Otology Seminar
Cholesterol Granuloma
R3 邱楠超
A. Introduction
1. Cholesterol granuloma (CG) is a histologic term used to describe
a chronic granuloma that represents a foreign body response.
2. It was called “idiopathic hematotympanum” in the middle ear.
3. CG is found in various organs.
4. The temporal bone is the most common site of detection.
5. First described by Manasse in 1917 but has been ignored.
6. Birrell (1956), Sheehy and McKibben (1956) and Friedmann
(1959) drew renewed attention to this lesion.
B. Pathology
1. Macro: brown glistening fluid and semisolid yellow gritty
material; may have two varieties, cystic or solid; often both are
found.
2. Micro: chronic inflammatory granulation tissue containing large
numbers of cholesterol crystals, surrounded and engulfed by
multinucleated foreign body giant cells; usually some clear
evidence of recent and old hemorrhage with hemosiderin
pigment.
3. Cholesterol is a substance of great resistance to the normal
process of absorption, and the deposited crystals tend to provoke
an intensive granulomatous reaction.
4. Giant cells act as phagocytic cells, actively removing the
cholesterol crystals.
5. Beside a large number of nuclei with large nucleoli, the giant
cells are rich in rough endoplasmic reticulum, ribosome,
mitochondria, and lysosomes.
6. CG of the PA vs. CG in the tympanomastoid compartment
C. Pathogenesis
I. Unclear
II. Obstruction-vacuum theory: mid-20th century (see figure)
- Why is PA CG not frequent in persons with long-standing
hypoventilation due to E-tube dysfunction?
- PA CG arise in only well-pneumatized Pas – a finding
indicative of freedom from mucosal disease.
- When PA air cell obstruction occur, the degree of vacuum
generated by gas absorption alone should be insufficient to
trigger hemorrhage.
- Once the apical air cells are fluid filled, the vacuum is abated,
and the mechanism underlying continued seepage as the
driving force for cyst expansion is not explained.
1. The obstruction-vacuum theory could explain only partially
the pathogenesis of tympanomastoid cholesterol granuloma.
2. Controversy still exists as to the source of the cholesterol
crystals.
Hemorrhage is the source:
- Sakamoto: small cholesterol clefts were always surrounded by
degenerated erythrocytes
- Hiraide and Kakoi: large amount of ferritin and transferrin in
the vicinity of the cholesterol clefts
Cellular breakdown
- Sade and Teitz: low cholesterol ester content in CGs compared
with the high cholesterol ester content in serum.
3. A key point in CG formation is that the hemorrhage occurs
into a sterile environement.
- Friedmann and Ruedi: sterile suspensions injected into the
experimental animals form CGs; experimentally infected ears
do not form CGs.
4. Dota et al. showed that in order for CG expansion and
adjacent bone resorption to occur, a sustaining source of blood
is necessary to feed a continuing foreign body reaction.
III. A new theory: exposed marrow
- Association with exceptional degrees of petrous apex
pneumatization.
- Lack of correlation with antecedent chronic otitis media.
- Lack of correlation with long-standing chronic effusion due
to poor E-tube function.
- Occasional bilateral occurrence.
- Sustained source of hemorrhage to drive progressive
granuloma expansion.
- Tendency for recurrence of postsurgical drainage.
1. As cellular tracts penetrate the apex during young adulthood,
budding mucosa invades and replaces hematopoietic marrow.
2. The bony interface becomes deficient, with coaptation of
vascular marrow and the mucosal air cell lining.
3. Hemorrhage from the exposed marrow coagulates within the
mucosal cells and occludes outflow pathways.
4. Sustained hemorrhage from exposed marrow elements
provides the engine responsible for the progressive cyst
expansion.
D. Symptoms and Signs
1. Middle ear: blue mass, conductive hearing loss, tinnitus, and
conditions associated with chronic otitis media.
2. Petrous apex:
- Involvement of internal auditory meatus or otic capsule: SNHL,
tinnitus, dizziness, or vertigo
- Involvement of the dura of the temporal and of the posterior
fossa: temporal headache
- Involvement of Meckel’s cave: trigeminal and abducens nerve
symptoms.
- Facial nerve paresis is less common, except in extensive lesion.
E. Image
1. On CT: Well defined expansile lesion with smooth margin
Isodense to brain
No significant contrast enhancement
A faint peripheral rim of enhancement may be present
2. On MRI: Hyperintense on T1-wighted and T2-weighted images
F. Differential Diagnosis
1. Solid Middle Ear Tumor
- Glomus tumor
- High jugular bulb
- Abberent carotid artery
- Brain hernia
2. Petrous Apex tumor
- cholesteatoma, mucocele, glomus, chondrosarcoma, chordoma,
meningioma, schwannoma, metastatic cancer (breast, lung,
kidney, and prostate)
G.
1.
2.
3.
4.
5.
6.
7.
Treatment
Observation
Steroid therapy, efficacy?
Insertion of a ventilation tube with mastoidectomy
Infralabyrinthine: serviceable hearing is preserved
Transcanal infracochlear: can be used in the presence of a high
jugular bulb
Translabyrinthine: no serviceable hearing; most direct route
Middle cranial fossa: the creation of a pathway of peranent
drainage is much more difficult; requires retraction of the brain.
Reference:
1.
Jackler RK, Cho M, A New Theory to Explain the Genesis of Petrous Apex Cholesterol
Granuloma, Otology & Neurology, 24: 96-106, 2003
2.
Maeta M, Saito R, Nakagawa F, Miyahara T, Surgical Intervention in Middle Ear Cholesterol
Granuloma, The Journal of Laryngology & Otology, May 2003, Vol 117, pp 344-348
3.
Miura M, Sando I, Orita Y, Hirsch B, Histopathologic Study of the Temporal bones and
Eustachian Tubes of Children with Cholesterol Granuloma, Ann Otol Rhinol Laryngol, 2002 July;
111: 609-15
4.
Friedmann, H, Graham M, The Ultrastructure of Cholesterol Granuloma of the Middle Ear: an
electron microscopy study, The Jounal of Laryngology & Otology, November 2002, Vol 116,pp
877-881
5.
Mosnier I, Gorse F, Grayeli A, et al, Management of Cholesterol Granuloma of the Petrous Apex
Based on Clinical and Radiologic Evaluation, Otology & Neurology, 23: 522-528, 2002
6.
Brackmann D, Toh E, Surgical Management of Petrous Apex Cholesterol Granuloma, Otology &
Neurology, 23: 529-533, 2002
7.
Biller J, Linthicum F, Cholesterol Granuloma, Otology & Neurology, 22: 569-570, 2001
8.
Fong B, Brackmann D, Telischi F, The Long Term Follow Up of Drainage procedures for Petrous
Apex Cholesterol Granuloma, Arch Otolaryngol Head Neck Surg, Vol 121, Apr 1995
9.
Hiraide F, Inouye T, Miyakogawa N, Experimental Cholseterol Grnauloma Histopathological and
Histochemical studies The Journal of Laryngolog and Otology, June 1982. Vol 96, 491-501