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Liver, Biliary Tract and Pancreas 179
r
d/dg islet aggregations in atrophic chronic pancreatitis may reach upto a few mm in but have multiple
cell types by hormone immuno and it is rare for these islets to completely merge
r
d/dg metastatic midgut carcinoids may be +ve for serotonin and substance P (unlike pancreatic 1
◦
)
r
d/dg metastatic RCC (esp. with clear cell/oncocytic variants): CK, EMA and vimentin +ve
r
d/dg pancreatoblastoma: has acinar cell differentiation, squamous corpuscles ± mesenchymal stroma
r
d/dg gangliocytic paraganglioma (vide infra)
Gangliocytic Paraganglioma/Hamartoma
◦
1
epithelioid NE cells may have a strikingly infiltrative pattern
◦
2
spindle cell component
(! d/dg carcinoma on FS) but this does not
◦
3
ganglion cells equate to aggressive/malignant behaviour
r
d/dg adenocarcinoma/carcinoid
Poorly-Differentiated Endocrine Carcinoma
r
Like pulmonary SmCC (see pp. 93–94) or with larger cells
r
d/dg PNET, lymphoma, metastasis, etc.
Pancreatic Transplant Pathology
Acute Rejection
r
Mixed septal inflammation: lymphocytes, plasma cells, eos.
r
Lymphocytic infiltration of the ducts (ductitis) and endothelialitis
r
Acinar cell loss
r
Islets spared or have ‘spillover’ infiltrates (recurrent ‘auto’immune insulitis is rare)
Chronic Rejection
r
Chronic graft vasculopathy (similar feature as for renal Tx see p. 208)
r
Almost complete loss of parenchyma
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Central Nervous System and Skeletal Muscle 181
13. Central Nervous System and Skeletal Muscle
CNS (Non-Neoplastic)
Dementia
General
r
Def
n
: chronic persistent global reduction in previously attained higher cognitive functions but with
normal consciousness, and of sufficient severity to increase dependency for normal daily activities
r
Normal ageing: normal weight (see p. 391) decreases after 65 years
↓cortex, ↓white matter, ↑ventricles, cerebellum is usu. spared
neuron loss, plaques, tangles
hippocampus: rare cells with granulovacuolar degeneration and Hirano bodies
For anatomy, see figure 4.1 (p. 36); for block-taking, see pp. 381–382.
Histological features seen in the most common dementias
r
Neuritic plaques (+ve for tau protein with A4 () amyloid core and more speckled A4 ())
r
Intraneuronal tangles (tau protein) – the term ‘tauopathy’ is applied to conditions with abnormal tau
protein inclusions including Alzheimer’s, Pick’s disease and corticobasal degeneration
r
Granulovacuolar degeneration of Simchowicz (multiple intraneuronal 3–5 clear vacuoles each with
a basophilic argyrophil central granule)
r
Hirano bodies: eosinophilic oval/rod-like pyramidal cell intracytoplasmic inclusions (= crystalline
actin)
r
Pick bodies: argyrophil and tau +ve neurofilament inclusions in superficial cortex neurons
r
Lewy bodies: two-tone concentric eosinophil cytoplasmic inclusions with dense core and pale rim (+ve
for -synuclein and ubiquitin). H&E morphology is less-well defined in cerebral ones
r
Congophilic amyloid angiopathy (CAA): +ve for A4 () ± evidence of previous haemorrhage
r
MND inclusions: ubiquitin +ve inclusions in cortical neurons and hippocampal dentate granule cells
r
Spongiform degeneration i.e. grey matter microvacuolation and reactive gliosis (=‘status spongiosus’
if advanced)
Mixed dementias
r
Alzheimer’s + vascular dementia or Alzheimer’s + DLB
r
Vascular dementia + other neurodegenerative disease (DLB, basal ganglia, Pick, etc.)
Primary dementias
r
Alzheimer’s (± Familial Alzheimer’s)
exaggerated ageing changes (esp. in hippocampus, amygdala, thalamus, neocortex, olfactory
bulb & basal ganglia); more than 1 or 2 hippocampal cells containing Hirano bodies or
granulovacuolar degeneration are suspicious (and lots of them are ≈ only seen in dementia)
CAA (see p. 72)
plaques containing tau protein (cf. A4 () amyloid only plaques) occurring together with
neocortical tangles favour Alzheimer’s over ageing changes
in the USA, the National Institute on Aging, and the Reagan Institute Working group issued
diagnostic guidelines based on the CERAD protocol which gives an age-related probability
of Alzheimer’s (‘definite’, ‘probable’ or ‘possible’) based on semiquantitative impressions
of plaque n˜os (none, mild, moderate, severe), and likewise tangle n˜os. The disease may be
‘staged’ according to the n˜o of brain sites involved using the ‘Braak stage’ criteria. For these
articles, see Bibliography; for UK autopsy and sampling guidelines, see pp. 381–382
r
Diffuse Lewy body disease (= dementia with Lewy bodies (DLB))
psychiatric Sx +/1
◦
dysphagia; neuroleptics are contra-indicated (they can be fatal)
Lewy bodies esp. in cingulate gyrus, hippocampus, amygdala and substantia nigra
paucity of plaques and tangles (unless combined Alzheimer’s + DLB)
r
Frontotemporal dementias
affective / disinhibitive Sx prior to memory problems
atrophy of superficial layers of frontotemporal cortex
Pick’s disease: ±superficial cortex neuronal Pick bodies ±ballooned eosinophilic ‘Pick cells’
(neurons containing tau and crystallin by immuno)
Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum. Paul J. Tadrous
Copyright
C
2007 by John Wiley & Sons, Ltd. ISBN: 978-0-470-51903-5
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Central Nervous System and Skeletal Muscle 182
MND inclusion dementia: MND inclusions in cortical neurons and hippocampal dentate gran-
ule cells ± clinical MND/AMLS
others: e.g. ‘corticobasal degeneration’ and ‘non-specific frontotemporal dementia’
r
Basal ganglia degenerationse.g. Huntingdon’s (selectivecaudate atrophy)/ Parkinson’s (depigmentation
of substantia nigra and Lewy bodies in substantia nigra, locus ceruleus and cortex)
Secondary dementias
r
Vascular (multi-infarct dementia and Binswanger’s disease)
suspect if younger patient (cf. pure Alzheimer’s) with step-wise clinical progression and PMHx
of IHD, HT, smoking, vasculopathy, SLE, etc.
features incl.: softening of white matter, lacunar spaces around small vessels in basal ganglia,
microinfarcts of the cortex and arteriosclerotic vessels
multi-infarct dementia shows cortex and white matter predominant damage – usu. with a total
≥50–100ml brain volume lost
Binswanger’s disease shows basal ganglia and white matter predominant damage ± Parkin-
sonian Sx.
r
Post-traumatic (e.g. chronic subdural haematoma / dementia pugilistica)
r
Post-infective:
AIDS (cognitive and motor complex, see ‘HIV encephalopathy’, below)
post-encephalitic
GPI (syphilis)
prion: (→ grey matter spongiform degeneration) suspect if rapid onset and progression
(<2 years), motor Sx e.g. myoclonus/cerebellar, ± characteristic EEG (absent in vCJD),
prior psychiatric +/ sensory disturbance (esp. in vCJD), FHx (in GSS/FFI/familial CJD)
r
Others: e.g. toxic, metabolic, ‘normal’ pressure (i.e. intermittent) hydrocephalus
Ischaemic Hypoxic Injury
r
Seen in sensitive brain areas after global circulatory collapse (shock, MI, etc.) or CO poisoning
r
Sensitive areas: sulci, CA1, deep white matter, striatum, boundary zones (see figure 4.1 on p. 36)
r
Macro: laminar dark/discoloured areas (esp. in CA1 and cerebral neocortex layers3&5
1
)
r
Neurons: shrink, ↑ cytoplasmic eosinophilia, nuclear pyknosis and angulation
r
Glia: gliosis (GFAP immuno: ↑cells in cerebral cortex layers 3 & 5, vertical processes in cerebellar
cortex)
r
Later: neuron loss, demyelination (due to oligodendroglial damage)
HIV Encephalopathy
r
Degree of synaptic damage and global ↓ in neuronal numbers correlates with ‘AIDS dementia’
r
Macro: ± ventricular dilatation and widened sulci
r
Multinucleated Giant Cell Encephalitis (in deep white/grey matter and corticomedullary junction):
microglial nodules (cellular foci)
multinucleated giant cells (most probably derived from glia)
prominent endothelial cells
demyelination and perivascular foamy M (lipid)
HIV is detectable (e.g. by p24 immuno) in microglia (which are CD4 +ve), GC and endothe-
lium
r
Lymphocytic meningitis: leptomeningeal and perivasc. heavy lymphoid infiltrate (but no bugs)
r
Leucoencephalopathy: multifocal/diffuse demyelination, M, gliosis, GC, sparse lymphocytes
r
Cerebral granulomatous angiitis: mixed chronic inflam
n
and GC in vessel walls ± necrosis
r
Diffuse poliodystrophy: astrocytosis of the grey matter (of bainstem nuclei, basal ganglia and cerebral
cortex)
r
IRDS encephalopathy: intense perivasc. M (lipid, Fe and p24) and T-cells with severe demyelination
r
2
◦
pathology: severe immuno↓→CMV, PML, NHL; milder→ toxoplasmosis, VZV, HSV
Multiple Sclerosis
r
Onset in youth (optic neuritis), chronic relapse/remit or continuous → ataxic paraplegia
r
CSF: ↑lymphocytes, ↑ -globulin:albumin ratio, oligoclonal bands
r
Acute: yellow and soft, peri-axial (e.g. angles of lateral ventricles), around small veins
lymphoplasmacytic cuffing (of vessels) ± vesicular oedema and fibrin if acute/active
lipid foamy M, esp. perivascular (may contain stainable myelin)
1
layers 3 & 5 (of total 6) are the two layers that contain pyramidal neurons. They are in the mid cortex separated by a narrow band
(= layer 4, composed of stellate cells)
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Central Nervous System and Skeletal Muscle 183
r
Chronic: grey and sclerotic, demarcated irregular areas (confluence) shadow plaques
paucicellular, gliosis, survival of neurons
axons survive initially then undergo Wallerian degeneration
r
Variants: Neuromyelitis Optica (= Devic’s disease 2
◦
to MS): adults, rapid blindness and para-
plegia (brain, optic nerve, spinal cord). d/dg Devic’s disease 2
◦
to a necrotic TB lesion
in the spinal cord
Sudanophilic Diffuse Sclerosis: children, acute and progressive, esp. occipital (M
aggregates and neuron loss)
Acute Dissemintated (Perivenous) Encephalomyelitis
r
Post viral (measles, mumps, rubella, chickenpox, resp. infection)/vaccination (rabies/smallpox)
r
Acute onset
r
Diffuse perivenular demyelination and PMN → mononuclear cells later
r
It is considered an EAE-type reaction / reaction to a virus. Similar lesions may be seen in Beh¸cet’s
Acute Haemorrhagic Leucoencephalopathy/Leucoencephalitis/Leucoencephalomyelitis
r
Post viral (incl. influenza)/resp. infection/shock/drugs/cerebral malaria. Rapidly fatal
r
Swollen brain, perivenular demyelination, venular necrosis, ball and ring haemorrhage
r
Initially PMN → mononuclear cells later
r
It is considered to be a hyper-acute EAE-type reaction
Other Forms of Paraxial Demyelination
r
Central pontine myelinolysis: due to too rapid correction of plasma [Na
+
] in alcoholics/malnourished/
generally ill patients
r
Toxic demyelination: due to tin/carbon monoxide poisoning (subcortical white matter may be spared)
r
Viral infection: PML: polyoma (JC), immunosuppression, abnormal oligodendrocytes (viral in-
clusions)
SSPE: measles (years before)/rubella, age <20, death within six months, menin-
goencephalitis, neuronophagia, inclusions
Miscellaneous Demyelinations
r
Subacute combined degeneration of the cord (vitamin B12↓): lateral and posterior columns affected
r
Alcoholic, diabetic and Guillain-Barr´e peripheral neuropathy: segmental myelin loss in periph. nerves
r
RadioRx (via toxic effects on oligodendrocytes)
CNS (Neoplasms)
Differential Diagnosis by Site and Age
TABLE 13.1 Tumours by site and age
Not all tumours are represented C = occurs in children, A = occurs in adults, G1-4 = tumour grade.
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Central Nervous System and Skeletal Muscle 184
Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma
See p. 59.
Schwannoma, Neurofibroma, MPNST
See pp. 315–316.
Pineal Tumours
r
Neuronal (well-diff to poorly diff, mitotic count is prognostic – worse if >6/10hpf.):
pineocytoma: usu. adults; sheets of uniform cells with small nuclei are punctuated by pockets
of eosinophilic fibrillar material (pineocytomatous rosettes) – these may interconnect
pineal parenchymal tumour: intermediate differentiation and features between pineocytoma
& pineoblastoma, ± lobulation
pineoblastoma: usu. children; sheets of pleomorphic SBRCT ± rare retinoblastomatous
rosettes
r
Germ cell: germinoma(≈seminoma, OCT4 +ve),teratoma (mature ones morecommon than immature)
Craniopharyngioma
r
Adamantinomatoid (see ameloblastoma on p. 128) – have an ill-defined ‘pseudo-invasive’ boundary
with the brain
r
Squamoid (papillary arch., not calcific or cystic – see d/dg) – are well circumscribed
r
± Ghost epithelium, Ca
2+
, cystic change (± cholesterol crystals) +/ xanthogranulomatous inflam
n
r
Immuno: +vity for CK5/6, CK17, CK19, CK7, 34E12 and hCG (may help in d/dg), −ve for CK20
r
d/dg pilocytic astrocytoma (because craniopharyngioma may have adjacent chronic astrocytosis with
Rosenthal fibres, etc.)
r
d/dg Rathke’s cleft cyst: lined by cuboidal/columnar epithelium with goblet cells, cilia and focal squa-
mous metaplasia (hence the possibility for confusion)
r
d/dg: epidermoid cyst: these tend to be unilocular, non-papillary squamous lesions with keratin
r
d/dg squamous metaplasia of the pars intermedia of the pituitary: .
.
. do not diagnose craniopharyngioma
just because you see some squamous tissue !
Chordoma
r
Axial notochordal sites – esp. extremes (sacrum or clivus)
r
Lobulated architecture on low power with fibrous septa and myxoid background (± chondroid)
r
Cords of eosinophilic cells with interspersed physaliphorous (bubble-bearing) cells
r
Variants: dedifferentiated (has spindle sarcomatoid areas) and chondroid: both show brachyury +vity
r
Immuno: brachyury nuclear +vity (very specific for notochord differentiation); for d/dg see Table 13.2:
TABLE 13.2 Immuno in the d/dg of chordoma
S100 CK Brachyury Other Features
chordoma ++ + GFAP (30%), galectin-3 (75%), CAM5.2, EMA &
MNF116 +ve; CK7, CK20, CEA & D2-40 −ve
chondrosarcoma +− − site is helpful, +ve for D2-40, −ve for EMA & galectin-3
liposarcoma +− − fibrous septa unusual (refers to myxoid/round cell type)
RCC −+ − fibrous septa/lobulation unusual in 2
◦
CA; vascularity
myxopapillary
ependymoma
±− − GFAP & vimentin +ve; AE1/AE3 ±ve; CgA, CEA, EMA
& CAM5.2 −ve; d/dg also includes paraganglioma
meningioma ±± ? refers to the chordoid variant of meningioma
Olfactory Neuroblastoma
r
Lobulated blue cell tumour in the sinonasal region presenting usu. in teens or middle-aged adults
r
Grade 1: obvious neurofibrillary material, no mitoses/necrosis, small uniform round cells, ± Ca
2+
r
Grade 2: few mitoses, no necrosis, little pleom., less neurofibrillar material, ± Ca
2+
r
Grade 3–4: ↑mitoses, necrosis, pleom.; ↓neurofibrillar material (≈ absent in G4), no Ca
2+
r
Immuno: NSE +ve, CK ±ve, −ve for CD99, desmin, HMB45, EMA, CEA; NE granules on EM
r
d/dg G3-4 vs. sinonasal undiff carcinoma (see Chapter 8: Respiratory and Mediastinum)
JWBK208-13 December 8, 2007 16:5 Char Count= 0
Central Nervous System and Skeletal Muscle 185
Astrocytomas
Immuno
r
GFAP: +ve in low grades, weak or variable +vity in higher grades; D2-40 +ve in glioblastoma
r
Prognostic markers: p53, pRb (p105), p16
Pilocytic astrocytoma (grade I)
r
Child, posterior fossa, curable by resection .
.
. best prognosis
r
Relatively well-circumscribed cf. other types
r
Bipolar cells: have long (‘matted hair’) fibrillar processes ± elongated nuclei
r
Biphasic pattern: compact (bipolar cells) and loose/spongy/microcystic (multipolar/stellate cells)
r
Eosinophilic carrot-shaped Rosenthal fibres and rounded granular/cytoid bodies (intra/extra-cellular)
differentiate them from most higher grade gliomas (but not gliosis); calcispherules may be present
r
If cystic, a vascular mural nodule may be present – d/dg haemangioblastoma (lipid +ve, GFAP and
calcispherule −ve)
r
Nuclear atypia, infarct-like necrosis, microvascular proliferation
2
and subarachnoid space infiltration
are not poor prognostics
r
Malignant degeneration is rare and usu. post radioRx (hypercellularity, multiple mitoses per hpf, pal-
isaded necrosis ± microvascular proliferation)
r
d/dg chronic astrogliosis adjacent to some other lesion .
.
. check representativeness of Bx and CPC
Sub-ependymal giant cell astrocytoma (grade I)
r
Grade I by definition; usu. occur in TS; well-circumscribed and periventricular; ± cysts / Ca
2+
r
The GC are astrocytic, usu. mononuclear and show variable neuronal differentiation; HMB45 is −ve
r
Smaller cells are admixed resulting in a hetrerogenous picture
r
Good prognosis even if: mitoses, microvascular proliferation and necrosis
Astrocytoma (grade II)
r
Not pilocytic and not anaplastic. This is also called ‘Diffuse Astrocytoma’
r
Mitoses should be ≈ absent: if >1 mitosis is seen over many hpf = anaplastic astrocytoma (q.v.)
r
Ki-67 LI is usu. <2%
r
Includes:
◦
1
Fibrillary (most common)
◦
2
Gemistocytic (must have >20% gemistocytes [abundant eosinophilic cytoplasm without
Nissl substance and eccentric nucleus ± pleom.], also has perivascular lymphoid
infiltrate; d/dg Sub-ependymal Giant Cell Astrocytoma)
◦
3
Protoplasmic (rare)
Anaplastic astrocytoma (grade III)
r
Mitoses and ↑cellularity (cf. grade II). (The exact boundary between grade II & III is blurred)
r
No coagulative necrosis/microvascular proliferation (unless part of a focus of oligodendroglioma dif-
ferentiation)
Glioblastoma multiforme – GBM – (grade IV)
r
Clin./radiol.: supratentorial ring-enhancing lesion (grade III astrocytomas are not ring-enhancing)
r
Generally, as for Grade III plus coagulative necrosis +/ microvascular proliferation (this manifests as
↑cellularity of vessel walls or glomeruloid multilumena on H&E and broadening of capillary outlines
on retic)
r
Cytological pleomorphism and mitoses may not be prominent on small Bx
r
Variants:
◦
1
Gliosarcoma (GFAP –ve spindle sarcomatoid component ± collagen production)
◦
2
Giant cell glioblastoma (multinucleate giant cells ++)
◦
3
Small cell glioblastoma
r
d/dg anaplastic oligodendroglioma/oligoastrocytoma (esp. since oligo may have necrosis and ↑vessels,
small cell GBM may look like oligo and any GBM may have minor foci of true oligo differentiation).
Glioblastoma cytology varies more within any given tumour cf. oligo (hence ‘multiforme’)
r
d/dg other lesions with necrosis/microvascular proliferation (e.g. sub-ependymal giant cell astrocytoma
(vide supra), ependymoma (vide infra), metastatic carcinoma, lymphoma and abscess)
r
d/dg meningioma vs. gliosarcoma (look for more typical GBM components)
r
d/dg radioRx effect: the necrosis is not palisaded, the atypical glial cells are not mitotic and the vascular
changes are those of radiation (see p. 72) not microvascular proliferation
2
‘microvascular proliferation’ is the newer term for ‘vascular endothelial proliferation’ used in the older literature. See the section
on Glioblastoma Multiforme for a description of its morphology.
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Oligodendroglioma/Oligoastrocytoma (Grade II) and Anaplastic Oligo/Oligoastro (Grade III)
r
An important diagnosis to get right because these are sensitive to chemoRx (esp. if there is del. 1p or
19q) and may mimic high grade astrocytomas
r
Evenly-spaced cells with central round nuclei (with chromocentres ± small nucleoli) and clear
cytoplasm
r
± Microgemistocytes (GFAP +ve, vimentin −ve) and reactive astrocytes (GFAP +ve, vimentin +ve)
r
Prominent chicken-wire capillaries (! do not confuse with true microvascular – endothelial – prolif
n
,
although this may also occur focally in grade II lesions)
r
± Mucin microcysts (proteinaceous microcysts also occur in astrocytomas) ± focal calcifications
r
Mixed tumours (oligoastrocytoma) must have a ‘prominent component’ of each type (oligo and
astrocytoma) that may be well-defined or diffusely admixed. Some suggest >30% astrocytoma and
>50% oligo but this is not universally agreed. (d/dg astro component vs. microgemistocytes and
reactive astrocytosis [vide supra])
r
Mitoses are sparse (Ki-67 LI is usu. <5%)
r
High grade (anaplastic) features: {
◦
1
↑ cellularity,
◦
2
↑mitoses and
◦
3
nuclear pleom.} – may be focal
or diffuse (= grade III if diffuse). Microvascular prolif
n
+/ necrosis in the oligo component don’t
change anything but if in the astrocytoma component = ‘GBM with an oligo component’ (grade IV)
r
Immuno: GFAP +ve in microgemistocytes but ±ve in oligo component, CD57 +ve, vimentin −ve,
EMA −ve, MAP-2 +ve.
r
d/dg other clear-cell/epithelioid neoplasms: meningiomas (have well-defined boundaries and opposite
immuno for CD57, EMA, vimentin and GFAP), pituitary adenoma (site and peptides), RCC/other
carcinoma (sharp demarcation + immuno), haemangioblastoma (lacks Ca
2+
), clear cell ependymoma
r
d/dg high grade astrocytomas esp. small cell GBM (vide supra)
r
d/dg reactive lipid M have foamy cytoplasm and bland, vesicular, eccentric, bean-shaped nuclei
Meningiomas
Typical meningiomas (WHO grade I)
r
Sites: spinal/cranial/ectopic; also in intra-osseous (petrous), intraorbital and intraventricular sites
r
Meningothelial meningioma:
epithelioid cells with poorly defined cell borders (‘syncytial’)
whorls of cells, sometimes around vessels
ovoid nuclei with bland chromatin ± intranuclear cytoplasmic inclusions
± psammoma bodies (may be numerous in psammomatous meningioma = psammoma)
r
Local invasion: into dura and bone →↑risk of local recurrence; into brain → see Grade II, below
r
Variants (mesenchymal): fibroblastic, angiomatous, metaplastic (contains bone/cartilage/adipose/
myxoid/xanthomatous components)
r
Variants (epithelioid): microcystic, secretory (PAS +ve)
r
Immuno: vimentin +ve, GFAP −ve, S100 variably +ve (usu. mesenchymal types), CK variably +ve
(esp. epithelioid types), EMA usu. +ve but may be patchy, CD57 −ve. CEA +ve in secretory type.
Some are D2-40 +ve; Ki-67 LI may be prognostic
Atypical meningioma (WHO grade II)
r
Aggressive epithelioid variants: clear cell (PAS +ve), chordoid, oncocytic
r
Any type with the following are features of atypicality (even if only focal):
mitoses ≥4 per 10 hpf (with an hpf area defined as 0.16mm
2
≈ 0.45mm ∅)
foci of geographic necrosis (not surgically induced)
hypercellularity
sheet-like growth
nuclear pleomorphism (incl. prominent nucleoli)
small cells with ↑NCR
r
Atypical meningioma may be diagnosed on the mitotic criterion alone or on the presence of 3 of the
non-mitotic criteria if mitotic count is low. Brain invasion is not considered a defining criterion for
Grade II tumours but if present in a grade I tumour it connotes grade II-like behaviour so it should be
sought (do GFAP immuno).
Malignant (anaplastic) meningioma (WHO grade III)
r
Aggressive epithelioid variants:
papillary (elongated cells, pattern may be focal, d/dg adenocarcinoma)
rhabdoid (may not be aggressive if only a minor focal component, d/dg oncocytic)
r
Any type with ≥20/10hpf mitoses or marked cytological atypia ± exaggerated atypical features listed
above
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Other 1
◦
Meningeal Tumours
r
Soft tissue tumours: benign (e.g. lipoma), HPC, SFT, sarcomas (osteosarcoma, chondrosarcoma esp.
mesenchymal chondrosarcoma, RMS, etc.)
r
Haemangioblastoma
usu. infratentorial/spinal cord (unless assoc
d
with VHL), often cystic
epithelioid foamy lipidised and glycogenated ‘stromal’ cells + fine branching vessels
± haemosiderin, mast cells
retic: pericellular and perivascular staining
immuno: NSE, vimentin and D2-40 +ve, EMA and CK −ve
d/dg meningioma / metastatic RCC / astrocytic lesion (because there may gliosis and Rosenthal
fibres adjacent to a haemangioblastoma)
r
Melanoma
Lymphomas
r
Most are high grade large cell lymphomas e.g. DLBCL, ALCL
r
Any other type can occur but 1
◦
HL is almost unheard of
Per-operative Diagnosis (Brain Smear/Frozen Section)
Differentiating glioma from gliosis
r
Usu. only a problem at the margin of a glioma .
.
. if unsure at frozen section ask for a deeper Bx
r
Mitoses and Ca
2+
suggest glioma but these are rare at the margins
r
Nuclear hyperchromasia and pleomorphism suggest glioma
r
Density: gliosis =uniform or gradient (in white matter) or banded with neurons (in grey matter)
glioma = uneven distribution, palisades, 2
◦
structures of Scherer
3
r
Nuclei touch / indent each other in glioma (but nuclei don’t touch in gliosis)
r
Characteristic features of specific glioma types e.g. proteinaceous microcysts in astrocytoma
r
Immuno: widespread p53 +vity favours neoplasia over gliosis
Features suggesting 1
◦
neoplasia
r
Coagulative tumour cell necrosis (esp. if geographic and palisaded
4
) is the hallmark of a high grade
neoplastic lesion (! exclude d/dg e.g. abscess or infarct with pseudopalisading necrosis)
r
Birefringent fibrils may be seen in astrocytomas (Rosenthal fibres are not birefringent)
r
Nuclear features:
hyperchromasia
pleomorphism
bare nuclei
nucleoli (!but can get regular nucleoli in reactive astrocytes and oligodendrocytes)
nuclear crowding (hypercellularity)
r
Microvascular proliferation (! not capillary proliferation) – this is rarely seen in metastases and is a
hallmark of 1
◦
brain tumours (although not necessarily malignant – see ‘Astrocytomas’, above)
r
! Vascularity and variable numbers of M may be seen in space occupying infarcts
r
! Mitoses can be seen in reactive conditions
Some typical lesions
r
Meningioma – vide supra, helpful features in per-operative diagnosis are:
intranuclear cytoplasmic inclusions
psammoma bodies
epithelioid cells / whorls
± bundles of spindle cells (d/dg Schwannoma)
r
Gliomas – vide supra – NB: the cytoplasmic clearing of oligos may not be seen in FS/smear but oligos
tend to have a uniform distribution of cells (cf. perivascular accentuation in astrocytomas)
r
Central Neurocytoma:
usu. young (20s), intraventricular, low grade and surgically curable
salt and pepper nucleus and perinuclear halos
embryonal neuropil-like areas
immuno: GFAP +ve, synaptophysin +ve in ≈ all cells (only focal in oligos)
d/dg oligodendroglioma/ependymoma
3
these are (almost organoid) aggregates of neoplastic glial cells in perivascular, perineuronal or sub-pial locations
4
i.e. aggregation of tumour cell nuclei at the periphery of the infarct appear palisaded at low power. Because these nuclei are not
actually lined up this appearance is also called ‘pseudopalisading necrosis’
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Central Nervous System and Skeletal Muscle 188
r
Ependymoma:
papillary formations and rosettes: true (ependymal) and pseudo (perivascular)
nuclei have coarse, clumped chromatin and are more uniform (cf. astrocyte nuclei)
degenerative changes: hyaline vessels, myxoid, cartilage/bone/Ca
2+
, haemorrhage, non-
palisaded tumour necrosis (does not upgrade the tumour unless palisaded)
all are grade II except myxopapillary and sub-ependymoma (grade I) and anaplastic (III)
anaplastic features: ↑cellularity, mitoses ++, microvasc. prolif
n
, palisading necrosis, D2-40
+ve
immuno: Ki-67 may be prognostic; +ve for GFAP, vimentin, EMA, S100; CK ±ve (focal)
variants: many, but ! distinguish tanycytic (Grade II, occurs within brain/cord parenchyma)
from sub-ependymal (Grade 1, mural nodule in ventricle) because these both have similar
histology of hyper and hypo cellular areas in a fibrillary background.
r
Choroid plexus tumours:
papilloma (grade I): monolayer of amitotic bland cuboidal/columnar cells + brush border
carcinoma (grade III): ≥1 of the following: pleom., mitoses ++, necrosis, ↑NCR, ↑cellularity
(incl. solid or spindle foci) – ! d/dg metastatic carcinoma (−ve for D2-40)
immuno: +ve for transthyretin, CK, vimentin, D2-40, S100; ±ve for GFAP and EMA
r
Medulloblastoma (grade IV):
infratentorial (cerebellar) location – otherwise it’s called a PNET
SBRCT of hyperchromatic cells (nuclei may be carrot-shaped) with ↑NCR
arch.: sheets and focal rhythmic palisaded architecture ± rosettes (vide infra)
neuropil fibrillary material emanating from the tumour cells (unlike d/dg lymphoma where
the background fibrils belong to the invaded neuropil). In this context Homer-Wright rosettes
(have fibrillary centres but no lumen) are useful if present (they are rarely seen in smears).
mitoses and apoptoses
immuno: ±ve for GFAP, synaptophysin, neurofilament protein, S100, NSE, D2-40
retic: intercellular fibres +ve (except in the hypocellular areas of the biphasic Desmoplastic
Medulloblastoma variant)
d/dg (esp. on smears): granule cells of cerebellum and lymphoma
Pituitary
See pp. 277–279.
Skeletal Muscle
Normal Skeletal Muscle
Staining properties
TABLE 13.3 Muscle fibre staining properties
FIBRE TYPE
I IIA IIB
Morphology/Physiology red, slow, fatigue resistant white, fast, fatigue resistant white, fast, fatigue sensitive
Myoglobin (eosinophilia) +++ + +
Glycogen (PAS) + +++ ++
Gomori’s trichrome +++ + +
Lipid (Sudan) ++ + ±
Mitochondrial enzymes
(NADH & cytochrome
oxidase)
+++ ++ +
ATPase pH 9.4 - pH 9.9 ±++/+++ +++
ATPase pH 4.4 - pH 4.6 +++ ± ++
ATPase pH 4.2 (or 4.3) +++ ± ±
Phosphorylase ± +++ +++
‘+++’ means an intense reaction/‘dark’ staining whereas ‘±’ means weak/‘light’ staining.
r
Developing (undifferentiated) muscle fibres (= Type IIC) show similar staining properties to Type IIB
but have no lipid and show greater ATPase activity at pH 4.2 and greater cytochrome oxidase and
succinate dehydrogenase activity
r
NADH is often stained for by the tetrazolium reductase method that gives a blue reaction product