Transcript Case Study - University of Pittsburgh

Case Study 48
Edward D. Plowey
Case History
 The patient is a 64 y/o woman with a 2.5 year history of
a left cerebellar hemisphere lesion initially discovered
and followed at an outside hospital on workup for
chronic headaches.
 The outside impression was initially a benign lesion,
possible encephalomalacia. However, interval
enlargement of the lesion prompted neurosurgical
intervention.
Question 1
Describe the major radiologic abnormality on the following
MRI.
Answer
Well-delineated T2 bright lesion in the left cerebellar hemisphere with
a thickened foliar architecture pattern. There is minimal surrounding
edema, no significant mass effect or midline shift. No hemorrhage is
seen on T1 and there is no abnormal contrast enhancement. (There
is also a small enhancing left retromastoid lesion with underlying
meningeal enhancement felt to be a hemangioma.)
L’hermitte-duclos disease was strongly suspected based on these
radiologic features.
The patient was taken to the OR for resection of the left cerebellar
hemisphere lesion.
Question
Describe the findings in the following images from the
intraoperative consultation.
Intraoperative Consultation
Frozen
Frozen
Smear
Answer
 An intraoperative smear preparation shows a heterogeneous cell
population with an large increase in the ratio of ganglion cells to
small granule neurons than is expected in the cerebellar cortex.
Occasional reactive astrocytes are also seen.
 A frozen section shows increased numbers of disordered ganglion
cells surrounding both sides of the foliar white matter. No normal
granule cell layer is seen in this folium.
 An intraoperative diagnosis of L’hermitte-Duclos disease was
rendered based on these pathologic findings and the MRI findings.
Question
 Describe the findings on the H&E stained permanent
sections of the lesion resection material.
 Click here to view virtual slide.
Answer
Histologic sections demonstrate areas with normal
cerebellar cortical architecture that abruptly yield to
abnormal cerebellar cortex in which the granule cell layer
is replaced by abnormal, disorganized ganglion cells.
These areas of cortex also lack Purkinje cells and show
expansion of the molecular layer with myelinated axons.
These findings are diagnostic of L’hermitte-Duclos
disease.
Question
 A NeuN immunostain was performed on the lesion.
Describe the significance of the findings.
 Click here to view virtual slide.
Answer
A NeuN immunostain is positive in both the normal
granule neuron layers and in the layer of dysplastic
ganglion cells.
These findings demonstrate that the ganglion cells are not
Purkinje neurons (which are normally NeuN negative);
they are phenotypically related to the granule neurons.
Question
 A neurofilament immunostain was performed on the
lesion. Describe the significance of the findings.
 Click here to view virtual slide.
Answer
A neurofilament immunostain highlights axons in the normal white
matter of the cerebellar cortex as well as the abnormal molecular
layer above the dysplastic ganglion cells.
These findings highlight the “inverted cerebellar cortical architecture”
characteristic of L’hermitte-Duclos disease.
Synaptophysin immunostaining was also
found in the abnormal molecular layer (right).
Synaptophysin
Question
L’hermitte-Duclos disease is pathognomonic for which of
the following genetic disorders?
A.Gorlin syndrome
B.Turcot syndrome
C.Cowden syndrome
D.Von Hippel Lindau syndrome
Answer
L’hermitte-Duclos disease is pathognomonic for which of the following
genetic disorders?
A.Gorlin syndrome
B.Turcot syndrome
C.Cowden syndrome
D.Von Hippel Lindau syndrome
Correct Answer: Cowden syndrome
Question
Which of the following cutaneous lesions are most likely
to be found in patients with L’hermitte-duclos disease?
A.Shagreen Patch
B.Ash-leaf spot
C.Café-au lait macule
D.Trichilemmoma
Answer
Which of the following cutaneous lesions are most likely
to be found in patients with L’hermitte-duclos disease?
A.Shagreen Patch
B.Ash-leaf spot
C.Café-au lait spot
D.Trichilemmoma
Correct Answer: Trichilemmoma
Question
L’hermitte-Duclos disease patients are likely to harbor
germ-line inactivating mutations in which of the following
tumor suppressor genes?
A.INI-1
B.PTEN
C.p16
D.TP53
E.retinoblastoma
Answer
L’hermitte-Duclos disease patients harbor germ-line inactivating
mutations in which of the following tumor suppressor genes?
A.INI-1
B.PTEN
C.p16
D.TP53
E.retinoblastoma
Correct Answer: Cowden syndrome is a PTEN hamartoma syndrome
Question
The diagnosis of L’hermitte-Duclos disease indicates that
our patient is at increased risk for which of the following
neoplasms?
A.Breast carcinoma
B.Endometrial carcinoma
C.Thyroid carcinoma
D.All of the above
Answer
The diagnosis of L’hermitte-Duclos disease indicates that
this patient may be at increased risk for which of the
following neoplasms?
A.Breast carcinoma
B.Endometrial carcinoma
C.Thyroid carcinoma
D.All of the above
Correct Answer: All of the above.
Question
Dysplastic cerebellar gangliocytoma is best characterized
as a neoplasm or hamartoma?
Answer
L’hermitte-duclos disease (dysplastic cerebellar gangliocytoma) is a
pathognomonic tumor for Cowden syndrome, otherwise known as
multiple hamartoma syndrome. L’hermitte-duclos itself is best
characterized as a hamartoma (see Ki67 proliferative index of 0% in
this case below) and is classified as a WHO Grade 1 tumor, although
tumor recurrence has been reported.
The clinical importance of recognizing this lesion is
its association with Cowden syndrome, a PTEN
hamartoma syndrome with increased risk for
epithelial malignancies of the breast, endometrium
and thyroid. Our patient has a history of multiple
thyroid FNAs diagnosed as colloid nodules, but no
history of malignancy.
Ki67