Evaluation of large clinically atypical vulvar pigmentation with RCM: atypical melanosis or early melanoma?

BACKGROUND: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. OBJECTIVE: To report our experience of initial evaluation and follow-up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). METHODS: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. RESULTS: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. CONCLUSIONS: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non-invasive monitoring of foci of melanocytic hyperplasia.

Reflectance confocal microscopy of mucosal pigmented macules: a review of 56 cases including 10 macular melanomas.

BACKGROUND: Although most mucosal pigmented macules are benign, it can be clinically challenging to rule out an early melanoma. Reflectance confocal microscopy (RCM) is a noninvasive imaging technique useful in discriminating between benign and malignant skin lesions. OBJECTIVES: To describe the confocal aspects of benign and malignant mucosal pigmented macules with histopathological correlations. METHODS: We retrospectively reviewed the confocal images of 56 labial or genital pigmented macules including 10 macular melanomas. According to the retrospective nature of the study, we evaluated the recorded images chosen by the physicians that performed the RCM examination for each case. RESULTS: In benign macules, the most frequently observed pattern was a ringed pattern characterized by round or polycyclic papillae, with a hyper-reflective basal layer; another pattern was characterized by sparse bright dendritic cells in the basal layer, the basal epithelial cells being otherwise less reflective. Roundish cells, a high density of dendritic cells with atypias and intraepithelial bright cells were clues to the presence of malignancy. CONCLUSIONS: Reflectance confocal microscopy seems to be a valuable tool to noninvasively differentiate benign from malignant mucosal pigmented macules and target biopsies in cases of equivocal features.

Features of pigmented vulval lesions on dermoscopy.

BACKGROUND: The dermoscopic criteria for benign and malignant lesions on the vulva are not well established due to the lack of large series of such lesions. Melanoma should always be included in the differential diagnosis of pigmented lesions on the vulva especially when they are wide, or of recent onset. Elsewhere on the skin dermoscopy plays an important role in the selection of suspicious pigmented lesions, as well as in the selection of the best site to perform the biopsy. OBJECTIVES: To analyse the dermoscopic patterns observed in pigmented lesions of the vulva. METHODS: We analysed a nonselected consecutive series of 68 histopathologically proven cases comprising five melanomas, 16 naevi, 20 lentigos, 12 benign vulval melanoses, 11 cases of postinflammatory pigmentation, three pigmented cases of usual vulval intraepithelial neoplasia (VIN) and one seborrhoeic keratosis seen at our institution. The dermoscope was covered by translucent disposable food wrap and/or antibacterial gel to prevent possible transmission of infections. Descriptive statistics were performed using multiple correspondence analysis. RESULTS: The parallel (37%), ring-like (9%), homogeneous (22%), globular-like (13%) and reticular-like (6%) patterns were observed on benign lesions (naevi, lentigo, vulval melanosis and postinflammatory pigmentation). The cerebriform pattern (6%) was observed only on VIN and seborrhoeic keratosis. The multicomponent pattern (6%) was associated with melanoma (60%). In cases of melanoma we also occasionally observed an irregular pattern, a whitish or blue-whitish veil, irregularly distributed dots and globules and atypical vascular pattern. Using multiple correspondence analysis, we designed a new algorithm for the early detection of vulval melanomas. CONCLUSIONS: Dermoscopy can play a role in the noninvasive classification of vulval melanosis. However, further studies of larger collaborative series are needed to validate our vulval melanoma diagnostic algorithm. VIN and seborrhoeic keratosis share the same dermoscopic features and biopsy should be considered for seborrhoeic-like keratosis. In case of doubt pathological examination of a biopsy remains mandatory.

Dermoscopic features of acral lentiginous melanoma in a large series of 110 cases in a white population.

BACKGROUND: Acral lentiginous melanoma (ALM) is a rare but distinctive subtype of melanoma. The diagnosis is often delayed and misdiagnosis is common, due to frequently unusual clinical presentation and a higher rate of amelanosis than in other melanoma subtypes. OBJECTIVES: We aimed to investigate the dermoscopic features of a large series of ALM in a white-skinned population, in order to emphasize their diagnostic value. METHODS: All recorded dermoscopic photographs of ALM, including nail unit variants, were collected from the files of the University Hospital Department of Dermatology (Lyons, France) and reviewed. RESULTS: In total 110 lesions, including 66 (60%) palmoplantar ALM and 44 (40%) ALM of the nail apparatus, were analysed for dermoscopic characteristics. The mean Breslow thickness was 2.6 mm. In volar skin melanomas, the two most prevalent patterns were irregular diffuse pigmentation (60%) and the parallel-ridge pattern (53%). Minor dermoscopic patterns, commonly noted in benign lesions, were also detected but only focally within the lesions. Among the 44 nail unit lesions, 31 (70%) presented irregular lines with variegations in colours, spacing, width and disruption of parallelism. Two cases of melanonychia striata had a triangular shape. Both corresponded to early ungual ALM. Association with subungual haemorrhage was not uncommon. The study included 37 (34%) amelanotic melanomas. However, dermoscopy enabled detection of microscopic remnants of pigmentation in most cases. The vascular pattern found in almost half of these lesions was polymorphous, with combinations of milky-red areas (95%), linear irregular vessels (49%), dotted vessels (43%) and hairpin vessels (41%). CONCLUSIONS: The presence of a parallel-ridge pattern and/or irregular diffuse pigmentation within the lesion is highly indicative of melanoma on volar skin. An irregular lines pattern is the most prominent dermoscopic feature of pigmented ALM of the nail apparatus. Amelanotic ALM either in volar skin or in nail apparatus is characterized by remnants of pigmentation and a polymorphic vascular pattern.

Methylaminolaevulinate photodynamic therapy in patients with multiple basal cell carcinomas in the setting of Gorlin-Goltz syndrome or after radiotherapy.

BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is a therapeutic challenge due to the multiplicity of cutaneous tumours. Photodynamic therapy (PDT) is increasingly used as an alternative treatment for superficial and in some countries nodular basal cell carcinomas (BCC). OBJECTIVE: To study the safety and efficiency of PDT in NBCCS. METHODS: We reviewed retrospectively the evolution of 62 lesions from patients with multiple BCC treated with PDT. RESULTS: The initial response rate (85.4%, 53/62) and recurrence rate (7.5%) appeared comparable to literature values in NBCCS and to those reported in the treatment of sporadic BCC. The clearance rate without recurrence was 79% (49/62), during a mean follow-up period of 13 months. The cosmetic outcome was excellent. Recurrences were found almost 2 years after treatment. CONCLUSION: PDT is a suitable therapeutic option in the management of NBCCS patients but requires a strict and long follow-up.

Haematodermic CD4+CD56+ neoplasm: complete remission after methotrexate-asparaginase treatment.

Haematodermic neoplasm is a recently recognized condition, characterized by tumour cells expressing CD4, CD56 and CD123. This phenotype is strongly suggestive of a plasmacytoid dendritic cell origin. This haematopoietic malignancy is a distinct clinicopathological condition with frequent skin involvement, an evolution toward leukaemia and a rapidly aggressive course. We report the case of a 64-year-old woman who presented with a haematodermic CD4+CD56+CD123+ neoplasm affecting the left cheek; the initial staging was otherwise negative. Despite this early stage of the disease, aggressive treatment including methotrexate-asparaginase and local radiotherapy was proposed as first-line therapy. Complete clinical remission was rapidly reached and the patient was still alive after > 30 months of follow-up. To date there is no consensus on the first-line treatment for such patients but intensive treatment is probably needed immediately even in cases of localized disease. The response obtained with CHOP (cyclophosphamide, doxyrubicin, vincristine, prednisone) or CHOP-like chemotherapy regimens is disappointing. Other regimens, such as those used in acute leukaemia, may improve the outcome of these patients.

Dermoscopy of fully regressive cutaneous melanoma.

BACKGROUND: Metastatic melanoma of unknown origin is a difficult challenge diagnostically and therapeutically. Diagnosis of the putative primary lesion is difficult. This difficulty increases when the primary lesion has undergone complete regression. OBJECTIVE: To define the dermoscopic features of fully regressed melanoma. PATIENTS AND METHODS: A single-institution, register-based study of an unselected consecutive series of seven cases of metastatic melanoma in the lymph nodes with no known or visible primary lesion was carried out. Skin examination included dermoscopy; when a suspicious area was found, observed dermoscopic features were recorded and a biopsy was performed. Diagnosis of completely regressive cutaneous melanoma was based on clinical-pathological correlation according to widely accepted criteria. RESULTS: Seven dermoscopic features were associated with completely regressive melanoma: scar-like depigmentation (100%); pink coloration of the background (100%); linear-irregular vessels (86%); globular pattern of the vessels (43%); remnants of pigmentation (86%), either macular (43%) or with a peppering aspect (43%); and white lighter transverse bands (43%). The last feature was only observed with polarized light dermoscopy devices. CONCLUSION: Dermoscopy more accurately distinguishes the vascular, pigmentary and scarring changes of fully regressive melanoma. We believe that dermoscopy should be included in the search for a regressive primary lesion in case of metastatic melanoma of unknown origin.

TGFbeta inhibits CD1d expression on dendritic cells.

The CD1 family of cell surface glycoprotein has been demonstrated to be a third lineage of antigen-presenting molecules for specific T cell responses. They present lipidic, glycolipidic antigen and hydrophobic peptide to T cells. CD1d restricted T cells play a role in autoimmune disease and in tumor immunity. Transforming growth factor beta (TGFbeta), a member of the family of polypeptide growth factors synthetized by human keratinocytes, has inhibitory effects on proliferation and differentiation of immune cells, especially on CD1d-restricted natural killer T cells. These properties led us to investigate the role of TGFbeta in CD1d expression on dendritic cells (DC), which are known to play a key role in initiation of the immune response. Here, we observed CD1d molecules on DC developed from PBMC with GM-CSF and IL4 but not with GM-CSF, IL4 and TGFbeta for 7 d. RT-PCR and FACS analysis (mAb 42.1) performed at various stages of differentiation on CD34+ HPC show that CD1d mRNA levels and CD1d molecule expression at the cell surface decreased progressively during the differentiation process. Thus, while committing DC-precursors differentiation toward the Langerhans cell (LC) pathway, TGFbeta likely inhibits CD1d transcription. Therefore, LC freshly recovered from epidermal sheet were evaluated by flow cytometry. In accordance with in vitro observation, they did not expressed measurable levels of CD1d molecules at the cell membrane. Thus, TGFbeta produced by keratinocytes contribute to selectively downregulate CD1d expression on intraepidermal-resident LC.

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.

Squamous cell carcinoma of the nail apparatus: clinicopathological study of 35 cases.

BACKGROUND: Subungual squamous cell carcinoma (SCC) is rare. Its diagnosis is often missed or delayed because the clinical presentation is often atypical and can mimic other conditions such as verruca vulgaris, onychomycosis, trauma-induced nail dystrophy or exostosis. OBJECTIVES: To define the different clinical presentations and the main pathological features and to evaluate the most appropriate surgical management of subungual SCC. METHODS: A retrospective review of all the cases of subungual SCC seen in our institution over a 5-year period. RESULTS: Thirty-five cases were selected. The spectrum of the clinical features encountered was extremely large including leuconychia, subungual hyperkeratosis, trachonychia, subungual tumoral syndrome, longitudinal erythronychia and melanonychia. Most cases (31 of 35) were invasive. Relapse rate after surgical treatment was low after wide surgical excision (5%) of the nail apparatus or amputation of the digit. However, limited surgical excision led to more frequent relapses (56%). CONCLUSIONS: Nail apparatus SCC is often misdiagnosed. Most cases are invasive at the time of diagnosis. Wide surgical excision bears a lower risk of relapse. Micrographic surgery should be considered for a better control in cases treated with limited surgical excision.

Fine-needle aspiration biopsy with ultrasound guidance in patients with malignant melanoma and palpable lymph nodes.

BACKGROUND: Recurrence after treatment of stage I-II melanoma involves regional lymph nodes in about 50% of patients. A reliable method is needed to evaluate lymph node status (metastatic or not) in the case of palpable lymph nodes. OBJECTIVES: To evaluate the efficiency of fine-needle aspiration biopsy (FNAB) in examining clinically detected suspicious lymph node in patients followed up after surgical removal of stage I-II melanoma. PATIENTS AND METHODS: One hundred and twenty FNABs were performed in 67 patients with a suspicious node in an open study conducted in a French melanoma regional referral centre, Hôpital de l'Hôtel-Dieu. Cytodiagnosis was classified as positive, negative, inadequate or inconclusive. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were calculated after final histopathological evaluation. RESULTS: Fifty-eight of 120 FNABs were positive (48%), 50 of 120 (42%) were negative, four of 120 (3%) were inconclusive and eight of 120 (7%) were inadequate. Among the 108 FNABs in which a definitive diagnosis could be given, sensitivity was 98.2% [95% confidence interval (CI) 90.7-99.9] and specificity was 96.1% (95% CI 86.8-98.9). CONCLUSIONS: FNAB under ultrasound guidance is an efficient tool to discriminate better between cases in which surgical treatment of the lymph node basin should be performed and patients who should return for follow-up. Surgical treatment appears to be required in cases of positive FNAB or in inconclusive cases.

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.