., Results: Intravitreal spirochetes consistent with Borrelia burgdorferi were found in this seronegative patient., Conclusion: Vitreous specimens of patients with choroiditis and vitritis of unknown cause should be examined cytologically, particularly when serologic results do not corroborate the clinical findings of Lyme disease.

A transvaginal sonographic (TVS) scoring system using morphologic features has been developed at our institution to maximize discrimination between benign and malignant ovarian and adnexal cysts. Low (4-7) or intermediate (8-9) scores have been found to correlate with benignity, hence TVS-guided or laparoscopically directed needle aspiration of low-scoring lesions may safely be performed. High-scoring lesions (10-14) are often malignant, therefore in situ needle aspiration of such lesions is not recommended. The aim of our study was to correlate the results of TVS characterization of ovarian and adnexal cysts with the aspiration cytologic evaluation. Twenty-three of the 43 cysts studied were aspirated in situ from the patient; 20 were aspirated from resected surgical specimens. Thirty-six benign cysts had TVS scores ranging from 4 to 12, with a median score of 7. All 25 cysts that were benign by TVS and/or histology were also cytologically benign as well as an additional 11 cysts that were not resected (TVS scores: 4 to 9). Seven cytologically and histologically malignant cysts had high TVS scores (TVS scores 10-14; median = 12). The combination of TVS and needle aspiration cytology is valuable, particularly in the diagnosis of cysts having low or intermediate TVS scores and benign cytology. Aspiration of cysts or masses with high TVS scores is not recommended. This combined evaluation may allow a more limited surgical approach, such as operative laparoscopy, or, in some cases, obviate the need for operative treatment altogether.

A retrospective study was performed on heavily pigmented pulmonary cytologic specimens from 14 hospital patients to determine the clinical features distinguishing these cases. The lavage fluid or sputum in each case was turbid and gray or black, exceeding the blackness usually seen in heavy tobacco smokers dwelling in the same urban environment. Excessive carbonaceous material was observed in the cytoplasm of pulmonary alveolar macrophages or the extracellular compartment of the smears. The latter feature is not seen in cigarette smokers. Many other pigmentary sources were ruled out, including melanin, hemosiderin, medicinal charcoal, India ink, and hematoxylin crystals. The common feature of the patients was that they recently or currently smoked the crack form of cocaine heavily; five patients also had positive toxicologic results for cocaine at admission. The authors suggest that blackened bronchoalveolar lavage fluid indicates the possibility of crack cocaine smoking and the associated sequelae, particularly when the carbonaceous material is present in the extracellular compartment.

Megakaryocytes were detected in a transbronchial brush cytology specimen. Their detection led to a diagnosis of essential thrombocythemia.

Transvaginal ultrasonography is routinely performed in the course of egg retrieval in patients presenting for in vitro fertilization (IVF) and results in the discovery of occult, subclinical ovarian cysts that would otherwise have gone undetected. This study (1) evaluated the cellular composition of the cyst fluids based on a comparison with cells obtained from cysts of known and documented histologic type, and (2) attempted to determine if the cytologic evaluation of cyst fluid was necessary to exclude occult ovarian cancer. During the 1.8 years of our study, 931 patients underwent 1,544 ultrasound-guided ovum retrievals; during this same period, 90 specimens of ovarian cyst fluid were examined. Of them, none contained cancer cells. A single case of cystic ovarian cancer was detected by ultrasound but was not aspirated. The cytologic diagnosis of endometriosis was established in 12 specimens from 10 patients, 5 of whom did not have a previously documented clinical diagnosis of endometriosis. The role of routine ovarian cyst fluid cytology as part of an IVF protocol may be of limited value in cancer diagnosis. However, until the incidence of ovarian cancer in the subset of women with both infertility and ovarian cysts is known, it would seem prudent to continue to examine any voluminous or discolored ovarian cyst fluid obtained from IVF patients. The presence of ovarian cysts did not affect the clinical pregnancy rate per retrieval.

With the use of fresh cell suspensions, the DNA ploidy of 11 benign and 27 malignant spindle cell soft-tissue lesions was determined by flow cytometry (37 cases) and/or image cytometry (35 cases). Of the 27 malignant lesions, 10 were low- or intermediate-grade sarcomas, and 17 were high-grade sarcomas. In the malignant lesions, the DNA ploidy was correlated with the histologic grade and the clinical outcome. Of the 11 benign lesions, six had a diploid DNA ploidy pattern, and five were nondiploid by either flow cytometry or image cytometry. All benign cases had a favorable outocome regardless of ploidy. Eight of the 10 low- or intermediate-grade malignant lesions were diploid, whereas two were nondiploid. Of the 17 high-grade sarcomas, 15 were nondiploid by either method of measurement and nine by both. Of the 10 diploid malignant tumors, only one had an unfavorable outcome (malignant mesothelioma with biopsy only), whereas of the 17 malignant lesions that were nondiploid, five had no evidence of recurrent disease, three cases recurred, eight patients died of disease, and one patient died of an unrelated cause. We concluded that (1) ploidy does not differentiate benign from malignant spindle cell soft-tissue tumors, (2) the nondiploid DNA pattern is more common in high-grade than in low- or intermediate-grade sarcomas, and (3) there is a statistically significant relationship between nondiploidy and a worse clinical outcome in sarcomas.

A study was undertaken to demonstrate the safety, efficacy and value of esophageal balloon cytology in the diagnosis of esophageal lesions and as a tool in screening a high-risk patient population. The sampling was performed 110 times on 96 patients, 11 with known obstructive carcinoma of the esophagus and 85 thought to be at risk for esophageal cancer: 74 with treated or untreated cancer of the head and neck area and 11 with dysphagia or other findings requiring clarification. The method was well tolerated by the patients, and the cytologic smears were of excellent quality. Malignant or suspicious cells were found in smears from 7 to 11 patients with documented esophageal cancer and in 7 of 85 patients believed to be at risk. In the latter group there were three unsuspected recurrent cancers of the oropharyngeal region and one unsuspected carcinoma in situ of the esophagus. There were no false-suspicious or false-positive results. This noninvasive technique of esophageal cytology obviously deserves additional trials as an adjunct in the diagnosis of carcinoma of the head and neck and upper gastrointestinal tract, especially in high-risk patients.

In six cases, fine needle aspiration (FNA) directed at prostatic lesions produced specimens containing megakaryocytes or ganglion cells, which are sources of potential diagnostic error in the interpretation of aspirates of the prostate gland. In three cases, apparent accidental penetration of the tip of the transrectal FNA biopsy needle into the ischium instead of the prostate resulted in the aspiration of megakaryocytes and other bone marrow elements; the megakaryocytes mimicked anaplastic cancer. Three additional FNAs of the prostate produced specimens containing a small number of ganglion cells mimicking well-differentiated adenocarcinoma; the accompanying strands of wavy neural tissue served as a clue to the ganglionic origin of these potentially misleading cells. The paucity of "atypical" cells and the sparsity or absence of prostatic epithelium in the aspirates were additional clues to the cytologist that the findings represented an anatomic misplacement of the FNA biopsy needle tip, rather than a prostatic cancer.