Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden.

In ultraviolet (UV) radiation-exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and the correlation between CMs and skin cancer risk are largely unexplored. We characterized 450 individual-matched sun-exposed (SE) and non-SE (NE) normal human skin samples. The number and relative contribution of CMs were significantly different between SE and NE areas. Furthermore, we identified hotspots in TP53, NOTCH1, and GRM3 where mutations were significantly associated with UV exposure. In the normal skin from patients with cutaneous squamous cell carcinoma, we found that the cancer burden was associated with the UV-induced mutations, with the difference mostly conferred by the low-frequency CMs. These findings provide previously unknown information on UV's carcinogenic effect and pave the road for future development of quantitative assessment of subclinical UV damage and skin cancer risk.

Common CT Findings of Novel Coronavirus Disease 2019 (COVID-19): A Case Series.

Given the highly infectious nature of the coronavirus disease 2019 (COVID-19) virus and the lack of proven specific therapeutic drugs and licensed vaccines effective against it, early diagnosis of the disease is of paramount importance. The common chest CT imaging of confirmed COVID-19 cases is discussed here, which shows ground-glass opacity, crazy paving, and consolidation.

Metastatic melanoma with features of blue nevus and tumoral melanosis identified during pembrolizumab therapy.

Metastatic melanoma may exhibit clinical or histologic features of blue nevus. Pembrolizumab therapy is associated with regression and tumoral melanosis. We report on a man with widespread metastatic melanoma on pembrolizumab therapy in whom a blue-grey papule developed on the left side of his neck that clinically resembled a blue nevus and histologically showed features of both blue nevus and tumoral melanosis. The subtle melanocytic component and prominent changes of regression evident on biopsy suggest that his immunomodulatory therapy may have influenced the histologic findings noted on biopsy. Physicians that treat patients with metastatic melanoma should be aware of the spectrum of histologic findings evident on biopsy not only to allow for early diagnosis but to also better understand the effects of treatment.

Pigmented epithelioid melanocytoma (animal-type melanoma): An institutional experience.

BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently described entity with unknown biologic behavior. There is a high rate of regional metastases, but limited evidence of distant metastases or disease-related death. OBJECTIVE: We sought to report our series of patients given a diagnosis of PEM at our institution and provide mutational analysis of genes commonly implicated in melanoma in 2 cases. METHODS: The pathology database was queried for cases of PEM diagnosed at the University of Rochester. Charts were reviewed for follow-up information. Mutational analysis of melanoma-associated genes was performed on 2 cases. RESULTS: Nine cases of PEM were retrieved in a 10-year retrospective review. Five patients underwent sentinel lymph node biopsy with 3 of 5 having a positive sentinel lymph node. All 9 patients are alive and disease-free with average follow-up of 38.75 months. Two tumors were tested for common melanoma-associated mutations, and were negative, except for a telomerase reverse transcriptase promoter deletion detected in 1 sample. The deletion has not been associated with melanoma, and therefore its biologic significance is unclear. LIMITATIONS: Small sample size, retrospective nature, and single institution experience are limitations. CONCLUSIONS: PEM appears to have an indolent behavior. However, currently the evidence is too limited to provide insight into its true biologic potential.

Detection of Occult Invasion in Melanoma In Situ.

Importance: It is unclear why some patients with in situ melanoma develop metastases. Few reports demonstrate occult invasion with immunohistochemistry staining, which were discordant with reports interpreting such staining as false-positive. Objective: To investigate the occurrence of occult invasive disease within in situ melanoma by using methods to circumvent potential limitations in prior study designs. Design, Setting, and Participants: Unequivocal in situ melanoma without associated nevi or regression was identified using a consecutive sample of 33 cases plus 1 index case in an academic medical center. After cutting deeper into the most representative tissue block, 3 sequential slides were stained with hematoxylin-eosin (H-E), melanoma antigen (melan-A), and again with H-E. Melan-A-stained slides showing definitive invasion were double-stained with Sry-related HMg-Box gene 10 (SOX10) to confirm the melanocytic nature of the cells of interest. The study evaluated the possibilities of occult invasion detected by immunohistochemistry, sectioning deeper into the tissue block, or both. Slides were independently scored by 3 dermatopathologists with interrater reliability assessed. The study was conducted from January 1, 2012, to July 31, 2014. Main Outcomes and Measures: Assessment of the occurrence of occult invasion, diagnosis of invasion by immunohistochemistry alone vs cutting deeper into the tissue block, and occurrence of false-positive results using immunohistochemistry alone. Results: Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and H-E staining, likely as a result of simply cutting deeper into the tissue block. Four cases (12%) showed a few melan-A-positive cells in the dermis, which was insufficient for a diagnosis of invasive melanoma and most consistent on a cytomorphologic basis with occult nevi. Conclusions and Relevance: Although rare, in situ melanoma may metastasize. Occult microinvasion was demonstrated in up to one-third of the specimens in the present study, which provides a plausible explanation for this adverse event. Thus, history and physical examination including regional lymph nodes, education, and surveillance recommendations should be based on a very low, but not zero, risk of metastasis.

2D/3D registration of endoscopic ultrasound to CT volume data.

This paper describes a computer-aided navigation system using image fusion to support endoscopic interventions such as the accurate collection of biopsy specimens. An endoscope provides the physician with real-time ultrasound (US) and a video image. An image slice that corresponds to the corresponding image from the US scan head is derived from a preoperative computed tomography (CT) or magnetic resonance image volume data set using oblique reformatting and displayed side by side with the US image. The position of the image acquired by the US scan head is determined by a miniaturized electromagnetic tracking system (EMTS) after calibrating the endoscope's scan head. The transformation between the patient coordinate system and the preoperative data set is calculated using a 2D/3D registration. This is achieved by calibrating an intraoperative interventional CT slice with an optical tracking system (OTS) using the same algorithm as for the US calibration. The slice is then used for 2D/3D registration with the coordinate system of the preoperative volume. The fiducial registration error (FRE) for the US calibration was 2.0 mm +/- 0.4 mm; the interventional CT FRE was 0.36 +/- 0.12 mm; and the 2D/3D registration target registration error (TRE) was 1.8 +/- 0.3 mm. The point-to-point registration between the OTS and the EMTS had an FRE of 0.9 +/- 0.4 mm. Finally, we found an overall TRE for the complete system to be 3.9 +/- 0.6 mm.

Design and application of an assessment protocol for electromagnetic tracking systems.

This paper defines a simple protocol for competitive and quantified evaluation of electromagnetic tracking systems such as the NDI Aurora (A) and Ascension microBIRD with dipole transmitter (B). It establishes new methods and a new phantom design which assesses the reproducibility and allows comparability with different tracking systems in a consistent environment. A machined base plate was designed and manufactured in which a 50 mm grid of holes was precisely drilled for position measurements. In the center a circle of 32 equispaced holes enables the accurate measurement of rotation. The sensors can be clamped in a small mount which fits into pairs of grid holes on the base plate. Relative positional/orientational errors are found by subtracting the known distances/ rotations between the machined locations from the differences of the mean observed positions/ rotation. To measure the influence of metallic objects we inserted rods made of steel (SST 303, SST 416), aluminum, and bronze into the sensitive volume between sensor and emitter. We calculated the fiducial registration error and fiducial location error with a standard stylus calibration for both tracking systems and assessed two different methods of stylus calibration. The positional jitter amounted to 0.14 mm(A) and 0.08 mm(B). A relative positional error of 0.96 mm +/- 0.68 mm, range -0.06 mm; 2.23 mm(A) and 1.14 mm +/- 0.78 mm, range -3.72 mm; 1.57 mm(B) for a given distance of 50 mm was found. The relative rotation error was found to be 0.51 degrees (A)/0.04 degrees (B). The most relevant distortion caused by metallic objects results from SST 416. The maximum error 4.2 mm(A)/ > or = 100 mm(B) occurs when the rod is close to the sensor(20 mm). While (B) is more sensitive with respect to metallic objects, (A) is less accurate concerning orientation measurements. (B) showed a systematic error when distances are calculated.

Design and application of an assessment protocol for electromagnetic tracking systems.

This paper defines a simple protocol for competitive and quantified evaluation of electromagnetic tracking systems such as the NDI Aurora (A) and Ascension microBIRD with dipole transmitter (B). It establishes new methods and a new phantom design which assesses the reproducibility and allows comparability with different tracking systems in a consistent environment. A machined base plate was designed and manufactured in which a 50 mm grid of holes was precisely drilled for position measurements. In the center a circle of 32 equispaced holes enables the accurate measurement of rotation. The sensors can be clamped in a small mount which fits into pairs of grid holes on the base plate. Relative positional/orientational errors are found by subtracting the known distances/rotations between the machined locations from the differences of the mean observed positions/rotation. To measure the influence of metallic objects we inserted rods made of steel (SST 303, SST 416), aluminum, and bronze into the sensitive volume between sensor and emitter. We calculated the fiducial registration error and fiducial location error with a standard stylus calibration for both tracking systems and assessed two different methods of stylus calibration. The positional jitter amounted to 0.14 mm(A) and 0.08 mm(B). A relative positional error of 0.96mm±0.68mm, range -0.06 mm; 2.23 mm(A) and 1.14mm±0.78mm, range -3.72 mm; 1.57 mm(B) for a given distance of 50 mm was found. The relative rotation error was found to be 0.51° (A)/0.04° (B). The most relevant distortion caused by metallic objects results from SST 416. The maximum error 4.2mm(A)∕⩾100mm(B) occurs when the rod is close to the sensor(20 mm). While (B) is more sensitive with respect to metallic objects, (A) is less accurate concerning orientation measurements. (B) showed a systematic error when distances are calculated.

Implementation, calibration and accuracy testing of an image-enhanced endoscopy system.

This paper presents a new method for image-guided surgery called image-enhanced endoscopy. Registered real and virtual endoscopic images (perspective volume renderings generated from the same view as the endoscope camera using a preoperative image) are displayed simultaneously; when combined with the ability to vary tissue transparency in the virtual images, this provides surgeons with the ability to see beyond visible surfaces and, thus, provides additional exposure during surgery. A mount with four photoreflective spheres is rigidly attached to the endoscope and its position and orientation is tracked using an optical position sensor. Generation of virtual images that are accurately registered to the real endoscopic images requires calibration of the tracked endoscope. The calibration process determines intrinsic parameters (that represent the projection of three-dimensional points onto the two-dimensional endoscope camera imaging plane) and extrinsic parameters (that represent the transformation from the coordinate system of the tracker mount attached to the endoscope to the coordinate system of the endoscope camera), and determines radial lens distortion. The calibration routine is fast, automatic, accurate and reliable, and is insensitive to rotational orientation of the endoscope. The routine automatically detects, localizes, and identifies dots in a video image snapshot of the calibration target grid and determines the calibration parameters from the sets of known physical coordinates and localized image coordinates of the target grid dots. Using nonlinear lens-distortion correction, which can be performed at real-time rates (30 frames per second), the mean projection error is less than 0.5 mm at distances up to 25 mm from the endoscope tip, and less than 1.0 mm up to 45 mm. Experimental measurements and point-based registration error theory show that the tracking error is about 0.5-0.7 mm at the tip of the endoscope and less than 0.9 mm for all points in the field of view of the endoscope camera at a distance of up to 65 mm from the tip. It is probable that much of the projection error is due to endoscope tracking error rather than calibration error. Two examples of clinical applications are presented to illustrate the usefulness of image-enhanced endoscopy. This method is a useful addition to conventional image-guidance systems, which generally show only the position of the tip (and sometimes the orientation) of a surgical instrument or probe on reformatted image slices.

Calibration and accuracy testing for image-enhanced endoscopy.

New surgical navigation techniques may combine the use of live video from a surgical endoscope with 3D volumetrically-reconstructed images of a patient's anatomy. This image-enhanced endoscopy requires calibration of the endoscope to ensure that the mapping of the real endoscope image to its virtual counterpart is properly performed. The application of a technique to calibrate an endoscope prior to use in a diagnostic or therapeutic procedure is described, as well as a simple yet effective linear method for lens-distortion compensation. The results of accuracy testing of the calibration technique using a dedicated testing apparatus are reported.