Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report

Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case ReportMaffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report
Swathi Velagapudi1 • Saad M. Alshammari2 • Suresh Velagapudi2
Received: 19 June 2018 / Accepted: 23 July 2018 / Published online: 10 August 2018
Association of Otolaryngologists of India 2018
Abstract Maffucci syndrome is an extremely rare sporadic
disease, characterized by multiple enchondromas and
associated with multiple hemangiomas and/or lymphan-
giomas. First case was reported in 1881, and fewer than
200 case have been reported to date. Potential sarcomatous
malignant transformation have been noticed in previous
cases. This report describes the case of 21 years-old male
complain of right sided nasal obstruction for 10 months,
and right sided aural fullness. Examination revealed mul-
tiple asymptomatic nodules in both hands since childhood,
that have not been investigated and a large nasopharyngeal
mass. Computed tomography, showed a 36 mm in 30 mm
diameter lesion extending from the inferior aspect of the
clivus and basisphenoid into the nasopharynx, which did
not seems to be highly vascular with angiogram. Incidental
radiological findings of multiple bubbly lytic bony lesions.
Endoscopic sinus surgery and clival lesion excision was
performed. Pathology confirmed diagnosis of clival
enchondroma with clinical and radiological features con-
sistent with Maffucci syndrome. Clear etiology have not
been established yet. Mutations in gene encoding
parathyroid hormone receptor 1 found in 10% of
enchondromatosis. Mutations in gene encoding isocitrate
dehydrogenase 1 and 2 (IDH 1&2) occur in some
enchondromas and spindle cell hemangiomas. Maffucci
syndrome usually presents with asymmetrical distribution
of multiple enchondromas. Malignant transformation is the
most concerning potential sequel. Many studies have
shown sarcomatous degeneration of enchondromas to
chondrosarcomas in average of 25% of cases. Patient
counselling and education are crucial in the management.
Surgical excision usually for symptomatic patients and
suspicious lesions. Nevertheless, all patient of Maffucci
syndrome will require a long term follow up and surveil-
lance for the lifelong risk of malignant transformation.
Maffucci syndrome diagnosis based on clinical presenta-
tion, radiological and histopathological findings. Surgical
excision offered for symptomatic patients and for suspi-
cious lesions. Lifelong risk of sarcomatous malignant
transformation necessitate a long term surveillance.
Keywords Maffucci syndrome Enchondromas Chondrosacomas Nasopharynx
Introduction
Maffucci syndrome is an extremely rare sporadic disease,
described for the first time in 1881. Fewer than 200 cases
have been reported in the literature. This disease recog-
nized by multiple enchondromas, a benign cartilaginous
tumor found at intramedullary bone near growth plate of
long bones, and associated with multiple hemangiomas
and/or lymphangiomas [1–5]. Malignant transformation of
these lesions into chondrosarcoma, fibrosarcoma, heman-
giosarcoma, hemangioendothelioma and lymphangiosar-
& Swathi Velagapudi
Andhra Pradesh, India
Communication Sciences, King Faisal Specialist Hospital
and Research Center, Riyadh, Saudi Arabia
123
dehydrogenase 1 (IDH1) or IDH2 gene mutations in
enchondromas and spindle cell hemangiomas [6]. Patients
are usually asymptomatic, although they might present
with nodules or masses, which in some cases discovered
incidentally during the physical examination or radiologi-
cal investigations. The long term follow-up and observa-
tion of these nodules are crucial, due to potential malignant
transformation, skeletal deformities and pathological
fractures.
patient with Maffucci syndrome like presentation with a
vascular, large clival mass in the nasopharynx. Diagnosis
of Maffucci syndrome with clival enchondroma had been
established.
Case Presentation
A 21 years old male, from the northern region of Saudi
Arabia, referred to otolaryngology, head and neck surgery
department of King Faisal Specialist Hospital and Research
Center in Riyadh with a complaint of nasal obstruction
affecting the right side more than the left, with a progres-
sive course for around 10 months prior to presentation. He
gave a history of severe epistaxis, controlled with posterior
packing which necessitated intensive care unit admission in
a local hospital, 6 months prior to the referral, where he
had a fiberoptic nasopharyngoscopy and computed
tomography that showed a nasopharyngeal mass. Referred
to us with a differential diagnosis of juvenile nasopharyn-
geal angiofibroma, nasopharyngeal carcinoma, Thornwaldt
cyst and minor salivary gland neoplasm.
The patient’s main complaint was nasal obstruction,
breathing difficulties during sleep, right sided aural fullness
and hearing loss. No symptoms of rhinorrhea, sneezing,
itching, anosmia/hyposmia, otorrhea, tinnitus, vertigo,
facial numbness/weakness, dysphonia, dysphagia, recent
trauma or laryngopharyngeal reflux was given. Patient did
not have any chronic medical illnesses such as diabetes
mellitus or bronchial asthma. He reported multiple
asymptomatic nodules in both hands since childhood, that
have not been investigated (Fig. 1). Patient was not on any
medications and no known food or drug allergies. The
patient denied any similar illnesses in the family.
Complete otolaryngology, head and neck examination
was performed. Findings of previously mentioned multiple
nodules in both hands and a right middle ear effusion
noted. Nasopharyngoscopy showed a large fleshy
nasopharyngeal mass completely obstructing choana in the
right side and reducing nasal airway in the left side
(Fig. 2). Computed tomography of the head and neck, an
axial contrast enhanced images with sagittal and coronal
reformations, showed 36 mm 9 30 mm diameter lesion
extending from the inferior aspect of the clivus and
basisphenoid into the nasopharynx and the posterior aspect
of the right nasal cavity (Fig. 3). Incidental radiological
findings of multiple bubbly lytic bony lesions are noted
involving the vertebra, bilateral scapula, left side more
severely than right side, bilateral ribs and sternum (Fig. 4).
CT Neck angiogram showed the enhancing vascular mass
but with no specific feeding vessel (Fig. 5). Magnetic
resonance imaging (MRI) of paranasal sinuses was
ordered, but the patient did not tolerate the procedure.
Skeletal dysmorphic survey was done. Ribs, scapula, pelvis
and lower limbs showed multiple expansive chondroid
Fig. 1 Clinical image of left hand multiple (asymptomatic) small
nodules
a large fleshy nasopharyngeal mass completely obstructing choana
with small blood vessels on the surface. S: nasal septum, IT: inferior
turbinate
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lesions with soft tissue nodules phleboliths suggestive of
hemangiomas (Fig. 7).
scopically, using coblator. Tumor was bloody with blood
loss of 1150 cc. Tissue sent for histopathological evalua-
tion. Pathology confirmed the diagnosis of clival enchon-
droma with clinical and radiological features consistent
with Maffucci syndrome. Patient was followed up, 10 days
after the operation, and he was satisfied with his nasal
breathing. A rigid nasopharyngoscopy showed a patent
nasopharynx and adequate airway (Fig. 8).
Discussion
disease. This disease recognized by the presence of mul-
tiple benign enchondromas that associated with heman-
giomas and/or lymphangiomas. Enchondromas are benign
cartilaginous tumors usually found at intramedullary bone
near growth plate of long bones. Other sites includes
phalanges and metacarpal bones [1–4]. Angelo Maffucci
was the first to describe this disease in 1881. Since then,
less than 200 cases have been reported in literature
worldwide [5]. Enchondromatosis with multiple cavernous
hemangiomas, dyschondrodysplasia, Kast syndrome,
hemangiomatosis chondrodystrophica and enchondro-
matosis Spranger type II are synonyms [7]. No clear eti-
ology has been established yet. Some studies correlate
mutations of the gene encoding parathyroid hormone
receptor 1 (PTH1R) with enchondromatosis. 10% of
enchondromatosis patients have mutation in PTH1R.
Usually patients are asymptomatic. Majority of cases
develop at adolescence, but few patients may manifest
earlier in life. Mutations in gene encoding isocitrate
dehydrogenase 1 and 2 (IDH 1&2) occur in some
enchondromas and spindle cell hemangiomas [6]. Maffucci
syndrome usually presents with asymmetrical distribution
of multiple enchondromas, variable in size and shape.
These enchondromas might lead to skeletal deformities,
pathological fractures, a discrepancy in limb length and
most important, a potential malignant transformation.
Hemangiomas can found in soft tissue, mucous membrane,
orbit, brain and/or gastrointestinal tract [8]. Many studies
have shown sarcomatous degeneration of enchondromas to
chondrosarcomas in average of 25% of cases [1]. Pro-
kopchuk et al. collected and described Maffucci syndrome
Fig. 3 Computed tomography images of (exophytic lesion) of the
central skull base extending into the nasopharynx and right choana.
The lesion eccentrically situated on the right side, predominantly
hypodense and contains small foci of calcification, suggestive of
chondroid calcifications
Fig. 4 Computed tomography images of deformity of the thoracic cavity secondary to multiple bilateral rib lesions associated with internal foci
of calcifications, suggestive of chondroid calcifications
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(1881–2015). Fibrosarcoma, hemangiosarcoma, heman-
gioendothelioma, lymphangiosarcoma have been reported
for Maffucci syndrome malignant transformations. Other
non-skeletal malignancy associated with Maffucci syn-
drome, such as hepatic adenocarcinoma, pancreatic cancer,
ovarian fibrosarcoma, brain glioma, astrocytoma and other
soft tissue sarcoma have been reported in literature [9–11].
Verdegaal et al. analyzed chondrosarcomas in Maffucci
syndrome in a retrospective multicenter study. They
grouped patients based on the site of enchondromas into
three groups. The first group included short tubular bone
involvement, while the second group included flat and long
tubular bone. The third group had both short and long bone
enchondromas. They found that the incidence of chon-
drosarcoma developed in these groups were 15, 43 and
46% respectively [12]. Maffucci syndrome diagnosed
clinically by clinical history, physical examination and
radiological evaluation [4]. Microscopic histopathological
examination helps to confirm the diagnosis of Maffucci
syndrome and presence of malignancy. Management of this
syndrome starts with patient counselling and education
about the nature of the disease and the possible outcomes.
Unfortunately, no effective medical therapy has been
Fig. 5 Computed tomography angiogram images of nasopharyngeal mass lesion appear partially calcified but do not appear highly vascular and
there are no enlarged feeding vessels adjacent to its cavity
Fig. 6 Serial X-ray for Skeletal
Survey demonstrate multiple
involving ribs, scapula, iliac
bone and left femur
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peutic option available now. Treatment might be initiated
based on patient symptoms or suspicion of malignancies.
Nevertheless, all patients of Maffucci syndrome will
require a long term follow up and surveillance for the
lifelong risk of malignant transformation [13]. In literature,
benign enchondromas were reported at the long bone and
malignant tumours presented in the nasopharynx. But to
our knowledge ours is the first report presenting the benign
chondroma in the nasopharynx.
enchondromas and hemangiomas or lymphangiomas.
Diagnosis based on clinical presentation, radiological and
histopathological findings. Surgical excision has a role in
symptomatic patients and suspicious lesions. However the
vascular nature of these tumours should be considered
before planning for surgery. Maffucci syndrome carries a
lifelong risk of sarcomatous malignant transformation
which necessitates long term surveillance.
Compliance with Ethical Standards
Conflict of interest The authors declare that they have no conflict of
interests.
References
1. Biber C, Ergun P, Turay UY, Erdogan Y, Hizel SB (2004) A case
of Maffucci’s syndrome with pleural effusion: ten-year follow-
up. Ann Med Singap 33:347–350
2. Zwenneke Flach H, Ginai AZ, Wolter Oosterhuis J (2001) Best
cases from the AFIP: Maffucci syndrome: radiologic and patho-
logic findings 1. Radiographics 21(5):1311–1316
3. Jermann M, Eid K, Pfammatter T, Stahel R (2001) Maffucci
syndrome. Circulation 104(14):1693
4. Silve C, Juppner H (2006) Ollier disease. Orphanet J Rare Dis
1(1):37
5. Gao H, Wang B, Zhang X, Liu F, Lu Y (2013) Maffucci syn-
drome with unilateral limb: a case report and review of the lit-
erature. Chin J Cancer Res 25(2):254–258
6. Pansuriya TC, van Eijk R, d’Adamo P et al (2011) Somatic
mosaic IDH1 and IDH2 mutations are associated with enchon-
droma and spindle cell hemangioma in Ollier disease and Maf-
fucci syndrome. Nat Genet 43(12):1256–1261
7. Pansuriya TC, Kroon HM, Bovee JV et al (2010) Enchondro-
matosis: insights on the different subtypes. Int J Clin Exp Pathol
3(6):557–569
8. Couvineau A, Wouters V, Bertrand G et al (2008) PTHR1
mutations associated with Ollier disease result in receptor loss of
function. Hum Mol Genet 17(18):2766–2775
9. Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D,
Friess H (2016) Maffucci syndrome and neoplasms: a case report
and review of the literature. BMC Res Notes 9(1):126
10. Schwartz HS, Zimmerman NB, Simon MA, Wroble RR, Millar
EA, Bonfiglio M (1987) The malignant potential of enchondro-
matosis. J Bone Jt Surg Am 69(2):269–274
11. Lewis RJ, Ketcham AS (1973) Maffucci’s syndrome: functional
and neoplastic significance. JBJS Case Connect 7:1465–1479
12. Verdegaal SHM, Bovee JVMG, Pansuriya TC et al (2011) Inci-
dence, predictive factors, and prognosis of chondrosarcoma in
patients with Ollier disease and Maffucci syndrome: an interna-
tional multicenter study of 161 patients. Oncologist
16(12):1771–1779
13. Ngai C, Ding DY, Rapp TB (2015) Maffucci syndrome. An
interesting case and a review of the literature. Bull Hosp Jt Dis
73(4):282–285
of hemangiomas
Fig. 8 Clinical image of right rigid nasopharyngoscopy (10 days post
operative) show a patent nasopharynx with some mucoid secretions
and crusts
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Maffucci Syndrome with Clival Enchondroma in Nasopharynx: A Case Report
Abstract
Introduction