Medulloblastoma Pathology and Subgroups

Shares of cases and histology associations follow St Jude Children’s Research Hospital, and the prognosis wording follows Brain Tumour Research.

Medulloblastoma histology is read alongside molecular testing. Classic blue-cell sheets, desmoplastic nodular architecture and large cell anaplastic change each lean toward particular groups, but none replaces group assignment.

For wider context on how embryonal tumors fit into central nervous system classification, see our overview of brain tumor pathology. The sections below follow the order of a slide review, from clinical setting to molecular confirmation.

Clinical setting and location

Medulloblastoma is mainly a mid-childhood tumor. St Jude reports that children ages 5–9 are diagnosed most often. An OUHSC pathology teaching page gives a peak incidence of 5–10 years of age. Cedars-Sinai lists children under age 8 as the higher-risk age band.

Before opening the slide, do three things in order:

1. Record the age. Mid-childhood fits the usual pattern.
2. Confirm the posterior fossa. OUHSC states that medulloblastomas occur exclusively within the posterior fossa under WHO criteria, so a tumor outside it calls the diagnosis into question.
3. Hold the subgroup call. Age is a clue to the likely group, not a classifier.

Reading the H&E slide

Classic cytology

Classic medulloblastoma is a small blue cell tumor. The OUHSC page describes a high nuclear-to-cytoplasmic ratio, with fine threads of cytoplasm, called neuropil, as rather typical. The chromatin is coarse and hyperchromatic regardless of nuclear size. St Jude notes that histology classes these tumors by the size and shape of the tumor cells and that this is assessed together with molecular testing.

Homer Wright rosettes

Homer Wright rosettes are an architectural feature of classic medulloblastoma, seen alongside the neuropil background. According to OUHSC they can be seen but are not frequent. Do not wait for rosettes before considering the diagnosis, and do not treat a rosette-rich field as evidence for any particular molecular group.

Histologic variants and their group associations

Three histologic patterns carry most of the practical weight: classic, desmoplastic nodular and large cell anaplastic. The table pairs each with the molecular groups it most often accompanies.

Variant associations follow St Jude, while the cytologic detail and survival range come from the OUHSC pathology page.

Desmoplastic nodular pattern

St Jude states that desmoplastic nodular tumors are almost always SHH-activated. That is the tightest histology-to-group link available in this outline. The word is almost, not always, so the molecular result still decides.

Large cell anaplastic pattern

OUHSC describes large cell size, increased variation in nuclear size and prominent, even eosinophilic nucleoli, with more mitoses and necrosis, and calls the prognosis less favorable. St Jude says these tumors mostly belong to Group 3 and SHH-activated categories. When you see this pattern, the question is which of those two groups, and the answer needs molecular data rather than a closer look at nucleoli.

Immunostains and molecular confirmation

Stains confirm the embryonal and neuronal phenotype; they do not name the group. In the OUHSC case discussion, synaptophysin was positive in most tumor cells. That is one case, an example of neuronal differentiation rather than a rule for every tumor.

Group assignment comes from molecular testing. St Jude is explicit that the tumor’s group affects treatment and prognosis, so molecular testing must be done. A practical sequence is:

1. Confirm the embryonal phenotype. Use the H&E picture and a stain such as synaptophysin.
2. Request group assignment. The molecular groups are WNT-activated, SHH-activated, Group 3 and Group 4. SHH-activated tumors are further divided into SHH-1, SHH-2, SHH-3 and SHH-4.
3. Check MYC when Group 3 is likely. Brain Tumour Research reports that Group 3 tumors usually carry extra copies of the MYC gene, called MYC amplification, and that tumors are tested for it because it is the most important indicator of a shortened prognosis in paediatric cases.

Subgroups and prognosis

Prognosis follows the molecular group more closely than the slide pattern. Brain Tumour Research considers WNT-activated medulloblastoma relatively low-risk with a better prognosis. It calls Group 3 the most aggressive form, one that tends to spread through the ventricles. Group 4 is the largest group at 35% of cases according to St Jude, yet histology alone does not identify it.

For overall figures, St Jude gives overall survival of 70–80% for childhood medulloblastoma in the United States. Treat that as a pooled number across all groups. It should not be applied to an individual tumor without the group and MYC status, and the classic-type range of 60–80% in the variant table is a different, histology-based figure.

Troubleshooting slide-to-group mismatches

• Classic slide, group unclear. Classic histology mostly belongs to WNT and Group 4 according to St Jude, so the slide cannot choose between them. Wait for molecular results before offering a prognosis.
• Nodular pattern without an SHH result. Because the link is almost always rather than always, recheck the molecular assay rather than overriding it with morphology.
• Anaplastic features in an older or very young patient. Large cell anaplastic tumors are mostly Group 3 or SHH-activated, and SHH is common in adults and young children. Age therefore helps decide between those two groups, but the result still needs confirmation.
• No rosettes. Absence of Homer Wright rosettes is unremarkable, since they are not frequent.
• No embryonal pattern at all. If the tumor lacks the small blue cell picture described here, compare it with the features in ependymoma histology and schwannoma histology before settling on the diagnosis.

Frequently asked questions