Multiple Myeloma – Top USMLE Diseases

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiates PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia vera is presumed to have a genetic basis due to mutations in the Janus kinase-2 gene. The clinical presentation may consist of symptoms related to increased blood volume and viscosity, such as headache, visual changes, and venous or arterial thrombosis; however, many cases are found incidentally with asymptomatic elevated hemoglobin levels on a CBC. Diagnosis is based on peripheral blood analysis and bone marrow biopsy findings. Management is with phlebotomy or drug therapy. The prognosis is generally good, and patient survival is anticipated to improve further with the wide use of new therapies.

Cancer immunotherapy is a rapidly advancing medical therapy that takes advantage of the immune system to contain or eliminate cancer cells. Currently, immunotherapies have been incorporated into treatment regimens for different types of cancer. Various therapeutic approaches exist, including using cytokines, vaccines, oncolytic viruses, T-cell manipulation or cellular adoptive immunotherapy, or antibodies to immune checkpoint molecules. These therapies provide new options for advanced cancers, including melanoma, renal cell carcinoma, prostate adenocarcinoma, lung cancer, urothelial carcinoma, Hodgkin lymphoma, and refractory B-cell ALL. With the immune system involved, these agents carry serious and potentially fulminant adverse effects and toxicities.

Non-Hodgkin lymphomas (NHLs) are a diverse group of hematologic malignancies that are clonal proliferative disorders of mature or progenitor B cells, T cells, or natural killer (NK) cells. Most pediatric cases are aggressive and high-grade (but curable); in adults, low-grade subtypes are more common. Like Hodgkin lymphoma, which has distinct pathologic features and treatments, NHL often presents with constitutional signs of fever, night sweats, and weight loss. Clinical features include lymphadenopathy and hepatosplenomegaly, but some individuals present with extranodal involvement and abnormal lab findings. B-cell NHLs include diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma, mantle cell lymphoma, and marginal zone lymphoma. T-cell NHLs include adult T-cell lymphoma and mycosis fungoides. Diagnosis is made by lymph node biopsy, bone marrow biopsy, or both. Management is with chemotherapy or targeted drugs. Radiation therapy is used in adults but not in children, and stem cell transplantation is used for patients with aggressive disease.

Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm characterized by the clonal thrombocytosis linked to somatic mutations involving Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL). Patients can be asymptomatic or present with vasomotor symptoms such as headaches, erythromelalgia, and transient visual disturbances. The clinical course can be complicated by thrombohemorrhagic events as well as progression to myelofibrosis and AML. The diagnosis is based on a laboratory finding of thrombocytosis, bone marrow biopsy, and genetic studies. Treatment aims to reduce platelet count by cytoreductive agents (hydroxyurea) and to decrease thrombosis with aspirin and systemic anticoagulation based on thrombosis risk stratification.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiate PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia vera is presumed to have a genetic basis due to mutations in the Janus kinase-2 gene. The clinical presentation includes disease-related symptoms that can affect various organ systems. Sometimes, the disease can be an incidental finding during laboratory testing. Diagnosis is based on peripheral blood analysis and bone marrow biopsy findings. Management is with phlebotomy or drug therapy. The prognosis is generally good and patient survival is anticipated to improve further with the wide use of new therapies.

Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Diagnosis relies on a thorough medical history and physical examination, which usually identify the underlying cause. When the cause is unknown, a biopsy may be necessary. Management is directed at the underlying infection, malignancy, or other cause.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by excess production of monoclonal B lymphocytes in the peripheral blood. When the involvement is primarily nodal, the condition is called small lymphocytic lymphoma (SLL). The disease usually presents in older adults, with a median age of 70 years. Clinical presentation is often asymptomatic and diagnosis is made when abnormal lymphocytosis is seen on laboratory testing. Cytopenias can also be seen. The B cells are functionally incompetent lymphocytes and thus may result in recurrent infections. Treatment can vary from watchful waiting for early stages to chemotherapy for later stages. Median survival is around 10 years.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Clinical presentation consisting of fatigue, bleeding, fever, and infection is related to anemia, thrombocytopenia, and a lack of functional WBCs. The onset of symptoms takes days to weeks. Additional findings in AML may include gingival hypertrophy and skin infiltration (leukemia cutis). Diagnosis is via peripheral blood smear and bone-marrow biopsy examination (shows myeloblasts). The precursor cells contain Auer rods. Immunophenotyping, histochemistry, and genetic analysis all aid in identifying and guiding the treatment of AML. Management is chemotherapy administered in phases (induction, consolidation, and maintenance) based on subtypes. Prognosis varies according to the age of onset and type of leukemia.

Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Osteoclastic activity results in bone resorption, bone pain, pathologic fractures, and metabolic disturbances. Excessive secretion of antibodies results in proteinuria and associated kidney damage as well as production and tissue deposition of amyloid fibrils. Metabolic disturbances combined with tissue amyloid deposition cause end-organ damage. Diagnosis is established by plasma electrophoresis and bone marrow biopsy. Treatments to slow down the disease progression are available; however, there is no cure for MM. The median survival is approximately 3 years.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis, which include severe fatigue, weight loss, and hepatosplenomegaly. Laboratory findings include anemia (and other cytopenias), and bone marrow biopsy reveals extensive fibrosis. Management is with hematopoietic stem cell transplantation and symptom-directed interventions.

Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy (neck most commonly involved), night sweats, weight loss, fever, and at times, splenomegaly and hepatomegaly. Diagnostic testing includes lymph node histologic analysis showing HRS cells, blood tests, and CT and PET scanning. HL is managed with chemotherapy and radiotherapy. The prognosis has improved significantly with the advent of chemotherapeutic regimens.