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 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.

Clinicopathologic Characterization of Bilateral Testicular Germ Cell Tumors With Immunohistochemical Evaluation of Mismatch Repair and BRAF (V600E) Genes Mutations.

The incidence of bilateral testicular germ cell tumor (TGCT) is 1% to 5%. Despite the high rate of treatment success, resistance to chemotherapy has a detrimental effect. Some studies found MMR and BRAF gene mutations to be associated with chemotherapy resistance, which has not been found by others. However, the role of microsatellite instability (MSI) and BRAF mutations in bilateral disease has not been investigated. In this article, we studied the clinicopathologic characteristics and immunohistochemical expressions of MMR and BRAF in 13 patients with bilateral TGCT. Bilateral tumors were found in 4% of patients in our data. The mean ages at the first and subsequent diagnoses were 26.9 and 28.3 years, respectively. Eleven patients had metachronous disease; and the mean period between both tumors was 4.9 years. Six had mixed GCTs (MGCT) initially and later developed contralateral seminoma, 3 had bilateral MGCTs; 1 initially had pure embryonal carcinoma and subsequently MGCT and finally, 1 patient had initial seminoma and contralateral germ cell neoplasia in situ only. Of the patients with synchronous GCT, 1 had a MGCT and contralateral non-seminoma and 1 had seminoma and contralateral MGCT. In metachronous cases, 40% and 78% had an initial and subsequent stage of pT1, respectively. Hormonal and/or metastatic recurrence was observed in 30% of metachronous tumors. Six patients received chemotherapy, including patients with metastasis. No progression occurred after therapy. MLH1, PMS2, MSH2, and MSH6 staining was retained in all tumors. No BRAF staining was found. In conclusion, we found no association between bilateral TGCT and the MMR/MSI pathway and that subsequent metachronous tumors behaved much more indolently.

Pathological risk factors for higher clinical stage in testicular seminomas.

AIMS: Testicular seminomas require accurate staging for effective management. Twenty per cent are metastatic at presentation, while 80% are clinical stage I, requiring only orchiectomy and surveillance. Tumour size, rete testis invasion, hilar soft tissue invasion and lymphovascular invasion have been shown to incur a higher risk of metastasis and recurrence in clinical stage I seminomas, with little congruence between studies. METHODS AND RESULTS: We reviewed 211 cases of testicular seminomas and recorded patient age, tumour size, lymphovascular invasion and rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea and tunica vaginalis involvement. A univariate and multivariate analysis was performed comparing clinical stage I to advanced clinical stage patients (stages II and III) in reference to these factors. We found that tumour size (P = 0.02), vascular invasion (P = 0.02) and invasion of rete testis stroma (P = 0.01), epididymis (P = 0.02), spermatic cord (P = 0.047) and hilar soft tissue (P = 0.04) were predictors of higher clinical stage at the univariate level. However, multivariate analysis showed that only tumour size and vascular invasion remained significant (P = 0.008 and 0.032, respectively). A tumour size of 4 cm was the cut-off size found to be significant. CONCLUSIONS: Tumour size and vascular invasion are the strongest predictors of higher clinical stage in testicular seminomas. Our univariate data suggest that rete testis and hilar soft tissue invasion relate to higher clinical stage. However, neither of these factors were found to be independent risk factors at multivariate analysis. Therefore, this study supports tumour upstaging based only upon size and vascular invasion.

The Significance of Spermatic Cord Involvement by Testicular Germ Cell Tumors: Should We Be Staging Discontinuous Invasion From Involved Lymphovascular Spaces Differently From Direct Extension?

The recent 8th edition of the American Joint Committee on Cancer (AJCC) staging manual had multiple changes concerning how pathologists should stage germ cell tumors (GCTs) of the testis. A significant one concerns the impact of different types of spermatic cord involvement, specifically direct tumor extension versus discontinuous involvement by invasion through lymphovascular spaces. We compared clinicopathologic findings and outcome data between 2 cohorts with these findings to evaluate the validity of the change in the AJCC 8th edition manual. GCTs (seminomatous and nonseminomatous) of the testis were identified that had previously been staged as pT3 due to involvement of the spermatic cord. Pathologic, radiographic, and clinical findings were reviewed. Tumors were restaged based on AJCC 8th edition criteria and the cohorts were split into direct extension by tumor into the spermatic cord (pT3), spermatic cord soft tissue invasion via spread from discontinuously involved lymphovascular spaces (pT2pM1), or a combination of both (pT3pM1). One hundred cases of primary GCTs of the testis, previously classified as pT3 by the AJCC 6th or 7th cancer staging manuals from 2007 to 2015, were selected. Mixed malignant GCTs were the predominant tumor type, comprising 66% of all cases. Pure tumor morphologies included embryonal carcinoma (n=17), seminoma (n=14), teratoma (n=2), and yolk sac tumor (n=1). The tumors either directly invaded into the spermatic cord (n=78), involved the cord discontinuously via spread from lymphovascular spaces (n=18), or had both findings (n=4). Overall, 93% of patients presented at advanced clinical stage (CS). Using the AJCC 8th parameters, 12% of all tumors were upstaged. Changes included CSI (n=1) and CSII (n=11) tumors being reclassified as prognostic stage group III. Clinical and/or pathologic recurrence was identified in 19% of all patients, including 12 pT3 and 7 pM1 patients (P=0.11). Overall mean time to recurrence was 24.6 months, with a mean of 28.0 months for pT3 tumors and 18.9 months for pM1 tumors. Five patients were dead at the time of this study, including 3 (4%) with pT3 tumors and 2 (9%) in the pM1 cohort. Our findings support that seminomatous and nonseminomatous GCTs with spermatic cord invasion have a high frequency of advanced CS at presentation, regardless of involvement by direct extension or discontinuous spread via invasion from lymphovascular spaces. By designating the latter as M1, a spurious upstaging to prognostic stage group III is required by the AJCC 8th edition. We were unable to identify statistically significant difference between the 2 groups as it pertained to CS at presentation and likelihood of recurrence. Conversely, statistical trends favor that pM1 patients have more likely recurrence and worse prognosis than pT3 patients.

Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3?

The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.

Paratesticular Soft-Tissue Masses in Orchiectomy Specimens: A 17-Year Survey of Primary and Incidental Cases From One Institution.

The paratestis (PT) is defined by the testicular tunics, epididymis, spermatic cord, rete testis, and embryonic remnants. It gives rise to a large diversity of pathologies, including those of soft tissue, which may prompt orchiectomy. We performed a 17-year search of our database for orchiectomies for a PT soft-tissue mass. In a total of 4741 orchiectomy specimens, 138 orchiectomies were performed for primary neoplastic or nonneoplastic masses of the PT soft tissue or had an incidental PT soft-tissue mass. Of these, 65.9% were neoplastic. The mean age was 40.2 years (range: <1 to 87 years) and was similar for neoplastic and nonneoplastic lesions. The most common malignancies were rhabdomyosarcoma (31/63 malignancies), liposarcoma (19/63), and leiomyosarcoma (5/63), with the former occurring in younger patients (average: 18.3 years). No malignancies were incidental. The most common benign neoplasm was spermatic cord lipoma (24/28 of benign neoplasms); however, most were incidental. This was followed by leiomyoma (3/28) and hemangioma (1/28). The most common nonneoplastic lesions were adrenal rests (22/47 nonneoplastic cases); however, all were incidental findings. Of 47 nonneoplastic masses, 22 prompted orchiectomy, and of these, the most common diagnosis was fibrous/nodular periorchitis (11/47). Of 88 nonincidental lesions, 25 were either benign neoplasms (3/25) or nonneoplastic (22/25). These data indicate that PT soft-tissue neoplasms prompting orchiectomy are disproportionately rhabdomyosarcomas, though these are principally in young patients. In older patients, malignancies are more frequently liposarcomas. However, almost one-third of orchiectomies performed for PT soft-tissue masses yield benign lesions, indicating an opportunity to reduce unnecessary procedures.