- Email: [email protected]
Pitfalls Concerning Tumors and Leukemia
Pitfalls Concerning Tumors and Leukemia DONALD PINKEL, M.D.
638. Failing to recognize the presence of leukemia. Leukemia is a great imitator that can mimic any other childhood disorder. Because of the highly varied nature of early leukemic infiltration, early symptoms may refer to any organ system and may resemble those of rheumatic fever, meningitis, appendicitis, nephritis, pneumonia, osteomyelitis and many other diseases.
639.
Relying upon a normal hemogram for ruling out leukemia. Early in the course of acute leukemia the hemogram may be within normal limits. A bone marrow examination should be performed when this diagnosis is suspected, even when abnormal leukocytes are not apparent in the peripheral blood.
640.
Discontinuance of antimetabolites too early. Antimetabolites (6-mercaptopurine and Methotrexate) used in the treatment of acute leukemia of childhood may require three to eight weeks of administration before maximal benefit is seen. Therefore, in the ab-
299
300
DONALD PINKEL
sence of progressive disease, an antimetabolite should be continued for at least that period of time before concluding that it will not prove beneficial.
641.
Failing to adjust the dosage of anticancer drugs to individual tolerance. The dosage of anticancer drugs must be adjusted to each patient's tolerance, because there is great variation in sensitivity of patients to their toxic effects. In addition to biological individuality, malnutrition, infection, prior treatment with ionizing radiation or cytotoxic agents, impaired renal function and marrow infiltration with tumor may cause patients to have severe toxic. reactions to moderate doses of anticancer drugs. The young infant is especially more sensitive to these agents. These factors must be weighed before drug administration, and each patient must be observed closely.
642.
Misinterpreting leukopenia occurring during the treatment of acute leukemia. Leukopenia occurring during the treatment of acute leukemia does not always indicate drug toxicity. During induction it may indicate a favorable response or progressive disease; during remission it may indicate relapse. When leukopenia occurs, a bone marrow examination is often necessary to clarify the Significance of the peripheral blood findings. On the basis of the marrow examination, treatment should be continued, interrupted, or changed to another agent as indicated.
643.
Continuous use of prednisone in leukemia.
PITFALLS CONCERNING TUMORS AND LEUKEMIA
301
The use of prednisone continuously for long periods of time in leukemic children may produce severe disabilities. Generalized osteoporosis with pathologic fractures, disabling muscular atrophy, and hypertension may ensue. Prednisone is good for inducing remissions, but generally should not be used for long-term maintenance therapy.
644.
Failing to protect children with leukemia from exposure to infectious diseases. Children with leukemia become severely ill with measles and chickenpox, owing partly to the disease and partly to the immunosuppressive effects of antimetabolites. Parents should be warned to avoid exposure and to report inadvertent exposure to the physician promptly. Should exposure occur, immune globulin should be administered immediately, 5 m!. per square meter of body surface area for measles and 25 m!. per square meter for chickenpox. Antimetabolites should be discontinued temporarily if possible, and prednisone dosage decreased to 10 mg. per square meter if possible.
645.
Failing to regard fever during leukemia as a symptom of infection. Fever occurring during the course of acute leukemia is often caused by bacterial, fungal or viral infection. The febrile child with acute leukemia requires complete study for infection and prompt antibiotic therapy.
646.
Failing to treat neutropenia during leukemia complicated by infection.
302
DONALD FINKEL
The child with leukemia and infection often has severe neutropenia, and does not recover from the infection until absolute neutrophil counts exceed 500 cells per cubic millimeter. In such instances infusion of fresh white blood cells, collected from 1 to 2 liters of fresh human blood by differential centrifugation, often seems beneficial, although no proof of this is available at this time.
647.
Failing to support the parents of a child with cancer. When talking with the parents of a child with cancer, a physician should never use the term "hopeless," say that "nothing can be done," or let the parents feel that he is abandoning the child. Parents need to feel that the physician is truly interested in their child and is doing his best to help him. As much as they may realize and accept a fatal prognosis, they need a physician who maintains a positive, helpful attitude while expressing an honest opinion. They need to hear repeatedly, "We will do all we can to prolong his life in comfort."
648.
Misdiagnosing rhabdomyosarcoma as a benign tumor. Rhabdomyosarcoma in children is frequently mistaken for a benign tumor. At orifices such as the ear, nasopharynx and vagina it may look like a benign polyp, and in soft tissue it may feel like a well demarcated, firm, but not hard, mass. Suspicious masses and polyps should be biopsied and examined by a pathologist
experienced in childhood tumor diagnosis.
649.
Failing to recognize and treat Wilms's tumor in newborns.
PITFALLS CONCERNING TUMORS AND LEUKEMIA
303
Careful palpation of the abdomen of the newborn may reveal Wilms's tumor when relatively small. Treatment with surgical excision alone during the early months of life carries an excellent prognosis.
650.
Failing to perform bone marrow examination when a malignant tumor is suspected. Bone marrow examination should be performed as part of the initial study of children with malignant tumors. It may help determine whether an abdominal tumor is a neuroblastoma or a Wilms's tumor. Neuroblastoma is often found in bone marrow aspirates, but Wilms's tumor has never been reported in them. Definite evidence of tumor cells in marrow indicates widespread disease and a poor prognosis. It also argues against radical surgery or intensive radiotherapy and calls for moderation in the dosage of anticancer drugs.
651.
Failing to examine the eyes of a newborn for retinoblastoma. It is important to examine the eyes of newborns for retinoblastoma. When it is diagnosed early and treated promptly, there is better opportunity for both preserving vision and curing the child.
652.
Overuse of radiation therapy. The only indication for radiation therapy in children is cancer, proved by biopsy, that cannot be completely excised. Epidemiologic evidence indicates that carcinoma of the thyroid in children could be virtually eliminated if the use of ionizing radiation for enlarged tonsils, hemangiomas, thymic shadows and other
DONALD PINKEL
304
benign conditions were discontinued. Also, some cases of leukemia and possibly other malignancies might be prevented.
653.
Failing to recognize that brain tumors in children may masquerade as behavior disorders. Early symptoms of brain tumors in children may mask as a behavior disorder; therefore children brought to the physician because of behavior problems should be considered brain tumor suspects and examined thoroughly and repeatedly. Electroencephalograms are of relatively little help in the diagnosis of brain tumors in children.
654.
Believing that neuroblastoma is always fatal. Young infants with neuroblastoma have been cured, even when their disease was widespread.
655.
Mistaking osteomyelitis or fractures for bone tumors. Chronic osteomyelitis or healing fractures may be mistaken for malignant bone tumors. Careful biopsy and thorough pathologic study are required for correct diagnosis of bone lesions.
656. . Excising malignant tumors. Incomplete excision of a malignant tumor may be more harmful than beneficial. The inoperable childhood ma-
PITFALLS CONCERNING TUMORS AND LEUKEMIA
305
lignant tumor should be biopsied and attempts made to reduce its size by chemotherapy or radiation therapy. Tumor reduction by chemotherapy or radiation therapy can be sufficient to allow complete excision of the tumor and improvement in prognosis.
638. Failing to recognize the presence of leukemia. Leukemia is a great imitator that can mimic any other childhood disorder. Because of the highly varied nature of early leukemic infiltration, early symptoms may refer to any organ system and may resemble those of rheumatic fever, meningitis, appendicitis, nephritis, pneumonia, osteomyelitis and many other diseases.
639.
Relying upon a normal hemogram for ruling out leukemia. Early in the course of acute leukemia the hemogram may be within normal limits. A bone marrow examination should be performed when this diagnosis is suspected, even when abnormal leukocytes are not apparent in the peripheral blood.
640.
Discontinuance of antimetabolites too early. Antimetabolites (6-mercaptopurine and Methotrexate) used in the treatment of acute leukemia of childhood may require three to eight weeks of administration before maximal benefit is seen. Therefore, in the ab-
299
300
DONALD PINKEL
sence of progressive disease, an antimetabolite should be continued for at least that period of time before concluding that it will not prove beneficial.
641.
Failing to adjust the dosage of anticancer drugs to individual tolerance. The dosage of anticancer drugs must be adjusted to each patient's tolerance, because there is great variation in sensitivity of patients to their toxic effects. In addition to biological individuality, malnutrition, infection, prior treatment with ionizing radiation or cytotoxic agents, impaired renal function and marrow infiltration with tumor may cause patients to have severe toxic. reactions to moderate doses of anticancer drugs. The young infant is especially more sensitive to these agents. These factors must be weighed before drug administration, and each patient must be observed closely.
642.
Misinterpreting leukopenia occurring during the treatment of acute leukemia. Leukopenia occurring during the treatment of acute leukemia does not always indicate drug toxicity. During induction it may indicate a favorable response or progressive disease; during remission it may indicate relapse. When leukopenia occurs, a bone marrow examination is often necessary to clarify the Significance of the peripheral blood findings. On the basis of the marrow examination, treatment should be continued, interrupted, or changed to another agent as indicated.
643.
Continuous use of prednisone in leukemia.
PITFALLS CONCERNING TUMORS AND LEUKEMIA
301
The use of prednisone continuously for long periods of time in leukemic children may produce severe disabilities. Generalized osteoporosis with pathologic fractures, disabling muscular atrophy, and hypertension may ensue. Prednisone is good for inducing remissions, but generally should not be used for long-term maintenance therapy.
644.
Failing to protect children with leukemia from exposure to infectious diseases. Children with leukemia become severely ill with measles and chickenpox, owing partly to the disease and partly to the immunosuppressive effects of antimetabolites. Parents should be warned to avoid exposure and to report inadvertent exposure to the physician promptly. Should exposure occur, immune globulin should be administered immediately, 5 m!. per square meter of body surface area for measles and 25 m!. per square meter for chickenpox. Antimetabolites should be discontinued temporarily if possible, and prednisone dosage decreased to 10 mg. per square meter if possible.
645.
Failing to regard fever during leukemia as a symptom of infection. Fever occurring during the course of acute leukemia is often caused by bacterial, fungal or viral infection. The febrile child with acute leukemia requires complete study for infection and prompt antibiotic therapy.
646.
Failing to treat neutropenia during leukemia complicated by infection.
302
DONALD FINKEL
The child with leukemia and infection often has severe neutropenia, and does not recover from the infection until absolute neutrophil counts exceed 500 cells per cubic millimeter. In such instances infusion of fresh white blood cells, collected from 1 to 2 liters of fresh human blood by differential centrifugation, often seems beneficial, although no proof of this is available at this time.
647.
Failing to support the parents of a child with cancer. When talking with the parents of a child with cancer, a physician should never use the term "hopeless," say that "nothing can be done," or let the parents feel that he is abandoning the child. Parents need to feel that the physician is truly interested in their child and is doing his best to help him. As much as they may realize and accept a fatal prognosis, they need a physician who maintains a positive, helpful attitude while expressing an honest opinion. They need to hear repeatedly, "We will do all we can to prolong his life in comfort."
648.
Misdiagnosing rhabdomyosarcoma as a benign tumor. Rhabdomyosarcoma in children is frequently mistaken for a benign tumor. At orifices such as the ear, nasopharynx and vagina it may look like a benign polyp, and in soft tissue it may feel like a well demarcated, firm, but not hard, mass. Suspicious masses and polyps should be biopsied and examined by a pathologist
experienced in childhood tumor diagnosis.
649.
Failing to recognize and treat Wilms's tumor in newborns.
PITFALLS CONCERNING TUMORS AND LEUKEMIA
303
Careful palpation of the abdomen of the newborn may reveal Wilms's tumor when relatively small. Treatment with surgical excision alone during the early months of life carries an excellent prognosis.
650.
Failing to perform bone marrow examination when a malignant tumor is suspected. Bone marrow examination should be performed as part of the initial study of children with malignant tumors. It may help determine whether an abdominal tumor is a neuroblastoma or a Wilms's tumor. Neuroblastoma is often found in bone marrow aspirates, but Wilms's tumor has never been reported in them. Definite evidence of tumor cells in marrow indicates widespread disease and a poor prognosis. It also argues against radical surgery or intensive radiotherapy and calls for moderation in the dosage of anticancer drugs.
651.
Failing to examine the eyes of a newborn for retinoblastoma. It is important to examine the eyes of newborns for retinoblastoma. When it is diagnosed early and treated promptly, there is better opportunity for both preserving vision and curing the child.
652.
Overuse of radiation therapy. The only indication for radiation therapy in children is cancer, proved by biopsy, that cannot be completely excised. Epidemiologic evidence indicates that carcinoma of the thyroid in children could be virtually eliminated if the use of ionizing radiation for enlarged tonsils, hemangiomas, thymic shadows and other
DONALD PINKEL
304
benign conditions were discontinued. Also, some cases of leukemia and possibly other malignancies might be prevented.
653.
Failing to recognize that brain tumors in children may masquerade as behavior disorders. Early symptoms of brain tumors in children may mask as a behavior disorder; therefore children brought to the physician because of behavior problems should be considered brain tumor suspects and examined thoroughly and repeatedly. Electroencephalograms are of relatively little help in the diagnosis of brain tumors in children.
654.
Believing that neuroblastoma is always fatal. Young infants with neuroblastoma have been cured, even when their disease was widespread.
655.
Mistaking osteomyelitis or fractures for bone tumors. Chronic osteomyelitis or healing fractures may be mistaken for malignant bone tumors. Careful biopsy and thorough pathologic study are required for correct diagnosis of bone lesions.
656. . Excising malignant tumors. Incomplete excision of a malignant tumor may be more harmful than beneficial. The inoperable childhood ma-
PITFALLS CONCERNING TUMORS AND LEUKEMIA
305
lignant tumor should be biopsied and attempts made to reduce its size by chemotherapy or radiation therapy. Tumor reduction by chemotherapy or radiation therapy can be sufficient to allow complete excision of the tumor and improvement in prognosis.