Treatment with ipilimumab: a case report of complete response in a metastatic malignant melanoma patient.

INTRODUCTION: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. CASE PRESENTATION: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy(®)), a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), as second-line treatment after progression with dacarbazine, for (wild-type BRAF) metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m(2) on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. CONCLUSION: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

BRAF test and cytological diagnosis with a single fine needle cytology sample.

OBJECTIVE: Recently, fine needle cytology (FNC) of the thyroid has been combined with biomolecular analysis. In particular, there has been detailed study of the V600E-BRAF mutation. The aim of our study is to demonstrate that with a single thyroid sample it is possible to obtain enough cellular material for both cytological diagnosis and a V600E-BRAF molecular test. STUDY DESIGN: FNC was carried out under ultrasound guidance aided by an echographist and cytopathologist. We acquired one biopsy for each nodule with a 23-gauge needle without suction. The preparations were smeared by the pathologist onto one glass slide, air dried and stained with Diff-Quick. Cell adequacy was evaluated for each patient. The needle was washed by aspirating 2 ml of physiologic solution which was collected into a tube. The material was collected for molecular testing. RESULTS: The following cytological diagnoses were made: not neoplastic, Tir2 (n = 227); indeterminate, Tir3 (n = 15); suspicious, Tir4 (n = 4), and malignancy, Tir5 (n = 12). The V600E-BRAF mutation was found in 0 of 227 Tir2 specimens, 2 of 15 (13.3%) Tir3 specimens, 2 of 4 (50%) Tir4 specimens and 9 of 12 (75%) Tir5 specimens. CONCLUSIONS: Our data showed that, in a routine clinical setting, FNC specimens can be handled properly to provide both morphological and molecular information. In fact, our tests show that with a single specimen it is possible to set up a slide for the cytological diagnosis and to obtain enough residual cellular material for DNA extraction (>70 ng) and for the identification of the V600E-BRAF mutation.

A case of abdominal sarcoidosis in a patient with acute myeloid leukemia.

The allogeneic bone marrow transplantation usually preceded by induction chemotherapy, in fit patients, represents the gold standard in the acute myeloid leukaemia. In the last years, many trials have been set up with the view of improving the number of remissions during the induction by adding new drugs. Several early or late side effects have been described in the literature. We herein present a patient with acute myeloid leukaemia patient who, after chemotherapy, developed ascites that turned out to be abdominal sarcoidosis.

Intestinal amyloidosis: two cases with different patterns of clinical and imaging presentation.

The involvement of the small bowel in systemic forms of amyloidosis may be diffuse or very rarely focal. Some cases of focal amyloidomas of the duodenum and jejunum without extraintestinal manifestations have been reported. The focal amyloidomas consisted of extensive amyloid infiltration of the entire intestinal wall thickness. Radiological barium studies, ultrasound and computed tomography (CT) patterns of diffuse small bowel amyloidosis have been described: the signs are non-specific and may include small-bowel dilatation, symmetric bowel wall thickening, mesenteric infiltration, and mesenteric adenopathy. No data are available about the positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) patterns of intestinal amyloidosis. We report two cases of small bowel amyloidosis: the former characterized by focal deposition of amyloid proteins exclusively within blood vessel walls of the terminal ileum, the latter characterized by diffuse intestinal involvement observed on MRI and PET/CT studies.

Consistent up-regulation of Stat3 Independently of Jak2 mutations in a new murine model of essential thrombocythemia.

Janus-activated kinase 2 (JAK2) mutations are common in myeloproliferative disorders; however, although they are detected in virtually all polycythemia vera patients, they are found in approximately 50% of essential thrombocythemia (ET) patients, suggesting that converging pathways/abnormalities underlie the onset of ET. Recently, the chromosomal translocation 3;21, leading to the fusion gene AML1/MDS1/EVI1 (AME), was observed in an ET patient. After we forced the expression of AME in the bone marrow (BM) of C57BL/6J mice, all the reconstituted mice died of a disease with symptoms similar to ET with a latency of 8 to 16 months. Peripheral blood smears consistently showed an elevated number of dysplastic platelets with anisocytosis, degranulation, and giant size. Although the AME-positive mice did not harbor Jak2 mutations, the BM of most of them had significantly higher levels of activated Stat3 than the controls. With combined biochemical and biological assays we found that AME binds to the Stat3 promoter leading to its up-regulation. Signal transducers and activators of transcription 3 (STAT3) analysis of a small group of ET patients shows that in about half of the patients, there is STAT3 hyperactivation independently of JAK2 mutations, suggesting that the hyperactivation of STAT3 by JAK2 mutations or promoter activation may be a critical step in development of ET.

Intestinal toxicity during induction chemotherapy with cytarabine-based regimens in adult acute myeloid leukemia.

BACKGROUND: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association of these symptoms with fever and melena is typical of necrotizing enterocolitis (NE), a life-threatening condition that can be documented by ultrasound abdominal scan. PATIENTS AND METHODS: We analyzed retrospectively the clinical course of 169 adult patients with AML treated by standard dose Ara-C-containing induction regimens, either by continuous venous infusion (group 1) or subcutaneous injection (group 2). Ultrasonography was employed as early diagnostic tool in a majority of patients with gastroenteric complications. Bowel wall thickening was accurately measured and used to confirm the diagnosis of necrotizing enterocolitis. RESULTS: In the first group of 115 patients (median age, 51 years), gastroenteric complications were observed in 55 patients (48%), and 10 patients (9%) received diagnosis of NE, which was fatal in four. Patients with NE had a median age older than that of patients without gastroenteric symptoms, and a more prolonged neutropenia. In the second group of 54 patients (median age, 60 years), gastroenteric events were observed in 14 patients (26%), and no case of NE was recorded. CONCLUSIONS: This retrospective analysis shows that NE is a serious complication occurring mainly in patients treated by Ara-C administered as continuous i.v. infusion.