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.     

Amelanotic blue nevus: a variant of blue nevus.

Blue nevi are typically heavily melanized. We report a variant of blue nevus that is minimally pigmented. Of the 1,358 blue nevi seen in our laboratory during the last 6 years, 38 (2.7%) were selected that had scant or absent melanin. We refer to these blue nevi as the amelanotic type. Approximately half of the cases in clinical diagnosis were nevus of some type, whereas other differential diagnoses were basal cell carcinoma, dermatofibroma, and lesion. Histologically all specimens were characterized by the spindle-shaped cells seen in blue nevi, but with very little or no obvious melanin. Some lesions were markedly cellular, resembling the features of cellular blue nevus. No hemosiderin was identified on Perls' stain, whereas Fontana-Masson stain was variably positive. Usually there was fibrous stroma. In most cases, the histologic differential diagnosis was dermatofibroma. Other histologic differential diagnoses included amelanotic and/or spindle cell melanoma, dermal Spitz nevus, neurofibroma, and scar. There was no pleomorphism or increased mitotic activity. Evidence of epidermal melanocytic hyperplasia was seen in two cases. Furthermore, the lesions had been present for many years without evidence of recent change. Immunohistochemistry showed all cases to be strongly positive with anti Mel-5 antibody, but only weakly positive or negative with anti S-100 and HMB-45 antibodies. We would like dermatologists and pathologists to be aware of this unusual and uncommon entity.     

Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus-like melanoma

Background: Blue nevus‐like melanomas are melanomas that arise in association with blue nevi or closely simulate the histopathologic appearance of a blue nevus, usually a cellular blue nevus (CBN). Although the majority of CBN can be readily distinguished from blue nevus‐like melanoma by conventional microscopy, there are a subset of cases where this distinction may be exceedingly difficult or impossible. Methods: In this study, we evaluated the ability of a fluorescence in situ hybridization (FISH) assay targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and the centromere of chromosome 6 (Cep6) to distinguish between CBN and blue nevus‐like melanoma. We identified five cases of blue nevus‐like melanoma and 12 cases of CBN. Results: The FISH assay was performed with 100% sensitivity and 100% specificity. Three of five cases met the 6p25/Cep6 criteria, all five met the 6p25 gain criteria and three of five met the 6q23/Cep6 loss criteria. None of the cases met criteria for gains in 11q13. None of the 12 CBN met any criteria for melanoma. Conclusions: A combined analysis of clinical aspects, histopathologic changes and FISH analysis could potentially contribute significantly to the ability of pathologists to discriminate between blue nevus‐like melanoma and blue nevi in challenging cases. Gammon B, Beilfuss B, Guitart J, Busam KJ, Gerami P. Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus‐like melanoma.     

Clinical aspects of blue nevus and its variants

In a 5-years' study, we investigated the correlation between clinical and histological diagnoses of blue nevi. In 24.7% of the cases, the clinical diagnosis turned out to be false; blue nevus was mostly confused with nevomelanocytic nevus (11.2%). Malignant melanoma was the primary differential diagnosis in 13 out of 89 cases. Differentiation of the histological subtypes identified 76.4% of the tumors as common blue nevi and 15.7% as cellular blue nevi. The remaining 7.9% were combined nevi. The average age of the patients with blue nevi at the time of excision was lower than that of the patients suffering from malignant melanoma during the same observation period. Comparison of the distribution of 89 blue nevi with 196 malignant melanomas revealed the different preferred areas of these tumors. We briefly refer to related dermal melanocytoses, such as Mongolian spot and Ota's nevus.     

Malignant blue nevus with lymph node metastases

Background:  Malignant blue nevi arise within cellular blue nevi and contain atypical mitoses, necrosis, nuclear pleomorphism and prominent nucleoli. Malignant blue nevus has been described as a distinct identity, a rare form of malignant melanoma, and a misdiagnosed melanoma.
Methods:  We present a patient with metastatic malignant blue nevus and studies on the histopathologic, immunohistochemical, and molecular features of the neoplasm.
Results:  Histology showed a malignant blue nevus arising in a combined intradermal and cellular blue nevus. CD117 (c-kit) staining showed diffuse cytoplasmic expression within the cellular blue nevus, decreased staining in the malignant component, and variable positivity within the lymph node metastases. Molecular loss of heterozygosity analysis showed different allelic patterns at the hOGG-1 locus between the melanoma and control skin specimens with a varying heterozygous allelic pattern in both the benign and malignant blue nevus.
Conclusions:  Our case of malignant blue nevus with lymph node metastasis involved mutation of the hOGG-1 DNA repair gene. CD117 showed decreased staining of the primary malignant blue nevus with marked upregulation in the metastatic lesion, unlike most metastatic melanomas. Further study is needed to determine if hOGG-1 mutation or c-kit upregulation play a role in the pathogenesis of dendritic melanocytic lesions (either benign or malignant).     

Acquired patch-type blue nevus with overlying vitiligo: a case report

Background Blue nevi are a group of congenital and acquired dermal melanocytoses characterized by a blue‐gray appearance on the skin. The common blue nevus and cellular blue nevus are the most common subtypes. Patch‐type blue nevus is rather rare. Observations We describe a 77‐year‐old Chinese male with a 6 × 8‐cm non‐palpable blue patch overlaid by a depigmented patch on the back of the left scalp. Histological examination of the blue‐gray patch showed numerous spindled and elongated bipolar dendritic melanocytes in the upper reticular dermis and an absence of epidermal melanocytes. Immunohistochemically, these dendritic melanocytes were positive for S‐100 and HMB‐45. A diagnosis of a patch‐type blue nevus with overlying vitiligo was made after the biopsy. Conclusions The patient presents an unusual manifestation of patch‐type blue nevi with overlying vitiligo. To the best of our knowledge, these features have not been previously described.     

Malignant melanoma arising in a blue nevus with features of pilar neurocristic hamartoma

A 65-year-old man presented with a history of a giant blue plaque of the parietal scalp since childhood. Biopsy revealed a cellular blue nevus. The blue nevus was observed for 10 years and thought to be unchanged until a new adjacent lesion was noted. Biopsy of the new lesion revealed metastatic malignant melanoma. A wide excision was performed of the original lesion which revealed malignant melanoma arising in a blue nevus. Areas within the blue nevus were consistent with a pilar neurocristic hamartoma, whereas other areas were consistent with a common blue nevus. Subsequent satellite metastases developed, with early metastases resembling blue nevi except for the absence of a stromal component and the presence of hyperchromatic nuclei. Later metastases were typical of metastatic melanoma. This case illustrates the uncommon evolution of malignant melanoma from a blue nevus. The histological features and relationship between melanoma, blue nevus, and pilar neurocristic hamartoma are reviewed.     

Histopathologic and mutational analysis of a case of blue nevus‐like melanoma

Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well‐defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus‐like melanoma remains diagnostically challenging. We report a case of a 46‐year‐old female with recurrent blue nevus‐like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus‐like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies     

Malignant blue nevus: a report of eight cases.

Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.     

Cellular blue nevus with nevus cells in a sentinel lymph node

Regional lymph node involvement by a cellular blue nevus has been reported. However, it has recently been suggested that specific cases with "benign metastasizing" cellular blue nevi are actually rare. This study describes a typical case of a cellular blue nevus with nevus cells in a sentinel lymph node. We demonstrated that a cellular blue nevus clearly involved the regional lymph node and investigated the immunohistochemical profiles of such nodal cellular blue nevus cells. The location of the nevus cells fundamentally indicated a benign type, with limitation to the capsule and the fibrous trabeculae. However, only a few, isolated nevus cells were also seen in the parenchyma of the lymph node. The nevus cells in the capsule and the fibrous trabeculae were positive for c-kit, like the migrating melanocytes from the neural crest. In cellular blue nevi or lesions with similar histopathological features, it may be appropriate to consider the predominant involvement of the capsule as well as the benign cytological features and the immunohistochemical profiles (Ki-67-, PCNA-, and c-kit+) of the nodal cells to be a benign sign.     

Plaque-type blue nevus of the oral cavity

BACKGROUND: The blue nevus of the oral cavity is a rare lesion with important differential diagnoses. The plaque-type blue nevus is an uncommon variant of the blue nevus. Because of its particular clinical appearance, it can easily be confused with satellite metastases from malignant melanoma. The diagnosis usually requires a biopsy. OBJECTIVES: To describe the clinical and histological features of a plaque-type blue nevus of the buccal mucosa in a 20-year-old white woman, to review all intraoral blue nevi and all plaque-type blue nevi reported in the literature so far and to compare the criteria of blue nevi and nevus of Ota. RESULTS: An intraoral blue nevus was described for the first time in 1959. Since then around 70 further cases have been documented. Our case is the first report of a plaque-type blue nevus of the oral cavity. CONCLUSIONS: The exceptional widespread intraoral blue nevus described herein can clinically be confused with an intraoral malignant melanoma, and it has a very similar clinical appearance as the intraoral part of nevus of Ota. Apart from the clinical resemblance, there is also some degree of histological overlap of the dermal melanocytoses. Transitional states between blue nevus and nevus of Ota may occur clinically and histologically.     

Large plaque‐type blue naevus with subcutaneous cellular nodules

We report a new case of ‘large plaque‐type blue naevus (PTBN) with subcutaneous cellular nodules’ involving the breast. A 25‐year‐old‐woman presented with a large plaque, 140 × 100 mm in size, on the right chest wall involving the right breast, associated with recent subcutaneous nodules. Histopathological examination revealed features of cellular and common blue naevus. Dermatoscopy was performed, and the diagnosis of PTBN was made. PTBN is a rare condition with an imprecise prognosis. In cases of PBTN lesions on the head, clinicians must keep in mind the risk of malignant transformation of PTBN or an association with cutaneous neurocristic hamartoma. For this new variant of PTBN appearing on the trunk, we propose close monitoring of the patient if surgical excision is impossible.     

Congenital pauci-melanotic cellular blue nevus

Unusual or atypical melanocytic nevi can be confused with malignant melanoma. Two patients are presented here with a rare variant of melanocytic nevus. Both were men. One was 39 years old and sought medical attention after trauma of a "congenital mole". The other was 24 years old and presented with a history of a slowly growing lesion, which had been known since childhood. In both patients, the lesion occurred on the buttock. They were dermal and superficial subcutaneous nodules measuring 1.5 and 2.3 cm in greatest dimension, respectively. The tumors were composed of densely cellular fascicles of melanocytes arranged in a lobulated growth pattern. Rare nests of small epithelioid melanocytes were also seen. No melanin pigment was seen on hematoxylin and eosin-stained sections. Focal minimal pigment was noted by Fontana-Masson stain in one case. Involvement of numerous peripheral nerve trunks by fusiform melanocytes was a prominent feature. Rare mitotic figures were seen in melanocytes [1-2 mitoses per 50 high-power fields (HPF)]. The MIB-1 labeling index was low (less than 5% of the lesional cell population was immunopositive). Both tumors were excised with negative surgical margins. One patient underwent sentinel lymph node biopsy because there was controversy regarding the biologic potential of the lesion. No melanocytic tumor deposits were found in the lymph nodes. On clinical follow up of 11 years and 18 months after complete excision, both patients are alive and well with no evidence of recurrence. We regard these lesions as congenital monophasic and pauci-melanotic variants of cellular blue nevus. The nevi are presented here to enhance our knowledge of the morphologic spectrum of melanocytic tumors and to help avoid confusion with malignant melanoma.     

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.     

Intraoral cellular blue nevus: report of a unique histopathologic entity and review of the literature

The blue nevus is found most frequently on the skin; however, in rare instances, it has been reported on oral mucous membranes. Intramucosal nevi make up more than one half of all reported intraoral melanocytic nevi. The common blue nevus is the second most common variant. Among the 3 variants of blue nevi, the cellular variant occurs less frequently than the common and combined variants. We present a rare case of intraoral cellular blue nevus that occurred on the oral mucosa of the hard palate. Because of the clinical and microscopic resemblance of the cellular blue nevus to melanoma and the rarity of this lesion in the oral cavity, recognition and accurate diagnosis are critical.     

Trichoepithelioma associated with cellular blue nevus

BACKGROUND: Epithelial elements, such as trichoepithelioma, are occasionally associated with melanocytic nevi. OBJECTIVE: A case of trichoepithelioma in association with cellular blue nevus is reported. METHODS AND RESULTS: A solitary, pigmented nodule was removed from the scalp of a middle-aged woman. Histopathologic examination demonstrated a circumscribed cellular blue nevus within which were embedded epithelial strands and cystic structures consistent with trichoepithelioma. CONCLUSION: Trichoepitheliomas have been described in relation to common acquired nevi, but an association with a blue nevus is rare. The intimate admixture of trichoepithelioma within the nodule of a nevus supports the concept of epithelial induction by melanocytic nevi.     

Balloon cell change in cellular blue nevus

Balloon cells are altered melanocytes with clear vacuolated cytoplasm caused by a defect in the process of melanogenesis. Although rare, balloon cell change has been observed in a variety of melanocytic proliferations, particularly intradermal melanocytic nevi and melanoma. When present, such features may lead to difficulties in diagnosis, particularly with other clear cell neoplasms. We report an unusual case of the development of balloon cell change in a cellular blue nevus, a phenomenon that has not been extensively addressed in the literature. The importance of recognizing this change in cellular blue nevus to avoid misinterpreting the lesion as malignant is discussed.     

Homogeneous blue pattern in an acral congenital melanocytic nevus

Dermoscopy in acquired acral melanocytic nevi has been widely studied. This is in contrast with the little information about the dermoscopic characteristics in congenital acral melanocytic nevi. We report a 46-year-old man who was referred due to a lesion on his right sole present since childhood corresponding to an acral congenital nevus. Dermoscopy showed a homogeneous blue pattern not previously described in acral benign tumors. The homogeneous blue pattern has previously been associated with blue nevus and skin metastasis of melanoma. The recognition of this pattern in benign acral congenital nevi is relevant in the clinical decision making concerning acral tumors.     

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.