A survey of United States obstetric anesthesiologists' perceived value of obstetric anesthesiology fellowship.

INTRODUCTION: Subspecialty training in obstetric anesthesiology is associated with improved patient outcomes and reduced anesthesia-related morbidity and mortality. Despite this, the demand for fellowship-trained obstetric anesthesiologists far exceeds the supply. This survey study aimed to evaluate the perceived value of obstetric anesthesiology subspecialty training on career trajectory, job satisfaction, quality of life, and job autonomy. METHODS: After Institutional Review Board approval, we conducted a cross-sectional study of fellowship-trained obstetric anesthesiologists in the United States of America. In March and April 2022, program directors of obstetric anesthesiology fellowships distributed an electronic survey link containing 29 multiple-choice questions to their program alumni. Survey content included respondent demographic characteristics, practice models, career information, and perceived value of an obstetric anesthesiology fellowship. RESULTS: We surveyed 217/502 (43%) fellowship-trained obstetric anesthesiologists with a response rate of 158/217 (73%). Most worked in urban, academic, and level IV perinatal health centers. The majority believed an obstetric anesthesiology fellowship was "extremely beneficial" (77%), enhanced quality of life (84%), improved the quality of patient care (99%), and was influential in helping obtain their first post-training job (86%). The perceived value of the fellowship included an enhanced career trajectory, a sense of purpose, improved job satisfaction, a sense of work community, lower burnout, involvement in maternal health initiatives, increased mentorship, and departmental leadership. CONCLUSION: In this survey study, fellowship-trained obstetric anesthesiologists perceived a positive impact of fellowship training on career trajectory, job protection and autonomy, quality of life, and job satisfaction. This information may be meaningful to trainees considering pursuing a fellowship and a career in obstetric anesthesiology.

The time is now: addressing the need for training in maternal critical care medicine.

Amongst many high-income countries, indirect medical conditions (e.g. cardiovascular disease, sepsis) now account for the majority of maternal deaths. In response to this concerning rise in indirect causes of maternal deaths, professional societies have developed guidelines that regionalize high-risk obstetric care and prioritize critical care expertise as a requirement for designated 'top' maternity hospitals. Critical care proficiency is mandated by the Accreditation Council for Graduate Medical Education for graduating obstetric anesthesiology fellows. Despite these requirements, no formal obstetric critical care educational curricula or fellowship pathways, combining critical care medicine and obstetric anesthesiology, currently exist. Dual subspecialty training in both obstetric anesthesiology and critical care medicine represents one strategy to improve the care of critically-ill obstetric patients and reduce maternal mortality and morbidity, which is one of the pressing healthcare issues of our time.

Readability, content, quality and accuracy assessment of internet-based patient education materials relating to labor analgesia.

BACKGROUND: With over 90% of parturients searching the internet for health information, the quality of information is important. Web-based patient education materials (PEMs) related to labor analgesia are frequently of low readability. This study compares the readability, content, quality and accuracy of labor analgesia-related PEMs from relevant healthcare society websites and the top internet search results. METHODS: The first ten PEMs from Google searches for "labor epidural" and "labor pain relief" were compared with PEMs from North American and United Kingdom anesthesiology, obstetric and medical society websites. Readability was assessed utilizing five validated readability indices. Quality was assessed using Patient Education Materials Assessment Tool for Print (PEMAT). The PEMs were graded for accuracy by four obstetric anesthesiologists. Readability, quality and accuracy scores were compared using the independent t-test and content using Chi-square analysis. RESULTS: Society PEMs were significantly more readable than non-society PEMs for three of five readability indices, though the mean of both groups was at or above an eighth-grade (average age 13-14 years-old) reading level. The PEMAT understandability and accuracy scores were significantly higher for society websites. The most frequently mentioned topics were benefits, effects of epidural analgesia on labor and delivery, definitions, post-dural puncture headache and alternative analgesics. CONCLUSIONS: Google search results for labor analgesia lead to PEMs of variable quality and readability. For readers to be better informed, web-based PEMs should be improved or women directed to society PEMs. Inaccurate information may lead to incorrect expectations and conflict during labor, with potentially lower maternal satisfaction.

Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) tumour genotyping is crucial to guide treatment decisions regarding the use of EGFR tyrosine kinase inhibitors in nonsmall cell lung cancer (NSCLC). However, some patients may not be able to obtain tumour testing, either because tissue is limited and/or tests are not routinely offered. Here, we aimed to build a model-based nomogram to allow for prediction of the presence of EGFR mutations in NSCLC. We retrospectively collected clinical and pathological data on 3,006 patients with NSCLC who had their tumours genotyped for EGFR mutations at five institutions worldwide. Variables of interest were integrated in a multivariate logistic regression model. In the 2,392 non-Asian patients with lung adenocarcinomas, the most important predictors of harbouring EGFR mutation were: lower tobacco smoking exposure (OR 0.41, 95% CI 0.37-0.46), longer time interval between smoking cessation and diagnosis (OR 2.19, 95% CI 1.71-2.80), advanced stage (OR 1.58, 95% CI 1.18-2.13), and papillary (OR 4.57, 95% CI 3.14-6.66) or bronchioloalveolar (OR 2.84, 95% CI 1.98-4.06) histologically predominant subtype. A nomogram was established and showed excellent discriminating accuracy: the concordance index on an independent validation dataset was 0.84. As clinical practices transition to incorporating genotyping as part of routine care, this nomogram could be highly useful to predict the presence of EGFR mutations in lung adenocarcinoma in non-Asian patients when mutational profiling is not available or possible.

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.

Cytopathology training in the United States - a personal view.

In this review we present an outline of cytopathology training in the United States, for a non-US readership.

Diagnostic dilemmas in pulmonary cytology.

BACKGROUND: Diagnostic difficulties in pulmonary cytology may be compounded by other medical problems, lack of pertinent information, and the presence of rare tumors. In the current study, the authors describe six cases of lower respiratory tract cytology that presented particular diagnostic challenges or pitfalls. METHODS: Three lung fine-needle aspiration biopsies (FNAB) from three patients, four bronchoalveolar lavages from two patients, and one bronchial washing from one patient, each with histologic confirmation, were reviewed. Cytologic material included direct smears, ThinPrep slides, and cell blocks. Cytologic findings were compared with established cytologic criteria for each final diagnosis. RESULTS: Two cases with Aspergillus infection that demonstrated reactive atypical cells were misinterpreted as squamous cell carcinoma and nonsmall cell carcinoma. Two cases diagnosed as significant atypia and negative, respectively, subsequently were found to show bronchioloalveolar carcinoma (as well as lymphangioleiomyomatosis, which was suspected clinically) and bronchogenic adenocarcinoma, respectively. One lung FNAB from a patient subsequently confirmed to have bronchiolitis obliterans-organizing pneumonia (BOOP) showed reactive pneumocytes that initially were misinterpreted as being suspicious for carcinoid. These reactive pneumocytes were identified histologically in the area of BOOP. The last case was an FNAB of a well differentiated fetal-type adenocarcinoma, an unusual variant of adenocarcinoma that to the authors' knowledge rarely is described in the cytology literature. CONCLUSIONS: Cytomorphologic features of lower respiratory tract pathology combined with appropriate clinical information and diagnostic discretion usually allow accurate diagnoses and should decrease both false-positive and false-negative result rates. Clinical information and radiologic findings may be invaluable, but may not always parallel the cytologic diagnosis.

A newly recognized syndrome--radiation-related bronchiolitis obliterans and organizing pneumonia. A case report and literature review.

Bronchiolitis obliterans and organizing pneumonia (BOOP) is a syndrome that has been associated with a variety of underlying disorders, including infection, collagen vascular diseases and toxic fume inhalation. Rarely, however, BOOP has been associated with radiation- or chemotherapy-induced pulmonary toxicity. Over the past 3 years, several case series have reported BOOP in the unique setting of radiation in breast cancer patients. This study describes our experience with this newly recognized syndrome and a review of the English-language literature on this syndrome.

Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens.

BACKGROUND: The distinction of a primary lung carcinoma from a metastatic lesion is important, because the treatment and prognosis differ for patients with these malignancies. Such a distinction can be difficult because of overlapping cytologic features. It has been shown that antibodies to thyroid transcription factor 1 (TTF-1) and PE-10 are fairly specific markers for primary lung tumors in histologic specimens. TTF-1 regulates the expression of surfactant protein production, and PE-10 is a monoclonal antibody against components of human surfactant proteins. The combination of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunoprofiling has been helpful in the identification of the primary site of origin of lung tumors. METHODS: In the current study, the authors evaluated the utility of TTF-1 and PE-10 immunostaining and also compared the staining with expression of CK7 and CK20 in the discrimination between primary lung tumors and metastatic lesions in 55 specimens from fine-needle aspiration (FNA) biopsies of the lung. Formalin fixed, paraffin embedded cell blocks from 35 primary lung tumors (16 adenocarcinomas, 8 squamous cell carcinomas, 6 large cell undifferentiated carcinomas, and 5 small cell carcinomas) and 20 metastatic carcinomas (6 breast lesions, 6 colon lesions, 3 urinary bladder lesions, 2 kidney lesions, 1 biliary tract lesion, 1 endometrial lesion, and 1 thyroid lesion) were immunostained with monoclonal antibodies to TTF-1, PE-10, CK7, and CK 20. Positive immunostaining for CK7, CK20, and PE-10 was based on cytoplasmic staining, whereas TTF-1 positive staining was based on nuclear staining of the neoplastic cells. RESULTS: Positive immunostaining with TTF-1 and PE-10 was noted in six primary lung tumors (17%). One metastatic lesion (5%) and two metastatic lesions (10%) were positive for TTF-1 and PE-10, respectively. The CK7 positive/CK20 negative immunophenotype was noted in 30 primary lung tumors (86%) and in 11 metastatic lesions (55%). The CK7 negative/CK20 negative immunophenotype was seen in four metastatic lesions and in the remaining five primary lung tumors. The CK7 negative/CK20 positive and CK7 positive/CK20 positive immunophenotypes were seen in two and three metastatic lesions, respectively, but in none of the primary lung tumors. When a CK7 positive/CK20 negative adenocarcinoma also demonstrated either TTF-1 positive or PE-10 positive staining, it was likely that the adenocarcinoma was of pulmonary origin (P < 0.035; Fisher exact test). The specificity of such a combination for discriminating between primary and metastatic adenocarcinomas was 94%. CONCLUSIONS: The results suggest that TTF-1, PE-10, or CK7/CK20 alone did not distinguish reliably between primary pulmonary tumors carcinomas and metastatic neoplasms of the lung in FNA biopsy specimens because of low sensitivity and specificity. The use of a panel of antibodies that includes CK7/CK20, TTF-1, and PE-10 may be helpful in discriminating between primary and metastatic adenocarcinomas of the lung. An adenocarcinoma is likely a primary lung tumor when it is of the CK7 positive/CK20 negative phenotype and demonstrates either TTF-1 positive or PE-10 positive staining.

Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases.

BACKGROUND: Epithelioid sarcoma is a rare tumor with characteristic morphologic and immunohistochemical features. It can be confused histologically and cytologically with a variety of benign and malignant lesions, including a granulomatous process, synovial sarcoma, melanoma, squamous cell carcinoma, and adenocarcinoma. The objective of this study was to define the cytologic features of this rare tumor. METHODS: The cytologic features of nine histologically confirmed epithelioid sarcomas were analyzed. The criteria evaluated included cell size and shape, cell borders, cluster organization, cytoplasmic characteristics, nuclear and nucleolar features, and background characteristics. RESULTS: In most cases, single, dispersed cells represented the predominant pattern, with only a few small clusters present. The cells were mostly round with interspersed spindle cells and mild to moderate pleomorphism. The nuclei were large and eccentrically located, with a plasmacytoid appearance. A pale zone in the perinuclear area was evident in three of nine cases. Well-defined cell borders with intercellular spaces between malignant cells were observed in eight cases. In three cases, a granuloma-like structure was identified. In two cases, the cells were mostly spindle and showed greater cellular pleomorphism. CONCLUSION: Epithelioid sarcoma is an uncommon tumor with a wide range of differential diagnoses, especially in cytology specimens. Awareness of its existence and knowledge of its cytologic features are important for a correct diagnosis.

Perineural antinociceptive effect of opioids in a rat model.

BACKGROUND: The research on conductive analgesia induced by perineural opioids generated a large body of conflicting data. In this study we reassessed the antinociceptive response to perineural administration of morphine, fentanyl or meperidine in a rat model. METHODS: Analgesia was assessed using the hind paw withdrawal latency (HPWL) response to radiant heat. The opioid dose producing 20% of maximal possible effect (20%MPE) for systemic analgesia was calculated for each drug. Then sciatic blockade was performed with the dose corresponding to 20%MPE. The injected hind paw was used to measure direct perineural effect and the contralateral hind paw was used as an indicator of systemic effect. RESULTS: The response latency produced by morphine or fentanyl was not significantly different for ipsilateral (perineural effect) or contralateral (systemic effect) paw (27+/-11 vs. 28+/-16 and 3l+/-16 vs. 23+/-16 s, respectively). However, the meperidine group showed significantly higher %MPE for the ipsilateral paw (79+/-32 s) than for the contralateral paw (27+/-22 s). CONCLUSIONS: The results indicate that perineural fentanyl or morphine do not produce analgesia. Perineural block produced by meperidine was attributed to local anesthetic-like effect, rather than to drug interaction with opioid receptor.

Calcifications highly suggestive of malignancy: comparison of breast biopsy methods.

OBJECTIVE: The purpose of this study was to compare the usefulness of, and cost of diagnosing with, different breast biopsy methods for women with calcifications highly suggestive of malignancy. MATERIALS AND METHODS: One hundred thirty-nine women with calcifications highly suggestive of malignancy underwent diagnostic biopsy. Of these, 89 women had stereotactic biopsy with a 14-gauge automated needle (n = 25), 14-gauge vacuum-assisted probe (n = 17), or 11-gauge vacuum-assisted probe (n = 47); and 50 women had diagnostic surgical biopsy. Medical records were reviewed. Cost savings for stereotactic biopsy were calculated using Medicare data. RESULTS: The median number of operations was one for women who had stereotactic biopsy versus two for women who had diagnostic surgical biopsy. The likelihood of undergoing a single operation was significantly greater for women who had stereotactic rather than surgical biopsy, among all women (61/89 [68.5%] vs. 19/50 [38.0%], p < 0.001) and among women treated for breast cancer (55/77 [71.4%] vs. 6/37 [16.2%], p = 0.0000001). Stereotactic 11-gauge vacuum-assisted biopsy, as compared with 14-gauge automated core or 14-gauge vacuum-assisted biopsy, was significantly more likely to spare a surgical procedure (36/47 [76.6%] vs. 16/42 [38.1%], p = 0.0005). Stereotactic 11-gauge vacuum-assisted biopsy resulted in the greatest cost reduction, yielding savings of $315 per case compared with diagnostic surgical biopsy; for women with solitary lesions, stereotactic 11-gauge biopsy decreased the cost of diagnosis by 22.2% ($334/$1502). CONCLUSION: For women with calcifications highly suggestive of malignancy, the use of stereotactic rather than surgical biopsy decreases the number of operations. Stereotactic 11-gauge vacuum-assisted biopsy, as compared with 14-gauge automated core or 14-gauge vacuum-assisted biopsy, is significantly more likely to spare a surgical procedure and has the highest cost savings.

Chordoma: a cytologic study with histologic and radiologic correlation.

BACKGROUND: Chordoma is a rare malignant tumor of fetal notochord origin that occurs along the spinal axis. The fine-needle aspiration biopsy (FNAB) findings are described, correlated with histology and radiology, and compared with previously reported descriptions of chordoma. METHODS: Fine-needle aspiration biopsies of 12 cases of chordoma with histologic confirmation were reviewed. Imaging studies were reviewed in seven cases. Cytologic material included smears, ThinPrep, and cell blocks. Immunostains were performed on selected cytologic and histologic specimens. Multiple cytologic parameters were studied. RESULTS: Eleven specimens were from the spinal axis, and one was from a chest wall metastasis. Ten cases were diagnosed as chordoma on cytologic material, one was positive for malignancy with a differential diagnosis of chordoma and well differentiated chondrosarcoma, and one was positive for malignancy, not further classified. Most smears were moderately to highly cellular and demonstrated typical physaliphorous cells and a myxoid background. Two of the 10 cases diagnosed as chordoma showed pleomorphic physaliphorous cells, nuclear inclusions, and binucleation. Nuclear inclusions were observed in three other cases diagnosed as chordoma. Histologic follow-up of one case with pleomorphic physaliphorous cells showed conventional chordoma with focal areas of increased cellularity and pleomorphism. Pleomorphic sarcomatous cells were the predominant cell type in one case that showed dedifferentiated chordoma histologically. Mitotic figures were rarely observed in cytologic material. CONCLUSIONS: Cytomorphologic features of chordoma allow accurate diagnosis by FNAB. Features associated with dedifferentiation include increased pleomorphism of physaliphorous cells and may include nuclear inclusions, bi- or multinucleation, and rarely, mitotic figures. Cancer (Cancer Cytopathol)

Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors.

INTRODUCTION: The role of fine-needle aspiration (FNA) and frozen section (FS) in the management of thyroid neoplasms continues to generate considerable controversy. We reviewed our recent experience to determine the clinical utility of FNA and FS in our surgical management and intraoperative decision-making. METHODS: All patients who had operations for thyroid disease between January 1996 and June 1999 were identified in our prospective database. Completion and incidental thyroidectomies were excluded. Data obtained from the pathology files included FNA, FS, and the final histologic diagnosis. RESULTS: Five hundred sixty-four patients, including 409 women (73%), with a median age of 50 years (range, 6-94) were identified, of whom 293 (52%) had cancer diagnosed on permanent sections. Three hundred twenty-nine patients (58%) had evaluable FNA, of which 91 (28%) were benign, 94 were malignant (28%), and 144 (44%) were suspicious (46% of these were malignant on final). Frozen section was performed in 397 (70%) patients; of these samples, 170 (43%) were found to be benign, 106 (27%) were malignant, and 121 (30%) were deferred (46% malignant on final). Fine-needle aspiration positively identified 51% of confirmed malignancies; 13% of patients with malignancy had a benign FNA result. Total thyroidectomy was performed in 64% of malignant tumors and 29% of benign thyroid disease (P < .001). Logistic regression revealed no association of extent of surgery with FNA results. A frozen section positive for malignancy was associated with total thyroidectomy (P < .001, RR 6 [CI 3-10]), and a negative frozen section report was associated with lobectomy (P < .05, RR 0.5 [CI 0.3-0.96]). Frozen sections results altered the preoperative plan in only 29 patients (5%). CONCLUSION: Results of preoperative FNA had no direct impact on the selection of the surgical procedure in this selected cohort. Intraoperative FS added very little to surgical management. The majority of thyroid operations at this institution are planned and performed based on known prognostic factors and intraoperative findings.

Large-cell neuroendocrine carcinoma of the lung: proposed criteria for cytologic diagnosis.

The category of large-cell neuroendocrine carcinoma (LCNEC) of the lung, proposed to expand the traditional scheme of typical carcinoid, atypical carcinoid (AC), and small-cell carcinoma (SCC), based on histologic features, has not been defined in cytology. We attempt to describe LCNEC cytologically. Cytologic features in 16 histologically confirmed LCNECs in fine-needle aspiration biopsies, cell blocks, bronchial brushes, washes, and sputum specimens stained with Diff-Quik, Papanicolaou, hematoxylin-eosin, chromogranin, and synaptophysin were analyzed. Three poorly differentiated nonsmall-cell carcinomas, 4 SCCs, and 2 atypical carcinoids were studied similarly. Twenty specimens from 16 histologically confirmed cases of LCNEC with original cytologic diagnoses including high-grade neuroendocrine carcinoma, large-cell carcinoma, nonsmall-cell carcinoma, poorly differentiated carcinoma, adenocarcinoma, and SCC, were examined. Features included flattened three-dimensional clusters with peripheral palisading, moderate to large single cells with scant (alcohol-fixed) or moderate (air-dried) cytoplasm; and large, oval, or polygonal nuclei with irregular contours, thickened nuclear membranes, and finely or coarsely granular chromatin, showing some molding and crush artifact. Nucleoli were generally present, and occasionally prominent. Mitosis and necrosis were apparent. Neuroendocrine stains were applied to all specimens, with at least one marker, commonly synaptophysin, positive in 18/20 specimens. LCNEC can be diagnosed in cytologic material, using morphology confirmed by immunocytochemistry. Treatment can be offered on the basis of cytologic examination.

Palpable breast masses: is there a role for percutaneous imaging-guided core biopsy?

OBJECTIVE: The purpose of this study was to evaluate percutaneous imaging-guided core biopsy in the assessment of selected palpable breast masses. MATERIALS AND METHODS: Of 1388 consecutive breast lesions that had percutaneous imaging-guided core biopsy, 155 (11%) were palpable. Palpable masses referred for percutaneous imaging-guided core biopsy included lesions that were small, deep, mobile, vaguely palpable, or multiple. Biopsy guidance was sonography in 140 lesions (90%) and stereotaxis in 15 (10%). Surgical correlation or minimum of 2 years follow-up is available in 115 palpable masses in 107 women. Medical records, imaging studies, and histologic findings were reviewed. RESULTS: Of 115 palpable breast masses, 98 (85%) were referred by surgeons to the radiology department for percutaneous imaging-guided core biopsy and 88 (77%) had percutaneous imaging-guided core biopsy on the day of initial evaluation at our institution. Percutaneous imaging-guided core biopsy spared additional diagnostic tissue sampling in 79 (74%) of 107 women, including 57 women with carcinoma and 22 women with benign findings. Percutaneous imaging-guided core biopsy did not spare additional tissue sampling in 28 women (26%), including 15 women in whom surgical biopsy was recommended on the basis of percutaneous biopsy findings and 13 women with benign (n = 7) or malignant (n = 6) percutaneous biopsy findings who chose to undergo diagnostic surgical biopsy. CONCLUSION: Percutaneous imaging-guided core biopsy is useful in the evaluation of palpable breast masses that are small, deep, mobile, vaguely palpable, or multiple. In this study, percutaneous imaging-guided core biopsy spared additional diagnostic tissue sampling in 74% women with palpable breast masses.

Fine-needle aspiration of a follicular dendritic-cell tumor: report of a case and review of the literature.

Follicular dendritic-cell tumors (FDCT) are rare neoplasms, well-characterized in surgical pathology material. There are, however, few cytopathology reports. We describe the fine-needle aspiration (FNA) findings of a histologically confirmed FDCT. Conventional smears and a cell block showed large spindle to oval neoplastic cells admixed with small mature lymphocytes. The neoplastic cells were present mainly in small syncytial clusters. Immunostains for CD21 and CD35, performed on the cell block, were positive in the neoplastic cells. The diagnosis was fully confirmed by the presence of typical immunohistochemical and ultrastructural features on the surgically removed tumor. The differential diagnosis of FDCT is broad and includes other tumors characterized by an admixture of large neoplastic cells and small mature lymphocytes, such as thymomas, lymphoepithelioma-like carcinomas, and interdigitating dendritic-cell tumors. It may not be possible to diagnose FDCT based on FNA material without the use of immunocytochemical and electron microscopic studies. Certain cytomorphological characteristics, however, might suggest its diagnosis and allow the practicing cytopathologist to perform confirmatory studies.

Cytokeratin immunoreactivity in Ewing's sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies.

Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are characterized by the presence of the specific t(11;22)(q24;q12) or variants thereof, producing diagnostic EWS fusion transcripts. Cytokeratin has been reported sporadically to be expressed in some cases of ES/PNET. However, its prevalence has not been assessed systematically in a series of cases with confirmatory molecular or cytogenetic evidence of a diagnostic translocation. We present in detail three index patients in whom strong cytokeratin immunoreactivity was a confounding factor in the diagnosis. To establish further the prevalence of cytokeratin immunoreactivity in a series of well-characterized ES/PNET, we then performed immunohistochemical studies with antibodies CAM5.2 and AE1/AE3 on 50 cases of ES/PNET diagnosed at Memorial Sloan-Kettering Cancer Center in which molecular evidence of a specific ES/PNET-associated translocation were available. Immunoreactivity to cytokeratin was present in 10 cases (20%), in five diffusely and five focally. There was no significant association between cytokeratin expression and the following parameters: patient age, sex, skeletal and extraskeletal primary site, and the type of EWS fusion transcript. Cytokeratin expression, a manifestation of epithelial differentiation, is present in as many as 20% of ES/PNET in either a diffuse or focal pattern.

Cytology of thymomas: emphasis on morphology and correlation with histologic subtypes.

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