alveolar ridge mass with multifocal intraosseous radiolucent...

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Alveolar ridge mass with multifocalintraosseous radiolucent lesionsSarah G. Fitzpatrick, DDS; Hussain Dashti, DDS; Donald M. Cohen, DMD, MS, MBA; Indraneel Bhattacharyya, DDS, MSD

JADA 142(4) http://jada.ada.org April 2011 411

THE CHALLENGE

A 56-year-old woman was evaluated in theDepartment of Oral and Maxillofacial Surgery,College of Dentistry, University of Florida,Gainesville, for a painful swelling of the leftmandibular vestibule (Figure 1). She reportedhaving experienced pain in the area, beginningas localized tooth pain, for several years. Shethen developed a mass in the left mandibularvestibule and a progressive loss of sensation tothe left mandibular lip and chin. The swellingand numbness had been present for about 10months at the time of her clinic visit. She alsonoted that her partial denture no longer fit sec-ondary to the pain and swelling. Her medicalhistory included type 2 diabetes mellitus, hyper-

A. Metastatic malignancyB. Langerhans cell histiocytosis

C. Multiple myeloma (plasma cell myeloma)D. Hyperparathyroidism (multiple brown

tumors)

tension, hypercholesterolemia, hypothyroidism,and glaucoma and cataracts. Her medicationsincluded several antihypertensive medications,insulin and thyroid hormones.

The clinical examination revealed a large leftvestibular swelling that had displaced hermandibular left posterior teeth (Figure 1). Apanoramic radiograph revealed a multilocularradiolucent lesion of the left mandible (Figure2). The patient underwent computed tomo-graphic imaging, which revealed a largedestructive lesion involving the left mandible(Figure 3). An oral surgeon performed a biopsy.The patient underwent further laboratory blood,serum and urine studies. A skeletal surveyrevealed radiolucent lesions in the skull (Figure4), clavicles, pubic bones and right humerus.

Can you make the diagnosis?

D I A G N O S T I C C H A L L E N G EC L I N I C A L P R A C T I C E

Figure 1. Oral examinationrevealed a large diffuse expansivemass with bony expansion on theleft mandibular vestibule with dis-placement of teeth.

Figure 2. Panoramic radiographshows multilocular radiolucency ofthe left mandible with destructionof adjacent teeth.

Figure 3. A computedtomographic scan showsexpansive intraosseous radio -lucency of the left mandiblewith significant destructionof both lingual and buccalcortical plates.

Figure 4. Skull radiographshows multiple “punched-out” radiolucencies (arrows).

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Multiple myeloma (plasma cell myeloma) con-sists of a monoclonal proliferation of malignantplasma cells. It accounts for about 1 percent ofmalignancies overall in the United States butnearly 50 percent of all primary bone malignan-cies in the United States.1 It affects primarilyan older population, and men are affected moreoften than are women. The etiology of this con-dition is not totally clear, but in some cases ahigher incidence has been seen in those exposedto radiation, pesticides and other chemical carcinogens.2

Clinical presentation. The most commonclinical presentation is that of bone pain.Anemia or thrombocytopenia also may occur.Renal insufficiency is a complication in laterstages of the disease, as can be pathologicalfractures.1,3 Diagnosis is made by means of iden-tification of an increase in plasma cells in thebone marrow (> 30 percent).4 Also required fordiagnosis are a monoclonal increase in a serumM protein other than immunoglobulin (Ig) M(usually IgG in 70 percent or IgA in 20 percentof all cases of multiple myeloma) and anincrease in either the κ or the λ light chain.Patients also may have free light chains in theurine (Bence Jones proteins). Multiple lyticlesions of bone are noted on radiographicskeletal surveys, with common sites being verte-brae, the skull, pelvic bones, the ribs, thehumeri and the femurs.5

About 70 to 96 percent of patients with mul-tiple myeloma in the United States may havelesions of the maxilla or mandible, according toRegezi and colleagues.6 Oral plasma cell neo-plasms may appear in several forms: localizedmultiple myeloma, solitary plasmacytoma ofbone or extramedullary plasmacytoma of softtissue. Approximately 3 percent of plasma cellneoplasms are solitary plasmacytomas involvingbone, according to Knowling and colleagues.7

Extramedullary plasmacytoma is rarer stilloverall, but it has been reported in the nasalcavity, larynx, nasopharynx and palatine tonsilsand intraorally in the tongue, palate andparotid gland.3,8 Multiple myeloma of the oralcavity can manifest as gingival masses, expan-sion of bone, toothache, tooth mobility or migra-tion, soft-tissue ulceration or gingival bleeding,or radiographically as multiple, “punched-out”radiolucent lesions that may be destructive or move teeth. The patient also may havemandib ular paresthesia, sometimes termed

“numb-chin syndrome.”1

In approximately 10 percent of patients, thesystemic deposition of amyloid material in softtissue is associated with multiple myeloma.6

Sites may vary throughout the body, but themost common oral site is the tongue, where itmanifests as a firm enlargement or macro -glossia.6 The primary microscopic feature ofmultiple myeloma is the presence of neoplasticplasma cells (Figure 5) that invade and replacenormal tissue.1,6 Immunohistochemical stainingperformed for antibodies against the λ and κlight chain immunoglobulins, which are pro-duced by the plasma cells, mark a mostly mono-clonal population of only one antibody type inmultiple myeloma, differentiating it frombenign or reactive plasmacytic proliferations.1

In normal B-cell populations, the κ:λ ratio isusually 2:1, and these two proteins are distrib-uted randomly with respect to one another.9 Inthe case described in this article, the cliniciansperformed immunohistochemical staining—including markers for plasma cells and lightchain immunoglobulins (Figures 6 and 7)—thatrevealed strong monoclonal positivity for λ, alight chain immunoglobulin. Blood studies per-formed for this patient revealed elevated IgA λmonoclonal proteins, and urinalysis demon-strated the presence of free λ light chains.

Treatment. Treatments for multiple myelomainclude radiation therapy and chemotherapy.Intravenous bisphosphonate chemotherapy maypose a dental complication in the form ofincreased incidence of bisphosphonate-relatedosteonecrosis of bone. In the majority of cases,the disease is aggressive and results in a poorprognosis, with a five-year survival rate ofapproximately 25 percent.1 The patientdescribed in this article underwent one round ofradiation therapy at our institution beforetransferring to another facility to continuechemoradiation therapy. Follow-up informationfor this patient is unavailable.

DIFFERENTIAL DIAGNOSESMetastatic malignancy. Metastatic cancers tothe jaw are most commonly from breast, lung,thyroid, colorectal, prostate and kidneycancers.1,6 Most patients are older than 60 years,and sex prevalence depends on the type of pri-mary cancer. The vertebrae, ribs, pelvis andskull are the most common sites of metastasis.1

The mandible is affected much more often than

THE DIAGNOSIS

C. Multiple myeloma (plasma cell myeloma)



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is the maxilla. Clinically, the patient usuallyexhibits a soft-tissue mass, pain, loosening ofteeth or paresthesia. Radiographically, thepatient usually has an ill-defined radiolucency,sometimes described as “moth-eaten,” that maymimic radiolucencies similar to those seen inperiodontal disease; the lesion can result inwidening of the periodontal ligament space andmay even appear as a mixed radiolucent-radiopaque lesion if it is the result of a bone-producing carcinoma.6 This patient’s lesionsradiographically were more well-defined thanwould be expected in metastatic malignancy. Inaddition, the histopathological examination of ametastatic lesion typically would demonstratefeatures similar to those of its origin.

Langerhans cell histiocytosis. Eosino philicgranuloma, the mildest form of Langerhans cellhistiocytosis (LCH), may be seen in the jaws andskull, as well as other areas such as the longbones, pelvis and vertebrae. In adults, it hasbeen estimated that the jaws are involved in 30percent of cases of LCH and the skull in 21 per-cent.10 The mandible is the more commonlyaffected jawbone. Oral manifestations mayinclude a soft-tissue mass, pain, gingivitis andloosening of teeth, and ulcer.11 Radiographic man-ifestation in the jaw lesions may vary but may bedescribed as a “teeth floating in air” similar tothe appearance of destructive periodontitis or asintraosseous round, oval or irregular radiolucen-cies that may appear punched out.6,12

However, LCH generally is considered a dis-ease of children and young adults; most patientswho have it are younger than 20 years. There-fore, this patient did not fall into the likelydemographic.11 The eosinophilic granuloma formof LCH, which would be the most likely of theforms to be seen in this patient’s age group, usu-ally is a solitary lesion, unlike the lesions in thiscase. In addition, the histopathological features

of LCH are characterized by the infiltration ofLangerhans cells (histiocytelike cells) and thepresence of varying numbers of eosinophils.1

Hyperparathyroidism (multiple browntumors). Brown tumors of bone are a signal ofthe terminal stage of hyperparathyroidism andmay be seen in the mandible, ribs, clavicles andmost often pelvis. The maxilla is involved lessoften.13 Clinically, brown tumors may appear asa mass or a bony expansion. Radiographically,they may appear as well-defined unilocular ormultilocular radiolucent bodies. The tumorsmay resorb roots. The lesions may be solitary ormultiple. A ground-glass radiographic appear-ance of bone and loss of lamina dura also can beseen and will be evident if the disease hasadvanced to a brown-tumor–production stage.1

Primary hyperparathyroidism most oftenaffects women older than 60 years (usuallyresulting from a parathyroid adenoma) and usu-ally manifests with hypercalcemia and hypo -phosphatemia. Secondary hyperparathyroidismusually is associated with chronic renal disease;patients with this condition will have hypocal-cemia and hyperphosphatemia.14 The patientdescribed in this article did not have laboratoryvalues consistent with these characteristics, norwas ground-glass bone or a generalized loss oflamina dura present on the panoramic radio-graph. Also, this diagnosis is seen rarely now, ashyperparathyroidism most often is diagnosedvia serum calcium level testing before it pro-gresses to this end stage.13 The histopathologicalfeatures of a brown tumor are similar to those ofcentral giant cell granuloma, in which the pres-ence of numerous giant cells with multiplenuclei is the distinctive feature.1

CONCLUSIONMultiple myeloma may manifest with a varietyof intraoral clinical findings, including bone


Figure 5. High-power view shows mono-clonal infiltration by atypical plasma cells(hematoxylin and eosin stain, originalmagnification ×40).

Figure 6. Negative or very low stainingfor κ light chain protein (hematoxylinstain, original magnification ×20).

Figure 7. Strong positive staining for λlight chain protein signifying monoclonalproduction of antibody by abnormalplasma cells (3,3’-diaminobenzidine stain,original magnification ×20).


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pain and paresthesia, soft-tissue swelling ormass, toothache, tooth mobility or movement,bony expansion, and radiographic findings gen-erally in the form of multiple radiolucenciesthat may have a punched-out appearance. Incases that appear initially in the oral cavity, itmay be difficult to differentiate clinically andradiographically between multiple myeloma orplasmacytoma and a range of other differentialdiagnoses, including even inflammatory lesionssuch as osteomyelitis. Clinicians should referany suspect lesions for biopsy and appropriatefollow-up testing to determine the diagnosis. Inaddition, in patients who have received a diag-nosis of multiple myeloma, the dentist shouldmanage dental care vigilantly and be aware ofaccessory complications related to the diseaseand treatment such as renal failure, bleedingdisorders, amyloidosis and potential develop-ment of bisphosphonate-related osteonecrosis. �

Dr. Fitzpatrick is a senior resident in oral and maxillofacialpathology, Department of Oral and Maxillofacial Diagnostic Sciences,University of Florida, Gainesville.

Dr. Dashti is a senior resident in oral and maxillofacial pathology,Department of Oral and Maxillofacial Diagnostic Sciences, OralPathology, College of Dentistry, University of Florida, Gainesville.

Dr. Cohen is a professor, Department of Oral and MaxillofacialDiagnostic Sciences, Oral Pathology, College of Dentistry, Universityof Florida, Gainesville.

Dr. Bhattacharyya is an associate professor, Department of Oraland Maxillofacial Diagnostic Sciences, College of Dentistry, Univer-sity of Florida, P.O. Box 100414, Gainesville, Fla. 32610-0414, e-mail“[email protected]”. Address reprint requests to Dr.Bhattacharyya.

Disclosure. None of the authors reported any disclosures.

Diagnostic Challenge is published in collaboration with the

American Academy of Oral and Maxillofacial Pathology and theAmerican Academy of Oral Medicine.

1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and max-illofacial pathology. 3rd ed. St. Louis: Saunders; 2009:604-606, 669-670, 838-840.

2. Munshi NC, Tricot G, Barlogie B. Plasma cell neoplasms. In:DeVita VT, Helmann S, Rosenberg SA, eds. Cancer: Principles &Practice of Oncology. 6th ed. Philadelphia: Lippincott Williams &Wilkins; 2001:2465-2499.

3. Stoopler ET, Vogl DT, Stadtmauer EA. Medical managementupdate: multiple myeloma. Oral Surg Oral Med Oral Pathol OralRadiol Endod 2007;103(5):599-609.

4. Lacy J, Seropian S. Disorders of lymphocytes. In: Andreoli TE,Carpenter CJ, Griggs RC, Loscalzo J, eds. Cecil Essentials of Medi-cine. 6th ed. Philadelphia: Saunders; 2004:476.

5. Lae ME, Vencio EF, Inwards CY, Unni KK, Nascimento AG.Myeloma of the jaw bones: a clinicopathologic study of 33 cases.Head Neck 2003;25(5):373-381.

6. Regezi JA, Sciubba JJ, Jordan RCK. Oral Pathology: ClinicalPathologic Correlations. 5th ed. St. Louis: Sanders/Elsevier; 2008:230-232, 296-297, 328-332.

7. Knowling MA, Harwood AR, Bergsagel DE. Comparison ofextramedullary plasmacytomas with solitary and multiple plasmacell tumors of bone. J Clin Oncol 1983;1(4):255-262.

8. Seoane J, Aguirre-Urizar JM, Esparza-Gómez G, Suárez-Cunqueiro M, Campos-Trapero J, Pomareda M. The spectrum ofplasma cell neoplasia in oral pathology. Med Oral 2003;8(4):269-280.

9. Barandun S, Morell A, Skvaril F, Oberdorfer A. Deficiency ofkappa- or lambda-type immunoglobulins. Blood 1976;47(1):79-89.

10. Baumgartner I, von Hochstetter A, Baumert B, Luetolf U, Fol-lath F. Langerhans’-cell histiocytosis in adults. Med Pediatr Oncol1997;28(1):9-14.

11. Hicks J, Flaitz CM. Langerhans cell histiocytosis: currentinsights in a molecular age with emphasis on clinical oral and max-illofacial pathology practice. Oral Surg Oral Med Oral Pathol OralRadiol Endod 2005;100(2 suppl):S42-S66.

12. Ardekian L, Peled M, Rosen D, Rachiel A, Abu el-Naaj I, LauferD. Clinical and radiographic features of eosinophilic granuloma inthe jaws: review of 41 lesions treated by surgery and low-dose radio-therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87(2):238-242.

13. Gnepp DR. Diagnostic Surgical Pathology of the Head andNeck. 2nd ed. Philadelphia: Saunders/Elsevier; 2009:774.

14. Triantafillidou K, Zouloumis L, Karakinaris G, Kalimeras E,Iordanidis F. Brown tumors of the jaws associated with primary orsecondary hyperparathyroidism: a clinical study and review of theliterature. Am J Otolaryngol 2006;27(4):281-286.


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