Melanoma arising from the mucosal surfaces of the head and neck

Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.     

Recognizing neoplastic skin lesions: a photo guide

Malignant lesions of the skin are common. Patients who develop squamous cell carcinoma and malignant melanoma often have recognizable precursor conditions. A few skin lesions resemble malignancies. Lesions that are growing, spreading or pigmented, or those that occur on exposed areas of skin are of particular concern. Knowing the similarities and differences between these lesions allows the primary physician to make a diagnosis in most cases by simple inspection and palpation. When in doubt, it is appropriate to perform an excisional biopsy of small lesions or punch biopsy of larger lesions. Removal of premalignant lesions will reduce the occurrence of malignant disease. Almost all skin cancers can be cured by early excision or destruction. For these reasons, physicians should be aware of the risk factors for skin cancer, educate patients about risk reduction and include skin inspection for premalignant and malignant lesions as a part of routine health maintenance examinations.     

Malignant melanoma

The incidence of malignant melanoma is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious pigmented lesion may first present to their primary care physician for evaluation. Therefore it is mandatory that the primary care physician be capable of distinguishing between benign and malignant pigmented lesions, know how to evaluate such patients, and know when to refer patients with suspicious or malignant pigmented lesions. Surgical removal remains the mainstay of treatment for patients with melanoma. Thus, to increase the cure rate for melanoma, both the public and nondermatologists need to be educated regarding the prevention and early detection of melanoma. Only in this way can the diagnosis of melanoma be made early before deep invasion has occurred and the patient placed at risk for systemic spread. In recent years, the surgical management of melanoma has become more conservative and rational. Limb amputation, arbitrary 5-cm margins of excision, and elective lymph node dissections are no longer performed. The recommended margins of excision are now based on objective pathologic and clinical data and are more conservative, and the sentinel node biopsy is now used to determine which high-risk patients should undergo a formal lymph node dissection. Although encouraging results are being seen with immunotherapy protocols, to date the only adjunctive therapy shown to increase survival in patients at high risk for systemic spread is alpha-interferon. With this drug, the improved survival is modest at best; it is expensive and a minority of patients can tolerate it in the doses recommended. Although response rates of 20% are seen with chemotherapy in patients with disseminated disease, these responses are short-lived, and there is no associated increased survival. Except for lentigo maligna, radiation therapy, even when its delivery is modified, still is useful only as an adjunct to surgery or for palliation.     

Subungual pigmented nevus: evaluation of DNA ploidy in six cases

The discrimination between subungual pigmented nevus and subungual melanoma in situ is still a clinical problem. We measured DNA ploidy in six cases of subungual melanotic lesions which exhibited the features of subungual pigmented nevus or lentigo simplex histologically. Five cases presented a diploid pattern with or without a slight increase of hyperdiploid cells. One case presented a polyploid pattern; it also exhibited histologically abnormal melanocytes with large nuclei and pigment-filled elongated dendrites. The DNA ploidy pattern and histologic features suggest that the lesion of this latter case contains abnormal melanocytes which probably have the potential to undergo a malignant transformation into a subungual melanoma. DNA ploidy analysis, therefore, is likely to provide information for evaluating the biologic behavior of subungual melanotic lesions.     

Retained intraocular foreign body simulating choroidal melanoma. A report of two cases

Many different lesions can be difficult to distinguish from malignant melanomas of the choroid. With the use of modern diagnostic facilities the misdiagnosis rate has been greatly reduced. In a recent report from the Collaborative Ocular Melanoma Study Group the incidence of misdiagnosis was only 0.48%. The presence of a retained intraocular foreign body presenting as a raised pigmented choroidal mass similar to a uveal melanoma is rare. We report two cases in which retained intraocular foreign bodies presented clinically as raised pigmented intraocular lesions. Retained intraocular foreign bodies should be considered in the differential diagnosis of ocular tumours, especially if there are any atypical features.     

Intravitreal invasion of malignant cells from choroidal melanoma after brachytherapy

We report intravitreal invasion by melanoma cells from a choroidal melanoma after brachytherapy. A malignant melanoma of the choroid with collar-button configuration was treated with iodine 125 brachytherapy. Years later, the collar button developed a dark-chocolate color and began shedding pigmented debris into the vitreous. Coalescence of this debris into spheroidal aggregates suggested the presence of malignant cells; the eye was enucleated. Histologic sections demonstrated a choroidal melanoma with intraretinal and intravitreal invasion by melanoma. Clinical evidence of intraretinal invasion by melanoma cells along with pigmented debris within the vitreous cavity, especially when clustered in spheroidal aggregates, suggests the presence of intravitreal invasion by malignant cells. In this case, intravitreal invasion was verified histologically.     

Atypical melanosis of the foot

We present a case of a seemingly malignant pigmented lesion on the foot, arising in a Japanese female. Clinically, the lesion was characterized by irregular borders and variegated pigmentation closely mimicking those of acral lentiginous melanoma in situ. However, the histologic findings revealed only focal, slight, melanocytic hyperplasia with minimal cytologic atypia along the basal layer. Despite the malignant clinical features, thorough histologic examination failed to disclose any area with significant melanocytic atypia or evidence of malignancy. To the best of our knowledge, no similar lesions with the clinical appearance of melanoma in situ and completely lacking histologic evidence of malignancy have been reported. We, therefore, prefer to designate this lesion as atypical melanosis of the foot, to highlight the clinically atypical findings and to distinguish this from malignant melanoma in situ of the foot (1).     

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.     

Pigmented spindle cell nevus: a clinicopathologic analysis of ninety-five cases

BACKGROUND: Pigmented spindle cell nevus (PSCN) is often interpreted as a Spitz nevus or misdiagnosed as malignant melanoma. OBJECTIVE: The purpose of this study was to analyze the clinical and histologic features and to determine the biologic behavior of 95 cases of PSCN. METHODS: We reviewed clinical data, follow-up information, and microscopic features of all 95 cases of PSCN. RESULTS: PSCNs are dark brown to black, 3 to 6 mm in diameter, and occur most commonly on the extremities (75%) and back (16%) with a predilection for the legs. These lesions are more common in women in the third decade of life. Microscopically, PSCNs are characterized by uniform, spindle-shaped, pigmented melanocytes. Although some histologic features overlap with those in spindle and epithelioid cell nevus, PSCN is a separate entity. In addition, PSCN must be differentiated from malignant melanoma. Fifty-seven patients (60%) observed for an average of 6 years did not develop local recurrence or metastasis. CONCLUSION: PSCN is a distinctive, acquired, benign melanocytic lesion, that should not be confused with spindle and epithelioid cell nevus or malignant melanoma. Complete excision is recommended for treatment.     

The recovery of visual performance in strabismus with eccentric fixation

Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.     

Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions

PURPOSE: To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS: A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS: The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION: Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.     

Pluripotential melanoblastoma, a unifying concept on malignancies arising in congenital melanocytic nevi: report of two cases

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.     

Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study

BACKGROUND: Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. METHODS: We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250). RESULTS: From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). CONCLUSIONS: About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.     

Production of macrocyclic ellagitannin oligomers by Oenothera laciniata callus cultures

Melanocyte-stimulating hormone (MSH) has been reported to enhance the experimental metastatic behaviour of melanoma cells in the mouse model. alpha-MSH production and MSH receptor (melanocortin 1 receptor gene) expression have been detected in cultured normal human melanocytes and metastasized melanomas. The exact role of MSH in the metastatic behaviour of human melanoma cells is, however, not yet known. To clarify a possible role of proopiomelanocortin (POMC)-derived peptides, including alpha-MSH, in melanoma development and progression, we analysed immunohistochemically the localization of alpha-MSH adrenocorticotrophic hormone (ACTH) and beta-endorphin in various kinds of benign pigmented naevocytic lesions and malignant melanomas. Three of 21 samples of common and dysplastic naevi showed detectable alpha-MSH staining in naevus cells, and five and six of 15 samples were weakly positive for ACTH and beta-endorphin staining, respectively. In melanoma samples, 24 of 45, 23 of 39 and 30 of 42 samples showed positive staining with alpha-MSH, ACTH and beta-endorphin antibodies, respectively. Furthermore, staining for all three antibodies was noted to be more intense and diffuse in samples of nodular melanoma, vertically growing acral lentiginous melanoma and superficial spreading melanoma as well as metastatic lesions compared with those of naevi. Although it is yet to be determined whether or not this strong staining for POMC-derived peptides in advanced melanoma cells indicates a role of autocrine or paracrine regulation, our results suggest a possible involvement of POMC gene products in melanoma progression.     

Dynamics of cell-associated viremia and antibody response during the early phase of lentivirus infection in sheep

OBJECTIVE: To investigate the characteristic epiluminescent microscopic features of early lesions of malignant melanoma affecting glabrous skin, which is the most prevalent site of the neoplasm in nonwhite populations. DESIGN: The epiluminescent microscopic features of various kinds of melanocytic lesions affecting glabrous skin were investigated using a videomicroscope. All the diagnoses were determined clinically and histopathologically using the standard criteria. SETTING: A dermatology clinic at a university hospital. PATIENTS: The following 130 melanocytic lesions consecutively diagnosed at our department were examined: 16 lesions of acral lentiginous melanoma, 6 lesions of malignant melanoma in situ, and 108 lesions of benign melanocytic nevus (acquired or congenital). MAIN OUTCOME MEASURE: The incidence of each characteristic epiluminescent feature was compared among disease categories. RESULTS: On epiluminescent microscopy, malignant melanoma in situ and the macular portions of invasive malignant melanoma showed accentuated pigmentation on the ridges of the skin markings, which are arranged in parallel patterns on glabrous skin. This "parallel ridge pattern" was found in 5 (83%) of 6 lesions of malignant melanoma in situ and in 15 (94%) of 16 lesions of malignant melanoma. The parallel ridge pattern was rarely found in the lesions of benign melanocytic nevus. Most benign melanocytic nevi showed 1 of the following 3 typical epiluminescent patterns: (1) a parallel furrow pattern exhibiting pigmentation on the parallel sulci of [he skin markings (54%), (2) a latticelike pattern (21%), and (3) a fibrillar pattern showing filamentous or meshlike pigmentation (15%). The remaining 11 benign nevi (10%) showed a nontypical pattern. CONCLUSION: Because epiluminescent microscopic features of early malignant melanoma on glabrous skin are characteristic, we can effectively detect early lesions using this noninvasive method.     

Melanoma mimicking dermal and Spitz's nevus ("nevoid" melanoma)

We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma.     

Melanoma of the oral cavity. Review of the literature

The location of melanoma in the oral cavity is extremely rare: its frequency varies between 0.2 and 8%. Oral melanoma strikes mainly male subjects and is more frequently seen at the level of the hard palate and gingiva. Today the clinicopathological classification of oral melanoma is not yet clearly outlined, and that is why the skin form is often taken as a reference. The acral lentiginous subtype proves to be the most common in this seat. In many cases (up to 50%) the diagnosis of melanoma is made on lesions which have evolved from the pre-existing pigmented lesions: as a consequence, every pigmented lesion of undetermined origin must be biopsied as a routine. The prognosis often proves poor and the surgical approach, combined with the chemotherapeutic one, is the first choice treatment. Lymph node dissection is not routinely practiced.     

Effects of outcome expectancies and disinhibition on ad lib alcohol consumption

CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target cells. It has recently been reported that melanoma cells in vivo express a significant amount of CD95L, thereby being immediately able to kill CD95-bearing immunocompetent cells specific for cancer antigens, which infiltrate the lesions. In this study, we employed immunohistochemistry using an antibody directed against CD95L to investigate at which stage the melanoma CD95L expression is turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These included benign and dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph node metastases. CD95L was expressed in all of the advance-phase melanomas as well as lymph node metastases of cutaneous origin, whereas neither melanoma in situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To investigate a link between positivity and tumour size, the data were analysed on the basis of Breslow thickness, and indicated that expression was observed only when tumours were thicker than 0.75 mm. We next compared expression of CD95L and HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage I, whereas HMB-45 was not only expressed in melanoma cells but also in benign pigmented naevi. This indicated the advantage of CD95L staining to diagnose melanoma. The present study indicates the significant correlation between tumorigenicity and expression of CD95L, and thereby raises the possibility that CD95L may be a useful diagnostic marker for malignant melanomas.     

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.     

Pigmented lesions in newborn infants

1058 newborn infants were examined. Forty-one (3-9%) had clinically discernible pigmented lesions compatible with melanocytic naevi. Biopsy was performed on thirty-four of the forty-one and of these; eleven, representing 1-01% of the infants, proved to be melanocytic naevi. No giant (garment) naevi were seen in this series. Two of the eleven naevi pathologically examined showed histological changes similar to those that have been reported in some giant naevi, but the remaining nine were not only different from criteria usually assigned to giant naevi, but they also differed from the usual adult naevi, in that most were predominantly junctional. None of the melanocytic naevi in this series showed any suggestion of malignant change. In newborn infants it is often impossible clinically to distinguish naevi from other types of pigmented lesions, as only eleven out of the thirty-four pigmented lesions were melanocytic naevi. Seven of the eleven melanocytic naevi were under 1-5 cm in diameter. No pigmented lesions were found on the palms, soles or genitalia.