ABSTRACT
Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive form of peripheral T-cell lymphoma (PTCL). It can present with signs and symptoms that have broad differentials, including fevers, night sweats, and skin rashes. In this case report, we present an interesting case of a young male of Nigerian descent with recently treated malaria who presented with such symptoms and a picture that was complicated, due to an inconclusive excisional biopsy for lymphoma. He was later diagnosed with AITL. Given the patient's recent exposure to malaria, we will discuss the potential role malaria has in the development of AITL.
ABSTRACT
Gray zone lymphoma (GZL) is an uncommon neoplasm with intermediate features of both classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). It was identified in the World Health Organization (WHO) classification as its own neoplasm in 2008. Patients infected with human immunodeficiency virus (HIV) have been rarely diagnosed with this type of lymphoma and treatment strategies for this subset of patients is not well described. Here we present two cases of patients with HIV that were diagnosed with GZL in a single community-based institution. A 68-year-old male with HIV/acquired immunodeficiency syndrome (AIDS) on highly active antiretroviral therapy (HAART) presented with 6-month history of dyspnea and weight loss. Computed tomography (CT) of the chest revealed multiple lung and mediastinal lesions, the largest measuring 9.4 × 5.5 cm lesion in the right perihilar region. Lymph node biopsy revealed abnormal lymphocytes with immunohistochemistry (IHC) positive for cluster of differentiation 30 (CD30), CD20 and Epstein-Barr virus (EBV), consistent with a diagnosis of GZL. The patient received dose-adjusted etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab (DA-EPOCH-R) and attained a complete response. He since completed maintenance rituximab therapy and remains disease-free at 33 months. A 40-year-old female with HIV/AIDS on HAART presented with high-grade fever, dyspnea, and weight loss. CT imaging revealed multiple lung lesions, hepatosplenomegaly and diffuse lymphadenopathy in the chest and abdomen. Lymph node and bone marrow biopsy revealed cells positive for CD20, CD30, and EBV within atypical lymphoid cells. With this, a diagnosis of GZL was made and she was treated with DA-EPOCH-R. She attained a complete response and was on maintenance rituximab therapy. At 9 months she relapsed, she has now received a bone marrow transplant. GZL is a rarely described neoplasm within the HIV population. Here we describe two HIV patients diagnosed with GZL that were successfully treated at our institution. DA-EPOCH-R was able to induce durable remission with limited side effects and it represents a viable strategy for treating patients in this population. Further studies need to be performed to better characterize this lymphoma, especially in HIV patients. Treatment strategies for this select group of patients also need to be better defined.
ABSTRACT
Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known driver mutation is platinum-based chemotherapy, which has a response rate of only 30-33%. Through an siRNA screen, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces clonogenicity of NSCLC cells by 98.7% (p < 0.001), increases DNA damage, and induces G1/S phase cell cycle arrest and apoptosis. PAPSS1 silencing also sensitized NSCLC cells to other DNA crosslinking agents, radiation, and topoisomerase I inhibitors, but not topoisomerase II inhibitors. Chemo-sensitization was not observed in normal epithelial cells. Knocking out the PAPSS1 homolog did not sensitize yeast to cisplatin, suggesting that sulfate bioavailability for amino acid synthesis is not the cause of sensitization to DNA damaging agents. Rather, sensitization may be due to sulfation reactions involved in blocking the action of DNA damaging agents, facilitating DNA repair, promoting cancer cell survival under therapeutic stress or reducing the bioavailability of DNA damaging agents. Our study demonstrates for the first time that PAPSS1 could be targeted to improve the activity of multiple anticancer agents used to treat NSCLC.
