Classification of Metastatic Lymph Nodes In Vivo Using Quantitative Ultrasound at Clinical Frequencies.

Quantitative ultrasound (QUS) methods characterizing the backscattered echo signal have been of use in assessing tissue microstructure. High-frequency (30 MHz) QUS methods have been successful in detecting metastases in surgically excised lymph nodes (LNs), but limited evidence exists regarding the efficacy of QUS for evaluating LNs in vivo at clinical frequencies (2-10 MHz). In this study, a clinical scanner and 10-MHz linear probe were used to collect radiofrequency (RF) echo data of LNs in vivo from 19 cancer patients. QUS methods were applied to estimate parameters derived from the backscatter coefficient (BSC) and statistics of the envelope-detected RF signal. QUS parameters were used to train classifiers based on linear discriminant analysis (LDA) and support vector machines (SVMs). Two BSC-based parameters, scatterer diameter and acoustic concentration, were the most effective for accurately detecting metastatic LNs, with both LDA and SVMs achieving areas under the receiver operating characteristic (AUROC) curve ≥0.94. A strategy of classifying LNs based on the echo frame with the highest cancer probability improved performance to 88% specificity at 100% sensitivity (AUROC = 0.99). These results provide encouraging evidence that QUS applied at clinical frequencies may be effective at accurately identifying metastatic LNs in vivo, helping in diagnosis while reducing unnecessary biopsies and surgical treatments.

Keratin 17 Is a Novel Cytologic Biomarker for Urothelial Carcinoma Diagnosis.

OBJECTIVES: The microscopic features of urine cytology specimens are subjective and may not reliably distinguish between benign urothelial cells and low-grade urothelial carcinoma (UC). Prior studies demonstrated that keratin 17 (K17) detection in biopsies is highly sensitive for UC. The current study aimed to define K17 diagnostic test performance for initial screening and detect recurrent UC in urine specimens. METHODS: K17 was detected by immunocytochemistry (ICC) in consecutively collected urine specimens (2018-2019). A qualitative score for the K17 test was determined in 81 samples (discovery cohort) and validated in 98 samples (validation cohort). K17 sensitivity and specificity were analyzed in both cohorts across all grades of UC. RESULTS: Based on the discovery cohort, the presence of 5 or more K17 immunoreactive urothelial cells (area under the curve = 0.90; P < .001) was the optimal threshold to define a K17-positive test. The sensitivity of the K17 ICC test for biopsy-confirmed UC was 35 of 36 (97%) and 18 of 21 (86%) in the discovery and validation cohorts, respectively. K17 was positive in 16 of 19 (84%) specimens with biopsy-confirmed low-grade UC and in 34 of 34 (100%) of specimens with high-grade UC. CONCLUSIONS: K17 ICC is a highly sensitive diagnostic test for initial screening and detection of recurrence across all grades of UC.

Keratin 17 testing in pancreatic cancer needle aspiration biopsies predicts survival.

BACKGROUND: Although pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers, differences in survival exist between patients with clinically identical characteristics. The authors previously demonstrated that keratin 17 (K17) expression in PDAC, measured by RNA sequencing or immunohistochemistry (IHC), is an independent negative prognostic biomarker. Only 20% of cases are candidates for surgical resection, but most patients are diagnosed by needle aspiration biopsy (NAB). The aims of this study were to determine whether there was a correlation in K17 scores detected in matched NABs and surgical resection tissue sections and whether K17 IHC in NAB cell block specimens could be used as a negative prognostic biomarker in PDAC. METHODS: K17 IHC was performed for a cohort of 70 patients who had matched NAB cell block and surgical resection samples to analyze the correlation of K17 expression levels. K17 IHC was also performed in cell blocks from discovery and validation cohorts. Kaplan-Meier and Cox proportional hazards regression models were analyzed to determine survival differences in cases with different levels of K17 IHC expression. RESULTS: K17 IHC expression correlated in matched NABs and resection tissues. NAB samples were classified as high for K17 when ≥80% of tumor cells showed strong (2+) staining. High-K17 cases, including stage-matched cases, had shorter survival. CONCLUSIONS: K17 has been identified as a robust and independent prognostic biomarker that stratifies clinical outcomes for cases that are diagnosed by NAB. Testing for K17 also has the potential to inform clinical decisions for optimization of chemotherapeutic interventions.

A correlation study of mismatch repair immunohistochemical protein expression of pancreatic solid tumors in cytology cell blocks and matching surgical specimens.

INTRODUCTION: Only 15%-20% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) cases are surgically operable. Cytology samples may be the only source for guiding clinical management. Current research indicates that mismatch repair (MMR) status could be valuable for implementing novel treatment modalities. In this study, immunohistochemical (IHC) MMR protein expression on cytology cell blocks was compared with that of the correlating surgical resection specimens. MATERIALS AND METHODS: A retrospective review of 120 pancreatic solid tumor needle biopsies from 2016 to 2019 was performed, and 15 experimental cases were selected comprising of cellular (>100 tumor cells and >100 benign positive control cells that include benign ductal cells and/or lymphocytes) alcohol-prefixed formalin-fixed cytology cell blocks (CB), and corresponding subsequent surgical resections (Surg). The cases include 13 PDACs (87%), 1 (6.5%) low grade neuroendocrine tumor (PNET), and 1 (6.5%) acinar cell carcinoma (ACC). A routine four-panel (MLH1, MSH2, MSH6, and PMS2) MMR IHC testing was performed. The percentage of protein expression was evaluated and compared between individual CB-Surg pairs. RESULTS: About 8 of the 15 (53.3%) cytology cases showed matching protein expressivity with the surgical specimens for all four MMR markers (Table 1). The remaining 7 pairs (46.7%) appeared to have a partial concordance, including 6 values for which a surgical marker showed less expression, and 13 values for which a cytological marker showed less expression. [Table: see text] CONCLUSION: Cytology CB MMR protein panel testing could be a useful consideration for inoperable patients who would benefit from medical therapy such as immune checkpoint inhibition. However, the cellularity and overall quality of the CB is expected to be paramount in obtaining satisfactory IHC MMR results. The MMR results could be more confidently trusted when the staining is intact, but when not retained, they should be interpreted with caution in a low cellularity sample to avoid mistakenly identifying MMR-deficient tumors.

Single-Pass vs 2-Pass Endoscopic Ultrasound-Guided Fine-Needle Biopsy Sample Collection for Creation of Pancreatic Adenocarcinoma Organoids.

Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancies, with a 5-year survival rate <8%.1,2 Suspicious lesions are typically diagnosed via endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).3 Fewer needle passes decreases the risk of postprocedure complications, including pancreatitis and hemorrhage, while allowing additional needle passes to be used for adjuvant tissue testing, such as organoid creation and DNA sequencing.

A correlation study between thyroid imaging report and data systems and the Bethesda system for reporting thyroid cytology with surgical follow-up - an ultrasound-trained cytopathologist's experience.

INTRODUCTION: Thyroid Imaging Reporting and Data Systems (TI-RADS) including a modified system (M TI-RADS) and American College Radiology (ACR) TI-RADS are introduced. Correlation studies between both TI-RADSs and The Bethesda System for Reporting Thyroid Cytology (TBSRTC) for Ultrasound-guided fine-needle aspiration (US-FNA) cases with surgical follow-up (SFU) are presented. MATERIALS AND METHODS: Three hundred and forty six thyroid US-FNA cases performed at the US-FNA clinic of Stony Brook University Hospital by an Ultrasound-trained interventional Cytopathologist between December 1, 2014 to February 28, 2018 were reviewed. All ultrasound images from 346 cases were evaluated and assigned M TI-RADS scores based on ultrasound features present in Table 1. One hundred and fifty four cases from Dcember 1, 2014 to February 28, 2016 were assigned scores using ACR TI-RADS.TBSRTC category along with SFU data was collected and correlated with both TI-RADS scores by using Pearson's correlation coefficient (r). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy for M TI-RADS and TBSRTC were also calculated using SFU diagnosis as a gold standard. McNemar test was applied to evaluate the significance of the difference between M TI-RADS and TBSRTC. RESULTS: Based on 346 thyroid nodules studied, the overall r-value between M TI-RADS scores and TBSRTC categories is 0.465. The r-values between Composition, Echogenicity, Shape, Margin, Echogenic foci, the summary points, and the converted TR level of ACR TI-RADS and TBSRTC are 0.145, 0.042, 0.259, 0.310, 0.405, and 0.379, respectively. Fifty (14.5%) cases have SFUs. Considering TI-RADS 5&6 and TBSRTC 5&6 as positives, and TI-RADS 2 and TBSRTC 2 as negatives, the Sensitivity, Specificity, PPV, NPV, and accuracy are 96%, 53%, 76%, 89%, 79% for TI-RADS vs 100%, 93%, 96%, 100%, 97% for TBSRTC, respectively (P = .038). The data for indeterminate cases are summarized. CONCLUSION: Both TI-RADSs could be helpful to a moderate degree. M TI-RADS appeared to correlate to TBSRTC slightly better than that of ACR TI-RADS. TBSRTC is significantly more accurate than M TI-RADS for the majority of determined cases.

Oncogenic KRAS Reduces Expression of FGF21 in Acinar Cells to Promote Pancreatic Tumorigenesis in Mice on a High-Fat Diet.

BACKGROUND & AIMS: Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms. We investigated how oncogenic KRAS regulates the expression of fibroblast growth factor 21, FGF21, a metabolic regulator that prevents obesity, and the effects of recombinant human FGF21 (rhFGF21) on pancreatic tumorigenesis. METHODS: We performed immunohistochemical analyses of FGF21 levels in human pancreatic tissue arrays, comprising 59 PDAC specimens and 45 nontumor tissues. We also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells (KrasG12D/+ mice) and fElasCreERT mice (controls). KrasG12D/+ mice were placed on an HFD or regular chow diet (control) and given injections of rhFGF21 or vehicle; pancreata were collected and analyzed by histology, immunoblots, quantitative polymerase chain reaction, and immunohistochemistry. We measured markers of inflammation in the pancreas, liver, and adipose tissue. Activity of RAS was measured based on the amount of bound guanosine triphosphate. RESULTS: Pancreatic tissues of mice expressed high levels of FGF21 compared with liver tissues. FGF21 and its receptor proteins were expressed by acinar cells. Acinar cells that expressed KrasG12D/+ had significantly lower expression of Fgf21 messenger RNA compared with acinar cells from control mice, partly due to down-regulation of PPARG expression-a transcription factor that activates Fgf21 transcription. Pancreata from KrasG12D/+ mice on a control diet and given injections of rhFGF21 had reduced pancreatic inflammation, infiltration by immune cells, and acinar-to-ductal metaplasia compared with mice given injections of vehicle. HFD-fed KrasG12D/+ mice given injections of vehicle accumulated abdominal fat, developed extensive inflammation, pancreatic cysts, and high-grade pancreatic intraepithelial neoplasias (PanINs); half the mice developed PDAC with liver metastases. HFD-fed KrasG12D/+ mice given injections of rhFGF21 had reduced accumulation of abdominal fat and pancreatic triglycerides, fewer pancreatic cysts, reduced systemic and pancreatic markers of inflammation, fewer PanINs, and longer survival-only approximately 12% of the mice developed PDACs, and none of the mice had metastases. Pancreata from HFD-fed KrasG12D/+ mice given injections of rhFGF21 had lower levels of active RAS than from mice given vehicle. CONCLUSIONS: Normal acinar cells from mice and humans express high levels of FGF21. In mice, acinar expression of oncogenic KRAS significantly reduces FGF21 expression. When these mice are placed on an HFD, they develop extensive inflammation, pancreatic cysts, PanINs, and PDACs, which are reduced by injection of FGF21. FGF21 also reduces the guanosine triphosphate binding capacity of RAS. FGF21 might be used in the prevention or treatment of pancreatic cancer.

Temporal mandibular joint chondrocalcinosis (tophaceous pseudogout) diagnosed by ultrasound-guided fine-needle aspiration.

Tophaceous pseudogout is a calcium pyrophosphate dihydrate crystal (CPPD) deposition disease that frequently affects elderly patient in the temporomandibular joint (TMJ). A diagnosis of CPPD deposition disease in the TMJ is challenging due to its mimicking of other benign and malignant entities. Surgical exploration followed by histologic examination is by far the most frequently used diagnostic modality. We present a case of an 87-year-old female who presented with a right TMJ mass. A final diagnosis of tophaceous pseudogout was made on cellular material obtained by ultrasound-guided fine-needle aspiration (US-guided FNA). Based on our case and current available literature, ultrasound-guided FNA is a reliable tool for diagnosing tophaceous pseudogout of the TMJ.

A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device.

BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Primary Colonic Angiosarcoma Seen in a Patient on Calcium Channel Blocker: A Case Report with Summary Analysis of 32 Other Cases from the Literature.

BACKGROUND Angiosarcoma is a rare malignant mesenchymal tumor of vascular endothelial cell origin. Its occurrence in the colorectal region is extremely rare. Only 32 cases of primary colorectal angiosarcoma are reported in the current literature. Angiosarcoma in association with calcium channel blocker has been rarely reported. We present such a case of a patient who had been on levamlodipine besylate, a calcium channel blocker, for over 10 years. CASE REPORT A 53-year-old female with hypertension presented with a fever, a dry cough, and hematochezia. Computed tomography (CT) scan and angiography demonstrated a 6-cm vascular mass in the ileocecal region. The clinical symptoms stopped soon after a right hemicolectomy. The histopathology with immunohistochemical studies confirmed the diagnosis of angiosarcoma. Three months after surgery, the patient had evidence of recurrence of the tumor, however, she no longer presented with a fever or a dry cough. The patient was receiving chemotherapy at the time of the report. CONCLUSIONS Colorectal angiosarcoma is a rare malignancy of endothelial origin with uncertain etiology and often has a poor prognosis. Angiosarcoma seen in a patient taking calcium channel blocker is rare but alarming. CT scan and angiography are helpful tools to raise the suspicion of the diagnosis. A definitive pathological diagnosis relies on histopathology with immunohistochemical stains of endothelial markers. Surgical resection is still the best choice of the different treatment options.

Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment.

BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately, most patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) sampling in patients with PDA. METHODS: In this prospective clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was performed for initial onsite diagnosis. Two additional needle passes were performed with a 22-gauge FNB needle for organoid creation. Primary outcome was successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no passages), confirmed by organoid morphology and positive genotyping. RESULTS: Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA organoid lines for ≥5 passages of growth (P5, five passages) was reached in 25 of 38 tumors (66%). In the single patient with successful P5 FNB sampling-derived and P5 surgically derived organoids, there was identical matching of specimens. There were no serious adverse events. Two patients developed bleeding at the EUS-FNB puncture site requiring hemostasis clips. CONCLUSIONS: Pancreatic cancer organoids can be successfully and rapidly created by means of EUS-FNB sampling using a 22-gauge needle at the time of initial diagnosis. Successful organoid generation is essential for precision medicine in patients with pancreatic cancer in whom most are not surgically resectable. (Clinical trial registration number: NCT03140592.).

Strategies for building a successful ultrasound guided FNA practice in department of pathology-Experience at a university hospital.

INTRODUCTION: Although pathology services focused on fine needle aspiration (FNA) biopsy of superficial palpable masses with on-site cytological evaluation are available in a wide range of clinical and academic settings, the addition of ultrasound (US) guidance into FNA practice by a cytopathologist group can be challenging. An US-FNA service provided by a cytopathologist in the department of Pathology is a relatively new practice in the field of medicine. This report summarizes our experience and strategies in achieving this objective and our successful preliminary results. MATERIALS AND METHODS: The US-FNA service includes (1) an FNA procedure to be performed by a cytopathologist under US guidance; (2) onsite adequacy evaluation and diagnosis to be done by the same cytopathologist; and immediate patient consultation and sample triaging carried out by the same cytopathologist in an FNA suite within the department of Pathology. The FNA suite including a procedure room equipped with a portable US machine, an exam/procedure table, a mobile cabinet with FNA supplies, a counter with sink, and a reception room with waiting area is set-up. RESULTS: The establishment of the US-FNA service is successful. There is an incremental growth of the service over the first 8 months. Among the 114 cases performed during the first 8 months, the case type distribution is shown to be 50% thyroid nodules, 33% lymph nodes, 5.5% salivary gland masses, 3.5% breast masses, and 8% soft tissue masses. CONCLUSIONS: The authors' initial 8 months experience and strategies in setting up a new US-FNA practice in a new institution are discussed to highlight obstacles encountered and approaches that promoted the successful establishment of a new service. A conservative approach, focusing on building partnerships with existing clinical services, can be successfully implemented in most institutions, if appropriate strategies are applied. The main strategy is to ensure that the best interests of patients remain the primary focus and that everything possible is done to improve the quality and effectiveness of patient care by providing the best possible diagnostic US-FNA service, to enable optimal clinical management.

Risk of Delayed Human Papillomavirus Vaccination in Inner-City Adolescent Women.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. METHODS: We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. RESULTS: Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1-.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2-1.0] and 0.3 [95% CI, .1-.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2-.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0-8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7-26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen. CONCLUSIONS: Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities.

Ultrasound guided FNA of thyroid performed by cytopathologists enhances Bethesda diagnostic value.

BACKGROUND: Ultrasound (US) guided fine needle aspiration (FNA) biopsy of thyroid are examined and reported by cytopathologists based usually on The Bethesda System for Reporting Thyroid Cytopathology (BTC) regardless of the procedure's performers. This study is designed to determine whether there is any performer-dependent difference. METHODS: Six hundred and fifty-one thyroid US-FNAs in correlation with surgical follow-up (SFU) were studied. The statistical analysis was performed using the surgical pathology diagnosis as the gold standard. RESULTS: Among the 283 cases performed by cytopathologists, there were 8 (2.8%) nondiagnostic (BTC I), 197 (69.6%) benign (BTC II), 31 (11%) atypical (BTC III), 14 (5%) suspicious for follicular neoplasm (BTC IV), 12 (4.2%) suspicious for malignancy (BTC V), and 21 (7.4%) positive for malignancy (BTC VI), and there were 55 (19.4%) cases with SFU. The 368 cases performed by others showed 76 (21%) BTC I, 238 (65%) BTC II, 26 (7%) BTC III, 10 (3%) BTC IV, 9 (2.5%) BTC V 5, and 9 (2.5%) BTC VI, and there were 26 (7%) cases with SFU. The cytopathologist group achieved better sensitivity (91.3 vs.78%); slightly better specificity (83.3 vs. 82%); better positive predictive value (87.5 vs. 70%); similar negative predictive value (88.2 vs. 88%); and better overall accuracy (87.8 vs. 81%) compared with the non-cytopathologist group. Overall the difference for all statistical values is significant different (P = 0.041). CONCLUSION: US-FNA performed by cytopathologists showed a lower unsatisfactory rate and significantly better overall statistical values. Cytopathologists may play an important role in thyroid patient care. Diagn. Cytopathol. 2016;44:787-791. © 2016 Wiley Periodicals, Inc.

Fine-needle aspiration of small pulmonary nodules yields material for reliable molecular analysis of adenocarcinomas.

INTRODUCTION: Early molecular characterization with Kirsten rat sarcoma factor, epidermal growth factor, and anaplastic lymphoma kinase are critical to manage pulmonary adenocarcinoma. Fine-needle aspiration (FNA) of lesions <2 cm are routine in our institution and are used in molecular analysis. We report our experience. MATERIALS AND METHODS: We searched our databank for primary pulmonary adenocarcinomas diagnosed by FNA between January 2009 and April 2013. Size of the lesion aspirated, molecular results, and sample source (FNA versus surgical specimen) were recorded. We compared the frequency of mutations identified by FNA versus surgical specimens and the frequency of mutations in lesions by size (<1 cm, 1-2 cm, >2 cm). RESULTS: We identified 397 primary pulmonary adenocarcinomas. Molecular studies were requested by the clinician in 89 (22%) of primary adenocarcinomas. FNAs were used in 55 cases; 51 (93%) yielded sufficient material for molecular studies; surgical tissue were used in 34 cases; 33 (97%) yielded sufficient material for molecular studies. The insufficient specimens came from 2 FNAs of 0.6 cm nodules, an FNA of a 2 cm nodule, and a core biopsy. CONCLUSIONS: FNA was adequate for molecular analysis of small nodules. In nodules greater than 0.6 cm, the adequacy is comparable to surgical tissue. There was no statistically significant change in mutation rate by size (53%-58%). Importantly, FNA of small lesions for cytological diagnosis and molecular analysis is encouraged by our data and experience in order to provide early treatment.

Collision tumor of primary merkel cell carcinoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, diagnosed on ultrasound-guided fine-needle aspiration biopsy: a unique case report and review of literature.

We report an extremely rare case of skin collision tumor between primary Merkel cell carcinoma (MCC) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) first diagnosed on ultrasound-guided fine-needle aspiration biopsy (US-FNA). A 95-year-old female with a history of CLL presented with a slow growing left malar mass was referred to our clinic for US-FNA. US scan showed a well-defined subcutaneous mass (2.78 cm) with complex echogenicity. On-site assessment showed a cellular aspiration which was interpreted as small blue round cell tumor. On further examination, smears and cell block showed dimorphic populations of relatively larger cells with neuroendocrine features and smaller lymphoid cells. Immunocytochemical studies of cell block sections revealed that the larger cells were positive for CD56, Chromogranin, Synaptophysin, CK8/18, CK20 (dot-like pattern); and the smaller cells were positive for CD45. Flow cytometric analysis showed a majority of CD16/CD56 positive cells, 17% of monoclonal B-cells, and 14% of reactive T cells. The immunophenotype of the monoclonal B cells were of CLL/SLL. The diagnosis of a collision tumor composed of primary MCC and CLL/SLL was confirmed. Surgical resection of the mass one month later concurred with the FNA cytological diagnosis. The fact that surgical specimen displayed a solid tumor with both CLL/SLL and MCC components ruled out the possibility that the FNA merely had MCC with peripheral leukemic blood contaminant. No additional MCC lesion was found in the patient, which ruled out the possibility of metastatic MCC to a lymphomatous lymph node.

Evaluation of a scoring system for predicting lymph node malignancy in ultrasound guided fine needle aspiration practice.

Ultrasound-guided fine needle aspiration (USG-FNA) has enabled cytopathologists to accurately diagnose smaller or non-palpable lymph nodes (LN) on a regular basis. Pre-FNA clinical and ultrasonographic factors, such as a patient's age, ratio of short to long axis diameter (S/L ratio), internal echogenicity, and the vascular pattern of a LN, are reported to be able to predict the benign or malignant nature of a LN. This study is designed to test the formula "0.06 × (age) + 4.76 × (S/L ratio) + 2.15 × (internal echo) + 1.80 × (vascular pattern)" generated from the study of Liao et al. as a scoring system for predicting LN malignancy in a cytopathologist operated USG-FNA practice. Eighty-three reports of USG-FNA of LNs issued between 7/1/2008 and 4/28/2010 were reviewed. Patient's age, S/L ratio, internal echo, and vascular pattern were used to generate scores based on the aforementioned formula. A score of seven was used as a cutoff for predicting benign (<7) and malignant (>7) LNs. FNA cytology diagnosis, flow cytometric analysis as well as subsequent surgical diagnosis in some cases served as gold standard for statistical analysis. Among 46 USG-FNA of LNs with scores > 7, 38 were malignant and eight were benign. All 37 USG-FNA of LNs with scores < 7 were proven to be benign. The scoring system achieved 100% sensitivity, 82% specificity, 83% positive predictive value, 100% negative predictive value, and 90% accuracy. Further study of the eight "false-positive" cases revealed that three of them (37.5%) were found to be malignant in follow-up FNA and/or surgical biopsy. This scoring system may serve as a complementary tool in determining how aggressive a FNA procedure should be performed, how a FNA sample of LN should be triaged for ancillary study, and how closely a patient with lymphadenopathy should be followed up.