Mutations of p53 gene in canine sweat gland carcinomas probably associated with UV radiation

Introduction Apocrine sweat gland carcinomas (ASGCs) are rare malignant skin tumours in dogs and humans. The literature published so far focuses mostly on the clinico-epidemiological aspect of these tumours, but little is known about their pathogenesis. In this study we aimed to determine whether the p53 gene is involved in the carcinogenesis of the apocrine sweat gland in dogs and whether ultraviolet radiation (UV) is related to it. Material and Methods Forty canine ASGCs were submitted to laser capture microdissection to isolate neoplastic cells, from which DNA was subsequently extracted. PCR amplification and sequencing of p53 exons 2–8 was then performed, followed by computer analysis of the obtained sequences. Results Sixteen mutations within the p53 gene were found in 13 tumours. The mutations involved C → T, T → C, G → A, and CC → TT transitions, C → G transversion and adenine deletion, which are gene alteration types known to be related to UV radiation in the process of skin carcinogenesis in humans. Six of the thirteen tumour cases displayed the C → T transitions in the same location in exon 4 and three of the thirteen cases displayed T → C in the same location in exon 5. Conclusion The results of the present study indicate both the participation of the p53 gene and the influence of UV radiation in the formation of ASGCs in dogs.

Proportion of Thick versus Thin Melanomas as a Benchmarking Tool

Background: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early melanoma because the NNE does not capture the most significant outcome for melanoma prognosis, which is linked to the Breslow thickness. A lower NNE could reduce health costs related to melanoma diagnosis only if doing so does not increase the proportion of thicker melanomas. Objectives: The diagnostic performance by two tertiary referral centres using the NNE and proportion of thick (Breslow thickness > 1 mm) versus thin (Breslow thickness ≤ 1 mm) excised melanoma (thick/thin ratio: TTR) was compared to determine if a lower NNE is associated with a greater proportion of thicker melanoma. Combining TTR with NNE allows a better estimate of the effectiveness in melanoma diagnosis, assessing both the overall cost for a given pool of excised melanomas and costs due to unnecessary nevi excision at a particular dermatology centre. Methods: Demographic data and Breslow thickness of excised melanoma were extracted from patient histologic records at two referral centres for melanoma (Parma Dermatology Unit and Ravenna and Meldola Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. IRCCS (IRST)) on all skin tumours excised between 2002 and 2011 and diagnosed as melanoma or melanocytic nevus. NNE and TTR were calculated and compared among the considered variables. Logistic regression was used to assess the contribution of each variable in predicting a higher TTR. Results: Data from 16,738 excised lesions were analysed. The IRST Unit reported a mean NNE of 4.6, whereas the Parma Unit excised 10.6 nevi for each melanoma. No statistically significant differences existed in the mean (IRST Unit, 0.56 ± 0.89 mm; Parma Unit, 1.07 ± 2.2 mm) and median (range) Breslow thickness (IRST Unit, 0.4 (9) mm; Parma Unit 0.4 (30) mm). The TTR between centres was significantly different (Parma Unit, 24%; IRST Unit, 12%; p < 0.001). Based on logistic regression, the diagnosing centre was the most powerful factor in determining a thickness of >1 mm among diagnosed melanomas (OR = 1.8; 95% CI, 1.2–2.7; p < 0.01), with all other factors being equal. The NNE decreased at both centres from younger-to-older patients, whereas the TTR increased simultaneously; however, the increase in TTR was non-significantly related to NNE reduction after adjusting for confounders (age, gender, and localization). Conclusions: A better diagnostic performance is capable of reducing the NNE and TTR, i.e., unnecessary excisions of melanocytic nevi can be reduced without increasing the risk of overlooking melanomas. The TTR, in addition to the NNE, allows stakeholders to better estimate the effectiveness in melanoma diagnosis because both overall costs for a given pool of excised melanomas and costs due for unnecessary nevi excision at a particular dermatology centre can be compared.

Bedside Differentiation Between Benign and Malignant Pigmented Skin Tumours by Four Diagnostic Imaging Technologies – A Pilot Study

Fast diagnosis of suspicious pigmented skin lesions is imperative, but current bedside skin imaging technologies are either limited in penetration depth or resolution. Combining imaging methods is therefore highly relevant for skin cancer diagnostics. This pilot study evaluates the ability of optical coherence tomography, reflectance confocal microscopy, photoacoustic imaging and high-frequency ultrasound to differentiate malignant from benign pigmented skin lesions. A total of 41 pigmented skin tumours were scanned prior to excision. Morphologic features and blood vessel characteristics were analysed in reflectance confocal microscopy, optical coherence tomography, high-frequency ultrasound and photoacoustic imaging images and diagnostic accuracy assessed. Three novel photoacoustic imaging features, 7 reflectance confocal microscopy features and two optical coherence tomography features were detected with a high correlation to malignancy, diagnostic accuracy > 71%. No significant features were found in high-frequency ultrasound. Conclusively, optical coherence tomography, reflectance confocal microscopy and photoacoustic imaging in combination enables image-guided evaluation of suspicious pigmented skin tumours at the bedside. Combining these advanced techniques may help to diagnose skin cancer more efficiently.

Hyperpigmented Nodular Dermatofibroma: Two Cases Report and Brief Literature Review

BACKGROUND: Dermatofibroma (DF) is a common benign skin tumor (Benign Fibrous Histiocytoma) that mostly affects the extremities with a tendency to occur more often in older females than males. It usually presents as a slow growing small brown dome shape papule on the extremities. DF has a chronic nature and can sometimes regresses spontaneously. Dermoscopy is essential in the evaluation of DF to help differentiate it with other skin tumors. The gold standard evaluation for diagnosis of DF is biopsy with histopathologic examination. Removal of DF is often due to cosmetic factors, with surgical excision being the preferred method for removal. DF has an excellent prognosis. CASE REPORT: We present two case reports of women with hyperpigmented nodules on the lower extremity. Dimple sign was positive. From dermoscopic study showed a pigment network and central white patch pattern. On histologic examination revealed proliferation of fibroblast such as spindle cells as a storiform pattern and hyperplastic epidermis with hyperpigmentation of the basal layer. Based on clinical features, dermoscopy and histopathological evaluation, the diagnosis of DF was established. Both patients were perform surgically excision and have a good result. CONCLUSION: Dermatofibroma is benign fibrous histiocytoma that represents one of the most common skin tumours. Nodular hyperpigmented dermatofibroma is a clinical variant of Dermatofibroma which can be treated with surgical excision with good prognosis.

Cutaneous Leiomyoma: A Clinical Study of 152 Patients

<b><i>Background:</i></b> Cutaneous leiomyoma (CL) is a benign smooth muscle tumour included in painful skin tumours. Multiple CLs are cutaneous markers of hereditary leiomyomatosis and renal cell cancer (HLRCC). <b><i>Objectives:</i></b> To retrospectively review our series of patients with CLs to analyse their clinical features and the association with HLRCC. <b><i>Methods:</i></b> Cases coded as CL in the database of the pathology department between 2004 and 2019 were included in the study. Medical records were retrospectively reviewed to obtain the following data: age, sex, location, number of lesions, diameter, evolution time at diagnosis, suspected clinical diagnosis, tenderness, status of resection margins, development of recurrence, follow-up time, and association with HLRCC. <b><i>Results:</i></b> 152 patients had CLs, 89 women and 63 men, mean age 56.26, SD 16.030 years. Subtypes were piloleiomyoma in 62 patients, angioleiomyoma in 80, and genital leiomyoma in 10. All of our 11 patients with multiple lesions corresponded to piloleiomyomas, and HLRCC was confirmed in 8 of them (73%). Patients with HLRCC were younger than patients with piloleiomyomas without HLRCC (34.88 vs. 56.17 years, <i>p</i> = 0.009). Vascular and genital leiomyomyomas were solitary and were not associated with HLRCC. <b><i>Conclusion:</i></b> In patients with multiple piloleiomyomas HLRCC must be ruled out as it is confirmed in a high proportion of cases. The probability of fumarate hydratase mutation is greater in multiple piloleiomyomas involving both the trunk and upper extremities in the same patient.