Case Study 57

1. Case Study 57 Kenneth Clark, MD

2. Question 1 • This is a 37-year-old woman who presented to the emergency room following minor accidental head trauma. An MRI of the head was performed. • Describe the MRI findings.

3. Axial T1 Axial T1 + Contrast Axial T2 FLAIR Sagittal T1 Coronal T1 + Contrast

4. Answer • A large complex (solid and cystic) heterogeneously enhancing intraventricular mass centered within the body of the left lateral ventricle. Solid components appear to enhance homogeneously. There is a moderate amount of surrounding parenchymal T2/FLAIR hyperintensity. The lesion appears fairly well-circumscribed.

5. Question 2 • What is the differential diagnosis of an intraventricular mass lesion?

6. Answer • Choroid Plexus Tumor • Ependymoma • Subependymoma • Meningioma • Central Neurocytoma • Oligodendroglioma • Astrocytoma • Medulloblastoma

7. Question 3 • A small piece of the lesion was submitted for intra-operative evaluation. What is your impression (i.e. what would your intra-op diagnosis be)? • Click here to see the frozen section slide

8. Answer • The smear shows a highly cellular lesion comprised of relatively monomorphic cells with generally round nuclei, evenly distributed, stippled chromatin, slight nuclear contour irregularities and modest amounts of pale pink cytoplasm. In some areas the cells appear dyscohesive while in others they appear to form papillary structures. No mitotic figures are seen. • A. Neoplastic • B. Defer definitive diagnosis to permanent sections

9. Question 4 • The lesion was resected and submitted for pathologic examination. Describe the H&E sections. • Click here to see the H&E slide

10. Answer • The tissue shows a cellular neoplasm arranged in nests and sheets with occasional acinar formation. The neoplastic cells show mild nuclear pleomorphism with stippled chromatin and inconspicuous nucleoli, and have predominantly eosinophilic cytoplasm with focal clearing. No readily identifiable mitoses are seen. The background tissue additionally shows eosinophilic hyaline material and abundant hemosiderin, cholesterol clefts, and scattered calcifications.

11. Question 5 • What is your diagnostic impression?

12. Answer • Neuroendocrine tumor • Choroid plexus tumor (adenoma, carcinoma) • Metastatic tumor (lung, kidney, thyroid, melanoma) • Unusual meningioma • Unusual lymphoid neoplasm • Hemangioblastoma

13. Question 6 • The differential diagnosis is broad. What stains would you order in order to better characterize this lesion and limit your differential?

14. Answer • Keratins (CK7, CK20, Cam5.2, AE1/3) • S100, MelanA, HMB45 (r/o melanoma) • Synaptophysin, Chromogranin (neuroendocrine markers) • EMA, p63, GFAP (meningioma, glial) • CD20, CD3, CD68, Pax-8 (inflammatory, lymph) • CD10, TTF1, Thyroglobulin (renal, lung, thyroid) • Transthyretin (choroid plexus tumors) • Ki67 (proliferation index) • Click to see Cam5.2, AE1/3, CK7, Transthyretin, Synaptophysin, Ki67, p53, GFAP, S100, Reticulin

15. Question 7 • Based on the H&E and immunohistochemical findings (see below), what is your diagnosis? • Cam 5.2 – positive in tumor cells • AE1/3 & cytokeratin 7 – focally positive in tumor cells • Transthyretin and Synaptophysin – strong positive in tumor cells • Ki-67 proliferation index - approximately 1-2% • p53 – focal weak nuclear staining of tumor cells • S100, GFAP – negative in tumor cells; highlights background parenchyma • CD3, CD20, CD68 – highlights scattered mature T-cells, B-cells and macrophages • Negative Stains - Cytokeratin 20, p63, chromogranin, calcitonin, thyroglobulin, TTF-1, EMA, CD10, PAX-8, HMB45, and Melanin A.

16. Answer • Choroid Plexus Papilloma, WHO grade 1

17. Question 8 • How are choroid plexus tumors graded?

18. Answer • Choroid Plexus Papilloma – WHO grade 1 • Atypical Choroid Plexus Papilloma – WHO grade 2 • Choroid Plexus Carcinoma, WHO grade 3

19. Question 9 • How are atypical choroid plexus papillomas (WHO 2) and choroid plexus carcinomas (WHO 3) distinguished from choroid plexus papilloma histologically?

20. Answer • CPP – Fibrovascular connective tissue fronds covered by single layer of cuboidal to columnar epithelium with basally situated monomorphic nuclei. Scant to no mitotic activity. • ACPP – Identical histology as CPP except for increased mitotic activity (2 or more per 10 HPF) • CPC – Frank signs of malignancy (need at least 4 of the following features): • >5 mitoses / 10 HPF • nuclear pleomorphism • increased cell density • tumor sheeting • necrosis

21. Question 10 • This tumor shows regions of increased cellularity and blurring of the papillary architecture. Are these features concerning?

22. Answer • No. Grade 1 choroid plexus papillomas can show focal regions of increased cellularity, pleomorphism, architectural blurring, necrosis and even brain invasion. However, without increased mitotic activity and/or at least 4 of these features together, the lesion should still be considered low grade.

23. Question 11 • How does the Ki67 proliferation index help in making a diagnosis?

24. Answer • Ki67 proliferation indices have been reported to range from 0.2-6% (mean 1.9%) in choroid plexus papillomas. • Reported Ki67 proliferation indices in choroid plexus carcinomas range from 7.3-60% (mean 13.8%). • Despite focal areas of atypical features seen in this lesion, the Ki67 index of 1-2% gives us more confidence in calling it a WHO grade 1 CPP.

25. References • Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of Tumours of the Central Nervous System. IARC: Lyon 2007. • Gyure K, Morrison A. Cytokeratin 7 and 20 expression in choroid plexus tumors: utility in differentiating these neoplasms from metastatic carcinomas (2000). Mod Pathology. 13(6):638-643.