Trabectedin in Ovarian Cancer: is it now a Standard of Care?

In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7.3 versus 5.8 months) and overall survival (22.2 versus 18.9 months) benefit compared with single-agent pegylated liposomal doxorubicin (PLD) in the OVA 301 phase III trial. This drug has been shown to prolong the time to first subsequent treatment and improve the efficacy of further platinum-based chemotherapy. The role of trabectedin/PLD followed by platinum combination compared with the reverse sequence in PPS is actually in evaluation in the INOVATYON phase III study, which will clarify the best sequence to be adopted in this setting. Trabectedin has been shown to be active in patient carriers of BRCA mutations, probably for its mechanism of action directly affecting DNA and it is actually tested as a single agent in some phase III trials in BRCA mutated and BRCAness ovarian cancer patients. Trabectedin is also active on the immune system. There is, therefore, the rational for new trials of a combination with immune checkpoint inhibitors.

Salivary epithelial-myoepithelial carcinoma: clinical, morphological and molecular features.

Epithelial-myoepithelial carcinoma (EMC) is a rare biphasic tumor accounting for less than 2% of all salivary gland malignancies. It presents as a slowly growing, asymptomatic small size mass, with ulceration of overlying mucosa in some cases. Microscopically, it is characterized by glands lined by the simultaneous presence of two different cell components, inner epithelial cells and outer myoepithelial cells. Immunohistochemical staining of myoepithelial cells is variably positive for vimentin, Smooth Muscle Actin (SMA), Muscle Specific Actin (MSA), S100, Smooth Muscle Myosin Heavy Chain I(SM-MHC), calponin and p63. Several molecular alterations, mainly point mutations, have been described. Mutations of HRAS, AKT1, CTNNB1 and PIK3CA were highlighted in variable percentage of EMC samples. EMC is considered a low-grade malignant tumor with a 5-year survival rate of 94% that may commonly recur locally after resection in 30-50% of cases. At the moment, adequate resection with negative margins is the minimum recommended and necessary treatment.

[Cervico-mediastinal carcinoma of the parathyroid: report of a case]. / Carcinoma cervicomediastinico della paratiroide: report di un caso.

Parathyroid carcinoma is a rare malignancy. We report the case of a 66 years old man referred to our department for a large substernal goiter suspected as a thyroid cancer associated with severe hyperparathyroidism. After normalization of serum levels of calcemia, total thyroidectomy and subtotal parathyroidectomy was performed. Histopathology revealed a parathyroid cancer of 450 g.

Warthin-like tumour of the thyroid gland: RET/PTC expression indicates it is a variant of papillary carcinoma.

AIMS: Three cases with features of so-called 'Warthin-like tumour' of the thyroid (WaLTT) are described, in order to evaluate its relationship with papillary carcinoma (PC). METHODS AND RESULTS: We performed an histological and immunohistochemical study with emphasis on RET/PTC expression. The most striking features are represented by marked lymphocytic infiltration in the stalks of papillae and by oxyphilic metaplasia of epithelium, resembling Warthin tumour of the salivary gland. In all cases, we found nuclear features reminiscent of PC. The neoplastic cells were strongly positive for Leu M1 and epithelial membrane antigen (EMA), less for thyroglobulin and negative for calcitonin. The lymphocytic infiltrate was composed of a mixed population of B and T-cells with sparse S100-positive Langerhans cells. An interesting finding was the strong positivity with the antibody against RET/PTC. CONCLUSION: All clinicopathological data along with the presence of the extensive lymphocytic infiltrate could imply a more favourable prognosis. The expression of RET/PTC fusion gene adds support to the hypothesis that this tumour is a variant of PC, probably related to the oncocytic variant of PC.

Post-operative complications after completion thyroidectomy for differentiated thyroid cancer.

The surgical approach to differentiated thyroid carcinoma is still controversial, as many authors consider it necessary to remove the whole gland. Therefore, when definitive histological diagnosis is made following limited resection, reoperation and completion thyroidectomy (CT) is sometimes recommended. The main indications are for follicular cancer or for patients with a carcinoma of > or = 1 cm previously treated with lobectomy or limited resection (early CT), or for local recurrence after previous treatment (late CT). Several authors, however, draw attention to the high rate of complications following completion thyroidectomy and advocate its use in more limited circumstances. The aim of the study was to evaluate the results of our experience with CT in the National Cancer Institute in Naples. Of 131 patients treated for thyroid cancer 35 (26.7%) underwent a CT. Re-operation was performed within 6 months in 26 cases (74.3%) and later in the remaining nine cases (25.7%): carcinoma in the residual gland was found in six cases (23%) of early CT, and in four cases (45%) in the late CT group with an overall incidence of 28.5%. Post-operative complications were: transient hypoparathyroidism, two cases (5.6%), permanent in one (2.8%). Transient recurrent laryngeal nerve palsy occurred in three patients (8.5%) and became permanent in one case (2.8%). Completion thyroidectomy can therefore be considered a safe procedure.