Non-acral Sites Research Articles

Acral pseudolymphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature

Acral pseudolymphomatous angiokeratoma of children (APACHE) is clinically characterized by angiomatous papules that preferentially affect acral areas of children. It is currently believed to be a variant of pseudolymphoma rather than angiokeratoma. Histopathologically, a mixed inflammatory cell infiltrate comprising B- and T-lymphocytes and a proliferation of thick-walled blood vessels are the hallmark. In the literature, although more adult cases are being described, the clinical, epidemiologic and histopathologic data of this presentation is scant. We report a 76-year-old man who presented with a 5-year history of progressively increasing asymptomatic dusky dome-shaped papules and plaques on his upper and lower extremities. Histology was consistent with APACHE. After reviewing all the adult cases in the literature and comparing them to the classical variant in children, we found no significant difference warranting separating these two variants. We prefer the designation "papular angiolymphoid hyperplasia" to APACHE as it encompasses all the childhood and adult cases involving acral and nonacral sites and highlights the histological and sometimes clinical similarities this entity shares with angiolymphoid hyperplasia with eosinophilia.

Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure

In melanoma, mutations in KIT are most frequent in acral and mucosal subtypes and rarely reported in cutaneous melanomas particularly those associated with intermittent UV exposure. Conversely melanomas arising within chronic sun damaged skin are considered to harbour KIT mutations at higher rates. To characterize the frequency of KIT mutations in a representative melanoma population, 261 patients from two Australian melanoma centres were prospectively screened for mutations in exons 11, 13 and 17 of the KIT gene. A total of 257 patients had cutaneous melanoma arising from non-acral sites and four were acral melanomas. No mucosal or ocular melanomas were analysed. KIT mutations were identified in five tumours (2% of the entire cohort) including two acral melanomas. Two of the three non-acral melanomas with KIT mutations were associated with markers of chronic sun damage as assessed by the degree of skin elastosis. In the remaining cohort, 43% had chronically sun damaged skin. This report confirms that within an Australian population, KIT mutations are infrequent in cutaneous melanomas associated with both intermittent and chronic sun exposed skin.

Melanoma: What Are the Gaps in Our Knowledge?

Cutaneous malignant melanoma (MM) falls into two main groups, based on aetiology [1–3]. First, a small minority of patients have acral MM, in which the disease occurs on the palms and soles. The incidence of acral MM is similar in people with widely different skin colours (and hence with different amounts of skin melanin), and at different latitudes. The palms and soles have a thick epidermis, and so few harmful photons of ultraviolet radiation (UVR) will penetrate to the germinative layers. Acral melanomas are therefore not believed to be causally related to UVR, and their aetiology remains a mystery. They will not be discussed further in this article. By contrast, more than 90% of MM occurs on non-acral sites and is thought to be caused by UVR [2,4]. The evidence for such causality comes from a variety of fields. MM is most common in those with pale skin, which has a relative lack of melanin, a substance that blocks photons from penetrating deeply into skin [2]. African people with very dark skin are hundreds of times less sensitive to the harmful effects of UVR than white Northern Europeans. Even within white Northern European populations, MM rates vary in relation to more subtle degrees of difference in sun sensitivity. Those with red hair, pale skin, and a tendency to freckle are about three times more likely to develop MM than those without these three features [2,5]. The dramatically elevated rate of MM in those with European ancestry in Australia is therefore what we would expect: susceptibility of the host coupled with enhanced environmental exposure leads to a high disease risk [4]. Linked Research Article This Research in Translation discusses the following new study published in PLoS Medicine: Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Garbe C, et al. (2008) Improving melanoma classification by integrating genetic and morphologic features. PLoS Med 5(6): e120. doi:10.1371/journal.pmed.0050120 Boris Bastian and colleagues present a refined morphological classification of primary melanomas that can be used to improve existing melanoma classifications by defining genetically homogeneous subgroups. However, it is not just epidemiology that implicates a key role for UVR. Patients with the rare Mendelian disorder xeroderma pigmentosa (see http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=278700) have a dramatically increased risk of most types of skin cancer, including MM. This disorder is characterised acutely by sun-burn in response to tiny amounts of UVR, and both this sun-burn and the elevated cancer rates are a result of an inability to repair the DNA damage induced by UVR. The lesson is quite clear: it is not sunlight per se, but the highly mutagenic UVR part of the electromagnetic spectrum that is important for skin carcinogenesis. Given that we know the major host and environmental factors that lead to non-acral melanomas, one might think that we know enough to reduce the incidence of MM. But our ability to change people's behaviour so that they reduce their exposure to UVR remains limited. In addition, as our knowledge of MM has increased, so has the incidence of disease. Puzzling gaps therefore remain in our knowledge of the aetiology of non-acral melanomas. So what important things do we not know?

Multiple Primary Acral Melanomas in African-Americans: A Case Series and Review of the Literature

Although melanoma accounts for only 4% to 5% of all skin cancers in the United States, it causes most skin cancer-related deaths. We describe a unique group of African-American patients with multiple primary acral lentiginous melanomas (ALMs). The purpose of this study was to review the case histories and management of a cohort of patients in the Mohs practice of our dermatologic surgeon with multiple primary ALM. This is a case series of patients with multiple ALM identified by chart review from 2000 to 2005. A thorough review of the literature was performed. Four patients, all African-American, were identified with multiple ALM. All patients were managed with excision or Mohs micrographic surgery utilizing permanent sections. None of the patients with ALM had melanomas at nonacral sites or other types of skin cancer. Several had acral melanosis. Information in the literature on patients with multiple primary acral melanomas was insufficient. Patients with multiple acral melanomas have not, to our knowledge, been reported thus far. It can be extrapolated from current literature, however, that appropriate management of these patients, including staging work and surgical intervention, is to be determined by the individual characteristics of the melanoma and the patient's concomitant risk factors, if any.

Multiple Primary Acral Melanomas in African-Americans

BACKGROUND Although melanoma accounts for only 4% to 5% of all skin cancers in the United States, it causes most skin cancer–related deaths. We describe a unique group of African-American patients with multiple primary acral lentiginous melanomas (ALMs). OBJECTIVE The purpose of this study was to review the case histories and management of a cohort of patients in the Mohs practice of our dermatologic surgeon with multiple primary ALM. METHODS This is a case series of patients with multiple ALM identified by chart review from 2000 to 2005. A thorough review of the literature was performed. RESULTS Four patients, all African-American, were identified with multiple ALM. All patients were managed with excision or Mohs micrographic surgery utilizing permanent sections. None of the patients with ALM had melanomas at nonacral sites or other types of skin cancer. Several had acral melanosis. Information in the literature on patients with multiple primary acral melanomas was insufficient. CONCLUSION Patients with multiple acral melanomas have not, to our knowledge, been reported thus far. It can be extrapolated from current literature, however, that appropriate management of these patients, including staging work and surgical intervention, is to be determined by the individual characteristics of the melanoma and the patient's concomitant risk factors, if any.

Acral pseudolymphomatous angiokeratoma of children (APACHE)

13-year-old girl presented with a 10-year history of multiple discrete red firm papules situated on her right upper arm. The histopathology examination revealed a massive subepidermal lymphohistiocytic infiltrate, consistent with acral pseudolymphomatous angiokeratoma of children. Treatment with topical application of mometasone furoate 0.1% cream once daily for 6 months improved the lesions partially. However, these papules returned to their pretreatment appearance and consistency within 6 months after the cessation of the topical corticosteroid. The authors prefer the term 'papular angiolymphoid hyperplasia' for this entity, based on the absence of histological angiokeratomatous features, the benign nature of the lesion and the previously reported cases from adults and non-acral sites.

Disturbance of thermal homeostasis during post-exercise hyperthermia.

The response of core temperature to exercise was investigated during recovery in order to avoid the antagonistic competition between exercise and thermal reflexes for the same effector systems which control skin blood flow. Five healthy, non-training males [mean (SD) age, 23.8 (2.04) years] were habituated to 29 degrees C at relative 50% humidity for more than 2 h and then exercised by treadmill running at about 75% maximum oxygen uptake for 18 min. They then remained at 29 degrees C for up to 65 min of recovery. Oesophageal (T(es)), rectal (Tre) and skin temperatures (Tsk) were recorded at 5-s intervals throughout. The abrupt fall of temperature gradient from the forearm to finger was used to identify the T(es) for skin vessel dilatation (Tdil) during exercise. Mean (SE) Tes rose from a resting value of 36.67 (0.15) degrees C to 38.22 (0.24) degrees C, mean Tre rose from 37.09 (0.25) degrees C to 38.23 (0.15) degrees C, and Tdil occurred at 37.39 (0.32) degrees C. Within 10 min of recovery mean T(es) fell to 37.31 (0.24) degrees C, where it remained a significant 0.64 degrees C above its pre-exercise (PrEx) level (P < or = 0.018) but insignificantly different from Tdil for the remaining 55 min of recovery. Meanwhile, Tre fell gradually throughout recovery to 37.64 (0.18) degrees C. The Tsk at all non-acral sites except the thigh had recovered to PrEx levels by 20-30 min post-exercise (PoEx).(ABSTRACT TRUNCATED AT 250 WORDS)

Suction-induced basal cell cytolysis in the Weber-Cockayne variant of epidermolysis bullosa simplex.

In the Weber-Cockayne form of epidermolysis bullosa simplex (EBS-WC), trauma induces blisters which are confined to the palms and soles. Histologically, basal cell cytolysis is seen. We studied 6 patients with EBS-WC to determine the ultrastructural level at which artificially-induced suction blisters form. Blisters were raised by application of a suction blister cup to uninvolved forearm skin, the cup being connected to a negative pressure of 200 mm of mercury. The blisters were biopsied and examined by light and electron microscopy. On light microscopy, all biopsies showed marked vacuolization of keratinocytes in the lower two-thirds of the epidermis, and in all but one there was a cleavage plane through the basal keratinocytes. These findings were confirmed by electron microscopy in 4 patients. The separation through the basal cells is in contrast to the situation in normal individuals in whom cleavage occurs below the level of the basal cells, within the lamina lucida. Thus, even apparently normal skin from non-acral sites has the same structural abnormality as the affected acral sites in EBS-WC.