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Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2–8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical–pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the “pattern analysis” approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of pati

The actual incidence of bone marrow infiltration of human melanoma in clinical practice is underestimated, given it is found in only 7% of in vivo staging procedures, whereas this percentage increases up to 45% of autopsy cases. We performed a systematic review, in order to highlight the main clinico-pathologic features of melanoma bone marrow metastases (BMM), by reviewing 2.526 studies; seventy-three reports were included in the analysis,reporting a total amount of 146 patients. Moreover, as clinical exemples, we also present a collection of three BMM cases, extracted from our Institutional casistic. We found a slight male prevalence, with a median age at the time of BMM of 56.6 years (range: 3-81 years). The skin was the primary site of involvement in most cases (52%), followed by mucosa in 6 cases (8.8%) and uvea in 14 cases (20.5%), while in 13 cases (19%) the primary site of melanoma was not detected. In 36% of cases, BMM were preceded by lymph node involvement, while 64% of cases did not show nodal metastases, but directly to bone marrow (23%), as well as to other anatomical sites (41%). Presenting symptoms of BMM mostly included pain (60.7%), while anemia was the main laboratory alteration (80%), followed by thrombocytopenia, leukoerythroblastosis, pancytopenia, and leukopenia. A disseminated intravascular coagulation (DIC) was detected in 6 (11%) cases. In 12 cases (23.6%) BMM were amelanotic. The prognosis for BMM is poor, with a median time of survival of only 2 months, since currently conventional therapies for this anatomical site of metastasis are still not very successful, therefore, we stress the importance to evaluate bone marrow as a possible metastatic site in melanoma patients.

Background: Agmination and or satellitosis in pigmented blue lesions is a phenomenon rarely mentioned in the literature and not well known. This phenomenon can be expressed by several benign and malignant pigmented blue lesions, such as blue nevi, Spitz nevi, melanocytoma and melanoma. On this spectrum, dermoscopy, reflectance confocal microscopy (RCM) and dynamic Optical coherence tomography (D-OCT) represent non-invasive imaging technologies, which may help clinicians in the diagnosis of melanoma and non-melanoma skin cancers in daily clinical practice. Methods: Currently, in the literature there is a lack of new data about agminated blue lesions and blues lesions with satellitosis, as well as the lack of a recent and updated review of the literature about this topic. Therefore, considering that clinicians must be confident with the diagnosis of these rare skin lesions, we decided to carry out this work. Results: In this paper, four new cases of agminated pigmented cutaneous lesions were described. Moreover, a review of the current literature on this topic was performed. Conclusions: A clinical pathological correlation is often needed to reach a correct diagnosis; currently, dermoscopy and non-invasive diagnostic techniques, such as reflectance confocal microscopy and optical coherence tomography, due to the depth of these skin lesions in the dermis, can only make a partial and limited contribution.

Introduction: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. Objectives: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. Methods: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. Results: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. Conclusions: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

The occurrence of bone marrow metastases (BMM) in melanoma patients is often underestimated, with only 7% detected during in-vivo staging procedures but rising to 45% in autopsy cases. This systematic review aims to shed light on the clinical and laboratory features of BMM in melanoma by analyzing 73 studies selected from 2 482 initially retrieved from PubMed, Embase, and Cochrane CENTRAL databases. Our findings reveal a slight male predominance, with a median age at BMM diagnosis of 56 years. Primary melanoma sites included the skin (52%), mucosa (8.8%), uvea (20.5%) and unidentified (19%). BMM was preceded by lymph node involvement in 36.5% of cases, whereas 63% showed no nodal metastases, with direct BMM occurring in 22.5% and metastases to other sites in 41%. Common BMM symptoms included pain (60.7%), anemia (80%), thrombocytopenia, leukoerythroblastosis, pancytopenia and leukopenia, while disseminated intravascular coagulation was detected in 11% of cases. In 23.6% of cases, BMM was amelanotic. The prognosis for BMM is grim, with a median survival of only 2 months. Conventional therapies for BMM remain largely ineffective, emphasizing the importance of considering bone marrow as a potential metastatic site in melanoma patients.

Background: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. Methods: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. Results: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. Conclusion: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.

Background: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. Objective: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. Methods: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. Results: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. Conclusion: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Immunohistochemical assessment with combined positive score (CPS) of programmed death-ligand 1 (PD-L1) is the prerequisite for administration of checkpoint inhibitor therapy in head and neck squamous cell carcinoma (HNSCC). Practicing pathologists are required to assess PD-L1 in routinary work and can be faced up with practical issues not always addressed in clinical trials or guidelines, such as choice of specimen to test, the intrinsic heterogeneity in PD-L1 expression in tumors and the potential impact of already administered therapy, given that patients’ material can be procured at several times of cancer natural history. In the present work, we review and discuss the recent literature regarding the assessment of PD-L1 in HNSCC from the perspective of the practicing pathologist, providing some evidence on the single issues. It emerges a general trend to an underestimation of PD-L1 expression in biopsies compared to resection specimens and to a higher degree of positivity in metastatic lymph nodes in respect to primary tumors. Moreover, therapy shows to have contrasting effect on PD-L1 expression. Although further studies are needed, taking into account the intrinsic heterogeneity in PD-L1 expression and the conflicting evidences, it may be speculated that the most recent material of patients in respect to the natural history of tumor can be the most reliable to evaluate PD-L1 expression.

Aims: intraductal tubulopapillary neoplasm (ITPN)of the pancreas is a recently recognized pancreatictumor entity. Here we aimed to determine the mostimportant features with a systematic review coupledwith an integrated statistical approach.Methods and results: PubMed, SCOPUS, and Embasewere searched for studies reporting data on pancreaticITPN. The clinicopathological, immunohistochemical,and molecular data were summarized. Then a compre-hensive survival analysis and a comparative analysis ofthe molecular alterations of ITPN with those of pancre-atic ductal adenocarcinoma (PDAC) and intraductalpapillary mucinous neoplasm (IPMN) from referencecohorts (including the International Cancer GenomeConsortium- ICGC dataset and The Cancer GenomeAtlas, TCGA program) were conducted. The core find-ings of 128 patients were as follows: (i) Clinicopathologi-cal parameters: pancreatic head is the most commonsite; presence of an associated adenocarcinoma wasreported in 60% of cases, but with rare nodal metastasis.(ii) Immunohistochemistry: MUC1 (>90%) and MUC6(70%) were the most frequently expressed mucins. ITPNlacked the intestinal marker MUC2; unlike IPMN, it didnot express MUC5AC. (iii) Molecular landscape: Com-pared with PDAC/IPMN, the classic pancreatic driversKRAS,TP53,CDKN2A,SMAD4,GNAS,andRNF43were less altered in ITPN (P<0.001), whereasMCLamplifications,FGFR2fusions, andPI3KCAmutationswere commonly altered (P<0.001). (iv) Survival anal-ysis: ITPN with a “pure” branch duct involvementshowed the lowest risk of recurrence.Conclusion: ITPN is a distinct pancreatic neoplasmwith specific clinicopathological and molecular char-acteristics. Its recognition is fundamental for its clini-cal/prognostic implications and for the enrichment ofpotential targets for precision oncology., Fondazione Cariverona Oncology Biobank Project; Fondazione Italiana Malattie Pancreas; Italian Ministry of Health; Associazione Italiana Ricerca sul Cancro (AIRC)

Item does not contain fulltext, Undifferentiated carcinoma (UC) and undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) are peculiar variants of pancreatic ductal adenocarcinoma (PDAC), characterized by hypercellularity and absence of glandular patterns. The inflammatory microenvironment is peculiar in UCOGC, since it is dominated by macrophages and osteoclast-like giant cells. However, from a molecular point of view, both UC and UCOGC are very similar to conventional PDAC, sharing alterations of the most common genetic drivers. Clinically, UC usually show a worse prognosis, whereas UCOGC may show a better prognosis if it is not associated with a PDAC component. To highlight potential biological differences between these entities, we investigated the role of the epithelial to mesenchymal transition (EMT) in UC and UCOGC. Specifically, we analyzed the immunohistochemical expression of three well-known EMT markers, namely Twist1, Snai2, and E-cadherin, in 16 cases of UCOGC and 10 cases of UC. We found that EMT is more frequently activated in UC (10/10 cases) than in UCOGC (8/16 cases; p = 0.05). Furthermore, in UCOGC, EMT was activated with a higher frequency in cases with an associated PDAC component. Snai2 was the most frequently and strongly expressed marker in both tumor types (10/10 UC, 8/16 UCOGC), and its expression was higher in UC than in UCOGC (mean immunohistochemical score: 4.8 in UC vs. 2.1 in UCOGC, p < 0.01). Our results shed new light on the biology of UC and UCOGC: EMT appeared as a more important process in UC, and Snai2 emerged as a central EMT effector in this setting.