Clinical Pathologic Conference Cases Presented at the ... Advance/journals/… · Academy of Oral...

Vol. - No. - Month 2015

Clinical Pathologic Conference Cases Presented at the Annual Meeting ofthe American Academy of Oral and Maxillofacial Pathology, April25-30, 2014

CLINICAL PATHOLOGIC CONFERENCE CASE 1: AMULTILOCULAR RADIOLUCENCY IN THE POSTERIORMANDIBLE Colin Eliot, DMD, MS. LCDR, DC, USNa,Harvey P. Kessler, DDS, MSb, aJoint Base Pearl Harbor-Hickam, Hawaii; bProfessor of Pathology, Department ofDiagnostic Sciences, Texas A&M University Baylor Collegeof Dentistry, Dallas, Texas

Clinical Presentation: A 22-year-old white female pre-sented to the general dentist with swelling in the right mandibleand submandibular area. Clinical examination confirmedexpansion of the right mandible. Panoramic radiographic ex-amination revealed a large, well-circumscribed multilocularradiolucency distal to the canine within the body of themandible (Figure 1). An incision and drainage procedure wasperformed but was unsuccessful. Aspiration of the lesion alsofailed to yield output.

Differential Diagnosis: Differential diagnosis of a well-circumscribed, corticated, multilocular radiolucency within themolar region of the mandible should include several categories ofpathology, including odontogenic cysts and tumors, non-odon-togenic tumors, and other non-neoplastic conditions.

A large number of intrabony jaw lesions originate fromodontogenic tissues; therefore, odontogenic cysts and tumorsshould be considered first in a differential diagnosis. Of theodontogenic cysts, odontogenic keratocyst (OKC) would be themost likely in the present case. OKCs affect the mandibleapproximately 70% of the time and demonstrate a tendency toinvolve the posterior body of the mandible and the ascendingramus.1 The majority of OKCs are identified in patients betweenages 10 and 40 years.1 The radiographic presentation of OKCsconsists of a well-defined radiolucency, with a smooth andoften corticated margin.1 Larger lesions may present as amultilocular process.2 In this case, we are not considering thedentigerous cyst, a common odontogenic cyst, because of theabsence of an unerupted tooth in the area, and the less commonglandular odontogenic cyst because of patient demographiccharacteristics and biologic behavior.3

Odontogenic tumors may also present as well-circumscribed,corticated radiolucencies, so a variety of odontogenic neoplasmsshould be considered in the present case. Given the patient de-mographic characteristics, ameloblastoma, odontogenic myxoma,and central odontogenic fibroma are considered. Ameloblastomais the most common clinically significant odontogenic tumor.About 80% of ameloblastomas are found within the mandible,with the molar-ascending ramus area being the most commonsite.4 The average age at diagnosis is the middle to late 30s,although a wide age range is common, and a second peak isseen in the seventh decade of life.4 Odontogenic myxomademonstrates a strong mandibular predilection, with thepremolaremolar area most commonly affected, although thelesion in the present case did not demonstrate the typical “soapbubble” radiographic appearance seen in myxomas.5 Centralodontogenic fibroma should also be considered in the presentcase. These unusual lesions present in a wide age range,although most patients present between the ages of 11 and

39 years.6 Central odontogenic fibromas exhibit a slightmandibular predilection, often posterior to the first molar, andmost notably demonstrate a strong female predilection.7 Theymay cause significant bony expansion and may present astotally radiolucent or with faint internal septa.6,7

As the lesion did not appear to be associated with a tooth, non-odontogenic neoplasms and tumors had to be considered in thedifferential diagnosis in the present case. Vascular lesions such ashemangiomawere unlikely, based on negative aspiration. A centralgiant cell lesion (central giant cell granuloma) had to be considered,as these non-neoplastic lesions are commonly seen before the age of30 and with a distinct female predilection.8 The mandible isaffected the majority of the time, although the lesions aretypically found anterior to the canines and without a corticatedborder. Central giant cell lesions have a tendency to causeexpansion and may result in tooth resorption.8 Finally, simplebone cyst (idiopathic bone cavity) had to be considered, as theselesions are typically seen between the ages of 10 and 20 yearsand are rarely seen in patients above the age of 30.9 Simple bonecysts are almost exclusively seen in the mandible and maypresent with slight expansion.9 Negative aspiration is commonlyseen, and surgical exploration is required for diagnosis.

Diagnosis and Management: Approximately 2 weeksfollowing the attempted, but unsuccessful, incision and drainageprocedure, an excisional biopsy of the lesion was performed.Aspiration of the lucent area was attempted before surgical entrybut proved to be negative. At surgery, the lucent defect was foundto contain a solid tissue mass without any evidence of a cysticcomponent. Curettage yielded enough tissue to fill three cassettes.

Histologic examination of the biopsy material revealed alarge majority of the tissue specimen to be composed of a rela-tively dense background stroma of fibrous connective tissue,within which there was an increased quantity of what appeared tobe mildly proliferative odontogenic epithelium (Figure 2A). Theodontogenic epithelium grew in thin but elongated strands,cords, and small islands, and the epithelium was fairlyuniformly spread through the background fibrous tissue(Figure 2B). In some areas, the background fibrous tissueappeared mildly hypocellular and hyalinized. However, otherfragments of tissue in the specimen showed a distinctlydifferent histopathologic appearance. These tissue fragmentsshowed a highly cellular proliferation of fibrohistiocytic-appearing cells surrounding an area of central hemorrhage(Figure 2C). Foreign bodyetype giant cells were scatteredthrough the background fibrohistiocytic stroma in a roughlycircular distribution around the areas of hemorrhage (Figure2D). In most areas, the odontogenic fibroma component of thelesion remained separate from, but abutted against, the giantcell component (Figure 3A). Focally, however, the two patternswere intermingled, and giant cells were occasionally founddirectly adjacent to the odontogenic epithelium (Figure 3B).

The diagnosis was hybrid central odontogenic fibroma/centralgiant cell lesion.

Discussion: The occurrence of central odontogenic fi-broma containing areas of central giant cell granulomaelike

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Fig. 1. A portion of the panoramic radiograph demonstrating thelesion in the right mandible.

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proliferation was first reported by Allen et al., in 1992, as“central odontogenic fibroma, WHO type, with an unusualassociated giant cell reaction.”10 Three cases were presentedin that initial report. Since 1992, only six additional reportsof this combination have appeared in the literature, withanother report of 19 cases added later.11-16 The trend withinthese seven publications is to label the lesion as a hybridcentral odontogenic fibroma/central giant cell lesion. Table Isummarizes the pertinent details of the cases reported in theliterature, including the case described in this report. Inaddition to these published reports, additional cases of thishybrid lesion have occasionally been reported in essaypresentations at the annual meetings of the AmericanAcademy of Oral and Maxillofacial Pathology. Fowler etal., in 1993, presented a review of 24 cases of centralodontogenic fibroma, which mentioned that three cases hada giant cell component.17 However, no further details ofthese three cases were provided. In 2008, Hassan et al.presented an essay detailing seven cases of hybrid centralodontogenic fibroma/giant cell granuloma.18 Although asummary of these seven cases was provided, specificdemographic and clinical data on the individual cases werenot included.

The hybrid central odontogenic fibroma/giant cell lesionoccurs over a wide age range with cases reported to occur fromthe first to the eighth decade of life. The majority of casescluster in the second and third decades of life. Females areaffected most often, in at least a 2:1 female-to-male ratio. Therace of the patient is documented in only six cases, but in allthese six cases, the patient was Caucasian. The mandible is thepreferred site of occurrence, with only two cases documentedin the maxilla. The premolaremolar region is most commonlyinvolved, with only one lesion identified as being exclusivelyanterior in its position. The case described by de Lima et al.13

is somewhat unique, with these authors reporting an extremelylarge lesion that extended from the left first molar regionacross the midline to the right first molar. However, thephotomicrographs included in this case report do not clearlydelineate a central odontogenic fibroma component of thelesion, leaving the accuracy of the diagnosis in question.Treatment typically entails excision or thorough curettage,usually with a good outcome. The literature documentsrecurrence in only 3 of the 19 cases in which follow-up wasdocumented,10-15 with a recurrence rate of 15.7%. However,the article by Hassan et al.18 describes three additionalrecurrences among their seven cases. Including these cases inthe total yields a recurrence rate of 23.1% (6 of 26). Five ofthe six recurrences are reported to have contained bothcentral odontogenic fibroma and giant cell granulomacomponents.10,11,18 One recurrence reported by Hassan et al.contained only the giant cell granuloma component.

The etiology of the hybrid central odontogenic fibroma/giantcell lesion has yet to be confirmed. One theory is that the lesionrepresents a “collision tumor” with a separate central odontogenicfibroma arising in juxtaposition to a central giant cell granuloma.

This theory has largely been discarded as highly unlikely giventhe rarity of the two lesions individually.10-13,15 In addition, oc-casional recurrences of the hybrid lesion have been reported tocontain both elements of the hybrid lesion, with the suggestionthat there is an interrelationship between the two processes.10,11,18

Several authors10,12,13 believe that the hybrid lesion initially de-velops as a central odontogenic fibroma, which subsequentlyresults in a giant cell lesion in response to some traumatic orirritating stimulus. In several of the reported cases, a potentialsource of trauma to the area of the tumorous proliferation waspresent in the history. Cases in which the odontogenic fibromacomponent is the predominant tissue present in the specimen withonly a very small proportion being the giant cell lesion are alsocited as evidence of origin as a central odontogenic fibroma.11

The case being presented here would appear to strongly supportthis concept. The history of a prior, nonproductive attempt atincision and drainage, combined with the histologic finding ofan area of central hemorrhage surrounded by a circular array ofgiant cells, suggests that the incision and drainage proceduremay have initiated bleeding in the odontogenic fibroma, withthe giant cell area representing a reactive response to the injury.Other authors believed that the hybrid lesion most likely beginsas a central giant cell granuloma.11,15 They cited evidence thatthe giant cells in giant cell granulomas secrete growth factors thatcan stimulate epithelial proliferation, initiating the odontogenicfibromaelike proliferation as a secondary effect of the giant cellgranuloma.13,15,16 One author also cited examples of hybrid le-sions in which the giant cell granuloma component is the pre-dominant tissue present in the specimen.15 A potential argumentagainst this theory is the general lack of odontogenic epithelialproliferation in the vast majority of cases of central giant cellgranuloma. Since giant cell granuloma routinely occurs in theareas of the jaws where odontogenic epithelium is expected tobe present, the question is: Why isn’t an associated epithelialproliferation a more consistent finding in giant cell granulomaif this is, in fact, the pathogenic mechanism of development ofthe hybrid lesion?

Fig. 2. A, Central odontogenic fibroma component. Densefibrous stroma with numerous mildly proliferative strands, cords,

and islands of odontogenic epithelium. B, Central odontogenicfibroma component. Thin elongated strands, cords, and smallislands of odontogenic epithelium fairly uniformly spread throughthe background fibrous tissue. C, Giant cell lesion component.Highly cellular proliferation of fibrohistiocytic appearing cellssurrounding an area of central hemorrhage. D, Giant cell lesioncomponent. Foreign body type giant cells were scattered throughthe background fibrohistiocytic stroma in a roughly circular dis-tribution around the areas of hemorrhage.

Fig. 3. A, In most areas, the odontogenic fibroma component ofthe lesion (right) remained separate from but abutted against thegiant cell component (left). B, Focally the two patterns wereintermingled, and giant cells were occasionally found directlyadjacent to the odontogenic epithelium.

Table I. Demographic and clinical data from 23 cases

Author/year Age Gender Race Jaw Location Radiograph

Allen,1992

66 F W Mandible Premolar/molar Multilocular14 F W Mandible Premolar/molar Unilocular30 F W Mandible Premolar/molar Multilocular

Odell,1997

5 F ? Maxilla Premolar/molar ?

11 M ? Maxilla Involvingantrum

Multilocular

20 F ? Mandible Premolar/molar Unilocular

(continued)

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Table I. Continued

Author/year Age Gender Race Jaw Location Radiograph

21 F ? Mandible Distal thirdmolar

Unilocular

22 F ? Mandible Premolar/molar ?39 F ? Mandible Premolar/molar ?43 F ? Mandible ? ?50 F ? Mandible Premolar Unilocular

Taylor,1999

17 F ? Mandible Canine/premolar Multilocular

De Lima,2008

24 F W Mandible Right to leftfirst molar

?

Younis,2008

57 F W Mandible Premolar/molar Unilocular

Tosios,2008

18 M ? Mandible Premolar/molar ?20 F ? Mandible Premolar/molar ?50 M ? Mandible Premolar/molar ?73 M ? Mandible Premolar/molar ?15 M ? Mandible Premolar/molar ?59 M ? Mandible Premolar/molar ?25 M ? Mandible Premolar/molar ?

Damm,2013

75 F ? Mandible Incisor Unilocular

This case 22 F W Mandible Premolar/molar Multilocular



References1. Myoung H, Hong SP, Hong SD, et al. Odontogenic kerato-

cyst: review of 256 cases for recurrence and clinicopathologicparameters. Oral Surg Oral Med Oral Pathol Oral RadiologyEndod. 2001;91:328-333.

2. Neville BW, Damm DD, Allen CM, Bouquot JE, eds.Odontogenic cysts and tumors. In: Oral and MaxillofacialPathology. 2nd ed. St. Louis, MO: Saunders and Elsevier;2002:595.

3. Fowler CB, Brannon RB, Kessler HP, Castle JT, Kahn MA.Glandular odontogenic cyst: analysis of 46 cases with specialemphasis on microscopic criteria for diagnosis. Head andNeck Pathol. 2011;5:364-375.

4. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: bio-logical profile of 3,677 cases. Eur J Cancer B Oral Oncol.1995;31:86-99.

5. Li TJ, Sun LS, Luo HY. Odontogenic myxoma: a clinico-pathologic study of 25 cases. Arch Pathol Laboratory Med.2006;130:1799-1806.

6. White SC, Pharoah MJ, eds. Benign tumors of the jaws. In:Oral Radiology Principles and Interpretation. 5th ed. St.Louis, MO: Mosby; 2004:438-439.

7. Handlers JP, Abrams AM, Melrose RJ, et al. Central odon-togenic fibroma: clinicopathologic features of 19 cases andreview of the literature. J Oral Maxillofac Surg.1991;49:46-51.

8. Nicolai G, Lorè B, Mariani G, Bollero P, De Marinis L,Calabrese L. Central giant cell granuloma of the jaws. JCraniofaci Surg. 2010;21:383-386.

9. Forssell K, Forssell H, Happonen RP, Neva M. Simple bonecyst: review of the literature and analysis of 23 cases. Int JOral Maxillofac Surg. 1988;17:21-24.

10. Allen CM, Hammond HL, Stimson PG. Central odontogenicfibroma, WHO type. A report of three cases with an unusualassociated giant cell reaction. Oral Surg Oral Med OralPathol. 1992;73:62-66.

11. Odell EW, Lombardi T, Barrett AW, Morgan PR,Speight PM. Hybrid central giant cell granuloma and centralodontogenic fibroma-like lesions of the jaws. Histopathology.1997;30:165-171.

12. Mosqueda Taylor A, Bermúdez Flores V, Díaz Franco MA.Combined central odontogenic fibroma and giant cell gran-uloma-like lesion of the mandible: report of a case and re-view of the literature. J Oral Maxillofac Surg. 1999;57:1258-1262.

13. de Lima Mde D, de Aquino Xavier FC, Vanti LA, deLima PS, de Sousa SC. Hybrid central giant cell granulomaand central odontogenic fibroma-like lesion of the mandible.Otolaryngol Head Neck Surg. 2008;139:867-868.

14. Younis RH, Scheper MA, Lindquist CC, Levy B. Hybridcentral odontogenic fibroma with giant cell granuloma-likecomponent: case report and review of literature. Head NeckPathol. 2008;2:222-226.

15. Tosios KI, Gopalakrishnan R, Koutlas IG. So-called hybridcentral odontogenic fibroma/central giant cell lesion of thejaws. A report on seven additional cases, including anexample in a patient with cherubism, and hypotheses on thepathogenesis. Head Neck Pathol. 2008;2:333-338.

16. Damm DD. Interradicular radiolucency. Hybrid giant cellgranuloma and odontogenic fibroma. Gen Dent. 2013;61:77-78.

17. Fowler C, Tomich C, Brannon R. Central odontogenic fi-broma: clinico-pathologic features of 24 cases and reviewof the literature. Oral Surg Oral Med Oral Pathol.1993;76:587.

18. Hassan S, Reich R, Freedman P. Central odontogenic fibromawith associated central giant cell granuloma (Collision tu-mor?): report of 7 cases. NY Hospital Queens, NY Abstract#8 presented at the 62nd Annual Meeting, American Acad-emy of Oral and Maxillofacial Pathology. April 4e9, 2008;San Francisco, CA.

CLINICAL PATHOLOGIC CONFERENCE CASE 2:PALATAL PERFORATION A. Dovigia, E. Natarajanb, aOralPathology Diagnostic Services, San Diego, California, USA;bSection of Oral Pathology, University of Connecticut,Farmington, Connecticut, USA

Clinical Presentation: A 41-year-old man presented witha 1-week history of a “hole in the roof of his mouth” with asso-ciated discomfort (Figure 1). He reported burning the roof of hismouth 4 weeks previously while eating a hot slice of pizza.Initially, there was a pin-sized hole on the palate that continuedto enlarge over 1 week. He had since been unable to eat or drinkanything comfortably, as whatever he ate or drank entered hisnasal passage. At his initial visit, he presented with an“obturator” that he fashioned out of chewing gum that allowedhim to sip on soup and Ensure. The patient’s medical historywas significant for back problems and chronic sinus infectionsmanaged with over-the-counter medications. The patientreportedly smoked 1 pack of cigarettes a day for many years anddid not consume alcohol. As a warehouse custodian, he reportedworking in a chalk-filled environment. He lived with his wife, 6-year-old son, 3 dogs, and 2 cats.

Oral examination revealed a uniformly round perforation,approximately 8 mm in diameter, in the left anterior hard palateregion, just off the midline and posterior to the palatal rughae(Figure 1). The defect did not have a base, and oralenasal

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communication was evident. The surrounding mucosademonstrated diffuse erythema, which extended posteriorly andacross the palatal midline.

Differential Diagnosis: The acute presentation of a uni-formly round perforation on the palate suggested several possi-bilities. Physical trauma was among the first considerations,especially in light of the patient’s own report of having burnt hispalate. However, it was highly unlikely that a pizza burn wouldcause destruction of underlying hard tissue. The round defect alsosuggested a physical injury with a foreign object (pencil, tool,etc.), but there was no history of such trauma. Nasotrachealintubation during general anesthesia administration can result inpalatal perforation, especially if the patient has diabetes or isimmunocompromised.1 Our patient reported being generallyhealthy, with no history of recent or past surgery.

Drug related chemical injury was considered highly likelygiven the clinical presentation and lack of other systemic orlocalized symptoms. Drugs such as cocaine when insufflated(snorted) can produce the type of defects presented due tolocalized vasculitis and ischemia.1-5 The patient did not report hisprevious history of cocaine abuse at this initial visit and admittedto it only after initial diagnostic radiographs were obtained.

A number of infectious diseases are known to cause palatalperforation in some cases. Tertiary syphilis can cause large areasof granulomatous inflammation and necrosis with perforation ofthe palatal bone resulting in an oronasal fistula.1,6 Other infectionsassociated with palatal perforation, necrosis, and destructioninclude zygomycosis, aspergillosis, sinonasal blastomycosis,histoplasmosis, coccidiodimycosis, tuberculosis, leprosy, rhino-scleroderma, toxoplasmosis, and leishmaniasis.7-9 At the initialvisit, at least on the surface, there appeared to be no granulo-matous inflammation with necrosis, ulceration, or both. Our pa-tient was generally healthy, with no history of constitutional signsor symptoms. His routine physical and bloodwork results werereportedly within normal limits. Furthermore, no necrotic or ul-cerative tissue was present, requiring biopsy and histopathologicexamination.

Next, an immune-mediated etiology was considered. Dis-eases, such as systemic lupus erythematosus, granulomatouspolyangitis (GPA, or Wegener disease), sarcoidosis, and othervasculitides,1,7 can potentially present with palatal perforation butusually present with evident necrosis and soft tissue destruction.Also, patients with these diseases present with generalizedmultisystem involvement with accompanying constitutional signsand symptoms. Our patient did not present with any of the abovefindings making these diagnoses unlikely.

Finally, a malignant neoplasm extending from the maxillarysinus or nasal cavity capable of causing the palatal perforation wasconsidered. These malignancies may include natural killerecell or T-cell lymphomas and other destructive midlinemalignancies, including olfactory neuroblastoma (esthesioneuro-blastoma) or sinonasal undifferentiated carcinoma.10-12 Palatal ma-lignant neoplasms that may also cause extensive tissue destructioninclude malignant salivary gland tumors (mucoepidermoid carci-noma, adenoid cystic carcinoma, and other malignancies of minorsalivary gland origin), malignant nerve sheath tumors, and metas-tasis.13 These processes are generally associated with a fungatingmass, with evident ulceration, as well as necrosis with or withoutconstitutional signs or symptoms. Our patient was asymptomatic,and the presenting lesion was inconsistent with a neoplastic process.

Given the initial clinical presentation, a diagnosis of eitherphysical trauma or drug-induced (cocaine) nasal floor perforationwas considered.

Diagnosis and Management: The patient’s initial inter-view was conducted in the presence of his 6-year-old son.Additional clinical information revealed that there was no historyof pain, paresthesia, exudative discharge, foul odor, or swelling.The patient was healthy and reportedly received a full physicalwith bloodwork 2 months ago, and the findings had been withinnormal limits. Extraoral examination was unremarkable, with noevidence of swelling or lymphadenopathy. Not surprisingly,following removal of the “obturator,” pronounced rhinolalia wasnoted upon enunciation. Oral examination revealed the perfora-tion described above. The further oral examination revealed amoderately restored, partially edentulous dentition. There was noevidence of ulceration, discharge, or swelling; the area in questionwas nontender to palpation.

A panoramic radiograph showed partially edentulous adultdentitionwith several restorations (Figure 2). The palatal perforationcould not be properly evaluated. Occlusal radiographic examinationconfirmed the presence of a large oralenasaleantral perforation(Figure 3). A large, partially defined radiolucency measuringapproximately 4 to 5 cm anteroposteriorly across the palatalmidline and 1 to 3 cm in width. This large radiographic defect, inthe absence of obvious swelling, necrosis, and discharge triggeredan otolaryngologic referral for nasal endoscopy and laryngoscopy.Diagnostic computed tomography of the head was requested aheadof the patient’s scheduled otolaryngology appointment.

The history, the presentation, and the notable findings notedon plain radiography suggested the possibility of substanceabuseeassociated palatal perforation. The patient was contactedthe day after his initial visit. He was asked again about anyprevious history of substance abuse. He admitted to a distanthistory of cocaine insufflation (>10 years) and reported beingaddiction free for over 10 years. He had been understandablyreluctant to discuss this the previous day because his son had beenpresent in the examination room.

Diagnostic computed tomography revealed perforation anddestruction of the nasal floor, palatal vault, and nasal septum anddiffuse lytic change involving the lateral nasal walls and turbi-nates (Figures 4A and B). Soft tissue sinus membrane thickeningwas noted in keeping with the patient’s history of sinusitis. Thefeatures were characteristic of midline destructive disease(MDL), which can be caused by a range of conditions,including cocaine abuse.

Following nasal endoscopy, laryngoscopy and a thoroughotolaryngologic evaluation the above findings of MDL wereconfirmed. However, there was no evidence of necrotic tissue ormass on examination. The perforation was surrounded by mildlyinflamed soft tissue but was described as being generally “clean.”Abiopsy of the areawas not indicated; further serologic tests were notperformed. Further audiometry revealed left-sided hearing loss.

The clinical history, presentation, and radiographic findingsprovided sufficient evidence to arrive at a final diagnosis ofpalatal perforation associated with so-called cocaine-inducedMDL (CIMDL).14,15 The patient’s previous history of cocaineabuse was responsible for the notable osseous destruction of themidface. The palatal burn caused by eating a hot pizza slice wasincidental and was the inciting agent that caused the mucosaldefect. The mucosa overlying this large submucosal osseousdefect was likely the only layer of integument separating the oralcavity from the floor of the nose. An acrylic obturator wasfabricated to improve function in the patient. The patient waspresented with the option of undergoing surgical reconstructionwith a palatal flap, especially given that he had been drug free formore than 10 years. At his 6-month and 1-year follow-up visits,

Fig. 1. Oral examination revealed a 8-10 mm diameter, sym-metric perforation in the left anterior hard palate. The surroundingmucosa demonstrates diffuse erythema.

Fig. 2. Panoramic radiograph. The palatal perforation is notproperly appreciated.

Fig. 3. Occlusal radiograph. The oral-nasal communication presentsas a large, partially defined radiolucency measuring approximately 4to 5 cm� 2 cm along the left anterior palate, and crossing themidline.



he reported being happy with the acrylic obturator and elected todefer surgical reconstruction of the midface to a later date.

Discussion: The patient’s initial clinical presentation wasa highly superficial manifestation of a substantially destructiveprocess. The presence of a clean oronasal perforation triggeredconventional radiographic and CT workup, which revealed thetrue extent of the loss of underlying tissue and generated a dif-ferential diagnosis for sinonasal midline destructive disease(MDL).16 The patient’s history of cocaine insufflation wassufficient to arrive at a final diagnosis of a cocaine-inducedmidline destructive lesion (CIMDL).15-17 This case underscoresthe importance of obtaining a thorough (past and present) andprivate social history (drugs, sexual history, etc.). It highlights thecomparable clinical features of various MDLs. In particular, itprovides an opportunity to review similarities in the pathogenesesof MDLs, especially those associated with vasculitis, ischemia,and immune-mediated destruction.16

Cocaine (benzoylmethylecgonine) is a powerful nervousstimulant and highly addictive substance used in multiple forms(powder, leaves, infusions, etc.). In its purest form, cocaine hy-drochloride is a white powder. However, “street cocaine” isfrequently cut with fillers or enhancers, such as baking soda, qui-nine, sugars, local anesthetic, or, more recently, levamisole.17,18

The most frequently used route of self-administration ofpowdered cocaine is intranasal insufflation (snorting, sniffing, orblowing). Habitual cocaine insufflation often causes sinonasalmucosal necrosis and sinusitis. Osteocartilaginous destruction ofthe nose, sinuses, and palate is less common (CIMDL). It is re-ported that less than 4.5% of patients present with MDL.14,15 It hasbeen observed that CIMDL presents with characteristic centrifugalbone destruction: nasal septum (75%), turbinates (63%), lateralnasal wall (31%), nasal floor (<20%), and soft palate (<1%). Thiscentrifugal pattern of destruction is not observed in patients withpolyangitides.15 In addition, what seems to distinguish patientswith CIMDL from those without it is the presence ofantineutrophil cytoplasmic antibodies (ANCAs) in CIMDL.14

The predominant ANCA types in CIMDL are HNE-ANCA andPR3-ANCA (c-ANCA).14 Cocaine adulterated with levamisole isassociated with increased p-ANCA and antiphospholipids inserology assays. The deposition of ANCAs along the bloodvessels in the sinonasal passages causes destruction of bloodvessels in the area, mediated by macrophages and Tlymphocytes, and subsequent ischemia and necrosis. Thesepatients do not respond to conventional immunosuppressive ormodulatory therapy. Although CIMDL appears similar to thevasculitis observed in polyangitides, such as GPA or Wegenerdisease, the localized anatomic distribution (areas exposed toinsufflated cocaine) and the subtle differences in the mechanismsinvolved set the two apart. Furthermore, the radiographic featuresdescribed above and serologic findings help differentiate betweenCIMDL and MDL caused by immune-mediated polyangitides(GPA, microscopic polyangitides, etc.).

Our patient presented with clinical and radiographic featuresthat were consistent with CIMDL, although they occurred yearsafter cessation of his cocaine habit. The tissues appeared other-wise intact on endoscopy. Further serologic tests were neitherindicated nor obtained at the time of presentation. Althoughsurgical management was an option, our patient elected tomanage his defect conservatively.

In summary, it is apparent that CIMDL is a result of ischemicnecrosis triggered by cocaine in a small subset of cocaine abusers,especially those that are predisposed to producing ANCAs (HNE,and PR3 types). This appears to be an emerging problem,

Fig. 4. Computed tomography. A, Axial viewdabsence of nasalseptum. B, Coronal viewdpalatal perforation with oral-nasalfistula; soft tissue mucoperiosteal thickening of maxillary sinusmembranes is noted in both views.

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especially in individuals who use cocaine adulterated with le-vamisole. Recognizing this emerging pattern (clinical, social,radiographic, and serologic findings) is important, especiallywhen trying to halt the disease process. Immunosuppressivetherapy has limited therapeutic benefit, and only abstinence andcareful debridement, in combination with conservative surgical orprosthetic management, appear to help patients with either activeor past CIMDL.

References1. Seyer BA, Grist W, Muller S. Aggressive destructive midfacial

lesion from cocaine abuse [review]. Oral Surg Oral Med OralPathol Oral Radiol Endod. 2002;94:465-470.

2. Jewers WM, Rawal YB, Allen CM, et al. Palatal perforationassociated with intranasal prescription narcotic abuse. Oral SurgOral Med Oral Pathol Oral Radiol Endod. 2005;99:594-597.

3. Serrano-Sanchez P, Bagan JV, Jimenez-Soriano Y,Sarrion G. Palatal perforations secondary to inhaled cocaineabuse. Presentation of five cases. J Clin Exp Dent. 2010;2:e105-e109.

4. Silvestre FJ, Perez-Herbera A, Puente-Sandoval A,Bagán JV. Hard palate perforation in cocaine abusers: asystematic review. Clin Oral Investig. 2010;14:62162-62168.

5. Mari A, Arranz C, Gimeno X, et al. Nasal cocaine abuse andcentrofacial destructive process: Report of three casesincluding treatment. Oral Surg Oral Med Oral Pathol OralRadiol Endod. 2002;93:435-439.

6. Mozaffari MP, Seyyedi S, Chaghmaghi AM. Palatal perfora-tion: causes and features. WebmedCentral Oral Medicine.2011;2(4):WMCOO1890.

7. Bains MK, Hosseini-Ardehali M. Palatal perforations: past andpresent. Two case reports and a literature review. Br Dent J.2005;199:267-269.

8. Katusiime C, Ocama P, Kambugu A. A case of palatalperforation caused by toxoplasmosis. South Afr J HIV Med.2010;11:35-36.

9. Lucatorto F, Eversole LR. Deep mycoses and palatal perfo-ration with granulomatous pansinusitis in acquired immuno-deficiency syndrome: case reports. Oral Med Quintessence Int.1993;24:743-748.

10. Barrak HA. Hard palate perforations due to mucormycosis: areport of four cases. J Laryngol Otol. 2007;121:1099-1102.

11. Khan AA, Garg A, Dhawan S, Agarwal PK, Siraj F,Aggarwal S. T-cell non-Hodgkin’s lymphoma with co-lesional mucormycosis presenting as palatal perforation: acase report. J Indian Med Assoc. 2012;110:499-500.

12. Chaudhary SV, Karnik ND, Sabnis GR, Patil MV,Bradoo RA. Extranodal NK/T cell lymphoma presenting aspalatal perforation with oronasal fistula. J Assoc PhysiciansIndia. 2011;59:112-114.

13. Bhatt VR, Koirala B, Terjanian T. Extranodal natural killer/Tcell lymphoma, nasal type presenting as a palatal perforationand naso-oral fistula. BMJ Case Rep. 2011;2011.

14. Trimarchi M, Bussi M, Sinico RA, Meroni P, Specks U.Cocaine-induced midline destructive lesionsdan autoim-mune disease? Autoimmun Rev. 2013;12:496-500.

15. Trimarchi M, Gregorini G, Facchetti F, et al. Cocaine-induced midline destructive lesions. Medicine. 2001;80:391-404.

16. Rodrigo JP, Suarez C, Rinaldo A, et al. Idiopathic midlinedestructive disease: fact or fiction. Oral Oncol. 2005;41:340-348.

17. Muirhead TT, Eide MJ. Toxic effects of levamisole in acocaine user. N Engl J Med. 2011;364:E52.

18. Ferrazzo KL, Schneider PP, Shinohara EH. An unusual caseof adenoid cystic carcinoma with hard palate perforation.Minerva Stomatol. 2011;60:83-86.

CLINICAL PATHOLOGIC CONFERENCE CASE 3: A 15-YEAR-OLD MALE WITH A RADIOLUCENT JAWLESION D. Whitea, L.A. Franklinb, aUniversity of Kentucky,Lexington, Kentucky, USA; bMadigan Army Medical Center,Tacoma, Washington, USA

Clinical Presentation: A 15-year-old male presentedto his dentist with a well-circumscribed radiolucent lesion inthe right posterior mandible (Figures 1 and 2). His medical

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Fig. 1. Right mandibular molar region showing well demarcated,multilocular radiolucency without cortical expansion.

Fig. 2. Radiographic image showing expansion and thinning ofthe mandibular buccal plate.

Fig. 3. Medium power microscopic view showing haphazardarrangement of fascicles of spindle-shaped cells (hematoxylin andeosin stain).

Fig. 4. Medium power microscopic view showing cytoplasmicpositivity for smooth muscle actin (immunohistochemical stain).



history was noncontributory, and it was reported that thepatient was quite active in sports with a particular interestin karate.

Differential Diagnosis: The differential diagnosis of amultilocular radiolucency in the posterior mandible in ayoung person involves consideration of a number of odon-togenic, non-odontogenic, and other non-neoplastic lesions.Additional information about the patient, such as a history ofinjury, symptoms, or a family history of syndromes wherelytic bone lesions are a component, would be helpful. In theabsence of a comprehensive medical history, it is appropriateto consider a broad category of cysts or tumors. The mostcommon odontogenic lesions with this presentation areodontogenic keratocyst (OKC; keratocystic odontogenic tu-mor), ameloblastoma, and odontogenic myxoma. Non-odon-togenic lesions would include idiopathic bone cavity,aneurysmal bone cyst, osteoporotic marrow defect, andcentral giant cell lesion. It is also prudent to consider des-moplastic fibroma in the differential diagnosis given thepatient’s age and the radiographic presentation.

The OKC is typically found in people between ages 10 and40 years; Brannon reported a mean age of 37 years 9 months.1

Larger cysts may result in clinical expansion and palpablethinning of the overlying cortical plate of bone;2 and in thiscase, expansion is evidently absent.2

Ameloblastoma and odontogenic myxoma are both odonto-genic tumors, which are typically demonstrated as multilocular

radiolucent lesions. Ameloblastoma is relatively rare in the 10- to19-year age group, and myxoma is often encountered in those inthe age group of 25 to 30 years.3 Moreover, the radiographicpresentation of the lesion in this patient did not have a “soapbubble” appearance.

Although this lesion is notably associated with the apicesof several mandibular molar teeth, it is appropriate to considernon-odontogenic pathology in the differential diagnosis. Theidiopathic bone cavity (simple, traumatic, or hemorrhagicbone cyst or solitary bone cavity) is most frequentlyencountered in patients in the 10- to 20-year age group.3 Onradiographs, the classic appearance is that of a radiolucentlesion, which scallops between the apices of adjacent teeth;however, other lesions may show a partial fill with bonethat will not scallop between teeth and therefore mayresemble odontogenic cysts or tumors.4

Aneurysmal bone cyst is a benign expansile cystlikeprocess of bone, which usually involves the long tubularbones of the extremities, vertebrae, or sacrum.2 Most casesarise in children and young adults, although the incidenceof aneurysmal bone cyst in reference to other non-odontogenic lesions is quite rare.3

Fig. 1. A 26-year-old man had a speckled plaque demonstratingcoalescing creamy-yellow papules.

OOOO ABSTRACTS


Focal osteoporotic marrow defect is a consideration, althoughthese lesions typically occur in patients over the age of 40 yearsand more often in females.3

Giant cell tumors are histologically benign, yet expansile andpossibly locally aggressive tumors formed by osteoclastic giantcells.2 Most patients who have a giant cell tumor are in the thirdor fourth decade of their lives.5 Although this type of lesion is aconsideration, most of these tumors are more common in theanterior portions of the jaws, and mandibular lesions frequentlycross the midline.3

Desmoplastic fibroma presents as an oval lytic defect thatis well demarcated. No mineral occurs within the lesionaltissue, but if the cortex of the bone is unevenly affected ordestroyed, areas of trabeculation may be apparent.5 This is anuncommon tumor of fibroblastic origin and yet occurscommonly in the mandible and is found in patients youngerthan 30 years of age.

Diagnosis: The final diagnosis in this case was solitarymyofibroma, a benign proliferation of fibroblast-like cells,which ultrastructurally demonstrate the presence of cyto-plasmic actin-like filaments. Two forms are recognized: (1)myofibromatosis represents a condition in which there aremultiple lesions in infants and childhood; and (2) the solitaryform is seen in older children and adults. This case representsthe latter.

The solitary form is more common, and the head andneck region, including the mandible, tongue, buccal mucosaand lips, is often the site of occurrence.6 Typically, thealteration presents as a nonspecific, painless swelling and ismost common during the first four decades of life. Aclinical differential diagnosis includes a number of softtissue or bone proliferations.

Microscopically, the tumor consists of a proliferation ofspindle-shaped cells with eosinophilic cytoplasm, in whichfascicles and swirls are formed (Figure 3).Immunohistochemistry in this case revealed the presence ofcytoplasmic smooth muscle actin (Figure 4), but the cellswere negative for desmin and S-100 protein.7 Thesemarkers are helpful in differentiating myofibroma fromother connective tissue proliferations.8

Management: Treatment is conservative surgical exci-sion. Recurrence is uncommon, although a small number mayrecur after excision.

References1. Brannon RB. The odontogenic keratocyst: a clinicopatho-

logic study of 312 cases. Part 1. Oral Surg. 1976;42:54-72.

2. Gnepp DR. Diagnostic Surgical Pathology of the Head andNeck. Philadelphia: Saunders; 2001:616.

3. Neville BW, Damm DD, Allen CM, et al. Oral and Maxillo-facial Pathology. 3rd ed. Philadelphia: Saunders; 2002:539-540. 551-552.

4. Marx RE, Stern D. Oral and Maxillofacial Pathology. 2nd ed.Hanover Park, IL: Quintessence Publishing; 2012:215-217.

5. Unni KK, Inwards CY, Bridge JA, et al. AFIP Atlas of TumorPathology, Series 4: Tumors of the Bones and Joints.Annapolis Junction, MD: ARP Press; 2005.

6. Foss RD, Ellis GL. Myofibroma and myofibromatosis of theoral region: a clinicopathologic analysis of 79 cases. OralSurg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:57-65.

7. Satomi T, Kohno M, Enomoto A, et al. Solitary myofibroma ofthe mandible: an immunohistochemical and ultrastructuralstudy with a review of the literature. Med Mol Morphol.2014;47:176-183.

8. Sundaravel S, Anuthama K, Prasad H, Sherlin HJ,Ilayaraja V. Intraosseous myofibroma of the mandible: ararity of jaws: with clinical, radiologic, histopathologicaland immunohistochemical features. J Oral Maxillof Pathol.2013;17:121-125.

CLINICAL PATHOLOGIC CONFERENCE CASE 4: AYELLOWISH SPECKLED PLAQUE OF BUCCALMUCOSA Tania Jhamb, DDSa, Barry H. Frank, DDSb,Lee J. Slater, DDS, MSc, aCase Western Reserve Univer-sity, School of Dental Medicine, Cleveland, OH; bDesertOral Surgery, Las Vegas, NV; cScripps Oral PathologyService, San Diego, CA

Clinical Presentation: A 26-year-old man presented withan asymptomatic lesion of unknown duration (Figure 1). The30 � 10 mm grayish-yellow, speckled plaque demonstratedsubtle peripheral mucosal erythema. The surgeon’s clinicalimpression was hyperkeratosis and cheek biting, with possiblesebaceous hyperplasia.

Differential Diagnosis: The clinical features were inter-preted to most likely be indicative of an inflammatory or infec-tious process; a neoplastic condition was regarded as less likely.On the basis of the clinical presentation, several possibilities wereconsidered in the differential diagnosis, including, from most toleast likely, pyostomatitis vegetans, allergic contact stomatitis,infection, Langerhans cell histiocytosis of soft tissue, and squa-mous cell carcinoma.

Pyostomatitis vegetans, a rare condition, is an oral manifes-tation of inflammatory bowel disease and is more commonly seenin patients with ulcerative colitis or Crohn disease. It is





























characterized by multiple pustules on an erythematous base.These pustules can appear yellow or white in color, and as theyerode, they form shallow “snail track” ulcers. The conditioncommonly affects multiple sites in the mouth, including the labialand buccal mucosa, the hard and soft palates, and the gingiva.The lesions are usually asymptomatic.1,2

Allergic contact stomatitis (hypersensitivity reaction) was alsoconsidered as part of the histopathologic differential diagnosis. Theoral lesions may appear as an acute or chronic manifestation of anallergic reaction. The lesions are usually symptomatic, and patientsoften describe a burning sensation. Allergic contact stomatitis canshow wide range of clinical patterns, and chronic cases may appearas erythematous or leukoplakic.3

The possibility that the lesion resulted from an infectiousprocess was also considered. Oral manifestations of infectiousdisease may either represent the primary site of infection or maybe secondary to widespread disease. Intraoral lesions can becaused by bacterial, fungal, or parasitic organisms (e.g., syphilis,tuberculosis, coccidioidomycosis, histoplasmosis, blastomycosis,and leishmaniasis). Clinically, infectious lesions may be solitaryor multiple. They may have an erosive, erythematous, and gran-ular appearance. Patients are usually symptomatic, presentingwith varying degrees of pain.4-7

Langerhans cell histiocytosis of soft tissue exhibits variationin appearance. Accordingly, lesions may appear leukoplakic orerythematous. Lesions may be solitary or multiple and may pre-sent as ulcerated or boggy. In one third of cases, lesions are seenin oral soft tissue structures, with or without simultaneous intra-osseous involvement.8

Squamous cell carcinoma of buccal mucosa comprises 10%of intraoral carcinomas in the United States and Europe. How-ever, its incidence is higher in Asia because of the habit of betelnut chewing. It is also associated with tobacco chewing or snuffdipping. Clinically, it usually appears as a white, verrucous-likelesion. Minimal pain may be present during the early growthphase.9,10

Diagnosis and Management: An incisional biopsydemonstrated evidence of candidiasis, with pseudohyphaefocally colonizing the parakeratotic layer. A strikinglydistinctive histologic finding was the presence of eroded su-perficial pustules that contained prominent eosinophils. Amyriad of conditions can manifest with increased eosino-phils,11-13 but their unusual distribution in subcornealeosinophilic pustules, together with a possible immunodefi-ciency-associated candidiasis, evoked consideration of hyper-immunoglobulin E syndrome (HIES) (Figures 2A and B). Thesurgeon confirmed that the patient had a history of HIES (Job

Fig. 2. A, Buccal mucosal biopsy exhibiting an eroded hyper-parakeratotic surface covered by a “smudged” fibrinous exudateshowing entrapped leukocytes (predominantly eosinophils);spongiosis with transmigrating eosinophils and lymphocytes; and,in connective tissue, a dense polymorphic inflammatory infiltrateof lymphocytes, plasma cells, and eosinophils. B, Surfaceepithelium displaying a plethora intraepithelial degranulatingeosinophils between keratinocytes of the superficial spinous layer.C, Degenerating degranulated eosinophils entrapped in a fibri-nous exudate covering eroded surface epithelium (an erodedeosinophilic pustule).

OOOO ABSTRACTS


syndrome); it manifested in the patient predominantly asrecurrent lung infections. Therefore, the buccal mucosallesion was diagnosed as an oral manifestation of HIES.

The patient has been under the care of his physician, andno significantly debilitating features of HIES have beenmanifested.

Discussion: HIES, or Job syndrome, was first describedby Davis et al. in 1966.14 It is a complex primaryimmunodeficiency associated with extremely high serumimmunoglobulin E (IgE) levels and susceptibility to infectionswith extracellular bacteria.15 It has no known associationswith race, ethnicity, or gender.15 It is characterized byeczematoid rashes, skin abscesses, recurrent sinopulmonaryinfections, mucocutaneous candidiasis, and malignancies,along with craniofacial, musculoskeletal, dental, and vascularabnormalities.15-24 This autosomal dominant condition iscaused by mutations in the gene STAT3 (signal transducer andactivator of transcription 3) located on chromosome 17 q21.25

STAT3 is integral to signal transduction for multiple cytokines,including interleukin (IL)-6, IL-10, IL-11, IL- 17, IL-21, IL-22, and IL-23.26,27 This pathway controls both theproinflammatory and anti-inflammatory aspects of the immuneresponse.26 Furthermore, mutations in STAT3 lead to failure ofT helper 17 (Th17) CD4 cell differentiation, which is STAT3dependent; this may lead to higher susceptibility to infectionseen in HIES.27,28

Clinical features of HIES include rashes that may resolve orpersist and are consistent with eczematoid dermatitis driven byStaphylococcus aureus infection. The skin infections lack warmthand erythema and thus are appropriately named “cold” abscesses,which are a universal feature of the disease.17,15,27 Anothercommonly seen feature of HIES is recurrent sinopulmonary in-fections, predominantly caused by S. aureus, which result inbronchiectasis and pneumatoceles.15,20 High rates of mucocuta-neous candidiasis are also commonly seen in the condition.15,20

Therefore, HIES is a disease of both excessive inflammation(exuberant purulence seen in pneumonias) and scant inflamma-tion (presence of cold abscesses).

Patients with HIES may have cutaneous abscesses and mayexhibit eosinophilic spongiotic dermatitis. Other histopathologicfindings included eosinophilic folliculitis, superficial and deepperivascular dermatitis with abundant eosinophils, and abundanteosinophils extending into the subcutaneous fat.17

The condition is associated with an increased risk of malig-nancies, such as non-Hodgkin lymphoma, predominantly of B-cellorigin.29 In HIES, nonimmunogenic features include increasedinteralar distance, prominent forehead and chin, coarse skin, andfacial asymmetry that becomes apparent in late childhood and earlyadolescence.17,24 Musculoskeletal abnormalities include hyper-extensibility, scoliosis,minor trauma fractures, and osteopenia.14,24

Vascular abnormalities lead to aneurysms, dilation and tortuosity ofmiddle-sized arteries, and lacunar infarctions.22

Dental manifestations of autosomal dominant HIES includeretention of deciduous teeth, delayed eruption of permanent teeth,and double dentition.16,19,23 Once deciduous teeth are removedbefore the teenage years, permanent teeth erupt normally. Patientsalso show high, arched palate, cleft lip and palate, midline sagittalclefts in the middle third of the tongue and multiple mucosalfissures.19 Oral superinfections of the mucous membrane (usuallymycotic) result in lesions, erythema, and atrophy.15

Laboratory abnormalities in HIES include eosinophilia andIgE levels usually elevated above 2000 IU/mL. HIES should besuspected in individuals with elevated IgE in addition to

immunologic and somatic features. A scoring system developedby Grimbacher et al. is useful in the diagnosis of HIES and aids inpredicting who is likely to have STAT3 mutations.30,31

Treatment of HIES is limited to proper skin care and preventionand aggressive treatment of infections. Several treatment modalitieshave been proposed for HIES, such as bone marrow trans-plantation,32,33 interferon-g,34 intravenous IgG,35 disodium cromo-glycate,36 isotretinoin,37 and double-filtration plasmapheresis.38 Thedata supporting the use of these are preliminary, and none of thetreatment modalities offers a cure.

References1. Hegarty AM, Barrett AW, Scully C. Pyostomatitis vegetans.

Clin Exp Dermatol. 2004;29:1-7.2. Woo SB. Oral Pathology: A Comprehensive Atlas and Text.

Philadelphia, PA: Saunders; 2012.3. Bakula A, Lugovi�c-Mihi�c L, Situm M, et al. Contact allergy in

the mouth: diversity of clinical presentations and diagnosis ofcommon allergens relevant to dental practice. Acta Clin Croat.2011;50:553-561.

4. Papini M, Bettacchi A, Guiducci A. Nodular secondarysyphilis. Br J Dermatol. 1998;138:704-705.

5. Samaranayake LP, Keung Leung W, Jin L. Oral mucosalfungal infections. Periodontol 2000. 2009;49:39-59.

6. Gill AM. Eosinophilia in tuberculosis. Br Med J. 1940;2:220-221.

7. Harley WB, Blaser MJ. Disseminated coccidioidomycosisassociated with extreme eosinophilia. Clin Infect Dis. 1994;18:627-629.

8. Cleveland DB, Goldberg KM, Greenspan JS, et al. Langer-hans’ cell histiocytosis: report of three cases with unusual oralsoft tissue involvement. Oral Surg Oral Med Oral Pathol OralRadiol Endod. 1996;85:541-548.

9. Diaz Jr EM, Holsinger FC, Zuniga ER, et al. Squamous cellcarcinoma of the buccal mucosa: one institution’s experiencewith 119 previously untreated patients. Head Neck. 2003;25:267-273.

10. Dorta RG, Landman G, Kowalski LP, et al. Tumour-asso-ciated tissue eosinophilia as a prognostic factor in oralsquamous cell carcinomas. Histopathology. 2002;41:152-157.

11. Mongomery ND, Dunphy CH, Mooberry M, et al. Diagnosticcomplexities of eosinophilia. Arch Pathol LabMed.2013;137:259-269.

12. Valent P, Klion AD, Horny H-P, et al. Contemporaryconsensus proposal on criteria and classification of eosino-philic disorders and related syndromes. J Allergy ClinImmunol. 2012;130:607-612.

13. Koslovsky DA, Kostakis VA, Glied AN, et al. An unusuallesion of the tongue in a 4-year-old with Job syndrome. JOral Maxillofac Surg. 2013;71:1042-1049.

14. Davis SD, Schaller J, Wedgwood RJ. Job’s syndrome.Recurrent, “Cold,” Staphylococcal abscesses. Lancet. 1966;1:1013-1015.

15. Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgEsyndrome with recurrent infectionsdan autosomal domi-nant multisystem disorder. N Engl J Med. 1999;340:692-702.

16. Aldous JA, Olson GJ, Parkin MJ. Dental Observations ofHyper IgE Disorder. J Clin Pediatr Dent. 2007;32:69-72.

17. Chamlin SL, McCalmont TH, Cunningham BB, et al. Cuta-neous Manifestations of Hyper-IgE Syndrome in Infants andChildren. J Pediatr. 2002;141:572-575.


















































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18. DeWitt CA, Bishop AB, Buescher LS, et al. Hyper-immunoglobulin E Syndrome - Two Cases and a Review ofthe Literature. J Am Acad Dermatol. 2006;54:855-865.

19. Domingo DL, Freeman AF, Davis J, et al. Novel IntraoralPhenotypes in Hyperimmunoglobulin- E Syndrome. OralDis. 2008;14:73-81.

20. Erlewyn-Lajeunesse MD. Hyperimmunoglobulin-E Syn-drome with Recurrent Infection: A Review of CurrentOpinion and Treatment. Pediatr Allergy Immunol. 2000;11:133-141.

21. Freeman AF, Collura-Burke CJ, et al. Brain Abnormalities inPatients with Hyperimmunoglobulin E Syndrome. Pediatrics.2007;119:e1121-e1125.

22. Ling JC, Freeman AF, Gharib AM, et al. Coronary ArteryAneurysms in Patients with Hyper IgE Recurrent InfectionSyndrome. Clin Immunol. 2007;122:255-258.

23. O’Connell AC, Puck JM, Grimbacher B, et al. DelayedEruption of Permanent Teeth in HyperimmunoglobulinemiaE Recurrent Infection Syndrome. Oral Surg Oral Med OralPathol Oral Radiol Endod. 2000;89:177-185.

24. Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE Syn-drome Update. Ann N Y Acad Sci. 2012;1250:25-32.

25. Holland SM, DeLeo FR, Elloumi HZ, et al. STAT3 Muta-tions in the Hyper-IgE Syndrome. N Engl J Med. 2007;357:1608-1619.

26. Chehimi J, Elder M, Greene J, et al. Cytokine and ChemokineDysregulation in Hyper-IgE Syndrome. Clin Immunol.2001;100:49-56.

27. Ozcan E, Notarangelo LD, Geha RS. Primary Immune De-ficiencies with Aberrant IgE Production. J Allergy ClinImmunol. 2008;122:1054-1062.

28. Milner JD, Brenchley JM, Laurence A, et al. Impaired T(H)17 Cell Differentiation in Subjects with Autosomal DominantHyper-IgE Syndrome. Nature. 2008;452:773-776.

29. Leonard GD, Posadas E, Herrmann PC, et al. Non-Hodgkin’slymphoma in Job’s syndrome: a case report and literaturereview. Leuk Lymphoma. 2004;45:2521-2525.

30. Grimbacher B, Schäffer AA, Holland SM, et al. GeneticLinkage of Hyper-IgE Syndrome to Chromosome 4. Am JHum Genet. 1999;65:735-744.

31. Woellner C, Gertz EM, Schaffer AA, et al. Mutations inSTAT3 and diagnostic guidelines for hyper-IgE syndrome. JAllergy Clin Immunol. 2010;125:424-432.

32. Gennery AR, Flood TJ, Abinun M, et al. Bone MarrowTransplantation Does Not Correct the Hyper IgE Syndrome.Bone Marrow Transplant. 2000;25:1303-1305.

33. Goussetis E, Peristeri I, Kitra V, et al. Successful Long-TermImmunologic Reconstitution by Allogeneic HematopoieticStem Cell Transplantation Cures Patients with AutosomalDominant Hyper-IgE Syndrome. J Allergy Clin Immunol.2010;126:392-394.

34. Pung YH, Vetro SW, Bellanti JA. Use of Interferons inAtopic (IgE-Mediated) Diseases. Ann Allergy. 1993;71:234-238.

35. Waldfahrer F, Pahl S, Federspil PA, et al. Hyper-IgE Syn-drome with ENT Manifestations. Overview and Case Reportof Successful Therapy with High Dosage I.V. Immunoglob-ulin. HNO. 1999;47:1063-1068.

36. Kojima K, Inoue Y, Katayama Y, et al. Improvementwith Disodium Cromoglycate of Neutrophil Phagocytosisand Respiratory Burst Activity in a Patient withHyperimmunoglobulin E Syndrome. Allergy. 1998;53:1101-1103.

37. Shuttleworth D, Holt PJ, Mathews N. HyperimmunoglobulinE Syndrome: Treatment with Isotretinoin. Br J Dermatol.1988;119:93-99.

38. Yamada H, Nagaoka I, Takamori K, et al. Double FiltrationPlasmapheresis Enhances Neutrophil Chemotactic Responsesin Hyperimmunoglobulin E Syndrome. Artif Organs.1995;19:98-102.

CLINICAL PATHOLOGIC CONFERENCE CASE 5: AMALE NAVY DIVER WITH ORAL AND SKINLESIONS Basile Ja, J.T. Castle, CAPT, DC USNb, aUniver-sity of Maryland Dental School, Baltimore, Maryland, USA;bNaval Medical Center Portsmouth, Portsmouth, Virginia,USA

Clinical Presentation: A 28-year-old male Navy diverpresented with a chief complaint of oral and skin lesionsfollowing an underwater port-clearing mission that occurredfollowing the Haiti earthquake in January 2010. He reportednumerous cause-and-effect factors for the lesions and stated thatthey could be controlled by diet and the use of a tanning bed. Atthe time of examination, he was applying gentian violet andiconazole nitrate to the lesions. On examination, the patientexhibited multiple impressive craterlike ulcers and erosions of theskin of the face and ears (Figure 1), the chin, and the back of thehead. Intraoral erosions of the buccal, labial, and vestibularmucosa were also present (Figure 2), along with fissures andsurface erosions at the corners of the mouth (Figure 3). Anadditional medical examination revealed lesions on the back ofthe neck, anus, penis, and scrotum in various stages of healing.Of particular note, the patient had a distinct “fishy” odor abouthim.

Differential Diagnosis: On the basis of the history ofspending a significant amount of time in the water, the differentialdiagnosis for this case should include conditions that developupon exposure to infectious organisms as well as hazardousmaterials or toxic substances released into the environmentfollowing an earthquake. High on this list would be bacterial orfungal infections, which could manifest as both mucosal and skinulcerations. This would include Mycobacterium tuberculosis, aparticularly hardy microorganism that can infect multiple tissues,leading to ulcerations from long-term granulomatous inflamma-tion. There are many reported cases in the literature documentingoral infections, with one case in particular closely resembling theoral lesions exhibited by the current patient.1 However, thepatient was not suffering from any systemic symptoms as mightbe expected.

Diphtheria should also be considered, since it can cause oralcavity lesions, similar to those shown in Figure 2, as well as skinlesions in the cutaneous form.2 What favors this diagnosis is the factthat systemic toxic manifestations are uncommon among those whohave been immunized, so the patient would not be expected toexperience any physical illness or the acute-phase reacton commonto bacterial infections. Although high on the differential list, theoral lesions of diphtheria are usually located more posteriorly, andthe skin ulcerations would be much larger, with raised, rolledborders and necrotic centers. Finally, infection with Bacillusanthracis, the organism that causes anthrax, can manifest as bothcutaneous and oropharyngeal ulcers. However, once again, in thiscondition, the ulcerations would be more alarming, with red,raised, highly inflamed borders and a black necrotic base.3 The







































































Fig. 1. Craterlike ulcer on cheek and erosion of tragus and helixwith re-epithelialization of the antitragus.

Fig. 2. Maxillary labial vestibular mucosa demonstrating multi-ple erosive areas extending to the wetedry line.

Fig. 3. Multiple skin ulcers and erosions in varying stages ofhealing, some showing scale crust formation, others with um-bilicated borders and peripheral erythema.

Fig. 4. Incisional biopsies of oral mucosa revealed acute andchronic inflammation. A, Low magnification. B, High magnifi-cation. (hematoxylin and eosin stain).

OOOO ABSTRACTS


skin ulcerations exhibited by the current patient, although slightlyinflamed, were flat and not likely necrotic. It also must be notedthat transmission of bacteria through contaminated seawater, asimplied by the history, would be rather unlikley.

Vesiculobullous disorders also need to be considered. Sincethe patient is suffering from both skin and mucosal lesions,pemphigus vulgaris would be high on the differential list, althoughthis condition affects an older population, usually related to he-redity (European Jewish and Mediterranean populations) and hasnot been known to arise acutely.

4 Paraneoplastic pemphigus can

arise acutely, but this disease generally affects older females, andthe patient does not have a history of a neoplasm. More closelyrelated to an environmental factor would be erythemamultiforme, which could account for the skin lesions. The lackof a history of “target” lesions and labial crusting and the factthat erythema multiforme favors skin over mucosa, whereas this



patient has extensive aphthae-like oral lesions, rule out thisdiagnosis. Another factor that rules out all of these conditions isthat there is no specific history of blisters that ruptured to formthe current lesions.

Contact dermatitis or mucositis should also be considered, asthe patient could have come into contact with some toxic sub-stance during his dives, perhaps multiple times, and eventuallydeveloped the reaction that brought him to the clinic. The varied,irregular appearance of the skin lesions, which could have startedas a rash, ulcerations, or both, rather than blisters, as well as theoral ulcerations, might be a result of an exuberant immune re-action that can manifest in any number of ways.

Diagnosis and Management: Incisional biopsy of the skindemonstrated parakeratosis, acute and chronic inflammation, andpolarizable foreign material, and prior biopsy had demonstratedpsoriasis. Direct immunofluorescence studies were negative. Inci-sional biopsy of the oral mucosa revealed acute and chronicinflammation (Figures 4A and B), and once again, directimmunofluorescence was negative. The results of basic metabolicpanels to include magnesium and phosphorus, as well as acomplete blood count with differential, were within normal limits.Fungal cultures of selected skin lesions showed no growth. Thepatient additionally stated that he had removed a worm from alesion of his face and was concerned that these worms weretracking through his brain. Following this admission, the patientwas referred for a psychological consultation, where he wasdiagnosed as suffering from schizophrenia and delusional disorderwith concomitant Munchausen syndrome and was placed onolanzapine (Zyprexa), aripiprazole (Abilify), and valproic acid(Depakote).

Discussion: On January 12, 2010, an earthquakemeasuring 7.0 on the Richter scale struck Haiti, the strongestever recorded in that country’s history. The earthquake inflictedsignificant damage to a population already suffering from aseries of hurricanes and tropical storms that occurred in 2008.The poorest country in the western hemisphere, Haiti’s alreadyweak infrastructure, including basic utilities, such as power,water, and sanitation, was almost completely destroyed,creating an environment favorable for the development of hy-giene-related and foodborne illnesses and diseases associatedwith overcrowding, which might be expected with populationdisplacement and relocation to shelters. In addition to the im-mediate concerns of wounds and injuries, the World HealthOrganization (WHO) anticipated that several vectorborne andcommunicable diseases, including pandemic influenza A (H1N1) 2009, diphtheria, dengue, hepatitis, leptospirosis, tubercu-losis, typhoid, measles, and pertussis, would arise under theseconditions.5

In the case presented here, the most unfortunate aspect wasthe fact that the patient sought out many providers at multiplemedical facilities who believed his fictitious report. None of theseproviders who saw the patient early on in his presentations(October 2011) were able to put together the fact that U.S. Navyoperations ceased in Haiti in June 2010 and therefore his oral andskin lesions were unrelated to his diving missions. The delay inthe detection of the truth about his condition was understandable,as most practitioners would find it difficult to believe that a pa-tient could or would use deceptive behaviors to alter their clinicalappearance. Munchausen syndrome, a term coined by Asher in1951,6 refers to patients who repeatedly request medical care forfictitious illnesses or conditions. A typical patient withMunchausen syndrome would present to multiple health care

facilities over time, often with spectacular and exaggeratedclinical signs or symptoms of a malady that is often difficult toascribe a particular cause or triggering event. The health careseeking behavior is personified by the “sick role” the patientspresent. Patients are eager to undergo wide-ranging and ofteninvasive testing procedures in an effort to have their clinicalsigns and symptoms investigated. The typical patient withMunchausen syndrome is well versed in medical language, ispersistent in his or her demand for higher levels of medicalattention, and requests multiple testing procedures andconsultations.7

Munchausen syndrome may be similar to malingering, a termthat refers to the intentional fabrication or exaggeration of mental orphysical symptoms by a person who is seeking to avoid of militaryduty, work, or incarceration; to obtain financial compensation ordrugs; or to evade prosecution.8 However, unlike Munchausensyndrome, malingering is not considered a mental disorder, as theintent seems to be the factor that determines the label given for theparticular actions.8 Malingering within the military ranks has beenestimated at 1 diagnosis per 28,000 outpatient encounters.9 Giventhe recent attention to post-war and post-tragedy outcomes,patients with these conditions seek legitimization whereby socialadvantages become available to them in a society that is moreready to accept to physical disorders compared with emotional orpsychological disorders.10

Recovery from Munchausen syndrome is rare, and treatmentis a difficult task, although addressing the issue in a noncon-frontational and accepting manner can facilitate the patient takingthe initial step toward resolution, whether that may be throughpharmaceutical therapy, supportive psychotherapy, or hospitali-zation psychiatric care.7 Long-term results in these patients arehard to predict and quantify, as many relapse after treatmenthas been completed. Understandably, substantial morbidity andmortality exist with this disorder.

Although it may be a delayed finding, cutaneous Munchau-sen syndrome should be considered when skin manifestations arespectacular and difficult to diagnose and the findings are normalwith routine or basic testing.7

DisclaimerThe opinions and assertions expressed herein are those of theauthors and are not to be construed as official or representingthe views of the Department of the Navy or the Department ofDefence. I certify that all individuals who qualify as authorshave been listed; that each has participated in the conceptionand design of this work, the writing of the document, and theapproval of the submission of this version; that the documentrepresents valid work; that if we used information derived fromanother source, we obtained all necessary approvals to use it andmade appropriate acknowledgments in the document; and thateach takes public responsibility for it. We are military servicemembers. This work was prepared as part of my official duties.Title 17 U.S.C. 105 provides that “Copyright protection underthis title is not available for any work of the United StatesGovernment.” Title 17 U.S.C. 101 defines a United StatesGovernment work as a work prepared by a military servicemember or employee of the United States Government as partof that person’s official duties.

References1. Kamala R, Sinha A, Srivastava A, et al. Primary tuberculosis

of the oral cavity. Indian J Dent Res. 2011;22:835-838.



Fig. 1. A & B, Extra-oral photographs show left facial fullnessand asymmetry. The left eye has been superiorly displaced. Theleft nostril is filled with mucous secretions.

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2. De Benoist AC, White JM, Efstratiou A, et al. Importedcutaneous diphtheria, United Kingdom. Emerg Infect Dis.2004;10:511-513.

3. Siddiqui MA, Hossain Khan MA, Ahmed SS, et al. Recentoutbreak of cutaneous anthrax in Bangladesh: clinico-de-mographic profile and treatment outcome of cases attended atRajshahiMedical College Hospital.BMCRes Notes. 2012;5:464.

4. Bickle KM, Roark TR. Autoimmune bullous dermatoses: areview. Am Fam Physician. 2002;65:1861-1871.

5. WHO Office, Haiti. Public Health risk assessment and in-terventions: earthquake, in Haiti; Communicable DiseaseWorking Group on Emergencies (WHO/HQ); CommunicableDisease Surveillance and Response (AMRO/PAHO).

6. Asher R. Munchausen’s syndrome. Lancet. 1951;1:339-341.7. Boyd AS, Ritchie C, Likhari S. Munchausen syndrome and

Munchausen syndrome by proxy in dermatology. J Am AcadDermatol. 2014;71:376-381.

8. Armed Forces Health Surveillance Center (AFHSC). Malin-gering and factitious disorders and illnesses, active component,U.S. Armed Forces, 1998-2012. MSMR. 2013;20:20-24. dis-cussion 23-24.

9. Lande RG, Williams LB. Prevalence and characteristics ofmilitary malingering. Mil Med. 2013;178:50-54.

10. Bass C, Halligan P. Factitious disorders and malingering:challenges for clinical assessment and management. Lancet.2014;383:1422-1432.

Fig. 2. Intraoral photograph shows a large, erythematous, exo-phytic mass of the left maxillary molar region.

CLINICAL PATHOLOGIC CONFERENCE CASE 6: PRO-LIFERATIVE MAXILLARY MASS K.G. Cordella, A. Arri-basb, K.C. Chanc, aLouisiana State University School ofDentistry, New Orleans, Louisiana, USA; bWest Texas Oraland Maxillofacial Surgery, El Paso, Texas, USA; cNew YorkUniversity College of Dentistry, New York, New York, USA

Clinical Presentation: A 77-year-old male presentedwith an asymptomatic, exophytic mass of the left posteriormaxilla. The patient had first noticed the mass 3 months beforepresentation. His medical history was significant for benignprostatic hyperplasia and cataracts. Medications included lisino-pril, hydrochlorothiazide, nepafenac, and tamsulosin. The patienthad been smoking at least one cigar a day for the past 40 years.Extraorally, the patient’s left face showed fullness and asymme-try, which extended posteriorly to the cheek. The left eye wasdisplaced superiorly. The left nostril had mucous secretions(Figures 1A and B). Intraorally, on the left posterior maxilla, therewas a large, erythematous mass, which extended onto the buccaland palatal alveolar mucosa. The patient’s left maxillary molarshad been extracted many years before the development of thelesion. Mandibular teeth were occluding against the mass,creating a wear pattern across the surface of the lesion(Figure 2). Cone beam computed tomography (CBCT) of thehead revealed a soft tissue mass occupying the entire leftmaxillary sinus. The mass had remodeled and eroded the orbitalfloor and had destroyed the lateral and medial walls of thesinus to occupy the left masseteric space and left nasal cavity.The mass obstructed sinonasal drainage. The ethmoid air cellswere completely opacified. The mass extended inferiorly to thealveolar process and had replaced the cancellous bone of theleft maxillary molar region. The buccal cortex of the leftmaxillary molar region was lost. The palatal cortex and floor of

the left nasal cavity were grossly intact, but there were pin-point breaks along the palatal cortex (Figures 3A and B).

Differential Diagnosis: Given the clinical and radio-graphic findings, the mass was consistent with a malignancy.Malignancies that most frequently affect the maxillary sinus in theolder adult population include carcinomas and hematopoieticmalignancies. Squamous cell carcinoma and salivary gland ade-nocarcinomas were considered. Sinonasal undifferentiated carci-noma was considered less likely, as some bone remodeling wasevident in the CBCT scan, a radiographic feature not typicallypresent in highly aggressive malignancies. Metastatic carcinoma,lymphoma, multiple myeloma, and plasmacytoma were consid-ered because they cause pin-point breaks along cortices.

Diagnosis and Management: Incisional biopsy of theintraoral lesion was performed and the specimen submitted forhistopathologic examination. Initial examination revealed a clearcell neoplasm with a prominent vascular component. The overallfeatures were highly suspicious for metastatic clear cell renal cellcarcinoma (RCC). After further communication with the























Fig. 3. A& B, Coronal images of the cone beam computed tomog-raphy of the head show a mass of soft tissue attenuation that has filledthe entire leftmaxillary sinus anddestroyed itsmedial and lateralwalls.Themasshas blocked sinonasal drainage andopacified the ethmoid aircells (asterisks). There is remodeling (arrowhead) and destruction ofthe left orbital floor. The palatal cortex of the left maxillary molarregion is grossly intact but has multiple pin-point breaks (arrows).

Fig. 4. A, Low power (�4) photomicrograph revealing oral mucosaand tumor with solid growth pattern infiltrating the underlying con-nective tissue. (hematoxylin and eosin stain). B, High power photo-micrograph (�40) of the neoplasm exhibiting formation of prominentduct-like structures resembling renal tubules with intervening thin-walled, delicate blood vessels (hematoxylin and eosin stain).



submitting surgeon, it was learned that the patient had no priorhistory of malignancy. The neoplasm exhibited a solid growthpattern infiltrating the connective tissue (Figure 4A). Formationof prominent ductlike structures that resembled renal tubules,with intervening thin-walled, delicate blood vessels, was noted(Figure 4B) Many of the vessels were congested witherythrocytes. The individual tumor cells had abundant clearcytoplasm, with round, uniform basophilic nuclei.

On the basis of the classic features identified, a small panel ofimmunohistochemical markers, including the renal cell carcinoma(RCC) marker and CD10, also called common acute lympho-blastic leukemia antigen, was selected. Each of these markers issensitive for neoplasms derived from renal proximal tubules,including clear cell and papillary RCCs.1 Both markers werepositive within the tumor cells. RCC is a 200-kD glycoprotein

found in normal kidney along the brush border of the parsconvoluta and pars recta segments of the proximal tubules.According to Ozcan et al. RCC marker is expressed in 72% to85% of primary clear cell RCCs and 35% to 46% of metastaticclear cell RCCs.2 The current tumor exhibited positiveexpression of RCC along the luminal surfaces of the ductlikestructures and also extended along some cytoplasmicmembranes (Figure 5A). Expression of CD10 was moreprofoundly positive within the same locations (Figure 5B).CD10has been shown to be strongly expressed by normalproximal tubular cells.1,3 CD10 has been found to be expressedin approximately 93% of primary clear cell RCCs and 100% ofmetastatic tumors, although these figures are based on a smallsample size.1,2

A diagnosis of clear cell carcinoma was rendered, with anextended comment that further systemic workup was recom-mended, as the features were consistent with metastatic RCC.The patient was subsequently referred to an oncologist andwas diagnosed with stage IV RCC. Abdominal CT revealedtwo hyperdense lesions within the lower pole of the left kid-ney, one measuring 4.8 cm in diameter and the othermeasuring 1.8 � 1.0 cm. An additional 1.2 � 1.4 cm hyper-dense lesion was identified within the right kidney. No biopsyof the lesions was performed; however, the interpretation of

Fig. 5. A, Medium power (�20) photomicrograph of immu-nohistochemical marker renal cell carcinoma revealing posi-tive expression along the luminal surfaces of the duct-likestructures, as well as extending along some cytoplasmicmembranes. B, Medium power (�20) photomicrographrevealing expression of CD10 within the same locationsdescribed in (A).

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the radiologist was that the lesions in the left kidney werehighly suspicious for malignancy. The patient received 10sessions of radiation for the maxillary tumor and was placedon oral sunitinib, 37.5 mg daily for 4 weeks on and 2 weeksoff, for approximately 9 months. At 7 months after diagnosis,the oncologist noted that the left maxillary facial swelling andgingival lesion showed significant resolution. No oral lesionwas detectable 1 year and 7 months after initiation of treat-ment, and follow-up abdominal CT examination revealed adecrease in the size of all three renal lesions.

Discussion: The lesion in the current case is believed tohave metastasized from the kidney to the bones of the left maxillaand eroded into the oral cavity, and filling the maxillary sinus anderoding the floor of the orbit. This was the initial presentation ofan occult primary tumor, as has been reported to be the case in23% to 25% of previously reported oral metastases.4,5 In men, the

most common malignancies that metastasize to the oral cavity arelung, kidney, liver, and prostate cancers, whereas in women, themost common primary sites are the breast, female genital organs,kidney, and colon or rectum.4 When presenting as intrabonyinvolvement, regardless of the type of primary tumor, the mostcommon clinical findings are swelling and pain, paresthesia, orboth. If metastasis to oral soft tissues occurs, findings typicallyconsist of a fast-growing, hemorrhagic lesion with an ulceratedappearance resembling a pyogenic granuloma.4,5 In a relativelysmall study cohort, Murillo et al. found that 50% of their patients(8 of 16) presented with both soft tissue and bone involvement.5

Although the histopathologic features in this case werestrongly suggestive of metastatic clear cell RCC, not every case isas straightforward and can represent a diagnostic challenge. Inthese cases, immunohistochemical markers are of utmost impor-tance in establishing the diagnosis. In addition to the alreadydescribed markers, RCC and CD10, PAX-2 has been reported tobe a useful marker in metastatic RCCs. A member of the pairedbox gene family, it is involved in development of the kidney.RCC tumor cells exhibit nuclear staining with PAX-2. Ozcan etal. reported that 74% of all metastatic RCCs exhibited positivitywith PAX-2, which is significantly higher than the 35% to 46% ofmetastatic RCCs positive with RCC marker.2

The prognosis of patients with metastatic RCC is poor, withthe 5-year survival rate reported to be less than 10%.6 Hirschberget al. reported in their review of metastases to the oral cavity thatthe average survival time was 7 months from diagnosis, whereasCohen reported that the median survival for metastatic RCC is 13months.7 This case highlights the possibility of an occult primarytumor, although rare in the oral cavity, initially presenting as ametastatic lesion in the oral cavity.

References1. Truong LD, Shen SS. Immunohistochemical diagnosis of renal

neoplasms. Arch Pathol Lab Med. 2011;135:92-109.2. Ozcan A, Zhai Q, Javed R, et al. PAX-2 is a helpful marker

for diagnosing metastatic renal cell carcinoma: comparisonwith the renal cell carcinoma marker antigen and kidney-specific cadherin. Arch Pathol Lab Med. 2010;134:1121-1129.

3. Chu P, Arber DA. Paraffin-section detection of CD10 in 505nonhematopoietic neoplasms frequent expression in renal cellcarcinoma and endometrial stromal sarcoma. Am J ClinPathol. 2000;113:374-382.

4. Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R.Metastatic tumors to the oral cavity-pathogenesis and analysisof 673 cases. Oral Oncol. 2008;44:743-752.

5. Murillo J, Bagan JV, Hens E, Diaz JM, Leopoldo M. Tumorsmetastasizing to the oral cavity: a study of 16 cases. J OralMaxillofac Surg. 2013;71:1545-1551.

6. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A,Ferrara J. Survival and prognostic stratification of 670 patientswith advanced renal cell carcinoma. J Clin Oncol. 1999;17:2530-4250.

7. Cohen H, McGovern F. Renal cell carcinoma. N Engl J Med.2005;353:2477-2488.
























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