Page 224 - Concise Pathology for Exam Preparation ( PDFDrive )

8 Genetic and Paediatric Disorders 209

Q. Describe the clinicopathological features of neuroblastoma.

Ans. Enlisted below are the important clinicopathological features of neuroblastoma:

Clinical Presentation
• Second most common solid malignancy of childhood after brain tumours; most
common in infants (,1 year of age).
• Mostly sporadic, rarely familial with AD transmission.
• Most common site is adrenal medulla; other sites—anywhere along sympathetic chain
(paravertebral region of the posterior mediastinum and lower abdomen).
• Familial cases are associated with germline mutations in the anaplastic lymphoma
kinase (ALK) gene. Somatic gain of function mutations also seen in less than 10% cases
(inhibitors of this kinase are being used as potential treatment for neuroblastoma).
Gross Morphology

• Neuroblastomas vary from being in situ lesions (small nodule) to large masses.
• In situ lesions may regress to leave only small foci of fibrosis and calcification (spontane-
ous regression or therapy-induced maturation).
• Some tumours appear encapsulated and sharply demarcated, while others are highly infiltrative.
• Cut surface is soft, grey, brain-like with areas of necrosis and haemorrhage.

Microscopic Features
• Tumour is constituted by small, primitive-looking cells having dark nuclei, scant cyto-
plasm and poorly defined cell margins arranged in sheets.
• Mitotic activity, nuclear breakdown (karyorrhexis) and pleomorphism is prominent.
• Eosinophilic fibrillary background (neurophil or neuritic processes of primitive
neuroblasts) is indicative of a neural origin.
• Homer Wright pseudorosettes (tumour cells arranged around a central space filled with
their fibrillar extensions) may be seen.
Clinical Features

• Usually present with a large abdominal mass, fever and weight loss.
• Metastases may cause hepatomegaly, ascites and bone pain.
• In neonates, disseminated neuroblastomas may present with multiple cutaneous
metastases and deep blue discolouration of the skin (blueberry muffin baby).
• About 90% tumours produce catecholamines and are associated with elevated levels
of catecholamine metabolites like vanillylmandelic acid (VMA) and homovanillic acid
(HVA) in the urine.
The important prognostic features of neuroblastoma are enlisted in Table 8.4.

TABLE 8.4. Prognostic indicators of neuroblastoma

Features Good prognosis Bad prognosis
Age ,18 months .18 months
Stage 1, 2a, 2b, 4s III or IV
Ploidy Hyperdiploid/near triploid Near diploid
1p deletion and N-myc amplification Absent Present
Expression of TrkA (high affinity growth Present Absent
receptor) indicating differentiation to-
wards sympathetic ganglia lineage
Expression of TrkB Absent Present
Mutations of neuritogenesis genes Absent Present
Morphology Presence of Schwannian stroma Absence of Schwannian stroma
and gangliocytic differentiation and gangliocytic differentiation
Mitosis-karyorrhexis index ,200/5000 cells .200/5000 cells

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