Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20‐year retrospective, single institutional study

Background Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. Methods Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. Results High‐grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low‐grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. Conclusions FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high‐grade (62%) than low‐grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established

Fine-Needle Aspiration Cytology of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma Is Cytomorphologically Distinct From the Invasive Counterpart

Objectives: To review a series of noninvasive encapsulated follicular variant of papillary thyroid carcinomas (FVPTCs) in an attempt to further define the role of cytopathology in the diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features and invasive FVPTC. Methods: Surgical pathology cases diagnosed as FVPTC with correlating thyroid fine-needle aspiration (FNA) were identified and divided into two FVPTC groups: noninvasive and invasive. Cytologic diagnoses were compared between them. Results: We identified 23 cases that met the criteria for noninvasive FVPTC and 27 cases that were typical infiltrative FVPTC (n = 16) or encapsulated FVPTC with either capsular and/or lymphovascular invasion (n = 11). Of the noninvasive FVPTC cases, there were four benign lesions, 14 follicular lesions of undetermined significance (FLUS), four follicular neoplasms (FNs), one suspicious case, and no papillary thyroid carcinomas (PTCs). In the invasive FVPTC group, there were no benign cases, four FLUS, three FNs, 12 suspicious cases, and eight PTCs. Conclusions: There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC ( P  < .05)

Fine-Needle Aspirates of Thyroid Microcarcinoma

Introduction Widespread use of ultrasound allows for detection of smaller thyroid nodules and preoperative evaluation with fine-needle aspiration (FNA). Both incidental and non-incidental microcarcinoma can be found, leading to uncertainty with clinical management. Materials and methods A retrospective analysis of thyroid FNAs performed at our institution was conducted for the 5-year period from 2010 to 2014. Aspirates were categorized using the Bethesda System for Reporting Thyroid Cytopathology. Cytologic diagnoses were then correlated with final histopathology. Among samples with malignancy on surgical resection, nodules were stratified by size. Results A total of 2531 thyroid FNAs were identified; 587 samples had histologic correlation, and 259 malignancies were reported. They were separated into nodules >1 cm (n = 144, 56%) and ≤1 cm (n = 115, 44%). Microcarcinoma was further subdivided into incidental (size ≤0.5 cm, n = 55, 48%) and non-incidental (size >0.5 cm and ≤1 cm, n = 60, 52%). The preoperative cytologic diagnoses for incidental microcarcinoma were: benign (B, n = 11, 20%), follicular lesion of undetermined significance (FLUS, n = 15, 27%), follicular neoplasm (FN, n = 11, 20%), suspicious for malignancy (SM, n = 7, 13%), malignant (M, n = 8, 15%), and nondiagnostic (ND, n = 3, 5%). The FNA categories for non-incidental microcarcinoma were: B (n = 13, 22%), FLUS (n = 3, 5%), FN (n = 3, 5%), SM (n = 10, 17%), M (n = 29, 48%), and ND (n = 2, 3%). Conclusions Incidental microcarcinoma is not an uncommon entity, making up 21% (55 of 259) of malignant nodules on thyroidectomy. Indeterminate diagnoses (FLUS + FN + SM) accounted for the majority (60%) of preoperative FNAs for incidental microcarcinoma, compared with 27% for those of non-incidental microcarcinoma (P < 0.05, χ2 test)

World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading in fine‐needle aspiration biopsies of renal masses

Background Utilization of fine‐needle aspiration (FNA) biopsy for the evaluation of renal masses has been increasing at our institution. At times diagnostic material on direct smears is superior to that in the cell block/core biopsy, therefore assigning an accurate nuclear grade in the cytopathology report would provide useful prognostic information. Methods Search of the pathology database identified renal FNAs performed during an 11‐year period (2006–2017). Corresponding core biopsies and resections were identified. Cases with a diagnosis of primary renal neoplasia on FNA, core biopsy, and/or resection were included. Two pathologists reviewed all cases and assigned a World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade to each FNA, core biopsy, and resection case. Results A total of 162 kidney FNAs were identified. Primary renal neoplasia was diagnosed in 137 cases on core biopsy/resection. Among diagnostic FNAs of clear cell RCC and papillary RCC with core biopsy/resection specimens for re‐review (n = 52), reviewers assigned a concordant WHO/ISUP grade to 83% (43/52) of cases. Among 9 cases with discrepant scores, all had a discrepancy of 1 grade and were undergraded on FNA. Using a two tier grading system (low vs. high grade), reviewers assigned a concordant grade to 88% (46/52) of cases. Among 6 cases with discrepant scores, all were classified as low grade (WHO/ISUP grade 2) on FNA versus high grade (WHO/ISUP grade 3) on resection. Conclusion The WHO/ISUP grade assigned on FNA shows good concordance with subsequent resection/core specimens (83%), with all discrepant cases being undergraded by one grade

Magnetic characterization of perpendicular recording media

In this paper, we describe techniques for the magnetic characterization of perpendicular recording media. Such measurements made using traditional techniques, such as the vibrating sample magnetometry (VSM) and alternating gradient force magnetometer (AGFM), have to be corrected for the sample shape demagnetizing factor, which is often found not to be equal to -4p. For measurements other than the simple hysteresis loop, such as remanence curves, this correction must be carried out in real time and we describe the method by which this can be achieved and the process for achieving the correct demagnetization of perpendicular films prior to measurements of the isothermal remanent magnetization curve. A further complication is that real perpendicular media have a soft underlayer beneath the recording layer, which swamps and confuses signals from instruments such as VSM or AGFM. Hence, we describe the construction and use of a magnetooptical Kerr effect magnetometer, which does not penetrate significantly into the soft layer and enables the perpendicular layer to be measured independently. We describe the properties of a traditional alloy perpendicular medium and a Co-Pd multilayer system, which in the latter case exhibits multiple switching behavior. We also address the issue of the effect of the soft underlayer on the coupling in similar longitudinal films and find that the presence of the underlayer induces significant additional coupling effects that may well give rise to an increase in noise in recorded signal

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX. Experimental Design: Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan–Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage. Results: Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 (N = 7), BRCA2 (N = 5), PALB2 (N = 3), MSH2 (N = 1), and FANCF (N = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29–1.14; log-rank P = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04–2.06; P = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15–0.94; P = 0.04) showed presence of DDR gene mutations was associated with improved OS. Conclusions: In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX

Multifocal High-Grade Pancreatic Precursor Lesions: A Case Series and Management Recommendations

Background: The risk of developing invasive cancer in the remnant pancreas after resection of multifocal high-grade pancreatic precursor lesions is not well known. We report three patients who were followed up after resection of multifocal high-grade pancreatic intraepithelial neoplasia (PanIN)-3 or intraductal papillary mucinous neoplasia (IPMN), two of whom eventually developed invasive carcinoma. Presentation: 1) 68-year-old woman who had a laparoscopic distal pancreatectomy for multifocal mixed-type IPMN, identified as high-grade on final pathology, with negative surgical margins. During semiannual monitoring, eight years from the first surgery, the patient developed suspicious features prompting surgical resection of the body with final pathology revealing invasive ductal adenocarcinoma in the setting of IPMN. 2) 48-year-old woman who had a distal pancreatectomy for severe acute/chronic symptomatic pancreatitis, with final pathology revealing multifocal high-grade PanIN-3, with negative surgical margins. Despite semiannual monitoring, two years from the first surgery, the patient developed pancreatic adenocarcinoma with liver metastasis. 3) 55-year-old woman who had a Whipple procedure for symptomatic chronic pancreatitis, with multifocal PanIN-3 on final pathology. The patient underwent completion pancreatectomy due to symptomatology and her high-risk profile, with final pathology confirming multifocal PanIN-3. Conclusion: Multifocal high-grade dysplastic lesions of the pancreas might benefit from surgical resection

Fine Needle Aspiration Cytology of Metastatic Plasmacytoid Urothelial Carcinoma- Report of Four Cases Including a Case of Mixed Plasmacytoid and Micropapillary Morphology

Objectives: The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC). Study Design: A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC. Results: The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to-moderate cellularity and consisted predominantly of single and dyshesive, medium-sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen. Conclusions: FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy

Excellent Response to Anti-PD1 therapy in a Patient with Hepatocellular Carcinoma: Case Report and Review of Literature

Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial). This has led to the off-label use of nivolumab after failure of treatment with sorafenib either due to intolerance or progression of disease. Although rare (<5%), clinical response to anti-PD-1 antibody may be preceded by "pseudoprogression" -- increase in the size and number of tumor lesions before actual tumor shrinkage. We report a case of pseudoprogression followed by an excellent response in an HCC patient treated with nivolumab and review the literature for ongoing trials of immune checkpoint blockade in HCC. The pseudoprogression in our case is supported by increase in both tumor size and alpha-fetoprotein after four treatments with nivolumab; however, regression of tumor size and normalization of alpha-fetoprotein occurred after subsequent treatments. To our knowledge, there are no reports of pseudoprogression in HCC although pseudoprogression has been well described in melanoma

Post-tuberculous fibrosing mediastinitis: a review of the literature.

Fibrosing mediastinitis (FM) is a rare disease where there is thickening of the fibrous tissue in the mediastinum. While histoplasmosis is the the most common recognised cause, the link with tuberculosis (TB) has been rarely documented. We review the link between TB and FM, and describe a case of probable TB-related FM.Our case is of a 74-year-old man who presented with breathlessness 3 years after fully treated TB. Scans revealed a calcified soft tissue mass within the mediastinum, and a diagnosis of fibrosing mediastinitis resulting in pulmonary hypertension was made. Tests for histoplasmosis and IgG4 staining were negative. Surgical intervention was not felt to be beneficial, and he was treated with prednisolone and mycophenolate mofetil.In the review, we highlight the two forms of mediastinitis-granulomatous versus fibrous, and how these two entities may be on a spectrum of disease progression. We also explore the prevalence, clinical presentation, pathogenesis, imaging techniques and treatment options of TB-related FM