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"Atypical" blue nevus, "malignant" blue nevus, and "metastasizing" blue nevus: a critique in historical perspective of three concepts flawed fatally.

The same errors that spawned, sustained, and continue to spur the notions of "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus are animating of 3 other concepts flawed equally, namely, those of "atypical blue nevus," "malignant blue nevus," and "metastasizing blue nevus." Our intention here is to compel to the conclusion, by way of critique in historical perspective, that all neoplasms claimed to be "malignant blue nevus" and "metastasizing blue nevus;" in fact, are melanomas, that all "atypical blue nevi" are either a nevus or a melanoma, and that the trio of curious designations that serve as title of this work are mere evasions transparently from a diagnosis, straightforwardly, of 1 of only 3 possibilities, to wit, "blue nevus," melanoma, or melanoma in association with a "blue nevus." Rather than admit uncertainty forthrightly, those who employ circumlocutions that we deplore, such as those under scrutiny here, resort to linguistic maneuvers that, at first blush, seem to have the cachet of scholarship (the jargon used being in keeping with a slew of other well-accepted, but equally bogus diagnoses in [dermato]pathology, among those being "minimal deviation melanoma," "borderline melanoma," "nevoid melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic proliferation of uncertain biologic potential"). All those terms and phrases are constructed in a manner designed to make them appear to convey unbridled confidence on the part of a histopathologist, rather than what they are in actuality, that is, a cover abjectly for tentativeness. Scrutiny of the lingo, in very abbreviated form, just catalogued reveals it to be devoid of content utterly. For example, "malignant blue nevus" and "metastasizing blue nevus" not only are contradictions in terms, but they are outrageous violations of principles fundamental to classic Virchowian pathology. We seek here to debunk that claptrap in the same manner we did "atypical Spitz's nevus," "malignant Spitz's nevus," and "metastasizing Spitz's nevus." It is our hope that readers will consider our arguments worthy because they are logical, will find them convincing because they are irrefutable, and will incorporate the lessons communicated through them so that their own professional life, pathology as a discipline, and, ultimately, patients, are the beneficiaries.

Adult↗

Hypopigmented common blue nevus.

Blue nevus is a benign pigmented lesion of dermal melanocytes with a number of histologic and clinical variants, of which the major types are the common blue nevus, cellular blue nevus and combined nevus. This study describes 9 cases of hypopigmented blue nevus (HBN), a variant of common blue nevus in which there is minimal identifiable melanin pigment. We also discuss the usefulness of the immunoperoxidase stain HMB-45 in relation to the diagnosis of HBN and the lesions with which it may be histologically confused, namely common intradermal nevus, dermatofibroma, neurofibroma, dermal scar and desmoplastic malignant melanoma. The HMB-45 stain was found to be uniformly positive in all 9 cases of HBN, in contrast to the other dermal lesions which have been reported as either negative or showing only focal positivity. The physical distribution and age range of the patients in this study was similar to the age and sites for common BN, supporting the relationship between the 2 lesions. The occurrence of HBN in predominantly young adults indicates that this lesion is not a phenomenon due to ageing or degenerative change, and should be regarded as a variant of common blue nevus.

Adolescent↗

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.

Adolescent↗

Melanoma associated with blue nevus and melanoma mimicking cellular blue nevus: a clinicopathologic study of 10 cases on the spectrum of so-called 'malignant blue nevus'.

The term "malignant blue nevus" refers to a rare and heterogeneous group of melanomas that arise in several clinical settings. This includes melanomas arising in association with a common or cellular blue nevus and those arising de novo and resembling cellular blue nevi. We reviewed the clinicopathologic features of 10 cases of malignant blue nevi. Six cases proved to be de novo melanoma mimicking cellular blue nevus, but lacking a clear-cut benign component. Two melanomas arose in association with a common blue nevus, and two with a cellular blue nevus. The patients' (5 males, 5 females) ages ranged from 11 to 77 years (average age, 48.1 years). The head and neck was the most common location (6 of 10 patients), with five scalp tumors. Four tumors were located on the trunk; none was located on the extremities. Tumor size ranged from 0.5 to 2.2 cm (average size, 1.1cm). Most lesions had been present for many years before surgical removal. Pigmented dendritic cells were observed in 9 of 10 cases. The malignant and benign components were easily distinguished in the four cases that arose in association with a common or cellular blue nevus. Abrupt transition between a benign blue nevus and melanoma was readily recognized at scanning magnification as distinctive nodules of epithelioid to spindled cells with a sheet-like growth pattern. In all cases, malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, hyperchromasia, and prominent nucleoli. All 7 patients with follow-up information experienced recurrence (3 patients) or metastasis (4 patients). Three patients died of disease. Malignant blue nevus is a heterogeneous group of melanomas that are highly aggressive and often lethal, with a propensity for metastasis to the lymph nodes and lungs.

Adolescent↗

Plaque-type blue nevus.

Blue nevus may rarely appear in plaque form. It seems to be a benign and asymptomatic lesion, but because of its rarity, no definite prognosis can be given. Only through reporting of additional cases and their follow-up will the prognosis become clear.

Adolescent↗

[Combined nevus: malignant blue nevus and giant pigmented nevus (author's transl)].

A combined nevus occurring on the right temporal region of a 30-year-old man with multiple giant pigmented nevi on the head, trunk and extremities was surgically removed. Histologically, the cellular blue nevus found in the deep corium fulfilled the criteria of malignancy in so far as mitoses and foci of tumor necroses were present.

Adult↗

Epithelioid blue nevus: a rare variant of blue nevus not always associated with the Carney complex.

Epithelioid blue nevus is a rare variant of blue nevus that has been recently described in patients with Carney complex. Some of the patients with Carney complex have multiple epithelioid blue nevi and a familial history of similar lesions is often recorded. Epithelioid blue nevus consists of an intradermal melanocytic nevus composed of polygonal epithelioid cells laden with melanin. Neoplastic cells show no maturation at the base of the lesion and, in contrast with the usual stromal changes in blue nevi, epithelioid blue nevus exhibits no fibrosis of the dermis. We have studied three cases of epithelioid blue nevus in three patients with no evidence of Carney complex. The lesions were solitary and there was no family history of similar lesions. Therefore, epithelioid blue nevus is a distinctive variant of blue nevus that may also appear as a sporadic lesion and is not always associated with Carney complex.

Adult↗

Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases.

We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence.

Adolescent↗

Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases.

Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN. Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically, they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl-2, and a proliferative index of 23+/-19 and 39+/-30 cells/10 high power field with antibodies to PCNA and Mib-1, respectively. No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib-1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA aneuploidy in both groups. Follow-up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow-up 42/32 months, range 15-96 months). No patient during this follow-up time has experienced either a local recurrence or lymph node or visceral metastasis. These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long-term follow-up.

Adolescent↗

"Compound blue nevus": a reappraisal of "superficial blue nevus with prominent intraepidermal dendritic melanocytes" with emphasis on dermoscopic and histopathologic features.

We describe 5 cases of "compound blue nevus" (CBN) ("superficial blue nevus with prominent intraepidermal dendritic melanocytes," "Kamino nevus"). Dermoscopically in 2 of 4 cases the bluish pigmentation characteristic of blue nevi was centrally replaced by a black lamella, with black dots and brown globules also observed in one case, thus revealing a structural asymmetry suggestive of melanoma. Histopathologically, pigmented parakeratosis was the underlying histopathologic finding of black lamella and dots/globules. Immunohistochemistry highlighted the unique histopathologic feature of CBN, namely, single dendritic melanocytes at the dermoepidermal junction with striking intraepidermal prolongations. Our findings confirm that CBN is a distinctive variant of blue nevus that may mimic cutaneous melanoma both clinically and dermoscopically.

Adolescent↗

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.

Adolescent↗

Malignant melanoma arising from unusual conjunctival blue nevus.

Cellular blue nevus is an uncommon pigmented tumor in the conjunctiva, where it generally appears as a deep, circumscribed, pigmented conjunctival mass. We report a case of conjunctival blue nevus that clinically resembled primary acquired melanosis and gave rise to conjunctival melanoma. A 41-year-old man developed a diffuse pigmented mass in the inferior fornix of his left eye. Over a 20-year period, he noted slight progression of the pigment. Foci of epibulbar pigmentation were also present. The lesion resembled primary acquired melanosis. Excisional biopsy and adjuvant cryotherapy were performed. Histopathologic examination disclosed an intense infiltrate of heavily pigmented dendritic melanocytes with aggregates of less pigmented plump cells in the substantia propria. The conjunctival epithelium was normal. Malignant cellular features consistent with melanoma were observed in some foci. Cellular blue nevus of the conjunctiva can simulate primary acquired melanosis and can give rise to malignant melanoma. Arch Ophthalmol. 2000;118:1581-1584

Adult↗