J Oral Maxillofac 49294~298.
Surg
1991
Wegener’s Granuloma tosis: Report of Three Cases With Oral Lesions CARL M. ALLEN, DDS, MSD,* CHARLES CAMISA, MD,* CAROL SALEWSKI, MD,+ AND JEFFREY E. WEILAND, MD3
Report of Cases
In 1936 and 1939, Friederich Wegener published descriptions of the clinical and autopsy findings of several patients who exhibited necrotizing granulomatous inflammation of small- to medium-sized blood vessels, with similar destructive infiltrates in the respiratory tract and kidneys.‘,’ Wegener’s granulomatosis (WG) has since become a wellrecognized disease the etiology of which remains obscure; many investigators believe that an immunologic pathogenesis is likely.3 The prognosis for untreated WG is poor, with most deaths resulting from renal failure secondary to glomerulonephritis.4 A much better prognosis is associated with the limited form of WG, which has respiratory, but not renal, involvement.’ In addition, a superficial form of WG has been described, manifesting as lesions that are confined to cutaneous or mucosal surfaces, that has an even better prognosis.6 Each of these forms of WG may present with oral lesions as an initial manifestation of the disease’; thus, prompt recognition by the clinician may lead to an earlier diagnosis and proper management. The purpose of this article is to describe
Case 1 A 20-year-old white woman was admitted to her local hospital in January 1989 for progressive ulceration of the soft palate associated with increasing oral discomfort for 5 months. The medical history was negative for previous disease, exposure to infection, use of immunosuppressive drugs, or oral trauma. She did, however, report a history of a positive PPD test. The past surgical history was positive for rhinoplasty, nasal polypectomy, and left breast cystectomy. Physical examination showed an afebrile woman with a large proliferative ulceration involving most of the soft palate and extending to the anterior tonsillar pillars. She had bilateral cervical adenopathy, but the remainder of the examination was negative. Hematologic evaluation showed a hemoglobin content of 13 g/dL, an hematocrit of 40%, and a platelet count of 262,000/mm3. The white blood cell count was 5,400/mm3, with a differential count of neutrophils 46%, lymphocytes 46%, and monocytes 8%. The erythrocyte sedimentation rate was 15 mm/h. A chemistry profile was normal. Results of the latex fixation test, and throat and soft palate cultures for P-hemolytic streptococci, viruses, acid-fast bacilli, and fungi were negative. Results of serum protein electrophoresis were normal, and results of a VDRL test were negative. Urinalysis results and chest radiograph were within normal limits. Bronchoscopy, esophagoscopy, direct laryngoscopy, nasopharyngoscopy, and examination of the oral cavity and pharynx were performed under general anesthesia. The nasopharyngeal surface of the soft palate was normal. The oral surface of the soft palate showed a large, ulcerative, indurated, irregular, fungating lesion. The base of the tongue and the hard palate were normal in appearance. Microscopic examination of a biopsy of the soft palate showed severe, chronic, inflammatory changes, with ulceration and pseudoepitheliomatous hyperplasia. No atypia or granulomas were detected. The patient was discharged with some improvement of pain, but over the next 6 weeks her condition gradually worsened to the point where she could barely eat or drink. In March 1989, she was referred to the Departments of Otolaryngology and Dermatology at the Cleveland Clinic Foundation. The proliferative, friable, ulcerated lesion now involved the posterior hard palate and
the clinical and microscopic findings of the oral lesions of WG in three patients who each presented with a different form of the condition.
* Associate Professor, Section of Diagnostic Services. College of Dentistry, The Ohio State University, Columbus. t Head, Section of Clinical Dermatology, The Cleveland Clinic Foundation, Cleveland. $ Resident Physician, Department of Medicine, The Cleveland Clinic Foundation. 8 Associate Professor, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus. Address correspondence and reprint requests to Dr Allen: Section of Diagnostic Services, College of Dentistry, The Ohio State University, Postle Hall, 305 W 12th Ave. Columbus, OH 43210-1241. 0 1991 American
Association
of Oral and Maxillofacial
Sur-
geons 0278-2391/91/4903-0014$3.00/0
294
295
ALLEN ET AL
FIGURE I. Case I, This 20-year-old woman had progressive involvement of her soft palate with this destructive lesion over a 5-month period.
FIGURE 3. Photomicrograph demonstrating a poorly defined granuloma that was also seen in the pafatal biopsy specimen of case 1 (hematoxylin-eosin, original magnification X 100).
extended onto the soft palate and uvula (Fig 1). The uvula was excised and sent for studies. Results of special stains and cultures for organisms were again negative, with the exception of a heavy growth of Candida albicans. The histologic diagnosis was reported as nonspecific chronic inflammation. Immunoglobulin and T-cell receptor gene analysis showed no gene rearrangements, compatible with a benign polyclonal lymphoid population. No additional routine laboratory abnormalities were detected. Ketoconazole. 400 mg daily, and chlorhexidine mouth rinse were prescribed. A biopsy of the left soft palate was repeated and submitted to the Department of Oral Pathology at The Ohio State University College of Dentistry. This specimen exhibited acute and chronic inflammation, vascular injury, and poorly defined granulomas suggestive of WG (Figs 2 and 3). Titer for neutrophil cytoplasmic autoantibodies was negative. Because no lung or kidney involvement was identified, a diagnosis of superficial WG was considered most appropriate. The patient was started on a combination chemotherapy regimen consisting of prednisone, 60 mg daily for 5 days each month. and cyciophosphamide, 50 mg daily. She responded very well to treatment, and within 8 weeks
the palate was completely healed (Fig 4). At one point, the patient stopped taking her medication for 2 days and claimed that six small nodules appeared on the soft palate, completely disappearing when she resumed the medication. After 8 weeks of treatment, the prednisone was discontinued, and the cyclophosphamide was prescribed for a total of 18 weeks. The patient remains free of any oral or systemic disease 5 months following cessation of all medications.
FlGURE 2. Photomicrograph demonstrating vasculitis in the palatal biopsy specimen of case 1. (hematoxylin-eosin. original magnification X 100).
FIGURE 4. Case I, Complete resolution of the palata! lesion of superficial Wegener’s granulomatosis after 8 weeks of prednisone and cyclophosphamide therapy.
Case 2 A 23-year-old black man was evaluated by a dentist for gingival hyperplasia in the left maxilla in January 1989. The clinician made a diagnosis of inflammatory hyperplasia, removed the lesion, and discarded the tissue. The condition recurred during the next month, and the patient was referred to an oral and maxillofacial surgeon. Clinical examination showed an erythematous, finely papular, enlargement of the maxillary buccal gingiva extending from the maxillary left canine posteriorly to the maxillary left second molar. Although the surface of the lesion appeared intact, at biopsy the tissue was quite friable. Microscopic examination showed severe chronic inflamma-
296
WEGENER’S GRANULOMATOSIS
FIGURE 5. Case 2, Photomicrograph demonstrating severe inwith WC (hematoxylin-
flammation with vasculitis, consistent eosin, original magnification X 100).
tion with vasculitis (Fig 5). Special stains showed no evidence of acid-fast bacilli or fungal organisms. Based on the clinical description of the oral lesions and the microscopic findings, a diagnosis of WG was suggested. Further evaluation showed normal values for complete blood count and SMA-20. A streaky right upper lobe infiltrate and a poorly defined cavitary mass were seen on the chest radiograph. No hematuria was detected, and the blood urea nitrogen and creatinine values were within normal limits. These findings were consistent with a diagnosis of limited WG. Antineutrophil cytoplasmic antibody titer was negative. Treatment was initiated with cyclophosphamide, 150 mg, and prednisone, 20 mg, four times daily. Minimal response was noted after 2 months, and the cyclophosphamide was then increased to 200 mg four times daily. A repeated chest radiograph in September 1989 showed no progression of the right upper lobe mass. At that time, the cyclophosphamide was increased to 250 mg four times daily, and by the end of October 1989, the oral lesions had resolved completely.
FIGURE 6. Case 3, This 62-year-old woman had been aware of this destructive palatal ulceration for approximately 1 month. An incisional biopsy was obtained from the periphery of this lesion. sinus, and her chest radiograph demonstrated bibasilar atelectasis. Results of routine laboratory studies, including urinalysis, were within normal limits. On the basis of the clinical and microscopic features of the oral lesions, a diagnosis of limited WG was made, and the patient was started on cyclophosphamide, 100 mg, and prednisone, 15 mg, four times daily. Minimal change in the oral lesion was seen after 1 month; however, by 2 months, marked resolution had occurred, and by 5 months, healing was complete. In September 1987, the patient was readmitted to University Hospitals in acute renal failure. Renal biopsy showed a crescentic glomerulonephritis, consistent with WG. Cyclophosphamide was continued at 100 mg four times daily; however, prednisone was increased to 60 mg four times daily. Renal function subsequently stabilized
Case 3 A 62-year-old white woman was seen by an oral and maxillofacial surgeon for evaluation and biopsy of a palatal ulceration that she had noticed for approximately 1 month. An incisional biopsy of the palatal lesion was performed and submitted with a provisional clinical diagnosis of malignancy. Microscopic examination showed poorly defined, necrotizing granuloma formation, with evidence of vasculitis. Special stains were negative for acid-fast bacilli and fungi, and it was suggested that WG be ruled out. The patient was referred to the Ohio State University Hospitals for further evaluation. Examination in January 1987 showed a 2 x 4-cm ulceration with irregular borders involving the left hard palate and gingiva (Fig 6). A granular, erythematous gingival enlargement, with associated petechial hemorrhage, was present in the mandibular right canine region (Fig 7). A computed tomography scan showed mucoperiosteal thickening of the left maxillary
FIGURE 7. Case 3, Focal involvement of the gingival tissue characterized by an erythematous enlargement, with a finely pebbled surface exhibiting petechial hemorrhage. Such lesions are virtually pathognomonic of Wegener’s granulomatosis.
297
ALLEN ET AL
during her admission,
and she was discharged on a taper-
ing schedule of prednisone. Discussion The cases presented illustrate the spectrum of disease that may manifest as WG, ranging from localized cutaneous/mucosal involvement through the classical description of pulmonary and renal lesions. The superficial form of WG, affecting only mucosal or cutaneous tissues, appears to have a much better prognosis initially in comparison to classic WG, but these patients may also progress to pulmonary and/or renal involvement.6 Similarly, the limited form of WG, which is characterized by upper and lower respiratory lesions, but not renal lesions, is not associated with the rapidly fatal kidney failure of classic WG.5 Because oral lesions may be found with any of these presentations of WG, the oral and maxillofacial surgeon should be familiar with their clinical features. The findings in our series are similar to those reported by other investigators,7-‘5 particularly with respect to oral ulceration and hyperplastic gingivitis. Our patients did not manifest clinically apparent facial swelling.” The oral ulcerations seen in WG may appear quite destructive as in cases 1 and 3, clinically mimicking a malignant process. The gingival lesions seen in cases 2 and 3 should be emphasized because they are virtually pathognomonic for WG. “*‘8 The gingival enlargement may initially be localized to a specific segment of the gingiva, beginning in the interdental region, but ultimately it can progress to involve the rest of the gingival tissues, eventually causing periodontal destruction and tooth Ioss.‘*‘~ On careful evaluation, no other condition will appear identical to the gingival lesions of WG. The surface of the gingival enlargement exhibits a finely papular, granular texture with an intact epithelial surface. Numerous petechiae are noted on the surface of the gingival enlargement. imparting a red to purple color to the lesion. If the characteristic gingival changes are present, the clinical diagnosis of WG should be relatively straightforward. In the presence of only oral ulcerations, however, an extensive differential diagnosis could be developed, and should include infectious, reactive, and neoplastic disease.” Special stains of biopsy material, cultures, and antibody titers can help rule out deep fungal infection (eg, histoplasmosis, cryptococcosis) or bacterial infection (eg, tuberculosis, tertiary syphilis). Histologic examination of lesional tissue will rule out reactive/ inflammatory lesions that could produce significant
oral ulceration (eg, necrotizing sialometaplasia, Crohn’s disease). Similarly, neoplastic disease (eg, lymphoma, polymorphic reticulosis, other malignancies) can be ruled out by means of biopsy. Thorough evaluation of the patient suspected of having WG is mandatory, particularly if the biopsy is only suggestive of the condition. Biopsies of oral lesions may show only pseudoepitheliomatous hyperplasia with relatively nonspecific acute and chronic inflammation.’ In our experience, careful examination of multiple sections may reveal the characteristic necrotizing vasculitis of WG. Radiographic examination of the chest and the sinuses should be performed to assess disease activity at those sites. Serum creatinine and urinalysis should be ordered to determine the extent of renal involvement.*’ A complete blood cell count and erythrocyte sedimentation rate are also useful baseline blood studies. Recently the assessment of neutrophil anticytoplasmic autoantibodies by means of indirect immunofluorescence*’ and/or enzymelinked immunoabsorbant assay (ELISA)*’ has proved helpful in supporting a diagnosis of WG. The presence of these autoantibodies in the patient’s serum appears to be highly specific for WG.*1,32 The sensitivity, however, seems to correlate with the severity of disease and disease activity, with 67% of patients with limited WG showing autoantibodies, in comparison with 96% of patients with generalized WG. ** The two patients described in this report who were evaluated for neutrophil anticytoplasmic autoantibodies had limited WG and negative findings, which does not rule out WG as a diagnosis.” While WG in the past was almost uniformly fatal, current management of this disease with cyclophosphamide and prednisone results in complete remission in over 90% of affected patients.4 Weekly monitoring of the white blood cell count is critical to prevent severe neutropenia induced by the cyclophosphamide. Adjustments in the dosage may be made accordingly. The oral lesions in our patients responded to this regimen gradually over periods ranging from 2 to 8 months, with all lesions healing completely. Careful follow-up of patients with WG is important, regardless of the initial stage of presentation. The superficial and limited forms of WG may eventually progress to more widespread disease, as in case 3, the patient who developed kidney involvement 9 months after the initial diagnosis was made. Fortunately, her renal disease was controlled by increasing the dosage of prednisone. Recognition of the oral manifestations of WG by the oral and maxillofacial surgeon is an essential
298
LIPOSARCOMA
initial step in diagnosing this important, enigmatic disease. A complete evaluation with biopsies, and medical management and monitoring, are necessary to minimize morbidity and prevent mortality. Acknowledgment The authors wish to thank Drs Peter Larsen and Pierre Lavertu for providing the information regarding cases 1 and 2.
1. Wegener F: Uber generalisierte, septische Gefaesserkrankungen. Verh Dtsch Ges Pathol 29:202, 1936 2. Wegener F: Uber eine eigenartige Rhinogene Granulomatose mit besondere Beteiligung des Arteriensystems und der Nieren. Beitr Path01 Anat Allg 102:36, 1939 3. Leavitt RY, Fauci AS. Pulmonary vasculitis. Am Rev Respir Dis 134:149, 1986 4. Fauci AS, Haynes BF, Katz P, Wolfe SM: Wegener’s granulomatosis: Prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76, 1983 5. Cassan SM, Coles DT, Harrison EG Jr: The concept of limited forms of Wegener’s granulomatosis. Am J Med 49:366, 1970 6. Fienberg R: The protracted superficial phenomenon in pathergic (Wegener’s) granulomatosis. Hum Pathol 12:458, 1981 7. Handlers JP, Waterman J, Abrams AM, Melrose RJ: Oral features of Wegener’s granulomatosis. Arch Otolaryngol Head Neck Surg 111:267, 1985 8. Morgan AD, O’Neil R: The oral complications of polyartertis and giant-cell granulomatosis (Wegener’s granulomatosis). Oral Surg 9:845, 1956
49:29&3oct
9. Cawson RA: Gingival changes in Wegener’s granulomatosis. Br Dent J 118:30, 1965 10. Kakehashi S, Hamner JE, Baer PN, et al: Wegener’s granulomatosis: Report of a case involving the gingiva. Oral Surg 19:120, 1965 11. Brooke RI: Wegener’s granulomatosis involving the gingiva. Br Dent J 127:34, 1969 12. Scott J, Finch LD: Wegener’s granulomatosis presenting as gingivitis. Oral Surg 34:920, 1972 13. Edwards MB, Buckerfield JP: Wegener’s granulomatosis: A case with primary mucocutaneous lesions. Oral Surg 46:53, 1978 14. Israelson H, Binnie WH, Hurt WC: The hypcrplastic
References
J Oral Maxillofac
ARISING IN THE CHEEK
15. 16.
17.
18.
19. 20. 21.
22.
gingivitis of Wegener’s granulomatosis. J Periodontol 52:81, 1981 Cohen PS, Meltzer JA: Strawberry gums: A sign of Wegener’s granulomatosis. JAMA 246~2610, 1981 Reed WB, Jensen AK, Konwaler BE, et al: The cutaneous manifestations in Wegener’s granulomatosis. Acta Derm Venereol43:250, 1963 Hansen LS, Silverman S Jr, Pons VG, et al. Limited Wegener’s granulomatosis: Report of a case with oral, renal and skin involvement. Oral Surg 60:524, 1985 Cawson RA, Eveson JW: Oral pathology and diagnosis. Color atlas with integrated text (ed 1). Philadelphia, PA, Saunders, 1987 (section 17.4) Sack KE: Wegener’s granulomatosis. West J Med 150:329, 1989 McDonald TJ, DeRemee RA: Wegener’s granulomatosis. Laryngoscope 93:220, 1983 Specks U, Wheatley CL, McDonald TJ, et al: Anticytoplasmic autoantibodies in the diagnosis and follow-up of Wegener’s granulomatosis. Mayo Clin Proc 64:28, 1989 Nell B, Specks U, Ludemann J, et al: Anticytoplasmic autoantibodies: Their immunodiagnostic value in Wegener’s granulomatosis. Ann Intern Med 111:28, 1989
Surg
1991
Liposarcoma
Arising in the Cheek:
Report of a Case and Review of the Literature LCDR DAVID R. CHARNOCK, MC, USNR,* LCDR THORNTON JETT, DC, USN,t LCDR GREGORY HEISE, DC, USN,t AND CDR ROBERT TAYLOR, MC, USN* Received from the US Naval Hospital, Oakland, CA. * Department of Otolaryngology-Head and Neck Surgery; currently, Head, Department of Otolaryngology, Naval Hospital, Guam. t Oral Surgeon, Dental Department. 8 Chairman, ENT Department. The Chief, Navy Bureau of Medicine and Surgery, Washington, DC, Clinical Investigation Program, sponsored this case report 89-48-1970-103. The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Govemment. Address correspondence and reprint requests to LCDR Charneck: Department of Otolaryngology, Naval Hospital, Guam, FPO San Francisco, CA %630.
Liposarcoma was first described by Virchow in 1857.’ Each year there are an estimated 5,100 new malignant soft-tissue tumors occurring in patients in the United States, 21% of which are liposarcomas.* These tumors are rare in the head and neck; most are located in the lower extremities and retroperitoneum. A study by Pack and Person3 from 1928 to 1954 found no reported cases of liposarcoma above the clavicles. To date, only 23 cases of liposarcoma in the oral cavity have been reported, 14 of which were located in the cheek.4 We describe the clinical and microscopic features, and treatment provided, of one additional case.
This a US government use.
Report of a Case Chinese male presented to the Oral Surgery Clinic in August 1988 with a 6-week history of an
work. There are no restrictions on its
0278-2391 I91 /4903-0015$0.00/0
A 63-year-old
Surg
1991
Wegener’s Granuloma tosis: Report of Three Cases With Oral Lesions CARL M. ALLEN, DDS, MSD,* CHARLES CAMISA, MD,* CAROL SALEWSKI, MD,+ AND JEFFREY E. WEILAND, MD3
Report of Cases
In 1936 and 1939, Friederich Wegener published descriptions of the clinical and autopsy findings of several patients who exhibited necrotizing granulomatous inflammation of small- to medium-sized blood vessels, with similar destructive infiltrates in the respiratory tract and kidneys.‘,’ Wegener’s granulomatosis (WG) has since become a wellrecognized disease the etiology of which remains obscure; many investigators believe that an immunologic pathogenesis is likely.3 The prognosis for untreated WG is poor, with most deaths resulting from renal failure secondary to glomerulonephritis.4 A much better prognosis is associated with the limited form of WG, which has respiratory, but not renal, involvement.’ In addition, a superficial form of WG has been described, manifesting as lesions that are confined to cutaneous or mucosal surfaces, that has an even better prognosis.6 Each of these forms of WG may present with oral lesions as an initial manifestation of the disease’; thus, prompt recognition by the clinician may lead to an earlier diagnosis and proper management. The purpose of this article is to describe
Case 1 A 20-year-old white woman was admitted to her local hospital in January 1989 for progressive ulceration of the soft palate associated with increasing oral discomfort for 5 months. The medical history was negative for previous disease, exposure to infection, use of immunosuppressive drugs, or oral trauma. She did, however, report a history of a positive PPD test. The past surgical history was positive for rhinoplasty, nasal polypectomy, and left breast cystectomy. Physical examination showed an afebrile woman with a large proliferative ulceration involving most of the soft palate and extending to the anterior tonsillar pillars. She had bilateral cervical adenopathy, but the remainder of the examination was negative. Hematologic evaluation showed a hemoglobin content of 13 g/dL, an hematocrit of 40%, and a platelet count of 262,000/mm3. The white blood cell count was 5,400/mm3, with a differential count of neutrophils 46%, lymphocytes 46%, and monocytes 8%. The erythrocyte sedimentation rate was 15 mm/h. A chemistry profile was normal. Results of the latex fixation test, and throat and soft palate cultures for P-hemolytic streptococci, viruses, acid-fast bacilli, and fungi were negative. Results of serum protein electrophoresis were normal, and results of a VDRL test were negative. Urinalysis results and chest radiograph were within normal limits. Bronchoscopy, esophagoscopy, direct laryngoscopy, nasopharyngoscopy, and examination of the oral cavity and pharynx were performed under general anesthesia. The nasopharyngeal surface of the soft palate was normal. The oral surface of the soft palate showed a large, ulcerative, indurated, irregular, fungating lesion. The base of the tongue and the hard palate were normal in appearance. Microscopic examination of a biopsy of the soft palate showed severe, chronic, inflammatory changes, with ulceration and pseudoepitheliomatous hyperplasia. No atypia or granulomas were detected. The patient was discharged with some improvement of pain, but over the next 6 weeks her condition gradually worsened to the point where she could barely eat or drink. In March 1989, she was referred to the Departments of Otolaryngology and Dermatology at the Cleveland Clinic Foundation. The proliferative, friable, ulcerated lesion now involved the posterior hard palate and
the clinical and microscopic findings of the oral lesions of WG in three patients who each presented with a different form of the condition.
* Associate Professor, Section of Diagnostic Services. College of Dentistry, The Ohio State University, Columbus. t Head, Section of Clinical Dermatology, The Cleveland Clinic Foundation, Cleveland. $ Resident Physician, Department of Medicine, The Cleveland Clinic Foundation. 8 Associate Professor, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus. Address correspondence and reprint requests to Dr Allen: Section of Diagnostic Services, College of Dentistry, The Ohio State University, Postle Hall, 305 W 12th Ave. Columbus, OH 43210-1241. 0 1991 American
Association
of Oral and Maxillofacial
Sur-
geons 0278-2391/91/4903-0014$3.00/0
294
295
ALLEN ET AL
FIGURE I. Case I, This 20-year-old woman had progressive involvement of her soft palate with this destructive lesion over a 5-month period.
FIGURE 3. Photomicrograph demonstrating a poorly defined granuloma that was also seen in the pafatal biopsy specimen of case 1 (hematoxylin-eosin, original magnification X 100).
extended onto the soft palate and uvula (Fig 1). The uvula was excised and sent for studies. Results of special stains and cultures for organisms were again negative, with the exception of a heavy growth of Candida albicans. The histologic diagnosis was reported as nonspecific chronic inflammation. Immunoglobulin and T-cell receptor gene analysis showed no gene rearrangements, compatible with a benign polyclonal lymphoid population. No additional routine laboratory abnormalities were detected. Ketoconazole. 400 mg daily, and chlorhexidine mouth rinse were prescribed. A biopsy of the left soft palate was repeated and submitted to the Department of Oral Pathology at The Ohio State University College of Dentistry. This specimen exhibited acute and chronic inflammation, vascular injury, and poorly defined granulomas suggestive of WG (Figs 2 and 3). Titer for neutrophil cytoplasmic autoantibodies was negative. Because no lung or kidney involvement was identified, a diagnosis of superficial WG was considered most appropriate. The patient was started on a combination chemotherapy regimen consisting of prednisone, 60 mg daily for 5 days each month. and cyciophosphamide, 50 mg daily. She responded very well to treatment, and within 8 weeks
the palate was completely healed (Fig 4). At one point, the patient stopped taking her medication for 2 days and claimed that six small nodules appeared on the soft palate, completely disappearing when she resumed the medication. After 8 weeks of treatment, the prednisone was discontinued, and the cyclophosphamide was prescribed for a total of 18 weeks. The patient remains free of any oral or systemic disease 5 months following cessation of all medications.
FlGURE 2. Photomicrograph demonstrating vasculitis in the palatal biopsy specimen of case 1. (hematoxylin-eosin. original magnification X 100).
FIGURE 4. Case I, Complete resolution of the palata! lesion of superficial Wegener’s granulomatosis after 8 weeks of prednisone and cyclophosphamide therapy.
Case 2 A 23-year-old black man was evaluated by a dentist for gingival hyperplasia in the left maxilla in January 1989. The clinician made a diagnosis of inflammatory hyperplasia, removed the lesion, and discarded the tissue. The condition recurred during the next month, and the patient was referred to an oral and maxillofacial surgeon. Clinical examination showed an erythematous, finely papular, enlargement of the maxillary buccal gingiva extending from the maxillary left canine posteriorly to the maxillary left second molar. Although the surface of the lesion appeared intact, at biopsy the tissue was quite friable. Microscopic examination showed severe chronic inflamma-
296
WEGENER’S GRANULOMATOSIS
FIGURE 5. Case 2, Photomicrograph demonstrating severe inwith WC (hematoxylin-
flammation with vasculitis, consistent eosin, original magnification X 100).
tion with vasculitis (Fig 5). Special stains showed no evidence of acid-fast bacilli or fungal organisms. Based on the clinical description of the oral lesions and the microscopic findings, a diagnosis of WG was suggested. Further evaluation showed normal values for complete blood count and SMA-20. A streaky right upper lobe infiltrate and a poorly defined cavitary mass were seen on the chest radiograph. No hematuria was detected, and the blood urea nitrogen and creatinine values were within normal limits. These findings were consistent with a diagnosis of limited WG. Antineutrophil cytoplasmic antibody titer was negative. Treatment was initiated with cyclophosphamide, 150 mg, and prednisone, 20 mg, four times daily. Minimal response was noted after 2 months, and the cyclophosphamide was then increased to 200 mg four times daily. A repeated chest radiograph in September 1989 showed no progression of the right upper lobe mass. At that time, the cyclophosphamide was increased to 250 mg four times daily, and by the end of October 1989, the oral lesions had resolved completely.
FIGURE 6. Case 3, This 62-year-old woman had been aware of this destructive palatal ulceration for approximately 1 month. An incisional biopsy was obtained from the periphery of this lesion. sinus, and her chest radiograph demonstrated bibasilar atelectasis. Results of routine laboratory studies, including urinalysis, were within normal limits. On the basis of the clinical and microscopic features of the oral lesions, a diagnosis of limited WG was made, and the patient was started on cyclophosphamide, 100 mg, and prednisone, 15 mg, four times daily. Minimal change in the oral lesion was seen after 1 month; however, by 2 months, marked resolution had occurred, and by 5 months, healing was complete. In September 1987, the patient was readmitted to University Hospitals in acute renal failure. Renal biopsy showed a crescentic glomerulonephritis, consistent with WG. Cyclophosphamide was continued at 100 mg four times daily; however, prednisone was increased to 60 mg four times daily. Renal function subsequently stabilized
Case 3 A 62-year-old white woman was seen by an oral and maxillofacial surgeon for evaluation and biopsy of a palatal ulceration that she had noticed for approximately 1 month. An incisional biopsy of the palatal lesion was performed and submitted with a provisional clinical diagnosis of malignancy. Microscopic examination showed poorly defined, necrotizing granuloma formation, with evidence of vasculitis. Special stains were negative for acid-fast bacilli and fungi, and it was suggested that WG be ruled out. The patient was referred to the Ohio State University Hospitals for further evaluation. Examination in January 1987 showed a 2 x 4-cm ulceration with irregular borders involving the left hard palate and gingiva (Fig 6). A granular, erythematous gingival enlargement, with associated petechial hemorrhage, was present in the mandibular right canine region (Fig 7). A computed tomography scan showed mucoperiosteal thickening of the left maxillary
FIGURE 7. Case 3, Focal involvement of the gingival tissue characterized by an erythematous enlargement, with a finely pebbled surface exhibiting petechial hemorrhage. Such lesions are virtually pathognomonic of Wegener’s granulomatosis.
297
ALLEN ET AL
during her admission,
and she was discharged on a taper-
ing schedule of prednisone. Discussion The cases presented illustrate the spectrum of disease that may manifest as WG, ranging from localized cutaneous/mucosal involvement through the classical description of pulmonary and renal lesions. The superficial form of WG, affecting only mucosal or cutaneous tissues, appears to have a much better prognosis initially in comparison to classic WG, but these patients may also progress to pulmonary and/or renal involvement.6 Similarly, the limited form of WG, which is characterized by upper and lower respiratory lesions, but not renal lesions, is not associated with the rapidly fatal kidney failure of classic WG.5 Because oral lesions may be found with any of these presentations of WG, the oral and maxillofacial surgeon should be familiar with their clinical features. The findings in our series are similar to those reported by other investigators,7-‘5 particularly with respect to oral ulceration and hyperplastic gingivitis. Our patients did not manifest clinically apparent facial swelling.” The oral ulcerations seen in WG may appear quite destructive as in cases 1 and 3, clinically mimicking a malignant process. The gingival lesions seen in cases 2 and 3 should be emphasized because they are virtually pathognomonic for WG. “*‘8 The gingival enlargement may initially be localized to a specific segment of the gingiva, beginning in the interdental region, but ultimately it can progress to involve the rest of the gingival tissues, eventually causing periodontal destruction and tooth Ioss.‘*‘~ On careful evaluation, no other condition will appear identical to the gingival lesions of WG. The surface of the gingival enlargement exhibits a finely papular, granular texture with an intact epithelial surface. Numerous petechiae are noted on the surface of the gingival enlargement. imparting a red to purple color to the lesion. If the characteristic gingival changes are present, the clinical diagnosis of WG should be relatively straightforward. In the presence of only oral ulcerations, however, an extensive differential diagnosis could be developed, and should include infectious, reactive, and neoplastic disease.” Special stains of biopsy material, cultures, and antibody titers can help rule out deep fungal infection (eg, histoplasmosis, cryptococcosis) or bacterial infection (eg, tuberculosis, tertiary syphilis). Histologic examination of lesional tissue will rule out reactive/ inflammatory lesions that could produce significant
oral ulceration (eg, necrotizing sialometaplasia, Crohn’s disease). Similarly, neoplastic disease (eg, lymphoma, polymorphic reticulosis, other malignancies) can be ruled out by means of biopsy. Thorough evaluation of the patient suspected of having WG is mandatory, particularly if the biopsy is only suggestive of the condition. Biopsies of oral lesions may show only pseudoepitheliomatous hyperplasia with relatively nonspecific acute and chronic inflammation.’ In our experience, careful examination of multiple sections may reveal the characteristic necrotizing vasculitis of WG. Radiographic examination of the chest and the sinuses should be performed to assess disease activity at those sites. Serum creatinine and urinalysis should be ordered to determine the extent of renal involvement.*’ A complete blood cell count and erythrocyte sedimentation rate are also useful baseline blood studies. Recently the assessment of neutrophil anticytoplasmic autoantibodies by means of indirect immunofluorescence*’ and/or enzymelinked immunoabsorbant assay (ELISA)*’ has proved helpful in supporting a diagnosis of WG. The presence of these autoantibodies in the patient’s serum appears to be highly specific for WG.*1,32 The sensitivity, however, seems to correlate with the severity of disease and disease activity, with 67% of patients with limited WG showing autoantibodies, in comparison with 96% of patients with generalized WG. ** The two patients described in this report who were evaluated for neutrophil anticytoplasmic autoantibodies had limited WG and negative findings, which does not rule out WG as a diagnosis.” While WG in the past was almost uniformly fatal, current management of this disease with cyclophosphamide and prednisone results in complete remission in over 90% of affected patients.4 Weekly monitoring of the white blood cell count is critical to prevent severe neutropenia induced by the cyclophosphamide. Adjustments in the dosage may be made accordingly. The oral lesions in our patients responded to this regimen gradually over periods ranging from 2 to 8 months, with all lesions healing completely. Careful follow-up of patients with WG is important, regardless of the initial stage of presentation. The superficial and limited forms of WG may eventually progress to more widespread disease, as in case 3, the patient who developed kidney involvement 9 months after the initial diagnosis was made. Fortunately, her renal disease was controlled by increasing the dosage of prednisone. Recognition of the oral manifestations of WG by the oral and maxillofacial surgeon is an essential
298
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initial step in diagnosing this important, enigmatic disease. A complete evaluation with biopsies, and medical management and monitoring, are necessary to minimize morbidity and prevent mortality. Acknowledgment The authors wish to thank Drs Peter Larsen and Pierre Lavertu for providing the information regarding cases 1 and 2.
1. Wegener F: Uber generalisierte, septische Gefaesserkrankungen. Verh Dtsch Ges Pathol 29:202, 1936 2. Wegener F: Uber eine eigenartige Rhinogene Granulomatose mit besondere Beteiligung des Arteriensystems und der Nieren. Beitr Path01 Anat Allg 102:36, 1939 3. Leavitt RY, Fauci AS. Pulmonary vasculitis. Am Rev Respir Dis 134:149, 1986 4. Fauci AS, Haynes BF, Katz P, Wolfe SM: Wegener’s granulomatosis: Prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76, 1983 5. Cassan SM, Coles DT, Harrison EG Jr: The concept of limited forms of Wegener’s granulomatosis. Am J Med 49:366, 1970 6. Fienberg R: The protracted superficial phenomenon in pathergic (Wegener’s) granulomatosis. Hum Pathol 12:458, 1981 7. Handlers JP, Waterman J, Abrams AM, Melrose RJ: Oral features of Wegener’s granulomatosis. Arch Otolaryngol Head Neck Surg 111:267, 1985 8. Morgan AD, O’Neil R: The oral complications of polyartertis and giant-cell granulomatosis (Wegener’s granulomatosis). Oral Surg 9:845, 1956
49:29&3oct
9. Cawson RA: Gingival changes in Wegener’s granulomatosis. Br Dent J 118:30, 1965 10. Kakehashi S, Hamner JE, Baer PN, et al: Wegener’s granulomatosis: Report of a case involving the gingiva. Oral Surg 19:120, 1965 11. Brooke RI: Wegener’s granulomatosis involving the gingiva. Br Dent J 127:34, 1969 12. Scott J, Finch LD: Wegener’s granulomatosis presenting as gingivitis. Oral Surg 34:920, 1972 13. Edwards MB, Buckerfield JP: Wegener’s granulomatosis: A case with primary mucocutaneous lesions. Oral Surg 46:53, 1978 14. Israelson H, Binnie WH, Hurt WC: The hypcrplastic
References
J Oral Maxillofac
ARISING IN THE CHEEK
15. 16.
17.
18.
19. 20. 21.
22.
gingivitis of Wegener’s granulomatosis. J Periodontol 52:81, 1981 Cohen PS, Meltzer JA: Strawberry gums: A sign of Wegener’s granulomatosis. JAMA 246~2610, 1981 Reed WB, Jensen AK, Konwaler BE, et al: The cutaneous manifestations in Wegener’s granulomatosis. Acta Derm Venereol43:250, 1963 Hansen LS, Silverman S Jr, Pons VG, et al. Limited Wegener’s granulomatosis: Report of a case with oral, renal and skin involvement. Oral Surg 60:524, 1985 Cawson RA, Eveson JW: Oral pathology and diagnosis. Color atlas with integrated text (ed 1). Philadelphia, PA, Saunders, 1987 (section 17.4) Sack KE: Wegener’s granulomatosis. West J Med 150:329, 1989 McDonald TJ, DeRemee RA: Wegener’s granulomatosis. Laryngoscope 93:220, 1983 Specks U, Wheatley CL, McDonald TJ, et al: Anticytoplasmic autoantibodies in the diagnosis and follow-up of Wegener’s granulomatosis. Mayo Clin Proc 64:28, 1989 Nell B, Specks U, Ludemann J, et al: Anticytoplasmic autoantibodies: Their immunodiagnostic value in Wegener’s granulomatosis. Ann Intern Med 111:28, 1989
Surg
1991
Liposarcoma
Arising in the Cheek:
Report of a Case and Review of the Literature LCDR DAVID R. CHARNOCK, MC, USNR,* LCDR THORNTON JETT, DC, USN,t LCDR GREGORY HEISE, DC, USN,t AND CDR ROBERT TAYLOR, MC, USN* Received from the US Naval Hospital, Oakland, CA. * Department of Otolaryngology-Head and Neck Surgery; currently, Head, Department of Otolaryngology, Naval Hospital, Guam. t Oral Surgeon, Dental Department. 8 Chairman, ENT Department. The Chief, Navy Bureau of Medicine and Surgery, Washington, DC, Clinical Investigation Program, sponsored this case report 89-48-1970-103. The views expressed in this article are those of the author(s) and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Govemment. Address correspondence and reprint requests to LCDR Charneck: Department of Otolaryngology, Naval Hospital, Guam, FPO San Francisco, CA %630.
Liposarcoma was first described by Virchow in 1857.’ Each year there are an estimated 5,100 new malignant soft-tissue tumors occurring in patients in the United States, 21% of which are liposarcomas.* These tumors are rare in the head and neck; most are located in the lower extremities and retroperitoneum. A study by Pack and Person3 from 1928 to 1954 found no reported cases of liposarcoma above the clavicles. To date, only 23 cases of liposarcoma in the oral cavity have been reported, 14 of which were located in the cheek.4 We describe the clinical and microscopic features, and treatment provided, of one additional case.
This a US government use.
Report of a Case Chinese male presented to the Oral Surgery Clinic in August 1988 with a 6-week history of an
work. There are no restrictions on its
0278-2391 I91 /4903-0015$0.00/0
A 63-year-old
