USCAP Neuropathology night panel CASE 4

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1 USCAP Neuropathology night panel CASE 4 B.K. Kleinschmidt-DeMasters MD University of Colorado Denver Denver, Colorado Sheep Mountain, Telluride, Colorado

2 Clinical History The patient is a 46 year old male who presented with approximately 1-2 years of shaking in the right hand, which progressed to increasing clumsiness of the hand, with dropping things. This prompted a visit to a neurologist. Neuroimaging studies showed several noncontiguous, intracerebral, non-dural based abnormalities in the left frontal lobe, associated with cerebral edema. These were interpreted as likely to be metastatic carcinoma or infectious in etiology.

3 Neuroimaging study of the lesions

4 Low power photomicrograph of the well-demarcated lesion, 4X

5 Medium power photomicrograph illustrating features of the lesion, 10X

6 Medium power photomicrograph illustrating features of the lesion, 10X

7 Medium power photomicrograph illustrating features of the lesion, 10X

8 Reticulin stain at interface between lesion (right) and brain (left), 20X

9 Trichrome stain at interface between lesion (left) and brain (right), 20X. Note Rosenthal fiber (red)

10 alcian blue CD68 GFAP

11 1. What is the diagnosis?

12 Fibro-osseous lesion of the central nervous system/ calcifying pseudotumor of the neural axis The diagnosis is fibro-osseous lesion of the central nervous system, also known as calcifying pseudotumor of the neural axis This uncommon lesion was first reported in 1978, and as of the last literature reviews on the topic published in 1999 and 2000, only 27 cases had been described

13 Fibro-osseous lesion of the central nervous system/ calcifying pseudotumor of the neural axis Both intra- and extra-axial lesions occur Most common locations are along the vertebral column in the epidural space (11/27 cases) and intracranially (16/27), often at the skull base Rare examples completely intraosseous All levels of cord (cervical, thoracic, lumbar) affected Intracranial examples usually extra-axial (10/27 cases) Intra-axial and intracranial locations are least frequent location Even in these cases, lesions often close to dura/ leptomeninges

14 Fibro-osseous lesion of the central nervous system/ calcifying pseudotumor of the neural axis Most patients harbor solitary lesions, although multiplicity is well described Lesion size varies from microscopic to 10 cm. in diameter Age range of affected patients is broad (12-83 years, mean 46 years) Lesions slow growing and prognosis is excellent with gross total excision

15

16 2. What is the differential diagnosis?

17 Medium power photomicrograph illustrating pathognomonic matrix of the lesion, 10X

18 3. What is the differential diagnosis for relatively localized, calcified nodules in the brain parenchyma/meninges?

19 3. What is the differential diagnosis for relatively localized, calcified nodules? a. Meningioangiomatosis b. Psammomatous meningioma c. Primary or metastatic tumors with extensive calcification d. Brain tumor S/P radio-/ chemotherapy e. Toxoplasmosis, remote f. Vascular malformations

20 Oligodendroglioma, WHO grade II, with extensive calcification, seen on preoperative neuroimaging T1 contrast T2

21 Extensive dystrophic calcification in a high grade glioma, S/P radiation and chemotherapy

22 Multifocal Ca++: toxoplasmosis in an adult Parasites ( as seen above) are usually not present at this remote stage of infection

23 Extensively ossified vascular malformation: cavernous angioma trichrome brain stone at low power Non-ossified portion seen nearby

24 4. What is the differential diagnosis for relatively localized, ossified nodules in the brain parenchyma/meninges?

25 dystrophic ossification in dura after surgery dura

26 Bone formation in a post-radiation CNS sarcoma

27 5. Since this case had multiple lesions in the brain are there any systemic disorders associated with mineralization that one should consider in the differential?

28 CT: Sturge-Weber disease with tram track calcifications R parietal lobe

29 Disorders Associated with mineralization of basal ganglia Greenfields Neuropathology, 6th Ed. Vol 2, p338 Table 6.18

30 Multifocal calcifications: systemic diseases (Fahr s, A,B) A B Post mortem brain radiograph shows symmetrical mineralization

31 Multifocal calcifications: congenital toxoplasmosis Courtesy, Dr. J. J. Kepes

32

33

34

35 6. What is the differential diagnosis for localized matrix-rich lesions?

36 7. What other inert-omas might I consider in my differential diagnosis?

37 Inert-oma : amyloidoma H&E Congo red USCAP 2006 Neuropathology Specialty Conference Case 3-Suzanne Z. Powell

38 inert-oma : amyloidoma Birefringence Perivascular location of amyloid USCAP 2006 Neuropathology Specialty Conference Case 3-Suzanne Z. Powell

39 inert-oma : fibrinoid material in parenchyma after radiation and chemotherapy for high grade glioma

40 inert-oma : xanthogranuloma of choroid plexus USCAP 2005 Neuropathology Specialty Conference Case 3-Gregory N. Fuller

41 inert-oma : cholesterol granuloma of bone/skull base

42

43 inert-oma : Gamna-Gandy body

44 inert-oma : Gamna-Gandy body

45

46 8. What is the likely etiology for calcifying pseudotumor of the neural axis?

47 9. So if this is reparative and dystrophic, does calcifying pseudotumor of the neural axis resemble other systemic lesions?

48

49 Take home bullet points: Calcifying pseudotumor of the neural axis is a rare entity with pathognomonic features of discrete, hypocellular nodule(s) of coarsely fibrillar, basophilic matrix with palisading of nuclei at the perimeter. The amount of calcification and ossification varies. Most reported lesions have occurred along the vertebral column or in dura/leptomeninges at the skull base. The entity is non-neoplastic, probably proliferative and reparative. Prognosis is excellent with complete surgical excision.

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