Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 8)

Granulocytosis Approximately 30% of patients with solid tumors have granulocytosis (granulocyte count 8000/µL). In about half of patients with granulocytosis and cancer, the granulocytosis has an identifiable nonparaneoplastic etiology (infection, tumor necrosis, glucocorticoid administration, etc.). The other patients have proteins in urine and serum that stimulate the growth of bone marrow cells. Tumors and tumor cell lines from patients with lung, ovarian, and bladder cancers have been documented to produce granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin 6 (IL-6). However, the etiology of granulocytosis has not been characterized in most patients. ...
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Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 8) Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 8) Granulocytosis Approximately 30% of patients with solid tumors have granulocytosis(granulocyte count > 8000/µL). In about half of patients with granulocytosis andcancer, the granulocytosis has an identifiable nonparaneoplastic etiology(infection, tumor necrosis, glucocorticoid administration, etc.). The other patientshave proteins in urine and serum that stimulate the growth of bone marrow cells.Tumors and tumor cell lines from patients with lung, ovarian, and bladder cancershave been documented to produce granulocyte colony-stimulating factor (G-CSF),granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin6 (IL-6). However, the etiology of granulocytosis has not been characterized inmost patients. Patients with granulocytosis are nearly all asymptomatic, and thedifferential white blood cell count does not have a shift to immature forms ofneutrophils. Granulocytosis occurs in 40% of patients with lung andgastrointestinal cancers, 20% of patients with breast cancer, 30% of patients withbrain tumors and ovarian cancers, 20% of patients with Hodgkins disease, and10% of patients with renal cell carcinoma. Patients with advanced-stage diseaseare more likely to have granulocytosis than those with early-stage disease. Paraneoplastic granulocytosis does not require treatment. Thegranulocytosis resolves when the underlying cancer is treated. Thrombocytosis Some 35% of patients with thrombocytosis (platelet count > 400,000/µL)have an underlying diagnosis of cancer. IL-6, a candidate molecule for theetiology of paraneoplastic thrombocytosis, stimulates the production of platelets invitro and in vivo. Some patients with cancer and thrombocytosis have elevatedlevels of IL-6 in plasma. Another candidate molecule is thrombopoietin, a peptidehormone that stimulates megakaryocyte proliferation and platelet production. Theetiology of thrombocytosis has not been established in most cases. Patients with thrombocytosis are nearly all asymptomatic. Thrombocytosisis not clearly linked to thrombosis in patients with cancer. Thrombocytosis ispresent in 40% of patients with lung and gastrointestinal cancers, 20% of patientswith breast, endometrial, and ovarian cancers, and 10% of patients withlymphoma. Patients with thrombocytosis are more likely to have advanced-stagedisease and have a poorer prognosis than patients without thrombocytosis.Paraneoplastic thrombocytosis does not require treatment. Eosinophilia Eosinophilia is present in ~1% of patients with cancer. Tumors and tumorcell lines from patients with lymphomas or leukemia may produce IL-5, whichstimulates eosinophil growth. Activation of IL-5 transcription in lymphomas andleukemias may involve translocation of the long arm of chromosome 5, to whichthe genes for IL-5 and other cytokines map. Patients with eosinophilia are typically asymptomatic. Eosinophilia ispresent in 10% of patients with lymphoma, 3% of patients with lung cancer, andoccasional patients with cervical, gastrointestinal, renal, and breast cancer.Patients with markedly elevated eosinophil counts (>5000/µL) can developshortness of breath and wheezing. A chest radiograph may reveal diffusepulmonary infiltrates from eosinophil infiltration and activation in the lungs. Eosinophilia: Treatment Definitive treatment is directed at the underlying malignancy: tumorsshould be resected or treated with radiation or chemotherapy. In most patients whodevelop shortness of breath related to eosinophilia, symptoms resolve with the useof oral or inhaled glucocorticoids. Thrombophlebitis Deep venous thrombosis and pulmonary embolism are the most commonthrombotic conditions in patients with cancer. Migratory or recurrentthrombophlebitis may be the initial manifestation of cancer. Nearly 15% ofpatients who develop deep venous thrombosis or pulmonary embolism have adiagnosis of cancer (Chap. 111). The coexistence of peripheral venous thrombosiswith visceral carcinoma, particularly pancreatic cancer, is called Trousseaussyndrome. Pathogenesis Patients with cancer are predisposed to thromboembolism because they areoften at bedrest or immobilized, and tumors may obstruct or slow blood flow.Chronic IV catheters also predispose to clotting. In addition, clotting may bepromoted by release of procoagulants or cytokines from tumor cells or associatedinflammatory cells, or by platelet adhesion or aggregation. The specific moleculesthat promote thromboembolism have not been identified. In additio ...