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Purpose: Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers., Patients and Methods: We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data., Results: Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology ( p < 0.05), Clark IV and V levels ( p < 0.05), vascular invasion ( p < 0.05), and biological mutants ( p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration ( p < 0.02) and the BRAF V600E mutation ( p < 0.02)., Conclusion: CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Caramaschi, Mangogna, Bertoni, Manfredini, Farnetani, Parente, Attino, Cazzato, Salviato, Pellacani and Reggiani Bonetti.)

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) may progress to severe liver fibrosis and cirrhosis. A limited number of studies with a long follow up assessed fibrosis progression and related predictors in untreated patients with a histological diagnosis of NAFLD. This study aims to investigate rate and predictors of NAFLD progression., Methods: For 9 (2-16.7) years, we followed up a cohort of patients histologically diagnosed. Disease progression was defined by a composite endpoint as evidence of cirrhosis in patients without cirrhosis at baseline, evidence of de novo occurrence of cirrhosis complications, histologically established worsening of stage 1 of fibrosis or increase of 20% in liver stiffness by transient elastography in patients rejecting a second liver biopsy., Results: A total of 91 patients were enrolled. Of them, 31 had NAFL and 60 NASH. A second liver biopsy was performed in 22 NASH patients and in 4 NAFL. Disease progression was observed in 38.5% NASH and in 12.0% NAFL ( p = 0.034). Patients with portal inflammation had a higher risk of progression (66.7% vs 26%, p = 0.021). High triglycerides levels, advanced fibrosis at baseline and the duration of follow-up predict disease progression ( p = 0.021; OR = 6.93, 95% CI 1.33-36.08, p = 0.43; OR 8.37; 95% CI 1.07-65.58 and p = 0.034; OR = 0.88; 95% CI 0.78-0.99, respectively)., Conclusions: Our results reinforce the evidence that, in the absence of pharmacologic treatment, NASH progresses in about 40% of patients. Liver biopsy is the only mean to discriminate NAFL from NASH. The prognostic role of portal inflammation needs to be explored in larger series.

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

Exogenous lipoid pneumonia (ELP) is caused by the inhalation of vaporized oily products. Long-term exposure can result in chronic disease, whereas acute form usually results from massive aspiration of fatty substances. It has an incidence of 1.0%-2.5%. In case of symptomatic patients, the clinical presentation mainly includes acute or chronic respiratory symptoms such as dyspnea, fever, cough and less frequently chest pain, hemoptysis, or weight loss. Radiological findings are often aspecific or misinterpreted, and ELP is sometimes misdiagnosed as a malignancy of the lungs. Patient history and radiological findings can lead to a suspicion of ELP, but histological microscopic findings of intra-alveolar lipid and lipid-laden macrophages are required to confirm the diagnosis The mainstay of treatment consists of avoiding ongoing exposure and providing supportive care as repeated whole-lung lavage, corticosteroids, and/or immunoglobulins. Surgery is reserved for cases of high suspicion of cancer or serious clinical impact (as recurrent infections). Prognosis is benign, even if it has been reported cases of progression to severe respiratory failure, cor pulmonale, superinfection, and association with lung cancer. Here, we describe a case of ELP due to chronic inhalation of oily product (Vaseline) used as a lubricant of tracheotomy cannula., Competing Interests: Conflict of Interest: Authors have no conflict of interest to declare.

Background & Aims: Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients., Methods: The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917., Results: Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG)., Conclusions: This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis., Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner., Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%., Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones).

Objectives: The aim of our study was to evaluate the nature of focal liver lesions detected during the ultrasound follow-up of a population (prevalently anti-hepatitis C virus [anti-HCV] positive) with chronic liver disease., Methods: The study population consisted of 1827 consecutive newly diagnosed chronic liver disease cases without liver nodules at enrollment. Patients were screened at 4-month intervals by ultrasound and serum alpha-fetoprotein assessment. All lesions detected on imaging studies (except those accompanied by diagnostic a-fetoprotein levels) were subjected to biopsy (histology and cytology)., Results: During the 7-yr follow-up period (mean = 43.1 months), one or more solid focal lesions were found in 287 patients. a-Fetoprotein was diagnostic for hepatocellular carcinoma in 51 patients. Ultrasound-guided fine-needle biopsy was performed in the remaining 236 patients, yielding a diagnosis in 214: 198 hepatocellular carcinomas, 11 dysplastic nodules, and five B-cell non-Hodgkin's lymphomas (all confined to the liver and all in patients with chronic HCV infection). Twenty-two patients with nondiagnostic biopsies received diagnoses of hepatocellular carcinoma (20) or dysplastic nodules (two) based on arteriography or surgical biopsy., Conclusions: Focal lesions arising in patients with HCV-related chronic liver disease can be other than hepatocellular carcinoma, and ultrasound-guided fine-needle biopsy plays an important role in their diagnosis. The prevalence of non-Hodgkin's lymphoma in this selected population was 0.31%. The fact that all five lymphoma patients had cirrhosis related to hepatitis C strengthens the hypothesis of an etiological correlation between the latter infection and B-cell lymphoproliferative disorders.