JAWBONES ILLNESSES.
CHANGES OF MAXILLOFACIAL SKELETON.
TUMOURS OF THE TEETH-JAW SYSTEM
Pyogenic osteomyelitis is almost always caused by bacteria. Organisms may reach the bone by (1) hematogenous spread, (2) extension from a contiguous site, and (3) direct implantation. Most cases of osteomyelitis are hematogenous in origin and develop in the long bones or vertebral bodies in otherwise healthy individuals. The initiating bacteremia may follow trivial occurrences, such as occult injury to the intestinal mucosa during defecation, vigorous chewing of hard foods, or minor infections of the skin.
Staphylococcus aureus is responsible for 80 % to 90 % of the cases of pyogenic osteomyelitis in which an organism is recovered (Table 1). Its propensity to infect bone may be related to the fact that it expresses receptors for bone matrix components such as collagen, thereby facilitating its adherence to bone tissue. Escherichia coli, Pseudomonas, and Klebsiella are more frequently isolated from patients with genitourinary tract infections or those who are intravenous drug abusers. Mixed bacterial infections are seen in the setting of direct spread or inoculation of organisms during surgery or open fractures. In the neonatal period, Haemophilus influenzae and group B streptococci are frequent pathogens; patients with sickle cell disease, for unknown reasons, are predisposed to Salmonella infection. In almost 50 % of cases, no organisms can be isolated.
|
TABLE 1 Etiology of pyogenic osteomyelitis |
|
|
Age group |
Most common organisms |
|
Newborns (younger than 4 mo.) |
S. aureus, Enterobacter species, and group A and B Streptococcus species |
|
Children (aged 4 mo. to 4 y.) |
S. aureus, group A Streptococcus species, Haemophilus influenzae, and Enterobacter species |
|
Children, adolescents (aged 4 y. to adult) |
S. aureus (80 %), group A Streptococcus species, H. influenzae, and Enterobacter species |
|
Adult |
S. aureus and occasionally Enterobacter or Streptococcus species |
The location of the lesions within specific bones is influenced by the vascular circulation, which varies with age. In the neonate, the metaphyseal vessels penetrate the growth plate, resulting in frequent infection of the metaphysis, epiphysis, or both. In children, localization of microorganisms in the metaphysis is typical. After growth plate closure, the metaphyseal vessels reunite with their epiphyseal counterparts and provide a route for the bacteria to seed the epiphyses and subchondral regions in the adult.
Morphology. The morphologic changes in osteomyelitis depend on the stage (acute, subacute, or chronic) and location of the infection. Once localized in bone, the bacteria proliferate and induce an acute inflammatory reaction and cause cell death. The entrapped bone undergoes necrosis within the first 48 hours, and the bacteria and inflammation spread within the shaft of the bone and may percolate throughout the haversian systems to reach the periosteum.
In children, the periosteum is loosely attached to the cortex; therefore, sizable subperiosteal abscesses may form, which can trek for long distances along the bone surface. Lifting of the periosteum further impairs the blood supply to the affected region, and both suppurative and ischemic injury may cause segmental bone necrosis; the dead piece of bone is known as the sequestrum. Rupture of the periosteum leads to an abscess in the surrounding soft tissue and the eventual formation of a draining sinus. Sometimes the sequestrum crumbles and forms free foreign bodies that pass through the sinus tract.
In infants, but uncommonly in adults, epiphyseal infection spreads through the articular surface or along capsular and tendoligamentous insertions into a joint, to produce septic or suppurative arthritis, sometimes causing extensive destruction of the articular cartilage and permanent disability. An analogous process involves the vertebrae, in which the infection destroys the hyaline cartilage end plate and intervertebral discs and spreads into adjacent vertebrae.
Over time, the host response develops, and after the first week of infection chronic inflammatory cells become more numerous. The release of cytokines from leukocytes stimulates osteoclastic bone resorption, ingrowth of fibrous tissue, and the deposition of reactive bone in the periphery. Reactive woven or lamellar bone may be deposited, and when it forms a sleeve of living tissue around a segment of devitalized bone, it is known as an involucrum. Several morphologic variants of osteomyelitis have been given eponyms because of their distinguishing features: Brodie abscess is a small intraosseous abscess that frequently involves the cortex and is walled off by reactive bone; sclerosing osteomyelitis of Garre typically develops in the jaw and is associated with extensive new bone formation that obscures much of the underlying osseous structure.
Clinical Course. Clinically, hematogenous osteomyelitis may manifest as an acute systemic illness with malaise, fever, chills, leukocytosis, and throbbing pain, often intense, over the affected region. The presentation may be subtler with only unexplained fever, particularly in infants, or only localized pain in the absence of fever in the adult. The diagnosis can be strongly suggested by the characteristic x-ray findings of a lytic focus of bone destruction surrounded by a zone of sclerosis.
Figure. Acute suppurative apical periodontitis with the transition of osteomyelitis (4).
Figure. Osteomyelitis of jaws. Osteonecrosis, acute inflammation and fibrosis.
In many untreated cases, blood cultures are positive, but biopsy and bone cultures are required to identify the pathogen in most instances. The combination of antibiotics and surgical drainage is usually curative. In 5 % to 25 % of cases, acute osteomyelitis fails to resolve and persists as chronic infection. Chronicity may develop when there is delay in diagnosis, extensive bone necrosis, abbreviated antibiotic therapy, inadequate surgical debridement, and weakened host defenses. Acute flare-ups may mark the clinical course of chronic infection; they are usually spontaneous, have no obvious cause, and may occur after years of dormancy. Other complications of chronic osteomyelitis include pathologic fracture, secondary amyloidosis, endocarditis, sepsis, development of squamous cell carcinoma in the sinus tract, and rarely sarcoma in the infected bone.
Figure. Chronic osteomyelitis of the jaw with the formation of sequestration.
ODONTOGENIC SEPSIS
A sepsis is the special form of infectious disease which often has hard development and is characterized by high lethality. Its polyethiologity (very much many microorganisms can be reason of illness), special reaction of the immune system on an infection, clinical (there is no recurrence in development, not depending on an exciter manifestation of sepsis of the same types), epidemiologys (not contagious disease), pathomorphological features, is characterized (the local and general changes do not have the specific manifestation).
In pathogenic of sepsis an important place is taken to bacteriaemia. Development of sepsis is predefined by the special reaction of macroorganism often it is hyperergic reaction, absence of immunoreaction, acyclicity of development, advantage of general reaction on the hit of microorganisms.
Pathomorphology of sepsis is presented by the local and general manifestation. The local changes develop in the hearth of penetration of microorganisms (septic hearth) or on the way of their distribution:
o lymphangitis,
o lymphadenitis,
o lymphotrombosis,
o phlebitis,
o thrombophlebitis.
A septic hearth more frequent shows up festering inflammation. The general changes are presented by dystrophic, inflammatory, hyperplastical processes in different organs. The dystrophic and inflammatory (intermediate or interstitial inflammation) changes develop in parenchimatous organs and vessels, that predetermines the increase vascular – tissue penetrating and development of hemorragic syndrome and hemolytic icterus.
Hyperplastic processes mainly develop in the lymphoid and hemopoetic system: a generalized lymphadenopathy is the increase of lymphatic knots; septic spleen – acutely megascopic, rose, loose, gives large scrape of pulpa; hyperplasia of marrow and his metaplasia; leukocytosis with development even leukemoid reaction.
Classification of sepsis is based on etiology, entrances gate clinical-morphological manifestation.
After etiology a sepsis can be related to the different microorganisms (by bacteria, fungi, and others like that). Today more frequent meets staphylococcus and pseudomonas aeruginosa sepsis.
After an entrances gate a sepsis is: surgical, therapeutic, wound, umbilical, fallopian, otogenic, odontogenic, tonsilogenic, urology, criptogene (an entrances gate not is known). Lately began to select a paratherapeutic sepsis, when an infection is brought in an organism during implementation of medical manipulations: incubation (an entrances gate is lungs), cannulation, imposition of vascular shunts, and others like that.
After clinical-morphological features distinguish the following forms of sepsis:
(1) septicaemia,
(2) septicopyemia,
(3) septic (bacterial) endocarditis,
(4) chroniosepsis.
SEPTICAEMIA is characterized to the fasts (a few days), sometimes by fleeting development, expressed intoxication (high temperature disorder of consciousness) enhanceable reactivity of organism (hyperergy), sometimes by absence of septic abscess, by predominance of general changes in an organism: dystrophy and intermediate inflammation of parenchimatous organs (septic spleen, and others like that), vasculites, DIC syndrome, hyperplasia of the lymphoid and hemopoetical systems. Development of Septicaemia is often related to streptococcus. On a skin, mucuses membranes there is the expressed hemorragic syndrome icterus. Patients die from endotoxical shock, hemorrhages in suprarenal glands with development of acute suprarenal deficiency.
Figure. Hemorrhagic rash with septicemia.
A SEPTICOPYEMIA is characterized by predominance of festering processes in a gate and distribution them on all organism due to development of bacterial embolies by staphylococcuss, pseudomonas aeruginosa in lungs, liver, kidneys, marrow, synovial membranes, on the valves of heart, membranes and tissue of cerebrum, by the protracted development – a few weeks hyperplastical processes, intermediate inflammation expressed insignificantly. Among complications select the empyema of pleura, peritonitis, phlegmons of skin.
Figure. Septic emboli in blood vessels in the lungs.
A SEPTIC (BACTERIAL) ENDOCARDITIS develops as a result of septic damage of valves of heart with the hyperergic manifestation as a result of circulation of toxic immune complexes.
Etiology – more frequent aureus and albe staphylococcus green streptococcus, rarer is enterococcus.
Classification.
1. By character of development:
o acute is duration about 2 weeks,
o subacute – 3 months,
o chronic are months and years.
2. Presence or absence of base-line disease:
o primary septic endocarditis or illness of Chornoguzov – develops on the unchanged valves (20-30%),
o second septic endocarditis – develops on a background the defect of heart (rheumatic, atherosclerotic, syphilitic, borning), on prosthesis of valves.
A pathoanatomy is presented by the local and general changes. A polypous-ulcerous endocarditis which more frequent develops on an aortic valve belongs to the local manifestation, rarer – on mitral, and at drug addicts – on tricuspidal. Macroscopically find the considerable areas of necrosises and ulcering with destruction of valve, formation at them of defects, sometimes with fenestration, tearing off of particle of valve and development of tissue embolism. Trombotical masses which spread on an endocardium and wall of aorta deposite often in ulcers. If a septic endocarditis develops on the damaged valves, here the phenomena of sclerosis, hyalinosis early calcification leaves of valves, hypertrophy of myocardium, take place. The microscopic changes are presented by polymorphic-nuclear leukocyte, lympho-macrophage infiltration of wall of valve, presence of colonies of microorganisms, considerable deposites of salts of calcium, in trombotical masses.
Figure. This is infective endocarditis. The aortic valve demonstrates a large, irregular, reddish tan vegetation.Virulent organisms, such as Staphylococcus aureus, produce an “acute” bacterial endocarditis, while some organisms such as Streptococcus viridans produce a “subacute” bacterial endocarditis [http://library.med.utah.edu].
Figure. The more virulent bacteria causing the acute bacterial form of infective endocarditis can lead to serious destruction, as shown here in the aortic valve. Irregular reddish tan vegetations overlie valve cusps that are being destroyed. Portions of the vegetation can break off and become septic emboli. [http://library.med.utah.edu].
Figure. This angiogram demonstrates the aortic arch and great vessels. An embolus from a cardiac valvular vegetation from the left side of the heart can travel out the systemic circulation. Shown here is a septic embolus from infective endocarditis travelling up the left common carotid artery, which could result in a cerebral infarction and/or abscess. [http://library.med.utah.edu].
Figure. In this case, the infective endocarditis demonstrates how the infection tends to spread from the valve surface. Here, vegetations can be seen on the endocardial surfaces, and the infection is extending into to underlying myocardium. [http://library.med.utah.edu].
Figure. Here, infective endocarditis on the mitral valve has spread into the septum all the way to the tricuspid valve, producing a fistula. [http://library.med.utah.edu].
Figure. Microscopically, the valve in infective endocarditis demonstrates friable vegetations of fibrin and platelets (pink) mixed with inflammatory cells and bacterial colonies (blue). The friability explains how portions of the vegetation can break off and embolize. [http://library.med.utah.edu].
Figure. Here is a valve with infective endocarditis. The blue bacterial colonies on the lower left are extending into the pink connective tissue of the valve. Valves are relatively avascular, so high dose antibiotic therapy is needed to eradicate the infection. [http://library.med.utah.edu].
The general manifestations of endocarditis are:
(1) septic spleen (megascopic in sizes, tense capsule, gives considerable scrape, often there are infarcts, at chronic development is sclerosis and compression);
(2) generalized alterative-productive vasculitis especially in the vessels of microcirculation with development of plural petechial hemorrhages on a skin, mucuses and serosal membranes conjunctiva (a lower eyelid near an internal edge are Lukin-Libman spots – pathognomical sign);
(3) immune complex diffuse glomerulonephritis;
(4) artritis;
(5) are tromboembolical complications with development of infarcts in a spleen, kidneys, cerebrum, gangrene.
Before the peripheral manifestation take also the knots bulges on the hands of brush are knots of Osler, bulges of nail flanks («drumsticks»), cells of necrosis in a fatty hypoderm, dermatorrhagias and hypoderm (spots of Jeynuey), icterus.
Figure. Seen here in the finger at the right are small splinter hemorrhages in a patient with infective endocarditis. These hemorrhages are subungual, linear, dark red streaks. Similar hemorrhages can also appear with trauma. [http://library.med.utah.edu].
Figure. Another small linear splinter hemorrhage is seen here subungually on the left thumb of a patient with infective endocarditis and blood culture positive for Staphylococcus aureus. [http://library.med.utah.edu].
Figure. Knots of Osler.
Figure. Spots of Jeynuey.
Chroniosepsis form of sepsis, which has the following signs:
o long-term development,
o decreasing of reactivity of organism,
o presence septic hearth which lasted does not heal (carious tooth, chronic tonsillitis wound, with suppuration),
o chronic intoxication with exhaustion (pyoresorptive fever),
o brown atrophy of organs (hearts, livers, and others like that),
o atrophy and hemosiderosis of spleen,
o lardaceous of internalss.
To the tumor-like lesions take:
Fibrous dysplasia is a benign tumor that has been likened to a localized developmental arrest; all of the components of normal bone are present, but they do not differentiate into their mature structures. The lesions appear in three distinctive but sometimes overlapping clinical patterns:
(1) involvement of a single bone (monostotic);
(2) involvement of multiple, but never all, bones (polyostotic);
(3) polyostotic disease, associated with cafe au lait skin pigmentations and endocrine abnormalities, especially precocious puberty.
The skeletal, skin and endocrine lesions result from a somatic (not hereditary) mutation occurring during embryogenesis that involves the gene that codes for a guanine nucleotide-binding protein (G-protein). The G-proteiormally couples receptors to the effector enzyme adenylyl cyclase, and the mutation results in constitutive activation of the enzyme so that excess production, of cAMP occurs, leading to hyperfunction of cells in the involved tissues.
Monostotic fibrous dysplasia accounts for 70 % of all cases. It occurs equally in boys and girls, usually in early adolescence, and often stops growing at the time of growth plate closure. The ribs, femur, tibia, jawbones, calvaria, and humerus are most commonly affected, in descending order of frequency. The lesion is asymptomatic and usually discovered incidentally. Fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the craniofacial skeleton is involved, disfigurement, sometimes severe, can occur. Monostotic disease does not evolve into the polyostotic form.
Polyostotic fibrous dysplasia without endocrine dysfunction accounts for 27 % of all cases. It manifests at a slightly earlier age than the monostotic type and may continue to cause problems into adulthood. The bones affected, in descending order of frequency, are the femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, and vertebrae. Craniofacial involvement is present in 50 % of patients who have a moderate number of bones affected and in 100 % of patients with extensive skeletal disease. All forms of polyostotic disease have a propensity to involve the shoulder and pelvic girdles, resulting in severe, sometimes crippling, deformities (e.g., shepherd-crook deformity of the proximal femur) and spontaneous and often recurrent fractures.
Figures. Deformation of person is at fibrous dysplasia.
Polyostotic fibrous dysplasia associated with cafe au lait skin pigmentation and endocrinopathies is known as the McCune-Albright-syndrome and accounts for 3 % of all cases. The endocrinopathies include sexual precocity, hyperthyroidism, pituitary adenomas that secrete growth hormone, and primary adrenal hyperplasia. The severity of manifestations in McCune-Albright syndrome depends on the number and cell types that harbor the mutation in the G-protein. The most common clinical presentation is precocious sexual development, and in this setting girls are affected more often than boys. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large; are dark to cafe au lait; have irregular serpiginous borders (coastline of
Morphology.
Figure. Representative panoramic radiographs (a) and photomicrographs of H&E-stained (b, c) gnathic fibrous dysplasia. In panoramic radiographs, gnathic fibrous dysplasia is homogeneously radio-opaque with a ground-glass appearance and poorly defined margins indicated by the red arrow. The photomicrographs show that gnathic fibrous dysplasia shows thin irregular-shaped woven bone that resembles membranous ossification.
Grossly the lesions of fibrous dysplasia are well-circumscribed, are intramedullary, and vary greatly in size. Larger lesions expand and distort the bone. The lesional tissue is tan-white and gritty and is composed of curvilinear trabeculae of woven bone surrounded by a moderately cellular fibroblastic proliferation. The shapes of the trabeculae mimic Chinese characters, and the bone lacks osteoblastic rimming. Nodules of hyaline cartilage with the appearance of disorganized growth plate are also present in approximately 20 % of cases. Cystic degeneration, hemorrhage, and foamy macrophages are other common findings.
Clinical Coarse. The natural history of fibrous dysplasia is variable and depends on the extent of skeletal involvement. Patients with monostotic disease usually have minimal symptoms. The lesion is readily diagnosed by x-ray because of its typical ground-glass appearance and well-defined margins. Lesions that fracture or cause significant symptoms are readily cured by conservative surgery. Polyostotic involvement is frequently associated with progressive disease, and the earlier the age at diagnosis, the more likely are severe skeletal complications, such as recurring fractures, long bone deformities, and distorting involvement of the craniofacial bones. A rare complication, usually in the setting of polyostotic involvement, is malignant transformation of a lesion into a sarcoma, such as osteosarcoma, or malignant fibrous histiocytoma. The risk of this occurrence is increased if the lesion has been irradiated.
Paget Disease (Osteitis Deformans).
This unique skeletal disease can be characterized as a collage of matrix madness. At the outset, Paget disease is marked by regions of furious osteoclastic bone resorption, which is followed by a period of hectic bone formation, and then finally the bone cell activity becomes markedly diminished. This repetitive and overlapping sequence forms the basis for dividing Paget disease into (1) an initial osteolytic stage, followed by (2) a mixed osteoclastic-osteoblastic stage, which ends with a predominance of osteoblastic activity and evolves ultimately into (3) a burnt-out quiescent osteosclerotic stage. The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and architecturally unsound.
Paget disease usually begins during mid-adulthood and becomes progressively more common thereafter. An intriguing aspect is the striking variation in prevalence both within certain countries and throughout the world. Paget disease is relatively common in whites in
Figure. The bust of Sir James Paget in the
Pathogenesis. When Sir James Paget first described this condition in 1876, he attributed the skeletal changes to an inflammatory process, hence the term osteitis deformans.
It is ironic that after numerous subsequent hypotheses were proposed, Paget may be finally proven correct. Current evidence suggests a slow virus infection by a paramyxovirus as the cause of Paget disease. This likens it to other slow virus diseases, such as subacute sclerosing leukoencephalitis, produced by the same family of viruses. Viral particles resembling the nucleocapsids of paramyxovirus have been seen in the cytoplasm and nuclei of osteoclasts, and immunologic analyses have identified antigens associated with both the measles and respiratory syncytial viruses (both paramyxoviruses) in osteoclasts from affected sites. Additionally, measles virus nucleocapsid transcripts have been identified in bone cells from pagetic tissue. Viruses such as the paramyxovirus can induce the secretion of IL-6 from infected cells. This cytokine, as well as M-CSF, are produced in large amounts in pagetic bone; they are potent stimulators of osteoclast recruitment and resorptive activity. Intriguing as these observations may be, to date no infectious virus has been isolated from affected tissue.
There is some evidence that osteoclasts are abnormal in this disease, and hyperresponsive to activating agents such as vitamin D and RANKL. Additionally, Paget disease has a hereditary component, as it has a high incidence within families and its predisposition has been linked to a locus on chromosome 18q.
Morphology. Paget disease is a focal process with remarkable variation in its stage of development in separate sites.
The histologic hallmark is the mosaic pattern of lamellar bone. This pattern, which is likened to a jigsaw puzzle, is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone. In the initial lytic phase, there are waves of osteoclastic activity and numerous resorption pits. The osteoclasts are abnormally large and have many more than the normal 10 to 12 nuclei; sometimes 100 nuclei are present. Osteoclasts persist in the mixed phase, but now many of the bone surfaces are lined by prominent osteoblasts.
Figure. Paget disease of the jawbone.
Figure. Mosaic pattern of lamellar bone pathognomonic of Paget disease.
Figure. Electron microscopic examination revealing microfilaments within remnants of a degenerating osteoclast nucleus. The arrow indicates microfilaments in adjacent cytoplasm.
The marrow adjacent to the bone-forming surface is replaced by loose connective tissue that contains osteoprogenitor cells and numerous blood vessels, which transport nutrients and catabolites to and from these metabol-ically active sites. The newly formed bone may be woven or lamellar, but eventually all of it is remodeled into lamellar bone. As the mosaic pattern unfolds and the cell activity decreases, the periosseous fibrovascular tissue recedes and is replaced by normal marrow. In the end, the bone becomes a caricature of itself: larger thaormal and composed of coarsely thickened trabeculae and cortices that are soft and porous and lack structural stability. These aspects make the bones vulnerable to deformation under stress; consequently, they fracture easily.
Clinical Course. Clinical findings are extremely variable and depend on the extent and site of the disease. Most cases are mild and are discovered as an incidental radiographic finding. Paget disease can, however, produce a variety of skeletal, neuromuscular, and cardiovascular complications.
The diagnosis can frequently be made from the radiographic findings. Pagetic bone is typically enlarged with thick, coarsened cortices and cancellous bone. Many patients exhibit an elevated serum level of alkaline phosphatase and increased urinary excretion of hydroxyproline.
Paget disease occurs in one or more bones. It is monostotic (tibia, ilium, femur, skull, vertebra, and humerus) in about 15 % of cases and polyostotic (pelvis, spine, and skull) in the remainder. The axial skeleton or proximal femur is involved in up to 80 % of cases. Even though no bone is immune, involvement of the ribs, fibula, and small bones of the hands and feet is unusual.
Pain is the most common problem and is localized to the affected bone. It is caused by a combination of microfractures and bone overgrowth that compresses spinal and cranial nerve roots. Bone overgrowth in the craniofacial skeleton may produce leontiasis ossea and a cranium so heavy that it becomes difficult for the patient to hold the head erect. The weakened pagetic bone may lead to invagination of the base of the skull (platybasia) and compression of the posterior fossa structures. Weight bearing causes anterior bowing of the femora and tibiae and distorts the femoral heads, resulting in the development of severe secondary osteoarthritis. Chalkstick-type fractures are the next most common complication and usually occur in the long bones of the lower extremities. Compression fractures of the spine result in spinal cord injury and the development of kyphoses. The hypervascularity of pagetic bone warms the overlying skin; in severe polyostotic disease the increased blood flow behaves as an arteriovenous shunt leading to high-output heart failure or exacerbation of underlying cardiac disease.
A variety of tumor and tumor-like conditions develop in pagetic bone. The benign lesions include giant cell tumor, giant cell reparative granuloma, and extraosseous masses of hematopoiesis. The most dreaded complication is the development of sarcoma, which occurs in 0.7 % to 0.9 % of all patients with Paget disease but increases to 5 % to 10 % in those patients with severe polyostotic disease. The sarcomas are usually osteosarcoma, malignant fibrous histiocytoma, or chondrosarcoma, and they arise in the long bones, pelvis, skull, and spine. In the absence of malignant transformation, Paget disease is usually not a serious or life-threatening disease. Most patients have mild symptoms that are readily suppressed by calcitonin and bisphosphonates.
ODONTOGENIC CYSTS, ODONTOGENIC TUMORS,
FIBROOSSEOUS, AND GIANT CELL LESIONS OF THE JAWS
Abstract
Odontogenic cysts that can be problematic because of recurrence and/or aggressive growth include odontogenic keratocyst (OKC), calcifying odontogenic cyst, and the recently described glandular odontogenic cyst. The OKC has significant growth capacity and recurrence potential and is occasionally indicative of the nevoid basal cell carcinoma syndrome. There is also an orthokeratinized variant, the orthokeratinized odontogenic cyst, which is less aggressive and is not syndrome associated. Ghost cell keratinization, which typifies the calcifying odontogenic cyst, can be seen in solid lesions that have now been designated odontogenic ghost cell tumor. The glandular odontogenic cyst contains mucous cells and ductlike structures that may mimic central mucoepidermoid carcinoma. Several odontogenic tumors may provide diagnostic challenges, particularly the cystic ameloblastoma. Identification of this frequently underdiagnosed cystic tumor often comes after one or more recurrences and a destructive course. Other difficult lesions include malignant ameloblastomas, calcifying epithelial odontogenic tumor, squamous odontogenic tumor, and clear-cell odontogenic tumor. Histologic identification of myxofibrous lesions of the jaws (odontogenic myxoma, odontogenic fibroma, desmoplastic fibroma) is necessary to avoid the diagnostic pitfall of overdiagnosis of similar-appearing follicular sacs and dental pulps. Fibroosseous lesions of the jaws show considerable microscopic overlap and include fibrous dysplasia, ossifying fibroma, periapical cementoosseous dysplasia, and low-grade chronic osteomyelitis. The term fibrous dysplasia is probably overused in general practice and should be reserved for the rare lesion that presents as a large, expansile, diffuse opacity of children and young adults. The need to use clinicopathologic correlation in assessing these lesions is of particular importance. Central giant cell granuloma is a relatively common jaw lesion of young adults that has an unpredictable behavior. Microscopic diagnosis is relatively straightforward; however, this lesion continues to be somewhat controversial because of its disputed classification (reactive versus neoplastic) and because of its management (surgical versus. medical). Its relationship to giant cell tumor of long bone remains undetermined.
INTRODUCTION
The jaws are host to a wide variety of cysts and neoplasms, due in large part to the tissues involved in tooth formation. Many benign jaw tumors and several cysts (some recently described), of both odontogenic and nonodontogenic origin, can exhibit a biologically aggressive course and can be diagnostically difficult. Traditional histopathology continues to be the mainstay for the diagnosis of these lesions, as immunohistochemistry and molecular techniques have had, as yet, little impact in this area.
ODONTOGENIC CYSTS OF DIAGNOSTIC SIGNIFICANCE
Odontogenic Keratocyst
The odontogenic keratocyst (OKC) is a commonly encountered developmental cyst (Table 2) of considerable importance because of its potential for aggressive clinical behavior and recurrence. Also, it may be a component of the nevoid-basal cell carcinoma (Gorlin) syndrome. OKC occurs anywhere in the jaws and in any position. It may be superimposed over the apices of tooth roots or adjacent to the crowns of impacted teeth. Radiographically, it appears as a well-defined lucency and is often multilocular. OKCs represent 5–15 % of all odontogenic cysts. The recurrence rate for solitary OKC is 10–30 %. Approximately 5 % of OKC patients have multiple jaw cysts (and no syndrome), and their recurrence rate is greater than that for solitary lesions.
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TABLE 2 Current Classification of Jaw Cysts |
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Odontogenic |
Nonodontogenic |
Pseudocysts |
|
Inflammatory |
Nasopalatine cyst |
Traumatic bone cyst |
|
Periapical cyst and granuloma |
|
Static bone cyst |
|
Developmental |
Hematopoietic bone marrow defect. |
|
|
Dentigerous cyst and eruption cyst |
|
|
|
Lateral periodontal cyst |
||
|
Odontogenic keratocyst |
||
|
Calcifying odontogenic cyst |
||
|
Glandular odontogenic cyst |
||
Figure. Odontogenic keratocyst of the entire right mandibular body.
Microscopically, the epithelial lining exhibits a characteristic thickness of 6–10 cell layers. The epithelium shows basal palisading and a thin refractile parakeratinized lining layer. Separation of the epithelium from the thin and uninflamed supporting fibrous wall is often seen. Budding of the basal layer and “daughter cyst” formation are frequently findings. If the cyst wall becomes secondarily inflamed, hyperplasia ensues and the characteristic microscopic pattern disappears. Sampling of large cysts may be important for identifying an underlying OKC that has become secondarily inflamed. The epithelial proliferation rate in the OKC is relatively high, especially in the case of those that are syndrome associated. Other advantageous growth mechanisms of OKCs include Bcl-2, cyclin D1, and MDM2 overexpression.
Figure. A: odontogenic keratocyst showing thin parakeratinized lining with basal palisading. Separation of epithelium from connective tissue wall is often seen in surgical specimens.B: orthokeratinized odontogenic cyst showing granular layer and in undistinguished basal layer.
There is an orthokeratinized variant known as orthokeratinized odontogenic cyst. It exhibits similar microscopic features, except that it has a granular layer, is orthokeratotic, and has a poorly organized basal layer. It is not syndrome-associated (see below) and seems to exhibit a less aggressive behavior than OKC. Rarely, OKCs may show foci of orthokeratinization in an otherwise parakeratinized lining.
Figure. Odontogenic keratocyst.
The nevoid-basal cell carcinoma syndrome is inherited as an autosomal dominant trait that consists principally of multiple odontogenic keratocysts, multiple basal cell carcinomas, skeletal anomalies, and cranial calcifications. Syndrome-associated OKCs have the highest recurrence rate and represent approximately 5 % of all OKC patients. Many other syndrome manifestations have been described, including medulloblastoma and other neoplasms. The basal cell carcinomas develop early in life and may number in the tens or hundreds. The most frequently cited skeletal anomaly is bifid rib. Calcified falx is also relatively frequently seen on skull radiograms. This syndrome has been linked to mutations in the PATCHED tumor suppressor gene that encodes a receptor protein that is a component of the hedgehog signaling pathway. Mutations of this gene have been found in syndrome-associated basal cell carcinomas and OKCs.
Calcifying Odontogenic Cyst
Calcifying odontogenic cyst (COC) is a developmental cyst that may exhibit occasional aggressive/recurrent behavior. This is particularly true of an occasionally encountered solid variant that is regarded as a neoplasm and termed odontogenic ghost cell tumor. A very rare malignant variety of odontogenic ghost cell tumor has been reported as odontogenic ghost cell carcinoma.
Figure. Calcifying odontogenic cyst featuring ghost cell keratinization with dystrophic calcification and palisaded basal layer.
COC shows a predilection for females and the maxilla. It occasionally is seen in the gingiva. It may be unilocular or multilocular and may show areas of opacification because of the partial calcification of keratinized lining cells. The distinctive microscopic feature of this lesion, be it cystic or solid, is “ghost cell” keratinization of the epithelial lining. The keratin may undergo dystrophic calcification and may incite a foreign-body reaction in the cyst wall, giving it features similar to the pilomatrixoma of skin. Ghost cells alone are not diagnostic, as they may occasionally be seen in other odontogenic tumors, such as ameloblastomas and odontomas.
Glandular Odontogenic Cyst (Sialo-Odontogenic Cyst)
This is a rare and recently described developmental jaw cyst that may superficially mimic a central mucoepidermoid carcinoma. It is seen in adults in any jaw site, although anterior regions are favored. This multilocular cyst is lined by nonkeratinized epithelium with focal thickenings composed of mucous cells in a pseudoglandular pattern. This lesion has shown local aggressiveness and has recurrence potential. Dentigerous cysts that exhibit occasional mucous goblet cells in their linings are not believed to be related to the glandular odontogenic cyst. The glandular odontogenic cyst should not be confused with the more exuberant intraluminal lobular proliferation of adenomatoid odontogenic tumor.
Figure. Glandular odontogenic cyst represented by a focal thickening in which there is mucin production and small pseudoglandular spaces.
DIAGNOSTICALLY CHALLENGING EPITHELIAL ODONTOGENIC TUMORS
Ameloblastoma
Ameloblastoma can exhibit one or more microscopic patterns, none of which is of more clinical significance than the others. Peripheral palisading and budding are a common denominator of all subtypes. The most recently described microscopic pattern is one in which there is extensive desmoplasia, and hence, the designation desmoplastic ameloblastoma. This microscopic subtype is usually seen in the anterior jaws. A plexiform microscopic pattern is often seen in association with ameloblastoma of sinonasal origin. The appearance of ghost cells, with or without dentin-like islands, in a tumor that otherwise has the appearance of ameloblastoma has prompted the designation of odontogenic ghost cell tumor (see COC). The behavior of this rare lesion is believed to be the same as that of ameloblastoma. The growth mechanisms that have been attributed to ameloblastomas have been overexpression of Bcl-2, Bcl-x, and MDM2 proteins. The proliferation index, as determined by Ki67 staining, is unexpectedly low. Expression of fibroblast growth factors, interleukins, and matrix metalloproteinases (MMPs) may account, in part, for the invasive capacity of these tumors.
Figure. Desmoplastic ameloblastoma showing compressed odontogenic epithelial nests in a desmoplastic stroma.
Cystic Ameloblastoma
This biologic subtype of ameloblastoma is also known as unicystic ameloblastoma and, occasionally, as plexiform unicystic ameloblastoma. It was separated from the solid type because it appeared at a younger age, had a lower recurrence rate, and seemed to require less aggressive surgery Recent evidence, however, indicates that cystic ameloblastomas can be destructive and can often recur after simple curettage.
Cystic ameloblastoma usually occurs in the 2nd to 3rd decades and usually in the mandibular molar area. Maxillary lesions are very uncommon. The lesion is entirely cystic and consists usually of a single space, although many have cystic loculations. Radiographically, the lesion is lucent with well-defined margins. It may appear at the apex of a tooth or around the crown of an impacted tooth. It is usually small, although it can reach several centimeters in size. Cystic ameloblastomas have the capacity to expand or perforate jaw cortex/
Figure. Computed tomography scan of a cystic ameloblastoma of the mandible showing cortical penetration.
Microscopically, this is a deceptively innocent appearing lesion that is often underdiagnosed as simple odontogenic cyst.
Figure. Recurrent cystic ameloblastoma. This completely cystic lesion was lined by edematous epithelium with palisaded basal cells.
Figure. Cystic ameloblastoma.
The diagnosis is often made in retrospect when the lesion recurs. The entire cystic epithelial lining represents neoplasm. The reason for the cystic change is unknown, although it may be related to enzymatic destruction of the epithelium by MMPs or serine proteinases. Features that help in microscopic diagnosis include basal cell palisading, epithelial invagination, and epithelial edema and separation. Mural invasion has been linked to an increased risk of recurrence. Clinicopathologic correlation is helpful.
Malignant Ameloblastomas
The malignant forms of ameloblastoma have been classified into two subtypes: (1) malignant ameloblastoma, or metastasizing ameloblastoma in which the metastatic lesion microscopically resembles ameloblastoma and (2) ameloblastic carcinoma, in which the primary and metastatic lesions show dedifferentiation and cytologic atypia. There is also another rare malignancy of odontogenic origin, called primary intraosseous carcinoma, that may occur centrally in the jaws. This lesion, thought to arise from odontogenic rests in bone, looks like squamous cell carcinoma and shows no microscopic features of ameloblastoma.
Figure. Ameloblastic carcinoma: initial lesion in which numerous mitotic figures were found with moderate nuclear atypia.
Figure. Ameloblastic carcinoma:. same tumor, now dedifferentiated, after 6 years, several recurrences, and extension to the base of the skull.
Malignant ameloblastomas occur at a younger age than their benign counterpart and are usually seen in the mandible. Metastasis is typically to the lung and occasionally to local lymph nodes.
Calcifying Epithelial Odontogenic Tumor
Also known as Pindborg tumor, calcifying epithelial odontogenic tumor (CEOT) is a rare odontogenic neoplasm of disputed histogenesis. Origin from stratum intermedium-type cells (enamel organ) and dental lamina have been hypothesized. This tumor occurs in the same age range (30–50 years) and in the same jaw sites (posterior mandible favored) as ameloblastoma. It is a slow-growing, benigeoplasm. It may be unilocular or multilocular. Because of focal areas of calcification, the radiographic image occasionally exhibits a mixed lucent-opaque pattern. This tumor rarely occurs in the soft tissues of the gingiva, in which case it is designated as peripheral CEOT. Believed to have a lower recurrence rate than ameloblastoma, CEOT is treated less aggressively than ameloblastoma.
CEOT consists of sheets of large epithelioid cells with zones of amyloid deposits that may show dystrophic calcification. The amyloid material is an epithelial product (keratins) that stains positive with Congo red and thioflavine T. The tumor cells may exhibit considerable range iuclear size and shape, but mitotic figures are not seen. The ratio of epithelium to extracellular product can be quite different from one tumor to the next, resulting in a histologic spectrum that ranges from lesions that are composed predominantly of epithelium, to lesions that are composed mostly of extracellular material and relatively little epithelium. Occasionally, the epithelial cells will exhibit clear cytoplasm producing the so-called clear-cell variant of CEOT.
Figure. Calcifying epithelial odontogenic tumor: sheet of atypical epithelial cells.
Figure. Calcifying epithelial odontogenic tumor: amyloid droplets with dystrophic calcification in epithelial field.
Squamous Odontogenic Tumor
Squamous odontogenic tumor is a benign odontogenic lesion that can be considered a hamartoma. Because of its presentation in the alveolar process, it is believed to originate (stimulus unknown) from rests of Malassez found in the periodontal ligament. It occurs in the mandible and maxilla with equal frequency and may be multiple. In the alveolar process, it is well circumscribed and is usually associated with the roots of teeth. It is typically small and characteristically appears radiographically as a wedge-shaped lucency at the crest of the alveolar process. As it seems to have limited growth potential, conservative surgical treatment is indicated.
Microscopically, squamous odontogenic tumor appears as islands of bland squamous epithelium (no cellular atypia or mitotic figures) without an inflammatory infiltrate. Peripheral palisades are not seen. The epithelial islands are occasionally closely associated with bone spicules. There is superficial resemblance to ameloblastoma (acanthomatous type) and well-differentiated squamous cell carcinoma
Figure. Squamous odontogenic tumor exhibiting characteristic bland epithelial islands in a fibrous stroma.
Clear-Cell Odontogenic Tumor (Carcinoma)
This is a rare jaw tumor that some consider to be a carcinoma because of reported metastases. The histogenesis is unknown, although it is believed to be derived from odontogenic epithelium because of its primary occurrence in the jaws. Clear-cell odontogenic tumor (carcinoma) has been described mostly in women over the age of 60 years. It may cause some pain. Radiographically, the lesion is lucent and either unilocular or multilocular. This rare lesion has an aggressive biologic behavior. Metastases to lung and regional lymph nodes have been reported.
Microscopically, nests and cords of clear cells are seen. Some peripheral palisading may be present. Differential diagnosis would include clear-cell variant of calcifying epithelial odontogenic tumor, central mucoepidermoid carcinoma, metastatic renal cell carcinoma, and poorly fixed ameloblastoma.
Figure. Clear-cell odontogenic tumor iested pattern.
MICROSCOPICALLY SIMILAR MYXOID/FIBROUS JAW TUMORS
Odontogenic Myxoma
This benign and sometimes clinically aggressive tumor mimics the dental pulp microscopically. However, immunohistochemical studies have been inconsistent and have not been able to confirm pulp tissue origin. Odontogenic myxoma occurs typically in adults (mean age, 30 years; range, 10–50 years) as a radiolucent lesion, often with small loculations (honeycomb pattern). This jaw neoplasm may exhibit aggressive growth and recurrence.
Odontogenic myxoma has a bland myxoid microscopic appearance. If collagen is prominent, the designation of myxofibroma or fibromyxoma may be used. Bony islands, representing residual trabeculae, are found throughout the lesion. Odontogenic epithelium is very uncommon in these lesions. If odontogenic rests are found in a myxomatous jaw lesion, follicular sac (normal tissue found around the crowns of unerupted teeth) should be seriously considered. Reduced enamel epithelium that is a part of the follicular sac residuum is also frequently found along one edge of these specimens. Occasionally, as part of a jaw biopsy, normal dental pulp of a developing tooth may be submitted for microscopic diagnosis. This tissue has the appearance of an odontogenic myxoma except for peripherally positioned columnar-shaped odontoblasts. An accurate clinical history and radiographs can be invaluable in separating follicular sac and normal dental pulp from this tumor. Odontogenic myxomas have a low proliferation rate (as determined by Ki67 staining) but overexpress Bcl-2 and Bcl-x proteins. Overexpression of MMP2 protein may contribute to their expansion (unpublished data).
Figure. A: odontogenic myxoma. B: myxoid follicular sac with odontogenic rests. Fragments of reduced enamel epithelium at far right.
Odontogenic Fibroma
This jaw tumor is considered a neoplasm that is derived from periodontal ligament or pulp-related fibroblasts. It is a tumor of adults and appears as a well-defined radiolucency in either jaw. It is not, however, particularly aggressive, and it infrequently recurs after simple curettage.
Microscopically, these lesions are more collagenous than myxomas but may range from myxofibrous to densely fibrous. Characteristically seen in odontogenic fibromas are few to many islands and strands of bland odontogenic epithelium. Calcific deposits may also be found. A variant (granular cell odontogenic fibroma), in which granular cells are seen in the connective tissue, has been described. The behavior of this tumor does not appear to be different from odontogenic fibroma. Abundant rest proliferation in follicular sacs can occasionally simulate the appearance of odontogenic fibroma or ameloblastic fibroma. Clinicopathologic correlation is important for the diagnosis of these lesions.
Figure. Odontogenic fibroma of the mandible containing odontogenic rests.
Figure. Desmoplastic fibroma of the mandible composed of evenly distributed and benign fibroblasts in a collagenous stroma.
Desmoplastic Fibroma
Figure. Desmoplastic fibroma.
This is a rare fibrous lesion of the jaws. It is benign, but aggressive, exhibiting a biologic behavior similar to fibromatosis of soft tissue or low-grade fibrosarcoma. It is seen in young adults, especially in the mandible. Radiographically, desmoplastic fibroma is lucent, with margins that may be distinct or poorly defined.
Histologically, these lesions exhibit an interlacing or fascicular growth pattern of benign fibroblasts and collagen. They neither contain epithelial rests nor make bone. Multinucleated giant cells are rarely present. Desmoplastic fibroma should not be confused with central low-grade osteosarcoma which is more cellular and has cytologic atypia.
DIFFERENTIAL DIAGNOSIS OF FIBROOSSEOUS LESIONS OF THE JAWS
Fibroosseous jaw lesions are a clinically diverse, but histologically similar group of conditions that are characterized microscopically by a benign fibroblastic stroma in which there is new bone deposition. Although ossifying fibromas and fibrous dysplasia are the most conspicuous examples of this group of jaw lesions, other commonly encountered fibroosseous jaw lesions, such as periapical cementoosseous dysplasia and chronic low-grade osteomyelitis, should be considered in differential diagnoses of these lesions. Fibroblastic and central low-grade osteosarcomas of the jaws may occasionally mimic benign fibroosseous lesions. Clinicopathologic correlation is essential for definitive diagnosis of a jaw fibroosseous lesion.
Ossifying Fibroma
Ossifying fibroma is classified as a benigeoplasm of bone. It is essentially identical to lesions that have been designated as cementifying fibroma and cemento-ossifying fibroma. Although the differentiation of ossifying fibroma from fibrous dysplasia may, at times, be difficult, the separation remains important because of differences in treatment and prognosis.
Ossifying fibroma is a slow-growing, well-circumscribed lesion that has a predilection for the mandibular body and ramus of the jaw. Usually, it is discovered on routine radiographic exam, though occasionally a patient may complain of facial asymmetry or painless swelling. It is most commonly seen in the third and fourth decades, and women seem to be more frequently affected than men. A variant designated as juvenile ossifying fibroma appears a decade earlier. Lesions in this latter subgroup have also been called active or aggressive juvenile ossifying fibroma. This variant is generally felt to have a greater propensity for recurrence and exhibits aggressive clinical behavior.
Microscopically, ossifying fibroma is well demarcated from surrounding resident bone. The tumor bone is seen as trabeculae and/or oval (spherical) islands distributed in a relatively uniform pattern throughout the lesion. Jaw lesions that contain predominantly oval hard-tissue islands, instead of osseous trabeculae, have been referred to as cemento- or psammomatoid-ossifying fibromas. This segregation is essentially academic because the behavior of these lesions are the same. Osteoblasts are usually prominent, typically rimming the new bone, and osteoclasts are scant.
Figure. Two ossifying fibromas of the mandible showing cellular stromas with trabecular (A) and droplet or psammomatoid (B) bone.
Stromal cellularity, which may vary slightly from one area to another, may be relatively high in contrast to fibrous dysplasia. The stroma in the so-called juvenile ossifying fibroma is particularly cellular but is still cytologically benign. The bone in these juvenile lesions appears in the form of strands or trabeculae, although psammomatoid or spheroid islands may be present. With time, ossifying fibromas show continued expansion, with little change microscopically.
Fibrous Dysplasia
Because of its self-limited growth and apparent responsiveness to the hormonal changes of puberty, fibrous dysplasia is classified as a dysplastic process. It may be limited to one bone (monostotic type), several bones (polyostotic type), or several bones with endocrine abnormalities and pigmented skin macules (McCune-Albright syndrome). It is a self-limiting, slow-growing process that starts in childhood and is usually diagnosed by age 20 years. A diagnosis of fibrous dysplasia of the jaws in an adult should be considered when there is excellent clinicopathologic correlation. Swelling is unilateral and asymptomatic. It exhibits ill-defined margins, blends into surrounding bone, and appears as a diffusely radiopaque lesion with a characteristic “ground glass” image. Although the affected bone may surround teeth, neither looseness or exfoliation are seen. Serum laboratory values are usually within normal limits, unless the patient has extensive polyostotic disease, in which case an elevation of serum alkaline phosphatase may be detected.
In the craniofacial complex, fibrous dysplasia is most commonly seen in the maxilla and calvarium, whereas in the remainder of the skeleton, it is seen in most frequently seen in the rib, femur, and tibia. The process usually stabilizes during puberty, persisting in a nearly quiescent state indefinitely. When treatment is necessary to alleviate unacceptable facial deformity, surgical recontouring rather than complete excision is preferred. Regrowth of surgically recontoured fibrous dysplasia is seen in approximately 25 % of cases. Complete or partial excision with bone grafting has been recently used with some success.
Microscopically, fibrous dysplasia consists of a relatively vascular and loose benign fibrous connective tissue stroma surrounding immature fibrillar or woven bony trabeculae. The stroma generally exhibits only low to moderate cellularity.
Figure. Fibrous dysplasia of the jaw showing fibrillar bony trabecular bone that is supposed to be characteristic of this condition.
The incompletely calcified bony trabeculae show some regularity in size and are uniformly distributed throughout, gradually blending into normal surrounding bone. Osteoclasts are typically inconspicuous, and osteoblasts are scant, providing an appearance to the tumor bone that has been referred to as osseous metaplasia. As patients with fibrous dysplasia age, affected bone may show some maturation in the form of lamellations.
Periapical Cementoosseous Dysplasia
That the name of this condition continues to change (cementomas, multiple cementomas, periapical osteofibrosis, cemental dysplasia) underscores our ignorance of its etiopathogenesis. This is an common reactive/dysplastic process of unknown stimulus. Its significance lies in its clinical and microscopic confusion with more important neoplastic and inflammatory jaw lesions. It occurs at the apices of vital mandibular (especially incisors) teeth, predominantly in middle-aged women. It is occasionally seen at the apex of posterior teeth, where it is more likely to be confused clinically with a periapical granuloma or cyst and microscopically, with fibroosseous disease. These lesions, unlike the typical anterior lesions, are likely to be biopsied. This asymptomatic process passes through several radiographic stages: lucent, mixed lucent-opaque, and opaque. This lesion is usually not biopsied or treated because the process is self-limited and is diagnostic on clinical-radiographic correlation. Microscopically, periapical cementoosseous dysplasia appears as a benign fibroosseous lesion. A benign fibroblastic matrix contains a heterogeneous distribution of new and old bone in the form of islands and trabeculae. Inflammatory cells are scant.
Florid cementosseous dysplasia is believed to be an exuberant form of periapical cementoosseous dysplasia. It may affect the entire jaw (usually mandible) and may be seen in association with traumatic bone cysts. Florid cementosseous dysplasia appears microscopically as a benign fibroosseous lesion. Bony islands and trabeculae are seen in a bland connective tissue matrix. Inflammatory cells are scant. Clinical correlation is necessary to make a definitive diagnosis. Unfortunately, florid osseous dysplasia may become secondarily inflamed, superimposing a chronic osteomyelitis on the process and making diagnosis more difficult. Florid cementosseous dysplasia, like its periapical counterpart, requires no treatment, unless secondarily infected.
Figure. Florid osseous dysplasia of the entire body mandible. A mixed lucent and opaque pattern is evident in this case.
Figure. Heterogeneous pattern of florid osseous dysplasia. The appearance is fibroosseous, with both immature and mature bone present.
Chronic Osteomyelitis
Chronic osteomyelitis (including Garre’s osteomyelitis) of the jaws is usually a low-grade inflammatory process that is often relatively asymptomatic. It is one of several lesions that may show microscopic overlap with fibroosseous lesions, especially ossifying fibroma and fibrous dysplasia. Inflammatory cells in chronic osteomyelitis may be quite scant, and there may be much new bone formation, giving the tissue a fibroosseous appearance. Both osteoblasts and osteoclasts are seen typically. The low-power microscopic pattern is heterogeneous, with new bony trabeculae admixed with more mature lamellated bone. The new bone is of irregular size, shape, and distribution.
Osteosarcomas
Fibroblastic osteosarcoma and central low-grade osteosarcoma may be a consideration in the differential diagnosis of fibroosseous jaw lesions because of the relatively well-differentiated and fibrous nature of these lesions.
Figure. Osteosarcoma.
Definitive diagnosis is based upon hematoxylin and eosin microscopy taken in an appropriate clinical context. Diagnosis of fibroblastic osteosarcoma and central low-grade osteosarcomas requires the finding of atypical cells in association with immature, haphazardly distributed osteoid. Peripheral margins are usually poorly defined. Central low-grade osteosarcomas typically have a prolonged course and a correspondingly good prognosis. Transformation to a higher grade osteosarcoma may be seen many years after the original diagnosis. Prognosis also worsens with this event because of a more aggressive behavior and increased risk of metastasis.
CENTRAL GIANT CELL GRANULOMA AND OTHER GIANT CELL LESIONS OF THE JAWS
Central giant cell granuloma (CGCG) appears to be a lesion that is unique to the jaws, although so-called giant cell reaction of the hands and feet shares many features. CGCG was formerly regarded as a reparative process and was, accordingly, called central giant cell reparative granuloma. Although this is not a granulomatous inflammatory process, the term granuloma has persisted in this case because of tradition/habit. Although many investigators believe that CGCG should be classified as a reactive lesion, numerous documented aggressive and recurrent cases suggest that it may behave as a neoplasm. There is currently no way to predict, either clinically or microscopically, which lesions will behave badly.
CGCGs occur typically in the second and third decades (mean age of approximately 25 years). Females are more frequently affected than males. CGCG has a predilection for the mandible, especially the body and anterior portions of the jaw. The lesion is radiolucent and usually multilocular. Resorption and/or movement of teeth may be seen, and penetration of jaw cortex may occur. Most patients are asymptomatic, although pain or paresthesia may be a presenting complaint, particularly in aggressive lesions. Recurrences are more likely to be seen in children than adults. Surgery has been the treatment of choice, although alternative medical therapy with calcitonin injections has shown some promising results in reducing the size of large lesions. A less rational therapy of corticosteroid injections has been advocated by some who believe that CGCGs are reactive lesions.
Microscopically, a number of patterns may be seen. The stroma may vary from vascular to fibrotic to myxoid in appearance. New bone, rimmed by osteoid, may be present, particularly at the periphery of the lesion. Recent and old hemorrhage is typically found, but necrosis is not seen. The dominant stromal cells are fibroblastic in origin. They are round, oval, or spindle in shape. They may be particularly numerous, and mitotic figures may be frequently seen (no prognostic significance). Although a heterogeneous pattern consisting of groups of giant cells separated by fibroblastic areas is typical of CGCGs, homogeneous patterns, in which large numbers of giant cells are evenly distributed throughout the lesion, are seen. The giant cells (CD68 positive) themselves vary in size, shape, and number. None of the histologic or immunohistologic features yet described have allowed separation of aggressive from nonaggressive lesions. CGCG appears to be a tumor in which osteoclasts or their precursors are recruited into a predominantly fibroblastic field. The fibroblasts are in cell cycle and may be responsible for production of cytokines or growth factors that support tumor growth.
Figure. Two central giant cell granulomas. A: the usual heterogeneous low-power appearance of the lesions. B: giant cells can occasionally be relatively large, evenly distributed, and contain many nuclei.
The aggressive, recurrent (50–60 %) giant cell tumor of long bone (GCT), which is generally believed to be an entity that is separate from the CGCG, probably makes a rare appearance in the jaws. Because CGCG and GCT have overlapping histopathologic features, separation of these two lesions can be difficult. Some features that suggest GCT over CGCG include very large giant cells, large numbers of nuclei in giant cells, central aggregation of giant cell nuclei, diffusely distributed giant cells, high stromal cellularity, and necrosis. Microscopic differential diagnosis of CGCG look-alikes include aneurysmal bone cyst, hyperparathyroidism, and cherubism, all of which can be considered rare in the jaws relative to the frequency of occurrence of CGCG. Microscopically, aneurysmal bone cyst is characterized by large sinusoidal spaces lined by connective tissue with giant cells. Hyperparathyroidism is essentially identical to that of CGCG; however, lab values are altered (elevated serum calcium and parathormone), and the radiographic picture can be distinctive (multiple lesions and loss of lamina dura around roots of teeth). Cherubism appears microscopically indistinguishable from CGCG, except occasionally, when a fairly characteristic condensation of perivascular collagen is evident. Clinicopathologic correlation (children, autosomal dominant, bilateral multilocular jaw lucencies) is definitive.
