Case Report: Durable complete pathologic response and organ preservation following ipilimumab and nivolumab for locally advanced primary vaginal mucosal melanoma.

Optimal management of locally advanced vaginal mucosal melanoma is poorly understood because of its rarity and unique biology. Patients have a poor prognosis despite aggressive management approaches including pelvic exenteration and adjuvant radiation that carry major morbidities. We report a case of a patient in early 40's who experienced complete pathologic response and organ preservation following immunotherapy consisting of 3 cycles of ipilimumab and nivolumab. Treatment was complicated by a high-grade immune mediated hepatitis that eventually resolved with immunosuppressive therapy. Immune monitoring studies utilizing vaginal tumor biopsies showed evidence of enhanced infiltration by CD3+/CD8+ cytotoxic T-cells and increased expression of MHC-I/PD-L1 within the tumor microenvironment following immunotherapy. The patient continues to be without evidence of disease recurrence by radiologic and gynecologic examinations with more than 2 years of follow up from the time of immunotherapy initiation. To our knowledge, this is the only case report in the literature of a patient with locally advanced vaginal mucosal melanoma experiencing a durable complete pathologic response and organ preservation following immune checkpoint blockade as the only treatment approach.

Diffuse intrasinusoidal hepatic metastasis from breast cancer: Multimodality imaging with pathology correlation.

Metastatic disease to the liver is a known and common site of breast cancer spread, classically presenting as either hypovascular or hypervascular masses. Rarely, hepatic metastatic disease may have an atypical diffuse and intrasinusoidal pattern of involvement, which may be radiographically occult or extremely challenging to diagnose even with multiphase contrast enhanced techniques. We report a case of a 28-year-old female with stage III invasive ductal carcinoma of the breast, who recently discontinued treatment due to pregnancy, presenting with progressive signs and symptoms of rapidly decompensating liver failure due to sinusoidal obstruction. Multimodality imaging was performed without evidence for focal hepatic metastatic disease; however, intrahepatic vein (IVC) compression was noted. Hepatic sinusoidal tumor infiltration was confirmed by liver biopsy. After palliative chemotherapy the disease became less infiltrative and more conspicuous on imaging, revealing itself as hepatic metastases, with decreased compression of the intrahepatic IVC and resolution of signs and symptoms of sinusoidal obstruction syndrome.

Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and RAS Mutations.

Background:RAS gene family mutations are the most prevalent in thyroid nodules with indeterminate cytology and are present in a wide spectrum of histological diagnoses. We evaluated differentially expressed genes and signaling pathways across the histological/clinical spectrum of RAS-mutant nodules to determine key molecular determinants associated with a high risk of malignancy. Methods: Sixty-one thyroid nodules with RAS mutations were identified. Based on the histological diagnosis and biological behavior, the nodules were grouped into five categories indicating their degree of malignancy: non-neoplastic appearance, benign neoplasm, indeterminate malignant potential, low-risk cancer, or high-risk cancer. Gene expression profiles of these nodules were determined using the NanoString PanCancer Pathways and IO 360 Panels, and Angiopoietin-2 level was determined by immunohistochemical staining. Results: The analysis of differentially expressed genes using the five categories as supervising parameters unearthed a significant correlation between the degree of malignancy and genes involved in cell cycle and apoptosis (BAX, CCNE2, CDKN2A, CDKN2B, CHEK1, E2F1, GSK3B, NFKB1, and PRKAR2A), PI3K pathway (CCNE2, CSF3, GSKB3, NFKB1, PPP2R2C, and SGK2), and stromal factors (ANGPT2 and DLL4). The expression of Angiopoietin-2 by immunohistochemistry also showed the same trend of increasing expression from non-neoplastic appearance to high-risk cancer (p < 0.0001). Conclusions: The gene expression analysis of RAS-mutant thyroid nodules suggests increasing upregulation of key oncogenic pathways depending on their degree of malignancy and supports the concept of a stepwise progression. The utility of ANGPT2 expression as a potential diagnostic biomarker warrants further evaluation.

Preoperative Radiographic Assessment Predicts Incomplete Cytoreduction in Patients with Low Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). METHODS: Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720-0.910] and 0.788 [0.667-0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. CONCLUSIONS: External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

Ultrasound characterization for thyroid nodules with indeterminate cytology: inter-observer agreement and impact of combining pattern-based and scoring-based classifications in risk stratification.

BACKGROUND: The American Thyroid Association (ATA) sonographic patterns stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs). This study aimed to (1) assess inter-observer agreement for sonographic features and patterns; (2) identify potential sources of disagreement; and (3) evaluate whether the number of suspicious features risk-stratifies non-ATA and high-suspicion patterns. METHODS: Three observers independently reviewed the ultrasound images of 463 ITNs with histological follow-up consecutively evaluated between October 2008 and June 2015 at an academic cancer center. Each observer evaluated individual sonographic features. ATA sonographic patterns were derived from the interpretation of sonographic features. Nodules not fitting into any of the proposed patterns were clustered into a non-ATA pattern. RESULTS: The inter-observer agreement for ATA sonographic patterns and echogenicity was fair, moderate for margins, good for composition and echogenic foci, and very good for extrathyroidal extension and lymph node metastasis. The interpretation of each sonographic feature was significantly different between observers, and there was complete disagreement in at least one of the features in 104 (22%) nodules. A total of 169 nodules (37%) were classified into the non-ATA pattern. The number of suspicious features allowed risk stratifying nodules with non-ATA and high-suspicion sonographic patterns. Most Non-invasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features had 0-1 suspicious features and none had >2. CONCLUSIONS: Echogenicity interpretation was the greatest source of disagreement. The number of suspicious features risk-stratifies ITNs with non-ATA or high-suspicion patterns. Future studies attempting to objectivize the interpretation of echogenicity and heterogeneity are needed.

Thyroid Nodules with Indeterminate Cytology: Utility of the American Thyroid Association Sonographic Patterns for Cancer Risk Stratification.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines recommend using a classification based on sonographic patterns to set the size threshold for biopsies. Each pattern is associated with a distinct estimated rate of malignancy that it was hypothesized should stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs). METHODS: Ultrasound images of 463 ITNs (38% atypia/follicular lesions of undetermined significance; 62% follicular neoplasms) with histological follow-up consecutively evaluated between October 2008 and June 2015 at the authors' academic cancer center were independently evaluated by three observers and classified into one of the five sonographic patterns proposed by the ATA. Nodules with sonographic patterns not defined in the classification were grouped into a non-ATA pattern category. Differences in clinical and histological findings between the sonographic patterns were assessed. The prevalence of malignancy and odds ratio for malignancy were calculated for each sonographic pattern (low and intermediate patterns were collapsed for the analysis). RESULTS: The distribution of size and cytological diagnosis was significantly different between sonographic patterns (p < 0.001). The overall rate of malignancy was 27%. The rate of malignancy for the very low, low/intermediate, high, and non-ATA patterns were 0%, 19%, 56%, and 36%, respectively, and were all significantly different. Compared to the low/intermediate suspicion patterns, the odds ratios for malignancy were 2.35 for the non-ATA and 5.18 for the high suspicion patterns (p < 0.001). The odds ratio of the non-ATA pattern was 0.45 over the high suspicion pattern (p = 0.04). Results were similar in both cytological categories and for each observer separately. Sonographic patterns were associated with distinct histopathological profiles (p < 0.001). CONCLUSIONS: ATA sonographic patterns are associated with distinct clinical features and pathological outcomes, and effectively stratify the cancer risk in ITNs. Thus, the ATA sonographic patterns should be used not only to set the size threshold for biopsy, but also to personalize management after the biopsy.

Retroperitoneal lymphangioleiomyoma with lymph node involvement: A pathologic-radiologic correlation of a rare form of myomelanocytic tumor.

Lymphangioleiomyomatosis (LAM) is a rare and slowly progressive disorder that usually arises in the lung, affects exclusively women in their childbearing years, and typically presents with progressive dyspnea on exertion and pneumothorax. Infrequently, extra-pulmonary LAM can occur in the retroperitoneum, uterine wall, mediastinum and intraperitoneal lymph nodes. Histologically, LAM is characterized by a proliferation of perivascular epithelioid cells (PEC) that express markers for both melanocytes and smooth muscle cells. We report a case of a peripancreatic retroperitoneal mass that was incidentally discovered on magnetic resonance image (MRI) scan of a 38-year-old female. The morphologic findings and the immunohistochemical staining were consistent with a lymphangioleiomyoma. The radiologic and pathologic correlation along with differential diagnosis of this rare entity is discussed.

Informatics in radiology: radiology gamuts ontology: differential diagnosis for the Semantic Web.

The Semantic Web is an effort to add semantics, or "meaning," to empower automated searching and processing of Web-based information. The overarching goal of the Semantic Web is to enable users to more easily find, share, and combine information. Critical to this vision are knowledge models called ontologies, which define a set of concepts and formalize the relations between them. Ontologies have been developed to manage and exploit the large and rapidly growing volume of information in biomedical domains. In diagnostic radiology, lists of differential diagnoses of imaging observations, called gamuts, provide an important source of knowledge. The Radiology Gamuts Ontology (RGO) is a formal knowledge model of differential diagnoses in radiology that includes 1674 differential diagnoses, 19,017 terms, and 52,976 links between terms. Its knowledge is used to provide an interactive, freely available online reference of radiology gamuts ( www.gamuts.net ). A Web service allows its content to be discovered and consumed by other information systems. The RGO integrates radiologic knowledge with other biomedical ontologies as part of the Semantic Web.

Dose reduction of 69% for computed tomography pulmonary angiography: reduced z-axis computed tomography pulmonary angiography retains accuracy in those younger than 40 years.

OBJECTIVE: We sought to determine whether reduced scan range (z axis) computed tomography pulmonary angiography (CTPA) technique in 18- to 40-year age group can accurately detect pulmonary embolism (PE) and other important conditions and to quantify the resulting dose reduction. METHODS: We retrospectively identified 200 patients in the age group of 18 to 40 years who underwent CTPA over a period of 3 years. These included 86 patients with PEs and 114 randomly selected patients negative for PE (control subjects). The scans were modified by reducing the scan coverage by eliminating images above the aortic arch and below the base of the heart. Two blinded experienced radiologists rescored them for PE and incidental and pertinent non-PE findings. Discrepancies between these and the original report were assessed by a third experienced radiologist. Separately, a departmental quality-control project was conducted in 15 patients to assess the dose length product along the z axis across the 3 zones of thorax. RESULTS: Pulmonary embolism was diagnosed in all 86 patients. No pertinent additional findings were missed. Only 7 incidental findings were missed (eg, benign thyroid nodules [n = 4], benign adrenal adenoma [n = 1], gallstones [n = 1], and hepatic hemangioma [n = 1]). None affected clinical outcome or management. Dose length product was reduced by a mean of 69% (60%-79%). CONCLUSIONS: Reduced z-axis CTPA for PE is definitely feasible in 18- to 40-year age group. There is a significant radiation reduction (69%) and hence should be considered in selected subgroups of patients.

Development of a pilot family medicine hand-carried ultrasound course.

BACKGROUND AND OBJECTIVES: A hand-carried ultrasound training session was organized as an initial step in developing a long-term ultrasound education program for family medicine residents and faculty. Comparative effectiveness studies examining the potential benefits, risks, and any possible cost savings associated with this technology will be predicated on having a sufficient number of primary care physicians trained and able to use hand-carried ultrasounds as part of routine care. The proposed training described here is a first step toward this broader conversation and empirical study of hand-carried ultrasound use in family medicine. METHODS: An 8-hour training consisting of didactic lectures, case review, and hands-on experience imaging standardized patients with ultrasound machines and an ultrasound simulator. The objective of the course was to introduce focused ultrasound acquisition and interpretation of the gall bladder, kidney, heart, and abdominal aorta to family medicine physicians. Participating physicians were evaluated for changes in self-perceived comfort and proficiency with the hand-carried ultrasound before and after the training. RESULTS: Statistically significant changes for most comfort and proficiency items were demonstrated. Importantly, the only item that did not show significant change dealt with basing clinical decisions on information obtained from the device. CONCLUSION: The subjective improvement suggests this approach is one potentially useful hand-carried ultrasound training framework. Future work should attempt to further develop curricula and address issues such as longitudinal training assessments and certification and the development of competency in the necessary skill sets.

Accurate determination of imaging modality using an ensemble of text- and image-based classifiers.

Imaging modality can aid retrieval of medical images for clinical practice, research, and education. We evaluated whether an ensemble classifier could outperform its constituent individual classifiers in determining the modality of figures from radiology journals. Seventeen automated classifiers analyzed 77,495 images from two radiology journals. Each classifier assigned one of eight imaging modalities--computed tomography, graphic, magnetic resonance imaging, nuclear medicine, positron emission tomography, photograph, ultrasound, or radiograph-to each image based on visual and/or textual information. Three physicians determined the modality of 5,000 randomly selected images as a reference standard. A "Simple Vote" ensemble classifier assigned each image to the modality that received the greatest number of individual classifiers' votes. A "Weighted Vote" classifier weighted each individual classifier's vote based on performance over a training set. For each image, this classifier's output was the imaging modality that received the greatest weighted vote score. We measured precision, recall, and F score (the harmonic mean of precision and recall) for each classifier. Individual classifiers' F scores ranged from 0.184 to 0.892. The simple vote and weighted vote classifiers correctly assigned 4,565 images (F score, 0.913; 95% confidence interval, 0.905-0.921) and 4,672 images (F score, 0.934; 95% confidence interval, 0.927-0.941), respectively. The weighted vote classifier performed significantly better than all individual classifiers. An ensemble classifier correctly determined the imaging modality of 93% of figures in our sample. The imaging modality of figures published in radiology journals can be determined with high accuracy, which will improve systems for image retrieval.