Atypical Presentation for Adult T-Cell Leukemia/Lymphoma: a Case Report and Short Review of the Literature.

Adult T-cell leukemia/lymphoma (ATLL) is a rare T-cell lymphoproliferative disease associated with human T-cell leukemia virus type 1. There are four subtypes of ATLL: smoldering, chronic, lymphoma and acute. All subtypes can exhibit extranodal involvement. Hepatic infiltration occurs in the chronic, lymphoma and acute types of ATLL, but symptoms are rare. We report the case of a 32-year-old patient with acute-type ATLL and atypical severe hepatic dysfunction at diagnosis. At first, the patient presented with non-specific signs and symptoms, including severe abdominal pain, jaundice, hepatosplenomegaly, ascites and small lymphadenopathies, as well as leukocytosis, which was initially considered reactive. After excluding acute abdomen, the patient was referred to the hematologist. The diagnosis of acute-type ATLL was unexpectedly suggested by peripheral blood smear and confirmed by immunophenotyping by flow cytometry. Multiple causes of liver dysfunction, including hepatic infiltration, paraneoplastic syndrome, infectious diseases, extrahepatic compression, hemophagocytic syndrome, alcoholic liver disease and drug- induced hepatotoxicity, were taken into account. Considering the concurrence of ATLL diagnosis with liver dysfunction, the favorable clinical and biological evolution after specific hematological treatment, and the absence of imaging supporting other possibilities, we concluded that diffuse hepatic infiltration was the most probable cause. When evaluating hepatic dysfunction, considering a broad differential diagnosis is crucial. While it is uncommon, lymphoma should be included in the list of potential causes.

Clinical Features and Survival Outcome in Aggressive-Type Adult T-Cell Leukemia/Lymphoma Patients: Real-Life Experience of a Single Center from an HTLV-1 Endemic Country.

Background and Objectives: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1). ATLL is a rare disease, found more frequently in HTLV-1-endemic areas, Romania being one of them. Despite treatment advances, the prognosis remains dismal. We aimed to describe the clinical, biological, and survival outcome features of Romanian patients with aggressive-type ATLL. Materials and Methods: We report the data of a prospective, observational, and unicentric study of all 20 patients diagnosed with lymphoma and acute types of ATLL at our center over the past 12 years. Data were collected from the patients' medical records. Results: Lymphoma-type ATLL (60%) was more common than acute-type ATLL (40%). Median age at diagnosis was 40.5 years, and most patients were female. Laboratory data revealed significant differences between acute and lymphoma-type ATLL, namely, higher leukocyte (p = 0.02) and lymphocyte counts (p = 0.02) and higher levels of corrected calcium (p = 0.001) in acute-type ATLL. All patients received chemotherapy, and only two underwent allogeneic stem cell transplantation. Only six patients obtained a complete or partial response to chemotherapy, mostly the lymphoma-type ones. The median survival for all patients was 6.37 months, with higher survival in the lymphoma-type ATLL (8.16 months) than in the acute-type (3.60 months). Normal calcium levels (p = 0.011), uric acid (p = 0.005), BUN score (p = 0.000), JCOG-PI moderate risk (p = 0.038), and obtaining complete or partial response (p = 0.037) were associated with higher survival. Conclusion: Aggressive-type ATLL among Romanian patients presents distinct characteristics, including younger age at diagnosis, female predominance, and higher incidence of lymphoma-type ATLL compared to currently reported data. Survival remains very low, with all subtypes experiencing a median survival of less than one year.

The Philadelphia Chromosome, from Negative to Positive: A Case Report of Relapsed Acute Lymphoblastic Leukemia Following Allogeneic Stem Cell Transplantation.

Relapsed acute lymphoblastic leukemia (ALL) represents a continuous challenge for the clinician. Despite recent advances in treatment, the risk of relapse remains significant. The clinical, biological, cytogenetic, and molecular characteristics may be different at the time of relapse. Current comprehensive genome sequencing studies suggest that most relapsed patients, especially those with late relapses, acquire new genetic abnormalities, usually within a minor clone that emerges after ALL diagnosis. We report the case of a 23-year-old young woman diagnosed with Philadelphia chromosome-negative B cell acute lymphoblastic leukemia. The patient underwent allogeneic stem cell transplantation (allo-HSCT) after complete remission. Despite having favorable prognostic factors at diagnosis, the disease relapsed early after allo-HSCT. The cytogenetic and molecular exams at relapse were positive for the Philadelphia chromosome, respectively for the Bcr-Abl transcript. What exactly led to the recurrence of this disease in a more aggressive cytogenetic and molecular form, although there were no predictive elements at diagnosis?

Particularities of Neurological Manifestations in Adult T-Cell Leukemia/Lymphoma: Need for a Multidisciplinary Approach-A Narrative Review.

ATL is a rare but a highly aggressive T-cell neoplasm associated with human T-cell leukemia virus-1 (HTLV-1) infection. Human T-cell lymphotropic virus type-1 (HTLV-1) is a oncogenic retrovirus responsible for the development of adult T-cell leukemia (ATL), but also for other non-malignant diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 has a higher prevalence in Japan, the Caribbean, South America, intertropical Africa, Romania, and northern Iran. ATL patients can have an extensive spectrum of neurological manifestations. Numerous factors can be implicated, such as central nervous system infiltrates, neurolymphomatosis, complications to medication or allogeneic stem cell transplantation, HAM/TSP, infections, metabolic disturbances. The neurological complications are not always easy to recognize and treat. Thus, this review underlines the necessity of a multidisciplinary approach in ATL patients with neurological symptomatology.

Taurine and Its Derivatives: Analysis of the Inhibitory Effect on Platelet Function and Their Antithrombotic Potential.

Taurine is a semi-essential, the most abundant free amino acid in the human body, with a six times higher concentration in platelets than any other amino acid. It is highly beneficial for the organism, has many therapeutic actions, and is currently approved for heart failure treatment in Japan. Taurine has been repeatedly reported to elicit an inhibitory action on platelet activation and aggregation, sustained by in vivo, ex vivo, and in vitro animal and human studies. Taurine showed effectiveness in several pathologies involving thrombotic diathesis, such as diabetes, traumatic brain injury, acute ischemic stroke, and others. As human prospective studies on thrombosis outcome are very difficult to carry out, there is an obvious need to validate existing findings, and bring new compelling data about the mechanisms underlying taurine and derivatives antiplatelet action and their antithrombotic potential. Chloramine derivatives of taurine proved a higher stability and pronounced selectivity for platelet receptors, raising the assumption that they could represent future potential antithrombotic agents. Considering that taurine and its analogues display permissible side effects, along with the need of finding new, alternative antithrombotic drugs with minimal side effects and long-term action, the potential clinical relevance of this fascinating nutrient and its derivatives requires further consideration.

Primary, secondary or less frequent causes of immune thrombocytopenia: A case report.

Primary immune thrombocytopenia (ITP) is characterized by isolated low platelet count and it is a diagnosis of exclusion, contrasting to secondary ITP. Therefore, a positive diagnosis is difficult and requires extensive investigation. Some of the underlying conditions that are associated with ITP are lymphoproliferative disorders and infections, especially viral ones. In the present study, the case of a patient diagnosed with diffuse large B-cell lymphoma, who received chemotherapy and autologous hematopoietic stem cell transplantation is presented. After a complete remission of four years, the patient presented with sudden intense hemorrhagic syndrome and severely decreased platelet count. The most frequent causes of secondary ITP were excluded, including lymphoma relapse, and intravenous corticosteroids were started. However, shortly after hospital admission, the patient developed neuro-psychiatric anomalies, fever and pancytopenia, and West-Nile encephalitis was diagnosed. Although the initial development was favorable, he started to complain of progressive severe muscle weakness and eventually succumbed to infectious complications in the setting of prolonged hospitalization, corticotherapy, and immobilization.

Synchronous Multiple Breast Cancers-Do We Need to Reshape Staging?

Background and Objectives: Current recommendations and treatment regimens in breast cancer are a reflection of its heterogeneity on multiple levels including histological subtypes, grading, molecular profiling, and numerous prognostic indices. Although based on extensive research, current guidelines are not explicit in the case of surgical specimens showing various degrees of mismatch between different parts of the same tumor and even more so between multicentric lesions. Synchronous breast cancer is the ideal prototype for studying inter- and intra-tumoral heterogeneity, therefore we envisaged that a study on patients with multicentric and multifocal lesions could contribute to the reshaping of the staging, prognosis, and treatment of breast malignancies. Material and Methods: A prospective observational study was conducted between January 2013 and May 2017 on 235 patients diagnosed with breast cancer (BC) and surgically treated at Emergency University Hospital, Bucharest. Thirty-seven patients had multiple breast tumors and were eligible for assessment of the heterogeneity of their lesions. Results: 6 were multicentric and 31 multifocal. The number of foci varied from 2 to 11. We encountered numerous mismatches between the index and the secondary tumors, as follows: 3 cases (8.1%) with histopathological mismatch, 13 (35.1%) with different grades of differentiation, 11 (29.8%) with ER (Estrogen Receptors) status mismatch, 12 (32.4%) with PR (Progesterone Receptors) status mismatch, 8 (21.6%) with molecular phenotype mismatch, and 17 (45.9%) cases with variable Ki-67. After careful analysis of index and secondary tumors, apart from the mismatches reported above, we discovered that the secondary tumors were actually dominant in 5 cases (13.5%), and therefore at least those cases had to be reclassified/restaged, as the supplementary data commanded changes in the therapeutic decision. Conclusions: For synchronous breast tumors, the current Tumor-Node-Metastasis (TNM) staging system ignores not only the histopathological and immunohistochemical characteristics of the secondary foci, but also their size. When secondary lesions are more aggressive or their cumulative mass is significantly bigger than that of the index tumor, the treatment plan should be adapted accordingly. We believe that information obtained from examining secondary foci in synchronous breast cancer and assessment of the cumulative tumoral mass should be reflected in the final staging and definitive treatment. The clinical benefit of staging the patients based on the most aggressive tumor and the cumulative tumoral burden rather than according to the biggest single tumor, will avoid under-treatment in cases with multifocal/multicentric BC displaying intertumoral mismatch.

Splenectomy in Lymphoproliferative Disorders: A Single Eastern European Center Experience.

Background and Objectives: Hematological malignancies are usually systemic diseases of life-threatening impact, and frequently require prompt and energetic therapeutic intervention. Due to systemic involvement, the role of surgery is generally limited to diagnostic approaches, and it is very rarely employed as a therapeutic modality. Splenectomy represents an exception to this paradigm, being used both as a diagnostic and tumor debulking procedure, notably in splenic lymphomas. Materials and Methods: We investigated the role of splenectomy in a single center prospective study of splenectomy outcome in patients with splenic involvement in the course of lymphoproliferative disorders. In the present study, we included all patients treated in our department for lymphoid malignancies over a period of six years, who underwent splenectomy as a diagnostic or debulking procedure after referral and workup, or had been referred to our department after first being splenectomized and diagnosed with splenic lymphoma. Patient characteristics and treatment outcome were investigated. Results: We enrolled 54 patients, with 34 (63%) splenectomized patients: 12 splenectomies (22.2%) for diagnostic purposes and 22 (40.7%) for treatment. Special attention was given to the 28 (51.85%) patients diagnosed with splenic marginal zone lymphoma (SMZL), a subtype with a clear therapeutic indication for splenectomy. Average age of patients was 57.5 (±13.1) years with a higher prevalence of feminine gender (66.67%). Age above 60 years old (p = 0.0295), ECOG (Eastern Cooperative Oncology Group) > 2 (p = 0.0402) and B-signs (p nonsignificant (NS)) were most frequently found in SMZL patients. Anemia, and notably autoimmune anemia, was more frequent in SMZL versus other small-cell lymphomas and also in splenectomized patients, as was leukocytosis and lymphocytosis. Treatment of patients with lymphoproliferative disorders consisted of chemotherapy and/or splenectomy. Most SMZL patients received chemotherapy as first line treatment (61.5%) and had only partial response (57.7%). Second treatment line was splenectomy in 80% of patients who required treatment, followed by a 60% rate of complete response (CR). Splenectomy offered a higher complete response rate (twice as high than in non-splenectomized, regardless of histology type, p = NS), followed by a survival advantage (Overall Survival (OS)~64 versus 59 months, p = NS). Particularly, SMZL patients had a 4.8 times higher rate of CR than other non-Hodgkin lymphoma (NHL) patients (p = 0.04), a longer progression free survival (73 months vs. 31 months for other small-cell NHLs p = NS) and a 1.5fold lower death rate (p = NS). The procedure was rather safe, with a 38.5% frequency of adverse reactions, mostly minor and manageable. Conclusions: Our data suggest that splenectomy is an effective and safe therapeutic option in patients with lymphoid malignancies and splenic involvement, particularly splenic marginal zone lymphoma.