Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location.

BACKGROUND: Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated. OBJECTIVES: To reveal dermoscopic and RCM features of scalp melanoma according to lesion location and histopathology. METHODS: We retrospectively retrieved images of suspicious, atypical excised, flat melanocytic lesions of the scalp, assessed on dermoscopy and RCM at five centres, from June 2007 to April 2020. Lesions were classified according to histopathological diagnoses of nevi, lentigo maligna melanoma (LM/LMM) or superficial spreading melanoma (SSM). Clinical, dermoscopic and RCM images were evaluated; LM/LMM and SSM subtypes were compared through multivariate analysis. RESULTS: Two hundred forty-seven lesions were included. In situ melanomas were mostly LM (81.3%), while invasive melanomas were mostly SSM (75.8%). Male sex, baldness and chronic sun-damaged skin were associated with all types of melanomas and in particular with LM/LMM. LMs were mostly located in the vertex area and SSM in the frontal (OR: 8.8; P < 0.05, CI 95%) and temporal (OR: 16.7; P < 0.005, CI 95%) areas. The dermoscopy presence of pseudo-network, pigmented rhomboidal structures, obliterated hair follicles and annular-granular pattern were associated with LM diagnoses, whereas bluish-white veil was more typical of SSM. Observations on RCM of atypical roundish and dendritic cells in the epidermis were associated with SSM (42.4%) and dendritic cells with LM (62.5%) diagnoses. Folliculotropism on RCM was confirmed as a typical sign of LM. CONCLUSIONS: Flat scalp melanomas reveal specific dermoscopic and RCM features according to histopathologic type and scalp location.

Reinterpreting dermoscopic pigment network with reflectance confocal microscopy for identification of melanoma-specific features.

BACKGROUND: Pigment network is an important dermoscopic feature for melanocytic lesions, but alterations in grid line thickness are also observed in melanomas. OBJECTIVE: To investigate features of thick, thin and mixed pigment networks at dermoscopy and their respective features at reflectance confocal microscopy (RCM) for differential diagnosis, correlated with histology. METHODS: All melanocytic lesions with histological diagnosis, evaluated between January 2010 and May 2014, were enrolled and classified according to dermoscopy evaluation of the pigment networks: thin, thick and mixed. RESULTS: Thin network in melanoma was characterized by a honeycombed pattern (P < 0.001), dendritic cells (P < 0.001), atypical ringed pattern (P = 0.035) and structureless area (P = 0.012), whereas round cells (P < 0.001), dendritic cells (P < 0.001) and atypical meshwork pattern (<0.001) characterized thick network in melanoma. Mixed network type in melanoma shared honeycombed (P = 0.049) and typical ringed patterns (P = 0.045) in the thin area and round cells (P < 0.001) and atypical meshwork pattern (P < 0.001) in the thick area. Thin network in nevi was characterized by cobblestone (P < 0.001) and typical ringed patterns (P = 0.035), whereas thick network in nevi showed a typical meshwork pattern (P < 0.001). Mixed nevi shared the same features and patterns, but more frequently with inflammatory infiltrate (P = 0.047). CONCLUSION: Differential diagnosis between melanocytic lesions (nevi or melanoma) in thin, thick and mixed pigment networks observed at dermoscopy can be assisted by RCM to improve diagnostic accuracy.

The smart approach: feasibility of lentigo maligna superficial margin assessment with hand-held reflectance confocal microscopy technology.

BACKGROUND: Lentigo maligna may be challenging to clear surgically. OBJECTIVE: To evaluate feasibility of using superficial skin cuts as RCM imaging anchors for attaining negative surgical margins in lentigo maligna. METHODS: Included patients presented with lentigo maligna near cosmetically sensitive facial structures. We evaluated, with hand-held-RCM, microscopic clearance of melanoma beyond its dermoscopically detected edges. Evaluated margins were annotated using shallow skin cuts. If a margin was positive at 'first-step' RCM evaluation, we sequentially advanced the margin radially outward at that segment by 2-mm intervals until an RCM-negative margin was identified. Prior to final surgical excision, we placed sutures at the outmost skin cuts to allow comparison of RCM and histopathological margin assessments. Primary outcome measure was histopathological verification that RCM-negative margins were clear of melanoma. RESULTS: The study included 126 first-step margin evaluations in 23 patients, median age 70 years (range: 43-91). Seventeen patients (74%) had primary in-situ melanoma and six (26%) invasive melanoma, mean thickness 0.3 mm (range 0.2-0.4 mm). Six cases (26%) showed complete negative RCM margins on 'first-step', 11 (48%) were negative at 'second-step', and four (17%) at 'third-step'. In two additional cases (9%), margins clearance could not be determined via RCM due to widespread dendritic cells proliferation. The RCM-negative margins in all 21 cases proved clear of melanoma on histopathology. Of the 15 cases that returned at 1-year follow-up, none showed any residual melanoma on dermoscopic and RCM examinations. Interobserver reproducibility showed fair agreement between bedside RCM reader and blinded remote-site reader, with Spearman's rho of 0.48 and Cohen's kappa of 0.43; using bedside reader as reference, the remote reader's sensitivity was 92% and specificity 57% in positive margin detection. CONCLUSIONS: Margin mapping of lentigo maligna with hand-held-RCM, using superficial skin cuts, appears feasible. This approach needs validation by larger studies.

Spitz naevi and melanomas with similar dermoscopic patterns: can confocal microscopy differentiate?

BACKGROUND: Differentiating Spitz naevi from melanomas can be difficult both clinically and dermoscopically. Previous studies have reported the potential role of in vivo reflectance confocal microscopy (RCM) in increasing diagnostic accuracy. OBJECTIVES: To define RCM criteria that can differentiate 'false twins', namely Spitz naevi and melanomas sharing similar dermoscopic appearance. METHODS: Lesions histopathologically diagnosed as Spitz naevi or melanomas were retrospectively retrieved. They were selected to cover all dermoscopic types and were put into couples sharing similar aspects. Lesions were classified into three main dermoscopic categories: globular and starburst pattern, spitzoid with dotted vessels, and multicomponent or aspecific pattern. RESULTS: RCM findings revealed that striking cell pleomorphism within the epidermis, widespread atypical cells at the dermoepidermal junction and marked pleomorphism within nests were significantly associated with the diagnosis of melanoma, while spindled cells and peripheral clefting were found exclusively with and pathognomonic of Spitz naevi. Furthermore, the analysis of a dermoscopic subgroup highlights the importance of striking pleomorphism and spindled cells as clues to differentiate 'false twins' with globular or starburst patterns. CONCLUSIONS: The current study highlights the role of RCM in discriminating 'false twins' of Spitz naevi and melanomas for lesions showing starburst and globular patterns on dermoscopy, whereas RCM is not useful in the other dermoscopic subgroups.

Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma.

BACKGROUND: The sub-optimal diagnostic accuracy for melanoma leads to excise a high number of benign lesions, with consequent costs. Reflectance confocal microscopy (RCM) improves diagnostic specificity, thus possibly inducing a reduction in unnecessary excisions and related costs. OBJECTIVE: To estimate the influence of RCM on number of benign lesions needed to excise (NNE) a melanoma, in term of clinical outcomes and costs per patient. PATIENTS AND METHODS: Skin neoplasms excised by the dermatology public service in the Province of Modena were retrieved form centralized pathology database. Differences in NNE between the territorial service (using dermoscopy only) and the University Hospital (adding also RCM to the patients' workflow) were calculated and cost analysis was performed through a micro-costing approach. RESULTS: A large reduction in benign lesions excised at University Hospital was evident, leading to NNE of 6.25 for University Hospital, compared to 19.41 for Territorial Dermatology. Since 4320 unnecessary excisions can be saved every million inhabitants, an overall yearly saving of over 280,000 Eur can be expected from the use of RCM. CONCLUSIONS: The systematic use of RCM was dramatically affecting the number of benign lesions excised, and this can be translated in a significant cost-benefit advantage.

CD271 is expressed in melanomas with more aggressive behaviour, with correlation of characteristic morphology by in vivo reflectance confocal microscopy.

BACKGROUND: Melanoma is the most highly aggressive type of skin cancer. Its resistance to existing treatments and the rapid rise in incidence underscore the importance of acquiring a better understanding of melanomagenesis. OBJECTIVES: To assess the impact of reflectance confocal microscopy (RCM) on the description of cell morphology, which may influence the growth pattern and changes with increasing tumour severity, correlating with biological aspects. METHODS: A retrospective analysis of 30 primary melanomas in vivo, evaluated by RCM, to correlate cell morphology and cellular arrangement with a marker of melanoma progression (CD271) using immunohistochemical evaluations. RESULTS: Typical cells organized in dermal nests with peculiar in vivo confocal morphology result in melanoma with high malignancy and positivity to CD271. This architecture might be due to the presence of a type of cells, intrinsically predisposed to invasion, as a result of dedifferentiation programming, revealed by expression of the neural crest marker CD271. CONCLUSIONS: With the hypothesis that dedifferentiated cells would be strongly responsible for initiation of tumour development and progression, we propose that CD271 detection could be associated with RCM evaluation in order to detect more aggressive melanoma subtypes.

Melanoma and naevi with a globular pattern: confocal microscopy as an aid for diagnostic differentiation.

BACKGROUND: Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution. OBJECTIVES: To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects. METHODS: Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed. RESULTS: Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma. CONCLUSIONS: So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.

Morphological features of naevoid melanoma: results of a multicentre study of the International Dermoscopy Society.

BACKGROUND: Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. OBJECTIVES: To describe the clinical and dermoscopic features associated with NeM. METHODS: Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. RESULTS: Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern (n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. CONCLUSIONS: While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM.

Grading keratinocyte atypia in actinic keratosis: a correlation of reflectance confocal microscopy and histopathology.

BACKGROUND: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, with progressive trend towards squamous cell carcinoma. OBJECTIVE: To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification, through a discrete ranking. METHODS: A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written software. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the image showing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. RESULTS: Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading. CONCLUSIONS: Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading.

Hyporeflective pagetoid cells: a new clue for amelanotic melanoma diagnosis by reflectance confocal microscopy.

BACKGROUND: Amelanotic melanoma represents a diagnostic challenge both clinically and dermoscopically. Few studies based on case series have explored the possibility of using reflectance confocal microscopy (RCM) to diagnose amelanotic melanoma. OBJECTIVES: To validate a new confocal feature, named hyporeflective pagetoid cells (HPCs), for the diagnosis of amelanotic melanoma. METHODS: A group of 20 amelanotic melanomas and a control population of nonpigmented melanocytic naevi (10), hypo/nonpigmented nonmelanocytic lesions (20) and pigmented melanomas (20), imaged by RCM, were retrospectively evaluated. The presence of HPCs and other diagnosis-specific confocal features was assessed and correlated with histopathology. RESULTS: HPCs were present, and usually abundant, in the majority of amelanotic melanomas (85%). As expected, they were also observed in Spitz naevi. On histopathology, they were correlated with pagetoid infiltration of hypomelanotic melanocytes in all melanocytic lesions. Few nonmelanocytic lesions (three squamous cell carcinomas, two seborrhoeic keratoses and one basal cell carcinoma) showed the presence of HPCs. In these cases, they corresponded to enlarged or dyskeratotic keratinocytes by histopathology. CONCLUSIONS: The identification of HPCs in the epidermis is a new parameter that is frequently found in amelanotic melanoma. Possible confounders are represented by atypical keratinocytes that can be present in nonmelanocytic lesions. However, the whole architecture and the presence of additional diagnostic criteria should be considered in order to obtain a correct diagnosis.

Non-invasive in vivo dermatopathology: identification of reflectance confocal microscopic correlates to specific histological features seen in melanocytic neoplasms.

BACKGROUND: Reflectance confocal microscopy (RCM) allows for non-invasive, in vivo evaluation of skin lesions and it has been extensively applied in skin oncology although systematic studies on nevi characterization are still lacking. OBJECTIVE: The aim of this study was to determine whether reliable RCM correlates to histological features used to diagnose melanocytic neoplasms exist. METHODS: We blindly evaluated the RCM and histological features of 64 melanocytic neoplasms (19 non-dysplastic nevi, 27 dysplastic nevi, 14 melanomas) and analysed the data using Spearman's rho calculation. RESULTS: Many histological features can be identified using RCM. Elongated rete ridges corresponded on RCM to edge papillae, whereas flattened rete ridges to several features which involve dermal-epidermal junction disruption. Bridging of junctional nesting (JN) corresponded on RCM to both JN with irregular size/shape and JN with short interconnections. While we could reliably identify dermal melanocytes, the RCM features did not reliably distinguish between benign and concerning dermal melanocytic arrangements, suggesting further refinement of dermal melanocytic RCM features is needed. CONCLUSION: Reliable correlates for epidermal and junctional histological features used to diagnose melanocytic neoplasms are identifiable on RCM, suggesting harnessing histological criteria may be a reasonable method to move beyond the algorithmic approach.

Towards an in vivo morphologic classification of melanocytic nevi.

BACKGROUND: Nevi are common benign neoplasms and the main diagnostic entity in the differential diagnosis of melanoma. Reflectance confocal microscopy (RCM), a novel technique for skin imaging at cellular-level magnification, has been shown to be useful for differentiating nevi from melanoma. However, systematic studies of the specific RCM features of nevi are still lacking. OBJECTIVE: To describe the characteristic RCM features of common melanocytic nevi and to correlate them with histopathology. METHODS: A total of 180 biopsy-proven nevi were imaged with RCM prior to excision. RCM images were evaluated for the overall nevus pattern and presence of specific RCM criteria. Upon histopathology, nevi were analysed for thickness using adapted Breslow depth and Clark's level grading. RESULTS: Observed RCM patterns varied according to anatomic depth of nevi. Junctional nevi were mainly characterized on RCM by a Ringed pattern, indicating a predominantly single cell proliferation of melanocytes; in contrast, the junctional component of compound nevi appeared on RCM as a Meshwork pattern, indicating a predominantly nested-proliferation. In compound nevi, the size of dermal nests was related to the thickness of nevi. Moreover, nevi extending deeper into the dermis were more likely to display a junctional component that extended laterally beyond the dermal component and appeared on RCM as either Ringed or Meshwork pattern. Intradermal nevi showed on RCM, in almost all cases, large clods. CONCLUSIONS: The possibility for in vivo histopathological classification of nevi may help in attaining a better understanding of the origin of nevi and of nevus-related melanoma risk.

[Dermatoscopy and reflectance confocal microscopy aspects of a "nested melanoma of the elderly"]. / Aspect en dermatoscopie et en microscopie confocale par réflectance d'un « mélanome en thèques du sujet âgé ¼

BACKGROUND: We report a case of a nested melanoma of the elderly, a recently described entity, and we describe its aspect under confocal reflectance microscopy. PATIENTS AND METHODS: A 70-year-old woman presented a pigmented lesion of the left leg measuring 2 × 2.5 cm in diameter which was increasing in size. Dermatoscopic examination showed a predominantly globular pattern, with globules of irregular color and distribution. Reflectance confocal microscopy revealed the presence of dense nests at the dermo-epidermal junction with cytologic atypia and pagetoid cells. The histological appearance was overlapping and a diagnosis of nested melanoma of the elderly was made. COMMENTS: The presence in an older subject of a large pigmented lesion with an irregular globular pattern should be suspected of nested melanoma of the elderly. Reflectance confocal microscopy may be useful in the case of such difficult lesions to proceed with more confidence to surgical excision.

Is confocal microscopy a valuable tool in diagnosing nodular lesions? A study of 140 cases.

BACKGROUND: Nodular lesions pose diagnostic challenges because nodular melanoma may simulate all kinds of melanocytic and nonmelanocytic lesions. Reflectance confocal microscopy (RCM) is a novel technique that allows visualization of the skin at nearly histological resolution although limited laser depth penetration hampers visualization of the deep dermis. OBJECTIVES: We sought to assess whether the diagnostic accuracy of RCM was comparable to histopathology for the diagnosis of nodular lesions, and to identify possible limitations of this technique. METHODS: We retrospectively evaluated 140 nodules by means of RCM while blinded from the histopathological diagnosis. At the end of the study the patient codes were broken and the evaluations were matched with histopathological diagnosis before performing statistical analysis. RESULTS: The study consisted of 140 nodular lesions (23 'pure' nodular melanomas, nine melanoma metastases, 28 BCCs, six invasive SCCs, 32 naevi, 14 seborrhoeic keratoses, 17 dermatofibromas, five vascular lesions and six other lesions). RCM correctly diagnosed 121 of 140 lesions (86.4%); eight of 140 (5.7%) lesions revealed discordance between histopathology and confocal microscopy. Eight of the 140 (5.7%) cases were not evaluable by means of RCM due to the presence of ulceration or hyperkeratosis and three cases showed a nonspecific pattern. Interestingly, confocal microscopy reached a 96.5% sensitivity and 94.1% specificity (area under curve 0.970) (95% CI 0.924-1.015) (P < 0.001) for the diagnosis of melanoma. CONCLUSIONS: The study is retrospective and lesions were not included on the basis of their diagnostic difficulty. Despite the limited laser depth penetration of RCM, this imaging tool represents an effective instrument in diagnosing nodular lesions; however, for fully ulcerated lesions or when a marked hyperkeratosis is present, biopsy should always be performed. Prospective studies on difficult-to-diagnose nodules should be performed to analyse further the pros and cons of RCM in skin cancer diagnosis.

Small-diameter melanocytic lesions: morphological analysis by means of in vivo confocal microscopy.

BACKGROUND: Small-diameter melanocytic lesions represent a diagnostic challenge for clinicians, as they do not follow the ABCD rule for diagnosis and do not always display reliable histopathological criteria. OBJECTIVES: To analyse the confocal features of small-diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphological criteria. METHODS: Twenty-four melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of the Pearson χ(2) test. Odds ratios and 95% confidence intervals were calculated for each parameter. Binary logistic regression was performed to identify the reflectance confocal microscopy (RCM) independently significant features for melanoma diagnosis. RESULTS: The seven-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. nonspecific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent diagnosis of small melanoma. The presence of atypical cells, more than five atypical cells per mm(2) , and roundish atypical cells at the dermoepidermal junction showed the highest odds ratios. From logistic regression, the presence of at least five pagetoid cells per mm(2) , tangled lines within the epidermis, and atypical roundish cells at the dermoepidermal junction resulted in the three independent confocal parameters that characterized small melanomas. CONCLUSIONS: Small melanomas frequently reveal specific dermoscopic and confocal features. Moreover, the combination of dermoscopy and RCM can lead to a correct diagnosis of a number of naevi that share some morphological aspects with melanomas.

Confocal microscopy of recurrent naevi and recurrent melanomas: a retrospective morphological study.

BACKGROUND: Repigmentation within a scar after different procedures (shave biopsy, partial excision, cryotherapy, laser) is a challenging diagnostic situation. OBJECTIVES: To determine distinct dermoscopic and confocal microscopic features in a series of histopathologically proven melanocytic proliferations within a scar. METHODS: Clinical, dermoscopic and confocal microscopic images were acquired before surgical excision in seven patients with repigmentation within a scar. The evaluation of the dermoscopic and confocal features was performed in blind to the final histopathological diagnosis that was obtained in all cases. RESULTS: Dermoscopically, the repigmentation in recurrent naevi (three patients) was confined within the scar while it extended beyond the scar in melanomas. This clue was more evident upon reflectance confocal microscopy (RCM). Confocally, recurrent naevi failed to exhibit prominent pagetoid or lateral spread of melanocytes and atypical nests at the junction, even though some cases showed atypical cells in the junctional component. However, these were few in number and cytologically monomorphous and allowed the diagnosis of a benign neoplasm with confidence. On the other hand, melanomas arising on a scar (four patients) revealed dendritic-shaped melanocytes arranged in sheets, and pagetoid and lateral spread of dendritic cells extending beyond the scar. Those confocal aspects were well correlated with the histopathological findings. CONCLUSIONS: The integration of clinical, dermoscopic and RCM aspects offers the possibility to discern reliably the nature in cases of repigmentation on a scar.