Indian Journal of Otolaryngology and Head & Neck Surgery

"Maffucci Syndrome with Clival Enchondroma in nasopharynx: a case report."

--Manuscript Draft--

Manuscript Number: IJOO-D-18-00333

Full Title: "Maffucci Syndrome with Clival Enchondroma in nasopharynx: a case report."

Article Type: Clinical Report

Keywords: Maffucci syndrome; Enchondromas; Chondrosacomas; Nasopharynx

Abstract: Abstract
Introduction: Maffucci syndrome is an extremely rare sporadic disease,characterized
by multiple enchondromas and associated with multiple hemangiomas and/or
lymphangiomas. 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.
Case presentation:This report describes the case of 21 years-old malecomplain of right
sided nasal obstruction for 10 months, and right sided aural fullness.Examination
revealed multiple 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
consistent with Maffucci syndrome.
Discussion: Clear etiology have not been established yet. Mutations in gene encoding
parathyroid hormone receptor 1 (PTH1R) found in10 % 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 chondrosarcomasin average of 25% of
cases. Patient counselling and education are crucial in the management. Surgical
excision usuallyfor symptomatic patients and suspicious lesions. Nevertheless, all
patient of Maffucci syndrome will require a long term follow up and surveillance for the
lifelong risk of malignant transformation.
Conclusion:Maffucci syndrome diagnosis based on clinical presentation, radiological
and histopathological findings. Surgical excision offered for symptomatic patients and
for suspicious lesions. Lifelong risk of sarcomatous malignant transformation
necessitate a long term surveillance.

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3 Introduction
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6 Maffucci syndrome is an extremely rare sporadic disease, described for the first time
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9 in 1881. Fewer than 200 cases have been reported in the literature. This disease recognized
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11 by multiple enchondromas, a benign cartilaginous tumor found at intramedullary bone near
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14 growth plate of long bones, and associated with multiple hemangiomas and/or
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16 lymphangiomas1–5. Malignant transformation of these lesions into chondrosarcoma,
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18 fibrosarcoma, hemangiosarcoma, hemangioendothelioma and lymphangiosarcomas has been
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21 reported. The exact etiology of Maffucci syndrome is unknown. Recent studies showed
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23 isocitrate dehydrogenase 1 (IDH1) or IDH2 gene mutations in enchondromas and spindle cell
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26 hemangiomas6. Patients are usually asymptomatic, although they might present with nodules
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28 or masses, which in some cases discovered incidentally during the physical examination or
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31 radiological investigations. The long term follow-up and observation of these nodules are
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33 crucial, due to potential malignant transformation, skeletal deformities and pathological
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fractures.
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39 This report describes the case of 21 years-old male patient with Maffucci syndrome
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41 like presentation with a vascular, large clival mass in the nasopharynx. Diagnosis of Maffucci
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syndrome with clival enchondroma had been established.
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3 Case presentation
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6 A 21 years old male, from the northern region of Saudi Arabia, referred to
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9 Otolaryngology, Head & Neck Surgery department of King Faisal Specialist Hospital &
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11 Research Center in Riyadh with a complaint of nasal obstruction affecting the right side more
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14 than the left, with a progressive course for around 10 months prior to presentation. He gave a
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16 history of severe epistaxis, controlled with posterior packing which necessitated intensive
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18 care unit admission in a local hospital, 6 months prior to the referral, where he had a
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21 fiberoptic nasopharyngoscopy and computed tomography that showed a nasopharyngeal
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23 mass. Referred to us with a differential diagnosis of juvenile nasopharyngeal angiofibroma,
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26 nasopharyngeal carcinoma, thornwaldt cyst and minor salivary gland neoplasm.
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29 The patient’s main complaint was nasal obstruction, breathing difficulties during
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31 sleep, right sided aural fullness and hearing loss. No symptoms of rhinorrhea, sneezing,
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34 itching, anosmia/hyposmia, otorrhea, tinnitus, vertigo, facial numbness/weakness, dysphonia,
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36 dysphagia, recent trauma or laryngopharyngeal reflux was given. Patient did not have any
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39 chronic medical illnesses such as diabetes mellitus or bronchial asthma. He reported multiple
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41 asymptomatic nodules in both hands since childhood, that have not been investigated (Fig.1).
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Patient was not on any medications and no known food or drug allergies. The patient denied
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46 any similar illnesses in the family.
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49 Complete Otolaryngology, Head & neck examination was performed. Findings of
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previously mentioned multiple nodules in both hands and a right middle ear effusion noted.
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54 Nasopharyngoscopy showed a large fleshy nasopharyngeal mass completely obstructing
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56 choana in the right side and reducing nasal airway in the left side (Fig.2). Computed
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59 tomography of the head and neck, an axial contrast enhanced images with sagittal and
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coronal reformations, showed 36 mm X 30 mm diameter lesion extending from the inferior

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2 aspect of the clivus and basisphenoid into the nasopharynx and the posterior aspect of the
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5 right nasal cavity (Fig.3). Incidental radiological findings of multiple bubbly lytic bony
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7 lesions are noted involving the vertebra, bilateral scapula, left side more severely than right
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10 side, bilateral ribs and sternum (Fig.4). CT Neck angiogram showed the enhancing vascular
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12 mass but with no specific feeding vessel (Fig.5). Magnetic resonance imaging (MRI) of
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15 paranasal sinuses was ordered, but the patient did not tolerate the procedure. Skeletal
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17 dysmorphic survey was done. Ribs, scapula, pelvis and lower limbs showed multiple
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expansive chondroid lesions (Fig.6). Left hand x-ray showed multiple bone lesions with soft
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22 tissue nodules phleboliths suggestive of hemangiomas (Fig.7).
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25 Patient was consented for endoscopic clival lesion excision. Radical tumor resection
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was preformed endoscopically, using coblator. Tumor was bloody with blood loss of 1150cc.
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30 Tissue sent for histopathological evaluation. Pathology confirmed the diagnosis of clival
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32 enchondroma with clinical and radiological features consistent with Maffucci syndrome.
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35 Patient was followed up, 10 days after the operation, and he was satisfied with his nasal
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37 breathing. A rigid nasopharyngoscopy showed a patent nasopharynx and adequate airway
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40 (Fig.8).
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43 Discussion
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46 Maffucci syndrome is a rare, non-hereditary, sporadic disease. This disease
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48 recognized by the presence of multiple benign enchondromas that associated with
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51 hemangiomas and/or lymphangiomas. Enchondromas are benign cartilaginous tumors usually
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53 found at intramedullary bone near growth plate of long bones. Other sites includes phalanges
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56 and metacarpal bones1–4. Angelo Maffucci was the first to describe this disease in 1881. Since
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58 then, less than 200 cases have been reported in literature worldwide5. Enchondromatosis with
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multiple cavernous hemangiomas, dyschondrodysplasia, Kast syndrome, hemangiomatosis

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2 chondrodystrophica and enchondromatosis Spranger type II are synonyms 7. No clear etiology
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5 has been established yet. Some studies correlate mutations of the gene encoding parathyroid
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7 hormone receptor 1 (PTH1R) with enchondromatosis. 10% of enchondromatosis patients
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10 have mutation in PTH1R. Usually patients are asymptomatic. Majority of cases develop at
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12 adolescence, but few patients may manifest earlier in life. Mutations in gene encoding
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15 isocitrate dehydrogenase 1 and 2 (IDH 1 & 2) occur in some enchondromas and spindle cell
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17 hemangiomas6. Maffucci syndrome usually presents with asymmetrical distribution of
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multiple enchondromas, variable in size and shape. These enchondromas might lead to
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22 skeletal deformities, pathological fractures, a discrepancy in limb length and most important,
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24 a potential malignant transformation. Hemangiomas can found in soft tissue, mucous
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27 membrane, orbit, brain and/or gastrointestinal tract8. Many studies have shown sarcomatous
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29 degeneration of enchondromas to chondrosarcomas in average of 25% of cases1. Prokopchuk
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32 et al. collected and described Maffucci syndrome association with skeletal and non-skeletal
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34 neoplasms (1881-2015). Fibrosarcoma, hemangiosarcoma, hemangioendothelioma,
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lymphangiosarcoma have been reported for Maffucci syndrome malignant transformations.
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39 Other non-skeletal malignancy associated with Maffucci syndrome, such as hepatic
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41 adenocarcinoma, pancreatic cancer, ovarian fibrosarcoma, brain glioma, astrocytoma and
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44 other soft tissue sarcoma have been reported in literature9–11. Verdegaal et al. analyzed
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46 chondrosarcomas in Maffucci syndrome in a retrospective multicenter study. They grouped
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49 patients based on the site of enchondromas into three groups. The first group included short
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51 tubular bone involvement, while the second group included flat and long tubular bone. The
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54 third group had both short and long bone enchondromas. They found that the incidence of
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56 chondrosarcoma developed in these groups were 15%, 43 % and 46 % respectively12.
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Maffucci Syndrome diagnosed clinically by clinical history, physical examination and
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radiological evaluation4. Microscopic histopathological examination helps to confirm the

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2 diagnosis of Maffucci syndrome and presence of malignancy. Management of this syndrome
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5 startes with patient counselling and education about the nature of the disease and the possible
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7 outcomes. Unfortunately, no effective medical therapy has been established yet. Surgical
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10 excision may be the only therapeutic option available now. Treatment might be initiated
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12 based on patient symptoms or suspicion of malignancies. Nevertheless, all patients of
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15 Maffucci syndrome will require a long term follow up and surveillance for the lifelong risk of
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17 malignant transformation13. In literature, benign enchondromas were reported at the long
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bone and malignant tumours presented in the nasopharynx. But to our knowledge ours is the
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22 first report presenting the benign chondroma in the nasopharynx.
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25 Conclusion
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28 Maffucci syndrome is a very rare disease with multiple enchondromas and
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31 hemangiomas or lymphangiomas. Diagnosis based on clinical presentation, radiological and
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33 histopathological findings. Surgical excision has a role in symptomatic patients and
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suspicious lesions. However the vascular nature of these tumours should be considered before
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38 planning for surgery. Maffucci syndrome carries a lifelong risk of sarcomatous malignant
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40 transformation which necessitates long term surveillance.
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Conflicts of Interest
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47 The authors have no conflicts of interest to declare.
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14 Fig. 1 Clinical image of left hand multiple (asymptomatic) small nodules.
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33 Fig. 2 Clinical image of right rigid nasopharyngoscopy findings, (*) a large fleshy nasopharyngeal mass completely
34 obstructing choana with small blood vessels on the surface S: nasal septum IT: Inferior turbinate
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Fig. 3 Computed tomography images of (exophytic lesion) of the central skull base extending into the nasopharynx and
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right choana. The lesion eccentrically situated on the right side, predominantly hypodense and contains small foci of
23 calcification, suggestive of chondroid calcifications.
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Fig. 4 Computed tomography images of deformity of the thoracic cavity secondary to multiple bilateral rib lesions
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associated with internal foci of calcifications, suggestive of chondroid calcifications.
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Fig. 5 Computed tomography angiogram images of nasopharyngeal mass lesion appear partially calcified but do not
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appear highly vascular and there are no enlarged feeding vessels adjacent to its cavity.
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22 Fig. 6 Serial X-ray for Skeletal Survey demonstrate multiple expansive lytic lesions with chondroid origin characteristics,
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41 Fig. 7 X-ray left hand demonstrates multiple metacarpal and phalangeal lesions and soft tissue nodules with phleboliths
suggestive of hemangiomas.
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57 Fig. 8 Clinical image of right rigid nasopharyngoscopy (10 days post operative) show a patent nasopharynx with some
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Fig. 1 Clinical image of left hand multiple (asymptomatic) small nodules. Click here to download Figure Fig_1.tiff
Fig. 2 Clinical image of right rigid nasopharyngoscopy findings,(*) a large fleshy Click here to download Figure Fig_2.tiff
nasopharyngeal mass completely obstructing choana with small blood vessels on the
Fig. 3 Computed tomography images of (exophytic lesion) of the Click here to download Figure Fig_3.tiff
central skull base extending into the nasopharynx and right
Fig. 4 Computed tomography images of deformity of the thoracic cavity secondary to Click here to download Figure Fig_4.tiff
multiple bilateral rib lesions associated with internal foci of calcifications, suggestive of
Fig. 5 Computed tomography angiogram images of nasopharyngeal mass lesion Click here to download Figure Fig.5.jpg
appear partially calcified but do not appear highly vascular and there are no enlarged
Fig. 6 Serial X-ray for Skeletal Survey demonstrate multiple expansive lytic lesions with Click here to download Figure Fig.6.jpg
chondroid origin characteristics, involving ribs, scapula, iliac bone and left femur.
Fig. 7 X-ray left hand demonstrates multiple metacarpal and phalangeal lesions and Click here to download Figure Fig.7.jpg
soft tissue nodules with phleboliths suggestive of hemangiomas.