Melanoma ex blue nevus: two cases resembling large plaque‐type blue nevus with subcutaneous cellular nodules

Large plaque‐type blue nevi with subcutaneous cellular nodules are rare tumors occurring on the trunk with deep extension into underlying soft tissues. The histopathologic appearance consists of deep nodules resembling cellular blue nevi with interspersed foci of common blue nevus. Conservative management has been recommended, and metastases have not been observed. This report discusses two cases with microscopic features of large plaque‐type blue nevi with subcutaneous cellular nodules in which comparative genomic hybridization showed chromosomal aberrations typical of melanoma. In both cases, the nodules showed gains involving chromosome 6p and losses involving chromosome 6q, which are among the most commonly found aberrations in melanoma. These copy number changes were not present in the less cellular surrounding areas that appeared characteristic of blue nevus. These cases illustrate that large blue nevi with a deep, multi‐nodular configuration should be interpreted with caution, and that superficial biopsies of such lesions can be misleading. Molecular techniques can provide valuable insights in these types of difficult melanocytic neoplasms.     

Agminated blue nevus with a GNAQ mutation: A case report and review of the literature

Agminated blue nevi are dermal melanocytic proliferations that classically present as dark blue macules or papules in a grouped, linear, or blaschkoid distribution. In their more common sporadic form, blue nevi manifest in young adulthood as solitary blue papules or macules on the scalp, face, hands, or feet. By contrast, agminated blue nevi tend to manifest earlier in life, and are distributed more evenly across anatomic sites. Recent studies have identified mutations in sporadic blue nevi in the genes encoding G Protein subunit alpha Q and G protein subunit alpha 11 (GNAQ and GNA11). It is unknown whether agminated blue nevi share the same genetic changes. In the present paper, we present a case of agminated blue nevus on the wrist, and identify an activating mutation (c.626A > T, p.Glu209Leu) in GNAQ. We hypothesize that GNAQ/GNA11 activating mutations arising earlier during development may trigger agminated blue nevi, explaining the broader field of involvement in these cutaneous lesions.     

Aggressive melanoma in an infant with congenital melanocytic nevus syndrome and multiple,NRAS and BRAF mutation‐negative nodules

We report the case of a newborn boy with multinodular NRAS and BRAF mutation‐negative congenital melanocytic nevi and cerebral lesions compatible with congenital intraparenchymal melanosis. Histopathology from skin lesions showed atypical nodular melanocytic proliferation with marked melanocytic atypia and a large number of mitoses and apoptosis, indicating aggressive proliferation. The child developed several new subcutaneous tumors and multiple internal lesions, which were confirmed to be metastases, and died at 5 months of age. This case may represent an infantile melanoma developing from a giant congenital melanocytic nevus or a congenital melanoma.     

Recurrent nodules in a periauricular plaque‐type blue nevus with fatal outcome

Plaque‐type blue nevus is a rare variant of blue nevus characterized by grouped nodules displaying histomorphological features of a cellular blue nevus. We report the clinical, histopathologic and immunohistologic features of a patient with recurrent nodules in a periauricular plaque‐type blue nevus with malignant transformation and fatal outcome. The nevus was characterized clinically by childhood onset, with slow enlargement during adolescence. At age 16, the patient presented with nodules located retroauricularly. Several surgical excisions with the intent of complete removal of the nodules and the nevus were performed. Histopathological, dermal and subcutaneous proliferations of pigmented melanocytes with melanophages were detected. The nodules showed some cellular atypia and few mitotic figures, (Ki67 estimated <1%). At age 20, the patient developed new nodules retroauricular, with histopathology similar to previous lesions; however, the proliferation rate was higher. A comparative genomic hybridization (CGH) showed chromosomal changes indicative of melanoma. At age 25, the patient developed multiple liver metastases and died after 4 weeks. A sequencing of the tumor DNA revealed a GNAQ Q209P mutation, whereas mutations of GNA11, BRAF, NRAS and cKIT were not detected. This case shows that nodules in plaque‐type blue nevus may have malignant potential which may be uncovered by CGH.     

A cellular blue nevus with pigmented epithelioid melanocytoma‐like pattern on the ipsilateral upper arm associated with a congenital plaque‐type blue nevus on the hand

A 36‐year‐old man presented with a subcutaneous nodule on the right upper arm. A small nodule had developed 8 years earlier, and grew in size, accompanied by a tingling sensation and numbness. In addition, he had a bluish irregular patch on the right hand since birth, which crossed from the palm to the dorsal hand. Skin biopsies from the hand showed a heavily pigmented melanocyte proliferation in the dermis with perieccrine, perivascular, and perineural involvement, and a diagnosis of congenital plaque‐type blue nevus was made. The tumor on the arm was located closely along the median nerve, and was observed as a large black pedunculated round tumor. Histopathologically, the tumor on the arm consisted of densely packed tissue with nevoid cells without atypia in the larger nodular part, and heavily pigmented spindle and epithelioid melanocytes in the slender stalk area, which was diagnosed as cellular blue nevus with pigmented epithelioid melanocytoma‐like pattern. Next‐generation sequencing revealed GNAQ mutations in the hand lesion, and in the lesions on the arm. This case suggests that the areas of skin following the same neural distribution of a congenital plaque‐type blue nevus on the extremities should be followed up for secondary changes.     

A giant melanocytic nevus treated with combined use of normal mode ruby laser and Q-switched alexandrite laser

We report a combination procedure that can improve the effectiveness of laser removal of giant congenital melanocytic nevi (CMN). A 2-year-old girl with a giant CMN was seen in our outpatient clinic. Histological findings showed a compound nevus without any evidence of malignancy or dysplastic changes. The patient was treated with the normal mode ruby laser and Q-switched alexandrite laser. The lesion was significantly improved in color and cosmetic appearance. Partial hypopigmentation and texture changes were observed. Histological findings showed a marked decrease in the number of junctional melanocytes and the nests in the papillary and reticular dermis. The combined laser treatment is an effective method for the treatment of giant CMN, but further study is warranted to follow-up questions of recurrence and malignant change.     

Acanthosis nigricans,hypochondroplasia, and FGFR3 mutations: Findings with five new patients,and a review of the literature

Early development of extensive acanthosis nigricans (AN) is a key feature in some patients who have hypochondroplasia (HCH) in association with FGFR3 mutations. We here report regarding five new patients with HCH who exhibited AN, and we compare their characteristics to the eight patients previously described in the literature. In these patients, the AN lesions began in childhood, and they were extensive. These lesions were located on the torso, the abdomen, and the face, in addition to the typical skin fold sites. Other skin lesions were frequently reported: café‐au‐lait macules, melanocytic nevi, lentigines, and seborrheic keratosis. The Lys650Thr mutation was the predominant reported mutation of FGFR3.     

Generalized congenital epithelioid blue nevi (pigmented epithelioid melanocytomas) in an infant: Report of case and review of the literature

The epithelioid blue nevus (EBN) is a variant of the blue nevus characterized by heavily pigmented epithelioid melanocytes and lightly or nonpigmented spindle cells. It may be associated with Carney complex, a multiple neoplasia syndrome. Congenital cases of EBN not associated with Carney complex are rarely reported. We herein describe an infant who presented with multiple blue‐gray nodules and papules involving the head, trunk, and extremities at birth, the corresponding histopathologic findings, and genetic testing results.     

Treatment of pigmentary disorders using picosecond laser in Asian patients: A meta‐analysis and systematic review

There were many studies evaluating the effect of picosecond (PS) lasers, but no meta‐analysis examined the effects of PS laser in the treatment of pigmentary disorders in Asians. The aim of this article was to review the before‐after effect of PS laser in Asians for the treatment of pigmentary disorders. PubMed, Embase, and Cochrane library were searched for articles published up to May 2020. The evaluations were summarized into a 4‐point scale that ranged from <25% (poor), 25%‐50% (fair), 50%‐75% (good), and 75%‐100% (excellent). Effect sizes (ESs) were calculated according to laser wavelengths and lesion types. There were two randomized controlled trials, three single‐arm trials, and three case series, with 200 patients. At 3 months after treatment, of all included patients, 3% (95%CI: 1%‐6%) were evaluated as poor or worse, 9% (95%CI: 2%‐21%) as fair, 29% (95%CI: 12%‐50%) as good, and 56% (95%CI: 28%‐83%) as excellent. The 532 and 1064, and 755 nm PS lasers had similar ESs across all four response groups. This meta‐analysis suggested that 56% of Asian patients who underwent PS laser for the treatment of pigmentary disorders were evaluated as “excellent” about the pigment clearance by a dermatologist at least 3 months after treatment.     

Phototherapy‐induced blistering reaction and eruptive melanocytic nevi in a child with transient neonatal porphyrinemia

Neonatal blue‐light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity‐induced epidermal injury, that of porphyrins and the influence of neonatal blue‐light therapy, in this unique phenomenon are discussed.     

Combined epidermal-connective tissue nevus of proteoglycan (a type of mucinous nevus): a case report and literature review

Mucinous nevus is a rare entity with only 11 cases reported previously. It may be divided into two histopathologic types: connective tissue nevus of the proteoglycan (CTNP) and combined epidermal-CTNP. We describe a boy with asymptomatic grouped brown papuloplaques on the lower back since birth. A diagnosis of mucinous nevus of the combined epidermal-CTNP type was made after a biopsy. We vaporized two lesions with carbon dioxide laser, and the wounds healed satisfactorily. We present a literature review indicating a striking preponderance of male patients (M : F = 5 : 1) for mucinous nevus. In half of the cases, mucinous nevus did not appear until childhood, adolescence or early adulthood. The predominantly affected site was the trunk. Half of the cases can be assigned to the CTNP type and the other half to the combined epidermal-CTNP type. We propose that carbon dioxide laser vaporization may be a treatment option for mucinous nevus of the combined epidermal-CTNP type with multiple lesions but not for the CTNP type.     

Congenital melanocytic nevi and nevus spilus have a tendency to follow the lines of Blaschko: an examination of 200 cases

There have been few reports about the characteristics of the pigmentary arrangement of congenital melanocytic nevi (CMN) and nevus spilus (NS). Though the lines of Blaschko, which don't correspond to other lines such as Langer's lines and skin dermatomes, are well known to be followed by some rare pigmentary disorders, the relationship between these two disorders and the lines of Blaschko has not been discussed. Therefore, through an examination of 200 cases, we investigated whether or not the arrangement of CMN and NS follow the lines of Blaschko. Thirty-nine out of 92 cases (42.4%) of CMN and 67 out of 108 cases (62.0%) of NS were considered to follow the lines of Blaschko. Today, the idea is widely accepted that two functionally different cells proliferate during early embryogenesis of the skin which is caused from mosaicism and, as a result, the lines of Blaschko appear visually. In our results, we found that there were some cases of CMN and NS which showed a relationship with the lines of Blaschko, which is meaningful considering that the lesions and the lines are both related to pigmentary gene anomalies. The result was compared with CMN and NS by the chi(2) test. NS showed a predominant tendency to follow the lines with a significant difference (P = 0.0055). This may indicate that the lines of Blaschko reflect more clearly the proliferation of the epidermal cells than other cells in growth of the skin of the embryo. Further studies are required to elucidate the reason why some cases follow these lines and others do not.     

The morphologic spectrum of germline‐mutated BAP1‐inactivated melanocytic tumors includes lesions with conventional nevic melanocytes: A case report and review of literature

Germline mutations in BRCA1‐associated protein 1 (BAP1) are associated with several neoplasms, including BAP1‐inactivated melanocytic tumors (BIMTs). BIMTs are classically described as biphenotypic melanocytic proliferations with BAP1‐deficient large epithelioid and rhabdoid melanocytes showing various degrees of cytologic atypia. This morphology has been traditionally classified as “spitzoid” despite the various differences between these lesions and the more classic Spitz nevi. Herein, we report a case of an otherwise healthy 11‐year‐old female patient with a family history of several malignancies who presented with multiple pink to brown papules. Histologic and immunohistochemical evaluation identified three lesions with loss of nuclear BAP1 staining. The histologic spectrum of these lesions included junctional spitzoid cells within a triphenotypic proliferation and a separate lesion composed entirely of dermal small to medium‐sized epithelioid melanocytes with maturation. BAP1 gene sequencing revealed a germline frameshift pathogenic BAP1 mutation, denoted c.1717delC. This case provides further evidence that not all BIMTs conform to classic morphological criteria and that the morphologic spectrum includes lesions resembling conventional nevi. As BIMTs can serve as an early marker of the BAP1 hereditary tumor predisposition syndrome, we believe a need exists for a more comprehensive combined clinical and pathological approach for BIMT identification.     

Congenital nevus comedonicus complicated by a hidradenitis suppurativa‐like lesion: Report of a childhood case

Nevus comedonicus is a rare, benign hamartoma of the pilosebaceous unit that may be isolated or part of the nevus comedonicus syndrome. Although rare in children, complication by hidradenitis suppurativa‐like lesions has been described. We present a report of a 9‐year‐old girl in whom surgical excision was curative, with a review of the relevant literature.     

Evaluation of the effect of narrow band‐ultraviolet B on the expression of tyrosinase,TYRP‐1, and TYRP‐2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study

Narrowband‐ultraviolet B (NB‐UVB) is considered one of the main therapeutic tools in vitiligo, which is able to induce repigmentation and halt depigmentation. However, little remains known about the effect of NB‐UVB on TYR gene family, the main pigmentary genes, in vitiligo patients. To assess the effect of NB‐UVB on expression of some genes related to the pigmentary problem of vitiligo; tyrosinase (TYR), tyrosinase related protein 1 (TYRP1) and tyrosinase related protein 2 (TYRP2), mRNA levels of those genes were quantitatively evaluated by Real‐Time quantitative Polymerase Chain Reaction (RT‐qPCR) in skin biopsies obtained from 30 patients with nonsegmental vitiligo and five healthy controls. Vitiligo patients were classified into two groups; group 1, involving 12 untreated vitiligo patients and group 2, including 18 vitiligo patients treated by NB‐UVB. The levels of TYR, TYRP‐1, and TYRP‐2 mRNAs in untreated group were significantly lower than in control subjects (P < .001). In NB‐UVB treated group, the three genes were significantly higher than in group 1 (P < .001), however, they were still significantly lower than in the control subjects (P < .001). A significant positive correlation was detected between TYR and TYRP‐2 genes in group 2 (P = .03). This study demonstrated that mRNA level of TYR, TYRP‐1, and TYRP‐2, which decreased in vitiligo, was significantly increased upon treatment with NB‐UVB. Accordingly, the mechanism of depigmentation in vitiligo disease and repigmentation by NB‐UVB treatment may be related to the changes in the expression of these genes.     

Laser therapy of a dermal nevus in the esthetic zone of the nasal tip: A case report and comprehensive literature review

This case report demonstrates the ablation of a dermal nevus using a diode laser in the esthetically very demanding facial area of the nasal tip. The clinical outcome shows good results and a high level of patient satisfaction. Due to effective wound granulation and healing, elaborate skin grafts could be avoided. The application of the contact laser ensures safe treatment in highly perfused areas thanks to haptic feedback and good coagulative effect. The method should therefore be considered as an alternative to other ablative procedures for benign lesions in the facial area.     

Congenital plaque‐like glomangioma treated successfully with dual wavelength pulsed‐dye and neodymium:yttrium‐aluminum‐garnet laser

Glomovenous malformations are disseminated variants of cutaneous glomus tumors. These malformations are subdivided into regional or localized, disseminated, and congenital plaque‐like forms. The congenital plaque‐like form is the rarest variant. Most treatment modalities have been disappointing in the treatment of large glomangiomas, leading to high recurrence rates. We report a case of a 34‐year‐old man with a congenital plaque‐like glomangioma on his left arm and forearm treated successfully with sequential pulsed‐dye neodymium yttrium aluminum garnet laser.     

Melanoma arising from a plaque‐type blue naevus with subcutaneous cellular nodules of the scalp

Plaque‐type blue naevus (PTBN) is a very rare variant of blue naevus (BN). The potential malignancy of subcutaneous cellular nodules (SCN) in PTBN was discovered in 2012, and there is currently no clear consensus on prognostic factors or management guidelines of such lesions. PTBN on the scalp have not been described in the literature. We report the clinical, histopathological and immunohistological features of a 50‐year‐old man who presented with a 30‐year history of scalp PTBN, with malignant proliferation of nodular elements and fatal outcome 8 years later. This case suggests that long‐term monitoring of patients with PTBN is required. Early surgical removal of such lesions should be considered, especially in the presence of any case of enlargement or change.