Solitary small active junctional nevi in juvenile patients

Solitary small very dark and papular pigmented nevi, less than 4 mm, are seen commonly in the second decade of life and have a distinctive histologic pattern. Microscopically these lesions show abundant intraepidermal melanin, included within the keratin layer, and proliferating single melanocytes or nevus cell nests. Prominent nucleoli in the melanocytic cells, occasional mitoses, and the invariable presence of moderate numbers of dermal melanophages and lymphocytes indicated the activity of the pathologic process. The benignity of the lesions in nine patients is supported by a benign course over a one- to three-year evaluation period after limited excisional biopsy procedures. The clinical and pathologic evidence of activity in these nevi suggests yet another possible precursor of malignant melanoma. The B-K mole syndrome and the dysplastic nevi syndrome differ from these cases both clinically and histologically.     

Congenital Spitz nevus clinically mimicking melanoma

The differentiation between atypical variants of Spitz nevus and melanoma is often difficult given the many clinical and histopathologic similarities between the two. We report a case of an infant with a congenital scalp lesion exhibiting clinical features of melanoma, including variegation and regression of pigmentation and a rapidly changing appearance. Histologic examination of the excised lesion revealed a benign congenital Spitz nevus. This case emphasizes the need for clinical and histologic correlation in determining the benign or malignant nature of atypical pigmented lesions in infants.     

The use of elastin immunostain improves the evaluation of melanomas associated with nevi

Background:  Twenty to 30% of malignant melanomas are associated with melanocytic nevi; however, sometimes it is difficult to distinguish the melanoma from the nevus by routine histology. We have previously described distinctive patterns of elastic fibers in nevi and in melanomas.
Methods:  We analyzed elastic fiber patterns using elastin immunostain and elastic van Gieson (EVG) stain in 30 cases of invasive melanomas associated with nevi, 12 control melanocytic nevi and 14 control invasive melanomas.
Results:  Elastin immunostain was superior to EVG in showing the elastic fiber patterns. In nevi, the elastic fibers were preserved between nests and often around individual melanocytes. In contrast, melanomas had markedly decreased elastic fibers in the stroma and within the nests of melanocytes. The melanoma pushed down the pre-existing thin elastic fibers of the papillary dermis, forming a compressed layer at its base, which separated the melanoma from the nevus. On sun-damaged skin, the solar elastosis had similar elastin and EVG patterns. In three cases with dense inflammation, the layer of elastic fibers between melanoma and nevus was still present but less evident.
Conclusions:  The distinctive patterns of elastic fibers, best shown by the elastin immunostain, were helpful in evaluating melanomas associated with melanocytic nevi.     

Broad spectrum of leukoderma acquisitum centrifugum.

A series of diverse neuroectodermally derived tumors associated with halos of leukoderma is presented. Clinically these lesions have in common a centrally placed, usually pigmented tumor encircled by a zone of hypopigmentation. The histological findings include (1) reduction or absence of epidermal melanin, but persistence of amelanotic melanocytes in the leukodermic halo; (2) a variety of tumors including nevus-cell nevus, neuroid nevus, blue nevus, neurofibroma, and malignant melanoma; (3) variable numbers of "small dark cells" whose nature is unclear, and which probably represent in part small nevus cells and in part lymphoid cells; and (4) damage to some tumor cells which presumably could be the cause of their destruction. Also presented are histochemical demonstrations of tyrosinase activity and immunohistochemical studies for presence of gamma-globulin in the tumors. Using the fluorescent antibody technique it was not possible to show gamma-globulins in patients' sera directed against their tumors. The relationship of developing hypopigmentation to the spontaneous regression of cutaneous neuroectodermally derived tumors is discussed.     

Comparison between familial and sporadic cutaneous melanoma in Valencia, Spain

Some clinical, pathological and genetic features have been associated to familial melanoma, particularly multiple melanoma and earlier age at diagnosis.
To compare the clinical, epidemiological and pathological differences between familial and sporadic melanoma patients in Valencia, Spain, a series of 959 patients with cutaneous melanoma were selected at a single institution. For this study the following variables were selected: age, sex, melanoma site and presence of solar lentigines on the melanoma surrounding skin, histological subtype, tumor thickness, stage, family and personal history of cutaneous melanoma and of other neoplasias, personal history of non-melanoma skin cancer, past personal history of severe sunburns, cutaneous phenotype (phototype, hair and eyes colors number of common nevus, number of atypical nevi, presence of solar lentigines).
Forty-one (4.28%) familial and 918 sporadic melanoma were identified. Among the multiple variables studied, a younger age at diagnosis (median age of 42 vs 53 years), higher frequency of the presence of at least one clinically atypical nevus (36.1% vs 17.7%), multiple melanomas (12.2% vs 3.4%) and red/blonde hair (33.3% vs 18.9%), and a lower rate of cases with solar lentigines in melanoma site (33.3% vs 56.3%) were found for familial cases. Except for hair color and age, the other variables remained statistically significant after the multivariate study. Interestingly, no acral melanomas were found among the familial cases.
In summary, phenotypic risk factors for familial melanoma are a tendency to develop multiple melanomas, to have clinically atypical nevi and to present less actinic damage at the melanoma site. All these results enhance the relevancy of genetic susceptibility associated to the ability to produce atypical nevi and partly to a higher sensitivity to the sun.     

Characteristic distribution of melanin columns in the cornified layer of acquired acral nevus: an important clue for histopathologic differentiation from early acral melanoma

Clinical and histopathologic differentiation between early acral melanoma and acral nevus is often difficult. Dermoscopy is helpful in this differentiation. On dermoscopy, early acral melanoma shows the parallel ridge pattern showing band-like pigmentation on the ridges of the surface skin markings, whereas a representative dermoscopic pattern in acquired acral nevus is the parallel furrow pattern showing parallel linear pigmentation along the surface furrows. The parallel furrow pattern suggests that melanocytes of acral nevus preferentially proliferate in the crista profunda limitans, an epidermal rete ridge underlying the surface furrow. In the present study, however, we found that in 13 of 18 acquired acral nevi, proliferation of melanocytes were detected not only in the crista profunda limitans but also in the crista profunda intermedia (CPI), an epidermal rete ridge underlying the surface ridge. Very interestingly, Fontana-Masson staining of these acral nevi revealed that even when proliferation of melanocytes was prominent in the CPI, melanin granules in the cornified layer were observed as regular melanin columns situated under the surface furrows and were hardly detected under the surface ridges. These findings indicate that in acral nevus, melanin granules produced by melanocytes in the CPI are not transferred to the upper epidermis. Hence, we must be careful not to overdiagnose an acral melanocytic lesion in which an increased number of melanocytes are detected in the CPI. Even in such a case, if melanin granules in the cornified layer are detected as melanin columns regularly distributed under the surface furrows, the lesion is strongly suggested to be a benign acral nevus.     

A statistical analysis of the characteristics of pigmented skin lesions using epiluminescence microscopy

Due to the fact that not all pigmented skin lesions (PSL) can be diagnosed solely by their clinical appearance, additional criteria are required to optimize the clinical diagnosis of atypical nevus and melanoma. Epiluminescence microscopy is a non-invasive in vivo examination that often helps to improve the accuracy of clinical diagnosis of such lesions. Years of experience have indicated some differential epiluminescent patterns for benign and malignant PSL but there is some controversy about certain borderline lesions for which histological examination is always necessary. In our study we performed a statistical analysis of data concerning 183 PSL to determine characteristics significantly associated with these lesions allowing identification of epiluminescent criteria suggestive of atypical nevus and malignant melanoma. Using the chi-quadro test and stepwise regression logistic model, we identified the following epiluminescent pattern as a risk factor for atypical nevus and malignant melanoma: irregular pigment network, presence of capillaries, irregular and abrupt ending of overall pigmentation, irregular brown globules and irregular shape and size of black dots.     

Clinical and Pathological Correlation of Malignant Melanoma

We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.     

A comparative study of fluorescence in malignant melanoma and nevocellular nevus using a fluorescence microscope and formalin-fixed specimens

Fluorescence in malignant melanoma cells was investigated. The specimens from 18 cases of malignant melanoma and 26 cases of nevocellular nevus, which were fixed with formalin and embedded in paraffin wax, were studied by the fluorescence microscopic method. On the fluorescence microscope, the malignant melanoma cells emitted intense fluorescence from the cytoplasm. The nevus cells with large amounts of melanin granules showed moderate fluorescence. The tumor cells of melanoma in situ and nevus cells with few melanin granules emitted little fluorescence. Not only malignant melanoma cells but also nevus cells in the formalin fixed specimens had various degrees of fluorescence. Many cases of malignant melanoma emitted intense fluorescence, but this was rarely found in nevocellular nevus. This method is also useful in differentiating melanoma from nevocellular nevus.     

Benign melanocytic lesions: Risk markers or precursors of cutaneous melanoma?

Background: The role of benign melanocytic lesions as precursors and not only as risk markers for the development of cutaneous melanoma is controversial.Objective: The purpose of the study was to assess the frequency of the histologic association of benign melanocytic lesions with cutaneous melanoma of a maximum thickness of 1.00 mm. The possibility that the spatial association of benign lesions with melanoma may be co-incidental was also investigated.Methods: The study subjects representing 289 cases of cutaneous melanoma of maximum thickness 1.00 mm (or less) were examined histologically for the presence of an associated benign melanocytic lesion(s), including lentiginous melanocytic proliferation; junctional, compound, or intradermal nevus; dysplastic nevus; and congenital nevus contiguous with or adjacent to the melanoma. The effects of age, tumor thickness, level of invasion, histologic type, and anatomic site on the association of benign melanocytic lesions with melanoma were assessed. In the control subjects 40 basal cell carcinomas and 38 compound nevi (not dysplastic) randomly chosen and matched for age (±1 year) and site (head/neck, trunk, upper and lower limbs) with a melanoma case were examined to assess the proportion of these cases associated with benign lesions compared with the matched melanoma cases.Results: A nevus was associated with melanoma in 51% of cases (n = 147). Of these, 82 (56%) were dysplastic nevi, 61 (41%) were common acquired nevi, and 4 (3%) were congenital nevi. Lentiginous melanocytic proliferation was present in the epidermis adjacent to 219 melanomas (75%) and in 44% of these cases (n = 97) a coexisting nevus was also present.Conclusion: The results of this study lend further support to the concept of common acquired nevi and dysplastic nevi as precursors of cutaneous melanoma. In addition, lesions diagnosed clinically as simple lentigo and solar lentigo may be important as potential precursors of melanoma, particularly in the elderly.     

Primary invasive melanoma and basal cell carcinoma (collision tumor) with blue nevus-like cutaneous metastases

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma and basal cell carcinoma (BCC) has been rarely reported in case reports, with most cases describing melanoma in situ and BCC. We present two cases of invasive melanoma (Clark level IV, no microscopic satellites present) intimately associated with BCC, and in areas distinction of the two lesions was difficult. Immunohistochemical studies delineated the two cell populations. In addition, one patient presented with multiple cutaneous metastases, all simulating blue nevi. The metastases occurred in the same anatomical region as the primary tumor, and histologically consisted of pigmented dendritic melanocytes and melanophages in the superficial and mid-dermis and arranged in a blue nevus-like lesion. Histologic clues suggesting the possibility of a metastatic melanoma included a sparse lymphocytic infiltrate, the presence of an epithelioid component and atypia of the dendritic melanocytes. However, without appropriate clinical history, the lesions could be overlooked as ordinary blue nevus. Collision tumors containing invasive melanoma and BCC are rare and this is the first report of a collision tumor with blue nevus-like metastasis. Awareness of this phenomenon and pattern of metastasis, together with the clinical findings will aid in the correct classification of these lesions.     

Expression of c-kit (CD117) in Spitz nevus and malignant melanoma

BACKGROUND: CD117, the receptor for kit-ligand, which is a growth factor for melanocyte migration and proliferation, has shown differential staining in various benign and malignant melanocytic lesions. The purpose of this study is to compare CD117 immunohistological staining in Spitz nevus versus malignant melanoma, to determine whether CD117 can aid in the diagnosis of these two lesions. METHODS: CD-117 immunohistological staining was performed in 22 clinically and pathologically diagnosed pigmented lesions including 9 cases of Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma. RESULTS: There was no significant difference in CD117 staining in either epidermis or dermis between Spitz nevi and primary melanomas. However staining of metastatic melanomas is less than dermal staining of primary MM and Spitz nevus. CONCLUSIONS: CD117 is unlikely a useful diagnostic tool in differentiating Spitz nevus from primary MM. On the other hand, CD 117 may be useful in differentiating metastatic melanoma from primary melanoma in patients who had a history of melanoma and who present with new dermal lesions.     

A Case of Spitzoid Melanoma

Spitzoid melanoma is a subtype of melanoma that, clinically and histologically, resembles a Spitz nevus. Clinically, spitzoid melanomas usually evolve from amelanotic nodular lesions, growing to 1 cm or more in diameter. They often remain clinically undiagnosed because of their wide variety of clinical appearances and a lack of pigmentation. Distinguishing a Spitz nevus from a spitzoid melanoma can be extremely difficult. Features that favor the diagnosis of a spitzoid melanoma are asymmetrical shape, diameter greater than 1 cm, a lesion with a deep invasive component, and a high degree of cytologic atypia. There have been only rare reports in the literature of the presence of giant cells in malignant melanoma, and the presence of these cells may result in its misdiagnosis as a histiocytic tumor. We present a case of spitzoid melanoma on the right ankle of a 22-year-old-woman.     

The misdiagnosis of malignant melanoma

Despite the increasing awareness of malignant melanoma over the last 40 years, clinical diagnostic accuracy remains disappointing. Malignant melanoma can masquerade clinically as benign lesions (false negatives), and benign pigmented lesions can clinically simulate malignant melanoma (false positives). Histologic examination of pigmented lesions is therefore important to ensure proper diagnosis and treatment. We review many of the published reports of benign lesions mimicking melanoma and melanoma masquerading as other entities as well as present additional cases of clinical misdiagnoses of melanoma.     

Multiple skin metastases of malignant melanoma with unusual clinical and histopathologic features in an immunosuppressed patient

Immunosuppressive regimens may have significant impact on the number of pigmented lesions and the clinical appearance of nevi. Whether immunosuppression can also influence the clinical and histopathologic appearance of malignant melanocytic lesions is still a matter of debate. A patient was immunosuppressed because of heart and bone marrow transplantation. A clinically inconspicuous mole was removed from the left flank and was considered to be a papillomatous nevus. After 1 year, the patient developed multiple pigmented lesions over the entire body, which presented clinically as benign papillomatous nevi and histologically as atypical Spitz nevi. Three months later melanoma metastases were removed from the patient's left axilla, which finally resulted in the death of the patient. Thus, in retrospect, the eruptive pigmented lesions have to be considered as cutaneous melanoma metastases. The atypical clinical and histopathologic appearance of the melanocytic lesions as well as the course of disease may have been influenced by the immunosuppression.     

骨桥蛋白在恶性黑素瘤中的表达

目的探讨骨桥蛋白在人恶性黑素瘤中的表达及意义,分析其与临床病理参数的关系。方法采用免疫组化SP法检测23例原发性恶性黑素瘤、17例转移性恶性黑素瘤及20例色素痣中骨桥蛋白的表达。结果骨桥蛋白在原发性恶性黑素瘤、转移性恶性黑素瘤、色素痣中的阳性表达率分别为91.3%,82.4%,15.0%,前两者阳性表达率明显高于后者,差异均有显著性意义(P均<0.05);骨桥蛋白的表达与年龄、性别、发病部位、是否淋巴结转移等病理因素均无关系(P均>0.05)。结论骨桥蛋白的表达可能与人恶性黑素瘤的侵袭行为的形成有关。     

Displacement of dermal solar elastosis in malignant melanoma

BACKGROUND: Ultraviolet radiation (UVR) is a major environmental causal factor for skin malignancy. In this study, we investigated the morphology of the solar elastosis (SE) band in benign and malignant melanocytic lesions. METHODS: We measured the SE band in perilesional and lesional skin of 13 melanomas (9 invasive and 4 in situ) and 11 melanocytic nevi (5 usual intradermal nevi, 4 blue nevi and 2 desmoplastic nevi) occurring in sun-exposed areas. RESULTS: The melanoma and nevus groups had similar age range, gender ratio and anatomic distribution. The mean SE thickness was 0.35 mm in melanomas and 0.29 mm in nevi (p = 0.56), indicating similar UVR exposure. There was a mean downward SE displacement (SED) of 0.43 mm in melanomas and essentially no displacement (-0.02 mm) in nevi (p < 0.005). Tumor cells and inflammatory host response were responsible for SED in melanoma. CONCLUSIONS: SED may help in the differential diagnosis of melanocytic lesions in sun-exposed areas. In melanoma, the new lesion depresses the pre-existing SE band. Conversely, the long-standing nevus co-exists with the SE band without significant displacement. Evaluation of the SE band may help to differentiate melanoma with chronic sun-induced damage as they have a distinct set of molecular alterations.     

The dysplastic nevus. Clinical and pathologic features

The dysplastic nevus has not only been considered to be a "marker," but also a formal "precursor" of malignant melanoma. Therefore, these lesions are important to recognize clinically. This article presents a classification of the dysplastic nevus based upon its variable clinical presentations. It is hoped that this classification will assist the physician to recognize many of the clinical variants of this unusual melanocytic nevus and, thus, to identify patients at greater risk for the development of malignant melanoma.     

Leukoderma acquisitum centrifugum. An unusual case.

A case is presented of a 9-year-old girl who developed a depigmented halo around a pigmented tumor of the skin on her shoulder. She also developed widespread metastases in the ipsilateral axillary lymph nodes, lungs, and, presumably, liver, and subsequently died of her disease. Histologic interpretations of the nature of the cutaneous tumor and axillary metastases are given and the suggestion made that the skin lesion was a malignant melanoma. Should this interpretation be correct, this case represents the first of its kind in which a lesion in a child with the clinical features of a halo nevus proved to be a fatal malignant melanoma.     

Trichoadenoma associated with an intradermal melanocytic nevus: a combined malformation

Melanocytic nevi have been associated with epidermal hyperplasia, adnexal hyperplasia with follicular and sebaceous differentiation, cysts, and tumors of epidermal or adnexal origin. We report a combined cutaneous hamartoma in a 29-year-old woman that comprised a trichoadenoma within an intradermal melanocytic nevus. Clinical diagnosis was a malignant transformation of a melanocytic nevus. Histopathologically, multiple keratinous cysts together with solid islands or masses of eosinophilic epithelial cells were closely intermingled with the nevus cells. Occasional nests of basaloid cells were present. Although to our knowledge this association has not been previously reported, it is worth considering that trichoadenoma and desmoplastic trichoepithelioma are the two ends of a spectrum of lesions. This combined hamartoma reported herein is important because growth of these lesions could be clinically misinterpreted as malignant transformation of a preexisting lesion. Histologic study will reveal the correct diagnosis in such cases.