Combined melanocytic nevi: histologic variants and melanoma mimics

Combined melanocytic nevi are composed of 2 or more distinct populations of nevomelanocytes. Most commonly used to describe the combination of blue nevi with common nevi, it may also be applied to other combinations of benign melanocytic proliferations, including Spitz nevi and nevi with deep dermal pigmented nevomelanocytes. We report the incidence and distribution of these tumors at the Massachusetts General Hospital over the past decade and review guidelines for diagnostic criteria and nomenclature. Between 2000 and 2010 we identified 511 cases of combined nevi, represented by 4 histologically distinct diagnostic categories: (1) blue nevus, (2) nevi with deep dermal pigmented nevomelanocytes (plexiform/deep penetrating, inverted type A/clonal), (3) Spitz or pigmented spindled cell nevus, combined with another type of nevus (usually common or dysplastic), and (4) other combinations including 2 or more nevus types. Nearly one fifth of these tumors displayed atypical features; atypia was observed more often in combined nevi with Spitz or deep pigmented elements (26 of 55, 47%, and 25 of 98, 26%, respectively) than in combined common and blue nevi (37 of 336, 11%). Clinical follow-up data were available for 83% of the patients with atypical combined nevi; none developed recurrence or metastasis with a mean follow-up of over 4 years.     

Regression of Atypical Nevus: An Anecdotal Dermoscopic Observation

BACKGROUND: Clark nevi (atypical melanocytic nevi) can be considered as risk markers and potential precursors of melanoma. The authors report on the morphologic changes of an atypical nevus by dermoscopic follow-up examination over a 7-year period. CASE REPORT: A 43-year-old man had a brown macule on his back, sized 5 mm, with an irregular shape, clinically and dermoscopically diagnosed as an equivocal melanocytic lesion. Dermoscopically during the initial examination, a predominant reticular pattern with peripheral eccentric hyperpigmentation in the lower portion of the lesion could be seen. After 7 months, the area of peripheral eccentric hyperpigmentation had regressed, and after 4.5 years the atypical pigment network had almost disappeared. After 7 years of follow-up, a diffuse area of hypopigmentation and a residual light brown pigmentation were detectable. The histopathologic diagnosis was consistent with an atypical junctional nevus with regression with features of a Clark nevus. CONCLUSION: Based on our observation, even a dermoscopically atypical nevus may undergo regression as documented by long-term dermoscopic follow-up.     

Genomic analysis of blue nevi and related dermal melanocytic proliferations

Blue nevi are benign dermal melanocytic proliferations that can sometimes share overlapping microscopic features with melanoma. We used comparative genomic hybridization to analyze three groups of dermal melanocytic proliferations. Group 1 consisted of 10 cellular blue nevi and 1 deep penetrating nevus, none of which showed chromosomal aberrations. Group 2 consisted of 11 lesions that were histopathologically ambiguous. Three of these lesions demonstrated chromosomal aberrations (three or fewer per lesion). Group 3 consisted of seven histopathologically malignant lesions, each showing three or more chromosomal aberrations. Moderate to severe cytologic atypia and a mitotic rate of three or more mitoses per 10 high power fields were present in six of eight (75%) lesions that had at least three chromosomal aberrations but were absent in 15 of 20 (75%) lesions without chromosomal aberrations. Necrosis was present in four of the 29 (13%) lesions, with every lesion with necrosis demonstrating three or more genomic abnormalities. In conclusion, histopathologically unequivocally benign or malignant dermal melanocytic proliferations show nonoverlapping patterns of chromosomal aberrations. Ambiguous lesions can be separated into lesions with and without chromosomal aberrations. Future studies with clinical follow-up are necessary to determine which aberrations are most informative for classification of these lesions.     

Juvenile conjunctival nevus: clinicopathologic analysis of 33 cases

Conjunctival nevi in children and adolescents often have histologic features that can be difficult to differentiate from malignancy. We have identified a subset of childhood nevi displaying a confluent growth pattern and a lack of maturation that we have defined as juvenile conjunctival nevi (JCN), with the aim of further describing the clinicopathologic features of these lesions. Lesions identified as conjunctival nevus in a tertiary referral hospital were reviewed and the subset of lesions identified as JCN were further evaluated. Clinical details including follow-up data were also gathered. Of the 40 conjunctival nevi identified, 33 fit the criteria for JCN. The mean age at time of excision was 10.9 years (range: 4 to 19 y). Thirty-two lesions were of the compound type; one was a junctional nevus. All showed a nested junctional growth pattern. In 17 lesions (61%), the junctional component extended beyond the subepithelial component (shoulder phenomenon). Maturation was absent in 21 of the compound nevi (66%, average age 10.3 y), and incomplete in the remaining 11 lesions (34%, average age 12.1 y). The nuclei of the subepithelial nevus cells were larger than the epithelial nevus cells in 19 nevi (59%) and the same size in 13 (41%). A lymphocytic host response was present in 17 lesions (52%). Mitotic figures were rarely seen. None of the lesions had recurred over an average follow-up period of 34 months. Recognition of JCN as a distinct morphologic variant of a conjunctival nevus with characteristic histologic features may help to distinguish this benign lesion from melanoma.     

Amelanotic cellular blue nevus: a hypopigmented variant of the cellular blue nevus: clinicopathologic analysis of 20 cases

Blue nevus and its variants typically present as pigmented lesions. Dermal melanin is responsible for coloration and is an expected histologic finding. Herein, we report 20 cases of an unusual amelanotic variant of cellular blue nevus. Our series showed clinical demographics similar to pigmented counterparts. Thus, there was a predilection for young individuals with a mean age of 24 years (range 6-74 years). Both sexes were affected, with a female-to-male ratio of approximately 2:1. The lower back, distal extremities, and scalp were the most common sites of occurrence. Importantly, the lack of pigmentation resulted in an atypical clinical appearance. A diagnosis of blue nevus by the attending physician was not considered in any of the reported lesions. All of the tumors extended deep into the reticular dermis or subcutaneous fat with a mean thickness of 5.5 mm (range 1.7-11 mm). Ulceration was present in two lesions. Mild cytologic atypia and pleomorphism were present in five cases. Mitotic activity (up to 3 mitoses/mm ) was observed in 11 lesions. A brisk lymphocytic host response was present in only one lesion. Tumor necrosis was not observed. Most, but not all, tumors showed reactivity for S-100 and HMB-45. Clinical follow-up (mean 32 months) was consistent with a benign course. Local recurrence was not observed after complete excision. None of the cases was associated with clinical evidence of lymph node or distant metastases. Recognition of amelanotic cellular blue nevus is important because the lack of expected pigmentation may result in clinical and pathologic diagnostic difficulty. In particular, amelanotic cellular blue nevus must be distinguished from malignant cellular blue nevus and other variants of melanoma.     

Congenital Spitz Nevus

BACKGROUND: Congenital Spitz nevus has been reported previously in the literature, but the histopathologic features have not been examined in detail. OBJECTIVE: To histologically examine and report on congenital Spitz nevus. METHOD: We examined 10 clinically submitted congenital melanocytic nevi that were histopathologically identified as congenital Spitz nevi and compared them to the characteristics seen in acquired Spitz nevus and superficial congenital melanocytic nevus. RESULTS: Of the 10 congenital Spitz nevi, 9 were compound and 1 was dermal. Two showed features of combined Spitz nevus (Spitz and blue). Six cases showed all 16 listed characteristics of acquired Spitz nevus, with two cases having 15 and two cases having 14 characteristics. Of the superficial congenital melanocytic nevus characteristics, all except three cases had all 12 attributes. The one dermal lesion had all the characteristics of the acquired Spitz nevus and all but one of the characteristics of the superficial congenital melanocytic nevus in regards to intradermal findings. CONCLUSIONS: Congenital Spitz nevi are true congenital lesions, with histopathologic features of both acquired Spitz nevus and superficial congenital melanocytic nevus.     

Histologic classification of the combined nevus. Analysis of the variable expression of melanocytic nevi.

The designation combined nevus gives recognition to mixed cytologic patterns. In the common variant, plump, pigmented spindle cells form fascicles among nests of ordinary nevus cells. In other variants, one or several cellular components that share cytologic features with either a blue nevus or a Spitz nevus are represented. Ninety-five cases, 49% of which were of the common type, were studied. Grossly, most of the lesions were darkly pigmented papules or nodules. The clinical diagnosis in three-fourths of the cases was nevus, blue nevus, or melanoma. Fifteen percent had concomitant histologic features of melanocytic dysplasia, and most of these lesions were of the common type. For the common variant, the cytologic features, pattern of apparent infiltration, and variable representation of the features of a premalignant melanocytic dysplasia often mislead a pathologist in interpreting and predicting biologic potential. In combined nevi, the phenotypic diversity and genetic lability of melanocytic nevus cells is manifested.     

Persistent (recurrent) Spitz nevi: a histopathologic, immunohistochemical, and molecular pathologic study of 22 cases

This report describes 22 Spitz nevi that seemed to have been clinically removed but persisted and clinically recurred at the biopsy site. These were evaluated in terms of histopathology, immunohistochemistry, and molecular pathology using comparative genomic hybridization (CGH) and fluorescent in situ hybridization. One of these 22 lesions was originally reported as an atypical melanocytic proliferation with some features of a Spitz nevus and was included in the study set at an early stage but was later recognized as melanoma after metastasis to regional lymph nodes 3 years after the local recurrence. We noted four histopathologic patterns in the recurrent lesions: 1) a predominantly intraepidermal pattern resembling "pseudomelanoma" as seen in recurrent "common" melanocytic nevi, 2) a compound, mostly nested pattern above or within a scar that was nearly identical to the originally biopsied Spitz nevus, 3) a nodular growth pattern that closely simulated invasive melanoma, and 4) a desmoplastic pattern resembling an intradermal desmoplastic Spitz nevus. Although the majority of recurrent lesions exhibited asymmetry and pagetoid spread, the dermal component usually had a low mitotic rate and retained architectural and cytologic maturation, which allowed distinction from invasive melanoma. Except for the metastasizing melanoma, the immunostaining pattern with S-100 and HMB-45 was identical to that previously reported for Spitz nevi. Ki67 revealed a very low proliferation rate in all cases, including the melanoma. CGH performed in 10 cases yielded results consistent with Spitz nevi in eight cases. The remaining two cases showed CGH profiles more typical of melanoma, and one of these was the above-referenced case of melanoma, proven by metastasis. Although ancillary molecular techniques such as CGH are of great help in distinguishing these from melanoma, until such techniques become widely available we advocate complete but conservative excision of any recurrent Spitz nevus.     

Large plaque-type blue nevus with subcutaneous cellular nodules

Unusual or atypical melanocytic nevi can be confused with malignant melanoma. The authors present two cases of an unusual variant of blue nevus that were misdiagnosed initially as malignancy. Both lesions were asymptomatic and characterized clinically by childhood onset, with slow enlargement during adolescence and subsequent nodule formation. One lesion, which measured 24 cm in greatest dimension, was located on the anterior chest wall of a 53-year-old woman. The other lesion, which measured approximately 15 cm in greatest dimension, was located on the lateral abdominal wall of a 20-year-old man. Both lesions were characterized by a multifocal dermal and subcutaneous proliferation of fusiform and dendritic pigmented melanocytes. The histologic appearance of individual foci ranged from dermal melanocytosis to common blue nevus and cellular blue nevus. The cellular foci were located in the subcutis and involved, in one patient, the stroma of the breast. The cells were immunoreactive for S-100 protein, gp100 (HMB-45), and Melan-A (A103). Ultrastructural analysis revealed melanocytes typical of blue nevus. The woman underwent complete excision of the lesion, and the man underwent only partial excision of the lesion. On clinical follow-up of 32 and 19 months, respectively, both patients are alive and well with no evidence of recurrence or progression. Because the lesions presented clinically as large plaques and were diagnosed histologically as blue nevi with subcutaneous foci of cellular blue nevus, we term this rare variant of blue nevus large plaque-type blue nevus with subcutaneous cellular nodules. Recognition of this lesion enhances our knowledge of the morphologic spectrum of melanocytic tumors and helps to avoid confusion with malignant melanoma.     

Acquired Melanocytic Lesions and the Decision to Excise: Role of Color Variegation and Distribution as Assessed by Dermoscopy

BACKGROUND: Because melanoma may sometimes be difficult to differentiate from nevi with clinical atypia, many benign lesions also undergo surgical removal. OBJECTIVE: To assess color type and distribution in dermoscopic melanocytic lesion images and to analyze the influence of color parameters on the diagnostic process and the decision to excise. METHODS: Overall, 603 images, referring to 112 melanomas and 491 nevi, were retrospectively subdivided into four groups: "clearly benign," "follow-up," "dermoscopic atypical nevi," and "dermoscopic melanomas," according to their dermoscopic aspects. The frequency of color type, number, and asymmetry were evaluated on digital images. RESULTS: With respect to lesions not eligible for excision according to dermoscopy (but excised for cosmetic reasons), those excised with a suspicion of malignancy showed a higher number of colors, whose distribution was also more asymmetric. Moreover, the frequency of the presence of black and blue-gray progressively increased from clearly benign lesions to atypical nevi and dermoscopic melanomas. CONCLUSION: In dermoscopic images, color parameters are essential elements for the diagnosis of atypical nevus, which can be differentiated from both a clearly benign lesion and a melanoma. Furthermore, pigmentation asymmetry and the presence of blue-gray represent the main color features, which should lead to the decision to excise.     

色素痣样皮损381例的临床与组织病理分析

目的:探讨381例色素痣样皮损的临床与病理之间的关系。方法:对381例色素痣样的病例做临床及组织病理诊断回顾性分析。结果:381例色素痣样皮损中,病理诊断符合色素痣327例,符合率为93.7%,组织病理类型:皮内痣219例(67%),混合痣89例(27.2%),交界痣8例(2.4%)及其他11例(3.4%);327例色素痣中,先天性色痣140例(42.8%),组织病理类型:皮内痣74例(52.9%),混合痣55例(39.3%),交界痣7例(5%)及蓝痣4例(2.8%);临床误诊为色素痣54例,病理诊断居前5位为脂溢性角化病、血管角皮瘤、基底细胞癌、黑素瘤、鳞状细胞癌。结论:色素痣样皮损的正确诊断需要结合组织病理分析。     

The Surgical Management of Spitz Nevi

BACKGROUND: The biologic behavior of Spitz nevi and atypical Spitz nevi ranges from completely benign to the rare malignant melanoma. Various recommendations for the surgical approach to these lesions have been proposed. OBJECTIVE: To determine any trend in the surgical management of Spitz nevi and atypical Spitz nevi among a community of dermatologists. METHODS: Retrospective review of the clinical features, surgical management and outcome of 89 patients with the diagnosis of Spitz nevus or atypical Spitz nevus. RESULTS: All biopsy techniques had a high incidence of involved margins: shave (67%), excision (28%), and punch (21%). Of the atypical Spitz nevi with positive margins on biopsy, there was a trend (7/9) toward reexcision with narrow margins (average 2.2 mm). CONCLUSION: The majority of atypical Spitz nevi incompletely removed by biopsy were excised with narrow uncontrolled margins. A stratified surgical approach depending on the clinical and histopathologic features of the Spitz lesion is proposed. More aggressive surgical management of Spitz lesions with atypical features may be warranted. Further studies to determine the biologic potential of these lesions are needed.     

HMB-45 staining of dysplastic nevi. Support for a spectrum of progression toward melanoma

Dysplastic nevi are melanocytic tumors that occupy intermediate positions in the spectrum of melanocytic proliferations. Although they are invariably cured if completely excised, their biologic potential if left untreated is unknown. We examined a series of such lesions with HMB-45, a melanocyte-specific antibody, in order to explore protein expression within these borderline lesions. HMB-45 has previously been shown to label intraepidermal melanocytes within melanomas and within all nevi. Intradermal melanoma cells also label with HMB-45, but dermal nevus cells within common melanocytic nevi do not normally stain. In contrast, we found mild to moderate staining of nevus cells within the papillary dermis of dysplastic nevi and within residual nevus cells adjacent to malignant melanomas. In the same lesions, we demonstrated strong staining of intraepidermal melanocytes. Thus, dermal nevus cells within dysplastic nevi and within residual nevus cells adjacent to malignant melanomas are expressing low-level amounts of a protein expressed by melanoma cells, but not by dermal nevus cells within wholly benign melanocytic tumors. This lends support to the concept of these lesions as precursor lesions with undetermined biologic potential.     

Low-risk and high-risk histologic features in conjunctival primary acquired melanosis with atypia: Clinicopathologic analysis of 29 cases

The current World Health Organization classification of conjunctival melanocytic proliferations divides them into conjunctival nevi and invasive melanoma but, in contrast to other anatomic sites, does not recognize melanoma in situ. All atypical intraepithelial conjunctival proliferations are included in a heterogeneous category designated as primary acquired melanosis (PAM) with atypia. We performed clinicopathologic analysis of 29 cases of PAM with atypia. On the basis of histologic features and frequency of association with invasive melanoma and metastases, we were able to divide our cases into 2 histologic groups. The low-risk group (13 cases) included lesions composed of small to medium size melanocytes with high nuclear to cytoplasmic ratio and small to medium size hyperchromatic nuclei devoid of nucleoli showing predominantly single cell lentiginous growth pattern. Invasive melanoma occurred in only 2 cases from this group. None of these lesions metastasized. The second, high-risk group (16 cases), showed increased frequency of association with invasive melanoma (15/16 cases, 94%) and metastases (4/16 cases, 25%). These lesions were more heterogeneous architecturally but were all composed of melanocytes showing various degrees of epithelioid features such as abundant cytoplasm, vesicular nuclei, or prominent nucleoli. In 4 cases discrete areas showing high-risk and low-risk features were identified. All 4 lesions were associated with invasion. Our findings offer a practical approach for prognostically useful subclassification of PAM with atypia, which emphasizes cytologic features of intraepithelial conjunctival melanocytic proliferation.     

Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus

In the course of a study of borderline melanocytic tumors, we observed a distinctive group of lesions characterized by features very similar to those previously described in the literature as "animal-type melanoma" and epithelioid blue nevus of Carney complex. We have designated these lesions as pigmented epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis of 41 consecutive PEM from 40 patients and compare them with 11 epithelioid blue nevi from patients with Carney complex. PEM occurred in both sexes of different ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide distribution with extremities being the most common site. The tumors were formed by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily pigmented epithelioid and/or spindled melanocytes. Five lesions were part of combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in 1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph nodes contained metastases (46%). Liver metastases occurred in 1 case. None of the patients died of disease. Clinical follow-up of more than a year (mean 32 months, range up to 67 months) was available in 27 cases (67%). We found no histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration was the only feature more common in PEM than epithelioid blue nevi of Carney complex. Otherwise, they were histologically indistinguishable. Our data show that PEM is a unique low-grade variant of melanoma with frequent lymph node metastases but indolent clinical course. We suggest that PEM be considered as a provisional histologic entity encompassing both animal-type melanoma and epithelioid blue nevus.     

Deep penetrating nevus

We report a clinical and histologic study of 70 patients, each with a single melanocytic lesion termed "deep penetrating nevus" (DPN). The lesions are most commonly found on the face, upper trunk, or proximal extremities of patients between the ages of 10 and 30 years. Typically they are darkly pigmented. Histologically they are characterized by loosely organized nests of pleomorphic pigmented cells that penetrate deep into the reticular dermis and often to the subcutaneous fat. Follow-up was obtained from 48 patients. It ranged from 1 to 23 years (mean, 7 years). Despite an initial histologic diagnosis of malignant melanoma in 29% of the cases, there were no local recurrences and no distant metastases. It is important to differentiate DPN from malignant melanoma. The characteristic histologic features of DPN also allow its differentiation from spindle cell and epithelioid cell nevi and blue nevi.     

Melanocytic nevi with an atypical epithelioid cell component: clinical, histopathologic, and fluorescence in situ hybridization findings

Combined melanocytic nevi can contain a phenotypically distinct population of large atypical epithelioid cells in a background of smaller banal-appearing melanocytes. On the basis of the pattern of proliferation and degree of pigmentation, nevi with this pattern have been referred to as nevi with an atypical epithelioid cell component (N-AECC). When N-AECC display sheet-like or an expansile nodular growth pattern, notable cytologic atypia, and any level of mitotic activity, they can be difficult to distinguish from melanoma. The clinical history and appearance of these lesions may similarly raise concern for melanoma. In view of this diagnostic problem, we present 28 cases of N-AECC from our dermatopathology consultation and in-house practice. All 28 cases were found to be negative on the basis of fluorescence in situ hybridization (FISH) for imbalanced chromosomal aberrations commonly found in melanoma. The clinical outcomes showed a benign clinical course for all cases for which the outcome information was available. FISH analysis also revealed that, in 4 of 28 cases (14%), the AECC of the lesion demonstrated polyploidy localized to the large epithelioid cell component. This is likely more common among cases of N-AECC that have an atypical spitzoid epithelioid cell component, particularly those with obvious senescent nuclear changes. Care must be taken to avoid the pitfall of misinterpreting these FISH findings as changes consistent with melanoma. The use of ancillary testing methods including FISH may be beneficial in improving the diagnostic accuracy involved in making the distinction of N-AECC from melanoma. Further, we report a novel finding of polyploidy seen in certain cases of benign N-AECC.     

超脉冲CO2激光治疗色素痣后皮损复发的组织病理学分析

目的 从组织病理学角度分析面部色素痣经超脉冲CO2激光治疗后皮损复发的原因。方法 1999年12月至2002年10月,129例临床诊断为色素痣的患者接受了超脉冲CO2激光治疗,在以后随访的89例患者中有7例出现皮损复发.皮损复发的部位经外科手术切除后进行了组织病理学的检查。结果 表皮中痣细胞的再生（病例1、2、3、7）、真皮浅层痣细胞的残留（病例4、5、6）、真皮乳头层纤维增生（微观瘢痕）的厚度不够（病例4），真皮深部大量的痣细胞远未得到清除（病例2、3、4、5、7）以及炎症后噬色素细胞的形成（病例1、4、5、6、7）都是色素再次出现的原因。皮损复发的7例患者中未发现痣细胞恶变以及假性黑色素瘤的形成。结论 所有复发病例中,痣细胞都未被真正完全清除。因此通过激光治疗色素痣的方法用于美容应慎重选择。