Cutaneous Breast Cancer Metastases Successfully Treated Using an Oxygen Flow Assisted Topical Administration of Methotrexate (OFAMTX).

INTRODUCTION: Cutaneous metastases of breast cancer remain a therapeutic challenge. Oxygen flow-assisted topical administration of methotrexate 5% (OFAMTX, 5% methotrexate in a carrier solution) has recently been proven to be an efficacious alternative treatment for extramammary Paget's disease, which is considered to be an in situ mammary adenocarcinoma of the epidermis. CASE REPORT: A 51-year-old patient with triple negative breast cancer presenting with biopsy-proven skin metastases on the chest agreed to a treatment with OFAMTX5%. The treatment duration was 2 weeks and consisted of twice-weekly sessions with OFAMTX5% applied to an area of skin of approximately 40 cm2. Skin biopsies were performed before and 2 months after procedure. The tolerance to the treatment was excellent, and no pain sensations were experienced. Two months post-procedure the treated area presented a post-inflammatory hyperpigmentation. No residual metastatic lesions were detectable on the control skin biopsy. Six months post-procedure the patient is still in clinical remission. DISCUSSION: OFAMTX5% represents an alternative skin-directed, painless, patient-friendly and efficacious adjuvant treatment for superficial metastatic lesions of breast cancer. Larger series are required to evaluate the potential of OFAMTX5% for the treatment of superficial metastatic lesions of breast cancer.

Giant morphea-form basal cell carcinoma of the umbilicus: Successful debulking with vismodegib.

Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus. A sequential treatment was initiated with debulking using vismodegib 150 mg per day for 4 months, followed by reconstructive surgery. To the best of our knowledge, this is the first report of a giant basal cell carcinoma of the morphea-form type of the umbilicus. The sequential treatment plan reduces the duration of vismodegib inherent adverse effects and significantly reduces the tumor mass prior to surgery. Besides increasing adherence to vismodegib treatment, this approach facilitates the surgical technique and improves cosmetic outcome.

Melanoma masquerading as nonmelanocytic lesions.

Increased awareness among dermatologists as well as the development of dermoscopy and sequential dermoscopy have contributed significantly toward an increase in the diagnostic accuracy of pigmented melanoma and even of amelanotic melanoma. However, the dermatologist's nightmare is the small group of melanomas that present as common skin diseases, often associated with a significant delay in diagnosis and hence a poor prognosis. The study was carried out to prospectively assess the number of melanomas lacking any clinical suspicion of melanoma and to describe their clinical and histological features over a 6-year observation period in an University Tertiary Skin Cancer Center. Out of 502 cases of newly diagnosed cases of melanoma, seven (1.4%) nonpigmented and nonamelanotic cases of melanoma were identified. The mean age of the patients was 69 years (two females/five males). All cases were discovered by chance on a punch biopsy. The clinical diagnostic suspicions were basal cell carcinoma, fungal intertrigo, keratoacanthoma, lichenoid keratoma, diabetic foot ulcer, eczema, and necrotic pressure ulcer. Dermoscopy, performed after the punch biopsies, was only partially contributive. The mean histological thickness was 2.7 mm, the mean number of mitoses was 7/mm, local micrometastases were present in 5/7 (71%), the mean Ki67 count was 18.9%, and a positive sentinel lymph node was observed in 4/6 (66%) cases. Nonpigmented and nonamelanotic melanomas are rare, are at high risk, and have a poor prognosis because of a delayed diagnosis. Dermoscopy is only of partial diagnostic aid. Treatment resistance or atypical behavior of the above-mentioned lesions should lead to biopsy.

Smouldering malignant melanoma and metastatic dormancy: an update and review.

The fund of knowledge regarding the versatility of presentation of MM metastases is still quite incomplete. The recent literature pertaining to the current understanding of the mechanisms underlying two special features of MM metastasis is reviewed. On the one hand, a long disease-free interval (MM dormancy) may occur before the surge of overt metastases. On the other hand, the so-called MM smouldering phenomenon refers to the condition where regional metastases wax and wane for long periods of time on restricted skin regions. It is important to emphasize that local micrometastases often predict sentinel lymph node involvement but may not reflect progression of the primary MM to full-blown visceral metastatic competence. It is likely that a combination of factors impacts the versatile MM metastasic progression. Among the main factors, one has to mention the phenotypic heterogeneity and variability in the phenotype of MM cells, the presence of MM stem cells and MM cells engaged in an amplification proliferation pool, as well as the host immune response, and possibly the induction of a particular stromal structure and vascularity.

Molecular dermatopathology in malignant melanoma.

At present, immunohistochemistry is taken for granted in the establishment of malignant melanoma (MM) diagnosis. In recent years, molecular diagnosis in dermatopathology has benefited from a vast array of advances in the fields of genomics and proteomics. Sensitive techniques are available for detecting specific DNA and RNA sequences by molecular hybridization. This paper intends to update methods of molecular cytogenetics available as diagnostic adjuncts in the field of MM. Cytogenetics has highlighted the pathogenesis of atypical melanocytic neoplasms with emphasis on the activation of the mitogen-activated protein kinase (MAPK) signalling pathway during the initiation step of the neoplasms. 20 to 40% of MM families have mutations in the tumour suppressor gene p16 or CDKN2A. In addition, somatic mutations in p16, p53, BRAF, and cKIT are present in MM. Genome-wide scan analyses on MM indicate positive associations for genes involved in melanocytic naevi, but MM is likely caused by a variety of common low-penetrance genes. Molecular dermatopathology is expanding, and its use in the assessment of melanocytic neoplasms appears to be promising in the fields of research and diagnosis. Molecular dermatopathology will probably make its way to an increased number of diagnostic laboratories. The expected benefit should improve the patient management. This evolution points to a need for evolution in the training requirements and role of dermatopathologists.

Intense pulsed-light therapy for proliferative haemangiomas of infancy.

Infantile haemangioma therapy has long been a wait-and-see policy. Since recent development of laser and light therapy, pulsed dye laser has been successfully used for treating superficial haemangiomas. Few studies have been published about treatment with intense pulsed light (IPL) to assess the risk/benefit of IPL in the treatment of infantile haemangiomas during their early proliferative phase. In the present retrospective cohort study, we retrieved data about a series of 14 Caucasian children (median age: 4.8 months) with infantile haemangiomas treated with Photoderm Vasculight flash lamp. All patients experienced a rapid regression of the haemangiomas after 3 treatments on average. Few adverse events were noted, including ulceration and crusts. No residual scarring and cosmetic damages were noticed. Fast growing haemangiomas should be treated with light therapy as soon as possible. This technology is safe, efficient, inducing regression, and preventing any further functional and aesthetic complications. The benefit-risk ratio favours the treatment of most types of haemangiomas which are out of the scope of betablocker administration.

Revisiting cutaneous adverse reactions to pemetrexed.

Pemetrexed (Alimta®) is a multitargeted antifolate drug approved as a single agent or in combination with cisplatin for the treatment of a small number of malignancies including advanced and metastatic non-squamous non-small cell lung cancer (NSCLC), and malignant pleural mesothelioma. This review reports the recent peer-reviewed publications and original findings regarding cutaneous adverse reactions (CARs) to pemetrexed. Pemetrexed-related CARs are frequently reported under the unspecific term 'skin rash'. However, more specific diseases were tentatively identified as alopecias, urticarial vasculitis, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, radiation recall dermatitis and pityriasis lichenoides. Most of the skin reactions occur shortly after pemetrexed administration. As with methotrexate-related CARs, the cell cycle arrest in the S phase may be regarded as a direct and major cause of the cytotoxic pathobiology. An adverse immune reaction is unlikely. In conclusion, pemetrexed is responsible for CARs exhibiting a variety of clinical presentations. Their origin is likely attributed to direct cytotoxicity following the cell cycle arrest in the S phase and cell necrosis.

'Malignant melanoma microecosystem': Immunohistopathological insights into the stromal cell phenotype.

Cutaneous malignant melanoma (MM) is rooted in the dermal connective tissue, which consists of apparently unremarkable stromal cells as they appear upon regular histopathological examination. However, a number of in vitro studies have shown that these cells produce diverse types of cytokines, growth factors and enzymes in excess. In addition, they store and probably release various structural components of the extracellular matrix (ECM). Most of the current information comes from in vitro experiments, and these findings do not always correlate with investigations carried out using excised human MM tissue. The MM-stroma connection appears crucial to the regulation of neoplastic growth, invasiveness and initial metastatic spread. However, little is known about the in vivo intracellular storage and extracellular deposits of specific ECM macromolecules located inside and around MM lesions. This review summarizes various distinct features of the peri-MM stroma, which shows an intracytoplasmic abundance of Factor XIIIa, versican and various α (IV) collagen chains. The area exhibiting such changes corresponds to the location where neoangiogenesis commonly develops and where extravascular unicellular metastatic MM lesions are possibly found. Some of these inconspicuous migratory malignant melanocytes may actually correspond to MM stem cells. Their presence was found to be significantly associated with an increased risk for distant metastases, particularly in the sentinel lymph nodes. Although much remains to be learned, active intervention of the ECM appears likely in the inconspicuous early dermal metastatic migration of MM cells.