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LECTURE CNS TUMOR and melanin production system

Classification and grading of intracranial neoplasms (WHO) Histological groups
•Sellar region
•Germ cell
•Cranial/spinal nerve
WHO grading
•Grade 1-slow growing, non-malignant, with long-term survival
•Grade 2-relatively slow-growing, recurrent, progress to higher grade
•Grade 3-malignant, recur as higher grade
•Grade 4-very aggressive malignant neoplasms
Neuroepithelial neoplasms
•Astrocytic tumours
•Oligoastrocytic tumours
•Oligodendroglial tumours
•Ependymal tumours
•Choroid plexus tumours
•Other neuroepithelial tumours
•Tumours of the pineal region
•Embryonal tumours (medulloblastoma, CNS Primitive Neuroectodermal Tumour/PNET,
atypical teratoid/rhabdoid tumour) Astrocytic neoplasms
Grouped by:
•Topography(supratentorial vs. infratentorial)
•Differentiation(fibrillary, protoplasmic, gemistocytic)
•WHO grade
1-(Pilocytic astrocytoma, chordoid glioma, desmoplastic astrocytoma, pituicytoma),
2-(Well-differentiated-low cellularity/ minimal pleomorphism, no vascular proliferation or
3-(Anaplastic-or malignant-high cellularity, marked pleomorphism, no vascular proliferation
or necrosis)
4-(Glioblastoma-high cellularity, marked pleomorphism with microvascular proliferation
and/or necrosis)
•Growth pattern(Expansile(WHO grade 1 and PXA-grade 2) vs. Diffuse(WHO grades 2 to 4))
Pilocytic astrocytoma
WHO grade 1 neoplasms of childhood
Occur in cerebellum, sellar region, brainstem and optic nerve
Cerebellar neoplasms have an excellent prognosis
Grossly cystic neoplasms with mural nodule
Biphasic pattern(solid and microcystic foci with bipolar cells associated with Rosenthal
fibresand eosinophil granular bodies)
grade 2
Low cellularity, mild pleomorphism, no vascular proliferation and no necrosis May progress
to grade 3 astrocytoma Median survival 6 years; peak 5thdecade of life Fibrillary astrocytoma
Small stellate, elongated cells with fibrillary processes Gemistocytic astrocytoma Large, plump
cells with abundant glassy eosinophilic cytoplasm and peripheral nuclei
Anaplastic astrocytoma, grade 3
Acquisition of additional mutations compared to grade 2 astrocytoma May progress to
secondary glioblastoma High cellularity, significant pleomorphism, but no microvascular
proliferation and no necrosis Median survival times of 2 years and peak in the 5th decade of life
Grade 4 neoplasm showing cellularity, pleomorphism and vascular proliferation and or
necrosis Peak in 6thdecade, but any age. Median survival of 1 year
Hemispheric gliomas of young/middle aged adults Frontal, temporal, parietal and occipital
lobes in ratio 3:2:2:1Calcification on X-ray/CT
Histology shows uniform cells with perinuclear haloes (fried egg) with chicken-wire
capillaries. Better prognosis than astrocytoma (mean survival-20yr grade 2 and 10yr grade 3).
Surgery, chemotherapy, and radiotherapy
Del 1p/19qhas good prognosis
Most sporadic; few familial in type 2 neurofibromatosis Arise from lining of fourth (children)
and lateral (adult) ventricles. Commonest spinal cord neoplasms
Grade 1-Subependymoma: rare incidental tumour; and myxopapillary ependymoma: cauda
Grade 2-well differentiated ependymoma
Grade 3-anaplastic ependymoma
Histological features:
1. Perivascular pseudorosettes
2. True rosetteswith central lumen having a limiting membrane
Ciliary basal bodies (blepharoplasts) can be demonstrated on electron microscopy
Choroid plexus neoplasms
Choroid plexus papilloma (CPP) Grade 1 childhood tumours of lateral ventricle. Grossly, pink
cauliflower like mass Cause hydrocephalus mainly by obstruction of flow, but also rarely, by
overproduction of CSF.Histologically are papillary neoplasms that recapitulate normal choroid
Atypical CPP-Grade 2
CP carcinoma-Grade 3
Malignant, invasive embryonal cerebellar tumour of children with neuronal differentiation,
and tendency to spread via CSF
Commonest malignant paediatric CNS neoplasm
Most are sporadic but familial cases with nevus basal cell carcinoma (Gorlin) or Turcot
syndromes may occur
Del 17p and isochromosome 17q
PTCH(Gorlin), APC(Turcot)
Variants-classical, large cell, anaplastic, desmoplastic
n some statistics, medulloblastoma is listed as the most common BT in children, representing
20% of all BTs. In other accounts, including the author's practice, it is the second most frequent
BT in children after pilocytic astrocytoma. Most medulloblastomas occur in the first decade of
life. There is a second peak in the early 20s. Several genetic tumor syndromes, including the
Turcot (familial adenomatous polyposis) and Gorlin (nevoid basal cell carcinoma) syndrome are
associated with medulloblastoma. Medulloblastoma is an embryonal tumor of the brain,
analogous to Wilms tumor of the kidney and neuroblastoma of the adrenal. Its embryonal nature
is underlined by its high incidence in infants and children and by its undifferentiated, immature
appearance, which resembles developing neural tissue. Some medulloblastomas are thought to
arise from stem cells located in the subependymal matrix and the external granular layer (EGL)
of the cerebellum. This layer is formed from precursor cells that migrate from the rhombic lip (the
most lateral and dorsal part of the hindbrain) to the surface of the developing cerebellum where
they divide and differentiate. Neurons then move inwards forming the permanent granular layer of
the cerebellar cortex. The EGL persists until the beginning of the second year of life. Different
stem cells from the subependymal matrix around the fourth ventricle give rise to the cerebellar
nuclei and Purkinje cells.
Origin from meningothelial arachnoid cellsof convexities, parafalcine, sphenoid, olfactory and
suprasellar regions, optic nerve and choroid plexus
Commoner in blacks (30-40%) than Caucasians (10-15%)
Females (steroid receptors)
Most sporadic; Familial in NF2
Recurrence rate is 11%
WHO grade 1-benign (del 22q)
Grade 2-atypical (del 14q)
Grade 3-malignant (del 1p)
Co-express EMA and vimentin
Pituitary adenoma
Sellar neoplasms are commoner in Nigeria (20-28%), than other parts of Africa (7.5-13.4%)
Pituitary adenomas comprise 2/3 of sellar neoplasms
Clinically manifest with
1. Mass effect(headache, vomiting, papilloedema)
2. Bitemporal hemianopsia
3. Pituitary hormone dysfunction(panhypo-or selected hyper-function)
Best grouped by immune or by EM
Atypical adenoma and pituitary carcinoma are uncommon
 Most common primary brain tumor (20 - 30% of brain tumors, 6 per 100K annually)
 Derive from arachnoid cap cells (associated with dura mater, choroid plexus)
 Grow along external surface of brain or within ventricular system
 Slow growing (may grow rapidly during pregnancy), symptoms vague or related to brain
 Usually adults
 Female predominance: 2/3 of cerebral meningiomas occur in women, 90% of spinal cord
meningiomas occur in women
 Usually solitary; multiple tumors (seen in 1 - 6%) are occasionally associated with
neurofibromatosis 2
 Three grades exist based on WHO criteria
Most are WHO grade I (benign)
~6% are WHO grade II (increased likelihood of recurrence)
Rarely are WHO grade III (malignant with metastatic potential)
 Many variants of meningiomas exist
Grade I variants
2% of all meningiomas
Vascular component should exceed 50% of total tumor area
Meningothelial cells are wrapped around small blood vessels
Also has large vessels
Mean Ki67 index is 2%
Do not recur if entirely resected (Am J Surg Pathol 2004;28:390)
Differential diagnosis includes hemangioblastoma, which stains positive with
inhibin and NSE
Firm tumors composed of spindle cells with indistinct cell boundaries
Sheet-like architecture, may not contain lobules or classic meningothelial whorls
Resemble schwannoma or solitary fibrous tumor but are focally EMA+, often
have thick bundles of collagen
Lymphocyte rich
May be associated with Castleman disease or other hematopoietic neoplasm
Most common variant
Syncytial and epithelial cells, indistinct cell borders and classic whorls
May have sparse psammoma bodies
May contain foci of bone, cartilage or fat
Rare to have extensive microcystic formation
Cells have elongated processes and loose myxoid background
Overall resembles microcysts
Has focal "classic" features
Variable pleomorphism
No cords or trabeculae, no inflammatory infiltrate
EM shows extracellular microcysts
Found in spinal region
Numerous psammoma bodies
Eosinophilic secretions
May have cytologic atypia
May secrete CEA
Meningothelial and fibroblastic features
Usually prominent whorls, psammoma bodies and clusters of syncytial cells
Grade II variants
Clear Cell
Grade III variants
Radiology description
Strong and homogenous enhancement on MRI with contrast
Usually display a "dural tail"
Usually isodense with the gray matter on T1 weighted MRI
 May show a so called "CSF crest" around the tumor indicating its extra-axial location
Case reports
11 year old boy with pediatric microcystic meningioma
 22 year old man with microcystic meningioma, WHO grade I
 37 year old woman with dural based intracranial masses)
 61 year old man with left brain mass)
 Angiomatous meningioma of orbit mimicking as malignant neoplasm (
 Breast carcinoma metastatic to meningioma
 Dumbbell meningioma of the upper cervical spinal cord
 Leukemic infiltrate within a meningioma)
Observation - if asymptomatic
 Gross total resection is usually curative
 Postoperative radiation if incompletely excised or WHO grade II or III
Gross description
Rounded and well circumscribed
Attached to dura
Tumor separates readily from brain
May grow en plaque (along dural surface) and cause reactive (hyperostotic) bone changes
CraniopharyngiomaAwelimobor, 2011
Majority originate from Rathke cleft remnants. Commonest childhood sellar region tumour.
Common in Nigeria and Japan.
Benign cystic locally invasive neoplasms with dark oily fluid and calcific material. Epithelial
islands with peripheral palisading and central stellate reticulum. Express steroid receptors.
Mutation of beta-catenin (CTNNB1) gene. Recurrence in 10-62%
Germ cell neoplasms
Origin from aberrant migrating germ cells in midline (pineal and suprasellar regions)
Rare (except in Taiwan and Japan)
Teratoma (mature, immature, with malignant transformation)
Yolk sac tumour
Embryonal carcinoma
Mixed germ cell tumour
Vestibular schwannoma-Cerebellopontine angle
Vestibular part of VIII nerve
Sporadic (unilateral in 95% of cases) or familial (bilateral in NF2)
Cellular (Antoni A) and loose (Antoni B) areas
A Practical Approach to the Diagnosis of Melanocytic Lesions
Melanocytic lesions are common in routine surgical pathology. Although the majority of these
lesions can be confidently diagnosed using well-established morphologic criteria, there is a
significant subset of lesions that can be diagnostically difficult. These can be a source of anxiety
for patients, clinicians, and pathologists, and the potential consequences of a missed diagnosis of
melanoma are serious. Objective.—To provide a practical approach to the diagnosis of
melanocytic lesions, including classic problem areas as well as suggestions for common
challenges and appropriate incorporation of ancillary molecular techniques. Data Sources.—
Literature search using PubMed and Google Scholar, incorporating numerous search terms
relevant to the particular section, combined with contemporaneous texts and lessons from
personal experience. Conclusions.—Although a subset of melanocytic lesions can be
diagnostically challenging, the combination of a methodical approach to histologic assessment,
knowledge of potential diagnostic pitfalls, opinions from trusted colleagues, and judicious use of
ancillary techniques can help the pathologist navigate this difficult area.
Histopathological spectrum of benign melanocytic istopathological spectrum of benign
melanocytic nevi – our experience in a tertiary care centre