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Histology of solid tumors outside the CNS

Most solid tumors in children are diagnosed using fine needle aspiration and punch biopsy. Biopsy is performed under general anesthesia. The pathologist participates during sampling as part of an interdisciplinary team together with a pediatrician, radiologist, and anesthesiologist. To begin with, multiple fine needle aspirations are performed to find the optimal non-necrotic representative area to be biopsied. This procedure with fine needle aspiration includes a quick stain and immediate microscopy making it possible to evaluate the quality and viability of the obtained material. This is then followed by 3-4 punch biopsies.

The primary microscopic evaluation of cytology material helps in determining the optimal procedure for obtaining a specific diagnosis. Additional methods and specific antibodies to be used can be determined after the primary microscopy. The additional tumor studies include FISH, immunohistochemistry and further molecular tests.

Small cell solid tumors are the most common type of malignant solid tumor in children. Different types of small cell tumors frequently are microscopically similar and often, can only be differentiated using additional methods.


Photomicrograph demonstrating a neuroblastoma in giemsa-stained smear. Click to enlarge. Photomicrograph showing HE-stained histological section from a neuroblastoma. Click to enlarge.

Neuroblastoma is en embryonal tumor originating from sympathetic neural tissue and containing immature precursors of ganglionic cells. This tumor can show maturation from a neuroblastoma without stroma through ganglioneuroblastoma to finally a benign ganglioneuroma.

Wilms' tumor (Nephroblastoma)

These tumors are malignant embryonal neoplasms originating from nephrogenic blastema cells. This type of tumor is heterogenous and contains various cell types such as blastemal epithelial cells and stromal components.

Photomicrograph demonstrating a cytological smear from nephroblastoma. Click to enlarge. Photomicrograph demonstrating HE-stained histological section from a nephroblastoma. Click to enlarge.

Blastemal components show small, immature cells with minimal differentiation, overlapping nuclei, often with rosette formations and many mitotic figures.
The epithelial components can appear as tubules, primitive rosettes, or even may simulate immature tissue. The stromal component can be spindled myofibroblastic cells or myxoid stroma with scanty cells or striated muscle tissue. The presence of heterologous components (cartilage, fat, osteoid, neuroglia) is not unusual.

Germ cell tumors

The microscopic profile of this type of tumor varies greatly. The benign tumors known as mature teratoma can contain many different types of tissue.
The malignant tumors are of different types:

  • immature teratoma
  • yolk sac tumor (endodermal sinus tumor)
  • dysgerminoma
  • embryonal carcinomas
  • choriocarcinomas

Malignant liver tumors

Hepatoblastoma is the most common malignant liver tumor and demonstrates immature liver tissue. In older children, hepatocellular carcinomas may occur.


Photomicrograph demonstrating cytological smear from a rhabdomyosarcoma. Click to enlarge. Photomicrograph demonstrating a histological section from a rhabdomyosarcoma. Click to enlarge.

  • Embryonal rhabdomyosarcoma is a malignant tumor phenotypically and biologically similar to embryonal striated muscle.
  • Alveolar rhabdomyosarcoma is a malignant small round cell tumor that demonstrates focal differentiation towards striated muscle tissue. 

Non-rhabdoid soft tissue sarcoma

These tumors are malignant tumors originating in other tissue than striated muscle, for example:

  • connective tissue 
  • nerve tissue
  • fatty tissue


Osteosarcoma originates in primitive bone producing mesenchymal stem cells, most often in long bones. Microscopically, they can be difficult to separate from other small, round, blue cell tumors.

Ewing’s sarcoma /pPNET (primitive neuroectodermal tumor)

Photomicrograph demonstrating cytological smear from an Ewing sarcoma. Click to enlarge.

This tumor is a malignant/sarcoma which shows a degree of neuroectodermal differentiation.

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