Case Study 36Henry Armah, M.D., M.Phil.

Question 1Clinical history: 14-year-old male with history of persistent headache and vomiting. Describe the abnormal cranial MRI findings?

Axial T1

Sag T1+C

AnswerContrast enhancing tumor in the fourth ventricle anteriorly impinging upon the lower pons, with no discernible hydrocephalus and no discernible meningeal enhancement.

Question 2What are your differential diagnoses based on the patients’ age and the radiological findings?

Answer1. Medulloblastoma

2. Atypical teratoid/rhabdoid tumor

3. Ependymoma

4. Choroid plexus carcinoma

5. Pilocytic astrocytoma

Question 3The neurosurgeon performs a craniotomy with biopsy of the mass and requested an intraoperative consultation. Describe the microscopic findings on this smear slide?

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AnswerNeoplastic proliferation of round-to-oval pleomorphic tumor cells with scant cytoplasm, nuclear molding, scattered mitotic figures and numerous apoptotic bodies.

Question 4

What is your intraoperative diagnosis? (A: Category such as Defer, Reactive/Non-neoplastic, or Neoplastic; B: More specific diagnosis or statement)

AnswerA. Neoplasm

B. Medulloblastoma

Question 5Subsequently, the mass was almost completely excised. The permanent section has returned from histology. Describe the microscopic findings on this H&E slide?

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AnswerNeoplastic proliferation of densely packed cells with round-to-oval or carrot-shaped hyperchromatic nuclei surrounded by scant cytoplasm. The tumor cells predominantly form sheets with vague areas of Homer-Wright rosettes. The vast majority of tumor cells show marked nuclear pleomorphism, nuclear molding, and cell-cell wrapping. Mitotic figures, including atypical ones, are readily identified. Numerous apoptotic bodies are noted. There is no evidence of nodularity.

Question 6What additional studies would you need to rule out other important differential diagnoses and confirm the final diagnosis in this case?

AnswerGFAP, INI-1, Synaptophysin, Neurofilament, EMA, CAM5.2, and Ki-67 (MIB-1).

Question 7What do you see on this GFAP immunostain slide?

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AnswerGFAP is negative in tumor cells, and highlights occasional entrapped reactive astrocytes.

Question 8What do you see on this INI-1 immunostain slide?

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AnswerINI-1 is strongly and diffusely positive in the nuclei of tumor cells.

Question 9What do you see on this Synaptophysin immunostain slide?

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AnswerSynaptophysin is focally and weakly positive in tumor cells.

Question 10What do you see on this Neurofilament immunostain slide?

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AnswerNeurofilament is negative in tumor cells.

Question 11What do you see on this EMA immunostain slide?

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AnswerEMA is negative in tumor cells.

Question 12What do you see on this CAM5.2 immunostain slide?

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AnswerCAM5.2 is negative in tumor cells.

Question 13What do you see on this Ki-67 (MIB-1) immunostain slide?

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AnswerKi-67 (MIB-1) is positive in the nuclei of 40-50% of tumor cells.

Question 14What is your final diagnosis in this case?

AnswerAnaplastic/Large Cell Medulloblastoma.

Question 15What is the corresponding WHO grade of this lesion?

AnswerWHO Grade 4.

Question 16Which of the following cytogenetic abnormality is associated with this lesion?

A.t (1;13)

B.monosomy 22

C.i (17)q

D.22q-

E.t (1;13)

AnswerC. i (17)q