Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases.

BACKGROUND: Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population. OBJECTIVE: To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings. METHODS: 1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting. RESULTS: Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas. CONCLUSION: Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.

Dermoscopic and reflectance confocal microscopy features of cutaneous squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) of the skin is a highly prevalent neoplasm. The management and the prognosis of this tumour are dependent on its invasiveness and its grade of differentiation. OBJECTIVES: To evaluate whether specific dermoscopic and reflectance confocal microscopy (RCM) criteria can predict the diagnosis of invasive SCC vs. in situ SCC and poorly differentiated compared with well- and moderately differentiated SCC. METHODS: Dermoscopic and RCM images of SCC were retrospectively evaluated for the presence of predefined criteria. RESULTS: Among 143 SCCs, 121 cases had a complete set of images and thus were included in the study set. The head and neck area was the most frequently involved body site (74/121; 61.1%) followed by extremities (36/121, 29.7%) and trunk (11/121, 9.1%). Seventy tumours were in situ (57.8%), while 51 were invasive (42.1%), of these 11 were poorly differentiated (21.5%), 16 were moderately differentiated (31.3%), and 24 were well differentiated (47.0%). Chi-squared analysis demonstrated that invasive SCCs were characterized by polymorphic vessels, erosion/ulceration, architectural disarrangement, speckled nucleated cells in the dermis, irregularly dilated vessels and absence of hyperkeratosis. Buttonhole vessels, white structureless areas and dotted or glomerular vessels were significantly associated with in situ lesions. Poorly differentiated SCCs were typified by red areas, erosion/ulceration and architectural disarrangement. Well- or moderately differentiated SCCs were associated with white areas and speckled nucleated cells in the epidermis. CONCLUSION: Clinical, dermoscopic and RCM images provide useful information that should be integrated in order to achieve the optimal therapeutic management for the patient.

A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index.

BACKGROUND: Actinic keratosis (AK) severity is currently evaluated by subjective assessment of patients. OBJECTIVES: To develop and perform an initial pilot validation of a new easy-to-use quantitative tool for assessing AK severity on the head. METHODS: The actinic keratosis area and severity index (AKASI) for the head was developed based on a review of other severity scoring systems in dermatology, in particular the psoriasis area and severity index (PASI). Initial validation was performed by 13 physicians assessing AK severity in 18 AK patients and two controls using a physician global assessment (PGA) and AKASI. To determine an AKASI score, the head was divided into four regions (scalp, forehead, left/right cheek ear, chin and nose). In each region, the percentage of the area affected by AKs was estimated, and the severities of three clinical signs of AK were assessed: distribution, erythema and thickness. RESULTS: There was a strong correlation between AKASI and PGA scores (Pearson correlation coefficient: 0.86). AKASI was able to discriminate between different PGA categories: mean (SD) AKASI increased from 2.88 (1.18) for 'light' to 5.33 (1.48) for 'moderate', 8.28 (1.89) for 'severe', and 8.73 (3.03) for 'very severe' PGA classification. The coefficient of variation for AKASI scores was low and relatively constant across all PGA categories. CONCLUSIONS: Actinic keratosis area and severity index is proposed as a new quantitative tool for assessing AK severity on the head. It may be useful in the future evaluation of new AK treatments in clinical studies and the management of AK in daily practice.

Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology.

BACKGROUND: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, with progressive trend towards squamous cell carcinoma. OBJECTIVE: To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification, through a discrete ranking. METHODS: A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written software. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the image showing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. RESULTS: Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading. CONCLUSIONS: Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading.

Update on non-invasive imaging techniques in early diagnosis of non-melanoma skin cancer.

UNLABELLED: Non-melanoma skin cancer (NMSC) is the most common malignancy in fair skinned populations. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are non-invasive imaging techniques that play an important role in diagnosis of skin tumors. The aim of this study was to provide new insights into the role of non-invasive tecniques in the diagnosis of non-melanoma skin cancers, concentrating especially on dermoscopy, RCM and OCT. The analysis of the studies obtained from the most recent literature, taking into account previous essential reported information in this field. A search concerning the role of dermoscopy, RCM and OCT in the diagnosis of NMSC was performed on PubMed. EXCLUSION CRITERIA: duplicated studies, single case report, and papers with language other than English New and old literature about early diagnosis of NMSC through non-invasive imaging techniques were analyzed. The role and the diagnostic accuracy of dermoscopy, RCM and OCT for the diagnosis of NMSC were reported according to the data given by literature. The development of non-invasive diagnostic devices (especially dermoscopy, RCM and OCT) allows tissue imaging in-vivo contributing to a more accurate diagnosis of skin cancer, sparing time for the patient and costs for the public health system.

Update on the use of confocal microscopy in melanoma and non-melanoma skin cancer.

Reflectance confocal microscopy (RCM) is a new technique enabling the visualization of the skin at a quasi-histological resolution, allowing the identification of clues for the diagnosis of skin diseases. The aim of this analysis was to provide new insights into the role of RCM in the diagnosis of skin cancers. Data comes from the most recent literature, taking into account previous essential reported information in this field. The study eligibility criteria were: studies providing update information, focusing on RCM findings in melanoma and non-melanoma skin cancers (NMSC), without restrictions for age, sex, ethnicity. Duplicated studies and single case report were excluded from this study. A search concerning the role of RCM in melanoma and NMSC was performed on the Medline. RCM clues were analyzed for different skin cancers, in particular melanoma and NMSC, in association with clinical, dermoscopic and histopathologic findings. Diagnostic accuracy, sensibility and specificity of the technique were reviewed. Furthermore, some new findings have been described and recent applications have been discussed. The selection of articles was limited in order to provide an up-to-date revision. In conclusion, several RCM features were implemented for the diagnosis of melanoma and NMSC, leading to a confocal-based classification in most cases.

Reflectance confocal microscopy as a second-level examination in skin oncology improves diagnostic accuracy and saves unnecessary excisions: a longitudinal prospective study.

BACKGROUND: Dermatoscopy increases both the sensitivity and specificity of melanoma diagnosis. Reflectance confocal microscopy (RCM) is a noninvasive technique that complements dermatoscopy in the evaluation of equivocal lesions at cellular resolution. OBJECTIVES: To determine prospectively the potential impact of confocal microscopy when implemented in a routine melanoma diagnosis workflow. METHODS: Patients referred to a single melanoma clinic were consecutively enrolled. At dermatoscopy, patients were referred to one of the following pathways: (i) no further examination or (ii) RCM examination. On examination atypical lesion(s) were referred for either (a) RCM documentation (lesions with consistent suspicious clinical/dermatoscopic criteria, already qualified and scheduled for surgical excision) or (b) RCM consultation for equivocal lesions, where RCM diagnosis would determine lesion definite outcome (excision or digital follow-up). RESULTS: Reflectance confocal microscopy examination was performed for 41% of 1005 patients enrolled. In two-thirds of these cases RCM influenced the lesion outcome. The systematic application of RCM for equivocal lesions saved over 50% of benign lesions from unnecessary excision. The number needed to excise a melanoma was 6·8 with RCM examination, compared with a hypothetical 14·6 without RCM evaluation. CONCLUSIONS: Reflectance confocal microscopy as a second-level examination to dermatoscopy proved to be highly accurate in diagnosis and reduced the number of unnecessary excisions. Improved accuracy, considering that RCM enabled the detection of the six melanomas (2%) in the group of 308 lesions eligible for follow-up, also minimizes the risk of referring a melanoma to digital dermatoscopy monitoring, and potentially losing the patient to follow-up.

[Dermatoscopy and reflectance confocal microscopy aspects of a "nested melanoma of the elderly"]. / Aspect en dermatoscopie et en microscopie confocale par réflectance d'un « mélanome en thèques du sujet âgé ¼

BACKGROUND: We report a case of a nested melanoma of the elderly, a recently described entity, and we describe its aspect under confocal reflectance microscopy. PATIENTS AND METHODS: A 70-year-old woman presented a pigmented lesion of the left leg measuring 2 × 2.5 cm in diameter which was increasing in size. Dermatoscopic examination showed a predominantly globular pattern, with globules of irregular color and distribution. Reflectance confocal microscopy revealed the presence of dense nests at the dermo-epidermal junction with cytologic atypia and pagetoid cells. The histological appearance was overlapping and a diagnosis of nested melanoma of the elderly was made. COMMENTS: The presence in an older subject of a large pigmented lesion with an irregular globular pattern should be suspected of nested melanoma of the elderly. Reflectance confocal microscopy may be useful in the case of such difficult lesions to proceed with more confidence to surgical excision.

Towards an in vivo morphologic classification of melanocytic nevi.

BACKGROUND: Nevi are common benign neoplasms and the main diagnostic entity in the differential diagnosis of melanoma. Reflectance confocal microscopy (RCM), a novel technique for skin imaging at cellular-level magnification, has been shown to be useful for differentiating nevi from melanoma. However, systematic studies of the specific RCM features of nevi are still lacking. OBJECTIVE: To describe the characteristic RCM features of common melanocytic nevi and to correlate them with histopathology. METHODS: A total of 180 biopsy-proven nevi were imaged with RCM prior to excision. RCM images were evaluated for the overall nevus pattern and presence of specific RCM criteria. Upon histopathology, nevi were analysed for thickness using adapted Breslow depth and Clark's level grading. RESULTS: Observed RCM patterns varied according to anatomic depth of nevi. Junctional nevi were mainly characterized on RCM by a Ringed pattern, indicating a predominantly single cell proliferation of melanocytes; in contrast, the junctional component of compound nevi appeared on RCM as a Meshwork pattern, indicating a predominantly nested-proliferation. In compound nevi, the size of dermal nests was related to the thickness of nevi. Moreover, nevi extending deeper into the dermis were more likely to display a junctional component that extended laterally beyond the dermal component and appeared on RCM as either Ringed or Meshwork pattern. Intradermal nevi showed on RCM, in almost all cases, large clods. CONCLUSIONS: The possibility for in vivo histopathological classification of nevi may help in attaining a better understanding of the origin of nevi and of nevus-related melanoma risk.

Confocal microscopy of recurrent naevi and recurrent melanomas: a retrospective morphological study.

BACKGROUND: Repigmentation within a scar after different procedures (shave biopsy, partial excision, cryotherapy, laser) is a challenging diagnostic situation. OBJECTIVES: To determine distinct dermoscopic and confocal microscopic features in a series of histopathologically proven melanocytic proliferations within a scar. METHODS: Clinical, dermoscopic and confocal microscopic images were acquired before surgical excision in seven patients with repigmentation within a scar. The evaluation of the dermoscopic and confocal features was performed in blind to the final histopathological diagnosis that was obtained in all cases. RESULTS: Dermoscopically, the repigmentation in recurrent naevi (three patients) was confined within the scar while it extended beyond the scar in melanomas. This clue was more evident upon reflectance confocal microscopy (RCM). Confocally, recurrent naevi failed to exhibit prominent pagetoid or lateral spread of melanocytes and atypical nests at the junction, even though some cases showed atypical cells in the junctional component. However, these were few in number and cytologically monomorphous and allowed the diagnosis of a benign neoplasm with confidence. On the other hand, melanomas arising on a scar (four patients) revealed dendritic-shaped melanocytes arranged in sheets, and pagetoid and lateral spread of dendritic cells extending beyond the scar. Those confocal aspects were well correlated with the histopathological findings. CONCLUSIONS: The integration of clinical, dermoscopic and RCM aspects offers the possibility to discern reliably the nature in cases of repigmentation on a scar.

Long-term results after atrial correction of complete transposition of the great arteries.

This study presents the late results for the first 104 consecutive patients surviving and atrial repair for transposition of the great arteries (TGA) between January 1971 and December 1978 (group 1). Mean follow-up was 12 years (range, 0.1 to 17.7 years). The actuarial survival rate at 18 years was 84.2% (70% confidence limits, 79% to 88%) for simple TGA and 93.7% (70% confidence limits, 84% to 97%) for complex TGA. Nine of the 11 deaths were sudden. Two (2.6%) of the 78 late survivors operated on for simple TGA are in New York Heart Association functional class III or IV versus 4 (26.7%) of the 15 survivors with complex TGA; the other patients are doing very well. To better assess long-term results, we report the findings for randomly obtained electrocardiograms, Holter monitor recordings, radionuclide angiographic studies, and cardiac catheterizations performed in 1987 in a larger group of 159 long-term survivors of atrial repair operated on at Ospedale Riuniti di Bergamo from January 1971 to December 1984 (group 2), which includes all of group 1. The findings confirm that the arterial switch repair is the procedure of choice for complex TGA and that there is a major incidence (approximately 10%) of systemic right ventricular dysfunction and rhythm disturbances after the atrial repair. On the other hand, our late survival rate at 18 years of 84% for simple TGA with 97.5% of the patients in functional class I is a result that should be kept in mind, especially in institutions where the arterial switch is a relatively new approach and presumably is a higher risk to cause early death.

[Circulatory assistance in high-risk coronary angioplasty]. / Assistenza circolatoria nell'angioplastica coronarica ad alto rischio.

Femoral vein to artery cardiopulmonary by-pass was used during coronary angioplasty in five high risk patients. In four patients the target vessel supplied more than half of the viable myocardium; in one of these, the ejection fraction of the left ventricle was less than 20%. In one patient the relative contraindications for surgery were the patient's age and the presence of concomitant renal failure. Cardiopulmonary support was established by using cut-down cannulae insertion in three patients and by using the percutaneous system in two. In the latter, the support was stand-by, but the abrupt closure of the artery ten minutes after the end of the successful procedure, required the prompt activation of the support and the patient was treated with emergency saphenous graft. The use of the cardiopulmonary support either as a prophylactic or as a stand-by, enabled coronary angioplasty to be performed on these high-risk patients. The clinical and anatomical data relative to the five patients as well as the possible use of the cardiopulmonary support system either as a prophylactic or standby application during high-risk PTCA are discussed.