NEOPLASMS OF CHILDHOOD

AND INFANCY

DR G SIRISHA
ASSISTANT PROFESSOR
DEPARMENT OF PATHOLOGY
• Malignant neoplasms constitute the second
most common cause of death in children
between the ages of 4 and 14 years.
• Heterotopia or choristoma refers to
microscopically normal cells or tissues that are
present in abnormal locations.
• Examples are a pancreatic tissue “rest” found
in the wall of the stomach or small intestine .
• Hamartoma refers to an excessive but focal
overgrowth of cells and tissues native to the
organ in which it occurs.
• Although the cellular elements are mature
and identical to those found in the remainder
of the organ, they do not reproduce the
normal architecture of the surrounding tissue.
•Many malignant pediatric neoplasms are
histologically unique.
• In general, they tend to have a primitive
(embryonal) rather than pleomorphic-anaplastic
microscopic appearance, and frequently they
exhibit features of organogenesis specific to the site
of tumor origin.
• Because of their primitive histologic appearance,
many childhood tumors have been collectively
referred to as small, round, blue cell tumors.
• These are characterized by sheets of cells with
small, round nuclei.
The tumors in this category include
•Neuroblastoma
• Lymphoma
• Rhabdomyosarcoma
•Ewing sarcoma (peripheralneuroectodermaltumor)
• Wilms tumor
•Retinolastoma
•Medulloblastoma
•Teratoma
•Ependymoma
 NEUROBLASTOMA
• The term neuroblastic includes tumors of the
sympathetic ganglia and adrenal medulla that
are derived from primordial neural crest cells
populating these sites;
• neuroblastoma is the most important member
of this family.
• It is the second most common solid malignancy
of childhood after brain tumors, accounting for
7% to 10% .
• In childhood, about 40% of neuroblastomas arise in the
• adrenal medulla.
• The remainder occur anywhere along the
• sympathetic chain, with the most common locations
being the paravertebral region of the abdomen (25%)
and posterior mediastinum (15%).
• Macroscopically, neuroblastomas range in size from
minute nodules (the in situ lesions) to large masses
weighing more than 1 kg
Histologically, classic neuroblastomas are composed of small,
primitive-appearing cells with dark nuclei, scant cytoplasm,
and poorly defined cell borders growing in solid sheets.

The background often demonstrates a faintly eosinophilic

fibrillary material (neuropil) that corresponds to neuritic
processes of the primitive neuroblasts.

Typically, so-called Homer-Wright pseudo-rosettes can be

found in which the tumor cells are concentrically arranged
about a central space filled with neuropil (the absence of an
actual central lumen garners the designation “pseudo-”).
 RETINOBLASTOMA

Retinoblastoma is the most common primary

intraocular malignancy of children

Approximately 40% of the tumors are

associated with a germline mutation in the RB1
gene and are therefore heritable.
The remaining 60% of the tumors develop
sporadically,and these have somatic RB1 gene
mutation
• Retinoblastomas tend to be nodular masses,
usually in the posterior retina, often with
satellite seedings.
• On light microscopic examination,
undifferentiated areas of tumors are found to
be composed of small, round cells with large
hyperchromatic nuclei and scant cytoplasm,
resembling undifferentiated retinoblasts.
• Differentiated structures are found within many
retinoblastomas,the most characteristic of these being
Flexner-Wintersteiner rosettes .
• These structures consist of clusters of cuboidal or short
columnar cells arranged around a central lumen (in contrast
with the pseudo-rosettes of neuroblastoma, which lack a
central lumen).
• The nuclei are displaced away from the lumen, which by light
microscopy appears to have a limiting membrane resembling
the external limiting membrane of the retina.
• Tumor cells may disseminate beyond the eye through the
optic nerve or subarachnoid space.
• The most common sites of distant metastases are the CNS,
skull, distal bone.
 WILMS TUMOR
• Wilms tumor, or nephroblastoma, is the most
common primary tumor of the kidney in
children.
• Most cases occur in children between 2 and 5
years of age.
• Three groups of congenital malformations are associated with
an increased risk for development of Wilms tumor.
• Of patients with the WAGR syndrome (i.e., Wilms tumor,
aniridia, genital abnormalities, and mental retardation),
approximately one in three will go on to develop this Tumor.
• Another group of patients, those with the so-called Denys-Drash
syndrome (DDS), also have an extremely high risk
(approximately 90%) for the development of Wilms tumor.
• This syndrome is characterized by gonadal dysgenesis and renal
abnormalities. Both of these conditions areassociated with
abnormalities of the Wilms tumor 1 gene(WT1), located on
11p13.
• The nature of genetic aberration differs, however: Patients with
WAGR syndrome demonstrate loss of genetic material (i.e.,
deletions) of WT1, and persons with DDS harbor a dominant
negative inactivating mutation in a critical region of the gene.
• A third group of patients, those with the
Beckwith-Wiedemann syndrome (BWS), also
are at increased risk for the development of
Wilms tumor.
• These patients exhibit enlargement of
individual body organs (e.g., tongue, kidneys,
or liver)
• Or entire body segments (hemihypertrophy);
enlargement of adrenal cortical cells (adrenal
cytomegaly) is a characteristic microscopic
feature.
• BWS is an example of a disorder of genomic
imprinting
• As seen on gross examination, Wilms tumor
typically is a large, solitary, well-circumscribed
mass, although 10% are either bilateral or
multicentric at the time of diagnosis.
• On cut section, the tumor is soft,
homogeneous, and tan to gray, with
occasional foci of hemorrhage, cystic
degeneration, and necrosis
• On microscopic examination, Wilms tumors are
characterized by recognizable attempts to recapitulate
different stages of nephrogenesis.
• The classic triphasic combination of blastemal,
stromal, and epithelial cell types is observed in most
lesions, although the percentage of each component
is variable .
• Sheets of small blue cells, with few distinctive
features, characterize the blastemal component.
• Epithelial “differentiation” usually takes the form of
abortive tubules or glomeruli.
• Stromal cells are usually fibrocytic or myxoid in nature.
• Rarely, other heterologous elements are
identified, including squamous or mucinous
epithelium,smooth muscle, adipose tissue,
cartilage, and osteoid and neurogenic tissue.
• Approximately 5% of tumors contain foci of
anaplasia (cells with large, hyperchromatic,
pleomorphic nuclei and abnormal mitoses)
• Nephrogenic rests are putative precursor lesions of
• Wilms tumors and are sometimes present in the renal parenchyma
adjacent to the tumor.

• Nephrogenic rests have a spectrum of histologic appearances,

from expansile masses that resemble Wilms tumors (hyperplastic
rests) to sclerotic rests consisting predominantly of fibrous tissue
with occasional admixed immature tubules or glomeruli.
• It is important to document the presence of nephrogenic rests in
the resected specimen, since these patients are at an increased
risk for the development of Wilms tumors in the contralateral
kidney.
THANK YOU