Neoplstic Disorders

Acute lymphoblastic leukemia

Neoplastic disorders


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Maintenance phase may lasts for 2-3yr , it involves daily mecaptopurine and weekly methotrexate , usually with intermittent doses of vincristine and corticosteroid .Relapse should be treated with intensive chemotherapy with agents not previously used , followed by Allogeneic Stem Cell Transplantation . Supportive care for the acute & long – term complication of ALL should include:-Rx for tumor Lysis syndrome by allopurinol , hydration Rx of severe myelosuppression by packed RBC & platelets Sepsis require high index of suspicion with aggressive empirical antimicrobial therapy in febrile children with neutropenia .

Pg. most children with ALL can now be expected to have survival rate >90% at 5yr . however prognosis can be divided into favorable & un favorable according to the following criteria .


Non - Hodgkin LymphomaNHL Is The 2nd Most Common Malignancy Of Childhood After ALL Usually Occurs In Older Children's ( Between 5-19 Years )• 60% Of All Lymphoma In Children• Burkitt lymphoma is the most common• Most children have no underlying condition• Related diseases : risk factors for NHL :- - Severe combined immunodeficiency ( SCID)- Wiskott - Aldrich syndrome- Ataxia telangiectasia- Bloom's syndrome- HIV- EBVClinical presentation• Rapidly growing tumors with symptoms based on size and location• Burkitt lymphoma of abdomen ( sporadic type ) more common in the USA• Burkitt lymphoma of head and neck ( endomic type ) more common in africa• Superior vena cava ( SVC ) syndrome - chest involvement• Intestinal obstruction - abdominal mass• Paraplegia with spinal cord involvement• Tumor lysis syndrome- Hyperkalemia , hyperuricemia , hyperphosatemia , hypocalcemia .

Diagnosis CXRCT abdomen and pelvis CBC , Mg , Phos , Uric Acid , LD EBVBiobsy Treatment• ChemotherapyPrognosis• Excellent in most of children

HL is rare before 10 yr of age , but it is very common in adolescent & young adults with male predominance . ET. Idiopathic. Some suggest genetic predisposition because some cases are cluster in families & the risk in monozygotic twins is 100-folds. Others are related to immunodeficiency & viral infection , especially EBV . Path. HL appears to arise from the lymphoid & speared to the adjacent LN , although hematological speared can occur to many organs.
Hodgkin Lymphoma



Reed — Sternberg cell . is pathognomonic for HL ( although similar cells are seen in infectious mononucleosis , NHL and other conditions ) it is a large cell with multiple or multilobulated unclei ; .The recent classification of HL involves 5 subtypes ; Lymphocyte rich, mixed cellularity , Nodular Sclerosis ( the most common type ) Lymphocyte depletion ( rare in children ) and Nodular Lymphocyte predominance .C.M. HL can be presented with 1 or more of the following manifestations : -• Commonly presented as painless , nontender, firm , rubbery , cervical ( or supraclavicular ) LAP.Manifestations of airway obstruction [ dyspnea , hypoxia , cough ] , pleural or pericardial effusion due to mediastinal LAP • Manifestations of BM infiltration e.g. anemia , neutropenia or thrombocytopenia .• Hepatocellular dysfunction .• Patients also exhibit cellular immune system dysfunction ( which may persist even after recovery )• Systemic (B) symptoms are considered important in the staging of HL . it included ; unexplained fever > 390C, drenching night sweats , and weight loss >10% of body weight over 3 mo. Less common symptoms included; lethargy , anorexia , & pruritus Note : these manifestations are similar to those of tuberculosis . Clinically , HL can be classified into A,B & E ; (A) for Asymptomatic patient ; (B) for patient who exhibit any of the B symptoms ( i.e. FUO sweating or wt loss ) , (E) for Extralymphatic manifestation of diseases . Inv. Any patient with persistent , unexplained LAP not associated with an obvious underlying inflammatory or infectious process should undergo .


CXR. If there is large mediastinal mass , then do lymph node biopsy ( needle biopsy or preferably excisional biopsy ) . Other tests include : CBP , ESP , Serum ferritin ( which is of some prognostic significance ) LFT,CT , or MRI of chest & abdomen , BM aspiration & biopsy . it also may include Bone scans by either Gallium or FDG- PET imaging . RX. There are many chemotherapeutic regimens for HL, all are effective in eradication of disease with high cure rate , especially if combined with radiotherapy . complete response of HL to therapy is defined as complete resolution of disease on clinical exam and imaging studies . Newer agents for HL include : Rituximab ( anti- CD20 antibody ) and Brentuximab ( anti - CD30 agent that target RS cells themselves ) as well as EBV- specific cytotoxic T lymphocytes ( CTLs) can also be generated from allogeneic donors for patient with advanced HL . Patients who never achieve remission and who experience early relapse are candidate for myeloablative chemotherapy +/- radiation therapy following by allogeneic / autologous stem cell transplantation. Pg. poor prognostic features include : big size of tumor , advanced stage of disease at diagnosis , presence of B symptoms & early relapse ( within 1 yr of Rx )


BRAIN TUMORSEpidemiology• Almost 20% of all pediatric cancers• Peak age 0-4 years• Most common cancer mortality in children - 25% of all deaths from cancer .Clinical presentationBased on location , size , growth rate and age• Increased intracranial pressure- HeadacheVomiting ( often morning ) Mental changes , irritability Visual disturbances■ Diplopia■ PapilledemaGait disturbances• Failure to thrive• Cranial nerve abnormalities• Focal neurologic deficits• Seizures

Pathologic diagnosis• Based on cell of origin• Can occur at multiple location in the CNSInfratentorial - 60 %Supratentorial - 40 %• Common in children- Astrocytoma 40 % of all CNS tumorsJuvenile pilocytic astrocytoma - most common subtype in children Classic site for JPA is cerebellum , but can occur anywhere in CNS- Treatment Surgery - primary treatmentChemotherapy Radiation therapy

- Medulloblastoma 20% of all brain tumors ( second most common ) 90% of embryonal tumors Arises in cerebellum and fourth ventricle May metastasize down spinal cord and rarely outside CNS Treatment■ Surgery - prognosis based on extent resection■ Chemotherapy■ Radiation therapy - EpendymomaDerived from the ependymal lining of the ventricles70% occur in the posterior fossaPineal tumorsGerm cell tumors■ Germinoma■ Yolk sac tumor■ Mixed germ cell tumor Pineoblastoma


- Graniopharyngioma7-10% of childhood brain tumors Suprasellar location Solid and cystic components Associated with panhypopitutarism and visual loss ■ Tumor related■ Treatment related NeuroblastomaEpidemiology• Third most common pediatric cancer• 8% of childhood malignancy• Most commonly diagnosed neoplasm in infants ( 28-30% ) of neonatal malignancies• Mean age is 2 years Clinical presentation• Fever , failure to thrive• Para neoplastic symptoms - Secretory diarrhea- Increased sweating- Hypertension- Opsoclonus , myoclonus ( dancing , eyes , and dancing feet )

• Most cases arise in abdomen- Abdominal pain- Distended abdomens , mass• Thoracic tumors- Occasional horner's syndrome• Spinal tumors- Paraplegias• Metastatic diseases- Bone pain ( bone mets )- Cytopenias ( bone marrow infiltrate )- Orbital proptosis and ecchymosis - "raccon eyes " ( retro - orbital soft tissue infiltration )- Bluish subcutaneous nodules ( skin infiltration ) Diagnosis• CT/MRI scans often show calcifications• Tumor markets - Urine homovanillic acid ( HVA ) , vanillylmandelic acid ( VMA )

Treatment

• Chemotherapy• Radiation therapy• Stem cell transplant• New vaccines / antibodies• Retinoic acid Wilms Tumor• WT -1 gene located on 11p13 Epidemiology• Peak incidence 2-5 years of age• 8 cases / million children < 15 years Clinical presentation• Abdominal mass often noted first by parents• Abdominal pain , vomiting , hematuria in 12-25%• Hypertension• Anomalies and syndromes associated with wilms tumor- Beckwith - wiedemann ( Organomegaly , macroglossia , omphalocele , hemi hypertrophy )- WAGR ( aniridia , genitourinary abnormalities , intellectual disability )


Diagnosis
• US , KUB , CT , and / or MRI Treatment• Surgery , chemotherapy , and radiotherapy• Poor prognostic factor- Large tumor >500g- Advanced stage ( III or IV )- Unfavorable histologic type Rheumatic diseases


InvestigationAcute phase reactants : prognostic only- ESR - CRPRheumatoid factor■ Antibodies reacting with Fc portion of IgG occurs in- Rheumatoid arthritis - SLE- Scleroderma- Chronic active hepatitis- Infections as viral ( EB ) or parasites- Malignancies as leukemia & lymphoma

- SLE Scleroderma Rheumatoid arthritis

- Chronic active hepatitis- Infections as viral ( EB ) or parasites- Malignancies as leukemia & lymphoma LE cells : PMNL ingested a nucleus & ANA Complement :■ Total complement hemolytic activity■ Complement level C3&4SERUM Ig level :HLA systemImmune complex determination Others- Chemistry- Urinalysis- CSF- Imaging : x-ray - cardiac evaluation ( Echo - ECG ) - U/S .- Slit lamp & fundus . Antinuclear antibodies
Antibodies against unclear components ( DNA - RNA ) occurs in

Juvenile rheumatoid arthritis

Definition Chronic synovitis with extra - articular manifestations
Etiology : see before- Age of onset after the 2nd year- Clinical onset may occur after■ Joint trauma■ Systemic infections■ Psychological stress PathologyI- Articular❖ Joint effusion❖ Thickening & projection of the synovial membrane ( pannus )❖ Erosion of the articular cartilageBone erosion below the cartilage & osteoporosisTenosynovitis & myositis ❖ SC skin nodules II-Extra articular❖ Chronic inflammatory cells infiltration surrounding fibrinoid matrial

Clinical Manifestations

Prognosis❖ Chronic joint disease , spondyloarthropathy & Iridocyclitis❖ Exacerbations & remissions❖ May lead to joint deformity



Clinical manifestations
■ Cutaneous manifestations- Butterfly rash ( malar ) : erythematous , scaly or bullous- Macules or punctuate lesions on palms & soles- Oral mucosal ulcers- Alopecia & photosensitivity Investigations• CBC : pancytopenia• Acute phase reactants : prognostic• ANA : present in all cases with active SLE• Anti-double stranded DNA : diagnostic• Hypocomplementemia• Urinalysis - KFT - abdominal U/S & renal biopsyDiagnosis 4 or more of the following criteria should be present Skin ⟶1- Malar rash2- Discoid erythematous rash3- Photosensitivity4- Mucosal ( oral ulcers )Joints⟶ 1- Arthritis 2- Polyserositis


Neonatal lupus Et. _It results from maternal transfer of IgG autoantibodies ( usually anti-Ro / SSA or anti - La / SSB ) between 12- 16 wk of gestation , but however only small percentage of offspring will develop the disease .
RX. It is mainly supportive because most manifestations resolve . fluorinated corticosteroids , IVIG , Plasmapheresis , ydroxychloroquin , and terbutaline ( combined with steroids ) have been used in pregnant women with anti- Ro or anti-La antibodies to prevent occurrence or progression of fetal cardiac abnormalities . Cardiac pacing may be done when it detected and found to be severe , even before delivery !, Conduction system abnormalities after birth are treated with cardiac pacing and occasionally IVIG and steroids , while severe cardiomyopathy may require cardiac transplantation .

Vasculitis syndromes

Definition- Inflammation of blood vessels of unknown etiology. It may affect• Small non muscular vessels: henoch - schonlein purpra• Medium sized arteries: Kawasaki disease- polyarteritis nodes• Large vessels: takayasu arteries Etiology
Henoch-Schonlein Purpura Anaphylactoid Purpura
- Unknown may be due to allergy to drugs or may follow URTI
Pathology- Inflammatory cells surrounding small blood vessels of the skin with IgA deposition in the dermisClinical manifestations: occur at any age ( 2-8 years) Skin Lesions: (100% )■ Erythematous raised macules & papules ( Purpura )■ Buttocks - things - trunk & may be upper limb Arthritis : ( 2/3 of cases)■ Affecting large joints■ Complete resolution with no residuals

Renal involvement : ( 50% )■ Hematuria - proteinuria - hypertension - ARF■ Recovery is the rule■ Few cases may have persistent urinary sediments for years & rarely CRF GIT■ Abdominal colic , vomiting , hematemesis■ Blood in stool■ May lead to intussusception & intestinal obstruction CNS■ Convulsions - weakness & coma Others■ Lymph node enlargement■ HSMInvestigations : no specific testCBC → ↑↑ TLCAcute phase reactants → ↑↑ ESR UrinalysisKFTStool analysis 4- Abdominal U/SPrognosis• Mild cases → complete cure within few days• Moderate & severe cases → may persist for a long course with frequent remissions & exacerbations

Differential diagnosis

■ Skin rash■ Arthropathy■ Renal affection■ GIT TreatmentSymptomatic → salicylates & NSAID ( fever & arthritis ) Prednisone 1-2 mg / kg / day for renal - GIT manifestations or CNS manifestation Management of ARF

Kawasaki disease

Mucocutaneous lymph node syndrome Infantile polyarthritis
Etiology : unknown ?? viral ( Rota )
Clinical manifestation : age the first 5 years of life
- Four of the following
• Bilateral non purulent conjunctivitis • Oropharynegecal mucosa ■ Red , dry & fissured lips ■ Strawberry tongue ■ Pharyngeal congestion • Skin rash - Generalized erythema maculopapular rash
• Extremities ( hands & feet ) - Edema , erythema in the palms & soles with peeling at the tips of fingers & toes .
• Lymph node enlargement - Cervical ( usually ) non suppurtive & non tender
- Rarely generalized
- Rare manifestations
Cough , diarrhea HSM Arthropathy
- Complications : ( 20-40% )
Pericarditis & endocarditis
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