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

Paraneoplastic Syndromes: Endocrinologic/Hematologic Part 8 Granulocytosis Approximately 30% of patients with solid tumors have granulocytosis granulocyte count > 8000/µL.. Tumors and

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

Patients with granulocytosis are nearly all asymptomatic, and the differential white blood cell count does not have a shift to immature forms of neutrophils Granulocytosis occurs in 40% of patients with lung and gastrointestinal cancers, 20% of patients with breast cancer, 30% of patients with brain tumors and ovarian cancers, 20% of patients with Hodgkin's disease, and 10% of patients with renal cell carcinoma Patients with advanced-stage disease are more likely to have granulocytosis than those with early-stage disease

Paraneoplastic granulocytosis does not require treatment The granulocytosis 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 the etiology of paraneoplastic thrombocytosis, stimulates the production of platelets in vitro and in vivo Some patients with cancer and thrombocytosis have elevated levels of IL-6 in plasma Another candidate molecule is thrombopoietin, a peptide hormone that stimulates megakaryocyte proliferation and platelet production The etiology of thrombocytosis has not been established in most cases

Patients with thrombocytosis are nearly all asymptomatic Thrombocytosis

is not clearly linked to thrombosis in patients with cancer Thrombocytosis is present in 40% of patients with lung and gastrointestinal cancers, 20% of patients

with breast, endometrial, and ovarian cancers, and 10% of patients with lymphoma Patients with thrombocytosis are more likely to have advanced-stage disease 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 tumor cell lines from patients with lymphomas or leukemia may produce IL-5, which stimulates eosinophil growth Activation of IL-5 transcription in lymphomas and leukemias may involve translocation of the long arm of chromosome 5, to which the genes for IL-5 and other cytokines map

Patients with eosinophilia are typically asymptomatic Eosinophilia is present in 10% of patients with lymphoma, 3% of patients with lung cancer, and occasional patients with cervical, gastrointestinal, renal, and breast cancer Patients with markedly elevated eosinophil counts (>5000/µL) can develop shortness of breath and wheezing A chest radiograph may reveal diffuse pulmonary infiltrates from eosinophil infiltration and activation in the lungs

Eosinophilia: Treatment

Definitive treatment is directed at the underlying malignancy: tumors should be resected or treated with radiation or chemotherapy In most patients who

develop shortness of breath related to eosinophilia, symptoms resolve with the use

of oral or inhaled glucocorticoids

Thrombophlebitis

Deep venous thrombosis and pulmonary embolism are the most common thrombotic conditions in patients with cancer Migratory or recurrent thrombophlebitis may be the initial manifestation of cancer Nearly 15% of patients who develop deep venous thrombosis or pulmonary embolism have a diagnosis of cancer (Chap 111) The coexistence of peripheral venous thrombosis

with visceral carcinoma, particularly pancreatic cancer, is called Trousseau's

syndrome

Pathogenesis

Patients with cancer are predisposed to thromboembolism because they are often at bedrest or immobilized, and tumors may obstruct or slow blood flow Chronic IV catheters also predispose to clotting In addition, clotting may be promoted by release of procoagulants or cytokines from tumor cells or associated inflammatory cells, or by platelet adhesion or aggregation The specific molecules that promote thromboembolism have not been identified

In addition to cancer causing secondary thrombosis, primary thrombophilic diseases may be associated with cancer For example, the antiphospholipid

antibody syndrome is associated with a wide range of pathologic manifestations About 20% of patients with this syndrome have cancers Among patients with cancer and antiphospholipid antibodies, 35–45% develop thrombosis