Case Study 41 Henry Armah, M.D., M.Phil.

Question 1 Clinical history: 41-year-old male presenting with headache, mild left-sided weakness, restlessness, confusion and behavioural changes. Describe the abnormal cranial MRI findings?

Axial T1

Axial T2

Ax T1+C

Answer Large heterogenously contrast rim-enhancing right frontal lobe mass with central region showing no enhancement suggestive of necrosis, significant perilesional edema and significant mass effect with midline shift to the left.

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

Answer High-grade Glioma Supratentorial Primitive Neuroectodermal Tumor (PNET) Abscess Malignant Lymphoma Metastases

Question 3 The neurosurgeon performs a craniotomy with resection of the mass, and requested an intraoperative consultation. Describe the microscopic findings on this smear slide? Click here to view slide.

Answer Neoplastic proliferation of round-to-oval pleomorphic tumor cells with scant cytoplasm, scattered mitotic figures, and several 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)

Answer Neoplasm Undifferentiated High-grade Tumor

Question 5 The permanent section has returned from histology. Describe the microscopic findings on this H&E slide? Click here to view slide.

Answer Fragments of a malignant neoplasm mainly composed of undifferentiated neuroepithelial cells with small round nuclei and high nucleus: cytoplasm ratios. There are focal areas of tumor cells with oval-to-elongated nuclei and fibrillary cytoplasm. There is anaplasia and brisk mitosis. Karyorrhectic, apoptotic and pyknotic nuclei are readily identified. Endothelial proliferation is noted. Rare small foci of necrosis are appreciated, but no pseudopalisading necrosis is present. Rare tumor cells with vesicular chromatin, nucleoli and Nissl substance are noted. There is no evidence of medullary-type epithelium, neuroblastic (Homer-Wright) rosettes, or ependymoblastic rosettes.

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

Answer GFAP EGFR p53 Ki-67 (MIB-1) Synaptophysin CAM5.2 LCA (CD45)

Question 7 What do you see on this GFAP immunostain slide? Click here to view slide.

Answer GFAP strongly stains the reactive glial tissue and occasional tumor cell processes.

Question 8 What do you see on this EGFR immunostain slide? Click here to view slide.

Answer EGFR is strongly and patchy positive in the tumor cells.

Question 9 What do you see on this p53 immunostain slide? Click here to view slide.

Answer p53 is not clonally expressed in the nuclei of tumor cells, but only positive in the nuclei of a few tumor cells.

Question 10 What do you see on this Ki-67 (MIB-1) immunostain slide? Click here to view slide.

Answer Ki-67 (MIB-1) is positive in the nuclei of 20-25% of the tumor cells.

Question 11 What do you see on this Synaptophysin immunostain slide? Click here to view slide.

Answer Synaptophysin show focal granular and rare diffuse cytoplasmic staining of tumor cells, with no evidence of neuropil formation.

Question 12 What do you see on this CAM5.2 immunostain slide? Click here to view slide.

Answer CAM5.2 is negative in tumor cells.

Question 13 What is your final diagnosis in this case?

Answer Supratentorial Primitive Neuroectodermal Tumor (PNET) with Glial Differentiation

Question 14 What is the corresponding WHO grade of this lesion?

Answer WHO Grade 4