Antonio De Leo

Molecular Profiling Improves Classification and Prognostication of Nodal Peripheral T-Cell Lymphomas: Results of a Phase III Diagnostic Accuracy Study

PURPOSE The differential diagnosis among the commonest peripheral T-cell lymphomas (PTCLs; ie, PTCL not otherwise specified [NOS], angioimmunoblastic T-cell lymphoma [AITL], and anaplastic large-cell lymphoma [ALCL]) is difficult, with the morphologic and phenotypic features largely overlapping. We performed a phase III diagnostic accuracy study to test the ability of gene expression profiles (GEPs; index test) to identify PTCL subtype. METHODS We studied 244 PTCLs, including 158 PTCLs NOS, 63 AITLs, and 23 ALK-negative ALCLs. The GEP-based classification method was established on a support vector machine algorithm, and the reference standard was an expert pathologic diagnosis according to WHO classification. RESULTS First, we identified molecular signatures (molecular classifier [MC]) discriminating either AITL and ALK-negative ALCL from PTCL NOS in a training set. Of note, the MC was developed in formalin-fixed paraffin-embedded (FFPE) samples and validated in both FFPE and frozen tissues. Second, we found that the overall accuracy of the MC was remarkable: 98% to 77% for AITL and 98% to 93% for ALK-negative ALCL in test and validation sets of patient cases, respectively. Furthermore, we found that the MC significantly improved the prognostic stratification of patients with PTCL. Particularly, it enhanced the distinction of ALK-negative ALCL from PTCL NOS, especially from some CD30+ PTCL NOS with uncertain morphology. Finally, MC discriminated some T-follicular helper (Tfh) PTCL NOS from AITL, providing further evidence that a group of PTCLs NOS shares a Tfh derivation with but is distinct from AITL. CONCLUSION Our findings support the usage of an MC as additional tool in the diagnostic workup of nodal PTCL.

First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation

The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients.

Solid Variant of Adenoid Cystic Carcinoma of the Breast: A Case Series With Proposal of a New Grading System.

Adenoid cystic carcinoma (ACC) of the breast is a low-grade malignancy “triple negative” breast tumor. ACC of the breast can present a great variety of morphological features having a prognostic impact. Recently, cases of ACC having solid-basaloid features (SBACC) have been described. In the present study, 6 cases of SBACC have been reported. All the cases affected female patients aged 47 to 69 years (mean = 54 years). Two patients had metastases to the axillary lymph nodes, and 2 patients experienced local recurrences. No deaths due to the tumor were observed. A review of the literature on breast SBACC showed that local recurrences and lymph node metastases are more frequent than in the ACC conventional type; nevertheless, no deaths due to the tumor are registered at the moment. On the contrary, cases of ACC with features of malignant transformation are on record. Therefore, a new grading system on breast ACC is proposed.

Liquid biopsy in the diagnosis of HPV DNA in breast lesions

AIM HPV DNA has never been investigated in nipple discharges (ND) and serum-derived extracellular vesicles, although its presence has been reported in ductal lavage fluids and blood specimens. MATERIALS & METHODS We analyzed 50 ND, 22 serum-derived extracellular vesicles as well as 51 pathologic breast tissues for the presence of 16 HPV DNA types. RESULTS We show that the presence of HPV DNA in the ND is predictive of HPV DNA-positive breast lesions and that HPV DNA is more represented in intraductal papillomas. We also show the presence of HPV DNA in the serum-derived extracellular vesicles. CONCLUSION Our data supports the use of liquid biopsy to detect HPV DNA in breast pathology.

A Single-Centre Experience on the Management of Adenosarcoma: A Successful Report of an Integrated Medical and Surgical Approach

Adenosarcomas are the rarest form of uterine sarcomas, and clinical experience with their management is still limited. Here, we reported 7 patients with uterine adenosarcoma referred to our institution, focusing on main pathologic features, their medical history, and long-term follow-up. Among these patients, we provided a detailed description of the medical history of a 49-year-old woman with advanced uterine adenosarcoma with sarcomatous overgrowth who presented a brilliant radiologic and pathologic response after 3 cycles of epirubicin and ifosfamide, ultimately achieving an extraordinary long-term outcome through an integrated surgical and medical approach. Our single-centre experience would suggest that aggressive uterine adenosarcomas with sarcomatous overgrowth are sensitive to standard epirubicin and ifosfamide and that an integrated approach, both medical and surgical, could be considered in clinical practice, again emphasizing the relevant role of multidisciplinary management for this extremely rare disease.