Cytologic mimics of non-Hodgkin lymphoma in the head and neck.

Non-lymphoid small round blue cell tumors of the head and neck are particularly difficult to diagnose when metastatic to a lymph node. The cytopathologist or surgical pathologist evaluating these lesions has to be aware of the various non-hematopoetic neoplasms that present in the head and neck area that can mimic non-Hodgkin lymphoma. Presented here are the various lesions commonly seen which needs to be entertained depending on where in the head and neck the lesion is located. More recently, a plethora of HPV related head and neck tumors has been described and these lesions add to the mix in this challenging milieu of cases.

High focal adhesion kinase expression in breast carcinoma is associated with lymphovascular invasion and triple-negative phenotype.

BACKGROUND: Focal adhesion Kinase (FAK) is a nonreceptor protein tyrosine kinase that is overexpressed in tumors and plays a significant role in tumor survival and metastasis. The purpose of the study is to perform correlation of FAK expression with patient prognostic factors using tissue microarrays (TMA) samples. METHODS: We analyzed FAK expression by immunohistochemical staining in 196 breast primary tumor samples from stage II-IV patients and in 117 metastatic tissues matched to the primary tumors using TMA that were stained with FAK monoclonal antibody. RESULTS: High FAK expression in primary tumors was associated with a younger age of patients (p = 0.033), lymphovascular invasion (p = 0.001) and with the triple-negative phenotype (p = 0.033). FAK expression in 117 metastatic tissues positively correlated with FAK expression in matched primary tumors by Spearman correlation analysis. In addition, a strong positive correlation was observed between high FAK expression and shorter overall survival and progression free survival in patients with metastatic tumors. CONCLUSIONS: The data demonstrate a high potential for FAK as a therapeutic target, especially in triple-negative breast cancer patients with high FAK expression.

Acute cholecystitis: do sonographic findings and WBC count predict gangrenous changes?

OBJECTIVE: The purpose of our study was to determine, first, if gallbladder wall striations in patients with sonographic findings suspicious for acute cholecystitis are associated with gangrenous changes and certain histologic features; and, second, if WBC count or other sonographic findings are associated with gangrenous cholecystitis. MATERIALS AND METHODS: Sixty-eight patients who underwent cholecystectomies within 48 hours of sonography comprised the study group. Sonograms and reports were reviewed for wall thickness, striations, Murphy sign, pericholecystic fluid, wall irregularity, intraluminal membranes, and luminal short-axis diameter. Medical records were reviewed for WBC count and pathology reports for the diagnosis. Histologic specimens were reviewed for pathologic changes. Statistical analyses tested for associations between nongangrenous and gangrenous cholecystitis and sonographic findings and for associations between wall striations and histologic features. RESULTS: Ten patients had gangrenous cholecystitis and 57, nongangrenous cholecystitis. One had cholesterolosis. Thirty patients had wall striations: 60% had gangrenous and 42% nongangrenous cholecystitis. There was no association with the pathology diagnosis (p = 0.32). There was no association between any histologic feature and wall striations (p ≥ 0.19). A Murphy sign was reported in 70% of patients with gangrenous cholecystitis and in 82% with nongangrenous cholecystitis; there was no association with the pathology diagnosis (p = 0.39). Wall thickness and WBC count were greater in patients with gangrenous cholecystitis than in those with nongangrenous cholecystitis (p ≤ 0.04). CONCLUSION: Gallbladder wall thickening and increased WBC counts were associated with gangrenous cholecystitis; however, there was considerable overlap between the two groups. Wall striations and a negative Murphy sign were not associated with gangrenous cholecystitis.

Identification of a Subset of Stage I Colorectal Cancer Patients With High Recurrence Risk.

BACKGROUND: A challenge in early-stage colorectal cancer (CRC) is identifying biomarkers that predict an increased risk for recurrence. A potential clinically adaptable biomarker is focal adhesion kinase (FAK), a tyrosine kinase that promotes invasion and metastasis. METHODS: An initial, single-institution, 298-patient cohort with all stages of CRC and long-term follow-up was assessed for FAK with tissue microarrays using immunohistochemistry. FAK expression was scored and dichotomized into high and low. Subsequently, a validation cohort of 517 early-stage CRCs from a separate institution was evaluated. All statistical tests were 2-sided. RESULTS: FAK overexpression did not correlate with any known histologic feature and was an early event in CRC, increasing from normal colon to stage I, and stage I to II, but not different at higher stages. High FAK was associated with decreased 10-year recurrence-free survival (RFS) among stage I patients (70.2% for high FAK vs 94.1% for low, P = .02), but not among higher stages in the initial cohort. The same finding was seen in the validation cohort (73.1% for high FAK vs 93.1% for low, P = .004). Multivariable survival analysis for stage I patients showed only two statistically significant factors predicting RFS: FAK (hazard ratio = 5.27, 95% confidence interval = 1.81 to 15.33, P = .002) and perineural invasion (hazard ratio = 7.38, 95% confidence interval = 1.01 to 53.96, P = .049). FAK was the only statistically significant factor in multivariable analysis across RFS, overall, and disease-specific survivals. CONCLUSIONS: High FAK expression identified a subset of stage I CRC patients with high incidence of recurrence and reduced survival, suggesting that FAK has important prognostic value. These patients would immediately benefit from more rigorous surveillance protocols for recurrent disease.

A role for the epithelial microenvironment at tumor boundaries: evidence from Drosophila and human squamous cell carcinomas.

Recent work has shown an increasing appreciation for the importance of the tumor environment, most commonly the overlying stroma. Less emphasis has been placed on the importance of local communication between transformed cells and their neighbors within the epithelium at tumor boundaries. We previously reported a Drosophila model that highlighted the importance of local interactions within the epithelial microenvironment: Src-transformed cells (Csk-deficient) were influenced by their immediate normal neighbors. The result was a consistent change in 'border cells' at the edge of transformed patches including delocalized p120-catenin and E-cadherin as well as invasive migration through the basal lamina. Here we show that the invasive properties of the boundary cells depend on up-regulation of Drosophila matrix metalloproteinase-1 as assessed by promoter activity, protein levels, in situ enzymatic activity, and tests of genetic modifier activity. Further, we provide evidence that these events at tumor borders may be evolutionarily conserved. We detected changes in 'boundary cells' within histological sections of human squamous cell carcinomas that were similar to those observed in Drosophila: both E-cadherin and p120-catenin exhibited normal junctional localization at the centers of the tumors but were reduced or delocalized at the boundary. Further, matrix metalloproteinase-2 was up regulated within these same boundary cells. These results support the view that local cell-cell interactions within the epithelial microenvironment impact tumor invasion and progression.

Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial.

BACKGROUND: Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. METHODS: Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II-III (> or = T2 and/or > or = N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m(2)) plus docetaxel (75 mg/m(2)) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. FINDINGS: Of the 120 patients initially enrolled, one withdrew after signing consent and one patient's baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline, DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group. At 3 months, 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs (p=0.054). The most common grade 3-4 toxicities were infection (five of 60 patients in the zoledronic acid group and six of 59 in the control group) and thrombosis (five of 60 in the zoledronic acid and two of 59 in the control group). There was one documented case of osteonecrosis in the zoledronic acid group. INTERPRETATION: Zoledronic acid administered with chemotherapy resulted in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery. Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs. FUNDING: Novartis Pharmaceuticals and Pfizer Inc.

Role of ProExC: a novel immunoperoxidase marker in the evaluation of dysplastic squamous and glandular lesions in cervical specimens.

Minichromosome maintenance and topoisomerase II alpha proteins play an important role in the regulation of eukaryotic DNA replication, and are overexpressed in a number of dysplastic and malignant tissues. ProExC antibody is a novel biomarker cocktail containing antibodies against topoisomerase II alpha and minichromosome maintenance 2 proteins. Our purpose was to evaluate the sensitivity, specificity, and predictive value of ProExC in dysplastic squamous and glandular lesions of the cervix. Nine low-grade squamous intraepithelial lesion, 35 high-grade squamous intraepithelial lesion, 23 squamous metaplasia, and 14 adenocarcinoma in situ specimens were retrieved from our hospital files. ProExC immunostaining was performed. ProExC had sensitivity, specificity, and positive and negative predictive value of 89%, 100%, 100%, and 82%, respectively, for distinguishing high-grade squamous intraepithelial lesion from squamous metaplasia, and 93%, 100%, 100%, and 98%, respectively, for distinguishing adenocarcinoma in situ from reactive benign endocervix. ProExC is a valuable marker for distinguishing dysplastic squamous and endocervical lesions of the cervix from squamous metaplasia in histologic sections. ProExC may eventually be used in conjunction with morphologic and human papillomavirus evaluation for better classification of indeterminate cervical lesions in Papanicolaou smears.

Exclusion of malignancy in thyroid nodules with indeterminate fine-needle aspiration cytology after negative 18F-fluorodeoxyglucose positron emission tomography: interim analysis.

BACKGROUND: In all, 20% of fine-needle aspiration (FNA) biopsies of thyroid nodules have an indeterminate diagnosis; of these, 80% are found to be benign after thyroidectomy. Some previous reports indicate that positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) imaging may predict malignancy status. We now report results on the first 51 patients in the largest prospective study of FDG-PET in patients with an indeterminate thyroid nodule FNA. METHODS: Eligible patients had a dominant thyroid nodule that was palpable or >or=1 cm in greatest dimension as seen by ultrasonography, and indeterminate histology of the FNA biopsy specimen. Participants underwent preoperative neck FDG-PET alone or FDG-PET with computed tomography (FDG-PET/CT). Images were evaluated qualitatively and semiquantitatively using the maximum standardized uptake value (SUV(max)). Final diagnosis was determined by histopathologic analysis after thyroidectomy. Descriptive statistical analysis was performed. RESULTS: A total of 51 patients underwent preoperative FDG-PET or FDG-PET/CT. Studies without focally increased uptake localized to the lesion were considered negative. For all lesions (10 malignant, 41 benign), the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) were 80%, 61%, 33%, and 93%, respectively. Postoperatively, two malignant and six benign lesions were found to be <1 cm by pathology examination; one lesion was not measured. When these lesions were excluded, the sensitivity, specificity, PPV, and NPV were 100%, 59%, 36%, and 100%, respectively. CONCLUSIONS: Based on these preliminary data, FDG-PET may have a role in excluding malignancy in thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing accrual to our target population of 125 participants.

Impact of a deep learning assistant on the histopathologic classification of liver cancer.

Artificial intelligence (AI) algorithms continue to rival human performance on a variety of clinical tasks, while their actual impact on human diagnosticians, when incorporated into clinical workflows, remains relatively unexplored. In this study, we developed a deep learning-based assistant to help pathologists differentiate between two subtypes of primary liver cancer, hepatocellular carcinoma and cholangiocarcinoma, on hematoxylin and eosin-stained whole-slide images (WSI), and evaluated its effect on the diagnostic performance of 11 pathologists with varying levels of expertise. Our model achieved accuracies of 0.885 on a validation set of 26 WSI, and 0.842 on an independent test set of 80 WSI. Although use of the assistant did not change the mean accuracy of the 11 pathologists (p = 0.184, OR = 1.281), it significantly improved the accuracy (p = 0.045, OR = 1.499) of a subset of nine pathologists who fell within well-defined experience levels (GI subspecialists, non-GI subspecialists, and trainees). In the assisted state, model accuracy significantly impacted the diagnostic decisions of all 11 pathologists. As expected, when the model's prediction was correct, assistance significantly improved accuracy (p = 0.000, OR = 4.289), whereas when the model's prediction was incorrect, assistance significantly decreased accuracy (p = 0.000, OR = 0.253), with both effects holding across all pathologist experience levels and case difficulty levels. Our results highlight the challenges of translating AI models into the clinical setting, and emphasize the importance of taking into account potential unintended negative consequences of model assistance when designing and testing medical AI-assistance tools.

Pancreatitis is frequent among patients with side-branch intraductal papillary mucinous neoplasia diagnosed by EUS.

BACKGROUND: Because of greater recognition and improved imaging capabilities, intraductal papillary mucinous neoplasms (IPMNs) are being diagnosed with increasing frequency. IPMNs of the main pancreatic duct cause symptoms and lead to pancreatitis. Side-branch (SB) IPMNs are thought to cause symptoms less frequently, and their association with pancreatitis is not well defined. OBJECTIVE: Our purpose was to ascertain whether an association exists between SB-IPMN and pancreatitis. DESIGN: Single-center, retrospective study. SETTING: Academic medical center. PATIENTS: A total of 305 patients underwent EUS examinations between October 2002 and October 2006 for pancreatic cystic lesions. MAIN OUTCOME MEASUREMENT: The main outcome measure was the frequency of acute or chronic pancreatitis that was not procedurally related. RESULTS: Thirty-two patients had SB-IPMNs, and 11 (34%) had pancreatitis. Three patients reported a single episode, and 8 patients reported having recurrent episodes of pancreatitis. Overall, 17 (53%) patients had symptoms possibly attributable to SB-IPMN. Female sex (73% vs 38%) and multiple pancreatic lesions (54% vs 24%) were more commonly seen in those with pancreatitis, but were not statistically significant factors. Larger cyst size or cyst fluid marker levels did not appear associated with pancreatitis occurrence. EUS-FNA demonstrated communication with the pancreatic duct in 94% and thick, mucinous fluid in 84%. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Pancreatitis was frequently associated with the presence of SB-IPMNs in our referral practice. SB-IPMNs should be considered in the differential diagnosis of patients with recurrent pancreatitis with cystic lesions seen on imaging studies. EUS-FNA was the most useful modality in helping to differentiate SB-IPMNs from other lesions.

Reliability of gross visual assessment of specimen adequacy during EUS-guided FNA of pancreatic masses.

BACKGROUND: In many centers, on-site cytopathologists are not available during EUS-guided FNA (EUS-FNA) examinations. Often, endosonographers request that technologists assess the adequacy of FNA by gross inspection of the slides. To date, there has not been a study that assessed the accuracy of experienced technologists in predicting tissue sampling adequacy by gross inspection before cytologic staining. OBJECTIVES: To assess a grading system used by cytotechnologists and EUS technologists during gross inspection of FNA slides in reliably predicting specimen adequacy compared with the final cytologic diagnoses. DESIGN: Prospective, double-blind, controlled study. SETTING: Academic tertiary-referral center with a high-volume EUS practice. PATIENTS: Fifty-one patients with a suspected solid pancreatic mass who were undergoing planned EUS-FNA. MAIN OUTCOME MEASUREMENTS: The degree of correlation in the assessment of specimen adequacy as exhibited by a weighted kappa statistic between 2 groups of technologists and a board-certified cytopathologist. RESULTS: FNA was performed in 37 cases with 234 individual slide specimens available for analysis. Only fair agreement was observed between cytotechnologists and EUS technologists versus final cytopathologic assessment of adequacy (kappa 0.20 and 0.19, respectively). The routine practice of 6 to 7 FNA passes yielded adequate tissue for assessment in 36 of 37 patients (97%). LIMITATIONS: Interobserver variability, single center, and findings applicable only to solid pancreatic lesions. CONCLUSIONS: Neither trained EUS technologists nor cytotechnologists were able to provide a reliable assessment of pancreatic-mass FNA adequacy by using gross visual inspection of the specimen on a slide. Rapid on-site cytopathology reduced the number of passes, ensured specimen adequacy, provided definitive diagnosis, and should be used in centers where available.

Isolation and molecular profiling of bone marrow micrometastases identifies TWIST1 as a marker of early tumor relapse in breast cancer patients.

PURPOSE: Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: Enrichment of TACSTD1 (EpCAM)-expressing cells from bone marrow of breast cancer patients was achieved using immunomagnetic beads. Gene expression profiles were compared between enriched cell populations and whole bone marrow from 5 normal volunteers and 23 breast cancer patients after neoadjuvant chemotherapy treatment. Enriched cells from bone marrow samples of breast cancer patients before treatment or at 1 year follow-up were also analyzed (total of 87 data sets). The expression of transcripts specifically detected in enriched cell populations from breast cancer patients was correlated with 1-year clinical outcome using quantitative reverse transcription-PCR in an independent cohort of bone marrow samples. RESULTS: Analysis of EpCAM-enriched bone marrow cells revealed specific expression of a subgroup of transcripts, including the metastasis regulator, TWIST1. Most transcripts identified, including TWIST1, were not expressed in enriched populations of bone marrow from normal volunteers, suggesting that this expression profile reflects a signature of breast cancer bone marrow micrometastases that persist after chemotherapy. In an independent set of bone marrow samples obtained before any treatment, TWIST1 expression correlated with early disease relapse. CONCLUSIONS: Disseminated breast cancer cells present in bone marrow after chemotherapy possess unique transcriptional signatures. Genes whose expression is overrepresented in these cell populations, such as TWIST1, may prove to be excellent markers of early distant relapse in breast cancer patients.

Fine-needle aspiration cytology of thymic basaloid carcinoma: case studies and review of the literature.

We report the features in fine-needle aspiration biopsy (FNAB) of thymic basaloid carcinomas. This is a rare neoplasm, of which there are only three documented in our hospital files. To the best of our knowledge, this is the first fine-needle aspiration (FNA) report on basaloid carcinoma of the thymus. This is a tumor in which the FNA diagnosis is difficult and the differential diagnosis is broad. We describe the cytologic features encountered in the three cases, and immunohistochemical and ultrastructural findings so as to raise awareness of this entity in the differential diagnosis of thymic neoplasms on FNABs. The cases studied included three male patients, aged 73, 65, and 50, who presented with anterior mediastinal masses, with no primary tumor elsewhere. FNAB was performed on two cases, followed by thymectomy. One case, additionally, had metastasis to a cervical lymph node, and the other two were associated with thymic cysts. The diagnoses on all three cases were thymic basaloid carcinoma.

Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation.

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples.A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation. The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions.

Primary pancreatic leiomyosarcoma with metastasis to the liver diagnosed by endoscopic ultrasound-guided fine needle aspiration and fine needle biopsy: A Case Report and Review of Literature.

Primary pancreatic leiomyosarcomas are rare tumors of the pancreas that are usually diagnosed after resection or by biopsy. One case in the literature has utilized endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology. We report a second case of a primary pancreatic leiomyosarcoma that yielded diagnostic material on EUS-FNA cytology. A 72-year-old female presented with 3-4 months of abdominal pain. A CT scan showed a large heterogeneous, lobulated pancreatic head and uncinate mass and multiple hypoattenuating liver lesions. An EUS-FNA was performed on one of the liver lesions with a 25-gauge needle, yielding an adequate sample with lesional cells. The initial read was a spindle cell neoplasm. A subsequent endoscopic ultrasound-guided fine needle biopsy with a 22-gauge needle was performed on the pancreatic head mass to rule out two primaries and to provide tissue for a mitotic index in the case of gastrointestinal tumor. Both the cell block of the EUS-FNA and the core biopsy were equally cellular and showed interlacing spindle cells that stained positive for SMA and negative for DOG-1, CD 117, and CD34. In addition, the core biopsy of the pancreas stained positive for Desmin. A diagnosis of a primary pancreatic leiomyosarcoma was made and the patient was started on systemic chemotherapy. Primary pancreatic leiomyosarcomas are rare pancreatic tumors that may yield diagnostic material by EUS-FNA with a 25-gauge needle. Diagn. Cytopathol. 2016;44:1070-1073. © 2016 Wiley Periodicals, Inc.

The value of ThinPrep and cytospin preparation in pleural effusion cytological diagnosis of mesothelioma and adenocarcinoma.

The diagnosis of malignant mesothelioma requires an integration of the clinical presentation, radiological studies, and immunohistochemical stain of histological sections. Cytological diagnosis on pleural effusions of mesothelioma and pulmonary adenocarcinoma is highly desirable but debatable. A spectrum of cytological features has been found to be associated more commonly with malignant mesothelioma (e.g., peripheral cytoplasmic skirt, bubbly cytoplasm, cyanophilic cytoplasm, and scalloped border of cell balls) vs. adenocarcinoma (e.g., two-cell population, inspissated cytoplasmic material, cytoplasmic vacuole, angulated and indented nuclei, and smooth border of cell balls) to only name a few. The current study is designed to assess whether the introduction of a liquid-based technology such as ThinPrep (TP) can provide additional diagnostic value in addition to the conventional cytospin Diff-Quik (DQ) preparations. Pleural effusion specimens were prepared with split samples for DQ-stained cytospin and Papanicolaou-stained liquid-based TP. Fifteen pleural effusion samples with immunohistologically confirmed malignant mesothelioma and 13 pleural effusion samples of immunohistologically confirmed pulmonary adenocarcinomas were retrieved from our files. Both DQ cytospin- and Papanicolaou-stained TP slides were evaluated for the known cytological features associated with malignant mesothelioma (25 cytological features) and adenocarcinoma (22 cytological features) without knowledge of the original cytological and histological diagnoses. The McNemar test was used to compare these two cytological preparations for both malignant mesothelioma and pulmonary adenocarcinoma. In the malignant mesothelioma group, 4 of 25 cytological features evaluated, bubbly cytoplasm (P = 0.002), vacuolated cytoplasm (P = 0.005), cell-in-cell arrangement (P = 0.007) and irregular nuclear contour (P = 0.083), were seen more frequently in the DQ cytospin preparation, as opposed to only one feature, nuclear size enlargement (P = 0.008), more readily seen using TP. In the pulmonary adenocarcinoma group, only 1 of 22 cytological features evaluated, presence of angulated or indented nuclei (P = 0.025), was seen more frequently in DQ as opposed to two features, presence of two- cell population (P = 0.04) and presence of micropapillary structures (P = 0.1), were seen more readily in TP. All other cytological features evaluated distinguishing mesotheliomas (20 features) and pleural adenocarcinomas (19 features) were seen equally readily in both types of specimen preparation techniques. This study suggests that the liquid-based TP preparation of pleural effusions does not appear to provide additional diagnostic value when compared with the DQ cytospin preparation in the cytological distinction between mesothelioma and adenocarcinoma in pleural effusions. Most cytological features evaluated, 20 of 25 (mesothelioma) and 19 of 22 (adenocarcinoma), can be seen in both preparation techniques.

Black Endobronchial Ultrasound.

The infrequent bronchoscopic finding of black airway pigmentation due to a variety of causes has been labeled as "Black Bronchoscopy." Black bronchioalveolar lavage has been sometimes described in tobacco, marijuana, and crack cocaine smokers. To add to this interesting panorama of bronchoscopic findings, we describe cases of black endobronchial ultrasound-guided transbronchial needle aspirates due to metastatic melanoma and anthracotic lymph nodes.

Pancreatic hepatoid carcinoma: a rare form of pancreatic neoplasm.

Primary pancreatic hepatoid carcinoma (PHC) is extremely rare, resembling hepatocellular carcinoma (HCC) in terms of morphology and immunohistochemical features. Hepatoid carcinoma can present in other organs, most noticeably in the stomach. PHC is present in two forms either a pure form like HCC or admixed with other histologic tumor components characteristic of the underlying primary site (endocrine tumors, ductal, or acinar adenocarcinomas). Here, we report a 69-year-old male patient with distal pancreatic mass incidentally found during a CT scan workup for a pulmonary nodule suspicious for metastatic prostate adenocarcinoma. We described the clinical, cytological, and histological finding and conducted a literature review.

Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages, and is associated with a high relapse rate. Patients in remission are ideal candidates for immunotherapy aimed at cure or prolonging disease-free periods. However, immunosuppressive pathways in the tumor microenvironment are obstacles to durable anti-tumor immunity. In a metastatic syngeneic mouse model of EOC, immunosuppressive macrophages and myeloid-derived suppressor cells (MDSCs) accumulate in the local tumor environment. In addition, resident peritoneal macrophages from non-tumor-bearing mice were highly immunosuppressive, abrogating stimulated T cell proliferation in a cell contact-dependent manner. Immunization with microparticles containing TLR9 and NOD-2 ligands (MIS416) significantly prolonged survival in tumor-bearing mice. The strategy of MIS416 immunization followed by anti-CD11b administration further delayed tumor progression, thereby establishing the proof of principle that myeloid depletion can enhance vaccine efficacy. In patients with advanced EOC, ascites analysis showed substantial heterogeneity in the relative proportions of myeloid subsets and their immunosuppressive properties. Together, these findings point to immunosuppressive myeloid cells in the EOC microenvironment as targets to enhance vaccination. Further studies of myeloid cell accumulation and functional phenotypes in the EOC microenvironment may identify patients who are likely to benefit from vaccination combined with approaches that deplete tumor-associated myeloid cells.

Fine needle aspiration of the thyroid: a cytohistologic correlation and study of discrepant cases.

OBJECTIVE: Fine needle aspiration (FNA) is a reliable method in the initial assessment of thyroid nodules. The purpose of this study was to evaluate the causes for discordance between the interpretation on FNA and the pathologic findings in the resected thyroid. METHODS: A computer search of all thyroidectomy specimens with previous FNA from January 1998 to December 2001 was obtained from the files of the Lauren V. Ackerman laboratory of surgical pathology, Barnes-Jewish Hospital. Excluded from the study were those FNAs performed for suspected and confirmed metastatic disease to the thyroid as well as those cases unavailable for review. A total of 45 FNA cases were identified with cytologic and histologic discrepancies. RESULTS: Of the 1253 individual thyroid FNA performed during the study period, 255 patients (20%) subsequently had an open surgical procedure on the thyroid. Of those who underwent surgery, 196 cases (77%) were concordant, whereas 45 patients (18%) were discordant, and 14 cases were excluded due to unavailability of slides for review (for example, returned consult slides). The causes of the 45 discordant cases were: 20 cases (44%) were unsatisfactory for diagnosis, 14 cases (31%) were due to interpretation error (false positive), and 11 cases (24%) were due to sampling error (false negative). CONCLUSIONS: The most common causes of our discrepant cases are those whose FNA diagnosis was interpreted as "unsatisfactory for diagnosis," in 20 (7.8%) of 255 surgical cases. The false negative rate due to sampling error in 11 (4%) of 255 cases was mainly due to the presence of microscopic papillary thyroid carcinoma (PTC); the false positive rate was due to interpretation error in 14 (6%) of 255 cases, and those were explained by the occurrence of overlapping cytologic features among adenomatous nodules, follicular neoplasms, the follicular variant of PTC, and Hashimoto's thyroiditis.