Minimal Deviation Melanoma Research Articles

A Pediatric Case of Spitzoid Melanoma with Subsequent Large Lymph Node Metastasis.

Dear Editor: The lack of reliable pathological criteria for distinguishing between benign and malignant melanocytic lesions makes it very difficult for clinicians and pathologists to diagnosis melanoma. Here, we describe a rare case of a young patient affected by Spitzoid melanoma of the left leg with left superficial inguinal lymph node metastasis. A 13-year-old boy was referred to our hospital for a 19×9-mm cutaneous dome-shaped pigmented nodule on his left lower leg (Fig. 1A). The nodule appeared 3 months prior and was asymptomatic. No lymphadenopathy was found on physical examination. Under the suspicion of Spitz nevus, the tumor was excised with a 2-mm free margin. Histological analysis demonstrated that it was a symmetrical melanocytic tumor; it exhibited prominent pleomorphism and definitely showed changes of maturation (Fig. 1B~D). We detected hemorrhage crusts on the horny layer, but these were caused by the patient's scratching. There was no bleeding in his clinical course. Atypical epithelioid and spindle-shaped melanocytes with large hyperchromatic pleomorphic nuclei were observed. No ulceration was present. These findings were discordant with pigmented epithelioid melanocytoma1. His immunologic profile was consistent with a melanocytic tumor: S-100, Melan-A, and HMB-45 positivity, and CD34 negativity. The presence of diffuse HMB-45 positivity, even deeper in a nest, was considered unusual in a Spitz nevus. The extremely controversial nature of the lesion led to a diagnosis of atypical Spitz neoplasm of indeterminate biologic potential or Spitzoid-type minimal deviation melanoma. After receiving informed consent from the patient's parents, we performed careful observation, considering the possibility of malignant tumor. He had a huge palpable inguinal lymph node on physical examination 4 months postoperatively. Magnetic resonance imaging and positron emission tomography scans showed a large metastatic superficial inguinal lymph node (Fig. 2). Under a diagnosis of Spitzoid melanoma with subsequent lymph node metastasis, we performed wide local excision (2-cm margin including the periosteum) of the lower leg and resurfaced the defect with a local flap procedure. Left inguinal lymph nodes including the superficial and deep node groups were completely dissected. Three of the nine harvested lymph nodes including the large lymph node exhibited metastasis. Atypical melanocytes similar to those in the leg lesion were found within the lymph node parenchyma. The patient was treated with adjuvant dacarbazine, nimustine, and vincristine chemotherapy 5 times over 6 months. At a recent follow-up 2 years later, he did not have any evidence of recurrence or metastasis. The 5-year survival rate of children between 11 and 17 years old with metastatic Spitzoid melanoma is 49%2. Recent studies suggest the prognosis of children with Spitzoid melanoma is better than that in adults even local metastases or positive sentinel lymph nodes are present3,4,5. However, some cases of incomplete excision of Spitzoid melanoma leading to systemic metastasis and death have been reported5. Therefore, in cases in which the diagnosis is uncertain despite further evaluations, it is necessary perform careful observation to prevent recurrence and metastasis as early as possible. Fig. 1 (A) A 10-mm dome-shaped pigmented nodule on the left lower leg. (B) Histopathology of the skin lesion; Breslow's thickness clearly exceeded 4 mm. No ulceration was present (H&E, ×10). (C) Abundant irregular nests of varying size and shape, ... Fig. 2 Magnetic resonance imaging (left panel) and anterior projection images from the positron emission tomography-computed tomography scan (right panel). Note the extensive left inguinal lymph node uptake (arrows). This sentinel lymph node was larger than ...

Unusual variants of malignant melanoma

A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called ‘minimal-deviation melanoma,' melanoma with prominent pigment synthesis or ‘animal-type melanoma,' and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase melanomas; these include those tumors whose morphological peculiarities mimic cancers of nonmelanocytic lineage and those melanomas that express aberrant antigenic profiles not commonly associated with a melanocytic histogenesis. Metaplastic change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid melanoma, small cell melanoma and rhabdoid melanoma all have the potential to mimic metastatic and primary neoplasms of different lineage derivations. Abnormal immunohistochemical expression of CD 34, cytokeratins, epithelial membrane antigen, and smooth muscle markers as well as the deficient expression of S100 protein and melanocyte lineage-specific markers such as GP100 protein (ie HMB-45 antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In this review, we will discuss in some detail certain of these novel clinicopathologic types of melanoma, as well as the abnormal phenotypic expressions seen in vertical growth phase melanoma.

"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.

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

Our purpose in undertaking this Arbeit was to review all articles published about "atypical" Spitz's nevus, "malignant" Spitz's nevus, and "metastasizing" Spitz's nevus, to criticize them in a fashion that illuminates, and to come to conclusions compellingly about those subjects. We found that an overwhelming majority of neoplasms that claimed to be "atypical Spitz's nevus," "metastasizing Spitz's nevus," and "malignant Spitz's nevus" were, in fact, melanomas ( Table 1). Moreover, in our estimation, those designations, and variants of them, like "atypical Spitz's lesion," "atypical dermal melanocytic lesion with features of Spitz's nevus," "atypical Spitzoid melanocytic neoplasm," and "problematic Spitzoid melanocytic lesion," are mere evasions from a diagnosis, straightforwardly, of either Spitz's nevus or melanoma. Diagnoses in pathology equally bogus are "minimal deviation melanoma," "borderline melanoma," "nevoid melanoma," "potentially low-grade melanocytic neoplasm," and "melanocytic lesion of uncertain biologic potential." Rather than admit uncertainty forthrightly, those who employ circumlocutions like those just mentioned resort to linguistic maneuvers that, at first blush, seem to be "academic" and constructed in such a way as to appear to convey confidence, rather than tentativeness, on the part of a histopathologist. On further scrutiny, however, each of those cliches is revealed to be devoid of content. For example, "malignant" Spitz's nevus and "metastasizing" Spitz's nevus not only are contradictions in terms, but they are outrageous violations of fundamental principles of classic Virchowian pathology, and "atypical" Spitz's nevus not only is a redundancy because the neoplasm was so atypical to Spitz, herself, she insisted (from the time she spawned the idea in 194 through 1951 it was a "malignant melanoma," but is abject intellectually, those who invoke it never setting forth, in clear-cut fashion, criteria for what constitutes a "typical" Spitz's nevus in contradistinction to an "atypical" one.

Ki-67 and p53 Expression in Minimal Deviation Melanomas as Compared with Other Nevomelanocytic Lesions

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional “primary configuration” melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P < .05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P = .08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P < .01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity.

Dermabrasion of large congenital melanocytic naevi in neonates.

We describe our findings in a series of 12 patients with large congenital melanocytic naevi treated with dermabrasion between the first and fourteenth week of life. Postoperative follow-up ranged from 1-16 years. In all but two cases dermabrasion resulted in an appreciable and stable reduction of the hyperpigmentation, possibly by reducing the number of pigmented cells in the epidermis. In six of our 12 patients, reconstruction using grafts and flaps was done to improve the aesthetic result. Seven years after dermabrasion, one patient developed a minimal deviation melanoma in the treated area, but his subsequent clinical course has been uneventful.

Dimensionalities: Borderline and intermediate melanocytic neoplasia

The concept of minimal deviation melanoma is presented in diagrammatic form. In this approach, the precursors of melanoma are presented as having two dimensions and melanomas as having three dimensions. In turn, the relativity between dimensionalities and recommendations for treatment (as indirect correlates of prognostications) provides guidelines for the structuring of two major boundaries along the axis of the diagram. Finally, the domains defined by the two boundaries include borderline lesions, intermediate lesions, and “real melanomas.” The lesions in the borderline and intermediate categories qualify as melanocytic neoplasias of indeterminant malignant potential; in these two categories, the predictability of metastases hardly justifies the use of the designation, malignant melanoma.

Variants of melanoma.

The current classification of malignant melanomas gives recognition to superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma, and nodular types. In addition, neurotropic and desmoplastic types are recognized. The relativity inherent in the diagnosis of melanoma, provides the basis for the classification of melanomas on the basis of size. Lesions measuring 1 mm or less in vertical dimensions are unlikely to metastasize; they qualify as borderline melanocytic neoplasia of indeterminant malignant potential. The current classification has little relevancy to the category of variant nevi with the exceptions of malignant cellular blue nevus and melanoma arising in giant congenital nevi. A classification of variant melanomas as related to variant nevi is proposed. From a different perspective, a classification of melanomas with attention to nesting and cytological patterns in vertical growth is proposed: this alternate approach gives recognition to lesions that might otherwise be classified as "nevoid" melanomas. It also provides a default category for lesions that might otherwise be assigned to the Spitz nevus-like category. All of these tools for the manipulation of the real and virtual images of melanomas have been emphasized in the concept of minimal deviation melanoma.

Malignant change in giant congenital nevocellular nevi: our experience

We present our experience in the surgical management of giant congenital nevocellular nevi (GCNN's). From 1983 to 1992, 13 cases were treated of which 11 were children and 2 were adults. The size of the lesions ranged between 3 and 60% of the body surface. All these patients underwent excision and skin grafting. In 6 cases, skin expansion was used. The patients were seen subsequently every 6 months with a 12 months minimum follow-up. In 2 pediatric patients, malignant degeneration of the lesion occurred: in the first case, a highly invasive nodular melanoma, in the second case, a lesion corresponding to minimal deviation melanoma. Our personal experience has shifted our attitude to the treatment of GCNN to a more aggressive approach. Early and radical excision of all the lesion is currently our first priority; esthetic refinements by means of skin expansion or other techniques are now delayed to subsequent procedures.

Giant congenital nevi: a conceptualization of patterns.

Patterns in giant congenital nevi are classified as to extent of cellular involvement of the reticular dermis and by the quality of the fibrous matrix. In addition, classifications are influenced by degrees of cellular atypia. Two general categories are defined. In one, the phenomena are relatively independent of those operative at the dermal-epidermal interface. The lesions are characterized as dermal congenital tumorous dysplasias-blastomas. They are subdivided into major, intermediate, and minor categories and into mature and immature variants. In these variants, disparate populations in the patterns of nodules and plaques (lumpy-bumpy variants) qualify as dermal variants of minimal deviation melanoma as seen in the setting of giant congenital nevi. The respective melanomas in this category are small-cell malignant neoplasms (melanoblastomas of infancy and childhood). In a second category in the clinical setting of giant congenital nevus, rare childhood and some adult melanomas of a more common histologic type evolve from lentiginous and junctional components in patterns that recapitulate those of the dysplastic nevus syndrome. The suspicious areas in all categories are evaluated by the same clinical criteria. In the dysplasia-blastoma category, enlarging nodules must be biopsied. The criteria for the evaluation of lesions in the dysplastic nevus syndrome and in the category of minimal deviation melanoma have application to the unstable regions in giant congenital nevi.

Giant Congenital Nevi: A Conceptualization of Patterns

Patterns in giant congenital nevi are classified as to extent of cellular involvement of the reticular dermis and by the quality of the fibrous matrix. In addition, classifications are influenced by degrees of cellular atypia. Two general categories are defined. In one, the phenomena are relatively independent of those operative at the dermal-epidermal interface. The lesions are characterized as dermal congenital tumorous dysplasias-blastomas. They are subdivided into major, intermediate, and minor categories and into mature and immature variants. In these variants, disparate populations in the patterns of nodules and plaques (lumpy-bumpy variants) qualify as dermal variants of minimal deviation melanoma as seen in the setting of giant congenital nevi. The respective melanomas in this category are small-cell malignant neoplasms (melanoblastomas of infancy and childhood). In a second category in the clinical setting of giant congenital nevus, rare childhood and some adult melanomas of a more common histologic type evolve from lentiginous and junctional components in patterns that recapitulate those of the dysplastic nevus syndrome. The suspicious areas in all categories are evaluated by the same clinical criteria. In the dysplasia-blastoma category, enlarging nodules must be biopsied. The criteria for the evaluation of lesions in the dysplastic nevus syndrome and in the category of minimal deviation melanoma have application to the unstable regions in giant congenital nevi.

Clinical and pathologic diagnosis, staging and prognostic factors of melanoma and management of primary disease.

To increase detection of melanoma, medical practitioners and the general public should know the signs of early invasive melanoma. The Scottish Melanoma Group recently presented a revised checklist of the major and minor signs. The validity of the reported clinical and histopathologic criteria for the dysplastic nevus, a precursor to cutaneous melanoma, is not fully established. However, expert pathologists agreed on the use of major and minor criteria. The differential diagnosis between spindle-epitheloid cell nevi and melanoma remains problematic, because the former lesions often show cellular atypia. Other lesions that can cause considerable diagnostic difficulties are melanoma in situ and minimal-deviation melanoma. Immunohistochemical studies of human melanocytic lesions have contributed to the diagnosis of poorly differentiated tumors but, so far, have not helped in the discrimination among benign, premalignant, and malignant lesions. They have provided additional prognostic information in cases of primary melanoma and locoregional melanoma metastasis. Quality control of antibody reagents continues to be a problem. Microstaging of primary melanoma using Breslow depth and Clark's level of invasion may be subject to considerable intra- and interobserver variation. To improve the accuracy of the measurements, using a vernier scale is recommended. The type of melanoma is relevant in considering clinicopathologic prognostic factors. Acral melanoma (for example, that arise from glabrous skin) has been reported to carry a grave prognosis. Polypoid melanoma may have a less unfavorable outlook than previously thought. DNA cytophotometry provides prognostic information in case of primary melanoma but loses significance when stratified for tumor thickness. In patients with lymph node-positive melanoma, however, DNA ploidy analysis appears to yield additional prognostic information. In the management of primary disease, the width of the surgical excision and whether to approach the regional lymph nodes remain the main issues. A multicenter study conducted by the World Health Organization Melanoma Programme has found that a "narrow" excision is a safe procedure for primary melanomas not thicker than 1 mm. Several investigators underline the need for continued annual follow-up for all melanoma patients; recurrence may occur late. Currently, elective lymph node dissection is not recommended in the management of "thick" primary melanoma. Because data from randomized trials conducted in patients with a tumor of intermediate thickness are not yet available, only guidelines on management offered by experienced surgeons can be given. Patients with the dysplastic nevus syndrome should be closely followed so that melanomas can be diagnosed as early as possible.

Re‐evaluating silver‐stained nucleolar organizer regions (AgNORs) in problematic cutaneous melanocytic lesions: A study with quantitation and pattern analysis

Previous studies enumerating AgNORs in cutaneous melanocytic lesions have produced inconsistent results. It is probable that such inconsistencies arise from differences in fixation, staining technique, and counting strategies. Our group, having demonstrated an improved method of silver staining and having optimized counting, is now able to reconsider the role of AgNORs in evaluating borderline melanocytic lesions. Diagnostic problems similar to those encountered in routine practice have been examined. It is shown that only by counting intra- and extranucleolar AgNORs in combination with assessing the pattern of AgNOR dispersal is it possible to (1) discriminate dysplastic naevi from melanoma and (2) distinguish Spitz naevi and pigmented spindle cell naevi from melanoma. An analysis of AgNOR numbers alone results in considerable overlap between the groups studied. The value of assessing patterns of AgNOR dispersal within and outside clustered nucleolar structures is emphasized. Lesions labelled as minimal deviation melanoma (by experts in dermatopathology) were also investigated. The majority of these specimens form a distinct group lying apart from control naevi and melanomas. This finding, whilst of interest, is difficult to evaluate because of poorly defined diagnostic criteria.

Minimal Deviation Melanoma (Halo Nevus Variant)

Twenty-eight cases of minimal deviation melanoma (MDM) in the histologic setting of halo nevus formed the basis for this study. Requisites for this study included at least one of the following: a remnant of a halo nevus in a MDM; remnants of both MDM and halo nevus in a common melanoma; and a MDM of Spitz or dermal type, or MDM arising in premalignant dysplasia in which the vertical growth components manifested distinctive cytologic features and cytophilia for lymphocytes. Many of the lesions apparently represented neoplastic progressions involving a population of cells at the dermal-epidermal interface (accretive growth). Some of the lesions qualified as dermal variants and apparently represented neoplastic progressions in a dermal component (interstitial growth). Most examples of MDM in this study were borderline in size (less than 1.00 mm in vertical dimensions). The borderline MDM were interpreted as brief (and in some cases perhaps ephemeral) neoplastic interludes. For the 12 cases with follow-up, there have been no metastases or local recurrences.

The spectrum of minimal deviation melanoma: A clinicopathologic study of 21 cases

A retrospective study of 21 patients with the histopathologic diagnosis of minimal deviation melanoma (MDM; n = 18) and borderline melanoma (BM; n = 3) was undertaken to determine the prognosis for these patients compared with that for patients with other types of malignant melanoma. The findings indicate that the prognosis for these uncommon nevomelanocytic tumors is somewhat better than that for other malignant melanomas. Follow-up periods in this series ranged from 18 to 96 months (mean, 57 months). Primary lesions ranged in thickness from 1.6 to 10.4 mm. The histopathologic subtypes included the Spitz variant (nine patients), the spindle cell variant (six patients), the combined spindle and epithelioid cell type (three patients), and the small epithelioid cell type (three patients). Only two of the patients died of widespread metastatic disease. Comparison of the histologic and clinical prognostic indicators of mortality in patients who have malignant melanoma with the clinical and pathologic features seen in this series of 21 patients would appear to indicate a diminished tendency toward metastatic or recurrent disease in patients with MDM and BM.

Pathology of Melanoma

The biologic behavior of several common clinicopathologic types of melanoma is generally predictable by the depth of tumor invasion. However, some individuals have tumors that do no behave as predicted. These include what some authors have called borderline melanoma and minimal deviation melanoma as well as desmoplastic melanoma, thin superficial spreading melanoma with marked regression, and melanomas arising within some nevi. The reasons for the erratic behavior of these melanomas remains enigmatic.

Melanoma and other melanocytic skin lesions.

The literature on malignant melanoma and other melanocytic skin lesions has expanded greatly in recent years making it difficult for the average clinician and pathologist to keep abreast of the recent trends. The introduction of new statistical techniques such as multiple regression analyses and the Cox proportional hazards model has provided new insights into the important prognostic variables in melanoma. Furthermore, several new concepts such as the dysplastic naevus syndrome and minimal deviation melanoma have emerged in recent years which have profound significance on the interpretation of some melanocytic lesions. It therefore seems timely to review this subject, with an emphasis on those aspects which have been published in recent years, or which are neglected in standard textbooks of dermatopathology.KeywordsThin MelanomaIntradermal NaevusSuperficial Spreading MelanomaDesmoplastic MelanomaAcral Lentiginous MelanomaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Minimal Deviation Melanoma: A Histologic Variant of Cutaneous Malignant Melanoma in Its Vertical Growth Phase.

Minimal Deviation Melanoma: A Histologic Variant of Cutaneous Malignant Melanoma in Its Vertical Growth Phase.

Neoplasms arising in congenital giant nevi

Congenital giant nevi are complex cutaneous malformations composed of melanocytic and occasionally neural supportive elements. Malignant neoplasms arising in this setting are not uncommon, and their histologic appearances often differ significantly from the typical pattern of malignant melanoma. We report six patients with neoplasms arising in congenital giant nevi and one patient with a neoplasm arising in an extensive congenital blue nevus, and present a description of the neoplastic patterns encountered. These patterns include 1) poorly differentiated small round cell cancer, 2) malignant cellular blue nevus, 3) spindle-cell malignant tumor with lamellar cell (pseudomeissnerian) differentiation, 4) so-called minimal deviation melanoma, 5) heterologous malignant mesenchymal differentiation including rhabdomyosarcoma and liposarcoma, and 6) undifferentiated spindle cell cancer. We have reviewed the literature in order to address the question of frequency of malignant transformation in congenital giant nevi, the reported experience with the morphology of these cancers, and the histogenesis of these sometimes complex neoplasms as it is illuminated by our current understanding of the embryology of the neural crest.

Metastatic Minimal-Deviation Melanoma

A case of metastatic minimal-deviation melanoma that appeared twelve months after radical surgery is presented. It is suggested that newly described varieties of melanoma be treated as standard varieties (on the basis of depth of invasion) until statistically significant numbers of such lesions are reported.