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.     

Dermoscopy of an acral congenital melanocytic nevus

Congenital melanocytic nevi carry a risk for malignant transformation into melanoma, therefore early detection of suspicious features is crucial to reduce mortality rates. Dermoscopy improves the early detection of melanoma while reducing the number of unnecessary excisions of benign pigmented skin lesions. Dermoscopically, congenital melanocytic nevi are often characterized by the presence of a cobblestone pattern, but to date, little is known about the dermoscopic features of acral congenital melanocytic nevi. We report an acral congenital melanocytic nevus typified by the presence of three different dermoscopic patterns that are commonly seen in acquired melanocytic nevi of palms and soles.     

Melanocytic neoplasia of the sole: diagnosis and therapeutic approach.

We examined retrospectively a series of 184 cases of melanocytic neoplasia of the sole observed and treated as out-patients from January 1977 to December 1987, comparing clinical and histological diagnoses. The original clinical diagnoses were divided into nevi, pigmented lesions of suspected malignancy, cutaneous melanomas and others. Of the 170 cases diagnosed clinically as nevus none was of melanoma. The risk that a pigmented skin lesion diagnosed as clinically benign is melanoma is so low as not to constitute a clinical problem. It is concluded that systematic removal of sole nevi is unjustified. If, however, there is the smallest doubt concerning a sole lesion, it should be removed and examined histologically.     

Epidermolysis bullosa nevus: an exception to the clinical and dermoscopic criteria for melanoma

BACKGROUND: Large acquired melanocytic nevi that occur in patients with epidermolysis bullosa (EB), referred to as EB nevi, may pose a diagnostic challenge because of their clinical and dermoscopic resemblance to melanoma. These unconventional melanocytic nevi have been encountered in all categories of hereditary EB, most of them in childhood. Although some of the reported cases have an alarming clinical appearance that is indistinguishable from melanoma, long-term follow-up has confirmed the benign nature of these rarely encountered melanocytic lesions. The histopathologic patterns of these nevi range from a banal congenital pattern to the problematic persistent pseudomelanoma pattern. OBSERVATION: We describe the clinical, dermoscopic, and histopathologic features of a large EB nevus in a toddler. Clinically, the lesion was markedly asymmetrical and irregularly pigmented with foci of stippled pigmentation and scarring, which easily fulfilled the ABCD criteria for melanoma. Accordingly, a false-positive score resulted when dermoscopy was performed. Histopathologically, a pattern of persistent melanocytic neoplasm was observed. In the following 18 months, dynamic changes of the lesion included near-complete disappearance of the pigment, which was replaced by scar, milia, and areas of healing ulcers. CONCLUSION: Epidermolysis bullosa nevi are dynamic melanocytic lesions that may simulate melanoma.     

Pointillist nevi

BACKGROUND: Atypical melanocytic nevi and cutaneous melanoma are often marked by variation in color. However, there are examples of "benign" explanations for irregularities in pigmentation, such as perifollicular hypopigmentation or hyperpigmentation. OBJECTIVE: The purpose of this study was to correlate the clinical and histologic features of 3 unusual melanocytic nevi consisting exclusively of multiple, tiny, dark brown to black dots on a skin-colored background, which we have termed pointillist nevi. METHODS: Histologic examination was performed of the single pointillist nevus from each of 3 patients (all women; aged 28, 39, and 47 years). RESULTS: The diameters of the pointillist nevi were 2, 3.5, and 5.5 mm. Individual dots were approximately 0.1-0.25 mm. Each of the 3 nevi showed a different histologic correlate for the dots, either (1) discrete, densely pigmented, junctional melanocytic nests; (2) isolated dermal pigmented melanocytic nests; or (3) discrete clusters of melanophages in the papillary dermis. CONCLUSION: Pointillist nevi are benign melanocytic nevi with histologic correlates similar to those of the "brown globules" observed by dermoscopy in uniformly pigmented nevi. However, the dots seen in pointillist nevi can be visualized without magnification. The clinical and histologic features of pointillist nevi add to the spectrum of unusual patterns of pigmentation that may be encountered in benign melanocytic lesions.     

Immunohistochemical expression of cyclooxygenage-2 in melanocytic skin lesions

Background Several reports have shown expression of cyclooxygenase‐2 (COX‐2) in malignant skin tumors. COX‐2 has also recently been reported as a marker of malignant melanoma (MM). Objective Our aim was to investigate whether there is a difference in the immunohistochemical expression of COX‐2 between malignant and benign melanocytic lesions of the skin. Methods We selected 40 archival cases of MM including 10 cases of superficial spreading melanoma, 10 of lentigo maligna melanoma, 10 of nodular melanoma, and 10 of acral lentiginous melanoma. For comparison, we also selected 35 benign melanocytic lesions, which included 15 nonatypical nevi and 10 atypical nevi. The remaining 10 cases were Spitz nevi. COX‐2 immunohistochemical staining was performed, and intensities were assessed quantitatively. Results The MM group and the benign melanocytic nevi group showed a highly statistically significant difference in the intensity of COX‐2 expression (P < 0.0001). Staining intensity in the dermal component of MM cases also showed a tendency to increase with increasing tumor depth. By contrast, the intensity of the dermal component in the melanocytic nevi group decreased with increasing depth as the nevus cells matured from type A to type C cells. No statistical difference was noted between the MM and Spitz nevi cases (P = 0.20). Conclusions Malignant melanoma shows stronger immunohistochemical expression of COX‐2 than benign melanocytic nevi. Although COX‐2 cannot be used alone to differentiate MM from melanocytic nevi, it may serve as an aid in the differential diagnosis of melanocytic skin lesions.     

Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs

Evaluation of the three benign lesions discussed here form the basis for dermoscopic evaluation of other pigmented skin lesions. The features of seborrheic keratosis, including [figure: see text] the various forms of fissures, comedo-like openings, and milia-like cysts, often allow easy interpretation of seborrheic keratosis; however, similar structures are commonly associated with melanocytic neoplasms, notably congenital nevi. Understanding solar lentigo and its dermoscopy features allows for the appreciation of pigment networks common in lentiginous melanocytic nevi and melanoma. The lichenoid keratosis is the model for lichenoid inflammation elsewhere, notably in halo nevi, regressing melanoma, and other melanocytic neoplasms with significant host inflammatory reactions.     

Dermatoscopy of amelanotic and hypomelanotic melanoma

Amelanotic melanoma is a subtype of cutaneous melanoma without pigment. The clinical diagnosis is challenging because it may mimic benign or malignant melanocytic and non‐melanocytic neoplasms and inflammatory skin diseases. In synchrony with the improvement of the diagnosis of pigmented lesions, dermatoscopy may assist the clinician in the diagnosis of non‐pigmented skin neoplasms in general and of amelanotic melanoma in particular. We have searched the literature to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypomelanotic melanomas by dermatoscopy. In addition we present eight consecutive cases and discuss their clinical and dermatoscopic characteristics in the light of published data.     

Optical transfer diagnosis of pigmented lesions: a pilot study

Objective: To evaluate the potential of a novel imaging technology, optical transfer diagnosis (OTD), for differentiation of benign from malignant pigmented melanocytic lesions.
Design: Patients with pigmented lesions suspicious for melanoma were referred for OTD. After scanning, lesions were biopsied for histopathologic examination, each by two separate dermatopathologists. To create morphologic–physiologic maps, the imaging system used the morphologic and physiologic parameters derived from prediction models of light absorption and scattering by chromophores such as hemoglobin, keratin, and melanin at different epidermal and dermal depths. The relative entropies were analyzed for output prediction of malignancy vs. nonmalignancy.
Setting: General dermatology clinic in a tertiary care academic medical center.
Patients: Fifty patients with suspected melanoma.
Intervention: OTD of pigmented lesions suspicious for melanoma, followed by biopsies for histopathologic examination.
Main outcome measures: Histopathologic confirmation of malignant lesions identified by OTD as melanoma.
Results: Sixty-three pigmented suspicious lesions were scanned before being biopsied for histopathologic examination by the two dermatopathologists. Of the 63 lesions, five were identified as melanoma and 58 were found to be benign (including three seborrheic keratoses and 55 melanocytic nevi). OTD was able to identify the malignant lesions with 100% sensitivity and 94.8–96.6% specificity.
Conclusions: Further study is indicated, but this technology is a promising adjunct to clinical skin cancer screening. Additionally, if the physiologic prediction models can be validated, OTD may facilitate the noninvasive study of some aspects of cutaneous physiology.     

Clinical guidelines for the early detection of plantar malignant melanoma

Of 144 pigmented lesions excised from the soles of Japanese patients, 140 were melanocytic. Apart from congenital melanocytic nevi, only a few benign acquired melanocytic nevi on the sole were more than 7 mm in maximum diameter and none exceeded 9 mm. In contrast, all plantar malignant melanomas, including malignant melanoma in situ, were 9 mm or more in maximum diameter. In addition, the majority of plantar melanocytic lesions excised from patients who were older than 50 years of age were malignant melanoma. On the basis of these data, we propose clinical guidelines for the early detection of plantar malignant melanoma.     

AgNOR (nucleolar organizer regions) staining in malignant melanoma.

Nucleolar organizer regions (NORs) are loops of ribosomal DNA seen in nuclei, which are demonstrable as black dots (AgNOR) in tissue sections by silver (Ag) colloid staining. The number of such AgNORs is correlated with cellular activity and is an indicator of the degree of malignancy. In this study, 76 melanocytic lesions were analyzed by AgNOR staining, and the clinical and histopathological characteristics of malignant melanoma and melanocytic nevi were considered. Although the AgNOR counts for melanocytic nevi were significantly different from those in malignant melanoma, an obvious overlap between them was detected. The number of AgNORs in melanocytic nevi per cell was usually 1 or 2. On the other hand, the number of AgNORs per malignant melanoma cell was variable. Morphologically, malignant melanoma cells often showed dispersal of AgNORs throughout the nucleus as well as multiple nucleoli containing clustered AgNORs, whereas melanocytic nevus cells tended to have a regular nucleolus with tightly clustered AgNORs. The correlation between AgNOR count and pathological staging was uncertain, but a slight correlation between AgNOR count and thickness of the primary lesion was obtained. However, the AgNOR count in malignant melanoma was not a prognostic factor for the disease. Therefore, the AgNOR method is difficult to use for differential diagnosis between benign pigmented lesions and malignant melanoma. Nonetheless, an AgNOR count of more than two per cell favors a diagnosis of malignant melanoma.     

Quantification of vascularity in nodular melanoma and Spitz's nevus

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity. The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi. In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europacus agglutinin I-stained sections by computer-assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD±5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD±3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85×10–4mm², SD±10.32; nodular melanomas: 7.88×10-mm², SD×5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling). Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas. Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.     

Follow-up of melanocytic skin lesions with digital epiluminescence microscopy: patterns of modifications observed in early melanoma, atypical nevi, and common nevi

BACKGROUND: Digital epiluminescence microscopy (DELM) has been reported to be a useful technique for the follow-up of melanocytic nevi. One of the promises of this technique is to identify modifications over time that indicate impending or incipient malignancy and to facilitate surveillance of melanocytic skin lesions, particularly in patients with multiple clinically atypical nevi. OBJECTIVE: Our purpose was to report on patterns of modifications over time observed in benign melanocytic skin lesions and melanoma. METHODS: A total of 1862 sequentially recorded DELM images of melanocytic lesions from 202 patients (mean age, 36.1 years; 54.0% female patients) with multiple clinically atypical nevi were included in the analysis. The median follow-up interval was 12. 6 months. Melanocytic lesions with substantial modifications over time (enlargement, changes in shape, regression, color changes or appearance of ELM structures known to be associated with melanoma) were excised and referred to histopathologic examination. RESULTS: A total of 75 melanocytic skin lesions (4.0%) from 52 patients (mean age, 33.3 years; 63.5% female patients) showed substantial modifications over time and were excised and referred to histopathologic examination. Eight changing lesions were histologically diagnosed as early melanomas. These lesions frequently showed focal enlargement associated with a change in shape as well as appearance of ELM structures that are known to be associated with melanoma. In contrast, the majority of benign changing lesions (common and atypical nevi) showed symmetric enlargement without substantial structural ELM changes. Six of the 8 patients in whom melanoma developed were unaware of the fact that the lesion had changed over time. CONCLUSION: We demonstrate that follow-up of melanocytic lesions with DELM helps to identify patterns of morphologic modifications typical for early melanoma. DELM may therefore serve as a useful tool to improve the surveillance of patients with multiple atypical nevi.     

Desmoplastic melanocytic nevi with lymphocytic aggregates

Desmoplastic melanocytic nevi can be difficult to distinguish from desmoplastic melanoma. The presence of lymphocytic aggregates in association with a sclerosing melanocytic proliferation is commonly regarded as a feature in support of a diagnosis of desmoplastic melanoma. However, the finding is not specific for melanoma. Herein we report six cases of sclerosing melanocytic nevi with associated lymphocytic aggregates. They occurred in five women and one man, ranging in age from 11 to 61 years. Three lesions were sclerosing Spitz nevi; one was an amelanotic sclerosing blue nevus, one an acquired intradermal sclerosing nevus, and one was a congenital compound melanocytic nevus with sclerosis of its dermal component. The lesions were interpreted as benign, i.e. melanocytic nevi, because of their histopathologic attributes (symmetric silhouette, benign cytologic features) and results from immunohistochemical studies (all lesions strongly expressed Melan-A and p16) and fluorescence in situ hybridization (FISH). Three lesions tested by FISH lacked copy number changes of 11p, 6q or 6p. None of the lesions recurred. The cases highlight that contextual information is essential for the diagnosis of desmoplastic melanoma and sclerosing nevus. The presence of lymphocytic aggregates per se does not prove that a sclerosing melanocytic proliferation is malignant.     

Clinical and histopathologic analyses of pigmented macular lesions on the soles of Japanese--proposal of a clinical guideline for detection of early malignant melanoma on the sole

Of 92 pigmented macular lesions on the soles of Japanese, 88 lesions were histologically confirmed to be melanocytic: 65 ordinary acquired melanocytic nevi, 9 congenital melanocytic nevi, 5 dysplastic nevi, and 5 possible and 4 definite lesions of early malignant melanomas. None of the ordinary acquired melanocytic nevi were more than 7 mm in maximum diameter. Excluding congenital melanocytic nevi, there were 8 lesions whose greatest diameters were more than 7 mm: 2 dysplastic nevi, and 2 possible and 4 definite lesions of early malignant melanoma. Judging from the data obtained in this study, we propose the following clinical guideline for the detection of early lesions of malignant melanoma on the sole. If the pigmented lesions have no possibility of being congenital melanocytic nevus, black heel, lesions of Peutz-Jeghers syndrome, or 5-FU induced lesions, measure the maximum diameters. 1) Lesions with a diameter of more than 7 mm should be excised for histological evaluation. 2) Lesions with a diameter between 6 and 7 mm should be examined histologically when they show conspicuous irregularity in shape, color and/or border or are observed on the soles of a patient older than 50.     

Tips and tricks in the dermoscopy of pigment lesions

ABSTRACT: Dermoscopy is a useful, widely used tool for examining pigmented lesions, especially helpful in cases of an uncertain nature. Nevertheless, doctors may experience diagnostic difficulties while using this method. An example of this may be found in the examination of subcorneal hematoma, dark nevi with black lamella or lesions of acral volar skin. In such cases, a few diagnostic tricks have proven to be helpful in achieving diagnostic accuracy. This paper reviews various methods of performing dermoscopy, suggesting a number of simple, yet helpful tests. These include the adhesive tape test, the skin scraping test and the ink furrow test. The adhesive tape test is helpful in differentiating between dark melanocytic nevi and melanoma. Hematoma may be more easily differentiated with the use of the socalled skin scraping test. The confirmation of benign and melanocytic lesions of acral volar skin, on the other hand, is more accurate when using the ink furrow test. These methods have been discussed here based upon a series of literary reviews, the authors own experience and, also, iconography. The present article describes novel methods used in dermoscopy, helping to bring about a faster, more accurate diagnostics of those lesions which have proven to be more difficult to recognize. Helpful tricks, such as have been known to professional literature, as well as the authors own experience (for instance, applying urea cream to hyperkeratotic lesions or using photographs of skin lesions taken with the aid of a mobile phone camera - all prior to surgery) will surely be considered beneficial to the practitioner, be it dermatologist or any other physician.     

Correlation between dermoscopic and histopathological diagnoses of atypical nevi in a dermatology outpatient clinic of the Medical School of S?o José do Rio Preto,SP, Brazil

BACKGROUND

The incidence of cutaneous melanoma is increasing worldwide. Since it is an aggressive neoplasm, it is difficult to treat in advanced stages; early diagnosis is important to heal the patient. Melanocytic nevi are benign pigmented skin lesions while atypical nevi are associated with the risk of developing melanoma because they have a different histological pattern than common nevi. Thus, the clinical diagnosis of pigmented lesions is of great importance to differentiate benign, atypical and malignant lesions. Dermoscopy appeared as an auxiliary test in vivo, playing an important role in the diagnosis of pigmented lesions, because it allows the visualization of structures located below the stratum corneum. It shows a new morphological dimension of these lesions to the dermatologist and allows greater diagnostic accuracy. However, histopathology is considered the gold standard for the diagnosis.

OBJECTIVES

To establish the sensitivity and specificity of dermoscopy in the diagnosis of pigmented lesions suspected of malignancy (atypical nevi), comparing both the dermatoscopic with the histopathological diagnosis, at the Dermatology Service of the outpatient clinic of Hospital de Base, São José do Rio Preto, SP.

METHODS

Analysis of melanocytic nevi by dermoscopy and subsequent biopsy on suspicion of atypia or if the patient so desires, for subsequent histopathological diagnosis.

RESULTS

Sensitivity: 93%. Specificity: 42%.

CONCLUSIONS

Dermoscopy is a highly sensitive method for the diagnosis of atypical melanocytic nevi. Despite the low specificity with many false positive diagnoses, the method is effective for scanning lesions with suspected features of malignancy.     

Weight of decision-making impairs clinical assessment of melanocytic lesions

BACKGROUND AND OBJECTIVE: We studied the weight of decision-making on clinical assessment of melanocytic lesions judging benign, atypical, and malignant lesions; common mistakes; and total removal rates, comparing dermatologists with nondermatologists. METHODS: Of 11,246 histopathology specimens, 3,768 had a clinical assessment of melanocytic lesions. Histopathologic diagnosis served as the gold standard. RESULTS: Benign nevi were assessed most accurately (77%). Dermatologists assessed benign nevi better (p < .0001). The accuracy of clinical assessment in atypical nevi and melanoma was lower (23% and 42%, respectively). Seborrheic keratosis was the most common mistaken diagnosis. Complete removal of clinically benign nevi, atypical nevi, and melanoma was 84%, 90%, and 89%. Decision-making impaired clinical assessement of melanocytic lesions by 5% for dermatologists and 9% for nondermatologists. CONCLUSION: The accuracy of clinical assessment of melanocytic lesions is high for benign nevi, with dermatologists outperforming nondermatologists. Clinicians overestimated malignant potential. Complete removal was more frequent in suspicious lesions. Clinical decision-making impaired assessment by 5 to 9%.     

Targetoid hemosiderotic nevus. A trauma-induced simulator of malignant melanoma

BACKGROUND: Simulators of malignant melanoma comprise a heterogenous group of melanocytic and nonmelanocytic lesions of the skin. Among frequent clinical mimickers of melanoma are injured melanocytic nevi. Any change in the clinical appearance of a pre-existing nevus should alert the clinician to exclude the possibility of malignant transformation in order to early identify a lesion at a stage when complete cure can still be achieved. OBJECTIVE: The purpose of this study was to present the clinical, dermoscopic and histopathologic findings of a series of acquired melanocytic nevi which abruptly developed a pigmented peripheral halo, presumably following minor trauma. METHODS: A series of 6 cases of acquired melanocytic nevi which suddenly developed a targetoid halo were included in the study. All lesions were evaluated by dermoscopy. Three cases were surgically removed at different stages of evolution and submitted to histopathologic examination. In all cases, follow-up was obtained. RESULTS: All the lesions arose on trauma-prone skin sites of young women. The sudden development of an asymptomatic, targetoid halo on a long-lasting, acquired exophytic nevus was the main presentation. Whereas the central nevus persisted, the ecchymotic halo ultimately disappeared. Histopathologic examination disclosed changes of the traumatized nevus in the central part, whereas the ring showed hemorrhage and hemosiderin deposits. Increased numbers of small vessels with hobnail characteristics were associated features. CONCLUSIONS: Targetoid hemosiderotic nevus is a distinctive clinicopathologic variant of traumatized acquired melanocytic nevus which should be included in the list of clinical simulators of melanoma.