Metastatic solid tumours to the penis: a clinicopathologic evaluation of 109 cases from an international collaboration.

AIMS: To elucidate the spectrum of metastatic tumours to the penis and their clinicopathologic features. METHODS: The databases and files of 22 pathology departments from eight countries on three continents were queried to identify metastatic solid tumours of the penis and to characterize their clinical and pathologic features. RESULTS: We compiled a series of 109 cases of metastatic solid tumours that secondarily involved the penis. The mean patient age at diagnosis was 71 years (range, 7-94 years). Clinical presentation commonly included a penile nodule/mass (48/95; 51%) and localised pain (14/95; 15%). A prior history of malignancy was known in 92/104 (89%) patients. Diagnosis was made mainly on biopsy (82/109; 75%), or penectomy (21/109; 19%) specimens. The most common penile locations were the glans (45/98; 46%) and corpus cavernosum (39/98; 39%). The most frequent histologic type was adenocarcinoma (56%). Most primary carcinomas originated in the genitourinary (76/108; 70%) and gastrointestinal (20/108; 18%) tracts, including prostate (38/108; 35%), urinary bladder (27/108; 25%), and colon/rectum (18/108; 17%). Concurrent or prior extrapenile metastases were identified in 50/78 (64%) patients. Clinical follow-up (mean 22 months, range 0-171 months) was available for 87/109 (80%) patients, of whom 46 (53%) died of disease. CONCLUSION: This is the largest study to date of metastatic solid tumours secondarily involving the penis. The most frequent primaries originated from the genitourinary and gastrointestinal tracts. Metastatic penile tumours usually presented with penile nodules/masses and pain, and they often occurred in the setting of advanced metastatic disease, portending poor clinical outcomes.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

EUS-guided fine needle aspiration-based clues to mistaken or uncertain identity: serous pancreatic cysts.

BACKGROUND/OBJECTIVES: Pancreatic serous cystic neoplasms (SCN) present a diagnostic challenge given their increasing frequency of detection and benign nature yet relatively high rate of misdiagnosis. Here, imaging and analyses associated with EUS-guided fine-needle aspiration (EUS-FNA) are evaluated for their ability to provide a correct preoperative diagnosis of SCN. METHODS: A surgical cohort with confirmed pathological diagnosis of SCN (n = 62) and a surveillance cohort with likely SCN (n = 31) were assessed for imaging (CT/MRI/EUS) and EUS-FNA-based analyses (cytology/DNA analysis for Von Hippel-Lindau [VHL] gene alterations/biomarkers). RESULTS: In the surgical cohort, CT/MRI and EUS respectively predicted SCN in 4 of 58(7%) and 19 of 62(31%). Cyst fluid cytology and VHL alterations predicted SCN in 1 of 51(2%) and 5 of 21(24%), respectively. High specificity cyst fluid biomarkers (vascular endothelial growth factor [VEGF]/glucose/carcinoembryonic antigen [CEA]/amylase) correctly identified SCN in 25 of 27(93%). In the surveillance cohort, cyst fluid biomarkers predicted SCN in 12 of 12(100%) while VHL alterations identified SCN 3 of 10(30%). CONCLUSION: High specificity cyst fluid biomarkers provided the most sensitive means of diagnosing SCN preoperatively. To obtain a preoperative diagnosis of SCN at the highest level of certainty, a multidisciplinary approach should be taken to inform appropriate SCN management.

Novel Approach to Outpatient Endometrial Biopsy to Detect Endometrial Cancer.

OBJECTIVE: To evaluate a new device for obtaining endometrial biopsies which combines global endometrial disruption using a brush with a built-in suction process. STUDY DESIGN: Endometrial biopsies were collected, using the GDP-Tao device, from fresh uteri hysterectomy specimens after completion of surgery. Results were compared to final hysterectomy pathology. Specificity and sensitivity and positive and negative predictive values were calculated. RESULTS: Based on a sample size calculation, 42 patients were included in this study. Endometrial tissue adequate for diagnosis was obtained in 93% (39/42) of biopsies. Classifying atypia as a positive result, the sensitivity of the new device was 96% (23/24), with specificity of 87% (13/15). The positive predictive value was 92% (23/25) and the negative predictive value, 93% (13/14). There were 2 nondiagnostic (ND) samples from GDP-Tao with final pathology of benign endometrium. One specimen was ND on both GDP-Tao and final pathology due to absence of tissue after prior endometrial ablation. When stratified by uterine size, benign or malignant, the results were similar. CONCLUSION: Our validation study showed encouraging results for the GDP-Tao, which combines tissue disruption and aspiration into a single process. The device provides a reliable means of obtaining adequate samples to accurately detect endometrial cancer with a high negative and positive predictive value.

Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic Smears of Lung Adenocarcinoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. METHODS: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. RESULTS: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. CONCLUSION: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity.

Utilization of cell-transferred cytologic smears in detection of EGFR and KRAS mutation on adenocarcinoma of lung.

Cell-transfer technique has been proven useful for performing immunocytochemistry on fine-needle aspiration smears. However, its utility for EGFR and KRAS molecular testing has not been validated. Molecular testing was performed using the cell-transfer technique on both Papanicolaou-stained ethanol-fixed and Hema 3-stained air-dried smears from 32 fine-needle aspiration samples that had diagnoses of adenocarcinoma of the lung, and then was compared to the results of the corresponding formalin-fixed paraffin-embedded tissues. The molecular testing was successfully performed on 32 of 32 ethanol-fixed and 31 of 32 air-dried samples. The molecular results on ethanol-fixed and air-dried smears showed 100% agreement. There is 100% (32/32) agreement for the EGFR and 97% (31/32) agreement for the KRAS between the cell-transfer technique and formalin-fixed paraffin-embedded tissues. One discrepant case was due to low percentage of tumor cells on the smears. Cell-transfer technique is a reliable alternative method for EGFR and KRAS testing if the cell blocks lack adequate cellularity.

Detection of BRAF mutation in metastatic melanoma utilizing cell-transferred cytological smears.

OBJECTIVES: Fine-needle aspiration (FNA) is frequently used to diagnose metastatic melanoma. In this study, we validated the use of cell-transferred cytological smears for BRAF molecular testing. STUDY DESIGN: We conducted a search of our laboratory information system for the period 2011-2013 in order to identify surgical pathology cases of either primary or metastatic melanomas in which BRAF mutation analyses had already been performed. Thirty FNA cases with diagnoses of metastatic melanoma from the same patients were identified. Direct smears from each FNA case were selected for mutation analyses using the cell transfer technique. RESULTS: Mutation analyses were successfully performed on 28 of 30 FNA cases (93%) using the cell-transferred cytological smears. In 25 cases (8 BRAF mutations and 17 BRAF wild types), there was 100% agreement for the BRAF mutation between the cell-transferred cytological smears and the formalin-fixed paraffin-embedded tissues. Three FNA cases showed BRAF mutations that had not been detected in the correlated surgical specimens which were tested twice, and 2 cases failed to work. CONCLUSIONS: Cell-transferred cytological smears are a reliable and alternative resource for detecting BRAF mutations in metastatic melanoma.

Integrated Molecular Characterization of Intraductal Papillary Mucinous Neoplasms: An NCI Cancer Moonshot Precancer Atlas Pilot Project.

Intraductal papillary mucinous neoplasms (IPMN) are cystic precursor lesions to pancreatic ductal adenocarcinoma (PDAC). IPMNs undergo multistep progression from low-grade (LG) to high-grade (HG) dysplasia, culminating in invasive neoplasia. While patterns of IPMN progression have been analyzed using multiregion sequencing for somatic mutations, there is no integrated assessment of molecular events, including copy-number alterations (CNA) and transcriptional changes that accompany IPMN progression. We performed laser capture microdissection on surgically resected IPMNs of varying grades of histologic dysplasia obtained from 23 patients, followed by whole-exome and whole-transcriptome sequencing. Overall, HG IPMNs displayed a significantly greater aneuploidy score than LG lesions, with chromosome 1q amplification being associated with HG progression and with cases that harbored co-occurring PDAC. Furthermore, the combined assessment of single-nucleotide variants (SNV) and CNAs identified both linear and branched evolutionary trajectories, underscoring the heterogeneity in the progression of LG lesions to HG and PDAC. At the transcriptome level, upregulation of MYC-regulated targets and downregulation of transcripts associated with the MHC class I antigen presentation machinery as well as pathways related to glycosylation were a common feature of progression to HG. In addition, the established PDAC transcriptional subtypes (basal-like and classical) were readily apparent within IPMNs. Taken together, this work emphasizes the role of 1q copy-number amplification as a putative biomarker of high-risk IPMNs, underscores the importance of immune evasion even in noninvasive precursor lesions, and reinforces that evolutionary pathways in IPMNs are heterogenous, comprised of both SNV and CNA-driven events. SIGNIFICANCE: Integrated molecular analysis of genomic and transcriptomic alterations in the multistep progression of IPMNs, which are bona fide precursors of pancreatic cancer, identifies features associated with progression of low-risk lesions to high-risk lesions and cancer, which might enable patient stratification and cancer interception strategies.

The utility of fine-needle aspiration in the diagnosis of primary and metastatic tumors to the lung: a retrospective examination of 1,032 cases.

BACKGROUND: With the emergence of improved treatment strategies for patients with malignant lung tumors, it has become increasingly important to adequately diagnose and subclassify lung lesions. In our large retrospective study, we assessed the utility of fine-needle aspiration (FNA) in the diagnosis of primary and metastatic tumors to the lung. METHODS: A computerized search of our laboratory informatics system was performed to identify cases from FNA of the lung and FNA of metastatic lung cancers to other sites. All of the corresponding surgical pathology reports were also reviewed. All of the cases were categorized as atypical (A), benign (B), malignant (M), nondiagnostic (ND), or suspicious (S) for data analysis purposes. RESULTS: A total of 1,032 FNA cases were categorized as follows: 34 (3.3%) A, 142 (13.8%) B, 717 (69.5%) M, 121 (11.7%) ND, and 18 (1.7%) S. Of the 717 cases of malignant FNA, a specific tumor type was able to be rendered on cytomorphology alone or with the help of immunostains in 99% as follows: adenocarcinoma (296 cases, 41%), squamous cell carcinoma (158 cases, 22%), metastatic tumors (123 cases, 17%), small cell carcinoma (56 cases, 8%), non-small cell lung carcinoma (NSCLC) (58 cases, 8%), neuroendocrine carcinoma (15 cases, 2%), and poorly differentiated carcinoma (4 cases, 1%). Out of all NSCLC cases, 89% were able to be subclassified as either adenocarcinoma or squamous carcinoma. The most frequent origins of metastatic tumors to the lung were renal cell carcinoma (n = 22), melanoma (n = 17), colon (n = 15), breast (n = 14), and urothelial carcinoma (n = 10). There was also metastasis from 18 other organs with fewer than 5 cases each. There were 333 correlated histologic specimens including 191 small biopsies and 142 resection specimens. Diagnostic sensitivity and specificity for malignancy were 96 and 100%, respectively. Diagnostic accuracy was 97%. Sampling error resulted in 8 false-negative cases on FNA. CONCLUSIONS: FNA is both sensitive and specific in the diagnosis and subclassification of both primary and metastatic lung tumors. Eighty-nine percent of NSCLC cases were able to be further subclassified as adenocarcinoma or squamous cell carcinoma by FNA.

The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation.

(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

BACKGROUND: The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. METHODS: Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). RESULTS: A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P = .0142) and SUMP NOS (P = .0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P = 1.0000) and O1 and O2 (65.2% vs 48.7%, P = .2349). CONCLUSIONS: The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P = .0142) and SUMP NOS (31.9%, P = .0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

The cytology of salivary gland neoplasms with globules of extracellular matrix: Case-based review of adenoid cystic carcinoma and its potential mimics.

Fine needle aspiration (FNA) cytology is an important tool for diagnosing salivary gland neoplasms and for guiding clinical management. The classic adenoid cystic carcinoma (AdCC) is a basaloid neoplasm with abundant extracellular matrix. The presence globules of extracellular matrix are quite characteristic of AdCC but not diagnostic. We selected from our files six FNA cases that contained at least some globules of amorphous matrix that are similar to the ones seen in AdCC. The aim of this case-based review is to discuss the pitfalls and some of the common differential diagnoses of AdCC in FNA cytology. By the end of this review, we hope to have shared with the readers the lessons we learned from these cases and to highlight the key criteria needed to make a correct diagnosis of AdCC based on cytomorphology. The importance of considering other entities, in addition to AdCC, whenever a salivary gland FNA presents with globules is emphasized.

The importance of risk of neoplasm as an outcome in cytologic-histologic correlation studies on thyroid fine needle aspiration.

BACKGROUND: The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) altered the practice of thyroid pathology and reduced the risk of malignancy (ROM) associated with the indeterminate categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC). It has been proposed that the evaluation of the risk of neoplasm (RON) is important in cytologic-histologic correlation studies. METHODS: A total of 5224 thyroid aspirates were performed at our institution during an 8-year period. Of the 1475 cases (28%) with surgical follow-up, the histologic diagnoses comprised benign non-neoplastic (BNN, n = 669), follicular adenoma (FA, n = 188), NIFTP (n = 42), papillary microcarcinoma (PMC) (n = 223), and malignant neoplasm excluding PMC (n = 353). The RON was calculated to include neoplasia with low risk biologic behavior (FA, NIFTP, PMC) and malignant neoplasms. In contrast, the ROM was reserved for malignant neoplasms excluding PMC. RESULTS: The RON for each TBSRTC category was: nondiagnostic (ND) 38.3%, benign 20.9%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) 63.2%, follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) 83.9%, suspicious for malignancy (SFM) 94%, and malignant 100%. The ROM excluding PMC was: ND 14%, benign 1.6%, AUS/FLUS 17.8%, FN/SFN 28.4%, SFM 84.4%, and malignant 99.5%. CONCLUSIONS: The RON and ROM support the recommended management guidelines from TBSRTC for all categories, except for FN/SFN. Histopathologic follow-up of FN/SFN aspirates in our study contain a very high rate of neoplasm (83.9%), which might support the management preference of conservative surgery.

Endoscopic Ultrasound-guided Sampling of Solid Pancreatic Lesions: A Comparative Analysis of 25 Gauge Versus 22 Gauge Core Biopsy Needles.

BACKGROUND: Pancreatic mass sampling has historically been performed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, its sensitivity has been reported to be within a wide range, which limits its reliability. Fine needle biopsy (FNB) has been shown to have superior diagnostic performance and is increasingly replacing fine needle aspiration. In FNA, 25 gauge (G) needles appear to outperform 22G. Data comparing these sizes in FNB platforms is limited. We aimed to prospectively compare the performance of 22G and 25G Franseen-tip core biopsy needles in the sampling of solid pancreatic lesions. PATIENTS AND METHODS: Patients who underwent EUS-FNB of pancreatic lesions at the Indiana University Hospital using 2 needle sizes: 25G (Study group) and 22G (Control group) using the Acquire needle (Boston Scientific Co., Natick, MA, USA) were enrolled. Needle choice was left to the discretion of the endosonographer. Tissue specimens were evaluated onsite, and underwent touch and smear and cellblock preparation. Specimens were independently evaluated by 2 expert cytopathologists blinded to diagnosis. Cytopathologists assessed cytological yield (on smears) and histological yield (on cellblock) using a validated scoring system reached by a consensus among our cytopathologists as we have previously published. RESULTS: A total of 75 patients (42 males, median=65 years) underwent EUS-FNB during the study period (2017-2018): 50 using 25G and 25 using 22G needle. Diagnostic yield was numerically higher in 25G (98% vs. 88%, p=0.105). Number of passes for smears were similar, however the 25G group required additional passes for cell-block (1.6 vs. 0.4, p=0.001). 25G was used more frequently for pancreatic head and uncinate process sampling (70% vs. 52%, p=0.126). Four patients had self-limited adverse events in the 22G group, but none in the 25G group. CONCLUSION: We report no difference in the diagnostic yield between 25G FNB vs. 22G sampling device with Franseen style tip, however, the 25G needle use was associated with the need of additional passes to collect a sufficient cell block.

Risk of malignancy in "atypia of undetermined significance" category of salivary gland fine-needle aspiration: A bi-institutional experience.

BACKGROUND: Many prior institutional and multi-institutional studies have applied the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) retrospectively to their specimens to determine the risk of malignancy (ROM) of each category. Most of these studies focused on general assessment of the system and risk classification. However, there seems to be less focus on the category of atypia of undetermined significance (AUS) that could be attributed to the low number of cases that could fit into this category. Herein, we present a bi-institutional experience with this category. METHODS: A computerized search of the databases was performed to identify all salivary gland fine-needle aspiration (FNA) in two institutions over a period of 12 years. The final diagnosis of each case was reclassified based on MSRSGC, and histology follow-up was retrieved. RESULTS: Sixty AUS cases (out of 1560 salivary gland FNA) were identified with a rate of 3.8%. Forty cases (66%) had a subsequent tissue material. Correlation with histology revealed that the estimated ROM is 37.5% (15/40) and the overall ROM is 25% (15/60). Fifty percent of the cases had a prominent lymphoid component and most commonly represented lymphomas, reactive lymph node or sialadenitis. CONCLUSION: The AUS category is a heterogeneous group of lesions with predominant lymphoid-rich entities. Some variability exists between institutions with most having higher ROM than the suggested 20% by the MSRSGC atlas.

Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis.

BACKGROUND: No specific therapy exists for acute pancreatitis (AP), and current treatment remains entirely supportive. Adipose stem cells (ASCs) have significant immunomodulatory and regenerative activities. We hypothesized that systemic administration of ASCs would mitigate inflammation in AP. METHODS: AP was induced in mice by 6 hourly intraperitoneal injections of cerulein. Twenty-four hours after AP induction, mice were randomized into four systemic treatment groups: sham group (no acute pancreatitis), vehicle, human ASCs, and human ASC-conditioned media. Mice were sacrificed at 48 h, and blood and organs were collected and analyzed. Pancreatic injury was quantified histologically using a published score (edema, inflammation, and necrosis). Pancreatic inflammation was also studied by immunohistochemistry and PCR. RESULTS: When using IV infusion of Hoechst-labeled ASCs, ASCs were found to localize to inflamed tissues: lungs and pancreas. Mice treated with ASCs had less severe AP, as shown by a significantly decreased histopathology score (edema, inflammation, and necrosis) (p = 0.001). ASCs infusion polarized pancreatic macrophages toward an anti-inflammatory M2 phenotype. ASC-conditioned media reduced pancreatic inflammation similarly to ASCs only, highlighting the importance of ASCs secreted factors in modulating inflammation. CONCLUSION: Intravenous delivery of human ASCs markedly reduces pancreatic inflammation in a murine model of AP ASCs which represent an effective therapy for AP.

Correlation between pretreatment serum biochemical markers and treatment outcome for prostatic cancer with bony metastasis.

BACKGROUND: This study was undertaken to evaluate whether or not pretreatment serum biochemical markers are prognostic factors for prostatic cancer with bony metastasis in patients on hormonal treatment. METHODS: Between 1983 and 1998, 127 patients with prostatic cancer and bony metastasis were included for evaluation. Serum prostate-specific antigen, alkaline phosphatase, calcium (Ca), lactic dehydrogenase, inorganic phosphate, gamma-glutamine transpeptidase, uric acid, albumin (Alb), iron, cholesterol (Cho), triglyceride, alanine aminotransferase, aspartate aminotransferase, and hemoglobin (Hb) were checked before treatment. The patients were divided into 2 groups according to their response (group 1, good response; group 2, poor response). RESULTS: There were 54 patients in group 1 and 73 patients in group 2. Pretreatment levels of serum Ca, Alb, Cho and Hb were higher in group 1 than in group 2, while the other parameters were lower in group 1 than in group 2; only pretreatment levels of serum Ca, Alb and Hb were significantly different between groups (p < 0.05). When stratified by tumor grading, patients in group 1 still had significantly higher pretreatment levels of Ca, Alb and Hb than those in group 2. CONCLUSION: Higher pretreatment serum levels of Ca, Alb and Hb are good prognostic factors for patients with metastatic prostatic cancer on hormonal treatment, irrespective of tumor grading.

Cytomorphologic comparison of type 1 and type 2 papillary renal cell carcinoma: A retrospective analysis of 28 cases.

BACKGROUND: Papillary renal cell carcinoma (pRCC) is classified as type 1 or type 2 on the basis of histomorphologic features. Type 1 pRCC typically carries a better prognosis, and renal cell carcinoma is often diagnosed by fine-needle aspiration (FNA). Thus, this study was designed to characterize cytomorphologic features present in FNA cases that could be used to discriminate between type 1 and type 2 pRCC. METHODS: Electronic records of Indiana University were searched for pRCC FNA cases (2007-2018). Corresponding surgical pathology reports were reviewed to classify patients as having type 1 or type 2 pRCC. FNA slides were reviewed to assess cytomorphologic features (ie, nuclear grade; cell size; cytoplasmic volume and quality; and the presence of single cells, papillary clusters, nuclear grooves, foamy histiocytes, hemosiderin pigment, psammoma bodies, and hyaline globules). A semiquantitative score was assigned to each feature. The nuclear grade was assigned with the World Health Organization/International Society of Urological Pathology grading system. The cytomorphologic features of type 1 and type 2 pRCC were compared. RESULTS: Sixteen patients with type 1 pRCC and 12 patients with type 2 pRCC were included in the study. Type 2 pRCC had a higher nuclear grade, a higher volume of cytoplasm, and more granular cytoplasm. Type 1 pRCC more frequently had nuclear grooves and clear cytoplasm. The remaining features (ie, cell size, papillary clusters, single cells, foamy histiocytes, hemosiderin pigment, psammoma bodies, and hyaline globules) were not statistically significant. CONCLUSIONS: Nuclear grade, cytoplasmic volume and granularity or clarity, and nuclear grooves are cytomorphologic features that may aid in the distinction between type 1 and type 2 pRCC.

Fine-needle aspiration cytology of metastatic spindle cell follicular thyroid carcinoma: A case report.

Follicular thyroid carcinoma, spindle cell variant is extremely rare. The tumor is predominantly composed of spindle cells with a fusiform appearance that are arranged in intersecting fascicles. Fine-needle aspiration biopsy of this entity has not been previously described. We report a case of a 58-year-old woman who presented with metastasis to a left neck lymph node 15 years after the original diagnosis. Fine-needle aspiration cytology showed numerous bland, spindled to epithelioid cells with thin, elongated, and plump nuclei with finely granular chromatin and inconspicuous nucleoli. The tumor cells had a moderate amount of cytoplasm with occasional elongated cytoplasmic tails. The cells were arranged in irregular aggregates with a fascicular pattern or singly dispersed. The tumor cells demonstrated positive staining for pan-keratin, PAX8, thyroid transcription factor-1, and thyroglobulin, which confirmed thyroid primary origin.

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine-needle aspiration.

BACKGROUND: The management of thyroid nodules with indeterminate cytology is challenging. Recently, molecular testing on fine-needle aspirates (FNAs) has been advocated to determine whether clinical follow-up or surgery is warranted for patients. Three different testing platforms were performed on aspirates from our institution (Afirma Thyroid FNA Analysis, RosettaGX Reveal, and Interpace ThyGenX/ThyraMIR). This study compares their diagnostic efficacy. METHODS: We conducted a retrospective analysis of indeterminate thyroid FNAs with correlating molecular testing over 4 years (2015-2018). The aspirates included diagnoses of follicular lesion of undetermined significance, follicular neoplasm, or suspicious for malignancy (SM). Based on cases that underwent surgical resection (Afirma, n = 37; Rosetta, n = 19; Interpace, n = 14), we calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for risk of malignancy and neoplasia. RESULTS: The three tests performed similarly when predicting risk of malignancy. They showed high sensitivity (80-100%) and NPV (90-100%) but lower specificity (10-64%) and PPV (21-44%). When assessing their value to predict neoplasia, each test had a high PPV (76-89%) but low NPV (20-33%). The sensitivity for neoplasm was intermediate to high (50-93%), and the specificity remained extremely variable (11-67%). CONCLUSION: Overall, these molecular platforms performed similarly, displaying high NPV but low to intermediate PPV for malignancy and low NPV but high PPV for neoplasm. The risk of neoplasm is a good index for surgery, and we argue that many of the neoplasms are low-risk tumors. We endorse conservative treatment with lobectomy for cases that are indeterminate at FNA but suspicious by molecular testing.