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Cutaneous melanoma is the most aggressive form of skin cancer and its incidence is unfortunately increasing. In the last decades, a progressive increase of new cases of diagnosed thin melanoma has been noted. This may be due to earlier detection, better surveillance, improved diagnostic criteria or increased exposure to sunlight. Despite the fact that Breslow tumor thickness has the strongest proven prognostic significance, there are still thin melanomas that metastasize and thick melanomas with favorable evolution. Therefore, the identification of strong predictive factors for survival is mandatory, particularly for patients with thin melanoma.

Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.

Epithelial-mesenchymal transition (EMT) is involved in physiologic processes such as embryogenesis and wound healing. A similar mechanism occurs in some tumors where cells leave the epithelial layer and gain mesenchymal particularities in order to easily migrate to other tissues. This process can explain the invasiveness and aggressiveness of these tumors which metastasize, by losing the epithelial phenotype (loss of E-cadherin, desmoplakin, and laminin-1) and acquiring mesenchymal markers (N-cadherin). Complex changes and interactions happen between the tumor cells and the microenvironment involving different pathways, transcription factors, altered expression of adhesion molecules, reorganization of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in specific microRNAs. The purpose of this review is to determine particularities of the EMT process in the most common malignant cutaneous tumors (squamous cell carcinoma, basal cell carcinoma, and melanoma) which still have an increasingly high incidence. More studies are required on this topic in order to establish clear correlations. High costs related to skin cancer therapies in general as well as high impact on patients’ quality of life demand finding new, reliable prognostic and therapeutic markers with significant public health impact.

Non-melanoma skin cancer (NMSC) is the most common type of neoplasm affecting Caucasian individuals, with squamous-cell carcinoma (cSCC) being the second most common type of NMSC after basal-cell carcinoma. The immunohistochemical study of cSCC is of particular importance, especially for the diagnosis of its rare forms, for which accurate and early diagnosis is crucial for survival. In the present review of the literature, the potentially significant value of immunohistochemical markers were highlighted to more accurately assess the biological behaviour, the prognosis of cSCC and to optimize case management. The immunohistochemical markers were classified from a pathophysiological point of view in order to present the mechanism by which carcinogenesis occurs with its subsequent evolution and therefore, to develop a more accurate novel risk staging criteria for this type of neoplasm.

Dendritic cells (DCs) are antigen-presenting cells with an important role in the innate and adaptive immune system. In skin lesions, cutaneous DCs (Langerhans cells, dermal DCs and plasmacytoid DCs) are involved in immune activation in inflammatory benign lesions, as well as in malignant lymphoid proliferations. Density and distribution of DCs in the dermal infiltrate can be helpful to differentiate benign, reactive infiltrate from malignant nature of the lymphoid population. We performed a retrospective study including 149 patients: 35 with mycosis fungoides, 35 with spongiotic dermatitis, 35 with psoriasis, 35 with lupus and 9 with cutaneous T-cell lymphomas (other than mycosis fungoides), diagnosed using histopathological and immunohistochemical stains. Density and distribution of DCs were evaluated using specific markers (CD1a, CD11c and langerin). In all cases, numerous DCs were identified in the dermal infiltrate. Their number was significantly increased in mycosis fungoides and T-cell lymphomas and moderately increased in inflammatory lesions. Variable patterns of distribution were identified such as clusters of DCs with arachnoid extension in mycosis fungoides, nodular pattern in inflammatory lesions and dispersed distribution with peripheric accumulation in T-skin lymphomas. Therefore, immunohistochemical characterization of DC distribution can be an adjuvant tool in differential diagnosis in inflammatory dermatosis and skin lymphomas.

Given the current outbreak of coronavirus disease 2019 (COVID-19) and the development and implementation of mass vaccination, data are being obtained by analyzing vaccination campaigns. In the present study, 69 healthcare workers who were exposed to patients with severe acute respiratory syndrome coronavirus-2 were monitored for specific immunoglobulin (Ig)G and IgA levels at different time periods. Prior to vaccination, after the first round of vaccination at 21 days (when the second dose of vaccine was administrated) and 24 days after the second round of vaccination, with an mRNA-based vaccine. The basal IgG and IgA levels in previously infected subjects and non-infected subjects notably differed. Vaccination increased the IgG and IgA levels after the first dose in most subjects from both groups, the levels of which further increased following the second round of vaccination. The associations between IgG and IgA levels following the first and second rounds of vaccination demonstrated that in the entire vaccination group, regardless of prior exposure to the infectious agent, the increment and levels of IgG and IgA were similar. Thus, the levels upon vaccination were statistically similar irrespective of the starting base line prior to vaccination. In the present study, seroconversion was achieved in all subjects following the second round of vaccination, with similar antibodies levels.

Skin endometriosis is a rare disease with variable clinical and histopathological characteristics that depend on hormonal stimuli. The skin is not a common location, as most cases of endometriosis involve pelvic sites, such as the ovaries, peritoneum and bowel. However, the most common extrapelvic site affected is the abdominal wall and this location of the disease is frequently associated with obstetric and gynecologic surgery. Here we report a case of skin endometriosis emerged as a painful subcutaneous nodule located near to the left side of an obstetrical surgery procedure scar. The patient affected was a woman in her reproductive age, with a history of right ovary endometriotic cyst laparoscopically removed and histologically confirmed as a primary endometriosis. Dermatologists should be aware of this condition in any woman with a painful lump located in the proximity of a pelvic surgery-induced scar. Its non-specific clinical appearance may confuse the clinician and may delay the diagnosis and management.

Wound healing is a complex biologic process evolving in three phases: inflammation, proliferation, and tissue remodeling controlled by numerous growth factors and cytokines. Oral mucosa wounds heal with significantly less important scars with less numerous macrophages and mast cells and more numerous myofibroblasts than cutaneous counterparts. We analyzed 32 cutaneous and 32 oral mucosa scars for TGFbeta1, TGFbeta2, TGFbeta3, TNFalpha, PDGF BB and FGF1 expression in mesenchymal cells, endothelial cells, macrophages, and multinucleated giant cells. We identified differences in the expression of profibrotic and antifibrotic factors in oral mucosa and skin scars; TGFbeta2 was positive in cutaneous multinucleated giant cells, TNFalpha was positive in cutaneous macrophages, and both were negative in oral mucosa while TGFbeta3 was positive in oral macrophages and mostly negative in cutaneous ones. PDGF BB and FGF1 were positive in oral endothelial cells and oral macrophages and negative in macrophages with opposite positivity pattern in cutaneous scars. Based on these findings, macrophage seems to be the key player in modulating pro- and antifibrotic processes in wound regeneration.

It is suggested that different neuropeptides are actively involved in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis acting as important effectors of the neuroimmune complex interactions, but the available data is limited and contradictory. The aim of this study was to determine whether the chronic infection generates changes in substance P (SP) and vasoactive intestinal peptide (VIP) gastric level and to evaluate the dependence of these potential effects on the degree of bacterial colonization or the severity of the inflammatory infiltrate. Therefore, immunohistochemical tests were performed to examine SP and VIP expression in mucosal nerve endings and myenteric neurons. Both SP and VIP levels were significantly higher in gastric samples of patients infected with H. pylori compared to uninfected individuals, confirming that these neuropeptides are neuroimmune modulators involved in the pathogenesis of H. pylori infection. Although their expression did not correlate with the intensity of mucosal inflammation nor with the bacterial density, we observed a strong association between SP neuronal level and the degree of myenteric ganglionitis, which in turn correlated with the severity of mucosal T-cell infiltration. These findings suggest that the mechanisms of neuroimmune cross-talk depend on some other factors that remain to be determined.

Cutaneous melanoma remains a major health issue and still an important challenge for research. Thus, omics complex evaluation can provide a more specific molecular classification for this heterogeneous disease. Complex omics analysis based on genomic and proteomic microarrays can identify disease markers that prognosticate disease evolution or can monitor therapies efficacy. Among the technologies that gained momentum in the last years, array-based comparative genomic hybridization offered the possibility to analyze chromosomal numerical aberrations within cutaneous melanomas providing important support for molecular classification of melanoma tumors. This technology can identify new chromosomal alterations and discover new deregulated melanoma genes that can be further used as therapy targets. Integrating genetic profiling with clinical and pathological parameters would lead to seminal improvements in diagnosis, prognosis, and therapy.

Diffuse large B-cell lymphoma (DLBCL) represents 30-40% of all non-Hodgkin lymphomas (NHL) and is a disease with an aggressive behavior. Because about one-third of DLBCL patients will be refractory or resistant to standard therapy, several studies focused on identification of new individual prognostic and risk stratification biomarkers and new potential therapeutic targets. In contrast to other types of cancers like carcinomas, where tumor microenvironment was widely investigated, its role in DLBCL pathogenesis and patient survival is still poorly understood, although few studies had promising results. The composition of TME and its interaction with neoplastic cells may explain the role of several genes (beta2-microglobulin gene, CD58 gene), receptor-like programmed cell death-1 (PD-1) and its ligand (PD-L1), or other cell components (Treg) in tumor evasion of immune surveillance, resulting in tumor progression. Also, it was found that “gene expression profile” of the microenvironmental cells, the phenotype of tumor-associated macrophages (TAM), the expression of matricellular proteins like SPARC and fibronectin, the overexpression of several types of matrix metalloproteinases (MMPs) like MMP-2 and MMP-9, or the tissue inhibitors of matrix metalloproteinases (TIMPs) may lead to a favorable or adverse outcome. With this review, we try to highlight the influence of microenvironment components over lymphoid clone progression and their prognostic impact in DLBCL patients.

Melanoma is the most severe type of skin cancer and its incidence has increased in the last decades. In the United States, it is the 6th most common cancer in both men and women. Prognosis for patients with melanoma depends on the stage of the disease at the time of diagnosis and it can be influenced by the immunologic response. Melanoma has been historically considered an immunogenic malignancy. It often contains great amount of immune cells (different subsets of T-cells, dendritic cells, macrophages, neutrophils, mast cells, B lymphocytes), which may reflect a continuous intercommunication between host and tumor. It is not established if tumor-infiltrating lymphocytes (TILs) are induced by tumor cells or by other components of the microenvironment or when they are a host direct immunologic reaction. It has been observed that in many cases, the presence of a dense TIL is associated with good prognosis. The pattern and activation state of the cells which constitute TIL is variable and modulates the clinical outcome. An important step in the understanding of tumor immunobiology is the analysis of the populations and subsets of immune cells that form TIL. Besides its prognostic significance, after approval of cytotoxic T lymphocyte antigen 4, programmed cell death-1 and programmed death-1 ligand antibodies for the treatment of melanoma, the assessment of immune infiltrate composition has become even more captivating, as it could provide new target molecules and new biomarkers for predicting the effect of the treatment and disease outcome in patients treated with immunotherapy. In this review we discuss current state of knowledge in the field of immune cells that infiltrate melanoma, resuming the potential of TIL components to become prognostic markers for natural evolution, for response to drugs or valuable targets for new medication.

Wound healing process comprises a complex network of cells and molecules that are regulated in order to pursue tissue regeneration. Our study focused on the capacity of alveolar blood clots (ABCs), platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) to induce in vitro fibroblasts proliferation and migration as a measure of alveolar regeneration. Using cellular impedance with xCELLigence technology we quantified the proliferation and the migration capacity of L929 fibroblast standard cell line in the presence of 4 different ABCs and 3 different PRFs harvested from healthy individuals during standard tooth extraction. We obtained a clear cellular proliferation induced by the compounds mainly after 24 h of cultivation, in a dose-dependent manner. After 48 h of cultivation we registered activated proliferation, but slightly decreased compared to the 24 h profile. Our data confirm that the presence of the blood clot is involved in the regenerative processes. The migratory capacity of fibroblasts was statistically activated by the PL compounds while not affected by the tested PRFs. The chemical mediators present within the blood clot, either produced by inflammatory cells captive within, or by endothelial or mesenchymal cells induced fibroblastic proliferation and subsequent collagen deposition.

(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC), (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC, (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035), (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.

Regression in melanoma is a frequent biological event of uncertain prognostic value as the lesion exhibits heterogeneous phenotypical features, both at the morphological and immunohistochemical level. In the present study, we examined the expression of tissue inhibitors of metalloproteinases (TIMP1, TIMP2 and TIMP3) in melanoma with regression. We specifically examined the expression levels of these TIMPs in regressed components (RC) and non-regressed components (NRC) of the tumor and compared their expression levels with those in non-regressed melanomas. We found that TIMP1 was overexpressed in the NRC of melanomas with partial regression (PR) compared with the NRC in melanomas with segmental regression (SR) (P=0.011). TIMP2 was overexpressed in the NRC of melanomas with PR compared with the NRC in melanomas with SR (PR/SR, P=0.009); or compared with the NRC in melanomas with simultaneous SR-PR (P=0.002); or compared with melanomas without regression (absence of regression) (P=0.037). Moreover, TIMP3 was overexpressed in the NRC of all melanomas with SR as compared to the RC component (P=0.007). Our findings on the differential expression of TIMP1, TIMP2 and TIMP3 in melanomas with regression support the hypothesis that the morphological differences identified in the melanoma regression spectrum may have a correlation with prognosis. This may explain the controversial findings within the literature concerning the biological and prognostic role of regression in melanoma.

Introduction. Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients. Methods. We analyzed 48 human kidney tissue samples divided into two study groups: the research group (43 renal tissue samples from diabetic or prediabetic patients), and the control group (5 renal tissue samples from patients without diabetes). Immunohistochemistry revealed expression of Bcl-2, APAF-1, CD-95 and Caspase-9 in the renal cortical structures. Statistical analysis was also performed (significance level P Results. We found a variable expression of the antiapoptotic Bcl-2 with a decrease of Bcl-2 expression in diabetes. The control samples render evident intensely positive immunostaining for CD-95. In diabetes and diabetic nephropathy, there was positive immunostaining for APAF-1 at tubular cell level. Nuclear and cytoplasmic positivity for Caspase-9 was more frequently recorded as kidney damage progresses. APAF-1 and Caspase-9 positivity are arguments for an intrinsic apoptotic mechanism of cell death in diabetic nephropathy. Conclusion. The mechanisms of apoptotic cell death identified in diabetic kidney samples prove that Bcl-2, CD-95, APAF-1 and Caspase-9 represent reliable markers of cell death in human renal tissue. Our results support the hypothesis that apoptosis is a pathogenic and initiator mechanism of renal remodeling in diabetic kidney disease.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results.

Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes. Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated. Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.

Wound healing process comprises a complex network of cells and molecules that are regulated in order to pursue tissue regeneration. Our study focused on the capacity of alveolar blood clots (ABCs), platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) to induce in vitro fibroblasts proliferation and migration as a measure of alveolar regeneration. Using cellular impedance with xCELLigence technology we quantified the proliferation and the migration capacity of L929 fibroblast standard cell line in the presence of 4 different ABCs and 3 different PRFs harvested from healthy individuals during standard tooth extraction. We obtained a clear cellular proliferation induced by the compounds mainly after 24 h of cultivation, in a dose-dependent manner. After 48 h of cultivation we registered activated proliferation, but slightly decreased compared to the 24 h profile. Our data confirm that the presence of the blood clot is involved in the regenerative processes. The migratory capacity of fibroblasts was statistically activated by the PL compounds while not affected by the tested PRFs. The chemical mediators present within the blood clot, either produced by inflammatory cells captive within, or by endothelial or mesenchymal cells induced fibroblastic proliferation and subsequent collagen deposition.

Methotrexate (MTX) is a folic acid analog with anti-proliferative (anti-neoplastic, cytotoxic), immunosuppressive and anti-inflammatory properties, which has been used in the treatment of various cutaneous disorders, such as psoriasis, keratoacanthoma, pityriasis rubra pilaris, atopic dermatitis, mycosis fungoides, bullous skin diseases, systemic sclerosis, morphea, lupus erythematosus, dermatomyositis and crusted scabies. Inhibition of cell proliferation is explained through its role in blocking DNA/RNA synthesis, by inhibiting dihydrofolate reductase, necessary for the production of pyrimidine and purine nucleotides. An anticancer effect can be related to α-oxoaldehyde metabolism (MTX increases methylglyoxal levels). Its anti-inflammatory property is based on the inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase, thus increasing intracellular and extracellular adenosine, a purine nucleoside with anti-inflammatory effect. This drug can limit inflammation by scavenging free radicals and decreasing malondialdehyde-acetaldehyde protein-adduct production. Moreover, the anti-proliferative and anti-inflammatory effects can also be related to inhibition of the DNA methylation pathway, thus inhibiting methionine formation. The aim of the present study was to report various dermatological cases from our daily practice that demonstrate the efficacy of MTX in the treatment of cutaneous diseases, highlighting different mechanisms of action: its anti-inflammatory effect in psoriasis and its anti-proliferative, and anti-neoplastic effect in well-differentiated squamous cell carcinoma or in keratoacanthoma. Moreover, different administration pathways and doses are addressed. Assessment of the treatment plan, clinical improvement of cutaneous lesions, biologic evaluation, final aesthetic result, quality of life, as well as potential adverse effects and drug tolerance related to each case mentioned.

Introduction. The clinical use of bioactive materials for bone augmentation has remained a challenge because of predictability and effectiveness concerns, as well as increased costs. The purpose of this study was to analyse the ability to integrate bone substitutes by evaluating the immunohistochemical expression of the platelet endothelial cell adhesion molecules, vascular endothelial growth factor, collagen IV, laminin, and osteonectin, in the vicinity of bone grafts, enabling tissue revascularization and appearance of bone lamellae. There is a lack of in vivo studies of inflammatory-driven angiogenesis in bone engineering using various grafts. Methods. The study was performed in animal experimental model on the standardized monocortical defects in the tibia of 20 New Zealand rabbits. The defects were augmented with three types of bone substituents. The used bone substituents were beta-tricalcium phosphate, bovine hydroxyapatite, and bioactive glasses. After a period of 6 months, bone fragments were harvested for histopathologic examination. Endothelial cell analysis was done by analysing vascularization with PECAM/CD31 and VEGF and fibrosis with collagen IV, laminin, and osteonectin stains. Statistical analysis was realized by descriptive analysis which was completed with the kurtosis and skewness as well as the Kruskal-Wallis and Mann-Whitney statistical tests. Results. The discoveries show that the amount of bone that is formed around beta-tricalcium phosphate and bovine hydroxyapatite is clearly superior to the bioactive glasses. Both the lumen diameter and the number of vessels were slightly increased in favor of beta-tricalcium phosphate. Conclusion. We can conclude that bone substitutes as bovine bone and beta-tricalcium phosphate have significant increased angiogenesis (and subsequent improved osteogenesis) compared to the bioactive glass. In our study, significant angiogenesis is linked with a greater tissue formation, indicating that in bone engineering with the allografts we used, inflammation has more benefic effects, the catabolic action being exceeded by the tissue formation.

Inflammatory bowel diseases (IBD) are a complex, heterogeneous, idiopathic, inflammatory, chronic entity with common clinical, endoscopical and histological features including some well-defined diseases (UC and CD), but also a group of indeterminate colitis. Ulcerative colitis is the most frequent and prominent member of IBD. The current study is trying to evaluate the impact of various histologic features on UC's evolution and outcome--an issue that has generated considerable interest in the academical environment. We gathered a cohort of 20 consecutive patients with positive clinical, endoscopical, histologic and imagistic diagnosis of UC who were prospectively enrolled for close clinical, biochemical, endoscopic and histologic surveillance. Every patient underwent an ileo-colonoscopy and multiple biopsies were taken from inflamed and normal areas of the mucosa. All these procedures were repeated after a year (12 months) of follow-up. This study is presenting the correlation between Mayo score for assessment of ulcerative colitis activity and several histologic features: Geboes histologic score for ulcerative colitis, basal plasmacytosis and vascular lesions using Pearson correlation test. The most promising prognosis value has basal plasmacytosis, confirming previous studies. These data emphasize the need of a more complex, clinical, endoscopic and histologic system of semi-quantitative assessment of UC lesions in order to stratify patients according to their risk to relapse.

Primary penile melanomas are exceedingly rare (less than 1% of primary penile cancers), 221 cases being reported to date in PubMed indexed medical literature. More than half of the cases occur on the gland, usually in older people than on cutaneous counterpart and have unfavourable prognosis mainly due to the belated diagnosis. We report the case of a 77 years old male diagnosed with a pigmented ulcerated nodular melanoma of the gland with maximal thickness of 4.5 mm, mitotic index 8 mitoses/mm2 and vascular emboli. No lymph node enlargements or distant metastases were identified at presentation. Six months after the diagnosis the patient was well, free of disease. Clinically, penile melanomas may be mistaken for several lesions such as squamous carcinoma, penile nevi, pyogenic granuloma, Kaposi sarcoma. Histopathologic diagnosis is usually straight forward except for highly pleomorphic tumors; discrimination between primary penile tumor and penile metastatic melanoma is the most delicate problem of differential diagnosis. The treatment is not standardized; surgical wide excision or partial/total penectomy completed with sentinel lymph node biopsy are the most frequent methods of treatment; multi-agent chemotherapy and/or high-dose interferon alpha 2b therapy are recommended for patients with locally un-controllable disease and/or metastases.