Acquired Hemophilia in an Elderly Patient with Carcinoma of the Ampulla of Vater.

Acquired hemophilia is a rare autoimmune bleeding disorder related to the production of autoantibodies that inhibit clotting factor VIII or IX. The underlying cause can be autoimmune disease, malignancy, pregnancy, or medications, but it is most commonly idiopathic. Here we present the case of an 81-year-old patient with locoregionally relapsed periampullary carcinoma who presented with soft tissue hematoma and an abnormally elevated activated partial thromboplastin time (aPTT) in the presence of a normal prothrombin time. A diagnosis of acquired hemophilia was established. The patient was managed with immunosuppressive prednisone and cyclophosphamide plus immunoglobulin G. He also received a cycle of chemotherapy with gemcitabine and oxaliplatin, because the underlying malignancy was the cause of the bleeding disorder. Care was complicated by neutropenia and nosocomial fever, but the patient eventually showed signs of clinical stability, while the aPTT decreased 2-fold. The patient was successfully discharged from the hospital and continued treatment in outpatient care.

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma.

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

A revised international prognostic score system for Waldenström's macroglobulinemia.

A staging system was developed a decade ago for patients with Waldenström's macroglobulinemia (WM), however, since then WM treatments have changed. A revised staging system could better capture prognosis of WM patients in the chemoimmunotherapy era. We developed a revised system based on data from 492 symptomatic patients with at least 3 years and a median of 7 years of follow up while an independent validation cohort included 229 symptomatic patients. We identified age (≤65 vs 66-75 vs ≥76 years), b2-microglobulin ≥ 4 mg/L, serum albumin <3.5 gr/dl, and LDH ≥ 250 IU/L (ULN < 225) to stratify patients in five different prognostic groups and identify a very-low risk as well as a very-high risk group with a 3-year WM-related death rate of 0, 10, 14, 38, and 48% (p < 0.001) and 10-year survival rate of 84, 59, 37, 19, and 9% (p < 0.001). We evaluated this staging system separately in patients >65 years and <65 years, according to the reason for initiation of treatment, among patients receiving frontline rituximab or in patients treated primarily without rituximab. With further validation before clinical use, this revised IPSSWM could improve WM patient risk stratification, is easily available and may be used in the everyday practice to provide prognostic information.

CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

Most primary cutaneous B-cell lymphomas (PCBCL) are CD5 negative, and only a few cases were found to express CD5. We report the first well-documented CD5+ primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT). A 71-year-old woman with a history of Multiple Sclerosis was admitted because of a nodule at the left thigh. Histological examination of the skin biopsy disclosed a diffuse dermal infiltration by large lymphoid cells. Immunohistochemistry revealed that these large cells were positive for CD5, CD20, CD79a, MUM1/IRF4, Bcl6, Bcl2, and cytoplasmic IgM/λ, whereas CD3, CD56, CD23, CD21, CD10, CD30, cyclin D1, CD68, lysozyme, myeloperoxidase, and CD34 were not detected. Thus, the diagnosis of a CD5+ PCDLBCL-LT was made. Despite treatment, the patient died 11 months after initial diagnosis.

Postoperative chemotherapy with single-agent fluoropyrimidines after resection of colorectal cancer liver metastases: a meta-analysis of randomised trials.

Surgical resection is the only option of cure for patients with metastatic colorectal cancer. Risk of recurrence after metastasectomy is around 75%. Use of adjuvant chemotherapy after metastasectomy is controversial. AIM: To address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone. METHODS: Systematic review of literature and meta-analysis of all available randomised evidence. Relative hazards (RHs) were summarised across trials and heterogeneity was assessed with the Q and I2 statistics. RESULTS: Five trials were eligible. Three trials, all using single-agent fluoropyrimidine chemotherapy, presented data valuable for analyses. 482 patients were included in the meta-analysis: 238 randomly assigned to receive postoperative chemotherapy and 244 to metastasectomy only. We found no overall survival (OS) benefit with the use of postoperative single-agent fluoropyrimidines compared with surgery alone, even if a trend for benefit was observed (relative hazard (RH)=0.781, 95% CI 0.593 to 1.030, p=0.080). Significant disease-free survival benefit with the use of postoperative chemotherapy was observed (RH=0.645, 95% CI 0.509 to 0.818, p=0.001). No quality of life (QL) data were available. All trials showed accrual delay, two stopped and one recruiting after 10 years. Long follow-up needs were evidenced since OS curves split only after 3.5 years. CONCLUSIONS: No OS benefit was documented from the use of postoperative monochemotherapy. Metastasectomy alone continues to be the standard of care. Combination chemotherapy regimens should be evaluated along with QL assessment in future trials appropriately designed for long-term accrual and follow-up.

Extranodal diffuse large B-cell lymphomas: A retrospective case series and review of the literature.

Non-Hodgkin lymphomas commonly show extranodal involvement (25-30%) but primary diffuse large B-cell lymphomas (DLBCL) with extranodal localization represent clinically and molecularly distinct entities. The present study involved retrospective analysis of case records of 4 patients who were diagnosed with extranodal DLBCL between 2010 and 2016 at the Medical Oncology and Hematology Departments of the Ioannina University Hospital, Greece. Median age of presentation was 69 years (range 60-77 years). There were 2 males and 2 females. The sites of DLBCL involvement included adrenal gland, mandible, cervix uteri, and ileum. Two patients had B symptoms while none had bone marrow involvement. After staging workup, all the patients fell into IE stage. The treatment approach included chemotherapy combined with rituximab (R), whereas one patient received additionally irradiation therapy. Post-treatment positron emission tomography-computed tomography scan was performed in 3 patients. In terms of the outcome, 3 patients are alive in complete response, whereas one was lost in follow-up. Further prospective data analyses are required so as to better elucidate the biology and course of extranodal DLBCL.

Nivolumab-induced hypothyroidism and selective pituitary insufficiency in a patient with lung adenocarcinoma: a case report and review of the literature.

Immune checkpoint blockade including programmed cell death 1 pathway inhibition with agents such as nivolumab is gaining ground in a wide array of malignancies, so far demonstrating significantly improved survival rates even in metastatic, often multiply pretreated settings. Although targeted in nature and generally well-tolerated compared with conventional anticancer treatments, these agents are often linked to a newly emerged group of adverse reactions, referred to as immune-related adverse events, which can also affect endocrine organs. This is a case report of a patient who received nivolumab for the treatment of recurrent metastatic non-small cell lung cancer and developed primary hypothyroidism and secondary adrenal insufficiency caused by selective pituitary dysfunction (with preservation of all other endocrine functions). After hormone replacement with daily administration of T4, T3 and hydrocortisone, the patient achieved complete recovery. Adequate characterisation of these rare yet potentially severe entities is essential for prompt diagnostic and therapeutic interventions that will permit us to fully benefit from these new agents' therapeutic potential.

Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment.

Loss of a section of the long arm of chromosome 5, as a sole cytogenetic abnormality, characterizes a rare type of myelodysplastic syndrome [del(5q) MDS] and the co-existence of the JAK2 V617F mutation occurs in a small subset of these cases. Patients with isolated del(5q) MDS have a relatively favorable prognosis, with transformation to acute myeloid leukemia occurring in <10%, and their disease responds well to lenalidomide. However the optimal therapeutic approach for patients with del(5q) MDS in coexistence with the JAK2 V617F mutation, which is common to myeloproliferative neoplasms, remains to be elucidated. The present study reports a 77-year-old, transfusion-dependent female patient diagnosed with del(5q) MDS and a concomitant JAK2 V617F mutation. The patient was started on 10 mg lenalidomide daily for 21 days in a 28 day-cycle and within the first month of treatment, the patient became transfusion-independent. The only toxicity observed was grade 3 neutropenia, which was managed with transient treatment discontinuation and dose reduction on restart (5 mg). The patient achieved a complete cytogenetic and molecular response (normal karyotype and undetected JAK2 V617F mutation) within 6 months of treatment. However, 12 months post treatment initiation and while on hematological, cytogenetic and molecular response, the patient was unwilling to continue on treatment and lenalidomide was discontinued. The patient remains in hematological response, which lasts for >5 years despite treatment discontinuation. The present case highlights the coexistence of the JAK2 V617F mutation in del(5q) MDS and suggests that lenalidomide treatment is beneficial and effective for these patients, leading to complete hematological, cytogenetic and molecular response. Hematological response may be sustained for long periods of time, even following the discontinuation of the treatment.

Prognostication in young and old patients with Waldenström's macroglobulinemia: importance of the International Prognostic Scoring System and of serum lactate dehydrogenase.

We analyzed 232 patients with previously untreated, symptomatic WM, of whom 10% were < or = 50 years of age and 21% were > 75 years of age. Disease features and response to treatment were similar among age groups. Patients > 75 years of age had significantly shorter survival (OS; 53 months vs. 113 months for those > 50-75 years vs. not reached for patients < or = 50 years of age; P < .001). Despite the fact that 33% of elderly patients died of causes unrelated to WM, disease-specific survival (DSS) was 72 months for patients > 75 years, 120 months for those > 50-75 years and not reached for patients < or = 50 years (P = .001). International Prognostic Scoring System for WM (IPSSWM) could discriminate 3 risk groups with significantly different OS or DSS. The addition of elevated serum lactate dehydrogenase in the IPSS improved the ability of IPSS to identify a group of patients with a significantly worse outcome (median survival, 55 months).

Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide.

PURPOSE: Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC). PATIENTS AND METHODS: Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5 (total dose, 1,000 mg/m2). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta2-microglobulin (43%). RESULTS: On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab. CONCLUSION: Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.

Primary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with multiple myeloma.

Fifty patients with multiple myeloma >or=75 years of age received primary treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20. This regimen was repeated every 5 weeks for three courses. Patients without evidence of disease progression received nine additional courses of MDT, but without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a partial response and 10% a complete response. The median time to response was 2 months. The median time to progression for all patients was 21.2 months. Deep venous thrombosis and peripheral neuropathy each occurred in 9% of patients.

Imipenem-cilastatin induced pure white cell aplasia.

Antibiotic-induced severe neutropenia and less frequently agranulocytosis has been reported. In most of these cases a relatively normal myelopoiesis is found. We report on the first case of agranulocytosis with histological evidence of pure white cell aplasia associated with imipenem-cilastatin treatment.