Overview of Pediatrics Malignancies

Muhammad Tahir Saleem

I am rotated in the pediatric hematology and oncology ward for clinical practicum as part of the Masters of Nursing (MSc.N) program. Hematology is the branch of medicine that deals with the diseases and related to blood and its functional abnormalities including anemia, polycythemia and hemophilia and all bleeding disorders (Brunner and Suddarth’s, 2010). Oncology is the branch of medicine that deals with the diagnosis and treatment of the cancer in the body (Brunner and Suddarth’s, 2010). Since human body is composed of cells so the cancer originates from abnormally occurring cells in the body (Porth & Matfin, 2009). There are many definition of the word cancer in medicine, but whatever the way of defining cancer is adopted, the definition should incorporate two properties: uncontrollable growth of cells originating from normal tissues, and property of killing of host by means of using components of surrounding tissues or by spreading to other organs (metastases) to other organ and systems of the human body (Itano & Taoka, 2005). Some experts define cancer as the autonomous growth of the body cells that is unresponsive to the physiological growth-control mechanism of the body which is responsible for homogenous development of all body organs normally. Other have define cancer as a condition in which normally growing cells lose their structure, appearance and functioning (shoib book). The cells also lose their self-destructive ability (apoptosis) to die after certain period of time as they do normally (e.g. red blood cells die after 120 days) and the cells tend to live longer and at times become immortal and disturb the functions of other normal cells.

There are certain terminologies that are frequently referred to the set of events occurred during the pathogenesis of cancer. These terminologies are dysplasia, metaplasia and anaplasia. Dysplasia is a disruption in the size, appearance, and arrangement of cells and tissues (Porth & Matfin, 2009). Dysplasia is abnormal tissue development but not yet cancerous. Dysplastic changes frequently occur in the mucosal lining of the mouth, nose, intestine and cervix where the cells keep on going under cellular multiplication, differentiation, organization and replacement of new cells (Porth & Matfin, 2009). The epithelial lining of elementary canal (mouth to anus) completely changes in three days. So it is the frequent site of papilloma formation as a result of dysplastic changes. The epithelial lining of the mouth of cervix also changes as a result of dysplastic changes due to human papilloma virus (Porth & Matfin, 2009). Dysplasia is also present in chronic inflammatory and proliferative lesions, and it is recognized as part of a developmental phase of many cancers. Metaplasia is the substitution of one cell type with another cell type, for example in smokers ciliated columnar bronchial epithelium is replaced by non-ciliated squamous epithelium due to the constant exposure of smoke to the bronchus (Porth & Matfin, 2009). Metaplasia is also considered as the developmental phase in many neoplasms. Anaplasia is the structural change and cellular appearance and inability to perform the normal functions of a cell. This stage of cellular changes is known as cancerous (Porth & Matfin, 2009). Anaplastic cells resemble the undifferentiated primitive cells that have not developed specialized structure and functioning typical of their tissue of origin. In other words, the newly formed tissue from muscle cell or nerve cell, for example ,remain in the premature state as a result of anaplastic changes and do not perform its original functions. The degree of anaplasia may differ from one type of cancer cells to other type of cancers from poorly differentiated to undifferentiated cells; sometimes the tumor cells are so undifferentiated that it is not possible to decide the tissue from which the cancer cells are originated (Porth & Matfin, 2009).

Here, the terms hyperplasia and hypertrophy are worth mentioning. Hyperplasia and hypertrophy are normal physiological responses. Hyperplasia is defined as an increase in the cellular count in a tissue or organ causing an increase in the size of that organ, whereas hypertrophy is the increase in the size of cells not the number (Porth & Matfin, 2009). Neither hypertrophy, nor the hyperplasia is the synonym of tumor growth. Hyperplasia is induced by know stimuli and it is a controlled process and it stops as the stimuli is removed. One example of stimuli induced hyperplasia is the increase in the size and number of cells of uterus in pregnancy under the influence estrogen for accommodation of developing embryo. The uterus comes to normal state after the stimuli of estrogen is gone after delivery. In addition, hyperplasia may also serve a useful role in the body, for example breast tissue undergoes hyperplastic changes after pregnancy for production of milk or re-forming the liver with structurally typical hepatocytes after partial hepatectomy. Abnormal cancerous development follows none of these usual physiological rules or purposes (Porth & Matfin, 2009). However, cancerous cells may eventually employ the hyperplasia in its pathogenesis pathways. Because, hyperplasia and dysplasia often fall into the development of many tumors by months or years, timely identification and proper treatment at this early stage in the pathological process may help to prevent malignancies (Porth & Matfin, 2009). For example, the Papanicolaou Smear (or pap smear) allows pathologists to distinguish between normal, dysplastic or cancerous cells. The pap-smear is a technique that allows early detection of the cervical cancer and it has enormously reduced the morbidity and mortality of cervical cancer.

Pathologically, tumors can be classified into benign and malignant. The word benign means kind, gentle or caring and suggests that such tumor are harmless. These tumors are mostly encapsulated by well defined fibrous cover that separates the mass from surrounding tissues. A benign tumor, neither invade surrounding tissue nor metastasizes. These tumor exhibit lesser degree of anaplasia and grow slowly. Recurrence is very rare after surgical removal in benign tumors. The benign tumors are named by adding suffix -oma in the name of tissue they are originating in. For example, Lipoma, Adenoma, fibroma and papilloma are some of the example of adding suffix –oma in the type of origin of tumor (Itano & Taoka, 2005). Whereas, malignant tumors usually infiltrate or invade surrounding tissues, these tumors are not encapsulated, genetically instable and with greater degree of anaplasia from the tissue of origin. They grow autonomously with no control of body homogenous development. The following table compares the properties of benign and malignant tumors (Itano & Taoka, 2005).

Difference Between Benign and Malignant Tumor

Characteristic

Benign Tumor

Malignant Tumor

Structure and differentiation

Typical of tissue of origin

Atypical of tissue origin

Rate of growth

Usually slow

May be slow, rapid, very rapid

Progression

Slowly progressive (may remain stationary; may regress): rarely fatal if treated

Usually progressive, almost always fatal if untreated

Mode of growth

Expansion with capsule

Local infiltration and/or metastasis to distant sites

Tissue destruction

None

Common, ulceration and necrosis

Recurrence

Rare

Common

Prognosis

Fatal only if surgically inaccessible

Fatal if uncontrolled (untreated)

Core Curriculum of Oncology Nursing. St. Louis, Messori: Elsevier; 2005

Cancer can also be characterized in two types on the basis of structure, solid tumor and cancer of the blood. Cancer of the blood and lymphatic systems are mostly leukemia and lymphomas, where as solid tumors are originating in the organ like central nervous system, kidneys, eyes, bones and in soft tissues. Childhood malignancies mostly originate in blood, bone marrow and in lymphatic systems. Cancer of genitourinary system, respiratory system, and caner of digestive system are rare in children as the statistics furnished by the cancer research organization UK, 2012 (www.cancerresearch.org).

The incidence chart of the childhood cancers is as follows:

The incidence chart of the childhood cancers

Cancer Type

Incidence

Leukemia

34%

CNS tumors

23%

Lymphoma

11%

Neuroblastoma

6%

Renal tumor (e.g. Wilm’s tumor)

6%

Soft tissue sarcomas

6%

Bone tumors

5%

Retinoblastoma

3%

Epithelial neoplasm’s

3%

Germ cell tumors

2%

Liver Tumors

1%

Oxford handbook of Pediatric hematology and oncology, 2010.

A brief description of pediatric cancers is given below.

Leukemia

Leukemia is the cancer that affects the cell lining of white blood cells. White blood cells are of tow type; granulocytes (Lymphoid cell) and agranulocytes (Myeloid cell). Lymphoid cells are further subdivided in B-cell Lymphocytes and T-Cell Lymphocytes, whereas, myeloid cells are of three types, Neutrophils, Basophils and Eosinophil (Porth & Matfin, 2009).

Leukemia is further sub divided into acute and chronic; acute leukemia are termed when the anaplastic changes occurred in the pre matured leukocytes that has just transformed from the stem cells in the bone marrow, whereas, chromic leukemias’ are termed when the anaplastic changes occur in more matured stage or adult leukocytes. The four types of leukemias are as follows

Acute Lymphocytic Leukemia

Chronic Lymphocytic Leukemia

Acute Myeloid Leukemia

Chronic Myeloid Leukemia

Acute Lymphoblastic Leukemia accounts for 80-90% among all types of leukemia in childhood. AML accounts for 15% and CML 5% (Itano & Taoka, 2005).

Acute Lymphoblastic Leukemia (ALL) is further subdivided incidence wise according to cell linage involved as elaborated by Moore and Hurvitz (2008).

Pre B-cell 70%
T-Cell 15-25%
B-Cell 15%

Treatment of acute leukemia involves induction for complete remission, followed by intensification and maintenance therapy. Prophylaxis to the CNS is done by Intra-thecal (IT) chemo administration. Standard treatment for ALL leads to long term remission in more than 85% of cases.

Induction therapy employs Vincristine, Prednisone, and L-Asparagenase +/- Danurubicin (depending upon risk satisfaction)
Intensification; all induction medicine with the inclusion of CNS prophylaxis
Maintenance therapy includes oral Mercaptopurin (6MP) with methotrexate (MTX) weekly for two to three years
Many patients in the chemo-pediatrics receive monthly intra-thecal (IT) pulses of Vincristine with prednisolone/dexa as part of maintenance.
One or two cycles of a re-induction regimen were often added but not in contemporary practice (Moore & Hurvitz, 2008).

Good prognostic factors for ALL: WBC<50,000/uL, Age 1-9 years at the time of diagnosis. Also include Pre B Subtype of cell, Hyperploid, Lack of organomegaly, low bone marrow blasts on day 7 of induction therapy, trisomy of chromosome 4 and 10, and t4:11 or Tel/AML1 translocation as the parameter of low risk stratification (Moore & Hurvitz, 2008).

Bad Prognostic factors for ALL: WBC>50,000/uL, age<1 year or age>10years,

Other poor prognostic factors are massive organomegaly, CNS involvement at diagnosis, medaistinal mass and failure to achieve remission by day 14 to 28 of induction, with presence of Philadelphia chromosome.

Acute Myeloid Leukemia (AML)

AML requires intensive chemotherapy followed by hemotopotic stem cell transplantation (HSCT) hematopoietic stem cell transplantation if a suitable matched related donor is available. Five years survivals for these patients are more than 85% with good prognosis (Bailey & Skinner, 2010).

Lymphomas

Hodgkin and Non Hodgkin Lymphomas: Lymphomas are the tumor of lymphocytes (B & T cells) that originate in the lymph tissue that is fixed to organs and lymph nodes not in peripheral circulation. As in the case of leukemias, lymphomas also involved both B-cell and T-cell lymphocytes but they are confined to the lymph nodes or other lymphatic organs not the peripheral blood. They typically presents with a solid mass in a lymph node, spleen, bone marrow and in any organ. Other than lymph tissue, they may present in tonsils, skin, brain, bowel and bone. Lymphomas are closely related to lymphoid leukemias that involves the circulating lymphatic cells. Lymphomas are better controlled by treating with chemotherapy. Five years survivals for these pediatric lymphoma patients are more than 90% with good prognosis (Itano & Taoka, 2005).

Brain tumors

These are of four types, depending upon the type of cells from where the tumor is initiating. Gliomas, Appendimomas, Meduloblastomas, and Schewanomas are some of the types of central nervous system tumors (CNS). Some CNS tumors are associated with high mortality and respond poorly chemo. Cranio-spinal radiation is often employed as part of the treatment regimen for older kids but radiation is deferred in children age less than 3 years due to the chance of fibrosis of growing skull bones and vertebral bones; however radiation is avoided in most of the younger children (Bailey & Skinner, 2010).

Tumor of the renal system

Wilm’s tumor is tumor of renal system. Histological name of the cancer is nephroblastoma. It needs radiation and chemo both for the eradication of disease. Size of the tumor is reduced by using chemo and radiation. After the shrinkage of renal tumor, surgery proved to be beneficial. Three years survival is 75% in patients of nephroblastoma (Bailey & Skinner, 2010).

Soft tissue tumors

Soft tissue tumors originate from connective tissue of cartilage and bone forming fibrous tissue, smooth muscles, blood vessels, lymphatic vessels, fat tissue, synovial tissue, and peripheral nerves. The most common type of soft tissue tumor in childhood is rhebdomysarcoma.

Rhabdomyosarcoma: It originates form the striated muscle tissue. It most commonly originates in head and neck area. Only 15% presents outside of the head and neck region. It is treated with chemo and radiation therapy. The prognosis of this cancer is good if treatment is started at early stage (Bailey & Skinner, 2010).

Retinoblastoma

Retina is nervous tissue. Retina is only neuronal tissue that is visible through the naked eye. The tumor that arises from it also primitive neuronal ectodermic stem cells that were remain undifferentiated in fetal life and present like tumor in the very first years of life. Most patient get die due to extension of these neuronal tumors to CNS through optic nerve. In localized tumor survival is 100% but in metastatic tumor the survival ratio decrease. As described by Bailey and Skinner, (2010) many chemotherapeutic agents are used in treatment of retinoblastoma e.g. Vincristine, Actinomycin D, cyclopahsmamide, and doxorubicin.

Germ Cell Tumors

This tumor arises from primitive stem cells of the fetal life that remained immature during fetal development and were not able to fully develop (differentiate) to mature cells of the organs. Human embryo develops from the three layers of the germ cells. These layers are ectoderm (outermost), mesoderm (middle layer) and endoderm (innermost). Ectoderm develops into skin, sweat glands and nervous system, mesoderm develop into bones flesh, blood vessels and lymphoid tissue whereas, endoderm develop into genitourinary, gastrointestinal and respiratory system. Germ cell tumor arises from the immature stem cells that were left undifferentiated in the fetal life. This tumor has good prognosis in early diagnosis (Langhorne, Fulton & Otto, 2007).

The rotation in pediatric oncology ward is challenging as well as exciting. The nurses here have to be extra conscious about all care related issues. Building rapport with the children is paramount to the effective nursing care of them. Childhood cancers are rare but children diagnosed with cancer may develop subtle anti social behavior during the long term therapy of the disease. This makes nurses to be equipped with extra psychosocial adaptation with children. As chemotherapy is widely used as the treatment modality besides surgery and radiation therapy, hence, pediatric population is vulnerable more than the adult in developing disease/treatment related debilitating symptoms like febrile neutropenia and tumor lysis syndrome . Parents’ education is paramount in adhering to the treatment regimen and prevention of nutropenia. Many patients came in pediatric oncology ward for port-a-cath needle insertion and dressing of PICC line. Nurses are meticulously involved in caring about the patients. Helping the physician in safely administration of intrathecal medication (IT) is also the job of nurses. The rotation bringing new horizons of learning and I am learning a lot about pediatric cancer care a lot.

Reference:

Moore, T.B. & Hurvitz, C.G.H. (2008). In Cassiato,D.A.& Territo, M.C. (2008). Manual of clinical oncology. 6^th Ede. Philadelphia: LWW. Ch 18. Pp 397-408.

Childhood cancer incidence:

Retrieved from: http://www.cancerresearchuk.org/cancer-info/cancerstats/childhoodcancer/

Site last updated 14/11/2012.

Bailey.S, & Skinner, R.(2010).Oxford specialist handbook of pediatric hematology and oncology. Oxford university press.

Porth, C.M, & Matfin, G., (2009). Pathophysiology concept of altered health. Ed 8^th. Philadelphia: LWW. Ch 5. Pp. 95-98.

Langhorne, M.E, Fulton, J.S, Otto, S.E., (2007). Oncology Nursing. Ed 5^th. St Louis, Messori: Mosbay. Ch3. P3.

Itano, J. K, & Taoka, K. N. (2005). Core Curriculum of Oncology Nursing. St. Louis, Messori: Elsevier. Ch 20. Pp 443.