Acral lentiginous melanoma: a clinicoprognostic study of 126 cases

BACKGROUND: Although the histopathological subtype of melanoma has not been clearly proven to carry independent prognostic significance, acral lentiginous melanoma (ALM) seems to confer a poorer prognosis mainly because disease is often more advanced at the time of diagnosis. OBJECTIVES: To investigate the distinctive epidemiological and clinical characteristics of ALM, a peculiar histological entity, and to identify prognostic factors. METHODS: We performed a register-based review of cases from a single large referral centre, the University Hospital Department of Dermatology, Lyons, France. We reviewed patient demographics, the initial presentation of the lesion, and clinical outcome. ALM-specific and disease-free survival were estimated using the KaplanMeier method and compared using the log-rank test. A Cox model was used to identify prognostic factors. RESULTS: One hundred and twenty-six patients were identified as having histopathology-proven ALM in our melanoma patient register from 1996 to 2004. There were 46 (37%) subungual ALM and 80 (63%) ALM on soles, palms and nonvolar sites. The mean age at diagnosis was 63 years. There were 44 (35%) men and 82 (65%) women, sex ratio M/F 1 : 1.86. The mean Breslow thickness was 2.51 mm (range: in situ to 20 mm). There was no evidence of overexposure to ultraviolet radiation, nor was there found a predisposing genetic trait. Only 16 (13%) patients recalled a history of trauma. Thirty-four ALM (28%) were unpigmented. The median ALM-specific and disease-free survival were 13.5 and 10.1 years, respectively. The 5-year survival rate was 76%. Multivariate analysis identified tumour thickness, male gender and amelanosis as independent clinical prognostic factors for both ALM-specific and disease-free survival. CONCLUSIONS: Our study provides specific information on the clinical characteristics and outcome of this uncommon histological subtype of melanoma. However, the pathogenesis remains unknown. Breslow thickness, male gender and amelanosis were significantly associated with a poorer prognosis.     

Acral lentiginous melanoma in situ: a study of nine cases

An acral lentiginous melanoma (ALM) is the most common type of cutaneous melanoma in Asians. However, it is unusual to encounter a patient showing only the histologic features of an ALM in situ. Here we describe clinical and histologic features of nine cases of ALM in situ including immunohistochemical staining with anti-S100 protein and HMB-45. All the patients had a long clinical history. Clinically, the lesions were characterized by a longitudinal pigmented streak in the nail plates, black pigmentation on the proximal or lateral nail fold, and an irregular border and variegated pigmentation on the sole or thumb. Total resections of the lesions were performed in all patients. All lesions, in both biopsy and excisional specimens demonstrated more melanocytes generally located in the basal layer of the epidermis. There was no dermal invasion. No recurrence of the disease had occurred in any patient after a follow-up period of between 6 months to 12 years after surgery. These results suggest that ALM can evolve slowly over many years.     

Acral lentiginous melanoma misdiagnosed as verruca plantaris: a case report

The ratio of acral lentiginous melanoma (ALM) to all melanomas among Caucasians is small, although this type of malignant melanocytic neoplasm comprises the majority of melanomas among those who have darker skin tone. Because of frequently atypical clinical morphology, and as a consequence of their relative rarity, ALM is often misdiagnosed. This case demonstrates the disastrous consequences of prolonged treatment of an ALM presumed to be a plantar wart. Pedal lesions require close observation and prompt biopsy when diagnostic uncertainty exists or when therapeutic interventions fail.     

Acral lentiginous melanoma misdiagnosed as tinea pedis: a case report

The incidence of acral lentiginous melanoma (ALM) varies in different ethnic groups. Volar skin is a relatively infrequent site of malignant melanoma in Caucasian patients, although the foot is the most common site of involvement in Asian and African populations. Diagnosis of ALM is usually delayed and melanomas can be diagnosed at advanced clinical stages, so the prognosis is often poor. We present a Caucasian Turkish man with ALM on the interdigital site of his foot, however, as a result of maceration of the surrounding skin, it seemed to be tinea pedis.     

Acral lentiginous melanoma: histopathological prognostic features of 121 cases

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth histopathological subtype of malignant melanoma, accounting for < 10% of all melanomas in white-skinned populations. It is characterized by a lentiginous pattern of proliferation of the intraepidermal component of the tumour. Its individualization is still controversial, especially in regard of its prognostic value. OBJECTIVES: To characterize better ALM from a pathological point of view and to assess the prognostic value of all histopathological features of ALM. METHODS: We performed a review of all cases of ALM followed from 1996 to 2004 at the University Hospital Department of Dermatology, Lyon, France. We examined all haematoxylin, eosin and saffron-stained tissue sections of the primary lesions. Several pathological parameters of interest in melanoma were evaluated for disease-free and specific survival with the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS: Representative histological material was available for 121 patients. The mean Breslow thickness was 2.5 mm (in situ-20 mm). Fifteen lesions (12%) were in situ, nine (7%) were at Clark level II, 35 (29%) at III, 40 (33%) IV and 22 (18%) V. Extension along adnexal structures was found in almost half of the ALMs (46%), without prognostic significance. Seventeen (14%) lesions showed no microscopic pigmentation. Remnants of pre-existing naevus were found in four (3%) melanomas. The width of the 36 (30%) ulcerated lesions ranged from 1 to 20 mm (mean 7.6). Ulceration and its width were both associated with a large tumour thickness (P < 0.01), a high level of invasion (P < 0.01), the presence of vascular invasion (P < 0.01) and the lack of pigment production (P < 0.01). Among the 99 ALMs which were in the vertical growth phase (VGP), 21 showed a high mitotic rate (> 6 mitoses mm(-2)). A high mitotic rate was found to be significantly associated with the presence of ulceration (P < 0.01). The presence of microscopic satellites was noted in 10 (10%) lesions. The uncommon presence of small cells (8%) in the VGP was statistically significantly (P < 0.01) associated with a worse prognosis compared with other cell types. Multivariate analysis identified mitotic rate (P < 0.01), microsatellites (P = 0.05), Clark level (P = 0.01) and gender (P = 0.03) as independent prognostic factors for disease-free survival. Only the presence of microsatellites (P = 0.02) and a high mitotic rate (P < 0.01) were independently correlated with specific survival in ALM. CONCLUSIONS: This is a detailed pathological study of a large cohort with ALM, an uncommon subtype of melanoma. Mitotic activity appears to be of particular importance in predicting the outcome of ALM.     

Acral lentiginous melanoma: an immunohistochemical study of 20 cases

BACKGROUND: Though acral lentiginous melanoma (ALM) is a major type of malignant melanoma, no immunohistochemical study on this type of melanoma has been reported. OBJECTIVE: The purpose of this study is to analysis the immunohistochemical findings of ALM using routinely used immune markers. METHODS: An immunohistochemical study was performed on paraffin sections of 20 ALMs using S-100 protein, HMB-45, MART-1, vimentin, epithelial membrane antigen (EMA) and CAM 5.2. RESULTS: S-100 protein (95%) was found to be a more sensitive marker than either HMB-45 (80%) or MART-1 (70%) for recognizing ALM. Melanin bleaching was useful for recognizing heavily pigmented ALM using both S-100 protein and HMB-45. The intensity of HMB-45 correlated well with the melanin content. However, there was no significant correlation between the intensity of S-100 protein and the melanin content. One and two out of 20 cases stained focally with EMA and CAM5.2, respectively, but these cases stained also with HMB-45 and/or S-100 protein. CONCLUSIONS: S-100 protein and HMB-45 were relatively sensitive markers for recognizing ALM. Despite the occasional positivity for the epithelial markers in ALM, all epithelial marker-positive cases stained also with HMB-45 and/or S-100 protein. Therefore, we recommend that the panel of antibodies used for recognizing ALM should contain at least S-100 protein and HMB-45.     

Acral lentiginous melanoma: conventional histology vs. three-dimensional histology

Background  Patients with acral lentiginous melanoma (ALM) seem to have a poor prognosis. ALMs represent 4–10% of cutaneous melanomas in white populations. Surgery is mostly based on conventional histological evaluation. With micrographic surgery, continuously spreading tumours can be excised with smaller excision margins for better cosmesis and function.
Objectives  Clinical parameters and surgical strategies influencing the prognosis of patients with ALM were evaluated.
Methods  Two hundred and forty-one patients (44% male, 56% female) with stage I/II ALM were recorded during 1980–2006. One hundred and thirty-three patients underwent complete histology of three-dimensional excision margins (3D histology) using the paraffin technique. Risk factors for disease-specific and recurrence-free survival were estimated.
Results  Patients were aged 26–87 years (median 63) with median tumour thickness of 2·0 mm. The median follow-up was 41 months. Multivariate analysis identified ulceration, conventional histology and tumour thickness as risk factors for recurrence-free and disease-specific survival. Using 3D histology, excision margins were significantly smaller (median 7 vs. 20 mm) without an increased risk of local recurrences. Patients with 3D histology had a 5-year survival of 81% compared with 63% with conventional histology. Retrospective analysis with immunohistological methods (anti-Melan-A) could improve the diagnostic specificity in detecting further melanocytic cell nests.
Conclusions  Clinical and surgical risk factors seem to have different influences on the outcome of ALM. 3D histology allows reduction of excision margins by two-thirds without an increased risk of local recurrences and with better prognosis. 3D immunohistology could be a valuable diagnostic tool to reduce the rate of local recurrences.     

Acral lentiginous melanoma mimicking benign disease: the Emory experience

BACKGROUND: Plantar and subungual melanoma exhibits a higher misdiagnosis rate relative to other anatomic sites. Misdiagnosis and delay in diagnosis are statistically associated with poorer patient outcome. Awareness of atypical presentations of acral melanoma may, thus, be important to decrease misdiagnosis rates and improve patient outcome. METHODS: We conducted a retrospective case review of plantar or lower-extremity subungual melanoma performed at Winship Cancer Center, a tertiary care, referral center affiliated with Emory University, between 1985 and 2001. RESULTS: A total of 53 cases of plantar or lower-extremity subungual melanoma were identified. Of 53 cases with a final diagnosis of melanoma, 18 were initially misdiagnosed. Misdiagnoses included wart, callous, fungal disorder, foreign body, crusty lesion, sweat gland condition, blister, nonhealing wound, mole, keratoacanthoma, subungual hematoma, onychomycosis, ingrown toenail, and defective/infected toenail. Of the 18 misdiagnosed cases, 9 were clinically amelanotic. CONCLUSION: Awareness that amelanotic variants of acral melanoma may assume the morphology of benign hyperkeratotic dermatoses may increase the rate of correct diagnosis and improve patient outcome.     

Acral lentiginous melanoma and lentigo maligna occurring in Werner's syndrome

Werner's syndrome is an adult progeria that predisposes affected individuals to various cutaneous and internal malignant neoplasms. Herein we report on a patient with Werner's syndrome who developed two primary melanocytic tumors.     

Acral lentiginous melanoma versus other melanoma: A single‐center analysis in Japan

We summarize herein our 14‐year experience of conventional treatment outcomes before the era of molecular‐targeted therapy and immunotherapy. Specifically, we conducted a retrospective review of our 252 patients with primary cutaneous melanoma (acral lentiginous melanoma [ALM], n = 121; non‐acral lentiginous melanoma [non‐ALM], n = 131), and compared the prognostic factors between ALM and non‐ALM. Melanoma‐specific survival and disease‐free survival were estimated using the Kaplan–Meier method. Regarding the results, all patients were Japanese (106 male and 146 female), with a mean age of 60.1 years. Among ALM patients, age was elder and primary tumor size was larger than non‐ALM. As for tumor thickness, in situ lesions were more frequently observed in ALM. There was no significant difference in the distribution of tumor thickness between the two groups when excluding the in situ lesions. For treatment of the primary melanoma, 248 patients (98.4%) had undergone curative surgical excision and 120 patients with more than 1 mm or ulcerated melanoma had undergone sentinel lymph node biopsy. Patients with systemic metastasis primarily underwent dacarbazine‐based chemotherapy. The Kaplan–Meier survival curves revealed no significant difference in melanoma‐specific survival and disease‐free survival between those with ALM and non‐ALM. The results also showed that both ALM and non‐ALM, when they initially metastasize, first affect the regional lymph nodes. Incisional biopsy was not an adverse prognostic factor. These results suggest that ALM does not differ in its biological behavior from non‐ALM, so we can consider ALM as being equivalent to non‐ALM. The initial treatment for ALM and non‐ALM can involve the same strategy.     

Acral lentiginous melanoma simulating "clear cell sarcoma of tendon and aponeuroses"

Clear cell sarcoma was closely mimicked in metastatic tumor deposits from two patients with acral lentiginous malignant melanoma. A subcutaneous deposit composed of glycogen-laden spindle cells dominated the presenting clinical picture in one patient. In the other, primary acral melanoma resembled a histiocytic tumor and metastatic tumor simulated clear cell sarcoma. The cases illustrate the pleomorphism that may be encountered in malignant melanoma.     

Acral lentiginous melanoma treated with topical imiquimod cream: possible cooperation between drug and tumour cells

An 85‐year‐old woman presented with a lesion on the sole of her right foot, which was histologically confirmed as acral lentiginous melanoma. Because of the large field involved and because the patient refused any invasive or painful treatment, topical treatment with imiquimod was commenced. At the 20‐month follow‐up, the patient was still continuing treatment with topical imiquimod, and no metastases to the lymph nodes or viscera were found, either clinically or in imaging studies. We believe that the success of the treatment cannot be explained only by the stimulation of the immune system induced by imiquimod. A possible explanation might be ‘tumour dormancy’, where a tumour grows very slowly because of a balance between the neoplasia and the immune (and nonimmune) mechanisms of tumour control. The use of imiquimod has so far allowed our patient to avoid surgery, and perturbation of the mechanisms of tumour regulation, such as local immunity and angiogenesis, has not taken place.     

Desmoplastic melanoma associated with an intraepidermal lentiginous lesion: case report and literature review

Desmoplastic melanoma tends to present as firm, amelanotic papules. Microscopically, it reveals a proliferation of fusiform cells in the dermis and variable collagen deposition, as well as intraepidermal melanocytic proliferation of lentiginous type in most cases. Biopsy in a 61-year-old white male patient, who had received a diagnosis of lentigo maligna on his face 10 years before, revealed a proliferation of dermal pigmented spindle cells and collagen deposition, reaching the deep reticular dermis, with a lentiginous component. Immunohistochemistry with S-100, Melan-A and WT1 showed positivity, but it was weak with HMB45. Desmoplastic melanoma associated with lentigo maligna was diagnosed. Several authors discuss whether desmoplastic melanoma represents a progression from the lentiginous component or arises "de novo". Desmoplastic melanoma represents a minority of cases of primary cutaneous melanoma (less than 4%). Identification of lentigo maligna indicates that desmoplastic melanoma should be carefully investigated.     

Histological evolution of lentiginous melanoma: a report of five new cases

BACKGROUND: The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single-cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases. METHODS: Histological review of routine sections with clinicopathological correlation. RESULTS: Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma. CONCLUSIONS: Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non-severely sun-damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment.