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HIV-salivary gland disease
IV-salivary gland disease Salivary scintiscanning with technetium pertechnetate Crispian Scully, PhD, MD, FDS, FRCPath,a Rhys Davies, CBE, MA, FRCPE, FRCR,b Stephen Porter, PhD, MBChB, FDS,a John Eveson, PhD, FDS, FRCPath,a and Jane Luker, PhD, FDSYa Bristol, U.K. CENTRE
FOR THE STUDY OF ORAL DISEASE, UNIVERSITY
PATHOLOGY, UNIVERSITY
AND MICROBIOLOGY, DEPARTMENT
BRISTOL DENTAL
OF CLINICAL
RADIOLOGY,
DEPARTMENT
HOSPITAL BRISTOL
OF ORAL MEDICINE,
AND SCHOOL, ROYAL
AND
INFIRMARY
The salivary disease in two patients with human immunodeficiency virus infection was investigated by technetium pertechnetate scintiscanning. Although there was good histologic evidence of benign lymphoepitheiial disease, scintiscanning failed to delineate any salivary lesions, Technetium pertechnetate scintiscanning seems to be of little value in the detailed investigation of salivary disease in human immunodeficiency virus infection, though gallium scanning can help. Fine needle aspiration or biopsy remain the main diagnostic tools. (ORAL SURC ORAL MED ORAL PATHOL 1993;76:120-3)
Swellings of the major salivary glands in patients infected with human immunodeficiency virus (HIV) may be related to lymph node enlargement, lymphomas, Kaposi’s sarcoma, acute sialadenitis, or other salivary gland disease. A sicca syndrome characterized typically by xerostomia, painless bilateral parotid mass or enlargement, lymphadenopathy and pulmonary insufficiency associated with a diffuse infiltrative lymphocytosis, has been described in some patients infected with HIV.‘-to Patients with HIV infection may develop multiple cystic benign lymphoepithelial lesions in the parotid glands.7-20 There is no evidence of viruses such as Epstein-Barr virus or cytomegalovirus in the salivary gland& or evidence of a direct effect of HIV on salivary function.21 This salivary disease in HIV infection, sometimes termed WIV-salivary gland disease or HIV-SGD, appears to be similar to, but distinct from, classic Sjogren’s syndrome. Autoantibodies Ro and La are lacking in HIV-SGD, and the disorder is influenced by a genetically determined host immune response to HIV, generally being associated with HLA-DR5 and a CD8 lymphocytosis 5,6 though some have HLA-DR3.9 There is also a CD8 lymphocytic focal infiltrate in the minor salivary glands.‘, 6 Patients with HIV disease can have a range of unpleasant symptoms, and the quality of their life is not improved by invasive investigative procedures. Imaging techniques may therefore have advantages over biopsies. Pathologic conditions in the major salivary glands in patients with HIV infection have been revealed radiographically with the use of computed %ristol Dental Hospital and School. bBristol Royal Infirmary. Copyright a 1993 by Mosby-Year Book, Inc. 0030-4220/93/$1.00+.10
120
7/16/44806
tomography, sialography, 67gallium citrate scanning, and magnetic resonance imaging.4, 5, ‘sUt7,19,2o Gallium scanning shows increased radionuclide uptake in salivary tissue and also in lacrimal and nasal areas.5,2o However, despite the fact that salivary scintiscanning with 9gtechnetium pertechnetate is a fairly widely available and proven investigative procedure in the diagnosis of Sjiigren’s syndrome,22>23we were not aware of reports of the value of this technique in the diagnosis of HIV-SGD. We have therefore investigated two patients with WIV-SGD by 99mTcscanning and present the preiiminary results. CASE I A 43-year-old HIV-positive
white homosexual man pre-
sented with xerostomia, bilaterally enlarged parotid salivary glands, oral candidiasis, hairy leukoplakia, and recurrent oral ulceration. CASE 2 A 36-year-old HIV-positive African woman, domiciled in the UK, had contracted HIV infection from a blood transfusion in Africa in 1983. She had a history of cervical lymph
node enlargement and had bilaterally enlarged parotid salivary glands. METHODS Technetium scans13,22 and salivary gland biopsies were obtained from each patient.t4 A biopsy was performed on the labial salivary glands in case 1 and the parotid salivary glands in case 2. The scan technique and analysis were the standard techniques used to gather these resultsz2 RESULTS
The labial gland biopsy specimen from case 1 included several lobules of seromucous minor salivary
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Volume 76, Number 1
Sadly et al.
121
Fig. 1. Labial salivary glands show extensive, predominantly interstitial lymphoplasmacytic infiltration in biopsy from case 1. (Hematoxylin-eosin stain; original magnification x60.)
gland tissue that showed extensive interstitial lymphoplasmacytic infiltration and areas of focal periductal lymphocytic infiltration but no evidence of duct proliferation (Fig. 1). These features were consistent with those found in connective tissue disorders. The major gland biopsy specimen from case 2 showed extensive acinar loss and lobules of salivary gland tissue replaced by a dense lymphoid infiltrate that contained focal lymphoid follicles. These follicles contained large numbers of macrophages with conspicuous tingiblle bodies. In addition, there were epimyoepithelial islands, some of which showed central cystic degeneration and dilatation (Fig. 2). The features were consistent with cystic benign lymphoepithelial lesion. However, despite the clear evidence of a pathologic condition in the salivary glands, no significant abnormalities in the rate of uptake, distribution of uptake, or release of 99mTc from the major salivary glands were seen in either patient, even in case 2 with histologically demonstrable cystic benign lymphoepithelial lesion (Fig. 3). DISCUSSION Results of the preliminary investigations on these two patients with salivary gland swelling associated with infection with human immunodeficiency virus indicate that salivary scintiscanning with technetium pertechnetate may be of virtually no value as a diagnostic tool. Why this should be so’ or if this is a universal finding in HIV-SGD is unclear because technetium scanning can be of value in the diagnosis of
classic Sjiigren’s syndrome.23 Further studies may be indicated in HIV-SGD. Gallium scanning in contrast reveals increased uptake in affected salivary, lacrimal, and nasal tissues, and others have found abnormal salivary gallium scintiscans in all investigated HIVinfected patients43 5,2o Most patients have increased bilateral uptake of gallium in both the parotid and submandibular salivary glands in HIV-disease, but of course gallium uptake is a nonspecific feature and such findings can also be seen in lymphomas and sarcoidosis. Reported sialographic changes in HIV-SGD are nonspecific and include acinar and ductal destruction and sialectasis.t6 Computed tomographyT scanning t5, I’, 19*2o and magnetic resonance imaging 16,17,l9 have proved useful to demonstrate parotid cysts in HIV-SGD, but again the findings are nonspecific. It would seem therefore that imaging techniques are currently of limited diagnostic value in HIV-SGD. A biopsy of labial salivary gland5> 6 and major salivary glandto is, however, of value in the diagnosis of HIV-SGD, as is fine needle aspiration.“, ls Therefore it would appear that the diagnosis of HIV-SGD is best made from the history and clinical and serologic findings, supported possibly by labial gland biopsy6 or fine needle aspiration of cystic lesions in the major glands.lO Because malignant conditions such as lymphomas may be occasionally associated with HIVSGD and cannot be reliably excluded radiographitally or by fine needle aspiration, parotid biopsy or superficial parotidectomy may well be indicated when this diagnosis is strongly entertained.‘O, 12,l5
122
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY July 1993
Scully et aE.
Fig. 2. Cystic benign lymphoepithelial inal magnification x60.)
lesion in parotid biopsy from case 2. (Hematoxylin-eosin
stain; orig-
Fig. 3. Technetium scintiscan (case 2) shows no abnormalities.
REFERENCES 1. Pahwa S, Fikrig S, Kaplan M. Expression of HTLV-III infection in a pediatric population. Adv Exp bled Biol1985;187:4551. 2. Ulirsch RC, Jaffe HS. Sjegren’s syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Path01 1987;18:1063-8.
3. Couderec LJ, D’Agay MF, Danon R, Harzic M, Brocheriou C, Clauvel JP. Sicca complex and infection with human immunodeficiency virus. Arcli Intern Med 1987;147:898-901. 4. Itescu S, Brancato LJ, Winchester R. A sicca syndrome in HIV infection: association with HLA-DR5 and CD8 lymphocytosis. Lancet 1989;2:466-8. 5. Itescu S, Brancato LJ, Buxbaum J, et al. A diffuse infiltrative
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 76, Number I
6. I.
8. 9.
10.
11. 12.
13.
14. 15.
CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5. Ann Intern Med 1990;112:3-10. Schiddt M, Greenspan D, Daniels TE, et al. Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients. J Autoimmun 1989;2:415-25. Espinoza LR, Aguilar JL, Berman A, Gutierrez F, Vasey FB, Germain BF. Rheumatic manifestations associated with human immuno~deficiency virus infection. Arthritis Rheum 1989;32:1615-22. Calabrese LH. The rheumatic manifestations of infection with the human immunodeficiency virus. Semin Arthritis Rheum 1989;18:225-39. Salvarani C, Macchioni P, Lodi L, et al. Sjiigren’s syndrome in human immunodeficiency virus (HIV) infection: association with HLA-DR.3 and CD8 lymphocytes in an Italian patient. Clin Exp Rheumatol 1991;9:437-41. Terry JH, Lorlee TR, Thomas MD, Marti JR. Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome. Am J Surg 1991;162:324-9. Sperling NM, Lin PT, Lucinte FE. Cystic parotid masses in HIV infection. Head and Neck 1990;12:337-41. Ioachim HL, Ryan JR, Blaugrund SM. AIDS-associated lymphadenopathies and lymphomas with primary salivary gland presentation. Lab Invest 1987;56:33. Poletti A, Manconi R, Volpe R, Carbone A. Study of AIDSrelated lymphadenopathy in the intraparotid and perisubmaxillary gland lymph nodes. J Oral Path01 Med 1988;17: 164-7. Smith FB, Rajdeo H, Panerar N, Bhuta K, Stahl R. Benign lymphoepithehal lesion of the parotid gland in intravenous drug users. Arch Path01 Lab Med 1988;112:742-5. Finfer MD, Schinella RA, Rothstein SG, Persky MS. Cystic parotid lesions in patients at risk for the acquired immunodeficiency syndrome. Arch Otolaryngol Head Neck Surg 1988; 114:1290-4.
Scully et al.
123
16. Marmary Y, Gamori JM, Nitzan DW. Lymphoepithelial parotid cysts presenting symptom of immunodeficiency virus infection: clinical, sialographic, and magnetic resonance imaging findings. J Oral Maxillofac Surg 1990;48:981-4. 17. Shugar JMA, Som PM, Jacobson AL, Ryan JR, Bernard PJ, Dickman SH. Multicentric parotid cysts and cervical adenopathy in AIDS patients: a newly recognized entity: CT and MR manifestations. Laryngoscope 1988;98:772-5. 18. Colebunders R, Francis H, Mann JM, et al. Parotid swelling during human immunodeficiency virus infection. Arch Otolaryngol Head Neck Surg 1988;114:330-2. 19. Tunkel DE, Loury MC, Fox CH, Goins MA, Johns ME. Bilateral parotid enlargement in HIV-seropositive patients. Laryngoscope 1989;99:590-5. 20. Rubin MM, Ford HC, Sadoff RS. Bilateral parotid gland enlargement in a patient with AIDS. J Oral Maxillofac Surg 1991;49:529-31. 21. Schiddt M, Greenspan D, Levy JA, et al. Does HIV cause salivary gland disease? AIDS 1989;3:819-22. 22. Rasker JJ, Jayson MIV, Jones DEP, et al. SjBgren’s syndrome in systemic sclerosis. Stand J Rheumatol 1990;19:57-65. 23. Scully C. Oral parameters in the diagnosis of Sjogren’s syndrome. Clin Exp Rheumatol 1989;7:113-8.
Reprint requests: Professor Crispian Scully Centre for the Study of Oral Disease University Department of Oral Medicine, Pathology, and Microbiology Bristol Dental Hospital and School Lower Maudlin Street Bristol U.K. BSl 2LY
FOR THE STUDY OF ORAL DISEASE, UNIVERSITY
PATHOLOGY, UNIVERSITY
AND MICROBIOLOGY, DEPARTMENT
BRISTOL DENTAL
OF CLINICAL
RADIOLOGY,
DEPARTMENT
HOSPITAL BRISTOL
OF ORAL MEDICINE,
AND SCHOOL, ROYAL
AND
INFIRMARY
The salivary disease in two patients with human immunodeficiency virus infection was investigated by technetium pertechnetate scintiscanning. Although there was good histologic evidence of benign lymphoepitheiial disease, scintiscanning failed to delineate any salivary lesions, Technetium pertechnetate scintiscanning seems to be of little value in the detailed investigation of salivary disease in human immunodeficiency virus infection, though gallium scanning can help. Fine needle aspiration or biopsy remain the main diagnostic tools. (ORAL SURC ORAL MED ORAL PATHOL 1993;76:120-3)
Swellings of the major salivary glands in patients infected with human immunodeficiency virus (HIV) may be related to lymph node enlargement, lymphomas, Kaposi’s sarcoma, acute sialadenitis, or other salivary gland disease. A sicca syndrome characterized typically by xerostomia, painless bilateral parotid mass or enlargement, lymphadenopathy and pulmonary insufficiency associated with a diffuse infiltrative lymphocytosis, has been described in some patients infected with HIV.‘-to Patients with HIV infection may develop multiple cystic benign lymphoepithelial lesions in the parotid glands.7-20 There is no evidence of viruses such as Epstein-Barr virus or cytomegalovirus in the salivary gland& or evidence of a direct effect of HIV on salivary function.21 This salivary disease in HIV infection, sometimes termed WIV-salivary gland disease or HIV-SGD, appears to be similar to, but distinct from, classic Sjogren’s syndrome. Autoantibodies Ro and La are lacking in HIV-SGD, and the disorder is influenced by a genetically determined host immune response to HIV, generally being associated with HLA-DR5 and a CD8 lymphocytosis 5,6 though some have HLA-DR3.9 There is also a CD8 lymphocytic focal infiltrate in the minor salivary glands.‘, 6 Patients with HIV disease can have a range of unpleasant symptoms, and the quality of their life is not improved by invasive investigative procedures. Imaging techniques may therefore have advantages over biopsies. Pathologic conditions in the major salivary glands in patients with HIV infection have been revealed radiographically with the use of computed %ristol Dental Hospital and School. bBristol Royal Infirmary. Copyright a 1993 by Mosby-Year Book, Inc. 0030-4220/93/$1.00+.10
120
7/16/44806
tomography, sialography, 67gallium citrate scanning, and magnetic resonance imaging.4, 5, ‘sUt7,19,2o Gallium scanning shows increased radionuclide uptake in salivary tissue and also in lacrimal and nasal areas.5,2o However, despite the fact that salivary scintiscanning with 9gtechnetium pertechnetate is a fairly widely available and proven investigative procedure in the diagnosis of Sjiigren’s syndrome,22>23we were not aware of reports of the value of this technique in the diagnosis of HIV-SGD. We have therefore investigated two patients with WIV-SGD by 99mTcscanning and present the preiiminary results. CASE I A 43-year-old HIV-positive
white homosexual man pre-
sented with xerostomia, bilaterally enlarged parotid salivary glands, oral candidiasis, hairy leukoplakia, and recurrent oral ulceration. CASE 2 A 36-year-old HIV-positive African woman, domiciled in the UK, had contracted HIV infection from a blood transfusion in Africa in 1983. She had a history of cervical lymph
node enlargement and had bilaterally enlarged parotid salivary glands. METHODS Technetium scans13,22 and salivary gland biopsies were obtained from each patient.t4 A biopsy was performed on the labial salivary glands in case 1 and the parotid salivary glands in case 2. The scan technique and analysis were the standard techniques used to gather these resultsz2 RESULTS
The labial gland biopsy specimen from case 1 included several lobules of seromucous minor salivary
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Volume 76, Number 1
Sadly et al.
121
Fig. 1. Labial salivary glands show extensive, predominantly interstitial lymphoplasmacytic infiltration in biopsy from case 1. (Hematoxylin-eosin stain; original magnification x60.)
gland tissue that showed extensive interstitial lymphoplasmacytic infiltration and areas of focal periductal lymphocytic infiltration but no evidence of duct proliferation (Fig. 1). These features were consistent with those found in connective tissue disorders. The major gland biopsy specimen from case 2 showed extensive acinar loss and lobules of salivary gland tissue replaced by a dense lymphoid infiltrate that contained focal lymphoid follicles. These follicles contained large numbers of macrophages with conspicuous tingiblle bodies. In addition, there were epimyoepithelial islands, some of which showed central cystic degeneration and dilatation (Fig. 2). The features were consistent with cystic benign lymphoepithelial lesion. However, despite the clear evidence of a pathologic condition in the salivary glands, no significant abnormalities in the rate of uptake, distribution of uptake, or release of 99mTc from the major salivary glands were seen in either patient, even in case 2 with histologically demonstrable cystic benign lymphoepithelial lesion (Fig. 3). DISCUSSION Results of the preliminary investigations on these two patients with salivary gland swelling associated with infection with human immunodeficiency virus indicate that salivary scintiscanning with technetium pertechnetate may be of virtually no value as a diagnostic tool. Why this should be so’ or if this is a universal finding in HIV-SGD is unclear because technetium scanning can be of value in the diagnosis of
classic Sjiigren’s syndrome.23 Further studies may be indicated in HIV-SGD. Gallium scanning in contrast reveals increased uptake in affected salivary, lacrimal, and nasal tissues, and others have found abnormal salivary gallium scintiscans in all investigated HIVinfected patients43 5,2o Most patients have increased bilateral uptake of gallium in both the parotid and submandibular salivary glands in HIV-disease, but of course gallium uptake is a nonspecific feature and such findings can also be seen in lymphomas and sarcoidosis. Reported sialographic changes in HIV-SGD are nonspecific and include acinar and ductal destruction and sialectasis.t6 Computed tomographyT scanning t5, I’, 19*2o and magnetic resonance imaging 16,17,l9 have proved useful to demonstrate parotid cysts in HIV-SGD, but again the findings are nonspecific. It would seem therefore that imaging techniques are currently of limited diagnostic value in HIV-SGD. A biopsy of labial salivary gland5> 6 and major salivary glandto is, however, of value in the diagnosis of HIV-SGD, as is fine needle aspiration.“, ls Therefore it would appear that the diagnosis of HIV-SGD is best made from the history and clinical and serologic findings, supported possibly by labial gland biopsy6 or fine needle aspiration of cystic lesions in the major glands.lO Because malignant conditions such as lymphomas may be occasionally associated with HIVSGD and cannot be reliably excluded radiographitally or by fine needle aspiration, parotid biopsy or superficial parotidectomy may well be indicated when this diagnosis is strongly entertained.‘O, 12,l5
122
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY July 1993
Scully et aE.
Fig. 2. Cystic benign lymphoepithelial inal magnification x60.)
lesion in parotid biopsy from case 2. (Hematoxylin-eosin
stain; orig-
Fig. 3. Technetium scintiscan (case 2) shows no abnormalities.
REFERENCES 1. Pahwa S, Fikrig S, Kaplan M. Expression of HTLV-III infection in a pediatric population. Adv Exp bled Biol1985;187:4551. 2. Ulirsch RC, Jaffe HS. Sjegren’s syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Path01 1987;18:1063-8.
3. Couderec LJ, D’Agay MF, Danon R, Harzic M, Brocheriou C, Clauvel JP. Sicca complex and infection with human immunodeficiency virus. Arcli Intern Med 1987;147:898-901. 4. Itescu S, Brancato LJ, Winchester R. A sicca syndrome in HIV infection: association with HLA-DR5 and CD8 lymphocytosis. Lancet 1989;2:466-8. 5. Itescu S, Brancato LJ, Buxbaum J, et al. A diffuse infiltrative
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 76, Number I
6. I.
8. 9.
10.
11. 12.
13.
14. 15.
CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5. Ann Intern Med 1990;112:3-10. Schiddt M, Greenspan D, Daniels TE, et al. Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients. J Autoimmun 1989;2:415-25. Espinoza LR, Aguilar JL, Berman A, Gutierrez F, Vasey FB, Germain BF. Rheumatic manifestations associated with human immuno~deficiency virus infection. Arthritis Rheum 1989;32:1615-22. Calabrese LH. The rheumatic manifestations of infection with the human immunodeficiency virus. Semin Arthritis Rheum 1989;18:225-39. Salvarani C, Macchioni P, Lodi L, et al. Sjiigren’s syndrome in human immunodeficiency virus (HIV) infection: association with HLA-DR.3 and CD8 lymphocytes in an Italian patient. Clin Exp Rheumatol 1991;9:437-41. Terry JH, Lorlee TR, Thomas MD, Marti JR. Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome. Am J Surg 1991;162:324-9. Sperling NM, Lin PT, Lucinte FE. Cystic parotid masses in HIV infection. Head and Neck 1990;12:337-41. Ioachim HL, Ryan JR, Blaugrund SM. AIDS-associated lymphadenopathies and lymphomas with primary salivary gland presentation. Lab Invest 1987;56:33. Poletti A, Manconi R, Volpe R, Carbone A. Study of AIDSrelated lymphadenopathy in the intraparotid and perisubmaxillary gland lymph nodes. J Oral Path01 Med 1988;17: 164-7. Smith FB, Rajdeo H, Panerar N, Bhuta K, Stahl R. Benign lymphoepithehal lesion of the parotid gland in intravenous drug users. Arch Path01 Lab Med 1988;112:742-5. Finfer MD, Schinella RA, Rothstein SG, Persky MS. Cystic parotid lesions in patients at risk for the acquired immunodeficiency syndrome. Arch Otolaryngol Head Neck Surg 1988; 114:1290-4.
Scully et al.
123
16. Marmary Y, Gamori JM, Nitzan DW. Lymphoepithelial parotid cysts presenting symptom of immunodeficiency virus infection: clinical, sialographic, and magnetic resonance imaging findings. J Oral Maxillofac Surg 1990;48:981-4. 17. Shugar JMA, Som PM, Jacobson AL, Ryan JR, Bernard PJ, Dickman SH. Multicentric parotid cysts and cervical adenopathy in AIDS patients: a newly recognized entity: CT and MR manifestations. Laryngoscope 1988;98:772-5. 18. Colebunders R, Francis H, Mann JM, et al. Parotid swelling during human immunodeficiency virus infection. Arch Otolaryngol Head Neck Surg 1988;114:330-2. 19. Tunkel DE, Loury MC, Fox CH, Goins MA, Johns ME. Bilateral parotid enlargement in HIV-seropositive patients. Laryngoscope 1989;99:590-5. 20. Rubin MM, Ford HC, Sadoff RS. Bilateral parotid gland enlargement in a patient with AIDS. J Oral Maxillofac Surg 1991;49:529-31. 21. Schiddt M, Greenspan D, Levy JA, et al. Does HIV cause salivary gland disease? AIDS 1989;3:819-22. 22. Rasker JJ, Jayson MIV, Jones DEP, et al. SjBgren’s syndrome in systemic sclerosis. Stand J Rheumatol 1990;19:57-65. 23. Scully C. Oral parameters in the diagnosis of Sjogren’s syndrome. Clin Exp Rheumatol 1989;7:113-8.
Reprint requests: Professor Crispian Scully Centre for the Study of Oral Disease University Department of Oral Medicine, Pathology, and Microbiology Bristol Dental Hospital and School Lower Maudlin Street Bristol U.K. BSl 2LY