A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA).

BACKGROUND: BRCA1/2-related metastatic breast cancers (mBC) are sensitive to DNA-damage agents and show high tumor-infiltrated lymphocytes. We hypothesized that the association between pembrolizumab and carboplatin could be active in BRCA-related mBC. PATIENTS AND METHODS: In this phase II Simon's design multicenter single-arm study, BRCA1/2-related mBC patients received carboplatin at area under the curve 6 every 3 weeks for six courses associated with 200 mg pembrolizumab every 3 weeks until disease progression or unacceptable toxicity. The primary aim at first stage was overall response rate (ORR) ≥70%. Disease control rate (DCR), time to progression (TTP), duration of response (DOR), and overall survival (OS) were the secondary aims. RESULTS: Among 22 patients enrolled at the first stage, 5 BRCA1 and 17 BRCA2, 16 (76%) were luminal tumors and 6 (24%) triple-negative BC (TNBC). In 21 patients, ORR and DCR were 43% and 76% (47% and 87% in luminal, 33% and 50% in TNBC), respectively. TTP was 7.1 months, DOR was 6.3 months, and median OS was not reached. Grade ≥3 adverse events (AEs) or serious AEs occurred in 5/22 patients (22.7%). Since the primary aim was not met, the study was terminated at the first stage. CONCLUSIONS: Although the primary aim was not reached, data on efficacy and safety of pembrolizumab plus carboplatin in first-line visceral disease BRCA-related luminal mBC were provided and they need to be further investigated.

Heavy metal and tattoo: an allergy and legislative problem.

We presented an interesting clinical case of a 23 years old man presented with a 2-week history of pruritus, erythema and papules on legs, arms and trunk. These lesions developed 2 months after tattooing. It showed positive patch test reaction to Copper and Disperse Blu.

Basal cell carcinoma: differences according to anatomic location and clinical-pathological subtypes.

AIM: Basal cell carcinoma (BCC) is the most common skin malignant neoplasm in humans. Its localization and its clinical-pathological aspects are fundamental for the treatment and the outcome of these tumors. We wanted to verify if different clinical-pathological subtypes of BCC may be present with different frequencies on single skin areas. METHODS: Three hundred six patients affected by BCC seen in Sant'Andrea Hospital, U.O.C. Dermatology, NESMOS Department, Faculty of Medicine, University of Rome "Sapienza", from January 2008 to December 2010, were retrospectively included in this study. Findings from all patients were tabulated and analyzed to characterize the clinical-pathological aspects of BCC according to their anatomic localization. We considered the following clinical subtypes of BCC, nodular, superficial, sclerodermiform, pearly and ulcerative. RESULTS: One hundred ninety-seven out of 306 patients (64.4%) were localized on the head, 6 (1.9%) on the neck, 73 patients (23.9%) on the trunk, 2 (0.6%) on the perineum, 4 (1.3%) on upper limbs and 24 (7.9%) on legs. On the head BCC were mostly nodular (44.7%). On the trunk they were mostly superficial (34.3%). BCC on legs were ulcerative in all the 24 patients. CONCLUSION: Our data confirm that BCC may have different clinical-pathological aspects on single skin areas. Interestingly in our casistic BCC on the legs were present in an uncommon high percentage. They presented as ulcerative lesions and this fact leads to conclude that in every patient presenting a chronic ulcer on the leg with difficulty to be cured a biopsy is mandatory to put in evidence the possible presence of BCC and consequently to perform the correct surgical treatment to obtain a complete response for the patient.

Magnesium stearate: an underestimated allergen.

Magnesium stearate is a substance often used as a diluent in the manufacture of medical tablets, capsules and powders. Moreover it is usually found as a food additive or pharmaceutical excipient. We report the first case of a 28 years old woman affected by an allergic reaction from this substance with an urticarial manifestation.

A case of periocular contact dermatitis caused by cypress allergy.

Airborne contact dermatitis is a dermatological disease manifesting predominantly on the face, neck and arms, which is caused by volatile substances which settle on exposed skin. Although the diagnosis is not difficult, the finding of causative allergens and the exclusion of differential diagnoses are still lacking by the treating dermatologists.

Psoriasiform dermatitis in a non-psoriatic patient treated with adalimumab.

Anti-TNF drugs may be associated with various adverse reactions including cutaneous ones. We describe the case of a 45-year-old woman affected by undifferentiated spondyloarthritis who presented a localized psoriasiformis dermatitis during treatment with adalimumab, without any medical history of psoriasis.

Ehlers-Danlos syndrome: case report and an electron microscopy study.

Ehlers-Danlos syndrome (EDS) type III is a inherited connective tissue disorders characterized by extensibility of the skin, hypermobility of the joints, chronic pain, tissue fragility, easy bruising, and delayed wound healing with result of atrophic scars. The patients report commonly a history of recurrent dislocations of the shoulders and knees after low-impact trauma, chronic joint pain, and early osteoarthritis, which lead to diagnosis. The pathogenesis of this condition is unknown, and the diagnosis is generally made in adult age, based only on clinical criteria. In this report, we describe a case of a 50-year-old woman with a 30-year history of recurrent dislocations and atrophic scars. We performed diagnosis of EDS type III after a complete clinical and instrumental evaluation, comprising of histological and electron microscopic studies, that highlighted collagen abnormalities.

An unusual case of annular bollous eruption of the inguinal folds.

Pemphigus herpetiformis is a rare clinical entity belonging to the group of autoimmune blistering disorders of the skin, that usually presents clinical features of dermatitis herpetiformis and immunologically findings of pemphigus. Because of the variety of its presentation, differential diagnosis with other bollous diseases is not simple and histopathological results have to be supported by direct immunofluorescence assay, for a correct diagnosis. We report the case of a young woman, where immunofluorescence was a fundamental tool to reach the diagnosis of pemphigus herpetiformis, because of the lack of acantholitic cells at histological sample.

An 18-year follow-up of a case of D-penicillamine-induced Elastosis perforans serpiginosa.

Elastosis perforans serpiginosa (EPS) is a rare complication of chronic therapy with a high-dose of D-penicillamine (1 g daily for more than 5 years), characterized by the elimination of abnormal elastic fibers from the upper dermis through the epidermis. D-penicillamine (DPA) is a heavy metal chelator primarily used for disorders such as cystinuria and Wilson disease. This therapy can lead to induction of EPS through a still unknown mechanism. We report the follow-up of a D-penicillamine-induced EPS in patient with Wilson disease, which prompted us to switch the therapy with trientine (another metal chelator). After 14 years the cutaneous lesions are still visible; therefore, we conclude that the DPA-induced cutaneous damage is irreversible.

Anetoderma: evidence of the relationship with autoimmune disease and a possible role of macrophages in the etiopathogenesis.

Anetoderma is a benign condition characterized by round or oval macular lesions with focal loss of dermal elastic tissue resulting in localized areas of flaccid or herniated saclike skin. Often, the anetoderma is associated with immuno-mediated pathogenetic mechanism. In this article, we describe the association between anetoderma and autoimmune diseases, by underlining the role and the action of macrophages as a possible etiopathogenesis.

[Infectious endocarditis following artificial insemination. A clinical case report and review of the literature]. / Endocardite infettiva seguita ad inseminazione artificiale. Descrizione di un caso clinico e revisione della letteratura.

We describe a case of infective endocarditis in a 33 year old patient, with mitral valve prolapse (MVP), who underwent nine attempts of artificial insemination with semen by donor. Several blood cultures demonstrated the presence of Enterococcus faecalis; the same agent was identified in some vaginal cultures. Despite antibiotic therapy, infective endocarditis was complicated by severe mitral regurgitation, followed by the rupture of a chorda tendinea. The patient underwent cardiac surgery: valvuloplasty of posterior mitral cusp, chordae tendineae in Goretex and anulus reinforcement with autologous pericardium. MVP is the most common heart disease associated with infective endocarditis in non-drug addict patients (32-54%). The review of the literature did not show any other case of infective endocarditis after artificial insemination procedures. Because of the large spread of these procedures, we think antibiotic prophylaxis of infective endocarditis should be considered in patients with MVP.

[Anti-arrhythmic action of magnesium sulfate in "torsade de pointes" ventricular arrhythmia]. / Azione antiaritmica del solfato di magnesio nella aritmia ventricolare a "torsione di punta".

A female patient with recurrent "torsades de pointes" and a long QT interval was successfully treated with i.v. magnesium sulfate. This work provides further support of the use of magnesium sulfate in this particular arrhythmia.