Search Results (159)

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare, high-grade soft-tissue sarcoma characterized by a patternless proliferation of bizarre pleomorphic tumor cells lacking identifiable lineage differentiation. Its occurrence in the oral cavity is exceptionally uncommon and poses significant diagnostic challenges due to its morphological overlap with a wide spectrum of other malignancies. Material and Methods: We report a novel case of oral UPS in a 54-year-old woman, characterized by an exceptionally large size and a rapidly progressive clinical course. The diagnostic evaluation included clinical, radiological, histopathological, immunohistochemical, and molecular analyses conducted within a multidisciplinary framework. A comprehensive review of the literature on oral UPS was also performed. Results: The patient underwent an aggressive demolitive surgical approach due to the extent of the lesion. Molecular analysis revealed a previously unreported SPECC1L::TERT gene fusion. The literature review highlighted the rarity of oral UPS, its geographic predilection for Central and East Asia, possible associations with traumatic events, and its heterogeneous clinical and histopathological presentations. Conclusions: This case underscores the critical importance of a thorough diagnostic workup to ensure the accurate diagnosis and appropriate management of this rare and aggressive tumor. Multidisciplinary evaluation is essential, especially in anatomically complex and diagnostically challenging presentations such as oral UPS. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Background: We herein review the most important clinico-pathological features of mycosis fungoides (MF). These evolving clinico-pathological aspects are paired with innovative therapeutic schemes. Moreover, we indicate cutaneous lymphomas as a new frontier of artificial intelligence application. Methods: We encompass new diagnostic and prognostic data derived from the recent medical literature describing the possible histological features which could be the targets of deep learning in conjunction with available clinical data. Results: In spite of decades of research, MF diagnosis still represents the most challenging debate from a dermatopathologist’s point of view. Genetic alterations have been identified mainly in late stages of the disease, and their importance for disease initiation is still unclear. The exploration of the genome-wide expression of individual genes in skin samples may be useful in elucidating MF pathogenesis and improving early diagnosis, while artificial intelligence could offer the possibility of searching for biomarkers of disease progression. Conclusions: MF still deserves the name of the ‘great imitator’, both clinically and histopathologically. The goal of summing up all the clinico-pathological information before reaching a final diagnosis is the approach needed to reach diagnostic accuracy, especially in early MF cases. It is advisable to think of the most common clinical presentations, to be aware of the most common histopathological features, and to interpret the results of ancillary studies only in the right clinico-pathological context. Full article

Congenital melanocytic nevi (CMN) are benign tumors present at birth or arising in the first few months of life. A small subset of these nevi present with mild atypical features and heterogeneous differentiation, including Schwannian differentiation. We present a case of a 3-week-old with a 7 cm red/purple scalp nodule consistent with CMN with mild atypical heterogeneous areas. On histology, there were dermal nests of spindle cells in a fibrillar matrix, with increased vessels and clusters of small round melanocytes interspersed between collagen bundles and around adnexal structures. The lesion also exhibited rare pagetoid ascent of melanocytes as single cells and nests. Overall, these features were consistent with a CMN with nodular proliferative neurocristic cutaneous hamartoma (NCH) with a component of a compound mild atypical melanocytic proliferation. Next generation sequencing (NGS) identified a novel SH2B1::BRAF fusion. This case highlights the diagnostic challenges of heterogeneous differentiation within CMN in young children. Full article

Artificial intelligence (AI) has emerged as a transformative tool in placental pathology, offering novel diagnostic methods that promise to improve accuracy, reduce inter-observer variability, and positively impact pregnancy outcomes. The primary objective of this review is to summarize recent developments in AI applications tailored specifically to placental histopathology. Current AI-driven approaches include advanced digital image analysis, three-dimensional placental reconstruction, and deep learning models such as GestAltNet for precise gestational age estimation and automated identification of histological lesions, including decidual vasculopathy and maternal vascular malperfusion. Despite these advancements, significant challenges remain, notably dataset heterogeneity, interpretative limitations of current AI algorithms, and issues regarding model transparency. We critically address these limitations by proposing targeted solutions, such as augmenting training datasets with annotated artifacts, promoting explainable AI methods, and enhancing cross-institutional collaborations. Finally, we outline future research directions, emphasizing the refinement of AI algorithms for routine clinical integration and fostering interdisciplinary cooperation among pathologists, computational researchers, and clinical specialists. Full article

BCC is the most prevalent form of skin cancer, characterized by diverse clinical and pathological subtypes ranging from indolent to highly aggressive forms. While the majority of BCC cases are treated effectively with surgery or local therapies, locally advanced BCC (laBCC) and metastatic BCC (mBCC) pose significant therapeutic challenges. Recent advances in HHIs and immunotherapy have transformed the treatment landscape in such cases. However, resistance and intolerance to these treatments necessitate alternative approaches, including chemotherapy. Platinum-based agents such as cisplatin and carboplatin have shown limited efficacy but remain viable options in rapidly progressive cases. Among the therapeutic innovations to be explored, further lines of immunotherapy as well as combination therapies involving immunotherapy and targeted therapy have been proposed. This review synthesizes the current understanding about BCC subtypes, risk stratification, and emerging treatments, with a particular focus on laBCC and mBCC. Full article

Background: Vulvar lymphangiectasia (VLA) is a rare condition characterized by the abnormal dilation of lymphatic vessels in the vulvar region, often secondary to surgery or radiation therapy for malignancies. Its clinical presentation closely resembles other dermatological conditions, posing challenges for accurate diagnosis and appropriate management. This study aims to present a rare case of VLA occurring decades after cervical carcinoma surgery, contributing to the limited literature on this condition and offering insights into its differential diagnosis and management. Methods: A 70-year-old female patient presented with multiple fluid-filled vesicles in the vulvar region appearing 36 years after undergoing radical hysterectomy with pelvic lymphadenectomy for cervical carcinoma. The lesions were biopsied, and histopathological and immunohistochemical analyses were performed to confirm the diagnosis. A review of the existing literature on VLA was conducted to contextualize this case. Results: A histopathological examination revealed papillomatous lesions with hyper-keratosis, dilated lymphatic vessels, and no signs of atypia, consistent with VLA. An immunohistochemical analysis confirmed the lymphatic nature of the lesions. Due to the patient’s comorbidities, asymptomatic presentation, and lesion stability, conservative management with regular follow-up was chosen. No progression or complications were observed during the 12-month follow-up period. Conclusions: This case highlights the importance of considering VLA in patients presenting with vulvar vesicles, especially those with a history of lymphatic disruption. An accurate diagnosis through histopathological and immunohistochemical techniques is essential to distinguish VLA from other conditions. Conservative management may be appropriate for asymptomatic cases, but tailored therapeutic strategies are needed to address symptomatic or disfiguring lesions. Full article

This report discusses a female patient with longstanding discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), refractory to multiple immunosuppressive and biologic treatments. Upon presenting with infiltrated, hypertrophic plaques in facial and décolletage regions, she was started on anifrolumab therapy after the histopathological confirmation of DLE. Following three infusions, significant clinical and dermoscopic improvements were observed, including the resolution of plaques and regression of scarring areas. This case highlights anifrolumab’s efficacy in severe lupus skin manifestations, emphasizing its potential to induce dermoscopic and histological remission. Additionally, it suggests that dermoscopy could be a valuable tool for monitoring therapeutic responses in DLE and cutaneous lupus erythematosus, warranting further investigation. Full article

Clear Cell Sarcoma (CCS) of soft tissue is a rare and highly malignant neoplasm primarily affecting young adults, often presenting in the deep soft tissues of the extremities. Despite morphological and immunophenotypic similarities to melanoma, CCS arises from connective tissues and is characterized by a distinct genetic hallmark: the EWSR1-ATF1 fusion resulting from t(12;22)(q13;q12) translocation. This genetic signature is absent in melanoma, making molecular diagnosis essential for accurate differentiation. Additionally, recent evidence highlights the utility of PRAME as an immunohistochemical marker to distinguish CCS from melanoma and other neoplasms. Clinically, CCS commonly involves tendons and aponeuroses, with metastatic potential leading to poor prognoses despite optimal local disease management. Histologically, CCS features lobular growth, spindle-to-epithelioid cells with clear cytoplasm, and low mitotic activity, often necessitating a multimodal diagnostic approach incorporating histopathology, immunohistochemistry, and molecular testing. Therapeutically, wide surgical excision remains the cornerstone for localized disease, with sentinel lymph node biopsy aiding in staging. Adjuvant radiotherapy is considered in select cases, while chemotherapy has limited efficacy in metastatic settings. Emerging treatments, including targeted therapies focusing on EWSR1-ATF1-driven pathways and immune checkpoint inhibitors, offer hope for improved outcomes. This review synthesizes current knowledge on CCS, emphasizing diagnostic challenges, the role of PRAME, and advancements in therapeutic strategies to enhance patient care. Full article

Background/Objectives: Selumetinib, a MEK1/2 inhibitor, is commonly used for treating neurofibromatosis type 1 (NF1) and is associated with cutaneous side effects such as paronychia and periungual granulomas. These complications can be painful and difficult to manage, often leading to the discontinuation of treatment. The objective of this study was to evaluate the effectiveness of photodynamic therapy (PDT) as a novel treatment for MEKi-induced paronychia in a patient with NF1. Methods: We present a case report of an 18-year-old patient with NF1 who developed painful periungual granulomas on the toenails after 12 months of Selumetinib therapy. PDT was administered using methyl aminolevulinate (METVIX^®) as the photosensitizing agent, followed by treatment with a red LED light source (630 nm, 37 J/cm² for 8 min and 30 s). The patient was followed up for two months post-treatment and then at two years. Results: After a single PDT session, the patient exhibited complete clinical remission of the periungual granulomas and associated pain. No recurrence of the lesions was noted during the two-year follow-up. The patient tolerated the procedure well, reporting only mild discomfort during treatment. Conclusions: PDT appears to be an effective, minimally invasive treatment for Selumetinib-induced paronychia and periungual granulomas. This case demonstrates that PDT can provide a complete resolution of symptoms with a single treatment session, offering an alternative to more invasive procedures. Further studies with larger cohorts are needed to establish PDT as a standard treatment option for this condition. Full article

Background/Objectives: People living with HIV (PLWH) are more susceptible than immunocompetent people to non-melanoma skin cancers. These tumors can arise de novo or from precancerous lesions, such as actinic keratosis (AKs). The management of AKs in PLWH has not been widely discussed in the literature. More specifically, the efficacy of the treatment of AKs in PLWH with modern topical drugs, such as tirbanibulin, is limited. The present work aims to evaluate the response rate to the intervention with tirbanibulin 1% ointment for treating AKs in PLWH. Methods: We retrospectively collected the data of the PLWH who visited the Dermatology Department of the Policlinico Riuniti (Foggia, Italy) between September 2023 and September 2024. PLWH who received the diagnosis of AKs and underwent treatment with tirbanibulin 1% ointment were studied. To assess the severity of AKs, the number of AKs and the AKs’ area and severity index (AKASI) score were calculated at the time of diagnosis (T0) and after treatment (T1). Results: Ten PLWH were found to have AKs and received topical therapy with tirbanibulin 1% ointment. On average, at T0, the number of lesions was 8.2 and the AKASI score was 4.20; at T1, the number of AKs was 1.7 and the AKASI score was 1.5. Only two patients reported a mild inflammatory reaction to applying tirbanibulin 1% ointment. Conclusions: The rate of satisfactory responses was in line with a recent multicentric Italian study performed on immunocompetent patients. Our results confirm the efficacy and tolerability of tirbanibulin 1% ointment in treating AKs in PLWH in particular. Full article

Cutaneous squamomelanocytic tumor (SMT) is a very rare cutaneous malignancy, composed of a dual phenotypic population of both malignant melanocytes and keratinocytes, intimately intermingled together. Herein, we report a new case of a SMT occurring in an 82-year-old man, located on the scalp. Histopathology revealed a mixed population consisting of squamous cell carcinoma and melanoma within the same lesion, also confirmed using immunohistochemical staining for high molecular-weight cytokeratins (HMWCKs) and Melan-A. Moreover, to the best of our knowledge, for the first time, we tested SMT for the preferentially expressed antigen in melanoma (PRAME), which revealed a strong and diffuse positivity in the melanocytic component. These tumors need to be distinguished by more frequent collision tumors and colonization. Furthermore, we provide a comprehensive review of the literature, focusing on clinical and histopathological aspects, biological behavior and still-debated, but fascinating histogenesis of this elusive entity. Full article

Background/Objectives: This study aims to evaluate whether the presence of isolated tumor cells (ITCs) correlates with specific stages of cutaneous melanoma, potentially shedding light on their prognostic significance and the paradoxical survival outcomes in stage IIIA. Methods: This study analyzed cases of sentinel lymph node biopsies for cutaneous melanoma between 2021 and 2023. It included patients with CM diagnoses, available histological slides, and clinical information about the neoplasia stage. The correlation between the primary tumor stage and the presence of isolated tumor cells was statistically analyzed. Results: This study analyzed 462 sentinel lymph node biopsies, revealing 77.1% negative cases and 22.9% positive cases. Isolated tumor cells were observed in 24 cases (5.2%), most commonly in the early stages (e.g., pT1b and pT2a). Statistical analysis confirmed a significant correlation between ITC presence and early-stage neoplasms (p = 0.014). Conclusions: Although ITCs prompt upstaging, their prognostic impact appears limited, especially in thin melanomas, where survival aligns more closely with stage IB than stage IIIA. This aligns with findings from breast cancer studies where ITCs are not equated to metastases in staging due to their minimal impact on prognosis. Current melanoma staging practices could benefit from differentiating ITCs from larger metastatic deposits to better reflect the actual metastatic burden and guide treatment decisions. Full article

Among gynecological pathologies, cervical cancer has always represented a health problem with great social impact. The giant strides made as a result of both the screening programs perfected and implemented over the years and the use of new and accurate technological equipment have in fact significantly improved our clinical approach in the management and personalized diagnosis of precancerous lesions of the cervix. In this context, the advent of artificial intelligence and digital algorithms could represent new directions available to gynecologists and pathologists for the following: (i) the standardization of screening procedures, (ii) the identification of increasingly early lesions, and (iii) heightening the diagnostic accuracy of targeted biopsies and prognostic analysis of cervical cancer. The purpose of our review was to evaluate to what extent artificial intelligence can be integrated into current protocols, to identify the strengths and/or weaknesses of this method, and, above all, determine what we should expect in the future to develop increasingly safer solutions, as well as increasingly targeted and personalized screening programs for these patients. Furthermore, in an innovative way, and through a multidisciplinary vision (gynecologists, pathologists, and computer scientists), with this manuscript, we highlight a key role that AI could have in the management of HPV-positive patients. In our vision, AI will move from being a simple diagnostic device to being used as a tool for performing risk analyses of HPV-related disease progression. This is thanks to the ability of new software not only to analyze clinical and histopathological images but also to evaluate and integrate clinical elements such as vaccines, the composition of the microbiota, and the immune status of patients. In fact, the single-factor evaluation of high-risk HPV strains represents a limitation that must be overcome. Therefore, AI, through multifactorial analysis, will be able to generate a risk score that will better stratify patients and will support clinicians in choosing highly personalized treatments overall. Our study remains an innovative proposal and idea, as the literature to date presents a limitation in that this topic is considered niche, but we believe that the union of common efforts can overcome this limitation. Full article