December 2019: Bilateral mandibular multilocular radiolucencies
Can you make the correct diagnosis?
This is an 11-year-old male who was referred to an oral surgeon by his pediatric dentist for evaluation of delayed eruption of teeth #s 18 and 31 and evaluation of bilateral, multilocular radiolucent lesions in the posterior mandible.
Sorry, you are incorrect!
A multilocular radiolucency in the mandible of a young patient should bring CGCG to mind. The site in the posterior molars and ramus argues against CGCG, however, as does the patient’s sex since CGCG tends to be more common in females. The bilateral presentation is not consistent with CGCG. The histology, however, is that of a giant cell lesion, which indicates a differential diagnosis of at least three conditions: CGCG, Cherubism, and hyperparathyroidism.
Central giant cell granuloma (CGCG) is described as a non-neoplastic process and yet can behave in a very aggressive and expansile manner, destroying bone and displacing teeth. Over 60% of CGCG cases occur in patients younger than 30 years of age, with twice as many occurrences in females. CGCG is classified into aggressive and non-aggressive types. The aggressive type tends to occur in younger patients with disfiguring results, especially after surgery. Over 70% of cases occur in the mandible anterior to the first molar tooth. The usual treatment for CGCG is surgery, ranging from curettage and en bloc to resection. The latter is used in aggressive and recurring cases. However, treatments alternative to surgery are also present and include steroid intralesional injections, the most successful alternative treatment thus far, which require injections weekly or every 2-3 weeks, have no known side effects (even in children), and are the least expensive alternative treatment. Another alternative treatment is calcitonin injections or nasal spray, which require daily injections or a nasal spray of salmon calcitonin for about a year and are safe for pregnant females. A third alternative successful treatment is the use of interferon alfa-2a injections, which are administered 2-3 times per week for several months and are the most expensive alternative treatment. Although the histology and some of the clinical and radiographic findings in this case are consistent with CGCG, the fact that this condition is symmetrically bilateral is not supportive of it.
Sorry, you are incorrect!
The multiple and multilocular radiolucencies in the jawbone should bring brown tumors of primary hyperparathyroidism to consideration on the differential diagnosis. The age and gender of the patient, however, argue against that diagnosis.
Three types of hyperparathyroidism—primary, secondary, and tertiary—are described: the primary type is the most common, while the secondary and tertiary types are the least common. All three types are characterized by excess parathyroid hormone production. Primary hyperparathyroidism is usually caused by adenoma of the parathyroid gland, but is sometimes a result of hyperplasia (in about 10% of cases) and is rarely caused by adenocarcinoma. Secondary hyperparathyroidism is a sequelae to chronic renal disease (renal osteodystrophy). Primary hyperparathyroidism is three times more common in females than males and typically occurs in patients in their fifties and older. The clinical presentation is characteristically referred to as “bones, stones, groans and moans”—affecting multiple organs including bones, kidneys (stones), the gastrointestinal system (groans), and muscles and the central nervous system (moans). The bone lesions are painful multiple unilocular and multilocular radiolucencies that affect the fingers and the skull, including the jawbones. The lesions in these bones are called ‘brown tumors’ because of the deep chocolate brown color of the specimens resulting from hemorrhage and hemosiderin pigmentation. Kidney stones are result of hypercalcemia affecting the kidneys and skin. The “groans” are related to intestinal ulcers and constipation, and “moans” are related to alteration in the central nervous system such as depression and sometimes seizures. This patient will be tested for hyperparathyroidism but the clinical presentation argues against it. Histologically, the lesion is made up of granulation tissue and giant cells but that is not enough to call it brown tumor of hyperparathyroidism.
Congratulations, you are correct!
The bilateral multilocular radiolucency involving the posterior mandible and ramus, when combined with the age of this patient, is consistent with the clinical presentation of Cherubism.
This benign condition involves bilateral swelling of the maxilla and/or the mandible. It was first described by Jones in 1933 as a familial multilocular cystic disease of the jaws. Most cases are hereditary (autosomal dominant) with 100% penetrance in males and 50-70% penetrance in females. A non-hereditary form is also described but is rare. Both types of Cherubism occur during childhood in patients as young as 1 year of age with an average age of 7. They typically regress after puberty; in rare cases, they may continue to grow even after age 20. They characteristically present with symmetrical bilateral cheek swelling involving the angle of the mandible. The mandible is more commonly involved, sparing the condyle and involving the coronoid process. It can affect all four quadrant and maxillary sinuses. The fullness of the maxilla and sinuses leads to the upward rotation of the eyes with a cherubic look—hence, the name “Cherubism”—due to orbital floor involvement. Diplopia is not present. Radiographically, there are multilocular radiolucencies with corticated borders. The multilocular compartments can be well defined with clear septa formation or can be coarse. The latter is seen during regression of the disease. Cherubism can be expansile and disfiguring. It may thin the bone to the point of perforation, but fracture is rare. Early resorption and exfoliation of the deciduous teeth is described. Displacement of permanent teeth has also been described. The histology of Cherubism consists of granulation tissue stroma, giant cells and blood vessels with hyaline deposits. The histology of the present case fits the characteristics well. Cherubism can spontaneously regress after puberty. Loss of loculation, of expansion and filling of the bony spaces with normal bone are signs of regression. However, if the lesion is large and disfiguring, surgical intervention is considered knowing that this lesion can spontaneously regress. Cherubism is also known to be associated with syndromes such as Noonan’s syndrome and is described to occasionally affect other bones such as the ribs.
Sorry, you are incorrect!
The site in the posterior mandible affecting the ramus and the radiolucent lesions is consistent with multiple odontogenic keratocysts (OKCs) associated with bifid rib-basal cell nevus syndrome. However, the patient’s age and the multilocular morphology are not typical of conventional OKCs. The gender is consistent with OKCs, conventional and syndromic.
Odontogenic keratocyst is an aggressive cyst of tooth origin. It is known for its rapid growth and its tendency to invade the adjacent tissues and perforate bone. The majority of OKCs occur as single and isolated lesions that are not associated with a syndrome. Conventional OKCs are usually unilocular with a scalloped border radiographically while this case shows bilateral multilocular radiolucencies. However, OKC can present in multiples as part of bifid-rib basal cell nevus syndrome (Gorlin syndrome). This syndrome is an autosomal dominant disorder arising from defects on chromosome 9q23.1-q31, and is often identified in juvenile kindred under 10 years of age. When so associated, the cysts are frequently multiple and the patient is generally young such as in the present case. They present more frequently in the mandible, can be multilocular and tend to grow in an anterior-posterior manner extending into the ramus. They are known to have a high recurrence rate, ranging from 13% to 60%. Complete surgical removal is the treatment of choice. Surgery combined with Carnoy’s solution or liquid nitrogen cauterization has been effective in reducing recurrence rate. At times, adjacent or associated teeth are extracted in the interest of complete removal. Some investigators advocate marsupialization and occasionally resection of the more aggressive cysts that tend to perforate buccal and lingual bone. Resection is a rare modality of treatment. Most cysts recur within the first three years while others may recur as late as after 16-26 years. Conservative surgical removal and long-term follow-up is the treatment of choice by most clinicians. OKCs have a specific histology which was not consistent with the histology of this case.