Neuropathology

41 year old man left sided weakness and visual symptoms (pathology)

2010-07-06T18:13:06Z

41 year old man left sided weakness and visual symptoms (clinical)

2010-07-06T18:07:32Z

Lymphomatoid granulomatosis

2010-04-05T14:23:54Z

The patient is a 21 year old who received a kidney transplant more than 10 years ago.

Central Neurocytoma

2010-04-05T14:18:42Z

The patient is a 20 year old with an intraventricular tumor

Hemangioblastoma

2010-03-19T15:25:59Z

This patient presented in his 20s with 2 months of progressive headaches and was found to have a right cerebellar cystic mass.

20x

40x

Hemangioblastoma (WHO grade I):
"Uncertain" Histogenesis

• Various cell lineages such as vascular, glial, neural, fibrohistiocytic, and smooth muscle/myofibroblastic have been proposed for the so-called stromal cells, which are thought to represent the neoplastic component of these lesions

- Neg for endothelial markers

- CD133, VEGF positive, Epo/EpoR coexpression'

- GFAP positive cells may result from phagocytosis

• The VHL gene is expressed particularly in Purkinje cells of the cerebellum (mutations may be inherited or somatic).

• VHL mutation may lead to developmental arrest of angioblasts. Pluripotent neoplastic angioblasts may be the cell of origin.

• Possible origin is 'angiomesenchyme' which may give rise to three cell types (stromal cells, pericytes, and endothelial cells).

Clinical Features

- 25 % occur in VHL Patients, 75 % occur sporadicly

- Locations : Cerebellum , brain stem,Spinal cord, Supretentorial sites more frequently in VHL patients

-Symptoms are associated with increased ICP, Secondary erythrocytosis secondary to EPO production

-MRI shows cystic lesion with enhancement

Histopathology

- Tumors consisting of numerous vessels intermixed with stromal cells

- Vessels have hyperplastic endothelial cells and pericytes

- Stromal cells have abundant lipid-rich clear cytoplasm with slight pleomorphic nuclei

-Rare mitosis

-Cyst wall may show reacive astrocytosis with Rosenthal Fibers

Immunohistochemistry

-Stromal cells are positive for: Vimentin,S100,Oil Red O

-Stromal cells are negative for :CD34,FVIII,CK,EMA,GFAP

DDX

-Metastatic Renal Cell CA: Non-cystic,Abundant mitosis,EMA,Vimentin and CK positive

-Pilocytic Astrocytoma: Fibrillary astrocytes, GFAP diffusely positive

17 month old female with a cystic insular, temporal lesion

2010-01-11T16:57:34Z

The patient is a 17 month old female with a cystic insular and temporal lobe lesion. There is some enhancement.

Desmoplastic infantile ganglioglioma (DIG)

- WHO grade I, glial or glioneuronal superficial tumors with prominent desmoplasia.

- Present in the first 2 years of life

- Supratentorium: Frontoparietal

- Symtoms of increased ICP

Histopathology

- Distinctive features include collagenized regions dominated by spindly astrocytes in fascicular or storiform array and admixed small cells of primitive appearance in nodular aggregates.

Immunohistochemistry

- GFAP-positive astroglial cells within the desmoplastic regions

- Synaptophysin and Neurofilament positive neuronal cells in non-collagenized areas

- Small cell populations can be positive for GFAP, Neuronal markers ( Synaptophysin, Beta-tubulin, NF, MAP-2

DDX

Fibrohistiocytic neoplasms

Intracranial fibromatosis

Fibroblastic meningioma

Fibrosarcoma

Spinal osteogenic meningioma

2009-11-09T15:23:27Z

This patient had a history of worsening bilateral leg numbness and was found with neuroimaging to have an extra-medullary, intradural thoracic mass.

Hypoxic-Ischemic encephalopathy

2009-11-09T15:12:48Z

The patient was a 35 year old woman who apparently suffered a cardiac event at home. She arrived at the hospital obtunded with minimal brainstem reflexes. Two days after admission she developed V-fib and became completely unresponsive. An MRI at this time showed severe anoxic changes. She was pronounced dead 12 days after the initial event.

Ependymoblastoma

2009-10-13T18:27:12Z

This 2 year old was noted to have a head tilt for 1 week. A well-circumscribed, enhancing lesion near the foramina of Luschka displaced the pons.

]]> Definition: A small cell, embryonal, CNS neoplasm with "ependymoblastic rosettes"

WHO Grade IV: PNET

Clinical features

Occurs most often in childhood, median age at diagnosis 3 years
Occasional congenital, Rare in adults
Slight male predilection.
68 % supratentorial locations, rare in leptomeninges,extradural sites
Most common presenting symptoms are hydrocephalus and increased ICP.

Imaging: Cystic lesion with vascular contrast enhancement

Histopathology

"True rosettes" and canals that are composed of multilayed, markedly atypical and mitotically active cells.
These pseudostratified"ependymoblastic rosettes" encircle a distinct lumen bounded by terminal bars
Geographical patterns of necrosis with pseudopalisading and microvascular hyperplasia in the form of endothelial proliferation are uncommon or absent.

Immunohistochemistry

Rosettes are positive for vimentin and S100 but negative for GFAP

Differential diagnosis

Anaplastic ependymoma (Geographical patterns of necrosis with pseudopalisading and microvascular hyperplasia plus nuclear pleomorphism)
Embryonal tumor with abundant neuropil and true rosettes
Malignant and immature teratoma
Medulloepitheliomas

Treatment and Prognosis

Aggressive tumors
One study showed half of the patients died within a year of diagnosis
Median survival time was 12 months.
Widespread CSF dissemination is recognized.

References

Surgical Pathology of the Nervous system and its Coverings, Fourth edition
Greenfield's Neuropathology,Sixth Edition
The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug;114(2):97-109.

Meningioma with clear cell features

2009-10-02T13:55:21Z

The patient is a 5 year old who had a meningioma involving the cavernous sinus at age 2 1/2. The tumor recurred within 2 years and has not responded well to radiation therapy.

Clear cell meningioma:

Incidence: 0.2 % of all meningiomas, rarest variant
WHO Grade II
Age: Younger patients
Sex:Female predilection in Ped CCMs
Locations: Cerebellopontine angle and Intraspinal
Recurrence: High rate, up to 61%

Histology: Solid, clear glycogen rich cells, round and innocuous nuclei, inconspicuous nucleoli, lack mitotic activity, distinctive hyalinised stroma.

Immunohistochemistry: EMA +ve,Vimentin +ve, Inhibin -ve,GFAP -ve , PAS +ve diastase sensitive material.High MIB-1 LI accounts for the high-recurrence rate.

DDX:Differential diagnoses include microcystic meningioma, hemangioblastoma, clear cell ependymoma and metastatic carcinoma.

References: Greenfield's Neuropathology, Sixth Edition

1: Clear cell meningioma, an uncommon variant of meningioma: a clinicopathologic study of nine cases. J. Neurooncol. 2007 Feb;81(3):315-21.

Primary CNS lymphoma

2009-09-30T14:23:05Z

This patient experienced a rapidly progressive decline in mental status. There was diffuse white matter signal abnormality associated with a focal enhancing lesion in the superior frontal lobe.

Primary CNS Lymphomas (PCNSL)

Rare form of Extranodal non-Hodgkin's Lymphomas
Prevalence: 2.2- 2.7% of all primary brain tumors diagnosed in the US.
Age: 60-70s, rare in children
Sex: male:female= 2:1
Locations: Throughout CNS, brain, leptomeninges, spinal cord, or eyes.
Risk factors:Congenital or Acquired immunodeficiency, HIV.
CNS lymphomas are likely to be diffuse, angiocentric growth pattern, solid sheets can be present with necrosis, hemorrhages are common.

Clinical: 70% had focal neurologic deficits, 43% had neuropsychiatric symptoms,33%had increased intracranial pressure,14%had seizures, and 4%had ocular symptoms.

Imaging: CT shows hyperdense masses at subcortical white matter with contrast-enhancement, peritumoral edema is less severe than malignant gliomas: MRI shows isointense to hypointense on T2-weighted MRI images.

Histology: Diffuse large B-cell lymphoma (DLBCL) is the most common type (90%): 10% are poorly characterized low-grade lymphomas, Burkitt's lymphomas and T-cell lymphomas

Immunohistochemistry: Positive for B-cell markers( CD20),CD45 +ve, small benign admixed cells are positive for CD3,BCL-2 +ve,BCL-6 +ve, MUM-1 +ve, GFAP +ve in gliotic areas.

DDX: Differential Diagnoses include Glioblastoma, Metastatic tumor, Infarction, Demyelination, Infections(Abscesses)

References:

1. Primary CNS lymphoma. Journal of Clinical Oncology, Vol 24, No 8 (March 10), 2006: pp. 1281-1288

2. Greenfield's Neuropathology, Sixth Edition.

3. Primary Central Nervous system Lymphoma. Archives of Pathology and Laboratory Medicine: Vol. 132, No. 11, pp. 1830-1834.

Olfactory Neuroblastoma

2009-09-30T14:21:23Z

This tumor involved the cribriform plate with extension into the brain and adjacent sinuses.

Olfactory Neuroblastoma: ONB

Also called" Esthesioneuroblastoma", Neuroepithelial origin
Age: Bimodal, 20－30 years and 60－70 years
Sex: Male predilection
Incidence: 2-3% of primary tumors that involve nasal epithelium
Locations: Roof of the nasal vault, upper third of nasal septum, superior turbinate, superior middle turbinate

Clinical: Slow growing tumors, nasal obstruction, anosmia, epistaxis, rhinorrhea, orbital invlovement or brain involvement

Neuroimaging: Homogeneous mass with uniform vascular enhancement

Histopathology: Neuroepithelial cells arranged in the classic pseudorosette pattern with fibrillar intracellular background, marked microvascularity. The cells are round or fusiform with few cytoplasms. Homer-Wright or Flexner like substances scatter within the tumor.

Immunohistochemistry: Synaptophysin +ve, MAP-2 +ve, Chromogranin A +ve, NSE +ve, CK +ve is less common, CEA -ve, EMA -ve, GFAP -ve, S100 +ve in isolated cells, CD99 +ve

DDX: Differential diagnosis include "Round blue cell tumors", lymphoma,Embryonal rhabdomyosarcoma, PNET/Ewing's sarcoma,Nasopharyngeal carcinoma,Sinonasal undifferentiated carcinoma, malignant melanoma

References: Greenfield's Neuropathology,Sixth Edition

1: Chin Med J 2007 Feb 5;120(3):224-7. Management of intracranial invasive olfactory neuroblastoma.

A meningothelial meningioma that was embolized prior to surgery

2009-09-24T18:43:14Z

Meningothelial Meningioma:

WHO Grade I
Age: middle-aged, can occur at any age,rare in children
Sex: Female predilection
Locations:Anywhere in along the neuraxis, intracranial,intraventricular, spinal,extracranial
Risk factor: Ionizing radiation, ?Progesterone, NF-2 in young onset
Clinical: Headache ,Seizure and Increased ICP, site specific symptoms

Neuroimaging: Unenhanced meningioma shows isodense, well-demarcated,lobulated mass associated with the dura, uniformly enhanced after contrast, edema associates with the breakdown of blood vessel

1: T1-weighted MRI shows isodense or hypodense mass in relation to the grey matter (enhances with contrast)

2: T2-weight MRI shows isodense or hyperdense lesion

Histopathology: Uniform tumor cells forming lobules surrounded by thin collagen septum, nuclei are round or oval,pale with clumped chromatin, intranuclear,pseudoinclusions common, cell membrane is frequently not well-defined resembling a syncytium, nuclear pleomorphism is not a sign of aggressive behaviour. Mitosis is low or absent.

Immunohistochemistry: EMA +ve, CK +ve,Vimentin +ve, GFAP -ve,S100 variable, MIB-1 labeling index above 5% suggests likelihood of recurrence

DDX: Differential Diagnosis include Schwannoma( EMA-ve,S100+ve, Vimentin +ve),Astrocytoma(+ve GFAP)

Cytogenetics: Monosomy 22

Post Embolization: Changes include necrosis (most common features), ischemic changes, intravascular Ivalon particles, fibrinoid necrosis of the vascular walls, Increased MIB-1 labeling index.

References:Lancet Neurol. 2006 Dec;5(12):1045-54. Histological classification and molecular genetics of meningiomas.

1: Greenfield's Neuropathology,Sixth Edition

2: The American Journal of Surgical Pathology: October 1996 - Volume 20 - Issue 10 - pp 1224-1230 .Histopathology of Post-embolized Meningiomas

An "arachnoidal" cyst in the lumbar spinal cord

2009-09-24T18:34:04Z

Microscopic evaluation showed the anatomy of the cyst wall to be consistent with cysticercosis. Histological characteristics include microvilli, thin tegument, tegument nuclei, and loose connective tissue, no hooklets or scolices were visible.

Spinal Cysticercosis (SNCC):

Cysticercosis is the most common parasitic disease affecting the central nervous system.
Caused by " larval stage" of the pig tapeworm Taenia solium
Infection caused by contamination of food by T.solium eggs
It's the least common site of Neurocysticercosis
Human is the" incidental intermediate host"
SNCC incidence is known to be 0.7- 5.85%

Low incidence of SNCC is explained by the sieve effect. The majority of cysticerci cannot pass through the subarachnoid space at the cervical level due to its size and the physiological sieve.CSF reflux at the craniovertebral junction, which propels floating cysts back into the intracranial space rather than the spinal canal, is an another possible reason of why SNCC is rare.

Intramedullary intraspinal cysticercal involvement, usually solitary, most probably occurs through arterial blood circulation

The cysticercus can cause direct mass effect, induce regional or distant inflammatory reaction, and medullary degeneration due to meningitis or vascular compression and insufficiency edema, which can damage medullary parenchyma. Inflammatory reaction against the dead parasite is associated with perilesional edema, which can damage medullary parenchyma.

Histopathology: All cysts have similar structure consisting of 3 layers: outer or cuticular layer, middle cellular layer and inner fibrillary layer.

Treatment: Surgical removal, Anti-cysticercal therapy (Albendazole +Praziquantel), Steroid

References: Greenfield's Neuropathology,Sixth Edition

1: Yonsei Med J. 2009 Aug;50(4):582-584. A Case of Extensive Spinal Cysticercosis Involving the Whole Spinal Canal in a Patient with a History of Cerebral Cysticercosis
2: Arg Neuropsiquiatr 2006 Mar;64(1):149-52. Intramedullary spinal cysticercosis simulating a conus medullaris tumor: case report.