Dermal Tumor Research Articles

Cytoarchitectonics and morphofunctional parameters of dermal mastocytomas in the area of the facial skeleton in dogs

The results of the analysis of the prevalence of primary spontaneous dermal mast cell tumors in dogs in the facial skeleton area study was conducted in 2021–2024. The object of the study were 63 dogs with primary spontaneous dermal mast cell tumors, confirmed histologically.The purpose of the work is to study the morphofunctional indicators of dermal mast cell tumors in the facial skeleton area in dogs and to assess their degree of malignancy.During the study, the degree of malignancy was determined according to two generally accepted classifications, according to Kupel and Patnaik — an important prognostic criterion for assessing primary spontaneous mast cell tumors in the facial skeleton area in dogs.According to the results of histological examination of primary spontaneous mast cell tumors in the facial skeleton area in dogs according to the Kupel classification, it was revealed that less aggressive tumors are more common and account for 65.08%, while highly aggressive mast cell tumors occur in 34.92% of cases according to our data, while according to the Patnaik classification, highly differentiated mast cell tumors were detected in 20.63% of cases, moderately differentiated were observed in 49.21% of cases, and poorly differentiated — in 30.16% of cases. From the obtained information on the classification of dermal mast cell tumors, it follows that the majority of moderately differentiated mast cell tumors according to Patnaik (G2) are highly differentiated according to Kupel (G1), which affects the prognostic assessment and choice of treatment tactics for sick dogs.

Atypical cellular neurothekeoma: a case report with a novel NF1 mutation

Atypical cellular neurothekeoma is a rare benign soft-tissue tumour that usually arises in the head and neck region, shoulder girdles, and proximal extremities, predominantly in young women. This dermal neoplasm is under-reported in the literature and is not uncommonly misdiagnosed as a malignant tumour due to its worrisome histologic characteristics. Currently, the diagnosis of cellular neurothekeoma relies on a panel of non-specific immunohistochemical markers and its etiopathogenesis is unknown.Herein, we present the case of an atypical cellular neurothekeoma in the arm of a 49-year-old woman, describing its microscopic features and immunohistochemical profile. Additionally, we present a novel heterozygous predicted inactivating NF1 mutation, not previously reported, which was identified using high-throughput molecular techniques. Such finding might provide insights into the pathogenesis of neurothekeoma, potentially contributing to future refinements in diagnosis, which would enable more precise identification of this neoplasm.

The State of the Art of Image Guided Superficial Radiation Therapy Treatment of Non-melanoma Skin Cancer in Outpatient Dermatology Clinics in the United States and Review of the Literature.

Image guided superficial radiation therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state-of-the-art operating principles in US dermatologic practices. A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors' published and unpublished documents, procedures, and clinical experience with IGSRT were synthesized for this paper. Studies have demonstrated IGSRT consistently delivers high cure rates (> 99%) with low complications for early stage (stage0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs micrographic surgery (MMS). This improvement is attributed to invivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand. While the safety and cosmetic benefits of SRT/XRT have been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists, and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis, and ability to treat multiple lesions per session using IGSRT are establishing this modality as a standard first-line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.

CK20-negative Merkel Cell Carcinoma with Concomitant Squamous Cell Carcinoma In-Situ and Metastasis to the Parotid Gland

Abstract Introduction/Objective This report presents a patient with an aggressive CK20-negative neuroendocrine tumor of the dermis with metastasis to the parotid gland and a concomitant squamous cell carcinoma in-situ (SCCIS) and highlights diagnostic challenges of CK20-negative tumors. Methods/Case Report A centennial female with a history of non-melanoma skin cancer and leukemia presented to the dermatology clinic with a one-year history of an enlarging skin lesion on her right cheek and a subcutaneous mass on the right central lateral neck. On examination, the lesion appeared as a rough and raised red papule with a central crust. On CT, a large heterogeneously enhancing right parotid mass with surrounding satellite nodules, adjacent necrotic adenopathy, and an ulcerating subcutaneous mass in the adjacent right face. An incidental 3 mm right upper lobe nodule was identified. The pathology report noted two distinct malignant neoplasms within the specimen. Microscopy revealed ulceration with acanthosis and full thickness keratinocyte atypia, suggesting Bowen’s disease. On microscopic examination of the separate dermal tumor, there were sheets of uniform small cells with a high nuclear to cytoplasmic ratio and scant cytoplasm. IHC staining was positive for the neuroendocrine markers AE1/AE3, CAM5.2, synaptophysin, and CD56. CK20, CK7, and TTF-1 were negative. As some MCC may be negative for CK20, CK20 was performed twice. Differential diagnoses included SCCIS with CK20-negative MCC versus a metastatic neuroendocrine carcinoma of parotid gland to the skin. The patient transitioned to hospice care soon after the diagnosis. Results (if a Case Study enter NA) NA. Conclusion Our patient presents with an interesting case of a CK20-negative MCC with metastasis to the parotid gland. Since CK20 was stained negative twice, it complicated the diagnosis of MCC vs. small cell carcinoma. We suspected a more likely diagnosis of MCC metastasis to the parotid gland due to multiple reported cases (Day et al. 2016). Our patient also had an identifiable Bowen’s disease borderline to the neuroendocrine carcinoma. It is well known of the coexistence of MCC and squamous cell carcinoma in a cutaneous lesion (Suaiti et al. 2019). Thus, a metastatic MCC to the parotid gland is more likely in this case. As MCC is an aggressive cancer that metastasizes quickly, accurate diagnosis is crucial. With recent literature reporting the association of CK20-negativity with VN-MCC, and the presence of UV signature mutations in CK20- negative MCC, genomic screening would be a useful diagnostic tool.

Epithelioid Fibrous Histiocytoma Is on a Continuum With Superficial ALK-rearranged Myxoid Spindle Cell Neoplasm: A Clinicopathologic Series of 35 Cases Including Alternate RET and NTRK3 Fusions.

Anaplastic lymphoma kinase (ALK) rearrangements drive most examples of epithelioid fibrous histiocytoma (EFH) and have been reported in an emerging family of receptor tyrosine kinase (RTK) fusion-positive mesenchymal neoplasms, including superficial ones described under the rubric of "superficial ALK-rearranged myxoid spindle cell neoplasm" (SAMS). Here, we describe 35 superficial tumors with SAMS morphology, which occurred in 18 females (51%) and 17 males at a median age at presentation of 39 years (range: 6 to 82y). Most tumors occurred on the lower extremity (25 tumors; 71%), followed by upper extremity (5; 14%), trunk (3; 9%), and face (2; 6%). Nine tumors were reported to have grown slowly before presentation, including >10 years in 2 cases. Tumors occurred primarily in the dermis (32 tumors; 91%) or subcutis (3; 9%); 8 dermal tumors extended into the subcutis. Median tumor size was 1.3cm (range: 0.5 to 8.0cm). Clinical follow-up was available for 12 patients (34%; range: 2mo to 21y; median: 2.7y), none of whom experienced metastasis. One incompletely resected tumor recurred locally at 19 months, and no other patients experienced recurrence. Histologically, tumors were characterized by bland spindle-to-ovoid cells showing whorled growth and myxoid-to-collagenous stroma. Recurrent features included an epidermal collarette (19/30; 63%), perivascular hyalinization (20/35; 57%), amianthoid collagen (14/35; 40%), and metaplastic ossification (2/35; 6%). Immunohistochemistry (IHC) demonstrated expression of ALK (24/31; 77%), CD34 (15/21; 71%), EMA (17/28; 61%), and S-100 (9/32; 28%). Eleven tumors showed hybrid morphologic features between EFH and SAMS; 9 of them (82%) showed cytomorphology typical of EFH but with whorled growth, myxoid stroma, and/or regions of spindle cell morphology. Two hybrid tumors showed sharp transitions between a region characteristic of EFH and a region characteristic of SAMS, with a concomitant sharp transition in EMA, CD34, and S-100 expression by IHC. Sequencing revealed ALK fusions in 15 of 19 tumors: 2 each with fusion partners FLNA, SQSTM1, and VCL, and 1 each with COL1A2, DCTN1, EML4, FXR1, MPRIP, PLEKHH2, PRKAR1A, SPECC1L, and TLN2. Thirteen of 14 ALK-rearranged tumors expressed ALK by IHC. Three tumors negative for ALK fusions instead harbored alternate RTK fusions (NCOA4::RET, TRIM27::RET, and VIM::NTRK3), and 1 tumor was negative for RTK alterations. CDKN2A/B deletions were found in 2 tumors with ALK fusions and both tumors with RET fusions. SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RET and NTRK3 fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologic similarities to EFH, we propose the diagnostic term "myxoid spindle cell variant of epithelioid fibrous histiocytoma."

S100 protein expression in PKC-fused blue naevi, cellular blue naevi and PRKAR1A-inactivated pigmented epithelioid melanocytomas

Recent data have redefined the genetic spectrum of pigmented epithelioid melanocytomas (PEMs). PEM is now defined by a secondary genetic event, a protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) inactivation, that confers the specific cytomorphology of the entity, but this event can arise within a naevus with a genetic background of common, blue or Spitz type. PKC-fused melanocytic proliferations, although they can exhibit PEM-like morphological features, have now been regrouped within the blue group of tumours. Past studies have shown that the latter group tends to lose S100 expression. Herein, we studied the nuclear expression of S100 by immunohistochemistry in 73 PKC-fused benign blue naevi. Histologically, the most frequent pattern found in PKC-fused blue naevi (51%) was a dermal biphasic architecture associated with a horizontal band of medium-sized bland melanocytes in the upper papillary dermis, with a deeper dermal expansion combining spindled and dendritic melanocytes with occasional small nests of bland melanocytes within a fibrous background. A PEM-like hyperpigmented hyperplasia of the epidermis was seen in 32% of cases. The immunohistochemical study found in 31 of the 37 (84%) dermal biphasic PKC-fused melanocytic tumour cases a significant loss of nuclear expression of S100 (in more than 50% of cells) in the superficial horizontal dermal band area and in 68% of the biphasic dermal component. However, the hyperpigmented PEM-like junctional components were not assessable by immunohistochemistry. An exploratory analysis of S100 expression in 21 blue naevi and in 25 PEM with confirmed PRKAR1A inactivation was also performed. In blue naevi, a loss of nuclear S100 expression in more than 50% of melanocytes was found in over 70% of these lesions both in the dendritic and epithelioid dermal components. By contrast, nuclear expression of S100 was most often preserved in PEM with PRKAR1A inactivation (85% preservation in the epithelioid component). These results suggest that searching for S100 expression loss by immunohistochemistry may be helpful in the diagnosis of PKC-fused blue naevus similarly as in dendritic and cellular blue naevi. This simple test, especially if a band-like structure is present in the upper dermis, can effectively support this diagnosis, as a genetic confirmation of these benign tumours is not warranted.

Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.

Advancing precision medicine in cutaneous oncology through 3D high-frequency ultrasound imaging.

e13625 Background: Clinical assessment of tumor depth and shape often requires biopsy, especially when evaluating skin cancers. High Frequency Ultrasound (HFUS) is a non-invasive clinical tool that can quickly produce high resolution images ideally suited for evaluating topical tumors. In comparison to other imaging modalities, HFUS do not always provide the spatial data required to model 3-dimensional (3D) tumors. Currently, 3D-images are an amalgamation of many segmented image slices. However, in outpatient clinics it is unrealistic for HFUS devices and clinicians to gather large sets of image data. In our present original research, we aimed to overcome limited number of HFUS and dermatoscopic images by constructing a simple framework to process sparse and non-spatial data into working 3D skin tumor models. Methods: We analyzed two different skin tumors, the dermal duct tumor (DDT) and basal cell carcinoma (BCC), each with different number of HFUS images at 30Hz and 50Hz respectively. 1 set of 6 parallel images were obtained for the BCC, while 2 orthogonal sets of 6 parallel images were obtained for the DDT. For each tumor, a single dermatoscopic photo and sets of bitmap HFUS images with a resolution of 1024 x 512 were taken. Our study was IRB-approved. Mathematica and MATLAB, both with accessible documentation, were used to process images. Results: We developed a novel algorithmic approach to produce 3D tumor models with limited medical data. Both tumors appear corporally hypoechoic under HFUS. Mathematica was used to first reduce HFUS image noise and binarize the tumor region with a bilateral Gaussian filter. The user-friendly MATLAB Image Segmenter application manually filled the region of interest. Next, Mathematica was used to orient and plot tumor borders in 3D. Finally, we encompassed the borders with a 3D convex hull to conservatively predict tight margins around the tumor. Conclusions: Our simplified approach allows clinicians and scientists to produce 3D renderings of tumor margins. Margin control must always be balanced with a positive surgical outcome. By approaching our 3D-model with a convex hull around sampled border cross-sections, we chose a conservative approach that focuses skin tumor margin evaluation. Our results promote precision medicine and planning into the current standard of skin cancer treatment. Our findings can allow tracking tumor progression or treatment possible via non-invasive evaluation of tumor depth and contour. An aim of our present research is to lower the barrier of 3D construction in clinical settings. Simple algorithms, such as shown in our work, transform orthogonal and sparse data into usable data that can be implemented to train machine learning and artificial intelligent programs. Future research tailoring this approach may allow instant programming of HFUS images to non-invasively render cutaneous tumor borders and depth in real time during clinical examination.

Quality of life in individuals with neurofibromatosis type 1 associated cutaneous neurofibromas: validation of the Dutch cNF-Skindex

BackgroundAlmost all patients with Neurofibromatosis type 1 (NF1) develop cutaneous neurofibroma (cNF), benign dermal tumours that have a large impact on the patient’s Quality of Life (QoL). The French cNF-Skindex is the first questionnaire to specifically assess cNF-related QoL in patients with NF1. We aimed to adapt and validate a Dutch version of the cNF-Skindex.MethodsThe questionnaire was translated using forward and backwards translation, and subsequently administered to a sample of 59 patients on two separate occasions. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating internal consistency and test-retest reliability, by calculating Cronbach’s alpha and Spearman’s rank correlation coefficients. The EQ-5D-5L and SF-36 were used to evaluate convergent validity, using Spearman’s rank correlation coefficients. An exploratory factor analysis was performed to study the data’s internal structure. Multivariable linear regression was used to model the relationship between patient characteristics and the cNF-Skindex.ResultsThe Dutch cNF-Skindex demonstrated excellent feasibility and reliability (Cronbach’s alpha 0.96, test-retest correlation coefficient 0.88). Convergent validity was confirmed for the EQ-5D-5L and relevant SF-36 scales. All items and subdomains from the original questionnaire were confirmed following exploratory factor analysis. The patient characteristics included in the multivariable linear regression were not significantly associated with the cNF-Skindex score.ConclusionsThe Dutch cNF-Skindex displayed excellent psychometric properties, enabling use in the Netherlands.

Giant fibroepithelial breast polyp

Introduction: Fibroepithelial polyps are common benign skin lesionsrarely noted in the female nipple. In this location, they have the potentialto ulcerate and cause bloody discharge.Case history: A 55-year-old female patient presented to a breast clinicwith a left nipple lesion present since childhood. The patient self-reportedthat the lesion had increased in size. Clinical examination revealed a 9 ×7 cm lesion with a soft and pliable stem extending from the left nipple.Mammography from 2017 revealed this previously measured 6 × 6 cm.An excision biopsy under general anaesthetic preserving the nippleanatomy was undertaken on 18/8/23. There were no immediate or subsequentcomplications. The final histology demonstrated the excised specimenweighed 131 g and measured 90 × 70 × 60 mm with an 8 mm base.The specimen was processed and microscopically found to be a giantfibroepithelial polyp (FEP). The central core of the lesion was formed byexcessive collagen deposition. Normal dermal structures including bloodvessels were still present with no glandular component and there was noevidence of atypia or malignancy.Discussion: FEPs are benign dermal mesenchymal tumours also knownas acrochordons. They are noted most commonly on the neck, axilla,perineum, and thighs but have also been found in the vagina, vulva, orcervix and present in < 2% of cases in the nipple area.FEPs rarely grow larger than 5 cm, with larger lesions rarely reportedin medical literature worldwide. It is possible to excise these lesions andpreserve the nipple anatomy with careful surgical planning.

Pilomatricoma: Clinical, Dermoscopic Findings and Management in 55 Pediatric Patients and Concise Review of the Literature with Special Emphasis on Dermoscopy.

Pilomatricoma is a benign adnexal dermal or subcutaneous tumor derived from immature hair matrix cells. The aim of our study is to evaluate clinical and dermoscopic features of pilomatricomas, with a specific focus on pediatric lesions, and to provide a concise review of the existing literature. A single-center retrospective study was undertaken on 55 patients with a histopathological diagnosis of pilomatricoma referred to the Dermatology Unit, University of Bologna, Bologna, Italy, between 2005 and 2023. Pilomatricomas were retrospectively evaluated relying on clinical and dermoscopic images. A PubMed search was conducted. All the relevant research up to July 31, 2023, was reviewed. We classified the cases as "typical" or "atypical" based on whether they were suspected of being pilomatricomas or not. A total of 55 children with pilomatricomas were observed and studied. Two patients presented with 2 pilomatricomas, leading to the identification of 58 pilomatricomas. 'Typical' pilomatricomas were observed in 79% of cases as nodular and pigmented lesions with one or more colors, ranging from blue-gray to red to yellow/white, evident on clinical examination and even better on dermoscopy. In 21% of cases, pilomatricomas presented in an 'atypical' form, which did not allow for a well-founded suspicion, placing them in differential diagnosis with other lesions and therefore requiring histological examination. According to our case series and systematic review of the literature, clinical appearance and dermoscopy may be sufficient to diagnose or suspect pilomatricoma in around 80% of cases, while histological examination is necessary to confirm the diagnosis in the remaining 20% of cases.

Abstract 3171: The effect of estrogen and phytoestrogens in Inflammatory breast cancer

Abstract Inflammatory breast cancer is an aggressive and lethal type of breast cancer. Frequently, this cancer is diagnosed in an advanced stage with metastasis. IBC diagnosis is associated with a worse survival rate than other types of breast cancer. The presence of dermal and stromal tumor emboli blocking the lymphatic vessels under the skin is considered a hallmark of IBC and assumed to be responsible for the high metastatic behavior and aggressiveness of IBC disease. To this date, there are no effective targeted therapeutics, especially for those patients that account for approximately 20-40% of IBC cases with triple-negative breast cancer (TNBC) classification. Several studies have shown that estrogen can exert non-genomic effects in IBC and non-IBC TNBC, mediated by the expression of alternate estrogen receptors including estrogen receptor alpha-36, and GPR30. In this context, estrogen can activate non-genomic signaling pathways involved in the acquisition of oncogenic phenotypes such as increased motility and invasion in IBC cells. Phytoestrogens, naturally derived structural analogs to 17β-estradiol (E2), were evaluated as an alternative treatment option using in vitro IBC cell models (SUM149 and SUM190). Given the estrogenic properties of phytoestrogens, the drugs were hypothesized to interact with targets in pathways similar to E2 in non-genomic signaling. Several phytoestrogens including coumestrol (Cou) can induce a cytotoxic effect in TNBC. We hypothesize (1) that estrogen non-genomic signaling has an active role in the aggressive metastatic phenotype of IBC, and (2) that Cou has anticancer activity by inhibiting estrogen non-genomic signaling in IBC. To test these hypotheses, IBC cells were treated with E2 or Cou to determine their effects on the activation of downstream kinases by western blot and phospho-kinase array assays. In addition, transcriptional effects upon treatment with Cou were identified using RNA-seq. A dose-response curve in 2D and 3D models was generated to determine the half-maximal inhibitory concentration (IC50) of Cou. Finally, treatment using the IC50 of Cou caused a decrease in cell viability in the TNBC cell line. Also, in comparison to E2, Cou decreases migration, proliferation, and tumor emboli formation in IBC cell lines. In addition, IBC cells were treated using monotherapy and combination therapy with phytoestrogens including Cou, genistein (GN), and/or 8-prenylnaringenin (8-PN). Observed reductions of cell viability in IBC cell lines treated with the different phytoestrogens and combinations make them worthy of further characterization as anti-cancer therapies in in vitro and in vivo models. In summary, IBC cells are responsive to E2 making this signaling pathway attractive for the development of innovative therapeutic strategies with phytoestrogens as potential candidates for treatment. Citation Format: Esther A. Peterson-Peguero, Keishla Rodriguez-Martir, Madeline Ganshert, Dalissa Negron-Figueroa, Ayeisha N. Colon-Ortiz. The effect of estrogen and phytoestrogens in Inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3171.

New duck papillomavirus type identified in a mallard in Missouri, USA.

Papillomaviruses are small circular DNA viruses that infect epithelial and mucosal cells and have co-evolved with their hosts. Some papillomaviruses in mammals are well studied (especially those associated with disease). However, there is limited information on papillomaviruses associated with avian hosts. From a cloacal swab sample of a mallard (Anas platyrhynchos) sampled in Missouri, USA (6 Jan 2023), we identified a papillomavirus (7839 nt) that shares ~68% genome-wide nucleotide sequence identity with Anas platyrhynchos papillomavirus 1 (AplaPV1) from a mallard sampled in Newfoundland (Canada) and ~40% with AplaPV2 from a mallard sampled in Minnesota (USA) with mesenchymal dermal tumors. The papillomavirus we identified shares 73.6% nucleotide sequence identity in the L1 gene with that of AplaPV1 and thus represents a new AplaPV type (AplaPV3). The genome sequence of AplaPV3 shares >97% identity with three partial PV genome sequences (1316, 1997, and 4241 nt) identified in a mallard in India, indicating that that virus was also AplaPV3.

Current common prodrug delivery methods and biochemical property

Prodrugs are pivotal in overcoming drug delivery and absorption challenges. These bioreversible derivatives are strategically designed to address medicines poor bioavailability and administration constraints. Prodrugs offer versatile solutions for various delivery methods, including oral, dermal, nasal, and central nervous system (CNS) routes and tumor targeting. This literature review aims to summarize several prodrugs delivery methods. The report also focuses on the common concepts of prodrug design. The utilization of prodrugs also includes innovative strategies, such as receptor-mediated internalization and responsive drug release, demonstrating promising outcomes for cancer therapy. The application of prodrug methods is comprehensive. Prodrugs emerged as a universal approach to improve drug administration and absorption, with their applications spanning diverse medical contexts. By tailoring prodrugs to specific delivery routes and addressing unique challenges, researchers open avenues for more effective and targeted therapies. Further exploration and optimization of prodrug strategies hold the potential to revolutionize drug delivery in clinical settings. Although prodrugs have many advantages, there are still many possible future improvements. Many diseases or target organs still need help applying prodrugs even though the current drug design needs this technology for administration. Future research should focus on the lack of chemical stability, including considering the balance between aqueous solubility and lipophilicity. Also, the elimination of the formation of degradation by-products or the design of acceptable metabolism pathways is another aspect that should be considered.

TFCP2L1 as a potential diagnostic gene biomarker of Keloid given its association with immune cells-a study based on machine learning and RNA sequence

Keloids represent a specific type of dermal tumor, where delayed treatment greatly heighten risks of recurrence. This study thus seeks to identify key genes for early keloid diagnosis and compare how immune cell infiltration between keloid lesion skin (KLS) and keloid adjacent non-lesional skin (KNL) differ. Utilizing two GEO datasets, which encompassed KLS (n=8) and KNL (n=6) samples, 564 differentially expressed genes (DEGs) were identified, with a primary emphasis on inflammation- and fibrosis-related pathways. The gene TFCP2L1 was pinpointed from the intersection of LASSO and SVM-RFE algorithms, exhibiting downregulation in KLS when juxtaposed with KNL. To aid prognosis and identification of potential immunotherapy targets, the CIBERSORT algorithm was employed to assess prelative proportions of immune cells. In the KNL samples, there was an observed increase in follicular helper T cells, activated NK cells, and activated dendritic cells. Conversely, M1 macrophages were elevated in KLS samples. TFCP2L1 exhibited a positive correlation with activated NK cells and activated dendritic cells, while it showed a negative correlation with M1macrophages. These findings highlight the intertwined roles of TFCP2L1 and immune cell infiltration, lending to TFCP2L1’s potential as a diagnostic biomarker for keloids and highlights how TFCP2L1 might influence keloid development through immune cell populations.

MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers—Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.

Poroid Neoplasms: A Clinicopathological Study of 13 Cases.

Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. It is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (February 2020-February 2024). We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12-70 years) with a slight female predominance. Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4-8 cm). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms.

Subtotal Thigh Flap for Large Abdominal Wall Defect Reconstruction in Patient With Recurrent Dermatofibrosarcoma Protuberans: A Case Report and Literature Review.

Harvesting an adequate-sized flap is challenging for reconstructing large defects on the abdominal wall. A subtotal thigh flap would be one of the choices as it provides a well-vascularized large flap with muscle components. Moreover, dermatofibrosarcoma protuberans (DFSP) is a low-grade dermal neoplasm with a high recurrence rate. There is still no consensus on the extent of resection to prevent a recurrence. We present a case of a patient who underwent the reconstruction of a large abdominal wall defect with a subtotal thigh flap after the resection of recurrent DFSP. A 59-year-old man killed from a recurrent huge mass in the lower abdomen with an invasion of the small intestine. His baseline characteristics and records of operations, medications, and outcomes were reviewed. After tumor excision, a 28 × 30-cm subtotal thigh flap was harvested from his left thigh to reconstruct the abdominal defect. A microvascular anastomosis with left deep inferior epigastric vessels was made eventually. The flap was in good condition, and the donor site was covered with a split-thickness skin graft. Subtotal thigh flap may be considered for large abdominal wall defect reconstruction as it allows good perfusion of relatively large skin paddles compared with other free flaps. Also, patients with DFSP need definite margin-free resection and close follow-up to prevent a recurrence.

Selective adhesion inhibition and hyaluronan envelope reduction of dermal tumor cells by cold plasma-activated medium

ABSTRACT The sensitivity to cold plasma is specific to tumor cells while leaving normal tissue cells unaffected. This is the desired challenge in cancer therapy. Therefore, the focus of this work was a comparative study concerning the plasma sensitivity of dermal tumor cells (A-431) versus non-tumorigenic dermal cells (HaCaT) regarding their adhesion capacity. We found a selective inhibiting effect of plasma-activated medium on the adhesion of tumor cells while hardly affecting normal cells. We attributed this to a lower basal gene expression for the adhesion-relevant components CD44, hyaluronan synthase 2 (HAS2), HAS3, and the hyaluronidases in A431. Noteworthy, after plasma exposure, we revealed a significantly higher expression and synthesis of the hyaluronan envelope, the HAS3 gene, and the transmembrane adhesion receptors in non-tumorigenic HaCaTs.

Comparison of Tumor Control and Skin Damage in a Mouse Model after Ultra-High Dose Rate Irradiation and Conventional Irradiation.

Recent studies suggest ultra-high dose rate radiation treatment (UHDR-RT) reduces normal tissue damage compared to conventional radiation treatment (CONV-RT) at the same dose. In this study, we compared first, the kinetics and degree of skin damage in wild-type C57BL/6 mice, and second, tumor treatment efficacy in GL261 and B16F10 dermal tumor models, at the same UHDR-RT and CONV-RT doses. Flank skin of wild-type mice received UHDR-RT or CONV-RT at 25 Gy and 30 Gy. Normal skin damage was tracked by clinical observation to determine the time to moist desquamation, an endpoint which was verified by histopathology. Tumors were inoculated on the right flank of the mice, then received UHDR-RT or CONV-RT at 1 × 11 Gy, 1 × 15, 1 × 25, 3 × 6 and 3 × 8 Gy, and time to tumor tripling volume was determined. Tumors also received 1 × 11, 1 × 15, 3 × 6 and 3 × 8 Gy doses for assessment of CD8+/CD4+ tumor infiltrate and genetic expression 96 h postirradiation. All irradiations of the mouse tumor or flank skin were performed with megavoltage electron beams (10 MeV, 270 Gy/s for UHDR-RT and 9 MeV, 0.12 Gy/s for CONV-RT) delivered via a clinical linear accelerator. Tumor control was statistically equal for similar doses of UHDR-RT and CONV-RT in B16F10 and GL261 murine tumors. There were variable qualitative differences in genetic expression of immune and cell damage-associated pathways between UHDR and CONV irradiated B16F10 tumors. Compared to CONV-RT, UHDR-RT resulted in an increased latent period to skin desquamation after a single 25 Gy dose (7 days longer). Time to moist skin desquamation did not significantly differ between UHDR-RT and CONV-RT after a 30 Gy dose. The histomorphological characteristics of skin damage were similar for UHDR-RT and CONV-RT. These studies demonstrated similar tumor control responses for equivalent single and fractionated radiation doses, with variable difference in expression of tumor progression and immune related gene pathways. There was a modest UHDR-RT skin sparing effect after a 1 × 25 Gy dose but not after a 1 × 30 Gy dose.