Pigmented actinic keratoses

Four cases of pigmented solar keratoses are reported. The brownish pigmented lesions on sun-exposed skin are clinically similar to lentigo simplex, lentigo senilis, lentigo maligna and pigmented seborrhoic keratosis. The surface is rather rough. Histologically, in addition to characteristic findings of solar keratoses, melanin can be found within the lower epidermis and within melanophages in the upper dermis (incontinence of pigment).     

Lentigo Maligna: Review of Salient Characteristics and Management

Lentigo maligna is a melanocytic neoplasm, often regarded as ‘melanoma in situ,’ which may progress to lentigo maligna melanoma. Lentigo maligna clinically presents as a pigmented, asymmetric macule that originates on the head and neck and spreads slowly. The preferred method for diagnosing lentigo maligna is excisional biopsy. Histology shows proliferation of atypical melanocytes at the epidermal–dermal junction in small nests or single cells. The differential diagnosis includes solar lentigo, seborrheic keratosis, lichen planus-like keratosis, pigmented actinic keratosis, and melanocytic nevus. Stains used in diagnosis include hematoxylin and eosin, HMB-45, MART-1/Melan-A, Mel-5, and S-100. Surgical excision is the preferred treatment for lentigo maligna. Second-line techniques include medical (topical imiquimod) and destructive therapy.     

Utilidad clínica de la microscopia confocal de reflectancia en el manejo del lentigo maligno melanoma

Facial lentigo maligna melanoma can be a diagnostic challenge in daily clinical practice as it has similar clinical and morphological features to other lesions such as solar lentigines and pigmented actinic keratoses. Confocal microscopy is a noninvasive technique that provides real-time images of the epidermis and superficial dermis with cellular-level resolution. We describe 3 cases of suspected facial lentigo maligna that were assessed using dermoscopy and confocal microscopy before histopathology study. In the first case, diagnosed as lentigo maligna melanoma, presurgical mapping by confocal microscopy was performed to define the margins more accurately. In the second and third cases, with a clinical and dermoscopic suspicion of lentigo maligna melanoma, confocal microscopy was used to identify the optimal site for biopsy.     

Diagnostic utility of dermoscopy in pigmented actinic keratosis

The diagnosis of pigmented actinic keratosis can be complicated in clinical practice. The differential diagnosis with lentigo maligna melanoma can be difficult due to common clinical and dermoscopic characteristics. We present 5 cases of pigmented actinic keratosis in 4 patients. The most common dermoscopic finding was a grayish-brown granulation with a perifollicular distribution, present in all lesions, followed by rhomboidal structures in 4 cases, and an annular-granular pattern in 3. In no case were asymmetrical pigmented follicular openings observed. We draw attention to key findings that aid preoperative diagnosis of pigmented actinic keratosis.     

Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis

Pigmented actinic keratosis is one of the simulators of early melanoma in situ from severely sun-damaged skin. Close scrutiny of the hematoxylin and eosin stained section does not always allow an unequivocal diagnosis, because it is sometimes difficult to distinguish pigmented keratinocytes from melanocytes. Immunohistochemical stains, such as S-100 and HMB-45, are used routinely to address this problem. Melan-A, also known as MART-1, is an additional melanocytic marker and has proved to be useful in identifying metastatic tumors of melanocytic origin. The usefulness of this marker to discriminate pigmented actinic keratosis from early melanoma in situ, however, has not yet been a subject of investigation. In this study we evaluated Melan-A expression in ten unequivocal cases of pigmented actinic keratosis and compared the staining pattern with that of S-100, HMB-45, and tyrosinase. In all ten cases the number of cells highlighted with Melan-A was by far larger than those labeled with S-100, HMB-45, and tyrosinase. Four cases showed clusters of Melan-A positive cells being suggestive of melanocytic nests. Even areas of normal skin adjacent to the actinic keratosis featured prominent staining of Melan-A, but only inconsistent labeling of intraepidermal melanocytes with S-100, HMB-45, and tyrosinase. We therefore believe that Melan-A is a more sensitive marker for intraepidermal melanocytes than S-100, HMB-45, and tyrosinase. In addition there may be expression of Melan-A in keratinocytes and nonmelanocytic cells. To avoid an erroneous diagnosis of malignant melanoma one should therefore interpret results obtained from Melan-A stained slides carefully and in the context with other melanocytic markers.     

Key points in dermoscopic differentiation between lentigo maligna and solar lentigo

A clinical diagnosis of lentigo maligna at an early stage is often difficult even for experienced dermatologists. Differential diagnoses would include solar lentigo, early lesions of seborrheic keratosis, lichen planus-like keratosis, pigmented actinic keratosis and melanocytic nevus. Dermoscopy has been shown to have higher diagnostic accuracy, especially in the diagnosis of pigmented skin lesions, in the past two decades. To aim of the present study was to review the diagnostic key points on dermoscopy in the published work to differentiate lentigo maligna from other differential diagnoses and reassess these important features on dermoscopy for specificity by describing the findings in detail. Diagnostic key points for lentigo maligna/lentigo maligna melanoma on dermoscopy are asymmetrical pigmented follicular openings, rhomboidal structures, annular-granular structures and gray pseudo-network. Lentigo maligna, at first, seems to occur as asymmetrical pigmented follicular openings and/or annular-granular structures, then expand and develop into the rhomboidal structures. Annular-granular structures and gray pseudo-network seem to be observed also in regressive areas of solar lentigo/initial seborrheic keratosis, lichen planus-like keratosis and pigmented actinic keratosis. The four important criteria on dermoscopy for the diagnosis of lentigo maligna have been reviewed, and the former two criteria seem to be more specific, but it might be difficult to recognize these findings without misinterpretation. The latter two seem to be not so specific as they would also be demonstrated in other pigmented epidermal lesions, although the distribution of the structures in these disorders would be inclined to be more homogeneous than that of lentigo maligna.     

Spreading pigmented actinic keratosis--diagnosis and therapy

Spreading pigmented actinic kereatosis is a rarely described premalignant epidermal lesion occurring on the skin following exposure to the sun. On clinical examination it may be difficult to distinguish it from pigmented seborrheic keratosis or lentigo maligna. Spreading growth and a diameter greater than 1.5 cm are characteristic features. We report a case of spreading pigmented actinic keratosis in a 61-year-old patient.     

Diagnosis and management of facial pigmented macules

The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided eye, the accurate diagnosis and management of pigmented facial macules remains one of the most challenging scenarios in daily practice. This is related to the fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and LM may reveal overlapping criteria, making their differential diagnosis clinically difficult. For this reason, practical rules have been introduced, which should help to minimize the risk for inappropriate diagnosis and management of LM.     

Atypical lentiginous junctional naevi of the elderly and melanoma

The diagnosis of atypical lentiginous melanocytic naevi in chronic sun-damaged skin is a clinical and pathological challenge. Mottled skin in the elderly is a result of extensive freckling, guttate hypomelanosis, solar lentigines, seborrhoeic keratoses and small dark lentigines. In addition, atypical lentiginous junctional naevi may be seen as isolated lesions and may merge with lesions that are indistinguishable from lentigo maligna. The predominant site distribution of such lesions on the trunk and limbs and the presence of a nested naevoid pattern on biopsy differs from classical lentigo maligna, which develops mainly on the head and neck. Based on case studies combining dermatoscopy with clinical and pathological features, we have found that atypical lentiginous junctional naevi of the elderly may evolve to lentigo maligna and in some cases to small cell (naevoid) melanomas. Such lesions have been previously classified as dysplastic naevi, atypical melanocytic hyperplasia, atypical melanocytic proliferation, atypical lentiginous melanocytic proliferation or premalignant melanosis (McGovern). The current definition of lentigo maligna appears too narrow and the pathway to lentigo maligna in the elderly skin may include a naevoid subset.     

Unstable solar lentigo: A defined separate entity

An unstable solar lentigo is a solar lentigo with areas of melanocytic hyperplasia not extending past the margin of the lesion. They are discrete, macular, pigmented lesions arising on sun‐damaged skin and a subset of typical solar lentigos. Clinically they differ from usual solar lentigines in often being solitary or larger and darker than adjacent solar lentigines. These lesions are of clinical importance as they can arise in close proximity to lentigo maligna and in a single lesion there can be demonstrated changes of solar lentigo, unstable solar lentigo and lentigo maligna. These observations led us to conjecture that unstable solar lentigos could be a precursor lesion to lentigo maligna. In this article we examine the possibility that lentigo maligna can arise within a solar lentigo through an intermediate lesion, the unstable solar lentigo. We propose that the histopathological recognition of this entity will allow for future research into its behaviour and thus management. We review difficulties in the diagnosis of single cell predominant melanocytic proliferations and the concept of unstable lentigo in view of the literature and clinical experience supporting the proposal of its recognition as a separate entity.     

Flat pigmented macules on sun-damaged skin of the head/neck: Junctional nevus,atypical lentiginous nevus,or melanoma in situ?

The clinical recognition of lentigo maligna (LM) in the mottled chronic sun-damaged skin can be challenging, because it shares many clinical features with other pigmented macules that commonly arise on sun-damaged skin. These include solar lentigo, flat seborrheic keratosis, and pigmented actinic keratosis, but almost never “nevus.” The reason nevus is not included in the differential diagnosis of LM can be explained by the fact that the stereotypical appearance of a facial nevus differs remarkably from that of an LM. Facial nevi in adults are usually nodular, dome-shaped, well-defined, and hypopigmented (ie, intradermal nevus of the Miescher type), whereas LM typically appears as a flat, ill-defined, and pigmented macule. Although this concept based on clinical observations sounds reasonable, clinicians apply it often only unconsciously and accept a given histopathologic diagnosis of a “junctional or lentiginous nevus” of a flat pigmented facial macule without the necessary criticism about its clinicopathologic validity.     

Merkel cell hyperplasia in hypertrophic varieties of actinic keratoses

Hyperplasia and dysplasia of the epidermal neuroendocrine cells (i.e., Merkel cells, MC) have been suggested in lesional skin of actinic keratosis and chronic radiation dermatitis. Because several histological types of actinic keratosis exist, we investigated the occurrence of such MC hyperplasia according to each of the histological patterns. Using an immunoperoxidase technique and the cytokeratin monoclonal antibody CAM 5.2, we counted 0.02 CAM 5.2 + cells (i.e., MC)/mm epidermis in normal-appearing perilesional skin; 0.05 MC/mm epidermis in nonhypertrophic actinic keratoses and 4.09 MC/mm epidermis in hypertrophic actinic keratoses. This number was as high as 14.40 MC/mm epidermis when hypertrophic actinic keratoses showed club-like epithelial proliferations. In contrast to normal epidermis, where MC were found isolated within the basal cell layer, MC clustered in these club-like epithelial proliferations as they did in the normal parakeratotic zone of the rabbit lip epithelium. The significance of this selective MC hyperplasia is discussed.     

Topical colchicine therapy for actinic keratoses

BACKGROUND: The beneficial effect of topical colchicine therapy for actinic keratoses has already been described in 1968. Objective: To confirm that the application of a 1% colchicine gel is a safe and effective treatment for actinic keratoses. METHODS: Twenty patients were included in a double-blinded protocol. They all had actinic keratoses on the scalp, most of which had been previously treated with 5-fluorouracil or cryotherapy. Ten patients applied twice daily on the forehead a hydrophilic gel (placebo group), while the other 10 where treated with the same gel containing 1% of colchicine (colchicine group). Erythema and efficacy were evaluated at each control on days 7, 30 and 60, with repetitive blood tests to exclude a possible systemic absorption. RESULTS: A complete healing of the solar keratoses was observed in 7 out of the 10 patients treated with 1% colchicine gel; these showed no recurrence after 2 months of follow-up. Burning and itching occurred only in the colchicine group after 2 or 3 days of application, with an inflammatory reaction on the areas where the gel was applied, while pustules and crusts were located specifically on the actinic keratoses. Repeated blood controls showed that there was no systemic absorption. CONCLUSIONS: This double-blind placebo-controlled study confirms the activity of colchicine for the treatment of actinic keratosis. A comparison with other topical treatments in terms of efficacy and practicability is needed.     

Pitfalls in the clinical and dermoscopic diagnosis of pigmented actinic keratosis

Pigmented actinic keratosis and melanoma may exhibit overlapping clinical features, thus representing a diagnostic challenge for dermatologists. Although the differentiation between these two entities is traditionally done by histopathology, dermoscopy has been utilized as a useful additional aid for improving the clinical diagnostic accuracy of such pigmented skin lesions. We report the clinical and dermoscopic features of two pigmented actinic keratoses to discuss the difficulties in their preoperative differential diagnosis.     

Simultaneous occurrence of multiple melanoma in situ on sundamaged skin (lentigo maligna), solar lentigo and labial melanosis: the value of dermoscopy in diagnosis

We report on a patient developing simultaneous occurrence of lentigo maligna lesions, solar lentigines and an extensive melanosis of the oral mucosa. Diagnostically, epiluminescence microscopy had a relevant role in the preoperative assessment and selection of suspicious pigmented lesions, as the lesions histologically labelled as lentigo maligna and solar lentigo were clinically indistinguishable. We review the clinical, dermoscopic and histopathologic differential diagnosis of solar lentigo, malignant lentigo and mucosal melanosis with other melanocytic and keratinocytic lesions and discuss the possible relationship between these entities.     

Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial

BACKGROUND: Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied. OBJECTIVE: We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines. METHODS: In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months. RESULTS: Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 +/- 0.9 (mean +/- SE) and 2.5 +/- 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 +/- 1.3 (P <.05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P <.05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P <.05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle. CONCLUSION: Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin.     

Topical and light-based treatments for actinic keratoses

Actinic keratosis is currently believed to be an early stage in the evolution of squamous cell carcinoma. Active and intensive treatment of actinic keratosis may prevent the formation of invasive squamous cell carcinoma and potential metastases. While destructive methods of treatment of actinic keratosis remain the gold standard for the eradication of visible and palpable actinic keratoses, new medical therapies may accomplish this goal more comfortably and reliably for the patient. Newer topical medications, light therapy and photodynamic therapy are generating promising results that presage more widespread use in the future. These novel therapies for the early treatment of actinic keratosis may be administered in combination or serially, with the locus of treatment at any given time possibly restricted to a region of affected skin. Treatment of incipient or subclinical lesions may mitigate the risk of future squamous cell carcinomas lesions. Widespread actinic keratosis constitutes a persistent medical problem that requires long-term management. The role of traditional and novel treatments in the routine treatment of actinic keratosis will be determined by the efficacy, limitations and the practicality of each of these methods in individual patients. As the first stage of squamous cell carcinoma, actinic keratosis is worthy of prompt evaluation and active treatment.     

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.     

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.     

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already‐described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non‐melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus‐like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.