Fibrous Dysplasia

                                         DR KS Dhillon

Introduction

Fibrous dysplasia is a benign bone lesion that is characterized by intramedullary fibro-osseous proliferation secondary to altered osteogenesis (1). It was first introduced by Lichtenstein and Jaffe in 1942 and originally termed Jaffe-Lichtenstein syndrome. Fibrous dysplasia can occur in monostotic form (single bone) or polyostotic form (multiple bones) (1). Fibro-osseous tissue replacement of normal bone can result in complications such as fractures or compression of adjacent soft tissues including neurovascular structures (2). Monostotic fibrous dysplasia is usually an asymptomatic clinical entity. The polyostotic form usually presents in childhood. Presentation in adults is often detected incidentally during imaging for unrelated indications (2). Fibro-osseous replacement of bone in fibrous dysplasia can lead to pathologic fracture, especially in weight-bearing bones or the upper extremities in athletes (3). Malignant transformation is rare. Radiation therapy has been reported as a risk factor (4). McCune-Albright syndrome is a relatively rare condition. It features polyostotic fibrous dysplasia with skin pigmentation lesions and endocrine dysfunction. Mazabraud syndrome is a very rare polyostotic variant. It features coexistent single or multiple intramuscular myxomas (5).

Etiology

Fibrous dysplasia etiology has been linked with a missense mutation in the GNAS1 gene on chromosome 20. Following an activating mutation abnormal proliferation of fibrous tissue ensues (6).

Epidemiology

The incidence of fibrous dysplasia has been estimated at 1 in 5,000 to 10,000 (7). Usually, fibrous dysplasia is first diagnosed in children or young adults. There is no predilection for gender. Fibrous dysplasia constitutes 5% of all benign bone lesions (2). The monostotic form is the most common. It accounts for 75% to 80% of fibrous dysplasia cases (8).

Histopathology

In fibrous dysplasia, there are histologic elements of immature collagen and immature bone trabeculae forming a fibrocellular matrix (9). The trabeculae are not rimmed by osteoblasts secondary to osteoblast maturation arrest. There is abrupt histologic transition from normal to abnormal bone (9). 

History and Physical Examination

Patients with monostotic fibrous dysplasia are usually asymptomatic, but they may occasionally present with bone pain. Pathologic fracture with minor trauma can be the first presentation (10). Pregnancy can increase disease activity and increase the risk of pain and pathologic fracture (11). 

In patients with asymptomatic osseous involvement history and physical examination may contribute little to disease evaluation. History will address the characteristics of bony protuberance, osseous asymmetry, tenderness, endocrine disturbance, and dermatologic complaints. There may be a family history of bone lesions in hereditary forms of fibrous dysplasia such as cherubism. Malignant transformation is rare. It occurs in less than 1% of the patients (12). A periodic evaluation for aggressive lesion growth should be performed in a patient with known fibrous dysplasia (13). In patients with hyperfunctioning endocrinopathy, McCune-Albright syndrome should be considered. 

Physical examination has a minor role in the evaluation of fibrous dysplasia lesions. Focal palpation may increase pain in patients with fractures. Visual inspection for skeletal deformities and asymmetries will show the sites of involvement. Leg length discrepancy may indicate the presence of disease such as the classic shepherd’s crook deformity of the proximal femur (14). Facial involvement can produce orbital asymmetry (15). Other possible face complications include frontal bossing, proptosis, or mandibular enlargement (16).

Deformity commonly occurs in the ribs, long bones, and craniofacial structures. Less often it occurs in the hands, sternum, and spine (17,18). In patients with McCune-Albright syndrome, the physical examination should include an examination of the skin to look for cafe au lait skin pigmentation. Skin acne can be a feature of endocrinopathy (Cushing syndrome) (19). A thorough physical examination to assess the endocrine system should be done. This would include cardiopulmonary, gastrointestinal, and thyroid evaluation (20). Assessment of hearing and vision in the setting of craniofacial manifestation of fibrous dysplasia is also important (2).

Evaluation

Imaging plays a main role in the diagnosis and evaluation of the extent of the disease. Radiography should be utilized first in an evaluation of fibrous dysplasia. Imaging such as magnetic resonance imaging (MRI) and computerized tomography (CT) can exclude other bone lesions; evaluate for soft tissue complications occurring from fractures, evaluate craniofacial neurovascular complications, and assess lesions for rare malignant transformation (21). MRI and CT also have a role in the evaluation of thyroid nodules, adrenal hyperplasia, and pituitary tumors (22,23). The bone lesions classically, have an internal ground glass matrix on radiographs and CT. The appearance can vary with lytic and/or sclerotic components, possible bone expansion, and cortical thinning (12). Bowing deformities such as femoral shepherd's crook deformity, limb length discrepancy, and short stature secondary to premature fusion of growth plates can be characterized with imaging (21). Bone scan demonstrating increased Technetium-99m radiotracer uptake can have a role in polyostotic cases to assess the extent of the disease (24). Biopsy with histologic evaluation may be necessary in some cases where imaging features mimic malignant lesions (14).

Management

Patients with monostotic fibrous dysplasia are usually asymptomatic. They can be followed periodically to look for new symptoms and to take radiographs (25). In asymptomatic cases, no treatment is required. Bone pain and disease-associated osteoporosis can be alleviated in adults with bisphosphonates (10). Bisphosphonates inhibit osteoclastic bone resorption and preserve cortical bone mass. Hence they reduce fracture risk (26,27). Surgery may be required in symptomatic fibrous dysplasia treatment. 

Surgery for internal fixation is needed in patients with pathologic fractures and for prophylactic internal fixation in lesions weakening weight-bearing bones (14). Surgical interventions may be required for the correction of extremity and spine deformities and for limb length inequality (14). Craniofacial surgery may be required to alleviate nerve compression symptoms (28). During surgery, bone lesion curettage, bone grafting, and insertion of metallic fixation rods, screws, and plates may be required (14).

Differential Diagnosis

Accurate assessment of the cafe au lait skin pigmentation lesions is important in patients with polyostotic McCune-Albright syndrome. The skin lesion borders have been described as serrated. This is in contrast to smooth skin lesion borders seen in neurofibromatosis (11).

Fibrous dysplasia usually has varied imaging presentation and varied osseous sites of involvement. Therefore other bone diseases must be kept in mind. Monostotic radiologic appearance can mimic simple bone cysts, fibroxanthomas, osteoblastomas, giant cell tumors, hemangiomas, osteofibrous dysplasia, and Paget disease.  Polyostotic appearance can mimic neurofibromatosis, enchondromatosis, hyperparathyroidism, and eosinophilic granuloma (11,25). Bone location, patient age, presence of ground glass matrix, and non-aggressive appearance are features that favor fibrous dysplasia (11). If malignancy cannot be excluded following clinical and imaging workup, bone biopsy does have a role (14).

Complications

Fibrous dysplasia is usually monostotic and asymptomatic. In patients with severe bone deformity, bowing may result in musculoskeletal dysfunction or acceleration of the development of osteoarthritis (29). Spine lesions can predispose to scoliosis and subsequent functional dysfunction (30). Craniofacial cases can have associated cranial nerve deficits with vision and hearing loss (31,32). In patients with prior history of radiation therapy, malignant transformation to sarcoma can occur although it is rare (33).

Conclusion 

Fibrous dysplasia is a benign bone lesion. It is characterized by intramedullary fibro-osseous proliferation secondary to altered osteogenesis. Fibro-osseous tissue replacement of normal bone can result in complications such as fractures or compression of adjacent soft tissues. Patient education regarding the risk of fracture is important (34). In patients with craniofacial disease, the patient should be coached to monitor for evolving cranial nerve deficits including vision and hearing loss. In patients with McCune-Albright syndrome genetic counseling would be required (35). Routine visits to an endocrinologist would also be required to monitor for symptoms of endocrine dysfunction.

Managing fibrous dysplasia involves an interprofessional team approach.  Craniofacial involvement should prompt, ophthalmology, neurology, audiology, and possible neurosurgery consultation (3,36). Additional support from physical therapist and psychiatrist in cases of disability or deformity may be needed (3).

References

1. Schoenau E, Rauch F. Fibrous dysplasia. Horm Res. 2002;57 Suppl 2:79-82.

2. DiCaprio MR, Enneking WF. Fibrous dysplasia. Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005 Aug;87(8):1848-64.

3. Leet AI, Collins MT. Current approach to fibrous dysplasia of bone and McCune-Albright syndrome. J Child Orthop. 2007 Mar;1(1):3-17.

4. Hansen MR, Moffat JC. Osteosarcoma of the Skull Base after Radiation Therapy in a Patient with McCune-Albright Syndrome: Case Report. Skull Base.

5. Munksgaard PS, Salkus G, Iyer VV, Fisker RV. Mazabraud's syndrome: case report and literature review. Acta Radiol Short Rep. 2013;2(4):2047981613492532.

6. Robinson C, Collins MT, Boyce AM. Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives. Curr Osteoporos Rep. 2016 Oct;14(5):178-86.

7. Pai B, Ferdinand D. Fibrous dysplasia causing safeguarding concerns. Arch Dis Child. 2013 Dec;98(12):1003.

8. Riddle ND, Bui MM. Fibrous dysplasia. Arch Pathol Lab Med. 2013 Jan;137(1):134-8. 

9. Riminucci M, Liu B, Corsi A, Shenker A, Spiegel AM, Robey PG, Bianco P. The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: site-specific patterns and recurrent histological hallmarks. J Pathol. 1999 Jan;187(2):249-58. 

10. Chapurlat RD, Gensburger D, Jimenez-Andrade JM, Ghilardi JR, Kelly M, Mantyh P. Pathophysiology and medical treatment of pain in fibrous dysplasia of bone. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1(Suppl 1):S3.

11. Kransdorf MJ, Moser RP, Gilkey FW. Fibrous dysplasia. Radiographics. 1990 May;10(3):519-37. 

12. Adetayo OA, Salcedo SE, Borad V, Richards SS, Workman AD, Ray AO. Fibrous dysplasia: an overview of disease process, indications for surgical management, and a case report. Eplasty. 2015;15:e6. 

13. Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer. 1994 Mar 01;73(5):1411-24. 

14. Stanton RP, Ippolito E, Springfield D, Lindaman L, Wientroub S, Leet A. The surgical management of fibrous dysplasia of bone. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1(Suppl 1):S1. 

15. Gupta S, Jain S, Newaskar V, Ali M. Craniofacial fibrous dysplasia with facial asymmetry, canted occlusion and open bite: a case report with 2 years follow-up. J Contemp Dent Pract. 2014 Sep 01;15(5):636-45. 

16. Sandhu SV, Sandhu JS, Sabharwal A. Clinicoradiologic perspective of a severe case of polyostotic fibrous dysplasia. J Oral Maxillofac Pathol. 2012 May;16(2):301-5.

17. Zorzin L, Palmieri G, Marrese C, Spagnoli LG. Polyostotic fibrous dysplasia involving the sternum. Clin Rheumatol. 1988 Mar;7(1):107-9. 

18. Batista KT, Araújo HJ, Schwartzman UP. Monostotic fibrous dysplasia of the metacarpal: a case report. Rev Bras Ortop. 2016 Nov-Dec;51(6):730-734. 

19. Dean L. McCune-Albright Syndrome. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries [Internet]. National Center for Biotechnology Information (US); Bethesda (MD): Mar 8, 2012. 

20. Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, Dinauer CA, Hamilton J, Hay ID, Luster M, Parisi MT, Rachmiel M, Thompson GB, Yamashita S., American Thyroid Association Guidelines Task Force. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2015 Jul;25(7):716-59.

21. Fitzpatrick KA, Taljanovic MS, Speer DP, Graham AR, Jacobson JA, Barnes GR, Hunter TB. Imaging findings of fibrous dysplasia with histopathologic and intraoperative correlation. AJR Am J Roentgenol. 2004 Jun;182(6):1389-98.

22. O'Laughlin RL, Selinger SE, Moriarty PE. Pituitary adenoma in McCune-Albright syndrome: MR demonstration. J Comput Assist Tomogr. 1989 Jul-Aug;13(4):685-8. 

23. Kirk JM, Brain CE, Carson DJ, Hyde JC, Grant DB. Cushing's syndrome caused by nodular adrenal hyperplasia in children with McCune-Albright syndrome. J Pediatr. 1999 Jun;134(6):789-92. 

24. Zhibin Y, Quanyong L, Libo C, Jun Z, Hankui L, Jifang Z, Ruisen Z. The role of radionuclide bone scintigraphy in fibrous dysplasia of bone. Clin Nucl Med. 2004 Mar;29(3):177-80.

25. Bousson V, Rey-Jouvin C, Laredo JD, Le Merrer M, Martin-Duverneuil N, Feydy A, Aubert S, Chapurlat R, Orcel P. Fibrous dysplasia and McCune-Albright syndrome: imaging for positive and differential diagnoses, prognosis, and follow-up guidelines. Eur J Radiol. 2014 Oct;83(10):1828-42.

26. Shahnazari M, Yao W, Dai W, Wang B, Ionova-Martin SS, Ritchie RO, Heeren D, Burghardt AJ, Nicolella DP, Kimiecik MG, Lane NE. Higher doses of bisphosphonates further improve bone mass, architecture, and strength but not the tissue material properties in aged rats. Bone. 2010 May;46(5):1267-74. 

27. Zacharin M, O'Sullivan M. Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the McCune Albright syndrome. J Pediatr. 2000 Sep;137(3):403-9.

28. Tan YC, Yu CC, Chang CN, Ma L, Chen YR. Optic nerve compression in craniofacial fibrous dysplasia: the role and indications for decompression. Plast Reconstr Surg. 2007 Dec;120(7):1957-1962. 

29. Kushare IV, Colo D, Bakhshi H, Dormans JP. Fibrous dysplasia of the proximal femur: surgical management options and outcomes. J Child Orthop. 2014 Dec;8(6):505-11. 30.

30. Mancini F, Corsi A, De Maio F, Riminucci M, Ippolito E. Scoliosis and spine involvement in fibrous dysplasia of bone. Eur Spine J. 2009 Feb;18(2):196-202.

31. Michael CB, Lee AG, Patrinely JR, Stal S, Blacklock JB. Visual loss associated with fibrous dysplasia of the anterior skull base. Case report and review of the literature. J Neurosurg. 2000 Feb;92(2):350-4. 

32. Boyce AM, Brewer C, DeKlotz TR, Zalewski CK, King KA, Collins MT, Kim HJ. Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia. JAMA Otolaryngol Head Neck Surg. 2018 Feb 01;144(2):102-107.

33. Qu N, Yao W, Cui X, Zhang H. Malignant transformation in monostotic fibrous dysplasia: clinical features, imaging features, outcomes in 10 patients, and review. Medicine (Baltimore). 2015 Jan;94(3):e369. 

34. Han I, Choi ES, Kim HS. Monostotic fibrous dysplasia of the proximal femur: natural history and predisposing factors for disease progression. Bone Joint J. 2014 May;96-B(5):673-6. 

35. Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008 May 19;3:12. [PMC free article] [PubMed]

36. Bowers CA, Taussky P, Couldwell WT. Surgical treatment of craniofacial fibrous dysplasia in adults. Neurosurg Rev. 2014 Jan;37(1):47-53.

         Cubital Tunnel Syndrome

                                  Dr. KS Dhillon

Introduction

Cubital tunnel syndrome is neuropathy of the ulnar nerve which causes symptoms of numbness and shooting pain along the medial aspect of the forearm and medial half of the fourth digit and the fifth digit. Compression or irritation of the ulnar nerve at the elbow region causes it.

Ulnar Nerve Anatomy

The C8 and T1 nerve roots join and give rise to the medial cord of the brachial plexus. The ulnar nerve originates as a branch of the medial cord. 

The ulnar nerve along with the brachial artery then travels down the arm towards the elbow joint.  At the middle of the arm, the ulna nerve enters the posterior compartment by piercing the intermuscular septum (arcade of Struthers). It then travels along the medial aspect of the triceps to enter the cubital tunnel. In the cubital tunnel, the ulnar nerve travels between the olecranon and the medial epicondyle beneath the Osborne ligament. After the ulna nerve exits the cubital tunnel, it passes under the aponeurotic head of flexor carpi ulnaris to enter the forearm. The cubital tunnel is where the ulnar nerve is most likely to be compressed due to its location and anatomy. The nerve can also get compressed at the arcade of Struthers or by the aponeurotic head of flexor carpi ulnaris. The ulnar nerve innervates the medial side of the forearm, the ulna side of the palm, the little finger, and the ulna half of the ring finger. The ulna nerve supplies motor branches to flexor carpi ulnaris, flexor profundus of the little and ring fingers, hypothenar muscles, adductor pollicis brevis, all the interossei, and the third and fourth lumbricals. 

Etiology

There are several causes of ulnar nerve compression at the cubital tunnel that can cause symptoms such as tingling along the medial aspect of the forearm, the little finger, and the medial aspect of the ring finger.

Pressure on the ulnar nerve is the most common cause of these symptoms. The ulnar nerve is quite superficial at the medial epicondyle region. This is why people may experience the feeling of shooting pain and electric shock in the forearm if they accidentally hit the elbow on a hard surface.

Stretching the ulnar nerve can also produce similar symptoms. During elbow flexion, the ulnar nerve can get stretched because of its anatomical position. Repetitive elbow flexion and extension can cause damage and irritation to the ulnar nerve. Some individuals sleep with elbows flexed. This can stretch the ulnar nerve for an extended period during sleep and cause irritation to the ulnar nerve.

Injuries to the elbow joint leading to fractures, dislocations, swelling, and effusions can cause anatomical damage which will cause symptoms because of compression/irritation of the ulnar nerve.

A study of 117 patients by Omejec and Podnar (1) identified that direct pressure on the nerve because of habits while sitting, or secondary to occupational activities is a significant cause of nerve damage as the nerve passes posterior to the medial epicondyle.

Epidemiology

After carpal tunnel syndrome, ulnar nerve neuropathy is the second most common compression neuropathy of the arm. Filippou et al (2) studied 91 patients and they found that nearly 60% of the patients had anatomical changes in the cubital tunnel that caused the ulnar nerve neuropathy, of which nearly 20% had a subluxation of the ulnar nerve. There were osteophytes in almost 7% of patients and luxation of the ulnar nerve in nearly 10% of the patients. Trauma also can cause symptoms in about 3.3% of patients (2).

Pathophysiology

The exact pathophysiology of the cubital tunnel syndrome is not known. Smoking is a risk factor for cubital tunnel syndrome (3). It is more common in males. The left side is more often affected (4).

History and Physical Examination

The patient typically presents with complaints of "pins and needles" in the forearm and the hand. The tingling sensation is usually present along the little finger and medial half of the ring finger. The symptoms are usually aggravated with elbow flexion. These symptoms are usually transient initially then gradually get worse. 

Examination may show reduced or complete loss of sensation on the palmar and dorsal aspects of the little finger and the medial part of the ring finger (5,6). Tinel's sign is usually positive along the cubital tunnel. Provocative tests like sustained elbow flexion for one minute or compression of the ulnar nerve at the cubital tunnel region may be positive, causing paresthesia along with the distribution of the ulnar nerve. The diagnostic value of these tests is however poor (7). In some patients, the ulnar nerve may subluxate over the medial epicondyle with elbow flexion.

Motor symptoms are uncommon and usually manifest in severe cases of ulnar neuropathy. Patients may complain of weakness in the hand. They frequently drop objects. Findings on examination could range from mild weakness of the interosseous muscles to severe atrophy of the hand intrinsics muscles and weakness of the handgrip. Froment's sign can be positive. It indicates weakness of the adductor pollicis, which is supplied by the ulnar nerve. Ulnar claw hand is unlikely in patients with cubital tunnel syndrome because the flexor digitorum profundus to the ring and little fingers is also denervated.

Evaluation

In evaluating patients with ulnar neuropathy a thorough knowledge of the motor and sensory distribution of the ulnar nerve is critical. Diagnosis can be made clinically. Nerve conduction studies are quite often used to confirm the diagnosis. In some patients, however, in the early stages of symptoms, the nerve conduction may be normal. Interpretation of nerve conduction studies should always be in a clinical context.

X-rays of the elbow joint can be done to exclude bony pathologies which may cause compression of the nerve (8).

Ultrasonic scanning (USS) and magnetic resonance imaging (MRI) have a sensitivity and specificity of over 80% in diagnosis. MRI and USS can also help to identify other causes of compression, which may not be picked up on plain radiographs such as soft tissue swelling and lesions such as ganglions, neuroma, and aneurysms (9).

Management

When deciding on treatment options, pathological findings should undergo careful evaluation. Often patients can benefit from non-surgical treatment. The clinician should, therefore, evaluate and determine an end goal of treatment with the patient before deciding on the method of treatment.

Non-surgical Treatment

In patients whose symptoms are due to mechanical factors such as leaning over the desk at work with weight on the elbows or sleeping with bent elbows, correcting these postures that provoke ulnar neuropathy can be the mainstay of treatment.

Padua et al (10) in an Italian study followed up 24 patients who had willingly declined surgery after the initial diagnosis. About half of their patients reported improvement in their symptoms during follow-up. Their further nerve conduction studies also showed improvement. This further supports the evidence that patients with mild symptoms can be managed without surgery (10).

Night-time splinting to keep the elbows straight has been suggested as an initial management option in patients with mild symptoms (6). Analgesics such as NSAIDs will help to relieve the pain.

Surgical Treatment

Patients with severe symptoms and signs such as atrophy of interossei and weakness of the hand grip might not improve with conservative treatment. Patients who have failed conservative treatment for 6 months would also require surgical intervention. Surgical treatment involves decompression of the nerve throughout the entire cubital tunnel. Some doctors release the pressure in the cubital tunnel region. Other doctors prefer free mobilization of the ulnar nerve. 

There are various methods of surgical treatment. Some of the well accepted surgical procedures include:

1) in-situ decompression

2) endoscopic decompression

3) decompression followed by subsequent subcutaneous transposition, intramuscular transposition, or submuscular transposition

4) medial epicondylectomy along with in-situ decompression (6)

In terms of clinical outcome, studies have shown no benefit of one over the other (11).

Differential Diagnosis

The differential diagnosis includes:

• Brachial plexus injuries

• Thoracic outlet syndrome

• Syringomyelia

• Lesions in the Guyon (ulnar) canal

• Cervical spondylosis

• Pancoast tumors

• Motor neuron disease

• Carpal tunnel syndrome

• Polyneuropathy

Prognosis

The symptoms improve with conservative treatment in about half of the patients (5).

Complications

After surgical decompression one in eight patients may find that their symptoms recur (12). Inadequate decompression is the most frequent cause of revision surgery. Recovery can be slow and incomplete. In some patients, symptoms may worsen before they improve.

Injury to the medial antebrachial cutaneous nerve of the forearm is a common complication following cubital tunnel release and can be painful (13).

Postoperative Care

A full range of motion of the elbow is usually allowed following surgical intervention. Usually, post-operative physical therapy is not required unless there is significant muscle weakness. Patients are allowed to return to light work in 3 to 4 weeks.

Conclusion

Ulnar nerve neuropathy can be due to several causes. Differential diagnosis have to be kept in mind while evaluating patients with ulnar neuropathy.  A thorough knowledge of the sensory and motor distribution of the ulnar nerve is critical in evaluating patients with ulnar neuropathy and identifying the site of pathology.

Input by an interprofessional team including a nurse, physical therapist, and doctor can enhance recovery. Physiotherapy can be useful if muscle weakness is present. The doctor should discuss the surgical approach and the potential risks/benefits of the procedure with the patient. 

References

1. Omejec G, Podnar S. What causes ulnar neuropathy at the elbow? Clin Neurophysiol. 2016 Jan;127(1):919-924.

2. Filippou G, Mondelli M, Greco G, Bertoldi I, Frediani B, Galeazzi M, Giannini F. Ulnar neuropathy at the elbow: how frequent is the idiopathic form? An ultrasonographic study in a cohort of patients. Clin Exp Rheumatol. 2010 Jan-Feb;28(1):63-7.

3. Frost P, Johnsen B, Fuglsang-Frederiksen A, Svendsen SW. Lifestyle risk factors for ulnar neuropathy and ulnar neuropathy-like symptoms. Muscle Nerve. 2013 Oct;48(4):507-15.

4. Kanat A, Balik MS, Kirbas S, Ozdemir B, Koksal V, Yazar U, Kazdal H, Kalaycioglu A. Paradox in the cubital tunnel syndrome--frequent involvement of left elbow: first report. Acta Neurochir (Wien). 2014 Jan;156(1):165-8.

5. Wojewnik B, Bindra R. Cubital tunnel syndrome - Review of current literature on causes, diagnosis and treatment. J Hand Microsurg. 2009 Dec;1(2):76-81. 

6. Assmus H, Antoniadis G, Bischoff C. Carpal and cubital tunnel and other, rarer nerve compression syndromes. Dtsch Arztebl Int. 2015 Jan 05;112(1-2):14-25; quiz 26.

7. Beekman R, Schreuder AH, Rozeman CA, Koehler PJ, Uitdehaag BM. The diagnostic value of provocative clinical tests in ulnar neuropathy at the elbow is marginal. J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1369-74.

8. Cutts S. Cubital tunnel syndrome. Postgrad Med J. 2007 Jan;83(975):28-31.

9. Ayromlou H, Tarzamni MK, Daghighi MH, Pezeshki MZ, Yazdchi M, Sadeghi-Hokmabadi E, Sharifipour E, Ghabili K. Diagnostic value of ultrasonography and magnetic resonance imaging in ulnar neuropathy at the elbow. ISRN Neurol. 2012;2012:491892.

10. Padua L, Aprile I, Caliandro P, Foschini M, Mazza S, Tonali P. Natural history of ulnar entrapment at elbow. Clin Neurophysiol. 2002 Dec;113(12):1980-4.

11. Zlowodzki M, Chan S, Bhandari M, Kalliainen L, Schubert W. Anterior transposition compared with simple decompression for treatment of cubital tunnel syndrome. A meta-analysis of randomized, controlled trials. J Bone Joint Surg Am. 2007 Dec;89(12):2591-8. 

12. Beekman R, Wokke JH, Schoemaker MC, Lee ML, Visser LH. Ulnar neuropathy at the elbow: follow-up and prognostic factors determining outcome. Neurology. 2004 Nov 09;63(9):1675-80. 

13. Lowe JB, Maggi SP, Mackinnon SE. The position of crossing branches of the medial antebrachial cutaneous nerve during cubital tunnel surgery in humans. Plast Reconstr Surg. 2004 Sep 01;114(3):692-6.

   Non-Ossifying Fibroma

                                  Dr. KS Dhillon

Introduction

Non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) are common bone lesions. They are usually found in skeletally immature patients under the age of 15 years (1). They are generally asymptomatic. They are typically discovered incidentally. They are the most common lesions that are referred to orthopedic oncology clinics (2). Their radiographic features are usually very characteristic. If these lesions are detected incidentally a biopsy is not required.

The two lesions have different imaging characteristics. FCDs are small lesions primarily located in the bone cortex, larger NOFs are on the other hand located eccentrically in the medullary cavity (1,3,4). NOFs are large and usually symptomatic. FCDs are small and usually asymptomatic (3).

FCD and NOF are present in up to 30% of children during their skeletal growth period (1,5). However, it is difficult to draw definitive prevalence

rates. Larger lesions can cause pain (1). The association between lesion size and pain is not well known.

Non‑ossifying fibromas and fibrous cortical defects

NOFs and FCDs are benign, well-circumscribed radiolucent lesions that are present in the metaphyseal portions of long bones. The lesions are usually located in the distal femur, proximal and distal tibia, and proximal humerus (3). Usually, the diagnosis can be made from characteristic radiographic findings (6). NOF can diagnosed if there is an oval, rounded or polycyclic, sharply marginated, intramedullary radiolucency in the metaphyseal portion of the distal femur or proximal tibia, with or without a rim of sclerotic bone.

FCD can be diagnosed if there is an oval or rounded, sharply marginated,  eccentric radiolucent zone in the medial metaphyseal cortex of the distal

femur.

The prevalence of NOF increases and that of FCD decreases with advancing age. About half of the patients with FCD complain of spontaneous pain. The lesion size and spontaneous pain, however, may not be associated.

NOF and FCD are metaphyseal fibrous defects. They have been considered to be synonymous because of similar pathologic findings, although they differ in size and primary locations in the long bones (4,9). NOF lesions are principally metaphyseal in location. The most common sites include the distal femur, proximal tibia, distal tibia, proximal humerus, fibula, and radius (3). About less than 5% of NOFs are multifocal. Most multifocal NOFs often develop sporadically. They also develop in patients with neurofibromatosis type 1 and Jafe-Campanacci syndrome (1).

More recently, NOF has been considered to be a neoplasm because of

Ras-MAPK activation by somatic mutation (10). Hence, these two lesions are different entities because of their differing clinical and biological characteristics. FCD maintains the same position (11), while NOF advances proximally or distally with age. FCD most likely occurs when tendons are inserted into the perichondrium of the epiphyseal plate (7,11,12). There is a male predominance (6,7,12). It has been estimated that NOF may be present in up to 30% of children (1,5). This prevalence may not be accurate because previous studies were retrospectively case series. Sontag and Pyle (11) examined the skeletal roentgenograms of healthy children until the age of 18 years. They found cystic lesions (consistent with FCD) in 22% of the girls and 53% of the boys. No similar research has been conducted on NOF. No ethnic prevalence has been described (3). The Ritschl classification of NOF is based on the clinical course of the healing process. According to Ritschl's classification stage A is the

most common (6).

FCD and NOF differ in terms of size and clinical course. These two lesions usually disappear with advancing age. NOFs are large and typically symptomatic, while FCDs are generally small and asymptomatic (3). 

Pathologic fractures occur in up to 20% of NOFs (13). Fractures are likely to occur in NOFs that are more than 33 mm long (9). It is, however, unclear whether the lesion size is associated with the occurrence of fracture (14). 

Absolute size parameters may be useful in predicting pathologic fracture rates. They however do not imply a requirement for prophylactic curettage and bone grafting. Patients with a stage B lesion have an increased risk of pathologic fractures (6). Thus, combining lesion size and Ritschl classification may be important for evaluating and predicting pathologic fracture.

Conclusion

Non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) are common bone lesions. They are usually found in skeletally immature patients under the age of 15 years. They are often discovered incidentally. FCD and NOF are present in up to 30% of children during their skeletal growth period. These two lesions usually disappear with advancing age. NOFs are large and typically symptomatic, while FCDs are generally small and asymptomatic (3). Pathologic fractures occur in up to 20% of NOFs. Prophylactic curettage and bone grafting is not required.

References

1. Baumhoer D, Rogozhin DV. Non-ossifying fibroma. In: WHO Classification of Tumours of Soft Tissue and Bone. 5th ed. Lyon: IARC Press; 2020. P.447–8.

2. Stacy GS, Dixon LB. Pitfalls in MR image interpretation prompting referrals to an orthopedic oncology clinic. Radiographics. 2007;27(3):805–26.

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