Kaposi sarcoma is a malignant neoplasm arising from the endothelial cell lining of blood and lymphatic vessels. Herein, we discuss etiopathogenesis, clinical presentation, diagnostic criteria, updated guideline-based approach to its management and newer experimental approaches. Given its efficacy and side effect profile, pegylated doxorubicin is the currently preferred first-line therapy in advanced disease. Paclitaxel remains an alternative first-line option. At the time of relapse, patients can be retreated with the same agents as they often maintain their clinical efficacy. New therapeutic options are on the rise, with pomalidomide being approved in 2020 as a second-line therapy. Optimal control of retroviral infection in human immunodeficiency virus (HIV) positive is instrumental in preventing disease occurrence in most patients. Suppressing human herpes virus type 8 (HHV-8) infection might also play a role in controlling Kaposi sarcoma growth, yet clinical trials are lacking. Unraveling the molecular and genetic intricacies of Kaposi sarcoma's pathogenesis might allow for the emergence of novel and effective therapeutic strategies. Clinical trials are currently underway to establish potential roles for various targeted agents, immune checkpoint inhibitors (ICIs) and experimental agents in the treatment of advanced Kaposi sarcoma.

Introduction Nivolumab is an immune checkpoint inhibitor used in the treatment of several malignancies. A number of immune-related endocrinopathies have been linked to its use. Case report We report a unique case of a 74-year-old man with well-controlled diabetes mellitus type 2 and metastatic mucosal anorectal melanoma who presented with diabetic ketoacidosis after receiving his third cycle of nivolumab 240 mg intravenous (IV) every 2 weeks. He was found to have autoantibodies against glutamic acid decarboxylase 65. Genotyping for human leukocyte antigens showed the presence of DQB1*02:01 and DRB1*03:01. Management and outcome His presentation was complicated by acute renal failure. He required aggressive fluid resuscitation and insulin supplementation to reverse severe acid-base disturbance and multiple electrolyte abnormalities. After an 8-week interruption, the patient restarted nivolumab without any further evidence of adverse events over the next 12 weeks. He continues to require insulin replacement therapy. Discussion and conclusion Development of type 1 diabetes with the use of immune checkpoint inhibitors has been increasingly reported in the literature. The exact mechanism for autoimmune diabetes precipitated by nivolumab is yet to be elucidated. Patient education about the symptoms of diabetes and regular glucose monitoring cannot be overemphasized. Testing for antibodies against glutamic acid decarboxylase 65, insulin receptors, and islet cells may also prove useful. Human leukocyte antigen DQ and DR haplotyping prior to immune checkpoint inhibitor treatment might help determine susceptibility toward developing type 1 diabetes, and provide opportunities for earlier recognition, intervention, and possibly prevention.

Introduction Although rare, Kaposi sarcoma is the most common malignant neoplasm associated with human immunodeficiency virus (HIV) infection. Several agents have now been approved in the treatment of this malignancy and are used with varying degrees of success. Case report We present a unique case of a 64-year-old man with well-controlled HIV infection who developed necrotizing leg gangrene from invasive cutaneous Kaposi sarcoma. He responded very well to systemic chemotherapy, thereby avoiding limb amputation. Management and outcome Pegylated liposomal doxorubicin (PLD) at a dose of 20 mg/m2 every 3 weeks was utilized, with a near-complete response after six cycles of therapy. The patient continues to receive maintenance treatment with PLD. His HIV infection remains in excellent control, with a high-normal CD4 T-cell count. Periodic echocardiogram evaluations have not shown any decline in left ventricular ejection fraction (LVEF) over time. Conclusion Most patients with Kaposi sarcoma achieve partial responses to treatment with PLD. Our case illustrates that near complete and complete responses are possible with this agent, leading to potential limb salvage in necrotizing gangrene.

Hairy cell leukemia (HCL) represents a heterogeneous group of mature, indolent B-cell lymphoproliferative disorders accounting for approximately 2% of all leukemias [1,2]. The median age of patients at diagnosis is 63, with HCL displaying a male predominance (M/F ratio 4:1). Caucasians are affected more than other ethnic groups. Annual incidence is approximately 3/1,000,000 worldwide [1]. Almost invariably, clinical presentation is dominated by splenomegaly and cytopenias, eventually leading to early satiety, fatigue, frequent infections, and/or increased bleeding risk. Pancytopenia is present in nearly half of patients, while 40% display a combination of two different cytopenias [1,2]. Bone marrow failure with or without fibrosis and hypersplenism are important mechanisms underlying cytopenias [2]. In recent years, massive splenomegaly has become less prevalent, perhaps owing to earlier diagnosis. Post-germinal center memory B-cells and/or splenic marginal zone B-cells are believed to be the cells of origin of HCL [3,4]. Two clinico-laboratory subtypes have long been identified – the more common, classic HCL, and the less common, HCL variant (HCLv). Today, several molecular subtypes are recognized, each displaying a distinct clinical course and ability to respond to therapy [5]. Flow cytometry and bone marrow immunohistochemistry are used to establish the HCL diagnosis and help differentiate between the existing subtypes. B-cells in HCL express strongly CD22, CD20, CD103, and CD11c. Classic HCL B-cells are also positive for CD25, tartrate-resistant acid phosphatase (TRAP), annexin 1A, and CD72 [1]. In addition, at least 85% of classic HCL cases express BRAF V600E mutation. Approximately 80% patients with classic HCL achieve complete clinico-laboratory remissions with single-agent purine analog therapy [3]. HCLv, on the other hand, lacks expression of CD25, TRAP, annexin 1A, and BRAF V600E mutation. This subtype is clinically more aggressive and less sensitive to purine analogs [1,3]. Typically, these patients present with monoclonal lymphocytosis and less severe cytopenias than classic HCL patients. Some investigators believe that HCLv is more prevalent than previously thought, and affects nearly 40% of HCL as opposed to the previously estimated 10–20% [6]. More recently, a molecularly distinct variant of HCL expressing an unmutated immunoglobulin rearrangement (IGHV4-34 +) has been described in the literature [7,8]. This variant has a similar immunophenotype to either HCL or HCLv, but characteristically lacks the BRAF V600E mutation. Even patients with ‘bright’ CD25 expression display clinical features similar to HCLv, including malignant lymphocytosis, massive splenomegaly, nodal disease, and a poorer response to purine analogs [1,8]. In one series, unmutated IGHV4-34 was detected in 10% of classic HCL and 40% of patients with HCLv [8]. Furthermore, nearly half of the patients with IGHV4–34+ HCL and HCLv harbor MAP2K1 (MEK) mutations [9,10]. New genetic and molecular alterations are constantly being discovered in HCL and could become drug targets in the near future [4].