Chondrosarcoma
of the Hand in Ollier¡¯s Disease: Case Report and Novel Approach for Surgical
Treatment
Mattia Pivato, Antonio Berizzi, Francesca
Simonato, Rocco Cappellesso, Stefania Vio, Leonardo Salviati, Doriano Zambon,
Giovanni Borso, Ambrogio Fassina
Mattia Pivato, Francesca Simonato, Rocco Cappellesso, Ambrogio Fassina, Department of
Medicine, Surgical Pathology & Cytopathology Unit; University of Padua;
Padua (PD), Italy
Antonio Berizzi, Doriano Zambon, Department of Surgical Oncology and
Gastroenterological Sciences, Orthopaedic Surgery Unit; University of Padua;
Padua (PD), Italy
Stefania Vio, Department of
Medicine, Radiology Unit; University of Padua; Padua (PD), Italy
Leonardo Salviati, Department of
Child and woman health care, Genetic
Unit; University of Padua; Padua (PD), Italy
Giovanni Borso, Department of
Neurosciences, Plastic Surgery Unit; University of Padua; Padua (PD), Italy
Correspondence to: Ambrogio Fassina, MD, Department of Medicine; Surgical Pathology &
Cytopathology Unit; University of Padua; Via Aristide Gabelli, 61; 35121, Padua
(PD), ITALY.
Email: ambrogio.fassina@unipd.it
Telephone:
+39-049-821-8999 Fax: +39-049-827-3782
Received: July 14, 2013
Revised: September 29, 2013
Accepted: October 6, 2013
Published online: April 18,
2014
ABSTRACT
Enchondromas are frequent benign cartilaginous
tumors that commonly arise in the hand. Ollier¡¯s disease is defined by the
presence of multiple enchondromas. Malignant transformation of an enchondroma
is very rare in the hand. We present the case of a 19 years old girl affected
by Ollier¡¯s disease, with a rapidly growing enchondroma involving the middle
finger with severe bone destruction and soft tissues infiltration. MRI of the
hand demonstrated the presence of low signals in T1-weighted sequences and finely
uneven medium-high intensity signal in T2-weighted sequences. Histology
demonstrated a grade 1 chondrosarcoma, which was treated by a successful
conservative surgical approach, with a strict follow-up due to the risk of
possible recurrences.
© 2014 ACT. All rights reserved.
Key words: Chondrosarcoma;
Hand cancer; Ollier¡¯s disease
Pivato M, Berizzi A, Simonato F, Cappellesso R, Vio S, Salviati L,
Zambon D, Borso G, Fassina A. Chondrosarcoma of the Hand in Ollier¡¯s Disease:
Case Report and Novel Approach for Surgical Treatment. Journal of tumor 2014;
2(4): 125-128 Available from: URL:
http://www.ghrnet.org/index.php/JT/article/view/653
INTRODUCTION
Ollier¡¯s disease, also called multiple
enchondromatosis, is a non-hereditary rare syndrome characterized by the
presence of multiple enchondromas. Ollier described the disease in 1898[1],
and, afterwards, several reports detailed the clinical and pathological
features. Although a common mutation of isocitrate dehydrogenase 1 (IDH1) has
been reported[3], to date, it is not completely clarified whether
this syndrome is due to a single mutation in this gene or if it is caused by a
combination of mutations (somatic and/or germ-line) involving several genes[2].
Enchondromas are benign cartilage tumors characteristically arising in
metaphysis, diaphysis, and, less frequently, epiphysis of long bones[4].
Epiphyseal enchondromas severely alter bone growth, deforming shape and length[4].
Patients usually present asymmetric distribution and extreme variability in
terms of size, number, evolution, and localization of enchondromas[2].
However, in most cases enchondromas are predominantly unilateral and benign[4].
The prevalence of Ollier¡¯s syndrome is estimated to be approximately
1/100000, the peak incidence is in the first decade of life, and the most
frequent location is at the extremities[2]. Two clinical subtypes of
the disease are described: enchondromatosis affecting mostly males, transmitted
in a Mendelian fashion, and Ollier disease affecting mostly females, with a
unilateral growth pattern and without familiarity.
Enchondromas are associated with a number of complications, such as
spontaneous fractures, deformities, bone growth deficit, compression of
vascular or nervous structures, and malignant transformation to chondrosarcoma
(CS).
Although the hand, particularly metacarpals and phalanges, is one of the
most common site for the enchondroma development, malignant transformation is
extremely rare and, so far, only 12 cases have been reported[4-9].
In this report we
present the case of a 19 years old female affected by Ollier¡¯s disease
complicated by development of hand CS, with the genetic assessment of the
lesion and review of the literature.
CASE REPORT
A 19 years old Caucasian girl affected by Ollier¡¯s disease referred to
our department for an important dysmetria between the two femurs, and for the
rapid growth in the last month of an enchondroma (5¡Á3 cm) involving
the first phalange of the third finger (Figure 1 A:
Preoperative presentation of the patient¡¯s right hand. Note the biggest mass at
the third ray and the multiple enchondromas involving the second and the fifth
finger; B: Intraoperative image of the neoplasm involving the third ray of the
right hand).
The mass was
firm and the skin above the lesion was thin, stretched, and ulcerated at the
volar side, with no vascular or nervous deficit. In the previous days, the
patient reported severe pain and a yellowish fluid leakage from the ulceration.
Standard radiographs demonstrated severe bone destruction and
infiltration of soft tissue. In particular, the lesion showed a thinning of the
upper cortex that exceeded the 2/3 of the total cortical thickness, with focal
complete cortical breaks. However, only moderate periosteal reaction was seen.
The persistence of calcifications gave evidence of a typical form of CS (the
major axis of the mass was 5.7 cm).
MRI detected
the presence of multiple foci with low signal in T1-weighted sequences and
finely uneven medium-high intensity signal in T2-weighted sequences, with
deformations of the proximal and intermediate phalanges of the second and the
third finger, the proximal phalanx of the fifth finger, the first metacarpal
and the distal portion of the second and the fifth finger. These structures
were deformed by the expansive lesions, characterized by an intrinsic-extrinsic
growth pattern and homogeneous MR signal. The largest mass was located at the
volar side of the first phalanx of the third finger, with oval morphology and
diameters of 5.2¡Á4.2¡Á3.4 cm, displacing the radial side of the flexor tendon of
the middle finger (Figure 2 A and B: Oblique and
Frontal XR of the right hand at presentation: note wide tissue component and
corresponding cortical interruption of the main lesion at the third finger. C:
coronal SE T2w sequences of the
main lesion protruding at the ulnar side of proximal and middle phalanges of
the third finger D: axial TSE T1w sequence of the main lesion.).
A total body 99Tc
scintigraphy demonstrated increased uptake in the third, the fourth, and the
fifth finger of the right hand, various ribs, the right sacro-iliac
synchondrosis, the whole right femur, the proximal part of the right tibia and
the second and third fingers of the left foot.
Incisional
biopsy specimens appeared pearly white and, at light microscopy, the lesion
showed a nodular growth pattern with vascular and stromal internodular septa,
with bone erosion and discontinuity of the cortical bone due to focal
resorption. Tumor cells were irregularly thickened and characterized by small
central hyperchromatic nuclei, clear cytoplasm with ill-defined margins, and
separated by abundant fundamental substance, with the final diagnosis of low
grade CS in multiple enchondromatosis Total body CT did not reveal parenchymal
or lymphatic metastases (Figure 3 A: The tumor showed a
nodular growth pattern with vascular and stromal internodular septa. B: Tumor
cells were irregularly thickened and characterized by small central
hyperchromatic nuclei, clear cytoplasm with ill-defined margins, and separated
by abundant fundamental substance. Mitotic index was low (2¡Á10 HPF) C and D:
Strong tendency to bone erosion and discontinuity of the cortical bone due to
focal resorption were also present. Hematoxylin and eosin stain. Original
magnifications 40¡Á, 100¡Á, and 200¡Á.).
The young age
of the patient, the absence of metastases, and the favorable anatomical
position, addressed the surgical choice to an in toto margin-free surgery of
the tumor, with reconstruction of the extensor tendon of the third finger. After
removal, tumor-free margins were histologically confirmed. No bone autograph
was need for the reconstruction of the third finger (Figure 4 A: Postoperative presentation of the patient¡¯s right hand B and C:
Oblique and Frontal XR of the right hand after surgical excision. Note the wide
thinning and destruction of the cortex. D: Coronal SE T1 w IR: after surgery;
note the complete removal of the cartilaginous mass on the ulnar side of middle
and proximal phalanges of the third finger.).
During surgery
we also carried out a lengthening of the right femur, with excellent aesthetic
and functional results. No radiotherapy or chemotherapy were administered after
surgery.
We screened
this patient by polymerase chain reaction (PCR) on genomic DNA extracted from
the formalin-fixed paraffin-embedded specimen of CS. The sequencing analysis of
IDH1 revealed a R132C mutation (CGT > TGT, codon 132) (Figure 5 IDH1 sequencing analysis of CS revealed a mutation involving codon 132.).
DISCUSSION
Ollier¡¯s disease is a very rare syndrome: its prevalence is estimated
to be 1:100000[2], being 10 times less frequent than a solitary
enchondroma. This syndrome is defined by the presence of multiple unilateral
enchondromas. As the most frequent benign intraosseous cartilaginous tumors,
enchondromas develop from normal cartilage and enlarge during normal bone
growth. Clinical complications associated with multiple enchondromatosis are
bone deformities, dysmetria caused by epiphyses involvement, and malignant
transformation.
Malignant CS
occurs in about 25% of the patients affected by Ollier¡¯s disease by the age of
40 years. As reported in literature, while distal femur, proximal tibia,
fibula, and pelvis are common sites of malignant transformation, hand CS in
multiple enchondromatosis are anecdotal. Indeed, among the 121 cases of CS reported
in the Mayo Clinic survey, no one involved the hand[4]. So far, only
12 cases of hand malignant involvement in Ollier¡¯s disease have been reported,
mostly classified as low-grade CS (5-7) (Table 1
Previously reported cases of chondrosarcoma of the hand secondary to Ollier
disease.).
Differential
diagnosis between ¡°active¡± chondroma and grade 1 CS is not possible with
histology alone, although hypercellularity, myxoid change, soft tissue
infiltration, necrosis, trabecular disruption, permeation, and double-nucleated
cells suggest malignant transformation.
The diagnosis
of low-grade CS can be establish only by integrating clinical, radiographical,
and histological features. Classical signs and symptoms of malignant
transformation are acute pain, rapid size enlargement, ill-defined margins,
cortical bone erosion, bone resorption, and soft tissues invasion. Indeed, as
reported by Ryzewicz and colleagues, the main radiological characteristics of
chondrosarcoma are the combination of major bone destruction, presence of
intralesional calcification, and a periosteal reaction. However, the most
suggestive radiographic finding for a high grade lesion is precisely the
destruction of the cortical bone. More frequently, especially in tumors
characterized by a low degree of malignancy, the cortex does not present a
full-thickness lesion but is irregularly thinned and only focally interrupted[10].
Endo-osteum
scalloping is considered a phenomenon due to the host¡¯s effort to contain the
tumor. Endo-osteum scalloping radiographically involving more than two-thirds
of the total cortical thickness with a length that is not less than two-thirds
of the tumor, has been reported by Murphey et al[11] to occur
up to 75% of chondrosarcomas, but in less than 10% of enchondromas. Another
important sign of malignancy is the periosteal reaction. Even this is an
attempt by the body to limit tumor progression outside of the medullary canal.
As regards
calcifications, Murphey et al found that there is a relationship between the
density of calcifications and the degree of malignancy of a CS. In fact, the
lower-grade lesions tend to be more densely calcified on radiographs compared
to high-grade lesions[11], which have a greater degree of anaplasia
and less capacity of calcium deposition.
The last
critical parameter that directs us to the diagnosis of malignancy is tumor
size. Geirnaerdt and colleagues stated that a major axis of greater than 5 cm
was the best predictor of malignancy in tumors involving the axial skeleton. The
same judgment has been validated also for tumors of the cartilage of the foot. In
the current case the cut-off was different. Indeed, at this level the mean
diameter of enchondromas was 2.7 cm, while for chondrosarcoma was 5.1 cm[12].
The gold-standard in CS treatment is represented by surgery, due to
radiotherapy and chemotherapy failure. Exner et al stated that phalanx CS are
locally aggressive, but compared to CS of other sites, they almost never
metastasize[13]. Based on the excellent survival data reported from
35 cases, Bovee and colleagues assessed that curettage followed by adequate
follow-up is a valid approach when technically feasible, although recurrence
risk can not be excluded[14]. Such technique is recommended in those
cases in which amputation would cause important disability. Also Dhalin and
Salvador declared that curettage, if adequately executed with tumor-free
margins, should be considered as curative, even if rarely associated with
recurrence[15].
Contrary to the previous cases reported in table 1, we did not perform
a ray amputation. The decision was taken in order to reach an appropriate
tumor-free margin debulking of the neoplasm considering the relative young age
of the patient.
The patient
harbored a mutation of IDH1, which was reported to impair the conversion of
isocitrate to ¦Á-ketoglutarate (¦Á-KG)[15]. Such mutation has been demonstrated to affect
cellular pathways controlling the epigenetic status of tumor cells in glioma
and acute myeloid leukemia. In particular, the R132 mutation of IDH1 produces a
cancer-related accumulation of 2-hydroxyglutarate[3]. To date, no
literature data are available about the diagnostic use of this mutation to
differentiate enchondroma from chondrosarcoma.
Our patient did
not show recurrence or distant metastases at 18 months follow-up after surgery.
She is now pain free and shows only modest strength deficit in pinching and
grasping. She is able to write, study, and make housewife-related tasks
independently. She showed a high grade of satisfaction for the good aesthetic
and functional results achieved.
A lifelong, three-months interval follow-up has been planned, to check
for local recurrence, other enchondromas malignant transformations, and
occurrence of metastasis. If any of these complications would appear,
amputation of the ray will be mandatory.
List of
abbreviations
MRI: magnetic resonance imaging; 99Tc: technetium 99; PCR:
polymerase chain reaction; IDH1: isocitrate dehydrogenase 1; CT: computed
tomography; ¦Á-KG: ¦Á-ketoglutarate;
CS: chondrosarcoma.
ACKNOWLEDGMENTS
This work was supported by a grant from the University of Padua
(Progetti di Ricerca di Ateneo 2010 and 2011), by the Veneto Region (Ricerca
Finalizzata 2006), and by the Cariparo Foundation Excellence-grant.
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Peer reviewer: Jeffrey Yao, MD, Associate Professor of
Orthopaedic Surgery and Surgery, Robert A. Chase Hand & Upper Limb Center,
Stanford University Medical Center, 450 Broadway Street, Suite C442, Redwood
City, CA 94063.
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