Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients With Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach.

In the era of artificial intelligence and precision medicine, the use of quantitative imaging methodological approaches could improve the cancer patient's therapeutic approaches. Specifically, our pilot study aims to explore whether CT texture features on both baseline and first post-treatment contrast-enhanced CT may act as a predictor of overall survival (OS) and progression-free survival (PFS) in metastatic melanoma (MM) patients treated with the PD-1 inhibitor Nivolumab. Ninety-four lesions from 32 patients treated with Nivolumab were analyzed. Manual segmentation was performed using a free-hand polygon approach by drawing a region of interest (ROI) around each target lesion (up to five lesions were selected per patient according to RECIST 1.1). Filtration-histogram-based texture analysis was employed using a commercially available research software called TexRAD (Feedback Medical Ltd, London, UK; https://fbkmed.com/texrad-landing-2/) Percentage changes in texture features were calculated to perform delta-radiomics analysis. Texture feature kurtosis at fine and medium filter scale predicted OS and PFS. A higher kurtosis is correlated with good prognosis; kurtosis values greater than 1.11 for SSF = 2 and 1.20 for SSF = 3 were indicators of higher OS (fine texture: 192 HR = 0.56, 95% CI = 0.32-0.96, p = 0.03; medium texture: HR = 0.54, 95% CI = 0.29-0.99, p = 0.04) and PFS (fine texture: HR = 0.53, 95% CI = 0.29-0.95, p = 0.03; medium texture: HR = 0.49, 209 95% CI = 0.25-0.96, p = 0.03). In delta-radiomics analysis, the entropy percentage variation correlated with OS and PFS. Increasing entropy indicates a worse outcome. An entropy variation greater than 5% was an indicator of bad prognosis. CT delta-texture analysis quantified as entropy predicted OS and PFS. Baseline CT texture quantified as kurtosis also predicted survival baseline. Further studies with larger cohorts are mandatory to confirm these promising exploratory results.

Novel cancer therapies for advanced cutaneous melanoma: The added value of radiomics in the decision making process-A systematic review.

Advanced malignant melanoma represents a public health matter due to its rising incidence and aggressiveness. Novel therapies such as immunotherapy are showing promising results with improved progression free and overall survival in melanoma patients. However, novel targeted and immunotherapies could generate atypical patterns of response which are nowadays a big challenge since imaging criteria (ie Recist 1.1) have not been proven to be always reliable to assess response. Radiomics and in particular texture analysis (TA) represent new quantitative methodologies which could reduce the impact of these limitations providing most robust data in support of clinical decision process. The aim of this paper was to review the state of the art of radiomics/TA when it is applied to the imaging of metastatic melanoma patients.

Sonographic appearance of sebaceous cysts. Our experience and a review of the literature.

Sebaceous cysts are benign enveloped nodules resulting from an obstruction of a hair follicle. Although they are very common, differential diagnosis is not obvious and may include many diseases. Ultrasound examination with high frequency probes, in the hands of a skilled operator, is the gold standard for noninvasive evaluation of these diseases. The aim of our study was to describe sonographic patterns found in our experience with high frequency probes. We decided to reevaluate the sonographic appearance of the last 100 patients with sebaceous cysts that were under our observation through conducting a retrospective study. All lesions were examined by a skilled radiologist with an Esaote MyLab 70 XVG ultrasound unit and a dedicated 18 MHz linear probe, sometimes supplemented by 20 MHz. In these skin lesions, we evaluated morphology, size, vascularity, and especially the visibility of skin pores, a characteristic of sebaceous cysts. We found 118 lesions that were mostly located on the trunk. In the majority of cases, the skin lesions had an oval-shaped morphology - 114 (96.6%) - and were hypoechoic in appearance -108 (91.5%). In 60 (50.8%) cases, the skin lesions showed a homogeneous appearance, known as "pseudotestis". The average ultrasound examines with very high frequency probes allowed to evidence skin pores. Our retrospective study on higher frequency probes confirms the data in literature regarding the diagnosis of sebaceous cysts, demonstrating the high incidence and clinical significance of evidence of the so-called epidermal punctum.

Color Doppler Sonography of Merkel Cell Carcinoma.

We illustrate the color Doppler sonographic findings in primary cutaneous Merkel cell carcinoma. Eight cases (4 female and 4 male; mean age, 75.4 years) were collected. The most common affected regions were the face (63%) and the hip/buttock (25%). The mean transverse diameter and thickness were 21 and 14 mm, respectively. Fifty percent were oval, and 50% were dome shaped. All lesions were hypoechoic, with variable degrees of heterogeneity. All but 2 lesions were poorly defined. An acoustic reinforcement artifact was present in 3 and epidermal thickening in 2. All tumors had prominent and chaotic hypervascularity with arterial vessels (mean peak velocity, 11 cm/s; mean resistive index, 0.57).

Color Doppler Sonography of Extradigital Glomus Tumors.

We retrospectively collected cases of surgically proven extradigital glomus tumor (EDGT) and reviewed their demographic, clinical, and sonography features. A total of 18 single, subcutaneous EDGTs were gathered. All but one were located in the extremities. EDGTs typically appear as a small, hypoechoic, homogeneous, or slightly inhomogeneous, well-delimited nodule, disposed horizontally and painful under probe pressure. Intranodular vascularization is always present. Feeding artery and efferent vein are typical but inconstant findings.

Electrochemotherapy of a Multirecurrent Dermatofibrosarcoma Protuberans of the Orbital Margin: A Case Report.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous sarcoma with high recurrence rate. Radical surgery is the treatment of choice, although in cosmetically-sensitive areas such as the head and neck, this option is often not pursued. Electrochemotherapy (ECT) is a minimal invasive anti-tumor modality which is increasingly being used to treat skin metastases from different malignancies. A 31-year-old woman presented with subcutaneous local multirecurring DFSP located at the proximal end of the left eyebrow. ECT was offered as a palliative treatment to avoid radical disfiguring surgery. Two days following ECT, the patient was discharged in good general health. Partial tumor regression was appreciable at two months' follow-up by ultrasound and magnetic resonance imaging. At six months, residual fibrotic tissue was observed; at three years, no evidence of the tumour was detected. In our case, ECT achieved good local tumor control with excellent cosmetic results, preserving the patient's quality of life.

HF ultrasound vs PET-CT and telethermography in the diagnosis of In-transit metastases from melanoma: a prospective study and review of the literature.

BACKGROUND: Over the past several years the incidence of cutaneous melanoma has rapidly increased. This tumor develops often in-transit metastases that significantly reduce patient survival at 5 years. To improve prognosis and quality of life in patients with melanoma metastases, a mini invasive procedure like electrochemotherapy (ECT) is adopted to remove superficial tissue lesions. To detect the melanoma metastases, high frequency (HF) ultrasound (US) is used. This technique, though, can be time-consuming and it needs an expert operator and a high performing machine. Therefore, we asked whether the US could be replaced or integrated with other less time-consuming techniques such as 18-FDG positron emission tomography/computed tomography (PET-CT) and telethermography (TT). METHODS: Fifteen patients (4 males and 11 females - age range: 63-91) affected whit advanced stage melanoma were enrolled. They presented 52 in-transit metastases as detected by the three techniques used, HF-US, PET/CT and TT within 30 days before ECT. RESULTS: All the 52 lesions were detected by HF-US (100%), 24/52 were detected by PET-CT (42,6%) and 15/52 were detected by TT (27,7%). PET-CT reported 3.7% false positives, while no false positive were reported by TT. CONCLUSIONS: As US detected 100% lesions, compared to the other two techniques used, US, along with clinical examination, has still to be considered as gold standard in the diagnosis of metastatic lesions. US, associated with an exhaustive anamnesis and accurate clinical examination, cannot be replaced by either PET-CT or TT. When US performing devices and experienced operators are not available, though, it is highly recommended to integrate US with at least one of the other techniques. Under certain circumstances, as in the case of obese and non-collaborating patients or in patients with lymphatic stasis, these techniques should be integrated to obtain exact in-transit metastases evaluation.

Can video thermography improve differential diagnosis and therapy between basal cell carcinoma and actinic keratosis?

Various noninvasive techniques (dermoscopy, confocal microscopy, etc.) have been introduced to help the clinical diagnosis in nonmelanoma skin cancer. Among them, the high definition video thermographic technique (VTG) has recently been proposed. The aim of this study is to define the VTG patterns, respectively of actinic keratosis (AK) and basal cell carcinoma (BCC), and to compare these data with them of dermoscopy. The study included 36 patients with a total number of 135 lesions who underwent clinical, VTG, and dermoscopic examination. The VTG showed the presence of a hyperthermic pattern in all the cases of AK, while in the case of the BCC, the pattern was hypothermic. Dermoscopy also showed distinct pattern for AK and for BCC, but in 22% of them the data were not conclusive. Our study permits us to define two specific VTG patterns, BCC and AK respectively.

The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours.

BACKGROUND: The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports. PATIENTS AND METHODS: From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up. RESULTS: The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US "positive" patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US "negatives", 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies. CONCLUSIONS: US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed.

Cutaneous melanoma follow-up: appropriateness of requests for ultrasound tests--the S.Gallicano National Referral Centre Experience.

BACKGROUND: Cutaneous melanoma is a malignant neoplasm with a constantly increasing incidence, the prognosis of which is largely dependent on early diagnosis. The appropriateness of requests for ultrasound (US) tests during melanoma follow-up of patients referred to our institute was evaluated. PATIENTS AND METHODS: The requests for US tests of all patients referred to our institute over a four-month period were assessed. In order to correctly evaluate the appropriateness of requests, patients were split into two groups on the basis of melanoma thickness: > 1 mm (Group A) and < 1 mm (Group B). RESULTS: 546 patients were enrolled in our study out of a total of 1240 US tests performed. Out of 290 Group A patients, 104 patients (35%) did not meet the established congruity criteria. Group B was composed of 256 individuals, 92 patients (35.9%) of which were found to have at least one inappropriate request. CONCLUSION: In our study, more than 30% of the requests for US tests were found to be inappropriate, to the detriment of those with a real need for diagnostic testing. This lengthens waiting lists and it may also increase public healthcare costs. Therefore, it is mandatory to adopt new, widely accepted and easily applicable guidelines.

Ultrasound morphology of inguinal lymph nodes may not herald an associated pathology.

BACKGROUND: Among patients undergoing follow-up after surgery for melanoma, ultrasound (US) very often reveals lymph nodes in groin area, that do not show clear characters of a metastatic lesion yet that have atypical US features, which could result in diagnostic uncertainty. We evaluated such lesions among a cohort of patients. METHODS: The study population consisted of patients who presented consecutively to our facility for a control between 1 January 2009 and 30 July 2010 and who had undergone surgery for a melanoma, at least 6 months earlier, in areas draining to lymph nodes of the groin but choosing - for this study - the opposite side to the natural drainage. The following parameters of the US performed on the lymph nodes were evaluated: number and size, aspects of the outline, including any extroflexion of the outline and contours morphology, homogeneity and thickness of the cortex and aspects of the hilus, characteristics of the vascularisation of the lymph node at color-power Doppler. A second US examination was performed on the same area after at least 12 months. RESULTS AND CONCLUSIONS: We found a very high number of patients (42/124) with lymph nodes that did not appear to be fully normal at US examination, particularly those with structural alterations in the hilus and slight loss of physiologic curvature of the outlines, with moderate thickening of the cortex. Of the 124 patients, who were followed for at least one year, 42 showed these characteristics, and none of these showed any progression to malignancy at follow-up. Based on these results, we can conclude that focusing excessively on such US findings could lead to the inappropriate performance of additional diagnostic tests, with a consequent increase in management costs and a worsening of the quality of life for these patients.

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?

BACKGROUND: Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease. METHODS: Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern. RESULTS: The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B). CONCLUSIONS: Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.

"Hypoechoic triangle": a new sonographic sign or marker of advanced autoimmune thyroiditis.

BACKGROUND: Ultrasonography (US) changes have been noted in patients with autoimmune thyroiditis (AT). Here, we report that some patients with late stage AT have a distinctive, previously unreported finding on US that we call the "hypoechoic triangle sign" (HET). METHODS: On US, the HET sign was characterized as a well-defined area of low echogenicity, about 10 mm in diameter, between the lateral margin of one or both thyroid lobes, the medial wall of the carotid artery, and, posteriorly, the prevertebral muscles. Twenty-six patients with AT who had the HET sign (Group 1) were compared with 71 patients with AT who had normal serum thyrotropin (TSH) and free thyroid hormones levels (Group 2) and with 154 normal controls (Group 3). TSH was tested at least twice, first as part of their regular clinical care and then in follow-up. The groups were similar in terms of age, sex, and body mass index. Thyroid volume by US, TSH, free triiodothyronine, free thyroxine, antithyroid antibodies, and l-thyroxine treatment were evaluated. Sonographic gray-scale analysis and three-dimensional reconstruction of HET region were performed in five of the Group 1 patients. RESULTS: Thyroid volume was significantly smaller (p < 0.01) in Group 1 than in Groups 2 and 3 (6.9 ± 2.18 vs. 10.4 ± 2.1 and 9.8 ± 2.5 mL, respectively). In Group 1, 61.5% of subjects were taking l-thyroxine for hypothyroidism; none of the Group 2 or 3 patients was taking thyroid hormone. Serum TSH was significantly higher (p < 0.01) in Group 1 versus Groups 2 and 3 (3.6 ± 1.3 vs. 2.18 ± 1.4 and 1.9 ± 1.1 mIU/L, respectively). None of the Group 2 or 3 patients had the HET sign. Gray-scale US demonstrated an overlap between HET zone and the surrounding muscle tissue. CONCLUSIONS: The HET sign seems to be specific for overt thyroid failure in patients with AT as it was not noted in patients with AT not having overt thyroid failure. The incidental finding of the HET sign during cervical US examination should prompt obtaining thyroid function tests to rule out hypothyroidism. Our study provides data regarding specificity but not sensitivity of the HET sign for AT and thyroid failure because a consecutive group of AT patients with thyroid failure was not studied. In addition, the specificity of the HET sign for AT needs to be evaluated further by studying a diverse group of thyroid diseases.

Epithelioma of Malherbe: new ultrasound patterns.

BACKGROUND: Calcifying epithelioma of Malherbe, or Pilomatricoma, is considered an uncommon cutaneous neoplasia, normally occurring in children as a solitary, firm, asymptomatic, hard, subcutaneous, slowly growing nodule on the face, neck, or proximal upper extremity. In literature, two Pilomatricoma ultrasound patterns are described: the totally calcified nodule and the hypoechoic nodule with internal calcific foci. High frequency ultrasound has not yet been applied for routine diagnosis of Pilomatricoma. The aim of the study was to retrospectively identify specific ultrasound features. METHODS: We retrieved 124 histologically Pilomatricoma cases: 28 patients with 32 lesions were preoperatively evaluated with ultrasound. RESULTS: 22/32 have shown a solid formation, hypoechoic, with a sharp outline. Of these 22, 10 lesions were completely calcifying and 12 partially calcified. In 3/32 lesions with uncertain diagnosis, ultrasounds showed a complex/mixed pattern with pseudo-fluid areas and microspots. 7/32 lesions with US different diagnosis included 3 complex lesions, 2 cystic lesions and 2 solid nodular lesions. CONCLUSION: In addition to well-known ultrasound patterns (completely calcified and partially calcified) we identified three new, not yet described, patterns that constitute the 31% of the cases: complex, pseudocystic and pseudotumoral.

Effective therapy with anti-TNF-alpha in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in sustaining the inflammatory process in the skin as well as in the joints of patients with psoriasis and psoriatic arthritis. In fact, biological therapies based on monoclonal antibodies against TNF-alpha have been proven to be effective on both the arthropathy and the cutaneous symptoms of the disease. Among the several effects produced by TNF-alpha on keratinocytes there is the induction of expression of MMP-9, a matrix metalloproteinase (MMP) produced mainly by monocytes and macrophages. In this article we refer to the results of a study on the behavior of MMP-9 in the sera and in the lesional skin in association with effective therapy with infliximab. Measurements of TNF-alpha, MMP-2, vascular endothelial growth factor (VEGF), and E-selectin were also performed in the same samples. Eleven psoriatic patients included in a therapeutic protocol based on the administration of infliximab monotherapy were collected before treatment and after 6 and 12 weeks of therapy. Significant decrease of MMP-9 and MMP-2 levels in the sera was associated with clinical improvement and with the decrease of TNF-alpha, VEGF, and E-selectin, angiogenic molecules already known to be implicated in the clinical expression of psoriasis. The clinical amelioration of the cutaneous expression of psoriasis was significantly associated with the decrease of MMP-9, TNF-alpha, and E-selectin levels, spontaneously released by lesional biopsy samples before and after therapy, measured in the culture supernatants by immunoenzymatic assays. In addition, significant correlations were found between the clinical score and TNF-alpha, MMP-9, and E-selectin lesional production. MMP-9 levels were significantly correlated with those of TNF-alpha. Our findings show the existence of a direct relationship between MMP-9 and TNF-alpha production, strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis, while a different role may be attributed to MMP-2.

Elastofibroma dorsi: histologic and echographic considerations.

BACKGROUND: Elastofibroma dorsi is a relatively rare soft-tissue tumor of the elderly with typical localization to the subscapular area. To date, few cases have been reported in the dermatology literature. The differential diagnosis includes frequently observed subcutaneous neoplasms such as lipoma, fibrolipoma or more aggressive tumors. The diagnosis is made with histologic examination. CASE REPORT: We present a typical case of elastofibroma dorsi, studied with ultrasound investigation and color-power Doppler, and discuss the correlation with the histologic picture. CONCLUSIONS: Considering the strict correspondence between the characteristic histologic findings of elastofibroma and the specific ultrasound pattern, we believe that ultrasound investigation with color and power Doppler allows, in typical cases, a definitive diagnosis of elastofibroma.