Celia Requena

Adverse reactions to injectable soft tissue fillers

In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler.

Adverse reactions to injectable aesthetic microimplants.

New inert materials such as polymerized silicones, Bioplastique, Artecoll, and Dermalive are now being used as injectable aesthetic microimplants. These substances are better than the old ones because they tend not to migrate and do not usually produce much of a host immune response. Adverse reactions after injection of these materials are rare, although there are a few reported cases as a result of bad technique or anomalous granulomatous reactions. We report on four patients with unsightly results after cosmetic microimplants, including one of Artecoll, one of Dermalive (to the best of our knowledge, the latter is the first such case reported), and two of silicone. This report describes the histopathologic features of cutaneous reactions to these injectable aesthetic materials.

Spitz nevus: a clinicopathological study of 349 cases.

Spitz nevus is an infrequent, usually acquired melanocytic nevus composed of epithelioid and/or spindle melanocytes that can occasionally be confused with melanoma. Currently, there are no immunohistochemical markers or molecular biology techniques that can be used to make an entirely safe diagnosis of Spitz nevus or melanoma in problematic cases. A retrospective study has been carried out that included all the cases diagnosed as Spitz nevus from our files. Follow-up information of the patients was unavailable. Three hundred forty-nine cases of unequivocal Spitz nevi were included, and their clinical and histopathological parameters were reviewed. One hundred and forty patients (40%) were 15 years old or younger, with a male to female ratio of 1:1. In patients older than 15 years, there was an evident predominance of women, with a male to female ratio of around 1:3. Spitz nevus was most commonly located on the lower extremities, followed by the trunk in both children and adults. Despite the fact that the head and neck were the third most common location in children, it was a much more frequent location in children than in adults. The constitution by epithelioid and/or spindled cells was the only histopathological finding present in 100% of cases. The other pathological findings studied were, from more to less frequent: maturation (72%), inflammatory infiltrate (70%), epidermal hyperplasia (66%), melanin (50%), telangiectasias (40%), Kamino bodies (34%), desmoplastic stroma (26%), mitosis (23%), pagetoid extension (13%), and hyalinization of the stroma (8%). Hyalinization was the only histopathological parameter that was statistically more frequent in adults than in children.

Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma.

We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.

Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1‐PDGFB ) study with therapeutic implications

Aims: To analyse the presence of collagen type I alpha 1–platelet‐derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables.

A variant in FTO shows association with melanoma risk not due to BMI

We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 × 10−12, per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTOs function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: Clinical and histologic outcomes

BACKGROUND Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. OBJECTIVES We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. METHODS Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. RESULTS In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. LIMITATIONS Only one cycle of imiquimod was administered. The follow-up period was brief. CONCLUSIONS Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy.

Primary cutaneous signet-ring cell melanoma: a clinico-pathologic and immunohistochemical study of two cases.

Signet-ring cell malignant melanoma is a rare histopathologic variant of malignant melanoma with only a few described cases. We report the clinical, histopathological, and immunohistochemical features of two cases of primary cutaneous signet-ring cell malignant melanoma. Neoplastic melanocytes showed abundant clear cytoplasm compressing the nuclei to the periphery, sometimes resulting in a signet-ring appearance. Immunohistochemically, neoplastic melanocytes in both cases expressed immunoreactivity for the usual melanocytic markers S-100 protein and Melan-A, although only the second case resulted HMB-45 positive. We review the literature about this rare cytologic variant of malignant melanoma and discuss the differential diagnosis with other cutaneous neoplasms that may show a signet-ring cell appearance of their neoplastic cells.

Animal type melanoma: a report of a case with balloon-cell change and sentinel lymph node metastasis.

Animal type melanoma is a rare histopathologic variant of melanoma characterized by sheets and nodules of heavily pigmented epithelioid melanocytes that involve the entire thickness of the dermis. This human neoplasm mimics melanocytic neoplasms seen in gray horses and laboratory animals; thus, is termed animal type melanoma. It is quite rare and, with only a few reported cases, its biological behavior is not well understood. We report an example of animal type melanoma on the back of a 27-year-old man. The lesion showed areas of melanoma in situ, which ruled out the possibility of metastatic melanoma. Features of regression were also seen at dermo-epidermal junction and papillary dermis. In some areas, neoplastic melanocytes exhibited a balloon-cell appearance; in others the neoplasm was composed of sheets and fascicles of heavily pigmented epithelioid melanocytes that permeated the entire dermis and extended into the dermal-subcutaneous interface, mimicking a cellular blue nevus. Epithelioid melanocytes in deeper areas showed abundant, heavily pigmented cytoplasm and pleomorphic nuclei with prominent eosinophilic nucleoli and some mitotic figures. The neoplastic cells did not show evidence of maturation in deeper areas of the lesion. In some sections, a nodule of heavily pigmented epithelioid melanocytes was seen far from the main bulk of the lesion, at the dermal-subcutaneous interface, raising the possibility of a satellite lesion. A lymphoscintigraphy showed a sentinel lymph node in the right axilla and a subsequent axillary lymphadenectomy demonstrated that the architecture of the sentinel lymph node was effaced by metastatic melanoma. The patient received adjuvant chemotherapy with inteferon alfa-2b and four months after this treatment the patient is alive and well, without evidence of recurrences or additional metastases.

Correlation Between Preoperative Magnetic Resonance Imaging and Surgical Margins with Modified Mohs for Dermatofibrosarcoma Protuberans

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is characterized by asymmetrical and poorly defined growth. Magnetic resonance imaging (MRI) has been proposed for the delimitation of this tumor. OBJECTIVES To study the utility of MRI in evaluating the depth of infiltration in DFSP and to compare the efficiency of clinical palpation with that of MRI in delimiting the invasiveness of DFSP. METHODS Observational, prospective study of DFSP cases. The MRI scans for all cases were compared with the exact histological infiltration plane obtained using modified Mohs micrographic surgery (MMS). RESULTS Forty‐three DFSPs were included: 22 primary, nine recurrent, and 12 extirpated with positive margins. Sensitivity for detecting deep invasion was 58% on examination using palpation and 67% using MRI. CONCLUSIONS We present the largest series of DFSP cases studied using MRI published to date. In primary cases, MRI has greater sensitivity than palpation for detecting depth of infiltration (67% vs 58%). MRI seems to be useful in primary DFSP in locations other than the head, neck, and upper part of the thorax. MRI is not useful for confirming tumor persistence in extirpated DFSP with positive margins or for studying lateral extension in primary DFSP. The authors have indicated no significant interest with commercial supporters.