Malignant blue nevus with lymph node metastases.
ABSTRACT 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.
We present a patient with metastatic malignant blue nevus and studies on the histopathologic, immunohistochemical, and molecular features of the neoplasm.
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.
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).
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ABSTRACT: Melanomas arising in association with blue nevi or mimicking cellular blue nevi comprise a relatively rare and heterogeneous group of melanomas. It remains controversial which prognostic indicators predictive of outcome in conventional cutaneous melanomas are applicable to this type of melanoma. Here, we describe the clinical and histopathologic features of 24 melanomas arising in association with blue nevi and correlate these with clinical outcome. The mean patient age was 49 years (range: 23-85) with a slight female predominance (15 females:9 males). The most common anatomic locations included the head and neck region (50%), the trunk (21%), and the buttock/sacrococcygeum (17%). Histologically, the tumors were typically situated in the mid to deep dermis with variable involvement of the subcutis, but uniformly lacked a prominent intraepithelial component. The mean tumor thickness (defined as either the standard Breslow thickness or, if not available due to the lack of orientation or lack of epidermis, the largest tumor dimension) was 20.9 mm (range: 0.6-130 mm). The mean mitotic figure count was 6.5/mm(2) (range: 1-30/mm(2)). Perineural invasion was common (38%). Follow-up was available for 21 cases (median 2.1 years). The median overall survival, recurrence-free survival, time to local recurrence, and time to distant recurrence were 5.2, 0.7, 2.6, and 1.6 years, respectively. Logistic regression analyses demonstrated a significant association between tumor thickness and recurrence-free survival (hazard ratio=1.02 per mm; P=0.04) and reduced time to distant metastasis (hazard ratio=1.03 per mm; P=0.02) with a similar trend toward reduced time to local recurrence (hazard ratio=1.02 per mm; P=0.07). No other parameters (age, anatomic location, mitotic figures, lymphovascular or perineural invasion, or type of associated blue nevus) emerged as significant. In addition, we provide a comprehensive review of 109 cases of melanoma blue nevus type described in the English literature and summarize our findings in this context.Modern Pathology advance online publication, 18 April 2014; doi:10.1038/modpathol.2014.62.Modern Pathology 04/2014; DOI:10.1038/modpathol.2014.62 · 6.36 Impact Factor
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ABSTRACT: The proto-oncogene KIT encodes a receptor tyrosine kinase which has been shown to be upregulated in canine melanomas. KIT mutations lead to constitutive phosphorylation and activation of KIT in the absence of ligand binding. The presence of KIT mutations and KIT protein expression was examined in a cohort of 49 dogs with canine malignant melanoma. An exon 11 synonymous nucleotide 1743C→T mutation was identified in five cases in which one also harbored a L579P mutation. Tumors that harbored the KIT exon 11 mutation(s) correlated significantly with disease recurrence (P=0.05). All 36 melanomas available for immunohistochemical analysis showed either weak (16 cases, 44.4%) or strong (20 cases, 55.6%) expression of the KIT protein. The five KIT mutation carriers were all strongly positive for KIT by immunohistochemical staining. These findings suggest that a subset of canine malignant melanomas harbors a KIT exon 11 mutation.The Veterinary Journal 10/2012; DOI:10.1016/j.tvjl.2012.09.005 · 2.17 Impact Factor
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ABSTRACT: Atypical melanocytic neoplasms present a therapeutic dilemma. Current consensus is to perform a sentinel lymph node (SLN) biopsy as part of management. However, it is unclear whether this is required in all patients. We present our experience with sentinel lymphadenectomy in these patients and examine the clinical and pathologic variables associated with a positive SLN. A prospectively maintained melanoma database was queried for patients with controversial melanocytic lesions. All patients between January 1997 and January 2009 were included. Demographic and pathologic information was collected and correlated with results of SLN biopsy. Thirty-one patients underwent SLN biopsy. Median patient age was 19 years (range 5 to 59 years) and median tumor Breslow depth was 1.35 mm. Five patients (16%) had a positive SLN. Those with a positive SLN were younger (median 11 vs 23.5 years, p = 0.02) and had a greater Breslow depth (median 1.90 vs 1.09; p = 0.03) than those who were SLN negative. Median follow-up was 16 months for patients with at least 6 months of follow-up time and there have been no recurrences identified. We report an SLN positive rate of 16% in patients with atypical melanocytic tumors. Younger age and greater Breslow depth are associated with having a positive SLN. These results confirm earlier work demonstrating the importance of SLN biopsy in this disease and highlight the need to measure Breslow depth in these lesions so that they can be appropriately stratified as to the need for SLN biopsy.Journal of the American College of Surgeons 12/2010; 211(6):744-8. DOI:10.1016/j.jamcollsurg.2010.07.020 · 4.45 Impact Factor