J Neurosurg Pediatrics 6:385–392,
6:000–000, 2010

Microfibrillar collagen hemostat–induced necrotizing
granulomatous inflammation developing after craniotomy:
a pediatric case series
Report of 3 cases
Liat Apel-Sarid, M.D.,1 Doug D. Cochrane, M.D., F.R.C.S.C., 2
Paul Steinbok, M.B.B.S., F.R.C.S.C., 2 Angela T. Byrne, M.B., F.F.R.R.C.S.I., 3
and Christopher Dunham, M.D., F.R.C.P.C.1
Department of Pathology and Laboratory Medicine, Division of Anatomic Pathology; 2Department of
Surgery, Division of Pediatric Neurosurgery; and 3Department of Radiology, Children’s and Women’s Health
Centre of British Columbia, University of British Columbia, Vancouver, British Columbia, Canada
1

Object. Microfibrillar collagen hemostat (MCH; trade name Avitene) is a partially water-insoluble acid salt of
purified bovine corium collagen. This agent has been widely used to control hemorrhage at surgery, and especially
during pediatric neurosurgeries at the authors’ institution. Despite its effectiveness, rare case reports detailing adverse
inflammatory reactions to MCH have been documented. Based primarily on MR imaging, postoperative reactions
have most commonly elicited clinical differential diagnoses of tumor recurrence or abscess. According to the literature, MCH induces a very characteristic mixed inflammatory response that is rich in eosinophils; in light of these
observations, many authors have suggested an allergy-based pathogenesis.
Methods. The authors retrospectively reviewed 3 pediatric neurosurgical cases treated at their institution, wherein a common histomorphological inflammatory reaction to MCH was elicited at the site of prior craniotomy.
Results. Case 1 is that of a 10-year-old girl whose diagnosis was a right temporal lobe ganglioglioma, classified
as WHO Grade I. Case 2 is that of a 9-year-old boy whose diagnosis was a left parietal lobe anaplastic ependymoma,
classified as WHO Grade III. Finally, Case 3 is that of a 15-year-old girl whose diagnosis was focal cortical dysplasia Type IIA affecting the left occipital lobe. Each patient presented with new or recurrent seizures 5–6 weeks after
the initial resection. The postsurgical reactions incited by MCH mimicked the radiological appearance of either an
abscess (Cases 2 and 3) or recurrent tumor (Case 1). Histologically, the mixed inflammatory infiltrate was typified by
the presence of MCH-centric necrotizing granulomas that were surrounded by a palisade of macrophages and often
several eosinophils.
Conclusions. The findings are in keeping with previous case reports describing the clinicopathological features
of adverse reactions occurring due to MCH. Based on the authors’ observations, the possibility of an idiopathic
inflammatory reaction to MCH should be considered when either seizures, a typical radiological appearance (that
is, consistent with tumor recurrence or abscess formation), or both arise shortly after initial surgery. A conservative
treatment approach to this type of inflammatory lesion appears to be the most appropriate management strategy.
(DOI: 10.3171/2010.8.PEDS10248)

Key Words • microfibrillar collagen hemostat
inflammation • textiloma • craniotomy

M

collagen hemostat (trade name
Avitene) is a partially water-insoluble acid salt
of purified bovine corium collagen. It is processed into microcrystals and used at the time of surgery
to control hemorrhage without the need for sutures. The
MCH is applied directly on the bleeding surface and induces platelet aggregation, the thrombotic cascade, and
ultimately the formation of a stable hemostatic plug.7,13
icrofibrillar

Abbreviations used in this paper: FCD = focal cortical dysplasia;
MCH = microfibrillar collagen hemostat.

J Neurosurg: Pediatrics / Volume 6 / October 2010

• Avitene

•

necrotizing granuloma

•

It was approved by the FDA in the US in 1977, and
since then it has been widely adopted by several surgical subspecialties as an effective bioabsorbable hemostatic agent.1,3,8–10,15,16,21,22 The neurosurgical use of MCH
is especially beneficial given the danger of postoperative hemorrhage in the closed and confined intracranial
space.6,17
This article contains some figures that are displayed in color
on­line but in black and white in the print edition.

385

L. Apel-Sarid et al.
Although the manufacturer (MedChem Products,
Inc.) describes several potential adverse effects that may
be associated with the use of MCH (including wound dehiscence, abscess formation, adhesion formation, allergic
reactions, and foreign-body responses), these reactions
are considered rare, and therefore, MCH is generally considered safe.1,2,14 However, some of the initial experimental animal literature did describe rare instances of significant postoperative inflammation after the use of MCH.14
Not surprisingly, multiple clinical case reports have
since documented adverse postoperative inflammatory
reactions to MCH throughout the body.1,3,5,10,15,16,18,19,21–23
Various terminologies have been used in the literature
to describe these lesions, including textiloma, gossypiboma, and muslinoma.22 These reactions have clinically
mimicked abscesses, tumor recurrence, or radiation necrosis.1,16,19,21–23 Intracranial reactions are uncommon, and
only 1 pediatric case has been described to date.5,18,19,22,23
In addition to reviewing the neurosurgical literature,
we report a series that includes 3 pediatric cases in which
a histological picture of necrotizing granulomatous inflammation emerged 5 to 6 weeks after the use of MCH.
These reactions mimicked tumor recurrence in 1 patient
and abscess formation in our other 2 cases.

Methods

Patients at Children’s and Women’s Health Center
of British Columbia with possible clinical or radiological
reactions to MCH were identified retrospectively with assistance from the Division of Pediatric Neurosurgery. The
clinical charts and pathological materials were reviewed
in each case with the approval of our local research ethics board (#H10–01293). Given the age of the histological
materials, occasionally slides were recut and stained to
facilitate microscopic assessment.

Case 1

Case Reports

This girl originally presented at the age of 7 months
with complex partial seizures. A head CT scan obtained
at that time revealed a partially calcified and cystic right
temporal lobe mass that measured 2.5 cm. When the patient was 10 years old, the seizures became increasingly
refractory to medication. Follow-up MR imaging studies
revealed enlargement of the cystic component of the lesion
and encroachment on the adjacent cerebral peduncle. Despite the history and imaging findings, no neurological or
other abnormalities were noted on physical examination.
A selective anterolateral temporal lobectomy was
performed at this time. Hemostasis during surgery was
achieved using bipolar cautery and application of MCH;
after irrigation of the tumor bed, only adherent MCH remained. The temporal lesion was gross totally excised,
but a nonresectable subarachnoid component remained
in the interpeduncular and ambient cisterns. Microscopy
revealed a ganglioglioma (WHO Grade I) (Fig. 1A). Adjuvant therapy was not immediately pursued.
The patient’s seizures ceased in the immediate postoperative period. However, approximately 6 weeks after

386

surgery, the patient’s typical seizure auras returned, and 2
generalized seizures occurred. Follow-up head CT scanning revealed a suggestion of subarachnoid tumor expansion, as well as a recurrent lesion in the previous resection
cavity that was typified by medial enhancement and mass
effect (Fig. 1B).
In light of the clinical differential diagnosis, which included a resolving hematoma, tumor progression, or postoperative scar, surgical reexploration was undertaken for the
purpose of biopsy sampling. At surgery, a very swollen and
firm cavity containing pockets of fluid was encountered.
Biopsy samples of the walls of the cavity were obtained
and sent for pathological review. Microscopy revealed necrotizing granulomatous inflammation. Acellular, fibrillary,
eosinophilic foreign material was closely surrounded by a
palisade of epithelioid macrophages. The latter was in turn
embedded in dense connective tissue containing a mixed
infiltrate of neutrophils, plasma cells, lymphocytes, and
multinucleated giant cells (Fig. 1C). Although also present,
eosinophils were only scattered.
Twenty-one months later, the patient presented with
back and leg pain and right-sided foot drop. Papilledema
was noted on examination. The MR imaging revealed
obstructive hydrocephalus that was thought to be due
to persistent intracranial subarachnoid disease. In addition, diffuse and extensive extraaxial metastatic disease
(that was not compressing the spinal cord) was suggested
throughout the spinal axis. A ventriculoperitoneal shunt
was placed, and the patient received craniospinal irradiation (3600 cGy in 20 fractions over 4 weeks) and chemotherapy. The latter consisted of vincristine and actinomycin D, but this chemotherapy was subsequently halted
after 1 cycle due to anorexia and weight loss. A small
biopsy of the abnormal tissue noted in the right temporal
lobe revealed tumor that was considered to be similar to
that obtained in the first surgery (it was reported as “low
grade astrocytoma” given the lack of neoplastic neurons
in the limited tissue submitted).
Despite the ominous clinical picture 21 months after her initial surgery, the patient, remarkably, improved.
At the last follow-up, the patient was 29 years old and
was alive and well. She was off medication and free of
seizures. Although MR imaging revealed generalized enhancement of the leptomeninges, there was no definitive
evidence of residual tumor. The cause of this latter generalized leptomeningeal enhancement was not definitively
determined.
Case 2

This 9-year-old boy originally presented to the emergency department with a 2-week history of progressive
headache that was associated with vomiting in the morning. Subsequently he developed right-sided weakness manifesting in clumsy hand function. His history also included
short periods of headache and neck pain in the months preceding presentation. A CT scan showed a large contrastenhancing left parietal mass that was cystic and calcified.
A gross-total resection was obtained at surgery. Hemostasis was achieved using cotton balls soaked in hydrogen peroxide, followed by the application of MCH.
The tumor bed was subsequently irrigated, and only adJ Neurosurg: Pediatrics / Volume 6 / October 2010

Postcraniotomy MCH-induced necrotizing granulomatous inflammation

Fig. 1. Case 1. A: Photomicrograph of a section of the initial right temporal lobe mass reveals a ganglioglioma, WHO Grade
I. Note the large abnormal ganglion cells with vesicular nuclei. H & E, original magnification × 200. B: Axial head CT scan
obtained at clinical repeat presentation 6 weeks after the initial craniotomy. A contrast-enhancing mass, suspected of being
recurrent tumor, is noted in the medial aspects of the prior resection bed. C: Photomicrograph of an H & E–stained section of
the mass depicted in B. A palisade of macrophages surrounds the eosinophilic MCH, some of which (upper part of the panel) is
necrotic. Multinucleated foreign-body type giant cells are easily identified in the mixed inflammatory infiltrate. Original magnification × 100.

herent MCH was left in situ. The original histological diagnosis was of a supratentorial primitive neuroectodermal
tumor, but recent review suggested an alternative diagnosis of an anaplastic ependymoma (WHO Grade III) (Fig.
2 left). Adjuvant treatment included craniospinal radiation and chemotherapy with the CCD-9892 protocol, consisting of vincristine, cisplatinum, and 1-(2-chloroethyl)3-cyclohexyl-1-nitrosourea (lomustine).
Five weeks after surgery, the patient presented with
right-sided focal motor seizures leading to progressive
weakness. Head CT scanning revealed a ring-enhancing
lesion and surrounding edema at the site of the previous
surgery. The clinical differential diagnosis included cerebral abscess (although there was no fever), recurrent tumor, postoperative change, or a reaction to radiotherapy.
Antibiotics were commenced and a second craniotomy
was performed to better delineate the disease process. At
surgery, a cystic cavity filled with xanthochromic fluid
was encountered. There was no obvious tumor tissue or
pus. The cavity did not look inflamed, but it was firm to

the touch. The dura mater was thick and calcified. Biopsy samples of the walls of the lesion were obtained and
sent for pathological review. Hemostasis was once again
achieved via intracavitary application of MCH, the excess
of which was removed by irrigation.
Microscopic examination revealed necrotizing granulomatous inflammation (Fig. 2 right). Partially necrotic
basophilic to amphophilic fibrillary material was closely
surrounded by a palisade of macrophages. These latter
regions were embedded within an eosinophil-rich mixed
inflammatory infiltrate that included neutrophils, plasma
cells, and multinucleated giant cells. Dense connective
tissue deposition was noted, but there was no evidence of
microorganisms or tumor.
At last follow-up, 3 years after treatment, the patient
was neurologically well and free of disease on neuroimaging.

Case 3

This 15-year-old girl presented with an 8-year history

Fig. 2. Case 2. Left: Photomicrograph of a section of the initial left parietal lobe mass reveals an anaplastic ependymoma,
WHO Grade III. Perivascular pseudorosettes are numerous and often contain microvascular proliferation. H & E, original magnification × 100. Right: Histological section of the ring-enhancing lesion identified 5 weeks after the original craniotomy. Note
the palisade of macrophages that surround the eosinophilic MCH. The background inflammation contains numerous eosinophils
and some multinucleated foreign-body type giant cells. H & E, original magnification × 200.

J Neurosurg: Pediatrics / Volume 6 / October 2010

387

L. Apel-Sarid et al.
of refractory partial seizures and intellectual impairment.
Her seizures were initially characterized by blurring of
vision, loss of vision or visual hallucinations followed by
nausea, vomiting, eye deviation to the left, occasional cyanosis, eyelid blinking, manual automatisms, and confusion. Her seizures were often associated with generalized
body stiffening and jerking, including secondary generalization. Seizures tended to occur in clusters and were
more frequent during sleep. She had numerous episodes
of status epilepticus, and she suffered from multiple daily
seizures that were refractory to anticonvulsants.
An extensive workup, including electroencephalography and neuroimaging (CT scans and MR imaging), suggested a left occipital epileptogenic focus emanating from
a subtle region of cortical dysplasia. The patient underwent an occipitoparietal cortical resection, during which
MCH was used for hemostasis. The MCH was placed in
the resection cavity at the end of the procedure, and the
excess was removed via copious irrigation. Microscopic
analysis revealed only mild FCD (most consistent with
Palmini Type IA: see below).20
Seizures continued despite this initial resection, and
the postoperative MR imaging results suggested residual
dysplastic tissue. One month later, when the patient was
taken back to the operating room for additional tissue resection and the placement of a subdural grid, MCH was
again used for hemostasis. The microscopic appearance
of this resected tissue was similar to that obtained at the
first operation.
Two days after the second resection, seizures were
persisting. Subdural grids mapped the epileptogenic focus as medial to the previous surgical sites; therefore, a
third resection was performed. Microscopic evaluation
revealed definitive FCD with abnormal, large, and disoriented neurons, but no balloon cells (that is, Type IIA) (Fig.
3A). In addition, a marked necrotizing granulomatous inflammatory reaction was observed. Ropy collagen-like
material, consistent with MCH, was partially necrotic and
surrounded by a palisade of macrophages. The latter was
in turn embedded in a sea of chronic inflammation that

was rich in eosinophils (Fig. 3B). A mild acute inflammatory reaction was also noted in the regions of previous
subdural electrode placement.
Seizure activity stopped after the third surgery. However, the skin wound over the craniotomy site was healing
poorly and there was some fluid drainage. Sixteen weeks
after the third resection, a small area of exposed calvaria
(deep to the scalp incision) was observed, and a subgaleal
swab of this site grew methicillin-sensitive Staphylococcus
aureus. The patient was well clinically, with no fever or seizures. On CT and MR imaging studies of the head, a possible area of osteomyelitis was demonstrated at the site of
bone exposure, and an intraaxial ring-enhancing area was
seen near the previous surgical bed (Fig. 3C). The clinical
concern was for an abscess. However, the possibility of an
inflammatory reaction to MCH was considered in light of
the histological findings from the prior resection. Debridement, reclosure of the scalp incision, and aspiration of the
cystic lesion were performed. The capsule of the lesion
was very firm, and 6 ml of dark red fluid was aspirated.
Histological examination of the aspirate failed to reveal
outright pus or microorganisms; acute and chronic inflammatory cells were accompanied by nondescript proteinaceous material. Culture results were negative. No other
surgical interventions were undertaken, and no antibiotics
were administered. A CT scanning study was repeated 3
months later, and revealed resolution of the intracerebral
ring-enhancing lesion. In retrospect, the lesion was thought
to be most consistent with an MCH-induced inflammatory
reaction (that is, a textiloma), given the following: 1) the
documented prior inflammatory reaction to MCH 5 weeks
after initial craniotomy; 2) the classic abscess-mimicking
radiographic appearance of the lesion, as previously described in the MCH literature; and 3) the sterile characteristics of the lesion.

Discussion

Microfibrillar collagen hemostat has been routinely
used for hemostasis during craniotomy at our institution

Fig. 3. Case 3. A: Photomicrograph of the original left occipital lobe underlying lesion reveals FCD Type IIA. Note the large,
dysplastic, disoriented ganglion cells that are located abnormally high in the laminar architecture of the neocortical gray matter.
H & E, original magnification × 200. B: Additional histological section of dysplastic tissue obtained 5 weeks after the initial
craniotomy. Ropy MCH is surrounded by a vague palisade of macrophages, which in turn is engulfed by an eosinophil-rich sea
of mixed inflammation. H & E, original magnification × 400. C: A T1-weighted axial MR image obtained with addition of Gd,
performed 4 months after the initial cortical resection, after persistent wound dehiscence and drainage. The image depicts a left
parietooccipital ring-enhancing lesion that was initially clinically suspected of being an abscess.

388

J Neurosurg: Pediatrics / Volume 6 / October 2010

Postcraniotomy MCH-induced necrotizing granulomatous inflammation
since 1979, and since that time, several hundred procedures have been performed (approximately 100 craniotomies per year). Over this period we identified 3 instances of patients who developed postoperative reactions
to MCH. Clearly, in our experience these foreign-body
reactions are rare. Each patient presented with new or recurrent seizures 5–6 weeks after the initial neurosurgical
procedure that involved MCH administration for hemostasis. On neuroimaging, the lesion in each case displayed
enhancement that either mimicked tumor recurrence
(Case 1) or abscess formation (Cases 2 and 3). However,
clinicopathological workup did not confirm these radiological impressions. In all 3 cases, microscopy revealed
necrotizing granulomatous inflammation directed at the
residual MCH particles within the resection cavity. The
MCH was partly necrotic and surrounded by a palisade
of macrophages. In turn, these foci were engulfed by a
sea of mixed inflammation that generally contained neutrophils, lymphocytes, macrophages, and plasma cells. In
Cases 2 and 3, this inflammatory population was rich in
eosinophils. Notably in Case 3, there was a time discrepancy between histological confirmation of an MCH reaction (5 weeks) and the neuroradiological appearance of a
ring-enhancing lesion (16 weeks). To our knowledge, this
is the first neurosurgical pediatric case series describing
postoperative inflammatory reactions to MCH.
In 2001, Kothbauer et al.11 described the only other
pediatric case series involving intracranial inflammatory
reactions to hemostatic agents. In their report, the authors
detailed the occurrence of foreign-body granulomas in 3
boys, in all of whom central primitive neuroectodermal
tumor was initially diagnosed. These reactions, which
according to the authors all mimicked tumor recurrence,
were identified radiologically 2–7 months after the initial
surgery. One reaction was attributed to gelatin sponges
(Gelfoam), whereas the other 2 were thought to be due
to oxidized cellulose (Surgicel). Notably, the presence of
an offending hemostatic agent was only confirmed in the
case in which gelatin sponges were used. In fact, the authors admit to the use of MCH in the 2 cases in which oxidized cellulose was assumed to have incited the inflammation. Because oxidized cellulose was not histologically
identified in these latter 2 cases, and given our experience
as described here, we would advocate for the possibility
that 2 of Kothbauer et al.’s 3 cases were due to MCHinduced inflammation.
The neurosurgical reports documenting inflammatory
reactions to MCH are infrequent (Table 1). Only Case 1
of Ono et al.,18 reported in 2009, and Case 3 of Gondo et
al.,5 published in 1989, lacked histological confirmation.
Most instances involving inflammatory reactions to MCH
have occurred after resection of a supratentorial neoplasm;
this latter finding may be in part reflective of patient age,
because most of the reported cases have affected adults.
Notably, our Case 3 is the only instance of a nonneoplastic
lesion antedating the MCH reaction.
Generally, loose MCH is first placed in an Aspeto syringe and puffed onto the resection margins. Occasionally the material is flattened, then placed as a small square
onto a specific bleeding point. The applied MCH is then
covered with cotton patties, which are subsequently reJ Neurosurg: Pediatrics / Volume 6 / October 2010

moved. Finally, all excess MCH, aside from that which
is adherent to blood clot, is flushed out with copious irrigation. With the exception of our small case series, this
surgical approach to the use of MCH has successfully
controlled hemorrhage and has not resulted in any significant clinical complications. However, in light these inflammatory reactions at our institution, one could rightly
argue against the routine use of MCH, especially given
that postoperative hemorrhagic complications rarely occur when MCH is not used.4 Unfortunately, our clinicopathological review has failed to reveal a salient explanation for these MCH-induced inflammatory reactions.
Although speculative, an underlying and inherent allergy
to MCH should be considered in these unusual cases.
Support for this hypothesis emanates from a case report
by Kitamura et al.10 published in 1995 that documented a
positive postoperative skin reaction to MCH after its use
during a cholecystectomy.
With respect to timing, all of the reported neurosurgical cases involving inflammatory reactions to MCH
have occurred within 4–8 weeks of the initial operative
procedure (see Table 1). This time window would be consistent with animal experiments that suggest complete
disappearance of MCH from operative sites 84 days after
administration.14 One exceptional instance is our Case 3,
where there was a discrepancy between the histological
documentation of the inflammatory reaction (5 weeks)
and when the ring-enhancing lesion was noted on imaging (16 weeks). As argued above, we believe that the latter imaging picture in Case 3 is indicative of an MCH
reaction, and this would extend the window within which
this reaction may be seen intracranially (that is, from 4–8
weeks to 4–16 weeks). This would be in keeping with
other non-CNS case reports in which MCH reactions occurred several months after initial surgery.1,16
Of the cases in which clinical signs and symptoms
were reported, new or recurrent seizure activity appears
to be the most frequent symptom correlated with the
presence of an MCH reaction (see Table 1). Other common symptoms included weakness (either focal or generalized), emesis, and fever. Given the typical location of
these inflammatory reactions (that is, at the site of prior
resection), it is not surprising that the postoperative clinical picture often mimics that of the original presentation.
Therefore, tumor recurrence is often foremost in the initial clinical differential diagnosis, and is assumed on the
basis of repeat neuroimaging. The latter often uncovers
ring enhancement and edema, raising the possibility of
recurrent tumor, radionecrosis (when clinically appropriate), or abscess.
The MCH-induced inflammatory reaction observed in
each of our 3 cases is similar to other descriptions in the
literature. An eosinophil-rich mixed inflammatory infiltrate, which typically contains multinucleate foreign-body
giant cells, surrounds MCH-centric granulomas. Typically,
a palisade of macrophages is seen immediately adjacent
to the MCH; Ribalta et al.22 have noted a similarity to the
pseudopalisading necrosis that is characteristic of highgrade gliomas. Although the MCH per se may be necrotic
(hence “necrotizing granulomas”), the more viable portions of MCH may take on a ropy/fibrillary connective
389

390

3, M medulloblastoma

Sani et al., 2008

O’Shaughnessy
et al., 2006

case 2

lt frontal

lt parietal

20, M anaplastic astrocytoma

rt frontoparietal

30, M oligodendroglioma frontoparietal

19, M astrocytoma

case 3

glioblastoma

57, F

case 2

Ribalta et al.,
2004
case 1

rt ventricular trigone

rt frontal

4th ventricle & vermis

rt parahippocampal
gyrus

Primary Lesion
Location

22, M oligodendroglioma lt ventricle

22, M meningioma

case 2

Gondo et al.,
1989
case 1

55, M meningioma

case 1

Ono et al., 2009

19, F

Authors & Year

dysembryoplastic
neuroepithelial
tumor

Age
(yrs),
Sex Primary Diagnosis

TABLE 1: Literature review of inflammatory reactions to MCH*

4

4

8

8

8

4–5

3–4

8

5

Clinical
Interval
(wks)†
Neuroimaging Features

NA

NA

NA

NA

NA

ring enhancement & edema in
surrounding parenchyma, &
fluffy intracavitary material

surgical cavity w/ ring enhancement & edema in surrounding
parenchyma

marked ring enhancement

ring enhancement

ring enhancement

recurrent numbness of lt arm & mo- enhancement of surgical cavity
tor weakness
wall, w/ surrounding edema
headache, focal sz involving lt arm faint enhancement around resection cavity w/ adjacent marked
edema, & midline shift w/ enlargement of inferior horn of lat
ventricle

emesis, generalized weakness (es- ring-enhancing 2.5-cm mass w/
pecially in legs), high fevers, gait
significant edema
ataxia, urinary retention, & a
positive L’hermitte sign
1 wk of headache, fever, intermittent heterogeneous enhancement
emesis, bilateral horizontal nystagmus/dysmetria, truncal
ataxia, & mild rt hemiparesis

Clinical Presentation

(continued)

degenerating eosinophilic to amorphous
MCH surrounded by a zone of palisading macrophages; prominent eosinophils; foreign-body type multinucleated
giant cells
mixed MCH-cotton granuloma; dense fibroblastic response & reactive vascular
proliferation in surrounding tissue

no histological confirmation

MCH & necrotic material

MCH & “granulation”

moderate lymphocytic invasion around a
basophilic MCH; lymphocytic/neutrophilic angiitis of vessels w/ wall thickening

no histological confirmation

broad bands of MCH adjacent to degranulating eosinophils; histiocytes, intact
eosinophils, & plasma cells in adjacent
tissue

MCH in approximation w/ foreign-body
type giant cells, lymphocytes, plasma
cells, histiocytes, & eosinophils

Histological Findings

L. Apel-Sarid et al.

J Neurosurg: Pediatrics / Volume 6 / October 2010

5‡
lt occipitoparietal
case 3

5
lt parietal

9, M anaplastic ependymoma
15, F FCD Type IIA

* NA = not applicable; sz = seizure.
† The time from the first craniotomy until the repeat presentation.
‡ The inflammatory reaction was first confirmed at 5 weeks after the initial craniotomy, but the ring-enhancing lesion on MR imaging was identified at 16 weeks after initial craniotomy.

medial enhancement & mass ef- necrotizing granulomatous inflammation;
rare eosinophils
fect in medial aspect of prior
surgical bed, plus expansion of
subarachnoid disease
rt-sided focal motor szs leading to
ring-enhancing lesion & surround- necrotizing granulomatous inflammation;
progressive weakness
ing edema
rich in eosinophils
poor wound healing & drainage; szs ring-enhancing lesion & surround- necrotizing granulomatous inflammation;
ing edema
rich in eosinophils
typical sz auras returned, plus 2
generalized szs
6
rt temporal
10, F ganglioglioma

case 2

Authors & Year

present study
case 1

Clinical
Interval
(wks)†
Primary Lesion
Location
Age
(yrs),
Sex Primary Diagnosis

TABLE 1: Literature review of inflammatory reactions to MCH* (continued)

Clinical Presentation

Neuroimaging Features

Histological Findings

Postcraniotomy MCH-induced necrotizing granulomatous inflammation

J Neurosurg: Pediatrics / Volume 6 / October 2010

tissue appearance. On H & E staining, MCH is typically
eosinophilic in color, but may be amphophilic to basophilic in appearance; this variability in hue may be related
to degeneration, because MCH is eventually absorbed by
the host. Moreover, in those cases in which electron microscopy was performed, the collagenous constitution of
MCH was confirmed by revealing the typical ultrastructural banding pattern expected of collagen.16,22 Both MCHcontaining textilomas reported by Ribalta et al.22 were described as inciting a striking eosinophilic infiltrate that was
claimed to be unique to this hemostatic agent. Our Case 1
was somewhat unusual in that eosinophils, although present, were somewhat infrequent. However, on review of the
literature, some cases of MCH-induced inflammation may
not display conspicuous eosinophils (see Ono et al., Case
2);18 accordingly, we would argue that an eosinophilic infiltrate, although common, may not be a universal feature of
MCH-induced inflammation. As is characteristic of MCHinduced inflammation, microorganisms were not identified
by microscopy (or clinically).
Awareness of the possibility of postoperative inflammatory reactions to MCH and the typical clinical presentation are key to diagnosis. Neuroimaging is essential to
the workup of these cases, and the differential diagnosis
raised usually includes recurrent tumor or abscess. Unfortunately, current MR imaging sequences do not assist in
distinguishing MCH-induced inflammation from recurrent
tumor or abscess. Likewise, the imaging results from our
Case 3 did not reveal a pathognomonic or distinguishing
MR appearance with respect to MCH. Martins et al.12 also
described similar nonspecific MR imaging characteristics
with respect to an intracranial gossypiboma, which in their
case was due to surgical gauze. Nonetheless, in the typical clinical context, the suggestion of a recurrent tumor or
abscess-like lesion based on MR imaging findings may be
enough to trigger the correct differential diagnosis of a hemostatic agent–induced inflammatory reaction. Because
these MCH-induced lesions inherently regress with time,
we would recommend a conservative approach to management. The utility of such an approach is borne out by our
experience in Case 3, in which the suspected abscess regressed after only minimal intervention (that is, aspiration
without resection). A reasonable approach would include a
routine infectious disease workup (including detailed history and physical examination, complete blood count with
differential, cultures, and prophylactic antibiotics) and, if
necessary, biopsy. Although unlikely to be seen, peripheral
eosinophilia may suggest the possibility of an allergic-type
response and a potential reaction to MCH.10 Moreover, if a
reaction to MCH is suspected, some clinicians have sought
out skin testing and confirmed an allergic response.10 It is
conceivable that such testing could be performed preoperatively in patients thought to be especially at risk for such a
reaction.

Conclusions

We have presented a pediatric neurosurgical case series wherein an inflammatory reaction to MCH developed
5–6 weeks after initial craniotomy. The presentation of
all patients included new or recurrent seizures. Neuro391

L. Apel-Sarid et al.
imaging suggested abscess in Cases 2 and 3, and tumor
recurrence in Case 1. Microscopy revealed necrotizing
granulomatous inflammation in all cases, and in keeping
with the literature, the areas of reaction in Cases 2 and 3
contained numerous eosinophils. These new cases add to
a limited neurosurgical literature regarding adverse inflammatory MCH reactions. Clinical awareness of this
entity and consideration of a conservative approach to
treatment are key to the appropriate management of these
cases.
Disclosure
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this
paper.
Author contributions to the study and manuscript preparation
include the following. Conception and design: Dunham. Acquisition
of data: all authors. Analysis and interpretation of data: all authors.
Drafting the article: Dunham, Apel-Sarid, Cochrane, Steinbok.
Critically revising the article: Dunham. Reviewed final version
of the manuscript and approved it for submission: all authors.
Administrative/technical/material support: Dunham, Apel-Sarid.
Study supervision: Dunham.
Acknowledgment
The authors thank Mr. Tony Borodovsky for his technical assistance during the preparation of this manuscript.
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Manuscript submitted June 2, 2010.
Accepted August 6, 2010.
This work was presented at the American Association of Neu­
ro­pathologists’ Annual Meeting in Philadelphia, Pennsylvania, on
June 11, 2010.
Address correspondence to: Christopher Dunham, M.D.,
F.R.C.P.C., Division of Anatomic Pathology, Children’s and Women’s Health Centre of British Columbia, University of British Co­­
lum­bia, 4500 Oak Street, Vancouver, British Columbia, V6H 3N1.
email: cdunham@cw.bc.ca.

J Neurosurg: Pediatrics / Volume 6 / October 2010