Sequential molecular and cytologic analyses provides a complementary approach to the diagnosis of pancreatic cystic lesions: a decade of clinical practice.

INTRODUCTION: Many pancreatic cystic lesions (PCL) are of neoplastic nature with potential to progress to pancreatic adenocarcinoma. Early stratification of patients to either clinical observation or surgical intervention can considerably increase the survival rate. Recent studies have shown the value of molecular analysis to current diagnostic modalities.The aim of this study is to evaluate the diagnostic improvement by utilizing multiple sequential cytologic and molecular cyst fluid analyses. MATERIALS AND METHODS: We prospectively evaluated 58 patients for whom multiple endoscopic ultrasound-guided fine-needle aspiration of cyst fluid specimens were available. Specimens were subjected to next generation sequencing to identify any recurrent gene mutations commonly found in PCL. The molecular findings were compared with cytologic and final diagnoses. RESULTS: Cytologic diagnoses were classified into 3 groups: non-diagnostic (first visit: 33.9%, cumulative: 15.8%, P = 0.03), negative (1st visit: 53.6%, cumulative: 56.1%, P = 0.85) and atypical/suspicious/positive (first visit: 12.5%, cumulative: 28.1%, P = 0.06). The mutational analyses were clustered into indeterminate/failure (first visit: 1.7%, cumulative: 0%), KRAS/GNAS/VHL group (first visit: 50.0%, cumulative: 53.4%) and any mutation (first visit: 50.0%, cumulative: 53.4%). Mutational analysis identifies up to 72% and 71% whereas cytologic analysis classified up to 46% and 63% of lesions correctly in first and multiple visits, respectively. CONCLUSIONS: The cytology and molecular analyses provide a complementary approach to patients with PCL. Power of molecular analysis in detection of a neoplastic lesion is significantly higher in one visit (P = 0.01) with comparable detection rates (P = 0.43) for both cytologic and molecular analyses after multiple visits.

Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool.

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management.

Five Top Stories in Thyroid Pathology.

CONTEXT: Thyroid carcinoma is the most common malignant tumor of endocrine organs, yet it only accounts for approximately 1% of all cancers in the United States with more than 35,000 new cases diagnosed each year and more than 450,000 people living with this disease. While most tumors can be diagnosed without much difficulty, a few tumor types, especially tumors with follicular pattern, sometimes pose a diagnostic challenge. OBJECTIVE: To discuss morphologic, immunohistochemical, and molecular features of thyroid tumors. We also explore the clinicopathologic features of papillary microcarcinoma and medullary microcarcinoma and how the latter is related and differentiated from C-cell hyperplasia. Finally with the ever-growing list of organ systems involved in immunoglobulin (Ig) G4-related diseases, we discuss the still not completely explored IgG-4-related thyroid disease. DATA SOURCES: Data were obtained from review of the pertinent peer-reviewed literature and institutional experience. CONCLUSIONS: Histomorphologic evaluation still remains the gold standard for diagnosis in most cases of thyroid diseases. The application of ancillary studies such as immunohistochemistry and molecular diagnosis, including next-generation sequencing, is becoming more common.

Patterns and signal intensity characteristics of pelvic recurrence of rectal cancer at MR imaging.

Magnetic resonance (MR) imaging is becoming the cross-sectional imaging modality of choice for follow-up of patients with previous rectal cancer to diagnose pelvic recurrence and plan for surgery. The authors conducted a retrospective review of MR imaging examinations performed at their institution for evaluation of local recurrence of rectal cancer in 42 patients. Twenty-six patients had undergone rectal anastomosis and 16 had undergone abdominoperineal resection. The mean interval between initial surgery and recurrence was 2.5 years. Recurrence sites were axial (involving the anastomosis) (n = 19); lateral (sidewall) (n = 6); anterior (prostate or seminal vesicle [n = 2], bladder [n = 4], ureter [n = 3], vagina or uterus [n = 5]); or posterior (presacral fascia [n = 11], sacrum [n = 2]). Other recurrence sites included the pelvic floor (n = 7), sciatic nerve (n = 2), obturator nerve (n = 1), perineum (n = 1), abdominal wall (n = 1), or adnexa (n = 1). Recurrence was confirmed at surgery or by evidence of tumor growth at follow-up imaging. Recurrence patterns, signal intensity characteristics, findings of unresectability, potential MR imaging pitfalls, and the role of MR imaging versus other modalities in evaluating recurrent rectal carcinoma are discussed. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg335115170/-/DC1.

Metastatic carcinoma to the thyroid gland: a single institution 20-year experience and review of the literature.

The thyroid gland is an uncommon site for metastatic disease but cases have been well-documented in the literature, particularly in autopsy series. A retrospective review of surgical pathology and autopsy pathology database for patients with metastatic carcinoma to the thyroid was performed at the University of Massachusetts Medical Center between January 1993 to January 2013. We identified a total of 10 patients with metastatic carcinoma to the thyroid; 6 were in surgical pathology specimens out of a total of 1,295 thyroid carcinoma (0.46 %) and 4 were diagnosed at autopsy out of a total of 2,117 (0.19 %) autopsy cases during this period. Cases with direct extension of the tumor into the thyroid from local primary sites such as larynx, esophagus or soft tissues of the neck were excluded. The primary tumors in these cases comprised of four lung carcinomas, three colorectal carcinomas, a renal cell carcinoma, a pleural malignant mesothelioma, and an unknown primary. Therefore, it is important to keep intrathyroidal metastases in the differential diagnosis when evaluating a thyroid nodule, particularly in patients with a previous history of malignancy. Furthermore, a literature review reveals over 1,400 cases have been previously reported, with the most common malignancies from the kidney (34 %), lung (15 %), gastrointestinal tract (14 %), and breast (14 %).