Benign Malformative Lesion of the Skull: Hamartoma with Ectopic Elements or Choristoma?
Ece MERAM1, Hakan KARABAĞLI2, Christine GLASTONBURY3, Tarik TİHAN1, Pınar KARABAĞLI4
1Department of Pathology, UCSF, SAN FRANCISCO, USA
2Department of Neurosurgery, Selçuk University Faculty of Medicine, KONYA, TURKEY
3Department of Radiology, UCSF, SAN FRANCISCO, USA
4Department of Pathology, Selçuk University Faculty of Medicine, KONYA, TURKEY
Keywords: Hamartoma, Choristoma, Ectopic tissue, Heterotopic tissue, Skull
Hamartoma and choristoma are terms that describe non-neoplastic,
mass-forming malformative lesions. Although each lesion has a
different composition, they have been used interchangeably in many
reports, especially for malformative lesions containing ectopic or
heterologous elements. We report a three month-old girl who was
brought to the clinic with a mass lesion at the posterior fontanel,
composed of predominantly osteo-cartilaginous tissue admixed
with skeletal muscle, peripheral nerve tissue, and ganglion. The
mass was resected completely. The composition of this benign lesion
with ectopic elements was consistent with an osteo-cartilaginous
hamartoma. We discuss the biological and clinical aspects such
malformative lesions within the skull to highlight the inconsistencies
of the nomenclature used in the literature.
Malformations of the skull and surrounding tissues are a
spectrum of diseases ranging from massive loss of tissue,
as in anencephaly, to a mass-forming lesion such as an
arteriovenous malformation. Two terms that are used to
define this group of malformative lesions are hamartoma
and choristoma. Hamartoma (hamartia [greek]=failure) is
an overgrowth of mature tissues that normally occur in an
expected area or organ, but with disorganization and often
with one element predominating1
. Choristoma (choristos
[greek]=separable, separated), on the other hand, is a mass
of tissue histologically normal for an organ or part of the
body other than the one in which it is located1
Choristoma is considered as a mass-forming, irregular, and
LJ100. Many reports use choristoma
and heterotopia interchangeably2
Hamartomas and choristomas can occur anywhere in the
body, and there have been many reports of such lesions in the skull, involving either the calvarium or the scalp,
or both. Some examples include fibrous hamartoma of
infancy3, neurocristic hamartoma4, folliculosebaceous
cystic hamartoma5, and meningothelial hamartoma6.
The lesions reported under these names have histological
features compatible with the definition of hamartoma,
yet many harbor heterotopic elements7,8. On the other
hand, neuroglial choristomas2,9, cutaneous meningeal
heterotopias10 have been described in the skull. The latter
group of lesions is more compatible with the definition of
choristoma, but the extent of heterologous elements in each
may vary substantially to cast doubt on the distinction
between a hamartoma and choristoma.
We present this unique case of a three-month old patient
with an osteo-cartilaginous hamartoma occurring in the
posterior fontanel admixed with skeletal muscle, peripheral
nerve, and ganglion.
A three-month old girl was brought to the clinic when the
mother noticed a bulging lesion on the posterior aspect
of the skull. It was not clear how long the mass had been
present. Physical examination was unremarkable except for
a firm mass eroding the scalp over the posterior fontanel,
with a distinct redness on the skin (Figure 1
tomography of head showed a heterogeneously bright
mass located at the inferior aspect of the posterior fontanel
with areas having a bone-like radiodensity. T1-weighted
magnetic resonance imaging demonstrated that the lesion
was extra-axial, and involved the calvarium and the scalp.
). Intraoperatively, the mass was found to
be located within the posterior fontanel and adjacent to
superior sagittal sinus and the right parietal bone. The lesion
had eroded the skull locally, reaching the subcutaneous
tissue of the scalp. Inferiorly, the mass was attached to the
dura mater but did not penetrate this structure. A grosstotal
resection was achieved without disrupting the dura.
Excised mass consisted of a single, irregular, firm bony and
fibrous tissue measuring 2.5x2.3x1.5 cm. Serial sections of
the mass demonstrated an admixture of dense, pearly white
cartilage tissue with bone and dark brown bone marrow
elements arranged in a haphazard fashion (Figure 3
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|Figure 1: Preoperative external view of the lesion showed
erythema and erosion of the scalp as well as swelling at the
expected location of the occipital fontanel.
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|Figure 2: A,B) Sagittal and axial T1-weighted MR
images demonstrate a heterogeneous extra-axial mass,
involving the calvarium and scalp soft tissues, that
lies just to the right of midline overlying the parietooccipital
sulcus, C) Axial T2 MR shows the mass to
be abutting and displacing parietal cortex, and there
is subtle superficial T1 and T2 hyperintensity which
may be due to the presence of fat (arrow, in B, C). The
deeper solid aspect of the lesion enhances on postgadolinium
T1 image D), as does the superior sagittal
sinus that appears displaced to the deep aspect of the
lesion (arrow, D). E) Sagittal MRV image demonstrates
indentation of the patent superior sagittal sinus by the
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|Figure 3: Macroscopic appearance of the surgical resection
material sectioned along the long axis demonstrated
predominantly bone and bone marrow admixed with dense,
white cartilaginous tissue arranged in a haphazard fashion.
The patient returned for a clinical visit 7 months following
the surgical procedure and radiological and clinical studies
demonstrated no evidence of disease.
Histopathological Findings: On histological sections,
the lesion was well-circumscribed and composed
predominantly of osseous tissue with mature bone marrow elements (Figure 4A). Bone marrow was hyperplastic and
showed tri-lineage hematopoiesis. In addition, there were
foci of peripheral nerve (Figure 4B), ganglion (Figüre 4D), and mature cartilage within the mass. The peripheral
nerve and ganglion tissues were present within the osseous
component, trapped among cartilaginous and osseous
elements. The lesion also contained skeletal muscle. In
addition, there was immature adipose tissue with dense
fibrous septa at the periphery, which was considered to
be normal subcutaneous adipose tissue (Figure 4E). The
osseous component had well-formed, unremarkable bony
lamellae as well as abnormal, woven bone and foci of irregular
maturation zones. Both the peripheral nerve tissue and the
ganglion within the osseous component demonstrated
strong positive staining with the antibodies against S-100
protein and Glial fibrillary acidic protein (GFAP) (Figure
4B-C). No glial elements were identified in the lesion
using GFAP and Olig-2 stains. An immunohistochemical
stain for Ki-67 (MIB1) showed no positive cells within the
osseous, peripheral nerve or ganglion tissue, but there were
abundant positive nuclei within the bone marrow.
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|Figure 4: Histological findings of the mass lesion A) Low power
magnification of the mass predominantly composed of bone,
bone marrow, and cartilage (H&E; x40). B) Peripheral nerve tissue
found within the osteo-cartilaginous lesion (H&E; x200), and
C) the S100 protein stains showing strong positive staining in the
nervous tissue (S-100; x200). D) Ectopic ganglion tissue within
the lesion (H&E; x100). E) Adipose tissue and skeletal muscle the
periphery of the mass (H&E; x100).
Presence of certain features in the aforementioned lesion,
such as mature tissue from two germ layers, ectopic
neuronal elements and overgrowth of indigenous tissues
were important in identifying this mass-forming skull
lesion as a malformative process. Thus, the terms teratoma,
choristoma or hamartoma were considered in the diagnosis
of this lesion.
The lesion showed elements arising from two different
germ layers (mesodermal and ectodermal), and it did
not have any immature components. The possibility of a
benign mature teratoma was entertained since there are
ample reports of benign mature teratomas or the so-called
dermoid cysts, found along the suture lines of cranial
bones11. Mature teratomas may show no or low mitotic
index and are mass forming lesions, and may demonstrate
heterologous elements such as skeletal muscle, cartilage or
neural tissue. In addition, some cranial teratomas can have
mature bone and bone marrow. In case the term teratoma
is used to characterize a hamartomatous lesion, it may be
possible to consider this lesion in this category. However, the
skull based teratomas or dermoid cysts are predominantly
composed of epidermal, dermal and adnexal structures
along with keratin, and they are not predominantly
composed of osteo-cartilaginous elements. Thus, our case is
not a dermoid cyst. Recent studies also suggested that some
lesions previously reported as teratomas are non-clonal
lesions, and are better classified as hamartoma12. If we
consider the usage of the term “teratoma” to represent a
neoplastic growth, then our lesion would not be considered
Choristoma could be considered in the differential
diagnosis of this lesion because of the presence of ectopic
or heterotopic non-neoplastic tissues including skeletal
muscle, peripheral nerve and ganglion. One does not expect
to identify skeletal muscle in this location even though the
tissue may be a remnant from the stage of skeletal muscle
development and migration in the lower occipital region.
The peripheral nerve tissue and ganglion were presumed to
be heterotopic tissue since they were within the mass lesion
amidst the osseous and cartilaginous elements, and not in
the surrounding soft tissue. However, the peripheral nervous
tissue could be considered not ectopic in this region, since
peripheral nerves can be found in the scalp, dura mater or
the periosteum. The ganglion found in this lesion should
be considered truly ectopic. The closest extra-axial ganglion
tissue to the lesion would be the base of the skull. Therefore,
presence of this heterotopic tissue raises the possibility of
a choristoma. Since aberrant rest of cells can be seen due
to directional disturbance of precursor tissue migration
rather than from implantation of foreign cells. Yet, this
process is still considered a choristoma. Differentiation of
neural crest cells and their development to bone, cartilage,
muscle, nerve and ganglion in the head and neck region13,14, make it plausible to think that such a lesion can be
formed through separation of a group of neural crest cells during their migration. Therefore, misplacement of cells to
be differentiated into various tissues can be the underlying
the pathophysiology of such a malformative lesion.
Despite the presence of small rests of ectopic tissues, the
overwhelming majority of the mass was mature bone,
cartilage and marrow that are native to the site. In addition,
the disorganized but mature tissue composition and nonneoplastic
histological features favors a hamartoma. Even
though some lesions in the oropharyngeal region were
reported as “osteo-cartilaginous choristoma”15,16, the
greatest portion of the abnormal tissue was not ectopic
to the site, and favored a predominantly hamartomatous
process with smaller ectopic elements. In contrast to this
report, Suster and Rosai have reported a lesion that they
defined as a scalp hamartoma with ectopic meningothelial
The uncertainty on the variation in the concepts and their
usage in the literature may be confusing, yet the lesion
in our patient was classified as a hamartoma since it was
predominantly a disorganized overgrowth of native osteocartilaginous
tissue. However, one could name this lesion
a “choristoma”, since heterotopic elements were found in
the lesion. In addition, many studies in the literature have
failed to provide a distinction between a choristoma and a
hamartoma with ectopia, and it is not really clear whether
there are any. This uncertainty results in the situation that
the same lesion could be reported as hamartoma by some,
choristoma by others, and yet, as both in other studies17. In fact, benign Triton tumors are often named as both
neuromuscular hamartoma and neuromuscular choristoma
in the same text18. In other studies, it is possible to see
the lesion described as a hamartoma19, or choristoma20, despite the same histological appearance.
There is little doubt that the classification of a particular
malformative lesion can change based on the authors'
interpretation of the terminology. While the natural
biology of both lesions are benign, and the name does not
significantly impact the patient's outcome, the usage of
these terms interchangeably and without concern to their
actual composition creates a diagnostic and classification
problem. Yet, the distinction of these two terms might be
significant in search of their underlying pathophysiology
as well as in recognizing syndromic patients in whom
lesions have originally been described as either one or
other. This confusion of terminology can also cause
patients to second-guess the accuracy and the reliability of
pathological diagnoses. Finally, regardless of the nature of
the lesions, accurate and scientific classification of diseases
is paramount to discovery of disease mechanisms.
The correct classification of a malformative lesion becomes
even more indecisive in the presence of heterotopic element
within what is essentially a hamartomatous formation. We are not quite certain that the extent of heterologous elements
in a particular malformative lesion would change the nature
or the name of the pathological process. Thus, it may be
worthwhile to consider what is meant by hamartoma with ectopic/heterotopic elements versus a mere choristoma.
Our case report of a predominantly osteo-cartilaginous
mass with skeletal muscle, peripheral nerve and ganglion is
aimed at demonstrating the difficulties in classification and nomenclature of these benign lesions, most probably due to
the fact that it has little, if any impact in patients' prognoses.
Yet such simplification in the usage of terminology and
confusion of terms can render the diagnosis suspect,
overlook a particular mechanism or etiology, and make the
study of such lesions quite cumbersome. Better recognition
of these pathological processes, their pathogenesis, and
accurate definition and use of terminology should help
clarify the confusion in the literature.
In conclusion, hamartoma and choristoma are commonly
used terms in medicine, yet certain lesions may be difficult
to define precisely as either one. Accordingly, categorization
of lesions as either choristoma or hamartoma is not always
straightforward, and some have even used these terms
interchangeably. Furthermore, it is not clear whether a
lesion should be called a hamartoma if it includes ectopic
(or heterotopic) tissue, since ectopic tissue has been
typically associated with the definition of choristoma. We
present this ambiguity in literature and a case of an osteocartilaginous
hamartoma in the skull of a three month-old
girl with ectopic elements of skeletal muscle, peripheral
nerve and ganglion.
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