Amelanotic lentigo maligna and amelanotic lentigo maligna melanoma: a report of three cases mimicking intraepidermal squamous carcinoma

The clinical diagnosis of amelanotic melanoma may pose diagnostic difficulties. We report three cases of amelanotic lentigo maligna, two of which developed an invasive component (lentigo maligna melanoma). The clinical appearances in each case mimicked intraepidermal squamous carcinoma.     

A comparison of dermoscopic features among lentigo senilis/initial seborrheic keratosis, seborrheic keratosis, lentigo maligna and lentigo maligna melanoma on the face

Clinical differentiation of facial lentigo senilis/initial seborrheic keratosis (LS/ISK), seborrheic keratosis (SK), lentigo maligna (LM), and lentigo maligna melanoma (LMM) can be difficult. Dermoscopy improves the diagnoses in pigmented skin lesions (PSLs), but it is not helpful for the sun-exposed face because of the flat rete ridges without network-derived features. Therefore, development of new diagnostic criteria for this particular localization is a current issue of dermatology. In this retrospective study, dermoscopic slides of facial pigmented skin lesions of 66 patients referred to two clinics in Turkey were evaluated. Our aim was to determine the reliability of dermoscopy in the differentiation of these entities. The facial PSLs of 66 patients (34 males and 32 females) (median age: 58.2) were photographed with a Dermaphot (Heine, Hersching, Germany) over a five year period from November of 1995 to May of 2000. All of the dermoscopic slides were analysed according to 27 dermoscopic criteria developed by Schiffner et al. This data set contained 22 histologically proven malignant (14 LM, 8 early LMM) and 44 benign (18 SK, 26 LS/ISK) PSLs. In general, asymmetric pigmented follicular openings, dark streaks, slate-gray streaks, dark globules, slate-gray globules, dark dots, dark rhomboidal structures, light brown rhomboidal structures, dark homogeneous areas and dark pseudonetworks were statistically significant for malignant growth. On the other hand, milia-like cysts, pseudofollicular openings, cerebriform structures, light brown globules, light brown dots, light brown homogeneous areas, yellow opaque homogeneous areas, and light brown pseudonetworks were statistically significant for benign growth. This research emphasizes that dermoscopic features on the face differ from criteria used in other locations of the body. Analysis of the data suggests that dermoscopy can be used in the differentiation of LS/ISK, SK, LM and LMM from each other.     

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.     

Amelanotic malignant melanoma following cryosurgery for atypical lentigo maligna

Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.     

Amelanotic lentigo maligna melanoma: a unique case and review of the literature

It has been estimated that 2 percent of all melanomas are clinically amelanotic, with amelanotic lentigo maligna melanoma being an even rarer presentation. These neoplasms have presented clinically as neurodermatitis, eczema, and erythema. Given the lack of clinical markers and subsequent delay in diagnosis of these lesions, they are potentially more dangerous than pigmented lentigo maligna melanomas. We report a case of an amelanotic lentigo maligna melanoma presenting as an ill-defined edematous area on the left cheek of an elderly woman.     

One-year follow-up of a lentigo maligna: first dermoscopic signs of growth

We report a 64-year-old man with a pigmented lesion on his forehead, initially thought to be actinic lentigo. At follow-up 1 year later the lesion had increased in size and showed new areas of pigmentation. Dermoscopic observation and biopsy led to a diagnosis of lentigo maligna and the lesion was excised. The dermoscopic features indicative of early growth of lentigo maligna are identified and discussed.     

Imiquimod: a novel treatment for lentigo maligna

Lentigo maligna is the in situ phase of lentigo maligna melanoma, and if left untreated it may progress to invasive melanoma. It most commonly occurs on the exposed sites of the face and neck of middle-aged or elderly patients. Conventional surgery using a 5-10 mm margin is the recommended treatment; however, lesions can be quite large and surgical removal may involve extensive plastic repair. We report an elderly patient with a large lentigo maligna on the scalp who was reluctant to have surgery. We tried topical imiquimod 5% cream (Aldara), a local immunomodulator, which has recently become available for the treatment of external genital and perianal warts. Initially used over a test area and then over the whole of the lesion, for a total of 7 months, the imiquimod cream resulted in complete clinical and histological cure. The patient has been followed up for 9 months without evidence of recurrence.     

Amelanotic lentigo maligna melanoma manifesting as a dermatitislike plaque

A 72-year-old man with a previous history of an amelanotic melanoma on his left forearm had an erythematous plaque excised from his right shoulder. Although the clinical impression was a dermatitis, a biopsy specimen revealed an amelanotic lentigo maligna melanoma. To our knowledge, this is the first patient described with an amelanotic lentigo maligna melanoma as a second primary tumor to an apparent previous amelanotic melanoma, manifesting as a dermatitislike plaque.     

Dermoscopy for early detection of facial lentigo maligna

Up until now, only lesions selected on the basis of their clinical atypia or which appear equivocal on naked eye examination have been shown to benefit from the use of dermoscopy. In our experience, dermoscopic evaluation of lesions located on the face may require a different approach, as a histopathological diagnosis of malignancy is not uncommon in clinically trivial lesions (i.e. lesions lacking the ABCD criteria for clinical suspicion). Moreover, at this site dermoscopy reveals specific criteria according to the particular histological architecture shown by sun-damaged skin. We report four cases of lentigo maligna (LM) of the face whose identification depended on dermoscopic examination which was performed routinely on all facial lesions, as the lesions did not show ABCD clinical criteria for malignancy. In our experience, the identification of early signs of malignancy by dermoscopy may indicate the excision of LM at an early phase, before the lesion is associated with the ABCD signs of melanoma. Dermatologists should avoid the mistake of immediately excluding a diagnosis of malignancy when examining an ABCD-negative pigmented skin lesion of the face.     

Following lentigo maligna may not prevent the development of life-threatening melanoma.

BACKGROUND--Management of lentigo maligna (Hutchinson's melanotic freckle, in situ lentigo maligna melanoma) by regular observation relies on the detection of invasive melanoma before it has developed significant life-threatening potential. Recent studies indicate that lentigo maligna melanoma does not have a better prognosis than other forms of melanoma. OBSERVATIONS--A case is reported of an amelanotic lentigo maligna that evolved from a macular lesion to a deeply invasive, amelanotic, lentigo maligna melanoma within 6 months. The melanoma was Clark level IV and measured 3.0 mm in maximum tumor thickness. CONCLUSIONS--Observation of lentigo maligna at 6-month intervals would not seem to be sufficiently reliable in detecting the development of invasive lentigo maligna melanoma before it becomes a life-threatening disease. Early surgical excision is the treatment of choice.     

Cryosurgical treatment of lentigo maligna

Background: Lentigo maligna (LM) is a common melanocytic malignancy which requires therapy because of the risk of progression to invasive lentigo maligna melanoma which a much worse prognosis. Patients and Methods: 18 patients with clinical and histopathological diagnosis of LM were treated with cryosurgery.The patients were older Caucasians (mean age 59.5 years) and 11 were male. They were chosen for cryosurgery because the lesion posed a surgical challenge or the patient was not a good surgical candidate. They were treated with two freeze-thaw cycles of liquid nitrogen under local anesthesia in a single sitting. Lesions larger than 2 cm² were divided into smaller segments for freezing. Results: The lesions resolved clinically in all cases, with no recurrence or metas-tasis detected during a mean follow-up of 75.5 months. Some patients developed hypopigmented scars. Conclusions: Cryosurgery with liquid nitrogen is an efficient, safe and in most cases aesthetically acceptable alternative method to treat LM.     

Aggressive amelanotic lentigo maligna

A 66-year-old woman had a long-standing, scaly erythematous lesion on her left temple which histologically showed features of amelanotic lentigo maligna. It had recurred on numerous occasions over a period of 17 years, in spite of multiple attempts at curative surgery. There were also recurrences within a skin graft which, to our knowledge, has not been documented previously with lentigo maligna. In spite of the prolonged course, and extensive intraepidermal melanocytic proliferation amounting to melanoma in situ, there has been no evidence of dermal invasion. The lack of pigmentation in such lesions means that clinical definition of margins is highly inaccurate. In view of the aggressive horizontal growth phase of this lesion, with rapid recurrence following surgery, it was treated with electron beam therapy, and this has resulted in complete clinical remission. This most unusual case illustrates the potential difficulties in diagnosis and management of amelanotic lentigo maligna.     

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.     

Amelanotic lentigo maligna managed with topical imiquimod as immunotherapy

Clinically amelanotic lentigo maligna often resembles an inflammatory lesion rather than a melanoma in situ. We present two cases of extensive amelanotic lentigo maligna presenting as gradually enlarging erythematous patches on the faces of women following incomplete excisions of lentigo maligna. Because of their site and size, therapeutic options were limited; the lesions have, however, resolved (clinically and histologically) following the topical application of 5% imiquimod cream. We discuss the rationale for the use of imiquimod in the treatment of lentigo maligna.     

Pagetoid malignant melanoma and lentigo maligna melanoma of toe

Summary Two cases of malignant melanoma on the toe of middle-aged women were examined chiefly by the fluorescence method of Falck and Hillarp. In one of the patients, histopathology of the pigmented tumor on the left middle toe was a Pagetoid (superficial spreading) melanoma in situ, and the subungual granulomatous lesion on the right great toe in the other patient was a lentigo maligna melanoma. On fluorescence microscopy, characteristic findings of the pigment cells lying in the epidermis of both types may be summarized as follows: In the Pagetoid melanoma, the melanoma cells are ovoid, lack dendritic processes, and emit specific yellow fluorescence. In the lentigo maligna melanoma, the pigment cells clearly show dendritic processes, and emit specific green fluorescence.     

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.     

Treatment of lentigo maligna

Lentigo maligna (LM) is the in situ phase of lentigo maligna melanoma (LMM) and, if left untreated, 30-50% of cases will progress to LMM, which is now thought to behave as aggressively as any other melanoma. Literature on the of treatment of LM including conventional surgery, micrographic Mohs surgery, cryosurgery, radiotherapy, electrodesiccation and curettage, 5-fluorouracil (5-FU), azelaic acid, retinoic acid and lasers are reviewed. It is concluded that micro-graphic Mohs surgery has the lowest recurrence rates and that conventional surgery, cryosurgery and radiotherapy all have recurrence rates in the order of 7-10%. Therefore, on the basis of the current literature available, all three of these methods could be recommended as primary treatment of LM. It is extremely important when choosing one of the above treatments that the physician is adequately trained in the appropriate technique and understands the limitation of the method used and the need for close follow up of the patient     

Prolonged evolution of a lentigo maligna

Lentigo maligna (LM) is a melanocytic lesion which is a potential precursor to melanoma and often has a prolonged intraepidermal growth phase before evolving into lentigo maligna melanoma (LMM). LM is also noted for its tendency to locally recur after treatment. We present a patient who had a persistent LM on her left cheek which, despite multiple excisions, persisted and transformed into a partially amelanotic LMM roughly three decades later. Our patient's course was also notable for this melanoma recurring at the edge of, and subsequently migrating into, a previously placed skin graft.     

Identification of progenitor cancer stem cell in lentigo maligna melanoma

ABSTRACT:  The potential role of stem cells in neoplasia has aroused considerable interest over the past few years. A number of known biologic characteristics of melanomas support the theory that they may originate in a mutated stem cell. Melanocytic stem cell markers have been described recently. Moreover, the CD133 cells that show surface markers for CD34 are stem cells primitive. These stem cells are capable of differentiating into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. The identification of cancer stem/initiating cells with a crucial role in tumor formation may open up new pharmacologic perspectives. The purpose of this study is to detect the expression of CD133 and CD34, two putative markers of cancer stem cells in the lentigo maligna melanoma. Thirty cases of lentigo maligna melanoma were analyzed using indirect immunohistochemical staining. The vast majority of the samples analyzed showed the presence of rare cells, which were clearly positive for CD133 and CD34. Strong CD133 and CD34 staining was found in the outer root sheath of the mid-lower hair follicles, intermixed with atypical melanocytes extending along layers of the hair follicles. A number of these staminal cells were adjacent and intermixed with melanoma cells. This study supports the stem cell origin of this tumor and suggests that the precursor of the melanoma in question is a stem-like cell rather than the primitive melanoblast committed to be exclusively involved in melanocytic differentiation.     

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.