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Multi-institutional studies are required for the validation of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). A total of 1,560 fine-needle aspirations of the salivary glands were retrieved from two institutions for a 12-year period. The diagnoses were reclassified based on the MSRSGC. Risk of malignancy (ROM) for each category was calculated based on 694 histologic follow-up cases. The ROM for each category was: 18.3% for nondiagnostic, 8.9% for nonneoplastic, 37.5% for atypia of undetermined significance (AUS), 2.9% for benign neoplasm, 40.7% for salivary gland neoplasm of uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 98.3% for malignant. The sensitivity, specificity, positive predictive rate, and negative predictive rates were 89%, 99%, 98%, and 96%, respectively. The results of the current study are in keeping with the MSRSGC. The indeterminate categories of AUS and SUMP showed intermediate ROMs at 37.5% and 40.7%, respectively.

The majority of lung adenocarcinoma patients with epidermal growth factor receptor- ( EGFR ) mutated or EML4–ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called ‘driver mutations’ could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR -targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

Accurate preoperative detection and staging of pancreatic cancer may identify patients with locoregional disease that is amenable to surgical resection. To compare endoscopic ultrasonography and multidetector computed tomography (CT) for the detection, staging, and resectability of known or suspected locoregional pancreatic cancer. Prospective, observational, cohort study. Single, tertiary referral hospital in Indianapolis, Indiana. 120 participants with known or suspected locoregional pancreatic cancer. Endoscopic ultrasonography followed by multidetector CT was performed in all patients. Patients with known or suspected pancreatic cancer deemed potentially resectable by 1 or both tests were considered for surgery. Detection, staging, and resectability of pancreatic cancer. Surgically resected pancreatic cancer with negative microscopic histologic margins was considered resectable. Of 120 patients enrolled, 104 (87%) underwent endoscopic ultrasonography and CT. Of the 80 patients with pancreatic cancer, 27 (34%) were managed nonoperatively, and 53 (66%) treated surgically had resectable (n = 25) or unresectable (n = 28) cancer. For the 80 patients with cancer, the sensitivity of endoscopic ultrasonography (98% [95% CI, 91% to 100%]) for detecting a pancreatic mass was greater than that of CT (86% [CI, 77% to 93%]; P = 0.012). For the 53 surgical patients, endoscopic ultrasonography was superior to CT for tumor staging accuracy (67% vs. 41%; P < 0.001) but equivalent for nodal staging accuracy (44% vs. 47%; P > 0.2). Of the 25 resectable pancreatic tumors in patients recommended for surgery, endoscopic ultrasonography and CT correctly identified 88% and 92%, respectively, as resectable. Of the 28 unresectable pancreatic tumors in patients recommended for surgery, endoscopic ultrasonography and CT correctly identified 68% and 64%, respectively, as unresectable. Radiologists who read the scans and endosonographers were not blinded to previous radiographic information. Because of the modest sample size, CIs of the sensitivity estimates were sometimes wide. Compared with multidetector CT, endoscopic ultrasonography is superior for tumor detection and staging but similar for nodal staging and resectability of preoperatively suspected nonmetastatic pancreatic cancer.

(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).

Immunocytochemistry (ICC) performed on the cell-transferred cytologic smears (CTCS) of fine-needle aspiration (FNA) is useful when the cell blocks lack adequate material. The comparison of the ICC results from the CTCS of FNA with the corresponding formalin-fixed paraffin-embedded tissue (FFPE) has not been reported previously. We applied 12 commonly used ICC antibodies on 160 pieces of ethanol-fixed, cell-transferred Papanicolaou-stained smears obtained from 42 FNA specimens and compared the staining results with the corresponding FFPE on which the same panel of immunostains was performed. Of the 160 pieces of transferred materials, only 3 (1.9%) were lost during specimen processing. In total, 153 of 157 (97.5%) showed staining results that agreed with the corresponding FFPE, including 78 of 81 positive staining and 75 of 76 negative staining cases. ICC performed on the cell-transferred FNA smears is reliable and shows staining results highly comparable with the corresponding FFPE tissue.

Objectives: To determine the utility of the cell transfer technique (CTT) for BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens. Methods: Polymerase chain reaction (PCR)–based BRAF molecular testing was performed on tissues obtained through CTT from both air-dried and ethanol-fixed direct smears of thyroid FNA specimens and then compared with the corresponding thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases. Results: BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of 30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13, and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was 96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues. Conclusions: PCR-based BRAF mutational testing can be reliably performed on the direct smears of the thyroid FNA specimens through the application of CTT.

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.

Pancreatic cysts are increasingly being identified by cross-sectional imaging studies. Pancreatic cystic lesions comprise a spectrum of underlying pathologies ranging from benign and pre-malignant lesions to frank malignancies. Magnetic resonance imaging with cholangiopancreatography is a non-invasive imaging modality used for the characterization of cystic pancreatic lesions. This article will review the most common pancreatic cystic neoplasms and the utility of MR imaging in the characterization of these cysts.

To report the development, in an adult patient, of Langerhans' cell histiocytosis (LCH) involving the thyroid and most probably the pituitary gland, lungs, and liver. We present a case report of a 29-year-old woman who requested a medical consultation because of polyuria and was found to have pituitary dysfunction. We describe the subsequent follow-up, which revealed progressive liver disease that necessitated transplantation and also the presence of a goiter, and discuss the unpredictable pathologic features of LCH. After the diagnosis of central diabetes insipidus and partial hypopituitarism, the patient was diagnosed 2 years later with sclerosing cholangitis. The hepatic involvement was progressive, and she required transplantation and immunosuppression. Three months before liver transplantation, a goiter was discovered. Fine-needle aspiration of the thyroid revealed infiltration by LCH. The goiter decreased in size after chemotherapy with vinblastine and prednisone. Computed tomography of the chest showed bilateral thin-walled cysts, consistent with eosinophilic granulomas. In patients with central diabetes insipidus and pituitary stalk thickening on imaging studies, LCH should be considered in the differential diagnosis. Other hormonal deficiencies may be present initially or may evolve after many years. Thus, continual surveillance is necessary. In addition, an ongoing potential exists for involvement of other organ systems such as the thyroid, liver, and lungs. We suggest consideration of LCH as a possible cause of a goiter in such patients. In our patient, it remains to be seen what effect the immunosuppressive therapy for the liver transplant has on the LCH disease process.

Dermatix is a Food and Drug Administration (FDA)-registered substantial equivalent to silicone gel sheeting for the prevention and management of hypertrophic scars and keloids. A 90-day prospective study evaluated the efficacy of Dermatix, silicone gel sheeting, and a combination of these treatments in improving scars for 30 patients. Each patient had a bilateral scar that served as an untreated control. The outcome measures included profilometry analysis of scar topography before and after punch biopsies of the control and treated scars, symptoms associated with the scars, and patient evaluations of the ease of treatment. The results showed better resolution and improvement of scars with Dermatix treatment or the combined use of Dermatix and silicone gel sheeting than with silicone gel sheeting alone. Wound erythema was reduced, and collagen architectural reorientation was demonstrated histologically. Patients rated Dermatix as easier to use than silicone gel sheeting. Both Dermatix and silicone gel sheeting reduced symptoms of itching, irritation, and skin maceration. The results of this study indicate that Dermatix is a useful treatment for the management of abnormal scarring.