Pathlet- By: Daniel Hans
Dx: Hemangioblastoma
A 45-year-old male. Fall 2008. San Francisco, CA.
Dexter Morgan, a 45-year-old male, at the insistence of his wife, presents to you, a
KCUMB alumni. For several years he has been getting ‘the run-around’ from
physicians who cannot seem to nail down his diagnosis. Initially his symptoms were
mild and attributed to middle age. However, slowly and steadily they have
progressed and are now greatly affecting his life.
His wife about 3 years ago, (his age at the time 42), began noticing slight memory
problems and lack of attention. He attributed this to selective hearing loss due to his
wife’s constant nagging. Within the last year both he and his wife noticed balance
and equilibrium issues that caused him to feel dizzy. He shared these symptoms
with his primary care physician, who referred him to an ENT. After a quick exam,
the specialist provided a working diagnosis of benign positional vertigo, and
preformed some inpatient procedures, which provided no relief. Although his issues
with equilibrium were annoying, Mr. Morgan did not get seriously worried about
the state of his health until six months ago when he began having trouble walking,
standing, and moving in a coordinated manner, which was significantly affecting his
life. At this point, he and his wife wanted to see a “better doctor” to find the
underlying cause of these health problems.
Mr. Morgan presents to you in your office, he is frustrated, short on attention, and
his wife insists that there must be a cure if you only look.
What key things in the history might suggest a specific disease process?
Same history as provided above. He also provides some vague family history of
some french sounding disease, but he will have to contact his father and get back
with you.
What key parts of the physical exam might be important to this diagnosis?
What radiologic studies need to be performed?
Gadolinium-enhanced MRI of the head: Results, two hyperdense tumors in the
cerebellum one slightly larger than the other, both are associated with irregularly
shaped adjacent cyst’s.
What lab studies would you order to confirm this diagnosis?
Note his hemoglobin is 22 (
normal)
normal), HCT 66% (
normal) RBC 8.5 million (
Cytogenics and molecular studies for VHL, show an allelic loss at chromosome 3p2526.
Ophthalmologic exam reveals a flame shape hemorrhage in the retina of the right
eye at the 1:00 o’clock position.
After consulting with the friendly neighborhood neurosurgeon and oncologist,
everyone agrees that the tumor needs to be cut out; sooner rather than later. The
next morning Mr. Morgan goes into surgery where the neurosurgeon successful
resects both tumors and associated cysts.
The resected specimen is sent to pathology, it consists of a 8.5 grams of tissue
composed of cyst wall fragments, and other fragments of soft red tissue that
measure in aggregate 4.8 X 4.0 X 3.0 cm.
Histologic sections show two main features, large vacuolated stromal cells and a rich
capillary network. Note the lipid vacuoles within the cells resulting in the typical
clear cell morphology. See figure XXXX Small foci of hemorrhage are seen in some
areas. Mitotic activity is low.
As an astute pathologist, what immunohistochemical stains, might you order?
In hemangioblastoma, stromal cells lack common endothelial markers such as Von
Willebrand factor, CD34 and CD31. Stromal cells are also negative for GFAP protein.
They are positive for NSE, Vimentin, and some express transforming-growth-factoralpha. Most express high levels of mRNA and a protein for (EGFR).
What metastatic renal tumor, with similar morphology, must be ruled out by
immunohistochemistry?
Cytokeratin, EMA, and pan-epithelial antigen are all negative in hemangioblastoma,
What ultrastructural features can be seen, in the stromal cells?
EM shows an abundance of lipid droplets in an electron-lucent cytoplasm.
Answer: Hemangioblastoma
You see the Mr. Morgan after the surgery; his wife is present with him and states she
spoke to his father (Mr. Morgan Senior) about his illness. Mr Morgan Senior
provided a family history of Von Hippel-Lindau disease being diagnosed in the
father, a daughter, and nephew.
Resources
1. Kaelin, William G (2005). "von Hippel–Lindau-associated malignancies:
Mechanisms and therapeutic opportunities". Drug Discovery Today: Disease
Mechanisms 2 (2): 225–231.