Wilms tumor lymphoma abcdefgh klmno pytri

Wilms tumor lymphoma

1. PE29.9 Discuss the etiology, clinical
presentation and management of lymphoma in
children
PE21.7 Enumerate the etio-pathogenesis,
clinical features, complications and
management of Wilms Tumor

2. Lymphoma
Lymphomas are the third most common
malignancy in children and adolescents, after
leukemia and brain tumors
60% are non-Hodgkin lymphoma and
40% are Hodgkin lymphoma.
uncommon below the age of 5 yr
incidence increases with age

3. Hodgkin Disease
Definition:
lymphoreticular neoplasm primarily of B
cell lineage involving lymph nodes andthe
lymphatic system with development of
specific infiltrate containing pathologic
Reed-Sternberg cells.

4. Because the lymphatic system
runs all through the body, you
can get Hodgkin's Disease just
about anywhere.

5. Epidemiology


2-4 cases per 100000 population / year
bimodal age distribution : 15-35 years and above 50
years
In low-income countries, uncommon below 5 years , the
early peak occurs before adolescence; three form of age
incidence curve in epidemiologic studies:≤14 years,
15–35 , 55-74 yr
aged 7 to 12 years male predominance M:F = 10:1 and
equal distribution after 12

6. etiology
multi-factorial,
genetic- Siblings have a seven fold increase in the risk. a 100-
fold increased risk in monozygotic twins compared dizygotic
twins.
Infectious agents - human herpesvirus 6, cytomegalovirus, and
Epstein-Barr virus (EBV) . EBV viral DNA found in RS cells
suggesting monoclonal proliferation of the neoplastic clone after
EBV infection. in young children with mixed-cellularity
Immune related - rheumatoid arthritis, SLE, sarcoidosis ,

7. Cell of origin ??
Malignant lymphoproliferative disorder
Cell of origin ??
B or T
Hodgkin’s lymphoma

8. Cell of origin ??
Isolated RS cells
separated by micro-dissection technique and
monoclonal immunoglobulin Ig gene
rearrangement
showed
B cell type in 98% of cases
T cell type in 2% of cases

9. Reed-Sternberg cell
large, abnormal
lymphocytes (a type of
white blood cell) that
may contain more than
one nucleus. These cells
are found in people
with Hodgkin
lymphoma.

10. •The RS cell, a pathognomonic HL, is a large cell (15-45
µm in diameter) with multiple or multilobulated nuclei.
•RS cell the hallmark of HL, although similar cells are
seen in infectious mononucleosis, non-Hodgkin
lymphoma, and other conditions.
•The RS cell clonal in origin and arises germinal center
B cells, typically lost most B-cell gene expression
• no single simple genetic aberration. somatic
mutations, chromosomal instability, and complex
chromosomal rearrangements with no particular
pattern.

11. Tumour tissue composed of
Minor subset
malignant cells
Reed-Sternberg or one of its variants

Major subset
normal reactive
lymphoid and inflammatory cells

12. Diagnostic Malignant cells
•Classic Reed-Sternberg RS cell
•Hodgkin cell HC
•Lacunar cell LC
•Lympho-histiocytic L&H or popcorn
cell

13. Clinical Presentation
• painless, nontender, firm, rubbery, cervical or
supraclavicular lymphadenopathy 60-80% and /or
mediastinal adenopathy 50%
•Splenomegaly 30% Hepatomegaly 5%
•Extranodal complications : airway obstruction plural
pericardial effusion hepatocellular dysfunction bone
marrow infiltration
•Nephrotic syndrome well-known, rare presentation

14. Clinical Presentation
systemic symptoms (B symptoms) 30%


fever (>38 C/100.4 ° F)
night sweats
unexplained weight loss (10% in 6 months)
Cyclical fever (Pel-Ebstein fever) VERY RARE: a
cyclical high-grade fever for 1-2 weeks, rises
and falls abruptly, followed by no fever for 1-2
weeks

15. Clinical Presentation
other symptoms

•fatigue, weakness, pruritus
•cough , chest pain, shortness of breath,
vena cava syndrome
•abdominal pain, bowel disturbances,
ascites
•bone pain

16. Diagnosis of Hodgkin Disease
Definitive diagnosis excisional biopsy and
microscopic examination of lymph node or other
involved tissue
DO NOT fine-needle aspiration or core-needle
biopsy.
it requires identification of RS cell or LP cell
within the specimen for a definitive diagnosis.

17. Diagnosis of Hodgkin Disease

function of major organs - LFT RFT , HepB&C
HIV
LDH levels correlate with the bulk of disease.
Serum cytokines IL 6, IL 10, and soluble CD 25
correlate with systemic symptoms and
prognosis.

18. •PET-CT scan help with staging a standard test for
assessment of treatment response in lymphomas
•Positron emission tomography (PET) scan. a
radioactive sugar is injected into the bloodstream.
•Cancer cells use more sugar than normal cells, so the
sugar will collect in cancer cells. A
special camera is used to see where the radioactive
sugar

19. Pathologic Classification NEW WHo
• Classical Hodgkin disease
•lymphocyte rich (LR)
•nodular sclerosis 1 and 2 (NS)
•mixed cellularity(MC)
•lymphocyte depletion(LD)
•Nodular lymphocyte predominance
(LP)

20. Staging Classification
Ann Arbor modified by Cotswolds
•Stage I: single lymph node region or lymphoid structure
•Stage II: two or more lymph node regions on same side
of diaphragm
•Stage III: involvement of lymph node regions or
structures on both sides of diaphragm
III
1
: with splenic hilar,celiac,portal nodes
III
2
: with para-aortic,iliac,mesenteric nodes
•Stage IV:involvement of extranodal site(s)

21. Ann Arbor modified by Cotswolds
A. Asymptomatic
B. Symptomatic (B symptoms)
X. Bulky disease ( > 1/3 widening of mediastinum,
> 10cm max.dimension of nodal mass)
Lugano Classification”
E. a single, localised, extranodal tissue, next to,
but is not part of the lymph system
S: Cancerous cells have been found in the spleen

23. Risk groups: depending on the bulk of the
tumor(s) and“B” symptoms
Low risk: Stage I or Stage II with no bulky
tumors or “B” symptoms
: Stage I or II with bulky
tumors OR “B” symptoms; OR Stage III or IV
with no “B” symptoms
High risk: Stage III or IV with “B” symptoms

24. Treatment of Hodgkin Disesae
•a pediatric oncology center where a multidisciplinary
team familiar with the treatment, acute long-term
complications of pediatric malignancies.
•Three standard treatment : Chemotherapy, Radiation
therapy, Targeted therapy ( drugs or other substances
attack specific cancer cells without harming normal
cells, e.g. monoclonal antibody, High-dose
chemotherapy with stem cell transplant, Surgery

25. •Low-Risk Childhood Hodgkin Lymphoma
combination chemotherapy with or without low-dose radiation
therapy to involved areas.
•combination chemotherapy with low-dose radiation therapy to
involved areas.
Intermediate-Risk Childhood Hodgkin Lymphoma
High-Risk Childhood Hodgkin Lymphoma
Intensive or high-dose combination chemotherapy with low-dose
radiation therapy to involved areas.
•Surgery - bulk disese -Nodular LP

26. Most chemotherapy protocols for childhood
Hodgkin lymphoma will involve some unique
mixture of three standardized drug combinations
ABVD (the most common treatment protocol for adult
Hodgkin lymphoma): Adriamycin® (doxorubicin) Bleomycin
Vinblastine Dacarbazine (DTIC) for 4-6 cycles
BEACOPP Bleomycin Etoposide (VP-16) Adriamycin
(doxorubicin) Cyclophosphamide (Cytoxan®) Oncovin®
(vincristine) Procarbazine Prednisone
Stanford V Doxorubicin (Adriamycin) Mechlorethamine
(nitrogen mustard) Vincristine Vinblastine Bleomycin
Etoposide Prednisone

27. Non-Hodgkin Lymphoma
•Non-Hodgkin lymphoma (NHL) comprises a
heterogeneous group of lymphoid neoplasms
derived from cells of the immune system.
• NHL most common age 10 to 20 years
•Pediatric NHL are high grade, diffuse and
aggressive propensity for dissemination.
•current treatment 80% of children and adolescents
with NHL will survive for at least 5 yr

28. Etiology
•Following chemotherapy for Hodgkin disease,
• associated with immunodeficiency and DNA repair
deficiency syndromes (Wiskott-Aldrich syndrome, X-linked
lymphoproliferative disorders, ataxia-telangiectasia),
•acquired immunodeficiency syndrome and organ
transplantation (post-transplant lymphoproliferative
disease).
•Infection with malaria and EB virus risk factors for Burkitt
lymphoma

29. pathological subtypes children
Four major pathological subtypes of NHL in
Burkitt or Burkitt like lymphoma,
Lymphoblastic lymphoma, (common in India)
Diffuse large B cell lymphoma.
Anaplastic large cell lymphoma.

30. Children with NHL presentation
extranodal disease mediastinum, abdomen, or head and neck
region
Intrathoracic NHL - T cell lymphoma present superior
mediastinal or superior vena caval syndrome. associated
pleural and/or pericardial effusion.
Cervical adenopathy, abdominal pain, ascites, palpable
mabdominal mass, intestinal obstruction or intussusception
(typically B cell disease), cranial nerve palsy, bone involvement,
jaw swelling and cytopenias due to bone marrow involvement

31. Diagnosis
Histology , with immunophenotypic and cytogenetic
studies.
the diagnosis may be made with less invasive
procedures, e.g. percutaneous needle aspiration of
accessible lymph node, examination of body fluids (e.g.
pleural fluid) or bone marrow (If the clinical condition is
not suitable for biopsy, due to a large mediastinal mass
causing superior vena cava syndrome)

32. St Jude staging system for childhood nonHodgkin
lymphoma
Low-risk (localized)
I Single tumor (extranodal); single anatomic area
(nodal) excluding mediastinum and abdomen
II Single tumor (extranodal) with regional node
involvement; primary gastrointestinal tumor
(completely resected, with or without involvement of
mesenteric node); two or more tumors or nodal areas
on one side of diaphragm

33. High-risk (advanced)
III Primary intrathoracic (mediastinal, pleural and
thymic) tumor; extensive primary intra-abdominal
disease; paraspinal or epidural tumors regardless of
other tumor sites; two or more nodal or extranodal
areas on both sides of diaphragm
IV Any of the above with central nervous system and/
or bone marrow involvement

34. Management
•Surgery for diagnostic purposes.
•Radiotherapy to emergency situations, e.g. superior vena
cava syndrome or spinal cord compression due to paraspinal
disease.
•regimens for lymphoblastic lymphoma based on protocols
for ALL. Cranial irradiation or prophylactic intrathecal
chemotherapy stage III and IV disease.
•The longterm survival lymphoblastic lymphoma with limited
disease is 80--90% and foradvanced disease 70--80%.

35. chemotherapeutic regimens for B cell lymphoma
(Burkitt and non-Burkitt)
intensive alkylating high dose methotrexate, vincristine,
anthracyclines, etoposide and cytarabine; CNS
prophylaxis is provided with intrathecal chemotherapy.
short duration (6 months)
Long terms urvival more than 90% patients with
limited disease and
anti-CD20 monoclonal antibodies (e.g. rituximab)
directed against B cell antigens

36. Wilms tumor (nephroblastoma)
The most common malignant kidney tumor
80% WT under 5 yr of age; M:F frequency equal
The peak age at diagnosis is 2-3 yr;
Most WT are sporadic, 1 - 2% may be familial.
Bilateral more common with familial WT
6% patients have bilateral disease.

37. develop in the foci of embryonal kidney tissue called nephrogenic rests.
Nephrogenic rests transform into WT.
WT1 is the best characterized Wilms tumor gene. located at
chromosome 11p13 and encodes for a transcription factor for normal
kidney development
Genetic syndromes are predisposed to developing Wilms tumor.
WAGR (genetic syndromes)Wilms tumor, aniridia, genitourinary
abnormalities like horseshoe or fused kidney and mental retardation,
del 11p13

38. Clinical Features
• an asymptomatic abdominal mass
•hematuria (10-25%) hypertension (25%) abdominal
pain (30%),
•fever (20%), anorexia and vomiting.
• anemia, thrombocytosis,
•acquired deficiency of von Willebrand factor and
factor VII and polycythemia.

39. differential diagnosis
neuroblastoma,
hydronephrosis,
multicystic kidney
rarely abdominal lymphoma and
retroperitoneal rhabdomyosarcoma.

40. Investigations
Abdominal ultrasound and Doppler
dentifies organ of origin, contralateral kidney and presence or
absenceof tumor thrombus in inferior vena cava
CT scan
Evaluation tumor extension into liver, spleen and colon;
visualization and function of contralateral kidney; evaluation
for pulmonary metastasis
Fine needle cytology Cytological confirmation prior to
chemotherapy

41. Prognostic Factors
Stage I: Tumor confined to kidney completely excised.
Stage II: extends beyond kidney but completely excised.
Stage III: Tumor infiltrates renal fat; Lymph node
involvement of hilum, para-aortic etc
Stage IV: Metastasis in lung or liver, rarely bone and
brain.
Stage V: Bilateral renal at time of initial diagnosis.

42. Prognostic Factors
The majority of patients have standard histology,
where precise treatment is determined by staging.
favorable pathology (focal anaplasia) only surgical
excision
unfavorable histology (diffuse anaplasia) pleomorphic
and ruptured and show early metastasis to bones.
Ploidy is another prognostic sign, diploid tumors have
a better prognosis than hyperdiploid tumors.

43. Treatment
•National Wilms’ Tumor Study Group (NWTSG)
surgey (removal of the affected kidney) first, then
chemotherapy
the International Society of Pediatric Oncology (SIOP)
surgey first, then chemotherapy
because it diminishes the size of the tumor and allows better
staging. By preoperative chemotherapy, using actinomycin D
and vincristine for a period of 4 weeks

44. Treatment
•Stage I and II tumors with favorable histology are usually
treated postoperatively with vincristine and actinomycin
D.
• advanced WT - combination of vincristine, actinomycin D
and adriamycin along with abdominal radiation.
• Radiation- Abdominal stage III disease, pulmonary
metastasis.
•With modem therapy, 80-90% of patients with Wilms
tumor are cured.