When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis.

Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.

Experimental Models for Rare Melanoma Research-The Niche That Needs to Be Addressed.

Melanoma, the tumor arising from the malignant transformation of pigment-producing cells-the melanocytes-represents one of the most severe cancer types. Despite their rarity compared to cutaneous melanoma, the extracutaneous subtypes such as uveal melanoma (UM), acral lentiginous melanoma (ALM), and mucosal melanoma (MM) stand out due to their increased aggressiveness and mortality rate, demanding continuous research to elucidate their specific pathological features and develop efficient therapies. Driven by the emerging progresses made in the preclinical modeling of melanoma, the current paper covers the most relevant in vitro, in vivo, and in ovo systems, providing a deeper understanding of these rare melanoma subtypes. However, the preclinical models for UM, ALM, and MM that were developed so far remain scarce, and none of them is able to completely simulate the complexity that is characteristic to these melanomas; thus, a continuous expansion of the existing library of experimental models is pivotal for driving advancements in this research field. An overview of the applicability of precision medicine in the management of rare melanoma subtypes is also provided.

3D Bioprinting of Model Tissues That Mimic the Tumor Microenvironment.

The tumor microenvironment (TME) influences cancer progression. Therefore, engineered TME models are being developed for fundamental research and anti-cancer drug screening. This paper reports the biofabrication of 3D-printed avascular structures that recapitulate several features of the TME. The tumor is represented by a hydrogel droplet uniformly loaded with breast cancer cells (106 cells/mL); it is embedded in the same type of hydrogel containing primary cells-tumor-associated fibroblasts isolated from the peritumoral environment and peripheral blood mononuclear cells. Hoechst staining of cryosectioned tissue constructs demonstrated that cells remodeled the hydrogel and remained viable for weeks. Histological sections revealed heterotypic aggregates of malignant and peritumoral cells; moreover, the constituent cells proliferated in vitro. To investigate the interactions responsible for the experimentally observed cellular rearrangements, we built lattice models of the bioprinted constructs and simulated their evolution using Metropolis Monte Carlo methods. Although unable to replicate the complexity of the TME, the approach presented here enables the self-assembly and co-culture of several cell types of the TME. Further studies will evaluate whether the bioprinted constructs can evolve in vivo in animal models. If they become connected to the host vasculature, they may turn into a fully organized TME.

Clear cell urothelial carcinoma of the urinary bladder - a rare pathological entity. A case report and a systematic review of the literature.

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). In contrast, the clear cell variant of urothelial carcinoma (CCUC) is quite a rare neoplasm. In this study, we report a case of an 81-year-old male, presenting with gross hematuria and acute urinary retention, which was subsequently diagnosed with CCUC at our pathology department. Furthermore, we provide a short systematic review of the literature (PubMed, Scopus, and Science Citation Index) for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

Expression of EGFR in Paired New and Recurrent Glioblastomas.

BACKGROUND: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM). MATERIALS AND METHODS: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong). RESULTS: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months). CONCLUSIONS: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.