Chronic Sun-damaged Skin Research Articles

Efficacy and toxicity of KIT targeted therapy in elderly patients with melanoma.

e23269 Background: Most cases of malignant melanoma are cutaneous, with ≈50% having a BRAF driver mutation that predicts response to MAPK pathway inhibitors. A small minority of melanoma cases harbor an activating KIT mutation, most notably in mucosal and acral melanomas (15-20%) and occasionally in those arising from chronic sun-damaged skin (2-3%). Only about a third of KIT mutated melanomas respond to targeted therapy with Imatinib, yet data is scarce and limited, especially in older patients. We sought to characterize the efficacy and toxicity of Imatinib in KIT-mutated melanoma patients over 65. Methods: We identified electronic medical records of patients over 65 that were treated with Imatinib for KIT mutated melanoma at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, response patterns and toxicity. Results: 10 patients were identified, 50% were males. The median age at treatment initiation was 75 years (71-100). 3 patients had cutaneous primary, 3 had Vulvar/vaginal primary, 3 had acral primary and 1 had anal canal primary. All patients had normal Lactate dehydrogenase at treatment initiation and ECOG performance status was 0-2 (median 0). 9 patients received Imatinib for stage IV disease with an overall response rate (ORR) of 55% (44% partial response, 11% complete response). Median duration of response was 4 months. Responses were seen in acral melanoma (67%), vulvar/vaginal melanoma (67%) and cutaneous melanoma (33%). Median Progression free survival was 4.3 months (1.8-44), median overall survival from treatment initiation was 22.6 months (4-64). 6 patients were treated as 2nd line with an ORR of 67% and 3 were treated as 3rd line with an ORR of 33%. There was one patient with M1d disease who did not respond to treatment either systematically or intracranially. 6 patients had Exon 11 mutations (V560D/G/E, N564S and L576P) of which 4 responded (67%). 2 had Exon 17 mutations (N822C/K) of which 1 responded (50%) and the 2 others had an Exon 14 (F681I) and Exon 13 (K642E) mutation that did not respond to treatment at all. Toxicity was moderate with 90% of patients experiencing any grade AE, yet only 1 experienced toxicity requiring dose interruption with two Grade 3 toxicities - Pneumonitis and decreased neutrophil count, leading to temporary treatment interruption, dose reduction and a course of corticosteroids. The rest of the patients experienced only Grade 1-2 toxicity. 4 patients needed dose reductions, there were no treatment discontinuations due to toxicity. Conclusions: Treatment with Imatinib for elderly KIT mutated melanoma patients is safe and well tolerated with no treatment discontinuations recorded. The response rate is encouraging yet seems to vary according to the KIT mutation present as previously reported. The duration of response is usually short-lived and alternative/combination treatments are still needed for this patient population.

Clinical, Dermoscopic, and Histological Characteristics of Melanoma Patients According to the Age Groups: A Retrospective Observational Study.

Although the role of melanoma risk factors is well documented, their correlation with patients' age is less frequently analyzed. The analysis was performed among 189 melanoma patients in different age groups, including <30 years, 31-60 years, and >60 years, to investigate the risk factors, topography, and coexistence of morphological features of 209 melanomas (dermoscopic and histopathological). Among the youngest age group, no correlation with the presence of estimated risk factors was found. The most common dermoscopic pattern was spitzoid and multicomponent asymmetric. The group of middle-aged patients was the most diverse in terms of the occurrence of risk factors, solar lentiginosis, dermoscopic patterns, topography, histological subtypes, and invasiveness of melanomas. The oldest group characterized a strong correlation between solar lentiginosis, NMSC comorbidity, the prevalence of facial melanomas, the dermoscopic pattern of melanoma arising on chronic sun-damaged skin, and regression. The findings regarding the presence of age-specific features in melanoma patients, especially in the youngest and middle-aged groups, might be helpful for clinicians and to target secondary prevention efforts.

Metabolism and Functions of Amino Acids in the Skin.

Amino acids are the building blocks of all proteins, including the most abundant fibrous proteins in the skin, as keratins, collagen and elastin. Sagging and wrinkled skin are features of chronic sun-damaged and aged uncared skin, and they are mainly associated with the deterioration of collagen and elastic fibers. The maintenance of skin structures by self-repair processes is essential to skin health. Thus, amino acids significantly impact the appearance of the skin. Amino acids are important nutrients required for (a) wound healing promotion and repair of the damaged skin; (b) acid-base balance and water retention in cellular layers, such as stratum corneum; (c) protection against sunlight damage; (d) maintenance of an appropriate skin microbiome. This review highlights the contribution of all proteinogenic amino acids and some related metabolites to the skin structures as constituents of the main cutaneous proteins or as signaling molecules for the regulation and determination of skin physiology.

Dermal Pleomorphic Sarcoma of the Scalp – Report of Two Cases

BACKGROUND:Neoplasias of the UV-exposed head-and-neck area of the elderly include non-melanoma skin cancers of various origin.CASE REPORT:We report two cases of rapid growing exophytic scalp tumors on chronic sun-damaged skin, in one case with a tendency of bleeding. The tumours were removed by wide surgical excision with 3D margin control, and the resulting defect was covered by a meshed split skin graft. Histopathologic examination disclosed a dermal pleomorphic sarcoma in both cases. The staging was unremarkable in both patients.CONCLUSIONS:Sarcomatous tumours of the scalp should be completely excised with a 3D margin control. Dermal pleomorphic sarcoma is a more aggressive variant compared to atypical fibroxanthoma despite some similarities.

LB947 Progression of chronic sun-damaged skin to actinic keratosis is associated with loss of E-cadherin in keratinocytes

LB947 Progression of chronic sun-damaged skin to actinic keratosis is associated with loss of E-cadherin in keratinocytes

642 Efficacy and photorejuvenation effect of conventional photodynamic therapy (PDT) and Er:YAG (erbium:yttrium-aluminium-garnet) ablative fractional laser – assisted PDT in multiple actinic keratosis

Actinic keratosis is the precancerous lesion of squamous cell carcinoma. Their multiple appearance on one area reflects field cancerization. Therefore active treatment of the field is necessary to avoid the development of incidental squamous cell carcinoma. Conventional photodynamic therapy (PDT) is a widely used therapeutic method for actinic keratosis. Er:YAG (erbium:yttrium-aluminium-garnet) ablative fractional laser (AFL) - assisted PDT is used to increase the therapeutic efficacy of conventional PDT. The aim of this study was to assess the differences between conventional PDT and Er:YAG - assisted PDT both in efficacy and rejuvenation effect. To investigate the therapeutic efficiency, sixteen patients with actinic keratosis and chronic sun-damaged skin were irradiated with wIRA lamp on the half side of the skin involved in actinic keratosis – after 20% 5-aminolevulinic acid was applied as photosensitizer. The other side of the skin was pre-treated with Er:YAG-AFL before 5-ALA. 24/48 hours and 3 months after the treatment biopsy samples were taken to measure the degree of the keratinocyte dysplasia compared to the control (untreated) samples. P53 mutant keratinocytes were detected with immunohistochemical staining. The number and grade of actinic keratosis and the objective signs of photoaging was also assessed. In our hands, both conventional PDT and Er:YAG-AFL - assisted PDT led to great reduction in the number of actinic keratosis, and this decrease was significantly higher in the case of Er:YAG-AFL PDT. Both improved global photoaging, but we found no significant differences between the two methods. According to the immunohistochemical staining, both decreased the number of p53 mutant keratinocytes in the epidermis. We found no significant differences in the therapeutic efficiency between Er:YAG-AFL PDT and conventional PDT regarding clinical and immunohistochemical evaluation.

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.

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.

Prognostic implication of KIT mutations in melanoma.

9049 Background: The natural history of BRAF and NRAS mutant (mut) melanoma (mel) has been described, but prognostic implications of KIT mut mel have not. Methods: We performed a single-center retrospective review of 180 patients (pts) enriched for mucosal, acral or chronic sun-damaged skin (CSD) mel and screened for KIT, BRAF, and NRAS mut from 4/07 - 4/10 as a part of a phase II imatinib study. Pt/disease characteristics were compared using the Kruskal-Wallis or Chi-square tests. Factors associated with outcomes were assessed by Kaplan-Meier methods and multivariable Cox regression. Results: Median age, 63.7 years; 54.4% male. Primary site: 40% mucosal, 29% acral, 22% CSD, 9% others. Mut rate: 18% KIT, 16% BRAF, 14% NRAS, 52% wild-type (wt). Pathologic subtype differed by genetic subgroup (p&lt;.001) while age, gender, and stage did not (all p&gt;0.05). 18/26 (69%) KIT mut pts received imatinib in the metastatic (met) setting; 6/18 received &gt; 1 other KIT inhibitor. 3/25 (12%) BRAF mut pts received vemurafenib. 8/27 (30%) KIT mut, 4/27 (15%) BRAF mut, 6/20 (30%) NRAS mut, and 6/20 (30%) wt pts received ipilimumab. 149/180 (83%) pts developed mets at a median of 2.15 years (95% CI: 1.72, 2.72). Median follow-up (FU) of pts not developing mets was 3.91 yrs (range: 0.25, 14.34). Older age (HR: 1.02, 95% CI: 1.00, 1.03) and pathologic subtype (mucosal vs CSD HR: 1.70, 95% CI: 1.02, 2.84; non-CSD/unknown vs CSD HR: 2.05, 95% CI: 1.00, 4.21) were associated with increased risk of mets but not with time from mets to death. Of 149 pts who progressed, 123 (83%) died during FU. Median time from met to death was 1.21 years (95% CI: 0.91, 1.67). Median FU from time of mets among those alive at last FU was 2.53 yrs (range: 0.06, 6.85). Mut status including KIT mut was not associated with time to first met or time from met to death. Pts who received ipilimumab from time of first distant met had reduced risk of death (HR: 0.55, 95% CI: 0.36, 0.87) independent of mut status. No impact was observed with KIT inhibition. Conclusions: KIT mut status is not an independent predictor of time to mets or survival in pts with mets. Ipilimumab improved pt outcomes regardless of mut status. The lack of impact of KIT inhibitors is likely due to the heterogeneity of KIT mut in mel but does not preclude efficacy in appropriately selected pts.

Improvement of crow's feet lines by topical application of 1-carbamimidoyl-L-proline (CLP)

Wrinkles, one of the characteristics of chronic sun-damaged and/or aged skin, are associated with psychological distress. Apart from the deterioration of collagen and elastic fibers in the dermis, which induces the loss of skin elasticity, it has been recently proposed that decreased flexibility or elasticity of the stratum corneum (SC) is also correlated with wrinkle formation. The elasticity of the SC has been shown to be regulated, at least in part, by the amounts and types of amino acids. To evaluate the ability of our newly developed amino acid-derivative (1-carbamimidoyl-L-proline; CLP), which recovers the elastic properties of the SC ex vivo, to improve wrinkles, a clinical test was performed with 126 Japanese female subjects aged 32-50 years who had crow's feet lines on their faces. Three eligible dermatologists evaluated the study according to authorized grades by the Japanese Cosmetic Science Society and scored the subjects who were much improved or improved as 29.7% and 57.8% of all CLP-treated subjects at 4 and 8 weeks, respectively. In contrast, only 1.5% and 8.1% of subjects improved with the placebo lotion at 4 and 8 weeks, respectively. These results suggest a significant efficacy of CLP to improve wrinkles. In parallel with the dermatologists' assessments, skin surface roughness in the CLP-treated group was significantly reduced after treatment with CLP for 4 and 8 weeks compared to the placebo-treated group. The sum of these data suggests that CLP is a promising and useful ingredient for the improvement of wrinkles through its ability to enhance the elasticity of the SC.

Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis

There have been conflicting data regarding the prevalence and clinicopathological characteristics of BRAF and NRAS mutations in primary cutaneous melanoma. To solve this controversy, this study used a meta-analysis to evaluate the frequencies of BRAF and NRAS mutations, and the relationship between these mutations and clinicopathological parameters of cutaneous melanoma. Data from studies published between 1989 and 2010 were combined. The BRAF and NRAS mutations were reported in 36 and 31 studies involving 2521 and 1972 patients, respectively. The effect sizes of outcome parameters were calculated by odds ratios (OR). BRAF and NRAS mutations were reported in 41% and 18% of cutaneous melanomas, respectively. The mutations were associated with histological subtype and tumour site, but not with age and sex. The BRAF mutation was frequently detected in patients with superficial spreading melanoma (OR=2·021; P<0·001) and in melanomas arising in nonchronic sun-damaged skin (OR=2·043; P=0·001). In contrast, the NRAS mutation was frequently evident in patients with nodular melanoma (OR=1·894; P<0·001) and in melanomas arising in chronic sun-damaged skin (OR=1·887; P=0·018). This pooled analysis shows that the incidences of BRAF and NRAS mutations in cutaneous melanomas differ according to histological type and tumour location based on the degree of sun exposure.

V559A and N822I double KIT mutant melanoma with predictable response to imatinib?

Dear Editor, Since the initial report of KIT mutations in subtypes of melanoma, several reports of KIT-targeted therapies have been published (Carvajal et al., 2009; Hodi et al., 2008; Lutzky et al., 2008). Activating KIT mutations have been documented in a variety of neoplastic diseases including, in addition to melanoma, mastocystosis, acute myeloid leukemia, seminoma and gastrointestinal stromal tumors (Went et al., 2004). Herein, we report a case of a KIT double mutation in anorectal melanoma not previously described in melanoma, but with a response to imatinib mesylate that might have been expected given the knowledge from other cancers. The patient is an 87-year-old woman who developed constipation and a palpable rectal mass in the summer of 2009. Biopsy of the mass demonstrated an ulcerated melanoma invading the submucosa and muscle to a depth of approximately 11 mm with angiolymphatic invasion. Computerized tomography (CT) scans of the chest, abdomen and pelvis revealed metastatic disease in the pelvis, inguinal region and lungs. Substantial growth of the disease was documented on serial CT scans 3 months apart with the largest lung nodule increasing 44% (14 to 25 mm). The patient declined treatment with systemic chemotherapy and was not a candidate for the available clinical trials but she did express an interest in some form of therapy. Her melanoma was assessed for KIT mutational status. A double mutation was identified, comprising the exon 11 mutation V559A and the exon 17 mutation N822I. The patient subsequently initiated treatment with imatinib 400 mg daily in November 2009. Surveillance CT scans in February 2010 revealed that most metastatic lesions were stable to minimally decreased, including a right inguinal lymph node (16 to 14 mm), a right upper lobe lung nodule (20 to 18 mm), a right lower lobe lung nodule (25 to 23 mm) and a right ischioanal lesion (19 to 15 mm). There was complete disappearance of multiple subcentimetre lung nodules; however, there was also some growth of other lung nodules, the largest of which increased from 25 to 28 mm. The findings were consistent with a mixed response, although in accordance with RECIST criteria, the patient’s response would best be classified as stable disease ( 7% decrease in sum of diameters of target lesions). No repeat biopsy was attempted. The dose of imatinib was titrated from 400 to 800 mg with the aim of overcoming any possible resistance to therapy and improving the patient’s response. Unfortunately, the patient developed significant fatigue, dyspnea on exertion and lower extremity edema. Treatment was held, and after recovery from these acute symptoms, attempts were made to reinitiate imatinib at the lower dose of 400 mg. The patient was not able to tolerate resumption of therapy, and she experienced further clinical decline and progression of disease; ultimately, she succumbed to her metastatic melanoma in August, 2010. Efforts to define the genetic landscape of melanomas have led to the recognition that alterations in the KIT gene constitute the predominant mutation in melanomas arising from chronic sun-damaged skin and acral and mucosal anatomical locations (Curtin et al., 2005, 2006). KIT mutations in melanoma are now only beginning to be catalogued. The experience with KIT mutations in GISTs, however, is much more extensive, and this experience provides a conceptual framework for understanding the pathobiology of and therapeutic approaches to treating neoplastic diseases driven by KIT mutations (Corless and Heinrich, 2008). KIT mutations underlie approximately 85% of GISTs; and the vast majority ( 70%) occurs within exon 11 corresponding to the autoinhibitory juxtamembrane domain. KIT exon 9 lies within the extracellular ligand-binding region, and mutations within this exon account for 10 to 15% of KIT mutations in GIST. KIT mutations within the kinase domain (either exon 13 or exon 17) occur with much less frequency (<5%). To date, molecular analyses have identified approximately two dozen unique KIT mutations in melanoma (Woodman and Davies, 2010). Similar to GIST, the majority of KIT mutations in melanoma occur within the juxtamembrane autoinhibitory region encoded by exon 11. Unique to melanoma, though, the

Melan-A-Positive “Pseudomelanocytic Nests”: A Pitfall in the Histopathologic and Immunohistochemical Diagnosis of Pigmented Lesions on Sun-Damaged Skin

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.

Mouse pigmentation mutants help identify a uveal melanoma oncogene

Mouse pigmentation mutants help identify a uveal melanoma oncogene

Monitoring efficacy of cryotherapy for superficial basal cell carcinomas with in vivo reflectance confocal microscopy: A preliminary study

Superficial BCCs (sBCCs) usually appear as multiple lesions in chronic sun-damaged skin of elderly people and may show a destructive growth if left untreated. Non-invasive treatment modalities, such as cryotherapy have been employed for sBCCs, all failing to provide tissue for confirming diagnosis and assessing adequacy of tumour removal. Reflectance confocal microscopy (RCM), a new non-invasive imaging technique has proven to be a useful tool for detection of basal cell carcinoma in vivo. To non-invasively assess efficacy of cryotherapy for sBCCs by cytomorphologic analysis using RCM. We examined 10 histologically proven sBCCs located on the trunk of 5 consecutive patients with a mean age of 84.6 years. SBCCs were frozen twice using a spray nitrogen cryoprobe. RCM imaging was performed in each sBCC before cryotherapy and after 5 and 24h to monitor resulting tissue injury. Distinct cytomorphologic characteristics were determined by three observers allowing non-invasive evaluation of therapeutic efficacy of treatment immediately after cryotherapy. Tumour clearance was assessed by RCM imaging 3 months after therapy followed by histopathologic examination. Characteristic RCM-features of BCC were present in all lesions before cryotherapy. Five hours after cryotherapy, all 10 sBCCs showed small bright round to polygonal structures at basal layer and black round to oval areas of varying size with such bright structures floating therein, correlating to cell necrosis and incipient blistering. Eight sBCCs showed also cell necrosis in upper dermis. After 24h all sBCCs showed necrotic cells beneath collagen bundles. Tumour clearance on later histopathologic examination was only proven in those lesions showing damage to the upper dermis after 5h with RCM. Early cell necrosis within upper dermal structures seems to correlate with ablation of overlying tumour tissue. When it is not produced by cryotherapy, a second treatment should be considered.

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.

Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus.

Moderate hyperplasia of Merkel cells (MC) in chronic sun-damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation-damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal-cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal-cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.

Small cell (naevoid) melanoma: a clinicopathologic study of 131 cases.

One hundred and thirty-one small cell melanomas were reviewed with respect to clinical data submitted with each specimen and the histological pattern of each tumour. Of the small cell melanomas, 80% developed in individuals over the age of 50 years. There was a 2:1 male predominance with 58% of the tumours in men occurring on the back. All but one melanoma showed a lentiginous intraepidermal pattern. The dermal component was characterized by cords and nests of hyperchromatic melanocytes associated with interstitial fibrosis. Small cell melanomas may be recognized as thin lesions and are commonly located in chronic sun-damaged skin of elderly individuals. They may represent a special naevoid variant of lentigo maligna melanoma.

The activity of metabolic enzymes of human epidermis in relation to age.

Summary.— The activity of 14 enzymes, representative of the main metabolic pathways, was studied in the epidermis of 63 normal human subjects ranging in age from 1 month to 90 years. The activity was assayed with microfluorometric methods which allow the use of samples of epidermis very much reduced in size (0·3 μg to 1 μg). No difference of activity was observed in any of the enzymes studied despite the varied ages. The lack of influence of age on the activity of the enzymes in human epidermis enhances the significance of the variations which are reported in some pathological conditions (like psoriasis, chronic sun-damaged skin and neoplasms).