[Nodulocystic eruption induced by sorafenib]. / Éruption nodulo-kystique induite par le sorafénib.

INTRODUCTION: Sorafenib is a multikinase inhibitor used in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid carcinoma. Cutaneous adverse events are numerous and occur frequently. PATIENTS AND METHODS: We present two cases of nodulocystic lesions associated with comedones in patients treated with sorafenib for hepatocellular carcinoma. In the first patient, a 64-year-old man, lesions appeared on the trunk one year after beginning sorafenib. Histopathological examination revealed a non-granulomatous, perivascular and perisudoral polymorphic cellular infiltrate associated with comedones and microcysts. These lesions progressed via inflammatory episodes interrupted by long periods of spontaneous remission without any specific treatment. In the second patient, a 53-year-old woman, a rash appeared on the buttocks three months after starting sorafenib and then spread to the lumbar region and thighs. Histopathological examination was consistent with granulomatous acne lesions. The initial treatment (oral tetracycline and zinc) given for 3 months proved ineffective. Patient follow-up over 3 years showed gradual regression without the appearance of any further lesions. DISCUSSION: In the literature, several reports discuss acneiform rashes in patients treated with targeted therapy. In most cases, these lesions were papulopustular without retentional lesions. There are few reports of nodulocystic eruptions associated with comedones following sorafenib therapy. The mechanisms of emergence of these lesions seem to involve inhibition of the RAF pathway, C-KIT, and the PDGF signaling pathway.

[Cutaneous pseudolymphoma caused by carbamazepine]. / Pseudolymphome cutané induit par la carbamazépine.

INTRODUCTION: Drug-induced cutaneous pseudolymphomas are poorly reported. They clinically and pathologically mimic malignant lymphomas but their evolution is benign after drug withdrawal. CASE REPORT: We herein reported a case of carbamazepine++-induced pseudolymphoma in a 30 year-old woman of particular interest because of the paucity of clinical symptoms (only six papules of less than one centimetre each). COMMENTS: Phenytoins, carbamazepine++, barbiturates and ACE inhibitors are the main drugs inducing cutaneous pseudolymphomas. These usually mimic T-cell lymphomas. The clinical spectrum of cutaneous pseudolymphomas is broad including severe aspects, such as erythroderma or tumoral eruption and benign appearing one as in our case. Drug investigation is mandatory for each patient with lymphoma appearing cutaneous infiltrates because dramatic and definitive healing of the lesion is always expected in case of pseudolymphoma.

The relationship between MIB-1 proliferation index and outcome in pancreatic neuroendocrine tumors.

The expression of the cell-cycle-associated Ki-67 antigen by MIB-1 monoclonal antibody was retrospectively assessed in 35 surgically resected neuroendocrine tumor specimens of the pancreas embedded in paraffin. The MIB-1 proliferation index was correlated with the classification of the neuroendocrine tumors of the pancreas proposed by Klöppel et al. Four prognostic factors showed a significant correlation with MIB-1: local invasion, metastases, tumor differentiation, and production of insulin. However, analysis by the Cox Proportional Hazards Regression Model showed that only local invasion was an independent predictor of outcome. Finally, our study showed a statistically significant increase in the number of deaths and a statistically significant decrease in survival time when the MIB-1 proliferation index was higher than 4%. We conclude that MIB-1 proliferation index is a simple and reliable tool to predict the clinical outcome of the neuroendocrine tumors of the pancreas. The index might be useful for determining the prognosis for an individual because of the significant decrease in survival when the index is higher than 4%.

In vitro cytotoxic effects of 4,4'-bipyridyl on normal human keratinocytes.

Recent epidemiological studies have brought to light a possible link between premalignant or neoplastic skin lesions (Bowen disease, squamous carcinoma) and occupational exposure to 4,4'-bipyridyl (4,4'B), a precursor in the synthesis of paraquat herbicide. The present study used a serum-free cell culture of normal human keratinocytes (NHK) and two skin-equivalent models to test the effects of exposure to different concentrations of 4,4'B. Cytotoxicity of 4,4'B on NHK was measured by neutral red release assay. Superoxide dismutase (SOD) activity and cell cycle were analyzed in exposed and nonexposed NHK cultures. Histological and immunohistological tests enabled evaluation of differentiation and proliferation effects in reconstructed-skin models. Results showed that significant cytotoxicity occurred after 5 to 11 days' exposure to 4,4'B concentrations of 10(-6)-10(-3) mol/L (IC50 between 10(-3) and 10(-4) mol/L 4,4'B after 11 days). Parallel modifications of SOD activity were recorded. Histological and immunohistological analysis revealed dose-related 4,4'B effects in reconstructed skin models. This involved abnormal terminal differentiation, connected with filaggrin expression, observed in skin models exposed to 10(-7) and 10(-6) mol/L 4,4'B. However, no modification of cell cycle or dysplasia was detected as a result of exposure to 4,4'B. Thus, 4,4'B appears to be cytotoxic for NHK, but as an isolated contaminant, and is unable to induce keratinocyte dysplasia in vitro. These preliminary results do not exclude a cocarcinogenic action of 4,4'B (with UVB for example).

[Transient bullous epidermolysis of the newborn infant. A benign clinical form of dystrophic bullous epidermolysis or an autonomous entity?]. / La dermolyse bulleuse transitoire du nouveau-né. Forme clinique bénigne d'épidermolyse bulleuse dystrophique ou entité autonome?

INTRODUCTION: Transient bullous dermolysis of the newborn is a bullous eruption limited to friction zones. It appears at birth and disappears during the first months of life. CASE REPORT: Immediately after delivery, an infant girl presented cutaneous bullae on areas of trauma which spontaneously regressed after a few weeks. The histology examination confirmed subepidermal involvement (the roof of the bullae took up the anticollagen IV antibody) and ultrastructure anomalies in the baseline membrane: intracellular vacuoles in the keratinocytes containing fibrillary material, disorganization of the anchoring fibers. DISCUSSION: Transient bullous dermolysis of the newborn is a rare (less than 15 cases reported in the literature) benign disease which regresses spontaneously, possibly an explanation of the small number of cases reported. The anomalies in the ultrastructure observed in the baseline membrane strongly suggest transient impairment in collagen VII maturation and excretion. These anomalies are not pathognomonic and can be observed in dystrophic bullous epidermolysis. Currently there is no specific genetic marker to established transient bullous dermolysis as unique entity.

[Stewart-Treves syndrome. Immunohistochemical study apropos of 2 cases]. / Syndrome de Stewart-Treves. Etude immunohistochimique de 2 cas.

Two women (63 and 68 years) presented with primary angiosarcomas of the skin which had developed on an area of chronic lymphoedema after radiosurgical treatment for breast cancer 4 and 13 years earlier. Immunohistochemistry tests formally eliminated epithelial metastasis and produced evidence in favour of lymphatic or capillary vascular proliferation. Endothelial affinity for anti-factor VIII and positive tests for certain markers of intermediary filaments (actin, vimentin) confirmed the vascular and conjunctive tissue origin of the tumours.

[Ploidy analysis in a case of ovarian small cell carcinoma with hypercalcemia]. / Analyse de la ploïdie dans un cas de carcinome de l'ovaire à petites cellules avec hypercalcémie.

The authors studied DNA content in a case of small cell carcinoma with hypercalcemia. This tumor exhibited typical clinical, histological, immuno-histochemical, ultrastructural and biological patterns. DNA content was measured both by flow and image cytometry performed on unfixed tumoral samples. The proliferation index was 10%. These results are similar to those of the literature obtained retrospectively from 10% formalin fixed tissues. The DNA content is a clue to distinguish this entity from other small cell carcinomas of the ovary because immunohistochemical findings are not always informative. The diagnosis of small cell carcinoma of hypercalcemic type should be questioned if DNA content is abnormal.

[Digestive system metastases from breast cancer. Report of two cases]. / Métastases digestives des carcinomes mammaires. A propos de deux observations.

We have reviewed two unusual cases of gastrointestinal metastases from a primary breast carcinoma. The first case was an unexpected microscopic discovery of metastases in an inguinal hernia sac, eleven years after the patient had surgery for breast carcinoma. The second case was a rectal localization from a unknown breast carcinoma. The incidence of gastrointestinal metastasis from breast carcinoma is underestimated because they have a long latency and screening is difficult. Histologically they are predominantly of the lobular type and the differential diagnosis from a primary gastrointestinal malignancy can be difficult. A wider knowledge of gastrointestinal metastases from primary breast carcinoma is important because an appropriate management allows a long survival period.