Tumors and Tumor Like Lesions of Infancy and Childhood

Slide 1 · Tumors and Tumor-Like Lesions of Infancy and Childhood

Pediatric pathology: developmental lesions, benign neoplasms and childhood malignancies

Classification • morphology • clinicopathologic reasoning

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals for the pediatric mass

Classify heterotopia, hamartoma and neoplasm without assuming that every mass is malignant.

Explain why mature, bland tissue can produce clinically important complications.

Recognize characteristic benign childhood tumor groups and the embryonal malignant phenotype.

Integrate location, morphology, molecular findings and developmental context in diagnosis.

Slide 3 · Why childhood masses require a distinct framework

Benign lesions outnumber malignancies in infancy and childhood.

Developmental abnormalities can mimic true neoplasia.

Lesion size and location may determine morbidity despite benign histology.

Pediatric malignancies differ from adult cancers in histogenesis and natural history.

Slide 4 · Childhood cancers: Uncommon but consequential

Only about 2% of malignant tumors occur during infancy or childhood.

Its cited U.S. Mortality context identifies cancer, including leukemia, as a major cause of death at ages 5–14 years.

These textbook figures describe epidemiologic context, not contemporary surveillance estimates.

Slide 5 · The first diagnostic fork is lesion type

Developmental tissue in an abnormal location

Overgrowth of native tissue with disturbed arrangement

True neoplastic proliferation

Ask whether the tissue belongs here, whether its architecture is normal, and whether the lesion represents a neoplasm.

Slide 6 · The word “tumor” does not establish neoplasia

Mass-forming process

A clinically visible or palpable lesion

May represent a developmental process

May have entirely mature cells

Neoplastic process

A proliferative lesion with neoplastic biology

Can be benign or malignant

Morphology and clinical context determine interpretation

Slide 7 · Architecture, location and behavior are separate axes

Location

Native site or ectopic site?

Architecture

Organized like normal tissue or disordered?

Behavior

Stable, enlarging, involuting, locally aggressive or metastatic?

One axis cannot safely substitute for the others.

Slide 8 · Heterotopia means normal tissue in an abnormal site

Heterotopia is synonymous with choristoma in this textbook context.

The cells and tissues are microscopically normal but anatomically misplaced.

A heterotopic focus may resemble a tumor during examination or imaging.

Most heterotopic rests have little clinical significance.

Slide 9 · Heterotopia: Site, not cytologic atypia, is abnormal

Microscopic identity

Mature tissue retains its recognizable differentiation.

Anatomic relation

The tissue is located outside its usual organ.

Interpretation

The mass is usually developmental rather than a primary malignancy.

Conceptual schematic: These boxes do not depict real histology.

Slide 10 · Ectopic pancreatic tissue as a heterotopia

Pancreatic tissue with mature differentiation

Pancreatic tissue in gastric or intestinal wall

May present as a focal mass

Pancreatic rests in stomach or small intestine as examples of heterotopia.

Slide 11 · Ectopic adrenal tissue as a diagnostic trap

Adrenal rests may occur in kidney, lung or ovary.

A mass composed of adrenal tissue in the ovary is not automatically an ovarian primary tumor.

Cell identity and anatomic setting must both be evaluated.

The rare possibility of a true neoplasm arising in an ectopic adrenal rest.

Slide 12 · Heterotopia and neoplasia are not mutually exclusive

Heterotopic mature rest

Uncommon secondary neoplastic transformation

True tumor at an unexpected site

The textbook example is an adrenal cortical carcinoma arising in ovarian ectopic adrenal tissue.

Slide 13 · Heterotopia: Practical diagnostic questions

Is the tissue identical to a mature tissue normally found elsewhere?

Is its location truly ectopic rather than an extension of the native organ?

Is there convincing neoplastic cytology, invasion or destructive growth?

Can the clinical and anatomic findings be explained by a developmental rest?

Slide 14 · Hamartoma is disorganized overgrowth at a native site

A hamartoma is a focal, excessive growth of tissue native to the affected organ.

Its cellular elements are mature and recognizable.

Normal tissue proportions or architecture are not faithfully reproduced.

Maturity does not guarantee that the lesion is harmless.

Slide 15 · The defining hamartoma problem is tissue arrangement

Cell identity

Mature, native tissue components.

Growth

Excessive local development or proliferation.

Architecture

Disordered relationships rather than normal organ pattern.

Simplified conceptual distinction; Not a photomicrograph.

Slide 16 · Why hamartomas are not simply normal tissue

Normal organ

Expected cell proportions and spatial relationships

Integrated organ architecture

No discrete expansile overgrowth

Hamartoma

Localized excess of native elements

Disrupted tissue organization

Can form a clinically significant mass

Slide 17 · Hamartoma versus benign neoplasm: A blurred boundary

The textbook cautions that both lesions may be clonal.

Clonality alone does not settle whether a lesion should be named hamartoma or benign neoplasm.

Clinical behavior, tissue organization and established entity definitions remain relevant.

Slide 18 · Entities variably called hamartomas

Vascular / muscular

Hemangiomas

Lymphangiomas

Cardiac rhabdomyomas

Glandular / cystic

Hepatic adenomas

Developmental cysts of kidney

Developmental cysts of lung or pancreas

Slide 19 · Cardiac rhabdomyoma illustrates organ-specific risk

Cardiac rhabdomyoma among lesions variably regarded as hamartomas or neoplasms.

The same bland histology can matter differently depending on location.

An intracardiac mass deserves assessment for functional effects rather than classification alone.

Slide 20 · Developmental cysts belong in the mass differential

Developmental cysts of kidney, lung and pancreas are listed among hamartoma-like lesions.

A cystic mass should not be presumed neoplastic solely because it distorts the organ.

Architecture, organ of origin and clinical impact guide interpretation.

Slide 21 · Why benign histology may still be dangerous

Nonmalignant tissue mass

Unfavorable site or substantial size

Compression, obstruction or impaired organ function

Biologic benignity and clinical harmlessness are different propositions.

Slide 22 · Risk assessment is not equivalent to malignancy grading

Histology

Does the lesion show malignant features?

Anatomy

Does it threaten vital structures?

Course

Is it growing, stable or involuting?

A bland lesion may still require careful clinical evaluation.

Slide 23 · Heterotopia, hamartoma and neoplasm compared

Feature

Heterotopia

Hamartoma

Neoplasm

Tissue location

Ectopic

Native organ

Variable

Cell differentiation

Usually normal/mature

Mature/native

Variable

Architecture

Often organ-like rest

Focally disordered

Entity-dependent

Key question

Why is it here?

Why is it overgrown?

What is its biologic behavior?

Slide 24 · Case: An ovarian mass containing adrenal tissue

CLINICOPATHOLOGIC APPLICATION

A young child has a small ovarian lesion composed of recognizable mature adrenal cortical cells.

Which diagnostic category should be considered before assuming an ovarian neoplasm?

What additional findings would suggest a true neoplasm in the ectopic rest?

Slide 25 · Benign childhood tumors have a different tissue spectrum

Pediatric solid tumors commonly arise from mesenchymal tissue.

The textbook contrasts this pattern with the predominance of epithelial tumors in adults.

Hemangiomas, fibrous lesions and teratomas receive special attention in infancy and childhood.

Slide 26 · Mesenchymal predominance: Practical implications

Childhood emphasis

Vascular proliferations

Fibroblastic/myofibroblastic lesions

Embryonal and germ-cell neoplasms

Adult contrast

Epithelial tumors are prominent

Organ-specific epithelial primaries dominate many common cancer sites

Age changes the prior diagnostic probability

Slide 27 · Vascular lesions are not a single biological group

Vascular mass in an infant

Proliferative vascular tumor OR vascular malformation

Interpret growth behavior and architecture

The term “hemangioma” has historically been used inconsistently for some malformations.

Slide 28 · Vascular tumor versus vascular malformation

Concept

Proliferative vascular tumor

Vascular malformation

Defining issue

Vascular cellular proliferation

Structural vascular anomaly

Terminology

Hemangioma used for many benign tumors

May also be mislabeled “hemangioma”

Diagnostic caution

Identify proliferation

Avoid deciding solely by surface appearance

Slide 29 · Where infantile vascular masses are encountered

Most arise in skin, especially head and neck regions.

They may form flat or raised red-blue masses.

The category includes lesions clinically described as port-wine stains.

A superficial color pattern is not sufficient to determine underlying biological type.

Slide 30 · Some vascular lesions enlarge then regress

Visible vascular lesion in infancy

Growth with the child or early enlargement

Spontaneous regression in some lesions

Variability; Involution is not a universal feature of vascular anomalies.

Slide 31 · Familial vascular malformations: A molecular example

A subset of CNS cavernous vascular malformations occurs in familial settings.

KRIT1, CCM2 and PDCD10 as implicated genes.

This illustrates that vascular anomalies may reflect inherited developmental signaling defects.

Slide 32 · Fibrous childhood lesions form a biologic spectrum

Fibromatosis

Sparsely cellular spindle-cell proliferation

Fibroblastic or myofibroblastic lineage

Behavior must be judged in context

Infantile fibrosarcoma

Cellular lesion resembling adult fibrosarcoma

Molecularly distinctive in many cases

Generally favorable prognosis relative to adult counterpart

Slide 33 · Fibromatosis: A spindle-cell pattern

Relatively sparsely cellular proliferations of spindle-shaped cells.

A spindle-cell appearance is a morphologic description, not a stand-alone risk category.

Anatomic extent and clinicopathologic context remain necessary.

Slide 34 · Infantile fibrosarcoma: Morphology can mislead

Histology may closely resemble adult fibrosarcoma.

Despite this resemblance, infantile fibrosarcoma generally has an excellent prognosis.

The distinction highlights why age and specific molecular alterations matter in pediatric pathology.

Slide 35 · ETV6::NTRK3 is a characteristic oncogenic fusion

T(12;15)(p13;q25)

ETV6::NTRK3 fusion transcript

Constitutively active TRKC kinase

The fusion is especially useful diagnostically among soft-tissue tumors account.

Slide 36 · How ETV6::NTRK3 produces a growth signal

Fusion kinase activation

RAS–MAPK and PI3K–AKT signaling

Oncogenic proliferative drive

A mechanistic rationale for targeted inhibition, rather than a generic histology label.

Slide 37 · Molecular classification can change treatment options

Infantile fibrosarcomas with ETV6::NTRK3 fusion may respond to selective NTRK inhibition.

Robbins specifically describes marked responses in previously unresectable fusion-positive lesions.

Treatment selection requires actual molecular characterization; Morphologic resemblance is insufficient.

Slide 38 · Teratomas illustrate differentiation versus behavior

Teratomas can contain tissue differentiated along germ-layer lineages.

The textbook separates mature, immature and overtly malignant forms.

A high degree of histologic maturation does not automatically settle clinical risk in every setting.

Slide 39 · Three germ layers underpin teratomatous tissues

Ectoderm

Examples include neural or squamous epithelial differentiation.

Mesoderm

Examples include muscle or connective tissue differentiation.

Endoderm

Examples include glandular epithelial differentiation.

Conceptual lineage map; These are examples of tissue differentiation, not a diagnostic micrograph.

Slide 40 · Teratoma categories differ in biological potential

Category

Core histologic pattern

Interpretation

Mature

Well-differentiated tissue types

Often benign; May be cystic

Immature

Immature tissue, commonly neuroepithelium

Potential correlated with immature tissue extent

Malignant

Unequivocal malignancy, often another germ-cell component

Requires identification of malignant component

Slide 41 · Sacrococcygeal teratoma is a characteristic pediatric site

Sacrococcygeal tumors as the most common childhood teratomas.

They are frequently congenital and may attain considerable size.

The anatomic setting creates a distinct clinical problem even before histologic classification.

Slide 42 · Teratomas can accompany congenital anomalies

Associations with hindgut and cloacal anomalies and midline defects.

Examples include meningocele and spina bifida.

The text does not attribute these anomalies simply to mass compression by the teratoma.

Slide 43 · Mature and immature tissue can coexist

A teratoma may include several well-differentiated tissue types.

Immature neuroepithelial elements are particularly relevant when assessing immaturity.

The search for an associated malignant germ-cell component is a separate diagnostic task.

Slide 44 · Benign lesion family: Integrate composition with course

Lesion group

Clue to identity

Important caveat

Heterotopia

Normal tissue outside native site

Unexpected location may simulate neoplasm

Hamartoma

Disorganized native mature tissues

Can be symptomatic despite benign histology

Vascular anomaly

Vascular morphology; Variable course

Tumor and malformation are not synonyms

Fibrous lesion

Fibroblastic spindle-cell pattern

Age/molecular data alter expected behavior

Teratoma

Multiple differentiated tissue types

Maturity and malignant components must be assessed

Slide 45 · Childhood malignancies differ from adult carcinomas

Hematopoietic, neural, soft-tissue, bone and renal sites are prominent in pediatric cancers.

Developmental pathways and constitutional predisposition play important roles.

Primitive embryonal histology is common among pediatric solid cancers.

Spontaneous differentiation or regression is documented in selected tumors.

Slide 46 · Anatomic distributions create age-related priors

Children

Hematopoietic system

Central and sympathetic nervous system

Soft tissue, bone and kidney

Adults

Common cancers frequently involve epithelial sites

Textbook examples: Lung, breast, prostate, colon and skin

Clinical differential changes with age

Slide 47 · Embryonal tumors resemble disrupted organogenesis

Primitive developmental precursor

Incomplete or abnormal differentiation

Embryonal-appearing malignant tumor

Organ-specific differentiation can still suggest the lineage of origin.

Slide 48 · Why some pediatric tumors look “small round blue”

Many malignant pediatric tumors comprise sheets of primitive cells.

Cells often have scant cytoplasm and small dark nuclei.

The shared appearance describes a pattern, not a single disease.

Different origins demand clinicopathologic and ancillary discrimination.

Slide 49 · The “-blastoma” suffix signals embryonal differentiation

Nephroblastoma, neuroblastoma and hepatoblastoma recall developing organ tissues.

The suffix is a naming clue, not proof of a shared molecular mechanism.

The anatomical site and observed differentiation constrain the diagnosis.

Slide 50 · Small round blue cell tumors: Differential

Category

Examples

Distinguishing context

Neural

Neuroblastoma, medulloblastoma, retinoblastoma

Anatomic site and neural differentiation

Renal

Wilms tumor

Developing renal structures

Hematolymphoid

Lymphoma

Lineage-specific studies

Mesenchymal

Rhabdomyosarcoma, Ewing sarcoma

Lineage morphology and molecular studies

Slide 51 · Site-first diagnostic reasoning reduces ambiguity

Age and anatomical site

Histology plus specific differentiation

Selected immunohistochemical or molecular tests

Location often makes the diagnosis possible, but some cases require ancillary studies.

Slide 52 · Developmental anomalies can signal tumor predisposition

A close relationship between teratogenesis and oncogenesis in some childhood cancers.

Congenital anomalies may identify an underlying tumor-predisposition syndrome.

Hereditary aberrations are relatively more prominent in some pediatric tumor groups.

Slide 53 · Spontaneous regression is a real but selective phenomenon

Selected fetal and neonatal malignancies may regress or differentiate spontaneously.

This phenomenon is especially important in some neuroblastic lesions.

Regression is not a general permission to assume that an undiagnosed pediatric mass is innocuous.

Slide 54 · Neuroblastic tumors arise along the sympathetic lineage

Neural crest–derived precursor

Sympathetic ganglia / adrenal medulla

Neuroblastoma and more differentiated relatives

Neuroblastoma is a key pediatric embryonal tumor, discussed in depth in its dedicated series topic.

Slide 55 · Where neuroblastoma begins and spreads

The adrenal medulla is a prominent primary site.

Other lesions occur along the sympathetic chain, including abdominal paravertebral and posterior mediastinal locations.

Advanced tumors can involve lymph nodes, liver, bone and bone marrow.

Slide 56 · Neuroblastoma has a recognizable primitive histology

Simplified Homer–Wright pseudorosette

Central neuropil + surrounding primitive neuroblasts

Sheets of small primitive cells contain dark nuclei and scant cytoplasm.

Faint eosinophilic fibrillary neuropil reflects neuritic processes.

Homer–Wright pseudorosettes contain central neuropil surrounded by neuroblasts.

PHOX2B is a useful immunohistochemical lineage marker.

Original editable schematic — not histology

Slide 57 · Neuroblastic tumors show a maturation continuum

Neuroblastoma: Primitive neuroblasts

Ganglioneuroblastoma: Mixed maturation

Ganglioneuroma: Mature ganglion cells and Schwannian stroma

These names denote differing degrees of differentiation rather than identical histology.

Slide 58 · Neuroblastoma can produce catecholamines

Most neuroblastomas synthesize catecholamines.

Elevated urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) can support diagnosis.

Catecholamine production does not imply that hypertension is as common as in pheochromocytoma.

Slide 59 · Neuroblastoma prognosis is biologically heterogeneous

Clinical stage / age

Pretreatment extent and younger age influence risk.

Tumor differentiation

Schwannian stroma and maturation are favorable features.

MYCN / ploidy

MYCN amplification is adverse; Whole-chromosome gains can be favorable.

Avoid treating every neuroblastoma as equivalent in expected course.

Slide 60 · Wilms tumor recapitulates developing kidney

Wilms tumor (nephroblastoma) is the most common primary childhood renal neoplasm.

Its cell populations represent abortive stages of nephrogenesis.

Congenital malformation syndromes and genetic lesions reveal developmental mechanisms.

Slide 61 · Triphasic Wilms tumor: Three diagnostic compartments

Blastemal

Primitive small blue cells

Epithelial

Abortive tubules or glomeruloid forms

Stromal

Fibroblastic or myxoid matrix

Simplified editable morphology schematic — not a specimen image

Slide 62 · WT1 is a developmental tumor-suppressor example

WT1 supports renal and gonadal development

Inherited or acquired WT1 dysfunction

Predisposition to Wilms tumor in defined settings

WAGR and Denys–Drash involve distinct WT1 abnormalities.

Slide 63 · WAGR and Denys–Drash show different WT1 lesions

Syndrome

Genetic mechanism

Associated features

WAGR

11p13 deletion affecting WT1 and PAX6

Aniridia and genitourinary abnormalities

Denys–Drash

Dominant-negative WT1 DNA-binding-region mutation

Gonadal dysgenesis and early nephropathy

Slide 64 · Beckwith–Wiedemann links imprinting to overgrowth

11p15.5 imprinting disturbance

Abnormal IGF2 dosage in some cases

Overgrowth phenotype and Wilms predisposition

This mechanism is distinct from the WT1 lesions implicated in WAGR or Denys–Drash.

Slide 65 · Nephrogenic rests connect malformation and cancer

Nephrogenic rests are persistent embryonal renal tissue considered precursor lesions.

They may be found near Wilms tumors and are particularly frequent in bilateral cases.

Recognition of rests has implications for contralateral renal surveillance.

Slide 66 · Anaplasia changes Wilms tumor risk

Anaplastic areas contain enlarged hyperchromatic, pleomorphic nuclei and atypical mitoses.

Anaplasia to TP53 alteration, chemotherapy resistance and adverse prognosis.

Documenting anaplasia is therefore more consequential than merely describing a high mitotic count.

Slide 67 · Two abdominal embryonal tumors: Major contrasts

Feature

Neuroblastoma

Wilms tumor

Lineage

Sympathetic neural crest / adrenal medulla

Developing renal tissue

Microscopic clue

Neuropil; Homer–Wright pseudorosettes

Blastema, tubules and stroma

Molecular clue

MYCN status in risk stratification

WT1 / imprinting pathways in predisposition

Clinical clue

Catecholamine metabolites may be elevated

Abdominal renal mass; Congenital associations

Slide 68 · Survivorship changes the long-term pathology burden

Advances in treatment have improved survival for many childhood cancers.

Late effects of chemotherapy and radiotherapy have become increasingly important.

Second malignancies can reflect treatment exposure, inherited risk or both.

Judicious treatment intensity is part of the long-term clinicopathologic perspective.

Slide 69 · Case integration: An infant with a spindle-cell mass

CLINICOPATHOLOGIC APPLICATION

An infant has a rapidly enlarging soft-tissue mass composed of cellular spindle cells.

Why should adult-type fibrosarcoma prognosis not be transferred automatically?

Which characteristic molecular finding would be worth investigating?

Slide 70 · Case integration: An abdominal embryonal tumor

CLINICOPATHOLOGIC APPLICATION

A toddler has a large abdominal mass; The biopsy shows sheets of small dark cells.

What additional anatomic information immediately narrows the differential?

Which findings favor neuroblastoma versus a Wilms tumor?

Slide 71 · A five-question checklist for any pediatric mass

Is this ectopic normal tissue, disorganized native tissue or a neoplasm?

Which developmental lineage and organ site are implicated?

Does histology demonstrate differentiation, invasion or anaplasia?

Which clinical course and molecular studies are characteristic?

Could benign histology still conceal substantial local functional risk?

Slide 72 · Synthesis: distinguish biology from clinical impact

Heterotopia: normal tissue located where it does not belong.

Hamartoma: excessive, disorganized overgrowth of tissues native to the organ.

A morphologically benign lesion may still be clinically important because of its location or size.

Childhood malignancies require age-appropriate, developmental and lineage-based interpretation.

Integrate anatomy, morphology, and targeted molecular evidence rather than relying on the appearance of a mass alone.