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A chronic nonhealing gingival mass
CLINICAL
PRACTICE
DIAGNOSTIC
CHALLENGE
A chronic nonhealing gingival mass Steven Barket, DMD; Bobby Collins, DDS, MS; Edward Halusic, DMD; Elizabeth Bilodeau, DMD, MD, MSEd THE CHALLENGE
A 47-year-old woman visited an oral and maxillofacial surgeon (E.H.) because of ulcerated, erythematous tissue of nine months’ duration on the right mandibular facial gingiva. The patient had no significant medical history. On oral examination, the clinician observed an isolated shallow ulceration of the gingival tissue in the area of teeth nos. 25 through 28; the ulceration measured approximately 1.5 centimeters in height. The tissue was friable and painful, bled on manipulation and was markedly erythematous (Figure 1). The lingual gingiva in the area was minimally involved, appearing only slightly inflamed. The patient had received implants in the area approximately 10 years previously; they were stable and nonmo-
Figure 1. An erythematous, ulcerated lesion with focal areas of necrosis is evident in the right mandibular gingiva. The ulcer bled and caused pain during eating and on clinical manipulation. It affected the attached and unattached gingiva. The appearance and long-term history made biopsy mandatory.
bile. The remaining teeth in the area had been treated endodontically. Overall, the patient’s oral hygiene was good. No significant periodontal pocketing was clinically evident, and the clinician observed no bony involvement on radiographs. The cortical plate also was intact, with no fenestrations. The oral and maxillofacial surgeon performed an incisional biopsy of the facial gingiva. Histologic examination of the biopsy specimen revealed connective tissue infiltrated with numerous chronic inflammatory cells (lymphocytes and histiocytes) (Figure 2). Also interspersed within the tissue were 2- to 4micrometer round, basophilic organisms with clear capsules highlighted by a fungal stain (Figure 3).
Figure 2. Numerous round basophilic organisms are seen in a lymphohistiocytic background. Epithelioid macrophages with vesicular nuclei and prominent nucleoli have engulfed clusters of basophilic fungal organisms. The macrophages are interspersed among lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×400).
Figure 3. Photomicrograph of the biopsy specimen with a Grocott-Gomori methenamine–silver nitrate stain highlights the round, yeast forms of Histoplasma capsulatum (original magnification ×400).
Can you make the diagnosis? A. squamous cell carcinoma B. peri-implantitis C. histoplasmosis
D. Wegener granulomatosis E. lymphoma JADA 144(5) http://jada.ada.org May 2013 491
Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
PRACTICE
DIAGNOSTIC
CHALLENGE
THE DIAGNOSIS
C. histoplasmosis Fungal infections such as candidiasis are considered superficial and usually can be treated with topical antifungal therapy. Deep fungal infections are more invasive and often require systemic therapy. The deep fungal infections include histoplasmosis, blastomycosis, mucormycosis, aspergillosis, cryptococcosis and coccidioidomycosis.1 The causative agent of histoplasmosis is Histoplasma capsulatum, and it is the most prevalent deep fungal mycosis in North America.2,3 H. capsulatum is a dimorphic fungus acquired through the inhalation of spores found in the soil or in bird and bat feces. Primary H. capsulatum infection is pulmonary, but disseminated infection can be seen in any organ system.4 In the United States, H. capsulatum infection is common to the Mississippi and Ohio river valley regions.5 Most infections result from inhalation and are self-limited, but the organism has the ability to cause acute and chronic pulmonary infections, which can disseminate in immunocompromised patients.4 Clinical manifestations can vary, depending on the immune status of the host. Clinically, practitioners should consider the diagnosis in patients who have a recent history of residence or travel in an area in which H. capsulatum infection is endemic, especially if engaged in occupations such as outdoor construction or street cleaning or in hobbies (for example, spelunking) that increase the likelihood of being exposed to fungal spores.6 Our patient lived in the Ohio River Valley. Patients with histoplasmosis appear chronically ill and can have diffuse mucocutaneous ulcerations, with isolated oral ulcers in the disseminated form of the disease.7 With disseminated infection, involvement of almost every organ system has been reported.4 Treatment for disseminated histoplasmosis consists of antifungal therapy—itraconazole or amphotericin B—which can range in duration from a few weeks to one year. Clinicians also can consider antifungal therapy for patients who are immunosuppressed with limited infection.8 Patients with disseminated histoplasmosis, including those with advanced AIDS, usually respond promptly to antifungal therapy; most deaths in immunosuppressed patients occur when the diagnosis is delayed. Patients in the fourth to sixth decades of life who have chronic, progressive disseminated histoplasmosis experience a slower, but usually favorable, response to therapy.4 Typical histopathological findings
in patients with disseminated histoplasmosis include macrophages in the submucosa, which are filled with many H. capsulatum yeast forms, each with a clear halo.9 In this case, the oral and maxillofacial surgeon (E.H.) who performed the biopsy was notified of the histological findings, which were consistent with histoplasmosis. The pathologists (S.B., B.C., E.B.) then ordered periodic acid– Schiff and Grocott-Gomori methenamine– silver nitrate staining on the biopsy specimen to confirm this finding. The oral and maxillofacial surgeon then referred our patient to her primary care physician—who consulted with an infectious disease specialist—for a complete workup to rule out any immunocompromised states. This workup included testing for endocrine disorders such as diabetes and infections such as human immunodeficiency virus (HIV). Testing to diagnose histoplasmosis depends on the suspected location of the infection.10 Culture of H. capsulatum is not feasible for dentists practicing outside the hospital setting and should be performed by medical care providers trained in the use of specialized procedures and culture media. The results of our patient’s urine H. capsulatum antigen test were negative, but a sputum culture revealed H. capsulatum, which was confirmed with a DNA probe. The patient complied with a medication regimen of 200 milligrams/milliliter (or 1 teaspoon of 10 mg/mL) of oral itraconazole four times a day prescribed by her primary care physician in consultation with an infectious disease specialist. During this time, she visited her dentist and primary care physician for routine care. At 10 months’ follow-up, the patient’s gingival lesion had resolved completely. She was able to tolerate dental treatment, as well as eat comfortably without pain or bleeding. After one year of itraconazole therapy, and a lack of systemic symptoms in a patient with a normal immune system, recurrent disease would not be expected. Differential Diagnosis
Squamous cell carcinoma. The clinical differential diagnosis for a nonhealing ulcerative lesion in this area should include squamous cell carcinoma (SCC). It is the most common malignancy of the oral cavity, and up to 12 percent of lesions manifest on the mandibular gingiva.11,12 SCC, however, is found primarily in men in the sixth to eighth decades of life and in patients
492 JADA 144(5) http://jada.ada.org May 2013 Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
with a history of tobacco use.13 Furthermore, our patient did not report using tobacco, and smoking is strongly associated with the development of oral cancer in older patients.14 Gingival SCC has a low association with tobacco use, and it occurs most often in women, making it an important consideration in the differential diagnosis.9 Clinicians should view any nonhealing ulceration of the oral cavity as suspicious for malignancy. We considered malignancy a possibility in our patient but ruled it out on biopsy findings. Peri-implantitis. Our patient received implants in the area of teeth nos. 25 through 28 approximately 10 years previously, and since then she has been receiving antibiotic treatment routinely. Although the incidence and assessment of peri-implant disease are difficult to determine because of nonstandardized definitions,15 it is characterized by bleeding on probing, changes in the crestal bone, deepening periodontal pockets around the implant and suppuration.16 Heitz-Mayfield and Lang17 and Roos-Jansåker and colleagues18 reported that peri-implantitis resolves after removal of local factors, such as plaque and calculus, in addition to antibiotic therapy. Our patient had good oral hygiene, was not a smoker and had minimal bone loss surrounding the implants. The absence of the above risk factors combined with the clinical and radiographic findings ruled out peri-implantitis. Wegener granulomatosis. Wegener granulomatosis is a systemic disease of unknown origin, characterized by small- and medium-sized vessel vasculitis and necrotizing granulomas.19 The disease classically involves the upper airways, lungs and kidneys, and most patients, if untreated, die within the first year after onset.20 The initial presentation often consists of respiratory symptoms,20 and while the disease is active, most patients exhibit nonspecific signs and symptoms such as malaise, weakness, arthralgia, anorexia and weight loss.21 Oral manifestations, such as gingival involvement, can be seen in 6 to 13 percent of patients, and the earliest manifestation may be in the form of nonspecific oral ulcerations.22 Gingival tissue can appear denuded and erythematous, and it can exhibit numerous short bulbous projections simulating an overripe strawberry. This is referred to as “strawberry gingivitis” and can be the hallmark presentation. However, it would be unusual for the process to be localized to one area.23 Because of the lack of clinical systemic manifestations, as well as the absence of vasculitis or granulomas on biopsy, three of us (S.B., B.C., E.B.) ex-
PRACTICE
DIAGNOSTIC
CHALLENGE
cluded this diagnosis. Lymphoma. When considering differential diagnoses of a nonhealing oral ulceration, clinicians must include a hematologic malignancy. Lymphomas have many different forms and presentations, including oral mucosal involvement and ulceration.24 Factors influencing this diagnosis include previous radiation therapy, an autoimmune disease such as Sjögren syndrome or immunosuppressive therapy.25 Malignant lymphomas often are found in the maxillofacial area; however, primary gingival involvement is uncommon.24 The majority of head and neck lymphomas arise in lymphoid tissue, especially in the cervical group of lymph nodes and in the Waldeyer ring.26 Radiographic, hematologic and histopathological evaluations are required to establish this diagnosis. The histopathological findings in the biopsy specimen in our case ruled out lymphoma. Conclusion
We have reported a case of histoplasmosis that manifested initially as an isolated ulcerated lesion. Clinicians should include deep fungal infections in the differential diagnosis for patients who have risk factors for exposure or who are immunocompromised.10 These can include patients who engage in activities that expose them to deep fungal spores, live in areas to which mycoses are endemic or are immunosuppressed, such as patients with uncontrolled diabetes or HIV infection or those receiving systemic steroid treatment. An incisional biopsy and appropriate histologic staining can be performed to confirm the diagnosis. n Dr. Barket is a resident, Oral and Maxillofacial Pathology, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, 3501 Terrace St., Room G-132, Pittsburgh, Pa. 15261, e-mail [email protected]. Address reprint requests to Dr. Barket. Dr. Collins is an associate professor and section chief, Oral and Maxillofacial Pathology, School of Dental Medicine, East Carolina University, Greenville, N.C. Dr. Halusic is in private practice, Oral and Maxillofacial Surgery, Mount Pleasant, Pa. Dr. Bilodeau is an assistant professor, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh. Disclosure. None of the authors reported any disclosures. Diagnostic Challenge is published in collaboration with the American Academy of Oral and Maxillofacial Pathology and the American Academy of Oral Medicine. 1. Glick M, Greenberg MS, Ship JA. Burket’s Oral Medicine. 11th ed. Hamilton, Ontario, Canada: BC Decker; 2008:70-72. 2. Akin L, Herford AS, Cicciù M. Oral presentation of disseminated histoplasmosis: a case report and literature review (published online ahead of print Dec. 9, 2010). J Oral Maxillofac Surg 2011;69(2):535541. doi:10.1016/j.joms.2010.05.053. 3. Cano MV, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect 2001;16(2):109-118.
JADA 144(5) http://jada.ada.org May 2013 493 Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
PRACTICE
DIAGNOSTIC
4. Goldman L, Schafer AI. Goldman’s Cecil Medicine. 24th ed. Philadelphia: Saunders; 2012:1977-1979. 5. Kauffman CA. Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis. Infect Dis Clin North Am 2006;20(3):645-662, vii. 6. Huhn GD, Austin C, Carr M, et al. Two outbreaks of occupationally acquired histoplasmosis: more than workers at risk. Environ Health Perspect 2005;113(5):585-589. 7. Flint PW, Haughey BH, Lund VJ, et al. Cummings Otolaryngology: Head and Neck Surgery. 5th ed. Philadelphia: Mosby; 2010: 226-227. 8. Knox KS, Hage CA. Histoplasmosis. Proc Am Thorac Soc 2010; 7(3):169-172. 9. Neville BW, Damm DD, Allen CM, Bouquot J. Oral and Maxillofacial Pathology. 3rd ed. St. Louis: Elsevier; 2009:224-226, 409-423. 10. DeRossi SS, Ciarrocca KN, Alawi F. Oral ulcerations in a patient with severe asthma. JADA 2010;141(1):47-51. 11. Bhaskar SN. Synopsis of Oral Pathology. 7th ed. St. Louis: Mosby; 1986:593-599. 12. Al-Rawi NH, Talabani NG. Squamous cell carcinoma of the oral cavity: a case series analysis of clinical presentation and histological grading of 1,425 cases from Iraq (published online ahead of print Aug. 16, 2007). Clin Oral Investig 2008;12(1):15-18. doi:10.1007/ s00784-007-0141-0. 13. Sasaki T, Moles DR, Imai Y, Speight PM. Clinico-pathological features of squamous cell carcinoma of the oral cavity in patients < 40 years of age. J Oral Pathol Med 2005;34(3):129-133. 14. Franceschi S, Barra S, La Vecchia C, Bidoli E, Negri E, Talamini R. Risk factors for cancer of the tongue and the mouth; a casecontrol study from northern Italy. Cancer 1992;70(9):2227-2233. 15. Heitz-Mayfield LJ. Diagnosis and management of peri-implant diseases (published online ahead of print May 22, 2008). Aust Dent J 2008;53(suppl 1):S43-S48. doi:10.1111/j.1834-7819.2008.00041.x. 16. Lang NP, Berglundh T; Working Group 4 of Seventh European Workshop on Periodontology. Periimplant diseases: where are we now?—Consensus of the Seventh European Workshop on Periodontology (published online ahead of print Feb. 16, 2011).
CHALLENGE J Clin Periodontol 2011;38(suppl 11):178-181. doi:10.1111/j.1600051X.2010.01674.x. 17. Heitz-Mayfield LJ, Lang NP. Antimicrobial treatment of peri-implant diseases. Int J Oral Maxillofac Implants 2004; 19(suppl):128-139. 18. Roos-Jansåker AM, Renvert H, Lindahl C, Renvert S. Nine- to fourteen-year follow-up of implant treatment, part III: factors associated with peri-implant lesions. J Clin Periodontol 2006;33(4): 296-301. 19. Napier SS, Allen JA, Irwin CR, McCluskey DR. Strawberry gums: a clinicopathological manifestation diagnostic of Wegener’s granulomatosis? J Clin Pathol 1993;46(8):709-712. 20. Knight JM, Hayduk MJ, Summerlin DJ, Mirowski GW. “Strawberry” gingival hyperplasia: a pathognomonic mucocutaneous finding in Wegener granulomatosis. Arch Dermatol 2000;136(2):171-173. 21. Doughan A. Disseminated histoplasmosis: case report and brief review (published online ahead of print April 19, 2006). Travel Med Infect Dis 2006;4(6):332-335. doi:10.1016/j.tmaid.2006.01.013. 22. Ponniah I, Shaheen A, Shankar KA, Kumaran MG. Wegener’s granulomatosis: the current understanding. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100(3):265-270. 23. Stewart C, Cohen D, Bhattacharyya I, et al. Oral manifestations of Wegener’s granulomatosis: a report of three cases and a literature review. JADA 2007;138(3):338-348. 24. Matsumoto N, Ohki H, Mukae S, et al. Anaplastic large cell lymphoma in gingiva: case report and literature review (published online ahead of print July 25, 2008). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106(4):e29-e34. doi:10.1016/j. tripleo.2008.05.037. 25. Hansen A, Daridon C, Dörner T. What do we know about memory B cells in primary Sjögren’s syndrome (published online ahead of print May 7, 2010)? Autoimmun Rev 2010;9(9):600-603. 26. Takahashi H, Fujita S, Okabe H, Tsuda N, Tezuka F. Immunophenotypic analysis of extranodal non-Hodgkin’s lymphomas in the oral cavity. Pathol Res Pract 1993;189(3):300-311.
494 JADA 144(5) http://jada.ada.org May 2013 Copyright © 2013 American Dental Association. All Rights Reserved.
PRACTICE
DIAGNOSTIC
CHALLENGE
A chronic nonhealing gingival mass Steven Barket, DMD; Bobby Collins, DDS, MS; Edward Halusic, DMD; Elizabeth Bilodeau, DMD, MD, MSEd THE CHALLENGE
A 47-year-old woman visited an oral and maxillofacial surgeon (E.H.) because of ulcerated, erythematous tissue of nine months’ duration on the right mandibular facial gingiva. The patient had no significant medical history. On oral examination, the clinician observed an isolated shallow ulceration of the gingival tissue in the area of teeth nos. 25 through 28; the ulceration measured approximately 1.5 centimeters in height. The tissue was friable and painful, bled on manipulation and was markedly erythematous (Figure 1). The lingual gingiva in the area was minimally involved, appearing only slightly inflamed. The patient had received implants in the area approximately 10 years previously; they were stable and nonmo-
Figure 1. An erythematous, ulcerated lesion with focal areas of necrosis is evident in the right mandibular gingiva. The ulcer bled and caused pain during eating and on clinical manipulation. It affected the attached and unattached gingiva. The appearance and long-term history made biopsy mandatory.
bile. The remaining teeth in the area had been treated endodontically. Overall, the patient’s oral hygiene was good. No significant periodontal pocketing was clinically evident, and the clinician observed no bony involvement on radiographs. The cortical plate also was intact, with no fenestrations. The oral and maxillofacial surgeon performed an incisional biopsy of the facial gingiva. Histologic examination of the biopsy specimen revealed connective tissue infiltrated with numerous chronic inflammatory cells (lymphocytes and histiocytes) (Figure 2). Also interspersed within the tissue were 2- to 4micrometer round, basophilic organisms with clear capsules highlighted by a fungal stain (Figure 3).
Figure 2. Numerous round basophilic organisms are seen in a lymphohistiocytic background. Epithelioid macrophages with vesicular nuclei and prominent nucleoli have engulfed clusters of basophilic fungal organisms. The macrophages are interspersed among lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×400).
Figure 3. Photomicrograph of the biopsy specimen with a Grocott-Gomori methenamine–silver nitrate stain highlights the round, yeast forms of Histoplasma capsulatum (original magnification ×400).
Can you make the diagnosis? A. squamous cell carcinoma B. peri-implantitis C. histoplasmosis
D. Wegener granulomatosis E. lymphoma JADA 144(5) http://jada.ada.org May 2013 491
Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
PRACTICE
DIAGNOSTIC
CHALLENGE
THE DIAGNOSIS
C. histoplasmosis Fungal infections such as candidiasis are considered superficial and usually can be treated with topical antifungal therapy. Deep fungal infections are more invasive and often require systemic therapy. The deep fungal infections include histoplasmosis, blastomycosis, mucormycosis, aspergillosis, cryptococcosis and coccidioidomycosis.1 The causative agent of histoplasmosis is Histoplasma capsulatum, and it is the most prevalent deep fungal mycosis in North America.2,3 H. capsulatum is a dimorphic fungus acquired through the inhalation of spores found in the soil or in bird and bat feces. Primary H. capsulatum infection is pulmonary, but disseminated infection can be seen in any organ system.4 In the United States, H. capsulatum infection is common to the Mississippi and Ohio river valley regions.5 Most infections result from inhalation and are self-limited, but the organism has the ability to cause acute and chronic pulmonary infections, which can disseminate in immunocompromised patients.4 Clinical manifestations can vary, depending on the immune status of the host. Clinically, practitioners should consider the diagnosis in patients who have a recent history of residence or travel in an area in which H. capsulatum infection is endemic, especially if engaged in occupations such as outdoor construction or street cleaning or in hobbies (for example, spelunking) that increase the likelihood of being exposed to fungal spores.6 Our patient lived in the Ohio River Valley. Patients with histoplasmosis appear chronically ill and can have diffuse mucocutaneous ulcerations, with isolated oral ulcers in the disseminated form of the disease.7 With disseminated infection, involvement of almost every organ system has been reported.4 Treatment for disseminated histoplasmosis consists of antifungal therapy—itraconazole or amphotericin B—which can range in duration from a few weeks to one year. Clinicians also can consider antifungal therapy for patients who are immunosuppressed with limited infection.8 Patients with disseminated histoplasmosis, including those with advanced AIDS, usually respond promptly to antifungal therapy; most deaths in immunosuppressed patients occur when the diagnosis is delayed. Patients in the fourth to sixth decades of life who have chronic, progressive disseminated histoplasmosis experience a slower, but usually favorable, response to therapy.4 Typical histopathological findings
in patients with disseminated histoplasmosis include macrophages in the submucosa, which are filled with many H. capsulatum yeast forms, each with a clear halo.9 In this case, the oral and maxillofacial surgeon (E.H.) who performed the biopsy was notified of the histological findings, which were consistent with histoplasmosis. The pathologists (S.B., B.C., E.B.) then ordered periodic acid– Schiff and Grocott-Gomori methenamine– silver nitrate staining on the biopsy specimen to confirm this finding. The oral and maxillofacial surgeon then referred our patient to her primary care physician—who consulted with an infectious disease specialist—for a complete workup to rule out any immunocompromised states. This workup included testing for endocrine disorders such as diabetes and infections such as human immunodeficiency virus (HIV). Testing to diagnose histoplasmosis depends on the suspected location of the infection.10 Culture of H. capsulatum is not feasible for dentists practicing outside the hospital setting and should be performed by medical care providers trained in the use of specialized procedures and culture media. The results of our patient’s urine H. capsulatum antigen test were negative, but a sputum culture revealed H. capsulatum, which was confirmed with a DNA probe. The patient complied with a medication regimen of 200 milligrams/milliliter (or 1 teaspoon of 10 mg/mL) of oral itraconazole four times a day prescribed by her primary care physician in consultation with an infectious disease specialist. During this time, she visited her dentist and primary care physician for routine care. At 10 months’ follow-up, the patient’s gingival lesion had resolved completely. She was able to tolerate dental treatment, as well as eat comfortably without pain or bleeding. After one year of itraconazole therapy, and a lack of systemic symptoms in a patient with a normal immune system, recurrent disease would not be expected. Differential Diagnosis
Squamous cell carcinoma. The clinical differential diagnosis for a nonhealing ulcerative lesion in this area should include squamous cell carcinoma (SCC). It is the most common malignancy of the oral cavity, and up to 12 percent of lesions manifest on the mandibular gingiva.11,12 SCC, however, is found primarily in men in the sixth to eighth decades of life and in patients
492 JADA 144(5) http://jada.ada.org May 2013 Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
with a history of tobacco use.13 Furthermore, our patient did not report using tobacco, and smoking is strongly associated with the development of oral cancer in older patients.14 Gingival SCC has a low association with tobacco use, and it occurs most often in women, making it an important consideration in the differential diagnosis.9 Clinicians should view any nonhealing ulceration of the oral cavity as suspicious for malignancy. We considered malignancy a possibility in our patient but ruled it out on biopsy findings. Peri-implantitis. Our patient received implants in the area of teeth nos. 25 through 28 approximately 10 years previously, and since then she has been receiving antibiotic treatment routinely. Although the incidence and assessment of peri-implant disease are difficult to determine because of nonstandardized definitions,15 it is characterized by bleeding on probing, changes in the crestal bone, deepening periodontal pockets around the implant and suppuration.16 Heitz-Mayfield and Lang17 and Roos-Jansåker and colleagues18 reported that peri-implantitis resolves after removal of local factors, such as plaque and calculus, in addition to antibiotic therapy. Our patient had good oral hygiene, was not a smoker and had minimal bone loss surrounding the implants. The absence of the above risk factors combined with the clinical and radiographic findings ruled out peri-implantitis. Wegener granulomatosis. Wegener granulomatosis is a systemic disease of unknown origin, characterized by small- and medium-sized vessel vasculitis and necrotizing granulomas.19 The disease classically involves the upper airways, lungs and kidneys, and most patients, if untreated, die within the first year after onset.20 The initial presentation often consists of respiratory symptoms,20 and while the disease is active, most patients exhibit nonspecific signs and symptoms such as malaise, weakness, arthralgia, anorexia and weight loss.21 Oral manifestations, such as gingival involvement, can be seen in 6 to 13 percent of patients, and the earliest manifestation may be in the form of nonspecific oral ulcerations.22 Gingival tissue can appear denuded and erythematous, and it can exhibit numerous short bulbous projections simulating an overripe strawberry. This is referred to as “strawberry gingivitis” and can be the hallmark presentation. However, it would be unusual for the process to be localized to one area.23 Because of the lack of clinical systemic manifestations, as well as the absence of vasculitis or granulomas on biopsy, three of us (S.B., B.C., E.B.) ex-
PRACTICE
DIAGNOSTIC
CHALLENGE
cluded this diagnosis. Lymphoma. When considering differential diagnoses of a nonhealing oral ulceration, clinicians must include a hematologic malignancy. Lymphomas have many different forms and presentations, including oral mucosal involvement and ulceration.24 Factors influencing this diagnosis include previous radiation therapy, an autoimmune disease such as Sjögren syndrome or immunosuppressive therapy.25 Malignant lymphomas often are found in the maxillofacial area; however, primary gingival involvement is uncommon.24 The majority of head and neck lymphomas arise in lymphoid tissue, especially in the cervical group of lymph nodes and in the Waldeyer ring.26 Radiographic, hematologic and histopathological evaluations are required to establish this diagnosis. The histopathological findings in the biopsy specimen in our case ruled out lymphoma. Conclusion
We have reported a case of histoplasmosis that manifested initially as an isolated ulcerated lesion. Clinicians should include deep fungal infections in the differential diagnosis for patients who have risk factors for exposure or who are immunocompromised.10 These can include patients who engage in activities that expose them to deep fungal spores, live in areas to which mycoses are endemic or are immunosuppressed, such as patients with uncontrolled diabetes or HIV infection or those receiving systemic steroid treatment. An incisional biopsy and appropriate histologic staining can be performed to confirm the diagnosis. n Dr. Barket is a resident, Oral and Maxillofacial Pathology, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, 3501 Terrace St., Room G-132, Pittsburgh, Pa. 15261, e-mail [email protected]. Address reprint requests to Dr. Barket. Dr. Collins is an associate professor and section chief, Oral and Maxillofacial Pathology, School of Dental Medicine, East Carolina University, Greenville, N.C. Dr. Halusic is in private practice, Oral and Maxillofacial Surgery, Mount Pleasant, Pa. Dr. Bilodeau is an assistant professor, Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh. Disclosure. None of the authors reported any disclosures. Diagnostic Challenge is published in collaboration with the American Academy of Oral and Maxillofacial Pathology and the American Academy of Oral Medicine. 1. Glick M, Greenberg MS, Ship JA. Burket’s Oral Medicine. 11th ed. Hamilton, Ontario, Canada: BC Decker; 2008:70-72. 2. Akin L, Herford AS, Cicciù M. Oral presentation of disseminated histoplasmosis: a case report and literature review (published online ahead of print Dec. 9, 2010). J Oral Maxillofac Surg 2011;69(2):535541. doi:10.1016/j.joms.2010.05.053. 3. Cano MV, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect 2001;16(2):109-118.
JADA 144(5) http://jada.ada.org May 2013 493 Copyright © 2013 American Dental Association. All Rights Reserved.
CLINICAL
PRACTICE
DIAGNOSTIC
4. Goldman L, Schafer AI. Goldman’s Cecil Medicine. 24th ed. Philadelphia: Saunders; 2012:1977-1979. 5. Kauffman CA. Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis. Infect Dis Clin North Am 2006;20(3):645-662, vii. 6. Huhn GD, Austin C, Carr M, et al. Two outbreaks of occupationally acquired histoplasmosis: more than workers at risk. Environ Health Perspect 2005;113(5):585-589. 7. Flint PW, Haughey BH, Lund VJ, et al. Cummings Otolaryngology: Head and Neck Surgery. 5th ed. Philadelphia: Mosby; 2010: 226-227. 8. Knox KS, Hage CA. Histoplasmosis. Proc Am Thorac Soc 2010; 7(3):169-172. 9. Neville BW, Damm DD, Allen CM, Bouquot J. Oral and Maxillofacial Pathology. 3rd ed. St. Louis: Elsevier; 2009:224-226, 409-423. 10. DeRossi SS, Ciarrocca KN, Alawi F. Oral ulcerations in a patient with severe asthma. JADA 2010;141(1):47-51. 11. Bhaskar SN. Synopsis of Oral Pathology. 7th ed. St. Louis: Mosby; 1986:593-599. 12. Al-Rawi NH, Talabani NG. Squamous cell carcinoma of the oral cavity: a case series analysis of clinical presentation and histological grading of 1,425 cases from Iraq (published online ahead of print Aug. 16, 2007). Clin Oral Investig 2008;12(1):15-18. doi:10.1007/ s00784-007-0141-0. 13. Sasaki T, Moles DR, Imai Y, Speight PM. Clinico-pathological features of squamous cell carcinoma of the oral cavity in patients < 40 years of age. J Oral Pathol Med 2005;34(3):129-133. 14. Franceschi S, Barra S, La Vecchia C, Bidoli E, Negri E, Talamini R. Risk factors for cancer of the tongue and the mouth; a casecontrol study from northern Italy. Cancer 1992;70(9):2227-2233. 15. Heitz-Mayfield LJ. Diagnosis and management of peri-implant diseases (published online ahead of print May 22, 2008). Aust Dent J 2008;53(suppl 1):S43-S48. doi:10.1111/j.1834-7819.2008.00041.x. 16. Lang NP, Berglundh T; Working Group 4 of Seventh European Workshop on Periodontology. Periimplant diseases: where are we now?—Consensus of the Seventh European Workshop on Periodontology (published online ahead of print Feb. 16, 2011).
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