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

Image of the month. Necrobiosis lipoidica

peer reviewe

Multifocal Germ Cell Tumors

peer reviewedA 16-year old male presented with a mediastinal germ cell tumor (seminoma) treated by combined surgery, radiotherapy and chemotherapy. Nine years later, he presented with an intracerebral germ cell tumor affecting both the suprasellar ventricles and the pineal area. After partial removal of the intraventricular tumor, the patient received radiotherapy and chemotherapy. No metastases could be found. He died 8 months later, probably from secondary cardiovascular disturbances. This case seems to be the first one to illustrate the possibility of multifocal extragonadal seminoma

Medische beeldvorming van een gebrekkige microdoorbloeding van de huid.

Le réseau microvasculaire de la peau joue des rôles physiologiques majeurs en oxygénant les tissus et en permettant des échanges thermiques finement régulés. Son parcours résistif et capacitif module les résistances périphériques au débit sanguin. La microvascularisation est sous l’influence de divers facteurs, mais globalement, elle semble presque immuable dans la peau saine. En revanche, certaines circonstances pathologiques engendrent des hyperplasies ou des hypoplasies vasculaires. Parfois aussi, le réseau semble garder son extension normale, mais sa structure intime est remaniée. Cette revue est un florilège d’aspects microscopiques associés à des perturbations majeures de la fonctionnalité vasculaire cutanée

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

Mammary Paget's disease

peer reviewedMammary Paget's disease is an intraepithelial carcinoma present on the nipple and its areola. The tumor typically develops in middle aged women. It is frequently associated or contiguous to an underlying galactophoric adenocarcinoma. The histopathologic and immunopathologic aspects are typical and linked to the presence of Paget's cells. Early diagnosis is required searching for a possible underlying carcinoma. The surgical treatment is directed by the characteristics of the deep mammary carcinoma