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Frontiers in Oncology 2021The "multidimensional" World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous... (Review)
Review
The "multidimensional" World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous melanoma) according to a progression model in which morphologically intermediate melanocytic tumors are cosidered as simulators and/or precursors to melanoma. These "intermediates" can be subclassified into: i) a "classical" subgroup (superficial/thin compound: dysplastic nevus), which is placed within the morphologic and molecular progression spectrum of classical (Clark's and McGovern's) melanoma subtypes (superficial spreading and, possibly, nodular); and ii) a "non-classical" subgroup (thick compound/dermal: "melanocytomas") whose genetic pathways diverge from classical melanoma subtypes. Such a progression model is aimed at giving a conceptual framework for a histopathological classification; however, routine clinicopathological practice strongly suggests that most melanomas arise and that the vast majority of nevi are clinically stable or even involuting over time. Clinicopathological correlation can help identify some severely atypical but benign tumors (: sclerosing nevus with pseudomelanomatous features) as well as some deceptively bland melanomas (: lentiginous melanoma; nested melanoma), thereby addressing some ambiguous cases to a correct clinical management. The recently available adjuvant therapy regimens for melanoma raise the problem of a careful distinction between severely atypical (high grade) melanocytoma and "classical" melanoma: conventional morphology can guide an algorithmic approach based on an antibody panel (anti-mutated BRAF, BAP1, PRAME, ALK, TRKA, MET, HRAS-WT, ROS; beta catenin; R1alpha; p16; HMB45; Ki67), a first-line molecular study (identification of hot spot mutations of and ) and an advanced molecular study (sequencing of ; fusions studies of ); as a final step, next-generation sequencing can identify melanocytic tumors with rare genetic signatures and melanocytic tumors with a high tumor mutation burden which should be definitely ascribed to the category of classical melanoma with the respective therapeutic options.
PubMed: 34277420
DOI: 10.3389/fonc.2021.675296 -
Indian Dermatology Online Journal 2016Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining...
INTRODUCTION
Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done.
MATERIALS AND METHODS
A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for "melanoma," "melanocytic nevus," and "blue nevus". Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica(®) 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient.
RESULTS
Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern.
CONCLUSION
The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.
PubMed: 26955582
DOI: 10.4103/2229-5178.174312 -
Dermatology Online Journal Feb 2014The melanocytic nevus is a benign and focal proliferation of nevus cells that can be congenital or acquired. Intraoral lesions are uncommon, and the etiology and...
The melanocytic nevus is a benign and focal proliferation of nevus cells that can be congenital or acquired. Intraoral lesions are uncommon, and the etiology and pathogenesis are poorly understood. The occurrence rate of oral compound nevus is about 5.9% to 16.5% of all oral melanocytic nevi. A 22-year-old male patient presented with a dark brown macule on the buccal mucosa of the maxilla in the region of tooth 26. The lesion was elliptical, 0.7 x 0.5 cm, well circumscribed, asymptomatic, and the evolution time was unknown. An excisional biopsy was performed and microscopic analysis revealed nests of nevus cells in the epithelium and underlying connective tissue that were compatible with melanocytic compound nevus. Owing to the clinical similarity between oral melanocytic nevus and oral melanoma, a histopathological analysis is mandatory for definitive diagnosis.
Topics: Biopsy; Humans; Male; Mouth Mucosa; Mouth Neoplasms; Nevus, Pigmented; Young Adult
PubMed: 24612575
DOI: No ID Found -
Frontiers in Pharmacology 2022Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate... (Review)
Review
Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate wavelength. It is a non-invasive therapeutic procedure widely used in oncodermatology for treatment of numerous skin cancers, but in the last years its use has been gradually extended to an increasing list of skin diseases of both infectious and inflammatory nature. Although PDT is proven as a safe and effective therapeutic option in adults, its use is not well standardized in the pediatric population. In this review, we will focus on clinical applications, mechanisms of action, protocols, and adverse events in children and adolescents. Most of pediatric experiences concerned treatment of skin cancers in Gorlin syndrome and xeroderma pigmentosum, acne vulgaris, and viral warts, but other applications emerged, such as cutaneous lymphoma and pseudo-lymphomas, necrobiosis lipoidica, hidradenitis suppurativa, dissecting cellulitis, leishmaniasis, angiofibromas, verrucous epidermal nevus, and linear porokeratosis. In these pediatric diseases, PDT appeared as an effective therapeutic alternative. The results on vitiligo were limited and not fully encouraging. Although highly versatile, PDT is not a therapy for all skin diseases, and a deeper knowledge of its mechanisms of action is required to better define its spectrum of action and safety in pediatric patients.
PubMed: 36052131
DOI: 10.3389/fphar.2022.879380 -
European Journal of Histochemistry : EJH Jun 2011C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign...
C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient's age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Cell Proliferation; Diagnosis, Differential; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Melanocytes; Melanoma; Middle Aged; Nevus; Proto-Oncogene Proteins c-kit; Retrospective Studies
PubMed: 22193299
DOI: 10.4081/ejh.2011.e20 -
Inflammatory juvenile compound conjunctival nevi. A clinicopathological study and literature review.Romanian Journal of Morphology and... 2017The conjunctival nevus affecting children and adolescents is a rare condition and the literature showed only few reports on this issue. The aim of this article is to... (Review)
Review
AIM
The conjunctival nevus affecting children and adolescents is a rare condition and the literature showed only few reports on this issue. The aim of this article is to determine the histopathological features for the correct diagnosis of an inflammatory juvenile compound nevus of the conjunctiva (IJCNC) in order to make the difference between this tumor and other lesions, like conjunctival melanoma or lymphoma, very similar from a gross point of view. This article is a clinical pathological study of two cases of IJCNC with particular histopathological characteristics, who were admitted at the 2nd Ophthalmology Clinic, "Prof. Dr. Nicolae Oblu" Emergency Clinical Hospital, Iasi, Romania, over a period of five years (from July 1, 2012 to June 30, 2017). Both patients were adolescents, a boy (13-year-old) and a girl (12-year-old). Both lesions were bulbar juxtalimbal located and grew in size over one year. Seen at slit-lamp biomicroscopy, the first one presented as a non-pigmented lesion, while the second was a pigmented nevus, but their dimensions did not exceed 10 mm in diameter. From a histopathological point of view, both of them showed a nested junctional growth pattern, along with intra- and subepithelial location, of the nevomelanocytes. Tumoral cells demonstrated different degrees of atypical cytology, but in the second case, it was more obvious. Microscopic examination also revealed epithelial cystic inclusions, and prominent inflammation in the stroma of these two nevi. One of the cases presented heavy inflammation that took the form of lymphoid follicles and sheets of eosinophils, but the other showed only diffuse inflammation with lymphocytes plasma cells, and eosinophils within its stroma. The immunohistochemical characterization (anti-melan A, anti-S100 protein and anti-cytokeratin AE1÷AE3 antibodies) of the tumoral cells helped to the diagnosis.
CONCLUSIONS
IJCNC represent a small group of nevi that develop in adolescents and have some particular histopathological features. The pathological diagnosis is difficult as the microscopic features are very similar to a conjunctival melanoma, but a detailed microscopic examination, immunohistochemical stainings and the young age of the patient could help in establishing the benign nature of these lesions.
Topics: Adolescent; Child; Conjunctival Neoplasms; Female; Humans; Male; Nevus, Pigmented
PubMed: 29250649
DOI: No ID Found -
Clinical, Cosmetic and Investigational... 2014Although common acquired melanocytic nevi are largely benign, they are probably one of the most common indications for cosmetic surgery encountered by dermatologists.... (Review)
Review
Although common acquired melanocytic nevi are largely benign, they are probably one of the most common indications for cosmetic surgery encountered by dermatologists. With recent advances, noninvasive tools can largely determine the potential for malignancy, although they cannot supplant histology. Although surgical shave excision with its myriad modifications has been in vogue for decades, the lack of an adequate histological sample, the largely blind nature of the procedure, and the possibility of recurrence are persisting issues. Pigment-specific lasers were initially used in the Q-switched mode, which was based on the thermal relaxation time of the melanocyte (size 7 μm; 1 μsec), which is not the primary target in melanocytic nevus. The cluster of nevus cells (100 μm) probably lends itself to treatment with a millisecond laser rather than a nanosecond laser. Thus, normal mode pigment-specific lasers and pulsed ablative lasers (CO2/erbium [Er]:yttrium aluminum garnet [YAG]) are more suited to treat acquired melanocytic nevi. The complexities of treating this disorder can be overcome by following a structured approach by using lasers that achieve the appropriate depth to treat the three subtypes of nevi: junctional, compound, and dermal. Thus, junctional nevi respond to Q-switched/normal mode pigment lasers, where for the compound and dermal nevi, pulsed ablative laser (CO2/Er:YAG) may be needed. If surgical excision is employed, a wide margin and proper depth must be ensured, which is skill dependent. A lifelong follow-up for recurrence and melanoma is warranted in predisposed individuals, although melanoma is decidedly uncommon in most acquired melanocytic nevi, even though histological markers may be seen on evaluation.
PubMed: 24672253
DOI: 10.2147/CCID.S57782 -
Journal of Medicine and Life 2017Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts...
Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period. Melanocytic nevi present a strict cellular architecture and an increased malignant transforming capacity. We investigated reelin presence in 32 melanocytic nevi (5 junctional, 27 compound or 14 dysplastic nevi and 18 non dysplastic nevi). The assessment of reelin presence was performed by histological semiquantitative criteria. Results showed the presence of reelin in 29 cases (29/ 32). The presence of reelin was elevated in junctional areas as in dysplastic nevi. VLDLR presented positive values in 16 cases (16/ 32) and ApoER2 was weak positive in 7 cases. Reelin or its receptors was peritumorally absent. Our study showed the presence of reelin in nevus cells from cutaneous melanocytic nevi and, in these cells, only the VLDLR receptor was present in half of the cases. The significance of the reelin presence in cutaneous nevus cells may be hypothetically considered correlated with the position maintenance of the nevus cells or migration of these cells in malignant transforming situation. ApoER2 = apolipoprotein receptor 2, VLDLR = very low density lipoprotein receptor, DAB-1 = DIABLO protein, HMB45 = gene HMB45.
Topics: Adolescent; Adult; Animals; Cell Adhesion Molecules, Neuronal; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; LDL-Receptor Related Proteins; Male; Middle Aged; Nerve Tissue Proteins; Nevus, Pigmented; Receptors, LDL; Reelin Protein; Serine Endopeptidases; Young Adult
PubMed: 28255385
DOI: No ID Found -
Experimental and Therapeutic Medicine Jan 2022Multiple primary cancers may occur in the same patient, with a prevalence that follows an ascendant trend. Their development is dictated by a complex interplay between a...
Multiple primary cancers may occur in the same patient, with a prevalence that follows an ascendant trend. Their development is dictated by a complex interplay between a variety of factors, both patient-dependent and external. The case of a 38-year-old female patient diagnosed and treated for pancreatic cancer (PC) is presented in whom the digital dermoscopic monitoring of melanocytic nevi revealed a marked change of two nevi that acquired rapidly highly atypical features. They were surgically excised and the histopathological examination revealed two completely excised dysplastic compound nevi. Clinicians should be aware of the strong association between dysplastic nevus syndrome and PC, a malignancy associated with an extremely poor prognosis. Familial atypical multiple mole melanoma syndrome (FAMMM) predisposes to the development of melanoma, pancreatic cancer and other neoplasms. The common genetic background of PC and hereditary melanoma is discussed and the importance of regular skin checkup and screening for PC in these patients is underlined.
PubMed: 34824639
DOI: 10.3892/etm.2021.10953 -
Molecules (Basel, Switzerland) Dec 2021Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the... (Review)
Review
Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the overexpression of tyrosinase may result in skin-related disorders such as aging spots, wrinkles, melasma, freckles, lentigo, ephelides, nevus, browning and melanoma. Nature expresses itself through the plants as a source of phytochemicals with diverse biological properties. Among these bioactive compounds, flavonoids represent a huge natural class with different categories such as flavones, flavonols, isoflavones, flavan-3-ols, flavanones and chalcones that display antioxidant and tyrosinase inhibitor activities with a diversity of mechanistic approaches. In this review, we explore the role of novel or known flavonoids isolated from different plant species and their participation as tyrosinase inhibitors reported in the last five years from 2016 to 2021. We also discuss the mechanistic approaches through the different studies carried out on these compounds, including in vitro, in vivo and in silico computational research. Information was obtained from Google Scholar, PubMed, and Science Direct. We hope that the updated comprehensive data presented in this review will help researchers to develop new safe, efficacious, and effective drug or skin care products for the prevention of and/or protection against skin-aging disorders.
Topics: Enzyme Inhibitors; Flavonoids; Humans; Monophenol Monooxygenase; Skin Diseases
PubMed: 34946631
DOI: 10.3390/molecules26247546