Malignancies in children and Homoeopathy

Dr Amala.A

ABSTRACT: It begins with genetic change in single cells, that then grow into a mass (or tumour), that invades other parts of the body and causes harm and death if left untreated. Unlike cancer in adults, the vast majority of childhood cancers do not have a known cause.

KEY WORDS:  Homoeopathy, children, cancer

 LEUKAEMIA

ETIOLOGY

• The etiology of childhood leukemia is unknown and is thought to be multifactorial with both genetics and environmental factors contributing to malignant transformation.
• In chronic myeloid leukemia (CML) and, less commonly, in acute lymphoblastic leukemia (ALL), a translocation involving chromosomes 9 and 22 (Philadelphia [Ph] chromosome) creates a novel fusion gene called BCR-ABL. This results in the production of a constitutively activated tyrosine kinase that drives the development of CML and Ph-positive ALL.
• In addition, a number of genetic syndromes/diseases including Down syndrome (Trisomy 21), Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, Wiskott-Aldrich syndrome, neurofibromatosis type 1, and rare familial leukemia syndromes can predispose children to the development of acute leukemia.
• Siblings of children with leukemia are at an increased risk of developing leukemia with an approximately two- to fourfold risk above the general pediatric population (approximately 25% risk for monozygotic twins).
• Environmental factors that may increase the risk of leukemia include ionizing radiation and chemical exposures including certain chemotherapy agents (particularly the topoisomerase II inhibitors).¹

EPIDEMIOLOGY
ALL accounts for approximately 75%, acute myeloid leukemia (AML) accounts for approximately 20%, and CML accounts for less than 5% of leukemia cases in the pediatric population. Other chronic leukemias, including juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, and chronic lymphocytic leukemia, are rare in childhood.

CLINICAL FEATURES

• Signs and symptoms of acute leukemia are related to the infiltration of leukemic cells into normal tissues, resulting in either bone marrow failure (anemia, neutropenia, thrombocytopenia) and/or specific tissue infiltration (lymph nodes, liver, spleen, brain, bone, skin, gingiva, testes). Common presenting symptoms are fever, pallor, petechiae and/or ecchymoses, lethargy, malaise, anorexia, and bone/joint pain.
• Physical examination frequently reveals lymphadenopathy and hepatosplenomegaly. The testes and central nervous system (CNS) are common extramedullary sites for ALL involvement; neurological symptoms or a painless enlargement of one or both testes may be seen.
• Patients with T-cell ALL often have high white blood cell (WBC) counts, an anterior mediastinal mass (mediastinal adenopathy and/or thymic infiltration), cervical lymphadenopathy, hepatosplenomegaly, and CNS involvement. In patients with AML, extramedullary soft tissue tumors may be found in various sites.

General Prognostic Factors in Acute Lymphoblastic Leukemia ¹

FACTOR   AGE GENDER Race and ethnicity Initial WBC count CNS disease at diagnosis. Immunophenotype Ploidy Genetics Minimal residual disease after remission induction

FAVOURABLE (Lower risk) 1.9yrs Female Caucasian, Asian <50,000/mm3 Absent B-lineage Hyperdiploidy t(12;21), trisomies of chromosomes 4 and 10 Negative

UNFAVOURABLE (Higher risk) <1yr or <10yrs Male African American, Hispanic, Native American. ≥50,000/mm3 Present T cell Hypodiploidy t(4;11), t(9;22), Ph-like, iamp21 positive

LABORATORY AND IMAGING STUDIES

• The diagnosis of acute leukemia is confirmed by findings of immature blast cells on the peripheral blood smear, bone marrow aspirate, or both. Most patients have abnormal blood counts; anemia and thrombocytopenia are common.
• WBC count of 50,000/mm3 or higher (hyperleukocytosis) at presentation. Definitive diagnosis requires the evaluation of cell surface markers (immunophenotype) by flow cytometry.
• Cytogenetic analysis should be undertaken in all cases of acute leukemia because many reoccurring cytogenetic abnormalities have prognostic implications and are used, in combination with other risk factors, to assign therapy to optimize outcome.
• Fluorescent in situ hybridization or polymerase chain reaction techniques are now used in most cases of leukemia because many chromosomal abnormalities are not apparent on routine karyotypes.
• DNA microarray techniques are becoming an important diagnostic and prognostic tool. Recently, a new high-risk subgroup called Philadelphia-like ALL has been identified using this technique.
• A lumbar puncture should always be performed at the time of diagnosis to evaluate the possibility of CNS involvement.
• A chest x-ray should be obtained in all patients to assess for an anterior mediastinal mass. Electrolytes (particularly potassium, phosphorous, and calcium), uric acid, and renal and hepatic function should be monitored in all patients to assess and treat patients at risk for tumor lysis syndrome.

COMPLICATIONS

• Pneumocystis carcini pneumonia.
• These sequelae include neurocognitive impairment, short stature, obesity, cardiac dysfunction, infertility, second malignant neoplasms, and psychosocial problems^{. 1}

LYMPHOMA
ETIOLOGY

• Lymphomas are malignancies of lymphoid tissues and are the third most common malignancy in childhood, behind leukemias and central nervous system (CNS) tumors.
• There are two major types of lymphoma: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
• The etiologies are multifactorial. Both congenital and acquired immunodeficiencies are more commonly associated with NHL, whereas the Epstein-Barr virus (EBV) has been associated with both HL and NHL. Almost all cases of NHL in childhood are diffuse, highly malignant, and show little differentiation.
• NHL has three histological subtypes: small noncleaved cell (Burkitt lymphoma), lymphoblastic, and large cell.. In Burkitt lymphoma, translocations occurring between chromosome 8 (c-myc oncogene) and the immunoglobulin gene locus (found on chromosomes 2, 14, or 22) lead to overexpression of c-myc, causing malignant transformation.

EPIDEMIOLOGY
The incidence of HL has a bimodal distribution with peaks in the adolescent/young adult years and again after age 50; it is rarely seen in children younger than 5 years of age. In children, boys are affected more commonly than girls; in adolescents, the gender ratio is approximately equal.

CLINICAL FEATURES

• The most common clinical presentation of HL is painless, firm lymphadenopathy often confined to one or two contiguous lymph node areas (most commonly the supraclavicular and cervical nodes).
• Mediastinal lymphadenopathy, which produces cough or shortness of breath, is a frequent presenting symptom.
• The presence of one of three symptoms has prognostic value: fever (>38°C for 3 consecutive days), drenching night sweats, and unintentional weight loss of 10% or more within 6 months of diagnosis.
• The sporadic (North American) form of Burkitt lymphoma more commonly has an abdominal presentation (typically with pain), whereas the endemic (African) form frequently presents with tumors of the jaw.
• The anterior mediastinum and cervical nodes are the usual primary sites for T-cell lymphomas. These lymphomas may cause airway or superior vena cava obstruction, pleural effusion, or both. ²

DIAGNOSIS

• The diagnosis of lymphoma is established by biopsy of an involved lymph node.
• Systemic symptoms such as fever and weight loss may be present, particularly in patients with anaplastic large cell lymphoma (ALCL), which can be insidious in onset.
• If the bone marrow contains 25% or greater blasts, the disease is classified as acute leukemia (either B-lineage acute lymphoblastic leukemia [ALL], T-cell ALL, or Burkitt leukemia). This distinction makes little prognostic or therapeutic difference as they all require aggressive, systemic therapy in addition to CNS-directed therapy.

LABORATORY/IMAGING STUDIES

• Patients suspected of having lymphoma should have a complete blood count, erythrocyte sedimentation rate, and measurement of serum electrolytes (particularly potassium, phosphorous, and calcium), lactate dehydrogenase, and uric acid as well as a chest x-ray to assess for a mediastinal mass .
• The diagnosis ultimately requires a pathological confirmation from tissue or fluid sampling (pleural or peritoneal fluid).
• For staging purposes, a bone marrow evaluation, positron emission tomography (PET) and, less commonly, a bone scan are indicated to assess extent of disease (staging).
• The pathological hallmark of HL is the identification of Reed-Sternberg cells. Histopathological subtypes in childhood HL are the same as those reported in adults. Nodular sclerosis (NS) is the most common subtype in adolescents/young adults, whereas mixed cellularity subtypes and nodular lymphocyte predominant are more common in younger children.
• Staging of HL is according to the Ann Arbor system.

MANAGEMENT
In general, four to six courses of chemotherapy are given. The use of anti-CD30 monoclonal therapy (Brentuximab vedotin) and the elimination of bleomycin is currently under investigation in pediatric HL. ²

CENTRAL NERVOUS SYSTEM TUMORS

ETIOLOGY

• Most central nervous system (CNS) tumors in children and adolescents are primary tumors that originate in the CNS and include gliomas (especially low-grade gliomas) and embryonic neoplasms (such as medulloblastoma and CNS primitive neuroectodermal tumors).
• In contrast, CNS tumors in adults are often high-grade astrocytomas or secondary tumors that are metastatic from other carcinomas.
• CNS tumors also may arise in patients previously treated with radiation therapy. CNS tumors are likely multifactorial in etiology.

CLINICAL FEATURES

• Increased intracranial pressure.
• Tumors that obstruct the flow of CSF quickly become symptomatic. Symptoms of increased intracranial pressure are lethargy, headache, and vomiting (particularly in the morning on awakening).
• Irritability, anorexia, poor school performance, and loss of developmental milestones all may be signs of slow-growing CNS tumors. In young children with open cranial sutures, an increase in head circumference may occur.
• Optic pathway tumors may lead to loss of visual acuity or visual field defects. Inability to abduct the eye as the result of sixth cranial nerve palsy is a common sign of increased intracranial pressure.
• Seizures occur in 20-50% of patients with supratentorial tumors; focal weakness or sensory changes also may be seen. Pituitary involvement can produce neuroendocrine effects such as precocious puberty or diabetes insipidus.
• Cerebellar tumors are associated with ataxia and diminished coordination. ³

LABORATORY/IMAGING STUDIES

• MRI
• Examination of CSF by cytocentrifuge histological testing is indicated to determine the presence of metastatic disease in primitive neuroectodermal tumors, germ cell tumors, and pineal region tumors.

     MANAGEMENT

• The therapy for children with CNS tumors is individualized and depends on the tumor type, location, size, and associated symptoms.
• High-dose dexamethasone is often administered immediately to reduce tumor-associated edema.
• Surgical objectives are complete excision, if possible, and maximal debulking if a complete excision is not possible. In children, radiation therapy is often combined with chemotherapy; in young children, radiation therapy may be delayed or avoided altogether.

NEUROBLASTOMA
ETIOLOGY

• Neuroblastoma is derived from neural crest cells that form the adrenal medulla and the sympathetic nervous system. Most cases occur in young children.. Mutations in the ALK, PHOX2B, and TP53 genes have been associated with familial cases. In sporadic cases, several somatic genetic mutations have been identified, with MYCN amplification being the most common.

CLINICAL FEATURES

• Children with localized disease are often asymptomatic at diagnosis, whereas children with metastases often appear ill and have systemic complaints such as fever, weight loss, and pain.
• The most common presentation is abdominal pain or mass. The mass is often palpated in the abdomen or flank and is hard and nontender. Approximately 45% of tumors arise in the adrenal gland, and 25% arise in the retroperitoneal sympathetic ganglia. Other sites of origin are the paravertebral ganglia of the chest and neck. Paraspinal tumors may invade through the neural foramina and cause spinal cord compression.
• Horner syndrome is sometimes seen with neck or apical masses. Several paraneoplastic syndromes, including secretory diarrhea, profuse sweating, and opsomyoclonus, are associated with neuroblastoma.
• Neuroblastoma may metastasize to multiple organs, including the liver, bone, bone marrow, and lymph nodes.
• Periorbital ecchymoses are a sign of orbital bone metastases.
• A unique category of neuroblastoma, stage MS, is defined in infants (<18 months old) with metastases limited to skin, liver, or bone Marrow.

LABORATORY/IMAGING STUDIES

• A complete blood count and plain radiographs may help identify patients with neuroblastoma.
• Calcification within abdominal neuroblastoma tumors is often observed on plain radiographs of the abdomen.
• About 90% of neuroblastomas produce catecholamines (vanillylmandelic acid; homovanillic acid) that can be detected in the urine.
• Definitive diagnosis of neuroblastoma requires tissue biopsy for microscopic examination and genetic testing.
• A computed tomography (CT) scan of the chest, abdomen, and pelvis; bilateral bone marrow aspiration and biopsies; and urinary catecholamines complete the evaluation.

MANAGEMENT
High-dose chemotherapy with autologous stem cell rescue; recent data suggest two courses of high-dose therapy are better than one. Radiation therapy is then administered to the primary tumor bed and areas of metastatic disease. ^1,3

WILM’S TUMOR

• Wilms tumor is thought to arise from primitive, metanephric blastema, the precursor of a normal kidney.

• Nephrogenic rests are foci of embryonal cells that are rarely (<1%) found in normal infant kidneys but commonly (25-40%) found in Wilms tumor–bearing kidneys.

• Although the cause of Wilms tumor is unknown, approximately 15-20% of sporadic tumors have WT1 mutations or deletions.
• Over 70% of Wilms tumors demonstrate loss of imprinting or loss of heterozygosity at 11p15, leading to overexpression of IGF2, thought to play a key role in tumorigenesis.

• Certain syndromes including Beckwith-Wiedemann and WAGR (Wilms tumor, aniridia, genitourinary anomalies, and retardation; mutation involving 11p13 region) are at increased risk of developing the disease.

CLINICAL FEATURES

• Abdominal mass in children that is discovered by their parents.
• Although many children do not have complaints at the time that the mass is first noted, associated symptoms may include abdominal pain (often mistaken for constipation), fever, hypertension, and hematuria.

LABORATORY/IMAGING STUDIES

• An abdominal ultrasound or computed tomography (CT) scan can usually distinguish an intrarenal mass from a mass arising from the adrenal gland (most commonly neuroblastoma) or other surrounding structures.
• Evaluation of the inferior vena cava is crucial because the tumor may extend from the kidney into the vena cava.
• The diagnostic work-up includes a complete blood count, urinalysis, liver and renal function studies, as well as a CT scan of the chest, abdomen, and pelvis to assess for metastatic involvement (pulmonary involvement is the most common metastatic site). The diagnosis is confirmed by histological examination of the tumor.

DIFFERENTIAL DIAGNOSIS

• Mesoblastic nephroma and Hamartoma.
• Neuroblastoma,
• Renal cell carcinoma, lymphoma, and retroperitoneal rhabdomyosarcoma.

MANAGEMENT

• Chemotherapy.
• Radiation therapy.
• Nephrectomy of the involved kidney. ^1,2

SARCOMAS

• Sarcomas are divided into soft tissue sarcomas and bone cancers.
• Soft tissue sarcomas arise primarily from the connective tissues of the body, such as muscle tissue, fibrous tissue, and adipose tissue.

• Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is derived from mesenchymal cells of muscle lineage.

• The most common malignant bone cancers in children are osteosarcoma and Ewing sarcoma.
• Osteosarcomas derive from primitive bone-forming mesenchymal stem cells. Ewing sarcomas are thought to be of neural crest cell origin.

ETIOLOGY

• Individuals with Li-Fraumeni syndrome (associated with a germline p53 mutation) and neurofibromatosis (associated with NF1 mutations) have an increased risk of soft tissue sarcomas.

• There is a 500-fold increased risk for osteosarcoma for individuals with hereditary retinoblastoma. Prior treatment for childhood  cancer with radiation therapy or chemotherapy (specifically alkylating agents), or both, increases the risk for osteosarcoma as a second malignancy.

CLINICAL FEATURES

• Periorbital swelling, proptosis, and limitation of extraocular motion may be seen with an orbital tumor.
• Nasal mass, chronic otitis media, dysphagia, neck mass, and cranial nerve involvement may be noted with tumors in other head and neck sites.
• Urethral or vaginal masses, paratesticular swelling, hematuria, and urinary frequency or retention may be noted with tumors in the genitourinary tract.

• Trunk or extremity lesions tend to present as rapidly growing masses that may or may not be painful. If there is metastatic disease to bone or bone marrow, limb pain and evidence of marrow failure may be present.

• Osteosarcoma is often located at the epiphysis or metaphysics of long bones that are associated with maximum growth velocity(distal femur, proximal tibia, proximal humerus), but any bone may be involved. It presents with pain and may be associated with a palpable mass.

• Ewing sarcoma can occur in almost any bone in the body, the femur and pelvis are the most common sites. In addition to local pain and swelling, clinical manifestations may include constitutional symptoms such as fever, fatigue,and weight loss

INVESTIGATIONS

• The radiographs usually reveal a lytic lesion, sometimes associated with calcification in the soft tissue surrounding the lesion.

LABORATORY/IMAGING STUDIES

• Tissue biopsy is needed for a definitive diagnosis of sarcoma.
• Under light microscopy, RMS and Ewing sarcoma appear as small, round, blue cell tumors.
• Osteosarcomas are distinguishable by the presence of
• Immunohistochemical staining for muscle-specific proteins, such as actin and myosin, helps confirm the diagnosis of RMS.
• Two major histological variants exist for RMS: embryonal and alveolar. The embryonal (ERMS; embryonal RMS) histological variant is most common in younger children with head, neck, and genitourinary primary tumors. The alveolar (ARMS; alveolar RMS) histological variant occurs in older patients and is seen most commonly in trunk and extremity tumors. Alveolar RMS is often characterized by specific translocations: t(2;13) or t(1;13).
• Metastatic evaluation for patients with RMS should include positron emission tomography (PET) scan (when available), chest computed tomography (CT), and bilateral bone marrow aspiration/biopsy.
• A lumbar puncture is required in patients with a parameningeal primary site due to the risk of direct extension into the central nervous system (CNS). The diagnosis of osteosarcoma is established with the presence of osteoid and immunohistochemical analysis of the biopsy material. The extent of the primary tumor should be delineated carefully with MRI.
• Ewing sarcoma is characterized by a specific chromosomal translocation, t(11;22), which is seen in 95% of tumors. MRI of the primary lesion should be performed to delineate extent of the lesion and any associated soft tissue mass.

GENERAL  MANAGEMENT

• Radiation therapy
• Chemotherapy ^1.3

HOMOEOPATHIC MANAGEMENT

• Calcarea fluorica: Knots and kernels are usually treated with the help of this medicine. Hardened in any part of the body. Stony hardness within indurated glands and enlargements . cancer of long bones. ⁵
• Lapis Albus: post cancer pains with yellow discharge from cancer, weakness post chemotherapy. ⁴
• Hecla Lava: This medicine can help in treating ivory tumours which are spongy in texture.⁵
• Conium: Hardness in the glands that have been infiltrated by the cancerous, multiplying cells.⁴
• Condurango: cancer of different parts of the stomach and abdomen,. It can help in treating open tumours. Symptoms of cancer that form in the epithelial cells of the body. ⁴
• Phytolacca:. These fatty tumours can be treated with this medicine . hardened lumps in glands. ⁵
• Arsenicum: Helps in treating Lupus as well as cancer. Weakness, debility , burning pain. ⁵
• Iodine: cervical cancer with extreme stiffness of neck. ⁴

 BIBLIOGRAPHY

• Nelson text book of paediarics, edition, Elseiver,Edition 8^th, pg 595-613.
• Gupta Piyush, PG text book of Paediatrics, 2^nd edition, Jaypee brothers publications, pg no 2607-2710.
• AIP text book of paediatrics, Jaypee brothers publishers, 5^th edition,pg 747-775.
• Clark Henry John, Condensed Homoeopathic Materia Medica and Repertory , B. Jain Publishers. Revised Ed, pg 58, 59, 83,67,
• ND Murphy Robin , Homoeopathic medical Repertory , Indian book periodal publishers, 1^st Ed pg 34, 42, 47, 53,

Author: Dr.Amala.A(M.D –Part 2).
Department Of Paediatrics.
Father Muller Homoeopathic Medical College, Deralakatte, Mangaluru- 575018

Under The Guidance Of: Dr Jyoshna Shivaprasad.
Professor And H.O.D, Paediatrics. Father Muller Homoeopathic Medical College