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The current theory of carcinogenesis for the deadliest of 'ovarian' cancers-high-grade serous carcinoma (HGSC)-holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at-risk women with germ-line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a 'catastrophic' model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long-term follow-up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.

Aims MYC is a proto-oncogene that is frequently dysregulated in various malignancies, through translocation or amplification. Radiation-associated angiosarcoma frequently shows MYC amplification, and immunohistochemical expression has been shown to be a reliable surrogate marker for amplification, but less is known about MYC expression in other sarcoma types, despite reports of MYC amplification in some undifferentiated/unclassified radiation-associated sarcomas (RASs). Distinguishing putative RAS from non-radiation-associated sarcoma or sarcomatoid carcinoma can be difficult. The aim of this study was to determine the prevalence and potential diagnostic utility of MYC in this context, by evaluating MYC expression in a cohort of RASs, non-radiation-associated sarcomas, and sarcomatoid carcinomas. Methods and results Three hundred and eighty-five neoplasms were evaluated, including 81 RASs (18 angiosarcomas; 57 undifferentiated sarcomas; three leiomyosarcomas; and three malignant peripheral nerve sheath tumours), 267 non-radiation-associated sarcomas, and 37 sarcomatoid carcinomas. Immunohistochemistry was performed with a monoclonal anti-MYC antibody. Staining in tumour cells was scored on the basis of extent (focal, 1-4%; multifocal, 5-49%; and diffuse, ≥50%) and intensity (strong, moderate, and weak). One hundred percent of radiation-associated angiosarcomas expressed MYC diffusely. Expression was infrequent among other types of RAS (9.5%), and the frequency was similar to that in non-radiation-associated sarcomas (9.7%). MYC expression was more common in sarcomatoid carcinomas, occurring in 43%. The extent and intensity of staining were variable in all groups. Conclusion MYC expression is infrequent among RASs other than angiosarcoma, and has a similar prevalence in sporadic sarcomas. Given the frequency of expression in sarcomatoid carcinomas, MYC expression outside the context of radiation-associated angiosarcoma is of limited diagnostic utility, and should be interpreted with caution after exclusion of sarcomatoid carcinoma where relevant.

Background Ewing sarcoma (ES) is a round cell sarcoma that can be challenging to diagnose on cytologic material given its significant overlap with numerous mesenchymal, epithelial, and lymphoid cytomorphologic mimics. The objective of this study was to assess the utility of a novel marker, NKX2.2, in the diagnosis of ES in cytologic material and its ability to distinguish ES from its mimics. Methods NKX2.2 immunohistochemistry was performed on cell blocks from 107 fine-needle aspirations, and nuclear expression was scored semiquantitatively for extent and intensity. The study cohort included ES (n = 10), well differentiated neuroendocrine tumor (n = 20), melanoma (n = 11), Merkel cell carcinoma (n = 10), small cell carcinoma (n = 10), alveolar rhabdomyosarcoma (n = 2), spindle cell/sclerosing rhabdomyosarcoma (n = 2), synovial sarcoma (n = 12), solitary fibrous tumor (n = 2), chronic lymphocytic leukemia (n = 10), lymphoblastic lymphoma (n = 11), adenoid cystic carcinoma (n = 6), and CIC-rearranged sarcoma (n = 1). Results NKX2.2 had high sensitivity (100%) and moderate specificity (85%) for the diagnosis of ES in cytologic material. NKX2.2 expression also was present in a subset of mesenchymal and epithelial mimics, and staining was most commonly observed in small cell carcinoma (80%) and well differentiated neuroendocrine tumor (45%). Among mesenchymal mimics, 42% exhibited NKX2.2 expression. NKX2.2 staining was absent in melanoma, adenoid cystic carcinoma, and lymphoproliferative neoplasms. Conclusions NKX2.2 is a highly sensitive but only moderately specific marker for ES. Neuroendocrine neoplasms exhibit variable NKX2.2 expression and remain a significant potential diagnostic pitfall. Thus, NKX2.2 expression should be interpreted in the context of an appropriate immunohistochemical panel (and often with confirmatory molecular testing) for the accurate diagnosis of ES.

Background Diagnosing giant cell-rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation-specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell-rich bone tumors on fine-needle aspiration and core needle biopsy specimens. Methods IHC was performed using monoclonal antibodies against histone H3.3 G34W and K36M in GCTs of bone (26 cases, including 2 malignant cases), GCT of Paget disease (1 case), chondroblastoma (8 cases), aneurysmal bone cyst (7 cases), and osteosarcoma (13 cases) with available fine-needle aspiration and/or core needle biopsy specimens from 2 institutions. H3F3A and H3F3B Sanger sequencing was performed on all 4 H3G34W IHC-negative GCTs. Results IHC for H3G34W was positive in 22 of 26 GCTs (85%) and negative in all histologic mimics. IHC for H3K36M was positive in all 8 chondroblastomas and negative in all histologic mimics. IHC results were concordant between biopsy and surgical specimens in 152 of 158 samples (96%). Sequencing identified alternate H3F3A G34L and G34V mutations in 1 IHC-negative GCT each, but no mutation was found in the remaining 2 cases. Conclusions H3G34W and H3K36M IHC is highly specific for GCT and chondroblastoma, respectively, among giant cell-rich bone tumors, and is useful for confirming the diagnosis in limited biopsies. The presence of alternate H3F3A mutations accounts for the H3G34W IHC negativity in a subset of GCT of bone cases. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Background The characterization of poorly differentiated neoplasms in fine-needle aspiration (FNA) and small biopsy specimens usually requires immunohistochemistry (IHC) with a panel of markers. Because of an increasing need to preserve limited diagnostic material for tumor genotyping and a mounting demand for cost containment, the authors investigated the usefulness of dual-color IHC with antibodies directed against broad-spectrum keratins and SOX10, a neuroectodermal transcription factor consistently expressed in melanoma, in the workup of epithelioid malignant neoplasms. Methods A total of 107 cases of FNA cell blocks (49 cases) and small biopsies (58 cases) were selected, including 34 melanomas, 31 epithelioid/pleomorphic sarcomas, and 42 carcinomas. IHC was performed on all specimens using a peroxidase-based brown chromogen for SOX10 and an alkaline phosphatase-based red chromogen for keratins AE1/AE3. The presence or absence of staining in lesional cells was scored. Results The majority of tumors demonstrated 1 of 3 distinct patterns: 1) malignant melanomas with nuclear SOX10 (sensitivity of 94% and specificity of 95%); 2) epithelioid/pleomorphic sarcomas negative for both SOX10 and AE1/AE3 (sensitivity of 84% and specificity of 88%); and 3) carcinomas with cytoplasmic AE1/AE3 (sensitivity of 76% and specificity of 98%). In addition, a fourth pattern with cytoplasmic AE1/AE3 and nuclear SOX10 was observed in a subset of carcinomas, most notably triple-negative breast cancers. Conclusions SOX10/keratin dual-color IHC appears to be an effective, sensitive, and specific test to distinguish between melanoma, sarcoma, and carcinoma. This approach can identify melanoma, prioritize additional studies, and limit the number of markers needed to workup an epithelioid malignant neoplasm, thereby potentially reducing costs and preserving valuable tissue for ancillary studies with which to guide therapy. Cancer Cytopathol 2018;126:179-89. © 2018 American Cancer Society.

BACKGROUND Histiocytic sarcoma (HS) is a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes. Molecular characteristics of HS and fine-needle aspiration (FNA) criteria for its diagnosis have not been established. METHODS A case series of HS in 8 FNA samples from 6 patients was reviewed along with histopathologic and clinical data. Immunohistochemistry was performed on cell blocks (3 cases), core biopsies (5 cases), and surgical specimens (4 cases). Targeted-exome next-generation sequencing (NGS) was performed on surgical resection specimens in 4 cases. RESULTS Four patients had a known history of hematolymphoid malignancy. Cytomorphologic features included variably cellular smears composed of large epithelioid cells with reniform nuclei and abundant vacuolated cytoplasm, in an inflammatory background, with occasional cytophagocytosis and lymphoglandular bodies. Marked pleomorphism, multinucleated monster cells, and binucleated histiocytoid cells with partially overlapping, eccentrically placed nuclei resembling Pac-Man were common. Most cases expressed histiocytic markers CD68 (6 of 7 cases), CD163 (5 of 5 cases), and PU.1 (3 of 4 cases). In 3 cases, NGS analysis revealed alterations in lysine methyltransferase 2D (KMT2D)/mixed-lineage leukemia 2 (MLL2), a gene involved in chromatin regulation and previously implicated in the pathogenesis of follicular lymphoma. CONCLUSIONS Although diagnosing HS with FNA alone is extremely challenging, the presence of pleomorphic and epithelioid large cells with binucleation and/or multinucleation in an inflammatory background should prompt the diagnosis of HS with judicious use of confirmatory histiocytic lineage markers. The detection of recurrent KMT2D/MLL2 alterations implicates epigenetic regulation in the pathogenesis of HS and supports the notion of transdifferentiation from a genetically similar but phenotypically distinct tumor of a different lineage. Cancer Cytopathol 2017. © 2017 American Cancer Society.

In the development of personalized medicine, the ultrasensitive detection of point mutations that correlate with diseases is important to improve the efficacy of treatment and guide clinical medication. In this study, locked nucleic acid (LNA) was introduced as an amplification suppressor of a massive number of wild-type alleles in an amplification refractory mutation system (ARMS) to achieve the detection of low-abundance mutations with high specificity and sensitivity of at least 0.1%. By integrating the length of clamp, base type, number and position of LNA modifications, we have established a "shortest length with the fewest LNA bases" principle from which each LNA base would play a key role in the affinity and the ability of single base discrimination could be improve. Finally, based on this LNA design guideline, a series of the most important single point mutation sites of epidermal growth factor receptor (EGFR) was verified to achieve the optimal amplification state which as low as 0.1% mutation gene amplification was not affected under the wild gene amplification was completely inhibited, demonstrating that the proposed design principle has good applicability and versatility and is of great significance for the detection of circulating tumor DNA. This article is protected by copyright. All rights reserved.

Purpose: Pseudoprogression (PsP) can mimic true tumor progression (TTP) on magnetic resonance imaging in patients with glioblastoma multiform (GBM). The phenotypical similarity between PsP and TTP makes it a challenging task for physicians to distinguish these entities. So far, no approved biomarkers or computer-aided diagnosis systems have been used clinically for this purpose. Methods: To address this challenge, the authors developed an objective classification system for PsP and TTP based on longitudinal diffusion tensor imaging. A novel spatio-temporal discriminative dictionary learning scheme was proposed to differentiate PsP and TTP, thereby avoiding segmentation of the region of interest. The authors constructed a novel discriminative sparse matrix with the classification-oriented dictionary learning approach by excluding the shared features of two categories, so that the pooled features captured the subtle difference between PsP and TTP. The most discriminating features were then identified from the pooled features by their feature scoring system. Finally, the authors stratified patients with GBM into PsP and TTP by a support vector machine approach. Tenfold cross-validation (CV) and the area under the receiver operating characteristic (AUC) were used to assess the robustness of the developed system. Results: The average accuracy and AUC values after ten rounds of tenfold CV were 0.867 and 0.92, respectively. The authors also assessed the effects of different methods and factors (such as data types, pooling techniques, and dimensionality reduction approaches) on the performance of their classification system which obtained the best performance. Conclusions: The proposed objective classification system without segmentation achieved a desirable and reliable performance in differentiating PsP from TTP. Thus, the developed approach is expected to advance the clinical research and diagnosis of PsP and TTP.

Giant cell-rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell-rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62-year-old male who presented with initial right jaw swelling. Radiologic work-up revealed a 6.2 cm mass involving the right parotid gland. Fine-needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell-rich osteosarcoma. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND Soft tissue perineurioma (STP) is a benign peripheral nerve sheath tumor demonstrating uniform perineurial cell differentiation. To the authors' knowledge, the cytomorphologic features of STP remain incompletely characterized, and the distinction between STP and its benign (intramuscular/cellular myxoma) and malignant (low-grade fibromyxoid sarcoma [LGFMS]) mimics is challenging. METHODS Fine-needle aspiration (FNA)/core needle biopsies of 25 low-grade myxoid spindle cell neoplasm cases including STP (5 cases), intramuscular/cellular myxoma (16 cases), and LGFMS (4 cases) were reviewed retrospectively for cytomorphologic and immunophenotypic comparison. RESULTS FNA smears of STP were hypocellular with scattered clusters of spindle cells with bland, slender nuclei; bipolar cytoplasmic processes; and scant myxoid to collagenous matrix. STP commonly lacked the abundant granular myxoid matrix material present in intramuscular/cellular myxoma (20% in STP vs 75% in intramuscular/cellular myxoma; P

Purpose: Spring-assisted surgery is an effective and minimally invasive treatment for sagittal craniosynostosis (CSO). The principal barrier to the advancement of spring-assisted surgery is the patient-specific spring selection. The selection of spring force depends on the suture involved, subtypes of sagittal CSO, and age of the infant, among other factors. Clinically, physicians manually judge the subtype of sagittal CSO patients based on their CT image data, which may cause bias from different clinicians. An objective system would be helpful to stratify the sagittal CSO patients and make spring choice less subjective. Methods: The authors developed a novel informatics system to automatically segment and characterize sutures and classify sagittal CSO. The proposed system is composed of three phases: preprocessing, sutures segmentation, and classification. First, the three-dimensional (3D) skull was extracted from the CT images and aligned with the symmetry of the cranial vault. Second, a “hemispherical projection” algorithm was developed to transform 3D surface of the skull to a polar two-dimensional plane. Through the transformation, an “effective” projected region can be obtained to enable easy segmentation of sutures. Then, the different types of sutures, such as coronal sutures, lambdoid sutures, sagittal suture, and metopic suture, obtained from the segmented sutures were further identified by a dual-projection technique of the midline of the sutures. Finally, 108 quantified features of sutures were extracted and selected by a proposed multiclass feature scoring system. The sagittal CSO patients were classified into four subtypes: anterior, central, posterior, and complex with the support vector machine approach. Fivefold cross validation (CV) was employed to evaluate the capability of selected features in discriminating the four subtypes in 33 sagittal CSO patients. Receiver operating characteristics (ROC) curves were used to assess the robustness of the developed system. Results: The segmentation results of the proposed method were clinically acceptable for the qualitative evaluation. For the quantitative evaluation, the fivefold CV accuracy of the classification for the four subtypes was 72.7%. This classification system was reliable with the area under curve (in ROC analysis) being greater than 0.8 for four two-class problems. Conclusions: The proposed hemispherical projection algorithm based on backtracking search can successfully segment sutures of the cranial vault. The classification system can also offer a desirable performance. As a result, the proposed segmentation and classification system is expected to bring insights into clinic research and the selection of the spring force to facilitate widespread application of this minimally invasive treatment.

BACKGROUND Epithelioid inflammatory myofibroblastic sarcoma (E-IMS) is a recently established rare variant of inflammatory myofibroblastic tumor. It is characterized by a distinctive constellation of clinical, pathological, and molecular features, including a nearly exclusive intraabdominal location, strong male predilection, aggressive clinical course, predominance of epithelioid tumor cells, and Ran-binding protein 2 (RANBP2)-anaplastic lymphoma kinase (ALK) fusion in the majority of cases. To the authors’ knowledge, the cytologic features of E-IMS have not been described to date. METHODS Cases of E-IMS that had corresponding cytology were searched. Six cytology samples (1 fine-needle aspiration sample, 2 imprint samples, and 3 effusion fluids) containing tumor cells were identified in 5 patients with E-IMS. RESULTS The cytomorphology included large monotonous epithelioid cells arranged in loose aggregates or singly, with admixed myxoid stroma, and an inflammatory background rich in neutrophils. The tumor cells had a large, round, eccentric nucleus with vesicular chromatin, prominent nucleoli, and moderate amounts of pale cytoplasm. Delicate thin-walled branching vessels traversing tumor aggregates was a prominent feature in a fine-needle aspiration sample. Immunohistochemically, ALK was positive in all 5 tumors, with a nuclear membranous staining pattern noted in 3 cases and a cytoplasmic pattern observed in the other 2 cases. ALK rearrangement was confirmed in all 5 tumors by molecular genetic studies. CONCLUSIONS The cytologic features of E-IMS recapitulate its histologic characteristics. E-IMS merits inclusion in the differential diagnosis of any intraabdominal, large epithelioid cell neoplasm. Confirmation of ALK rearrangement is advisable because patients may benefit from targeted therapies. Cancer (Cancer Cytopathol) 2015;123:495–504. © 2015 American Cancer Society.

Purpose: Cardiac computed tomography (CT) is widely used in clinical diagnosis of cardiovascular diseases. Whole heart segmentation (WHS) plays a vital role in developing new clinical applications of cardiac CT. However, the shape and appearance of the heart can vary greatly across different scans, making the automatic segmentation particularly challenging. The objective of this work is to develop and evaluate a multiatlas segmentation (MAS) scheme using a new atlas ranking and selection algorithm for automatic WHS of CT data. Research on different MAS strategies and their influence on WHS performance are limited. This work provides a detailed comparison study evaluating the impacts of label fusion, atlas ranking, and sizes of the atlas database on the segmentation performance. Methods: Atlases in a database were registered to the target image using a hierarchical registration scheme specifically designed for cardiac images. A subset of the atlases were selected for label fusion, according to the authors’ proposed atlas ranking criterion which evaluated the performance of each atlas by computing the conditional entropy of the target image given the propagated atlas labeling. Joint label fusion was used to combine multiple label estimates to obtain the final segmentation. The authors used 30 clinical cardiac CT angiography (CTA) images to evaluate the proposed MAS scheme and to investigate different segmentation strategies. Results: The mean WHS Dice score of the proposed MAS method was 0.918 ± 0.021, and the mean runtime for one case was 13.2 min on a workstation. This MAS scheme using joint label fusion generated significantly better Dice scores than the other label fusion strategies, including majority voting (0.901 ± 0.276, p < 0.01), locally weighted voting (0.905 ± 0.0247, p < 0.01), and probabilistic patch-based fusion (0.909 ± 0.0249, p < 0.01). In the atlas ranking study, the proposed criterion based on conditional entropy yielded a performance curve with higher WHS Dice scores compared to the conventional schemes (p < 0.03). In the atlas database study, the authors showed that the MAS using larger atlas databases generated better performance curves than the MAS using smaller ones, indicating larger atlas databases could produce more accurate segmentation. Conclusions: The authors have developed a new MAS framework for automatic WHS of CTA and investigated alternative implementations of MAS. With the proposed atlas ranking algorithm and joint label fusion, the MAS scheme is able to generate accurate segmentation within practically acceptable computation time. This method can be useful for the development of new clinical applications of cardiac CT.

Purpose: Myocardium segmentation in cardiac magnetic resonance (MR) images plays a vital role in clinical diagnosis of the cardiovascular diseases. Because of the low contrast and large variation in intensity and shapes, myocardium segmentation has been a challenging task. A dynamic programming (DP) based segmentation method, incorporating the likelihood and shape information of the myocardium, is developed for segmenting myocardium in cardiac MR images. Methods: The endocardium, i.e., the left ventricle blood cavity, is segmented for initialization, and then the optimal epicardium contour is determined using the polar-transformed image and DP scheme. In the DP segmentation scheme, three techniques are proposed to improve the segmentation performance: (1) the likelihood image of the myocardium is constructed to define the external cost in the DP, thus the cost function incorporates prior probability estimation; (2) the adaptive search range is introduced to determine the polar-transformed image, thereby excluding irrelevant tissues; (3) the connectivity constrained DP algorithm is developed to obtain an optimal closed contour. Four metrics, including the Dice metric (Dice), root mean squared error (RMSE), reliability, and correlation coefficient, are used to assess the segmentation accuracy. The authors evaluated the performance of the proposed method on a private dataset and the MICCAI 2009 challenge dataset. The authors also explored the effects of the three new techniques of the DP scheme in the proposed method. Results: For the qualitative evaluation, the segmentation results of the proposed method were clinically acceptable. For the quantitative evaluation, the mean (Dice) for the endocardium and epicardium was 0.892 and 0.927, respectively; the mean RMSE was 2.30 mm for the endocardium and 2.39 mm for the epicardium. In addition, the three new techniques in the proposed DP scheme, i.e., the likelihood image of the myocardium, the adaptive search range, and the connectivity constrained DP algorithm, improved the segmentation performance for the epicardium with 0.029, 0.047, and 0.007 in terms of the Dice and 0.98, 1.31, and 0.21 mm in terms of the RMSE, respectively. Conclusions: The three techniques (the likelihood image of the myocardium, the adaptive search range, and the connectivity constrained DP algorithm) can improve the segmentation ability of the DP method, and the proposed method with these techniques has the ability to achieve the acceptable segmentation result of the myocardium in cardiac MR images. Therefore, the proposed method would be useful in clinical diagnosis of the cardiovascular diseases.

BACKGROUND The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated. METHODS A total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections. RESULTS The majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Mullerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers. CONCLUSIONS A WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions. Cancer (Cancer Cytopathol) 2014;122:586–595. © 2014 American Cancer Society.

Chordoma is a neoplasm of notochordal differentiation that typically occurs in the axial skeleton. Accurate diagnosis is therapeutically important but can be challenging, especially in fine-needle aspiration (FNA) and core needle biopsy (CNB). Immunohistochemistry for the transcription factor brachyury (T) has recently proven diagnostically useful in whole-tissue sections. Our aim was to compare brachyury performance with conventional markers (S-100, EMA, keratin) and to evaluate its utility in distinguishing chordoma from cytomorphologic mimics. Brachyury immunohistochemistry was performed on chordoma (8 FNA, 12 CNB), chondrosarcoma (10 FNA), and metastatic mucinous adenocarcinoma (12 FNA). Immunohistochemistry performed at the time of diagnosis was also reviewed. Brachyury was positive in 17 (85%) cases of chordoma and typically showed moderate-to-strong nuclear staining. Of five sets of concurrent FNA and CNB, four pairs were positive for brachyury in both samples and one pair was positive for brachyury in the CNB and negative in the cell block. S-100, EMA, and keratin stains were available for 13 chordomas: 9 (69%) cases (including the 3 negative for brachyury) were positive for S-100 and keratin or EMA; 4 cases were keratin positive but S-100 negative. No nuclear brachyury staining was seen in chondrosarcoma or adenocarcinoma, though two adenocarcinomas showed cytoplasmic staining. Brachyury separates chordoma from cytomorphologic mimics with high sensitivity and specificity in small biopsies. As a single test, brachyury has higher sensitivity than a combined panel of S-100 and epithelial markers. When added to the conventional panel, brachyury increases sensitivity to 100% without sacrificing specificity.

The past 20 years have witnessed extraordinary advances in the field of cytogenetics, with the discovery that a multitude of neoplasms is characterized by identifiable chromosomal changes. The ability of Cytogenetics to aid in the identification and precise classification of a variety of neoplasms has not gone unnoticed by Cytology. In particular, Cytology has recognized Cytogenetics as a welcome companion in the evaluation of soft tissue tumors, lymphomas, renal and urothelial tumors, and mesothelioma. This relationship requires a good understanding of the proper handling of specimens for optimal evaluation by Cytogenetics. The marriage of Cytology and Cytogenetics will likely grow stronger as more solid tumors (eg, salivary gland neoplasms) are discovered that harbor characteristic chromosomal abnormalities. Cancer (Cancer Cytopathol) 2012;000:000–000. V C 2012 American Cancer Society. ‘‘Dearly Beloved, we are gathered here to join in happy matrimony ... ’’ Cytology and Cytogenetics?! Could anyone imagine a more unlikely pair? Cytology: mature, established, and unpretentious; and Cytogenetics: young, hip, flirtatious. Yet friends have been noticing the growing attraction between the two in recent years; therefore, few were truly surprised when the engagement was announced. To understand the growing connection, it helps to understand the individuals a bit better. Cytogenetics In the past 2 decades, Cytogenetics, devoted to the study of chromosomes, has witnessed remarkable development with significant relevance to the science and clinical practice of oncology. For the hematologist, recurring chromosomal abnormalities are important diagnostic and prognostic indicators. The identification of specific chromosomal changes in solid tumors lagged behind hematologic malignancies for technical reasons, mostly related to obtaining sufficient representative tumor cells for study, but recent years have witnessed burgeoning discovery. Beyond the clinical relevance of cytogenetic studies for diagnosis, prognosis, and treatment, Cytogenetics is used in gene mapping and gene identification and has led to the cloning of genes responsible for specific diseases. Currently, various approaches are used to provide evidence of chromosomal and molecular aberrations in

Although primary basal cell carcinoma (BCC) represents an extremely common malignancy, metastases derived from BCC are exceedingly rare. The prognosis for metastatic BCC is poor, and little consensus exists regarding predictive factors or optimal treatment strategies. Here, we present the case of a 63-year-old man with BCC of the neck who subsequently developed multiple metastases to subcutaneous tissue, lymph nodes, and the parotid gland. Risk factors and clinical features of metastatic BCC are reviewed, as is the relationship of histopathologic subtype to metastatic behavior. Current chemotherapeutic and targeted therapies also are discussed in the context of recent advances in molecular biology. Gropper AB, Girouard SD, Hojman LP, Huang SJ, Qian X, Murphy GF, Vleugels RA. Metastatic basal cell carcinoma of the posterior neck: case report and review of the literature.

BACKGROUND. Ependymoma cells are known to occasionally exfoliate into cerebrospinal fluid (CSF). However, the frequency of CSF involvement in patients with ependymoma is unclear, and to the authors' knowledge the cytomorphologic features of the tumor cells have not been described in detail to date. In this study, the CSF findings in patients with ependymal neoplasms are summarized and the cytomorphologic features of ependymoma, including its variants, are illustrated. METHODS. A search of the pathology databases of 2 medical centers was performed to identify all patients with a histologic diagnosis of ependymoma in whom CSF samples were examined. Slides from CSF samples originally reported as atypical, suspicious, or positive were reviewed and the cytomorphologic features assessed. Follow-up included a review of the medical records and histologic correlation. RESULTS. In all, 177 patients with a diagnosis of ependymoma were identified. Of these, 48 had a total of 94 cytologic preparations of CSF. Positive, suspicious, atypical, negative, and nondiagnostic results were noted in 6.4%, 5.3%, 4.3%, 79.7%, and 4.3%, respectively, of the specimens. The detection rate of tumor cells in CSF was 6.7% in 15 adults and 21.2% in 33 children, with an overall rate of 16.7%. Of the 8 patients with positive and/or suspicious diagnoses, 5 ependymomas exhibited anaplastic features and 1 tumor was a myxopapillary ependymoma. The positive samples were usually hypercellular, with cohesive epithelioid cells; long cytoplasmic processes resembling bipolar tanycytes were observed in the tanycytic variant of ependymoma. CONCLUSIONS. Exfoliated cells from ependymomas are recognizable in CSF samples, especially in patients with myxopapillary tumors and tumors with anaplastic features. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.

Purpose: Cerebrospinal fluid (CSF) segmentation in computed tomography (CT) is a key step in computer-aided detection (CAD) of acute ischemic stroke. Because of image noise, low contrast and intensity inhomogeneity, CSF segmentation has been a challenging task. A region-based active contour model, which is insensitive to contour initialization and robust to intensity inhomogeneity, was developed for segmenting CSF in brain CT images. Methods: The energy function of the region-based active contour model is composed of a range domain kernel function, a space domain kernel function, and an edge indicator function. By minimizing the energy function, the region of edge elements of the target could be automatically identified in images with less dependence on initial contours. The energy function was optimized by means of the deepest descent method with a level set framework. An overlap rate between segmentation results and the reference standard was used to assess the segmentation accuracy. The authors evaluated the performance of the proposed method on both synthetic data and real brain CT images. They also compared the performance level of our method to those of region-scalable fitting (RSF) and global convex segment (GCS) models. Results: For the experiment of CSF segmentation in 67 brain CT images, their method achieved an average overlap rate of 66% compared to the average overlap rates of 16% and 46% from the RSF model and the GCS model, respectively. Conclusions: Their region-based active contour model has the ability to achieve accurate segmentation results in images with high noise level and intensity inhomogeneity. Therefore, their method has great potential in the segmentation of medical images and would be useful for developing CAD schemes for acute ischemic stroke in brain CT images.