LymphoepitheUal Cysts of the Salivary Glands Histologic and Cytologic Features JAMES N. ELLIOTT, M.D. AND YOLANDA C. OERTEL, M.D.
Fourteen cases of surgically excised lymphoepitheUal cysts (13 from the parotid gland and 1 from the submandibular gland) were reviewed for diagnostic histologic features. They showed squamous epithelium-lined cysts within lymph nodes. Lymphocytes, histiocytes, and plasma cells were found in the walls of the cysts. Multinucleated giant cells were present in four cases. The five patients tested for human immunodeficiency virus (HIV) infection were positive, both by enzyme-linked immunosorbent assay (ELISA) and Western Blot. Fine-needle aspiration (FNA) was performed on five cases (two were confirmed histologically). Diff-Quik®-stained smears showed a proteinaceous background and a mixed population of lymphocytes, histiocytes, plasma cells, and metaplastic squamous cells. When the above cytologic findings are present on fine-needle aspiration of a major salivary gland lesion, the diagnosis of lymphoepithelial cyst should be considered. (Key words: Fine-needle aspiration; Lymphoepithelial cyst; Salivary glands) Am J Clin Pathol 1990;93:39-43
Department of Pathology, The George Washington University Medical Center, Washington, D.C.
LESIONS OF THE PAROTID GLAND are easily noticed and are a source of concern for both the patient and the physician. Also, anxiety mounts as the patient awaits surgery and the subsequent pathology report to learn the diagnosis. The cause and course of the lymphoepithelial lesion have been studied intensively. Another lesion that has generated controversy about its histogenesis is the cystic intraparotid lesion. Bernier and Bhaskar introduced the term "lymphoepithelial cyst" to stress that this lesion is not an embryologic remnant. 2,3 Lymphoepithelial cysts are considered distinct entities from the lymphoepithelial lesions.1 In the past six years an increasing number of lymphoepithelial cysts have been diagnosed at The George Washington University Medical Center. The purpose of this study is to identify histologic and cytologic features useful in the diagnosis of the lymphoepithelial cyst.
Results
Patients and Methods Our surgical pathology files were reviewed, and all cases of lymphoepithelial cyst and lymphoepithelial lesion were retrieved from February 1968 to July 1988. Nineteen of
Received February 28, 1989; accepted for publication March 28, 1989. Address reprint requests to Dr. Oertel: Cytopathology Service, Room 2221-South, The George Washington University Medical Center, 901 23rd Street, NW, Washington, D.C. 20037.
39
Fourteen lymphoepithelial cysts were diagnosed in 11 patients (see Table 1). Thirteen cases occurred within the past six years. Two of the patients were women and nine were men. Three had bilateral lesions. Their ages ranged from 29 to 58 years. Five patients were tested for evidence of human immunodeficiency virus (HIV) infection (enzyme-linked immunosorbent assay [ELISA] and Western Blot procedures), and they showed positive results. Six patients (including four HIV-positive patients) had varying degrees of lymphadenopathy. The sexual preferences of most of our patients were not recorded except for one homosexual man who was infected with HIV. There was no known history of intravenous drug abuse among the patients. There were five cases of lymphoepithelial lesion diagnosed in four patients (see Table 2). All of the cases occurred between 1975 and 1982. Two patients were men and two were women. One patient had bilateral lesions.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
these entities (14 lymphoepithelial cysts and 5 lymphoepithelial lesions) were diagnosed in 15 patients. The clinical information was obtained from the medical records at the hospital and from private physicians' offices. The surgical pathology slides and smears from fine-needle aspirations (FNAs) were reviewed by both authors. Special stains for mycobacteria, fungi, and spirochetes (Fite, Gomori methenamine silver, Warthin-Starry) were performed on all cases with multinucleated giant cells. The diagnosis of lymphoepithelial cyst was made when epithelial-lined cysts were observed in a lymph node, adjacent to or embedded in a major salivary gland. A lymphoepithelial lesion was diagnosed when partial or complete replacement of the salivary gland by lymphohistiocytic infiltrate with islands of epimyoepithelial cells was observed and when gross or microscopic evidence of an epithelial-lined cyst was absent.
ELLIOTT AND OERTEL
40
A.J.C.P. • January 1990
Table 1. Lymphoepithelial Cysts Patient
Sex
Age (years)
HIV Tests
Date of Surgery
Location
Bilateral
1 2 3 4 5 6 7 8 9 10 11
F M F M M M M M M M M
58 32 32 46 43 46 31 40 44 36 29
ND ND ND + ND ND + ND + + +
02-27-68 01-19-82 07-23-82 07-17-87 09-08-87 03-04-88 03-30-88 07-21-87 10-09-87 06-27-85 04-03-87
Right parotid Right parotid Right parotid Left submandibular Left parotid Right parotid Left parotid Right parotid Left parotid Right parotid Right parotid
No No Yes No Yes No No No No Yes No
Comment
Contralateral lesion excised 4-22-83 Contralateral lesion excised 5-4-88
Contralateral lesion excised 8-13-85
ND = not done ; + = positive.
Gross and Microscopic Findings Lymphoepithelial Cysts. The parotid gland was involved in 13 cases. A single case involved the submandibular gland. The cysts varied in size from 0.5 to 4.5 cm and occurred on both sides. A contralateral cyst occurred in three patients within a year. The cysts were mostly single, but multiple small cysts were present in two cases. The cysts contained yellow to brown nonviscous fluid. The inner lining of the walls was gray and had multiple small nodules covered by a smooth membrane. The cyst walls were of variable thickness. In the thicker parts, the cut surfaces were grayish-white. Histologic examination revealed keratinaceous debris and serous proteinaceous material in the lumen. The walls of the cysts were lined by metaplastic squamous epithelium (Fig. 1) and occasionally by cuboidal epithelial cells infiltrated by mature lymphocytes. A lymphohistiocytic infiltrate underlay the epithelial layer. Follicular lymphoid hyperplasia (Fig. 2) with prominent plasma cell prolifer-
ation was present in eleven of the fourteen cases. Multinucleated giant cells (Fig. 3) with abundant eosinophilic cytoplasm were found in four cases. They were seen in the lumen of the cyst, or just below the epithelial lining, or surrounding invaginations of the epithelial lining, or among the lymphohistiocytic infiltrate. Special stains for mycobacteria, fungi, and spirochetes (Fite, GMS, Warthin-Starry) were negative. Remnants of salivary gland parenchyma and metaplastic duct epithelium were found trapped within the lymphohistiocytic infiltrate. The cyst and the trapped parenchymal components were partially, and in some cases completely, surrounded by lymph nodal tissue (recognized as such by the presence of a fibrous capsule and marginal sinuses). In two cases there was lymphocytic infiltrate around interlobar ducts away from the cyst. In one case some sections showed extensive lymphohistiocytic infiltrate of the salivary gland parenchyma and epimyoepithelial islands identical to the histologic findings in the lymphoepithelial lesion, whereas other sections showed an epithelial-lined cyst; hence, we classified it as a cyst. Fine-needle aspirations were performed on 2 of the 14 cases of lymphoepithelial cysts before surgery. The cytologic findings included a proteinaceous background with a mixture of small and large lymphocytes (some with "nuclear clearing" [Fig. 4], others with degenerative changes) and clumps of lymphoid cells and "lymphoid
Table 2. Lymphoepithelial Lesions Patient
Sex
Age (years)
HIV Tests
Date of Surgery
Location
Bilateral
Comment
1 2 3 4
F F M M
64 38 30 68
ND ND ND ND
11-10-75 03-07-77 06-24-81 03-09-82
Left parotid Left parotid Left parotid Right parotid
Yes No No No
Contralateral lesion excised 11-13-76
ND = not done.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Their ages ranged from 30 to 68 years. No history of intravenous drug abuse, homosexual preference, or lymphadenopathy was recorded. Both female patients gave a history of Sjogren's syndrome and Raynaud's phenomenon. None of the patients had been tested for evidence of HIV infection.
•**
v-.
•j%'^*'-l
FIG. 1 (upper, left). Wall of lymphoepithelial cyst lined by metaplastic squamous cells. Note the lymphoid infiltrate in the wall. Hematoxylin and eosin (X400). FIG. 2 (lower, left). Wall of lymphoepithelial cyst with follicular hyperplasia. Pale area represents germinal center. Hematoxylin and eosin (X100). FIG. 3 (upper, right). Wall of lymphoepithelial cyst. Multinucleated giant cells mixed with lymphocytes. Hematoxylin and eosin (X200). FIG. 4 (lower, right). FNA of lymphoepithelial cyst. Proteinaceous background, lymphocytes with nuclear clearing (arrow) and cholesterol crystals. Diff-Quik® (X200).
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
«•""»> 'J
ELLIOTT AND OERTEL
42
Discussion Within the past six years, ten patients with 13 lymphoepithelial cysts have been diagnosed at our institution.
In all our cases, the cysts were within a lymph node. This finding suggests that a salivary gland inclusion within a lymph node is a prerequisite for the development of a lymphoepithelial cyst and also supports Bhaskar and Bernier's hypothesis about their origin. 23 Five patients tested for HIV infection had positive results; the other six were not tested. Plasma cell proliferation and follicular hyperplasia were present in 11 of 14 cases. Clonal expansion of B-cells with associated polyclonal gammopathy occurs in some viral infections, including HIV infection.6 The atrophy of the surrounding salivary gland parenchyma with lymphocytic infiltration of the ductal epithelium suggests cell-mediated immune destruction of the ductal epithelial cells. Destruction of virally infected cells, as the body's response to viral replication, has been described previously for many viruses and recently for HIV infection.912 Although no viral agent has been etiologically linked to the lymphoepithelial cyst, the Epstein-Barr (EBV) virus is thought to replicate in salivary gland parenchyma. 78 None of the HIV-positive patients was leukopenic or had an opportunistic infection at the time of presentation. This suggests that these patients probably had generated
FIG. 5 (left). FNA of lymphoepithelial cyst. Stacks of cholesterol crystals in an inflammatory background. Diff-Quik® (X200). FIG. 6 (right). FNA of lymphoepithelial cyst. Tingible-body macrophage (thick arrow) surrounded by degenerated acinar cells. Metaplastic squamous epithelial cells (thin arrow), and a multinucleated histiocyte. Diff-Quik® (X400).
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
tangles." Dispersed among the lymphocytes were cholesterol crystals (Figs. 4 and 5), hemosiderin-laden and tingible-body macrophages, squamous metaplastic cells (singly and in small clusters), multinucleated histiocytes, and degenerated acinar cells from salivary gland parenchyma (Fig. 6). A few capillaries were found in one case. Lymphoepithelial Lesions. The specimens from the five cases of lymphoepithelial lesions were lobulated and graytan. No cysts were identified on sectioning. A contralateral lesion occurred in one patient within a year. All the cases lacked a cystic component, grossly and/ or microscopically. The salivary gland parenchyma was infiltrated by mature lymphocytes mixed with histiocytes. Acinar atrophy and ductal epithelial metaplasia were present. The destruction of the ductal epithelial cells was associated with obliteration of the lumina. Scattered among the lymphocytes were epimyoepithelial islands. The histologic findings varied in severity in each case. No fine-needle aspirations of these lesions were performed.
A.J.C.P. • January 1990
Vol. 93 • No. I
43
LYMPHOEPITHELIAL CYSTS References
1. Batsakis JG. Tumors of the head and neck: clinical and pathological considerations. 2nd ed. Baltimore: Williams and Wilkins, 1979: 105-117. 2. Bernier JL, Bhaskar SN. Lymphoepithelial lesions of salivary glands. Histogenesis and classification based on 186 cases. Cancer 1958; 11: 1156-1179. 3. Bhaskar SN, Bernier JL. Histogenesis of branchial cysts. A report of 468 cases. Am J Pathol 1959;35:407-423. 4. Couderc U, D'Agay MF, Danon F, Harzic M, Brocheriou C, Clauvel JP. Sicca complex and infection with human immunodeficiency virus. Arch Intern Med 1987;147:898-901. 5. Gordon JJ, Golbus J, Kurtides ES. Chronic lymphadenopathy and Sjogren's syndrome in a homosexual man. N Engl J Med 1984;311:1441-1442. 6. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983;309:453-458. 7. Morgan DG, Niederman JC, Miller G, Smith HW, Dowaliby JM. Site of Epstein-Barr virus replication in the oropharynx. Lancet 1979;2:1154-1157. 8. Niederman JC, Miller G, Pearson HA, Pagano JS, Dowaliby JM. Infectious mononucleosis: Epstein-Barr virus shedding in saliva and the oropharynx. N Engl J Med 1976;294:1355-1359. 9. Plata F, Autran B, Martins LP, et al. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature 1987;328:348-351. 10. Smith FB, Rajdeo H, Panesar N, Bhuta K, Stahl R. Benign lymphoepithelial lesion of the parotid gland in intravenous drug users. Arch Pathol Lab Med 1988;112:742-745. 11. Ulirsch RC, Jaffe ES. Sjogren's syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Pathol 1987;18:1063-1068. Acknowledgments. The authors thank Frank Janotta, M.D., for pro- 12. Weinhold KJ, Lyerly HK., Matthews TJ, et al. Cellular anti-gpl20 viding histologic sections fromfiveof the cases. They would also like to cytolytic reactivities in HIV-1 seropositive individuals. Lancet thank Violet Jamison and Troy Tortorella for typing the manuscript. 1988;1:902-904.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
an immune response to virally infected ductal epithelial cells. A similar response may account for the sicca complex and lymphoepithelial lesion reported in some HIVinfected patients. 4,5,10 " Fine-needle aspirates of two lymphoepithelial cysts showed a proteinaceous background with small and large lymphocytes, lymphoid tangles, hemosiderin-laden macrophages, squamous metaplastic cells, cholesterol crystals, multinucleated histiocytes, and salivary gland acinar cells. Warthin's tumors have to be considered in the differential diagnosis because some smears may show similar cytologic findings as described above. Also, the small clumps of metaplastic squamous cells can mimic or vaguely resemble the oncocytic cells found in Warthin's tumors. However, oncocytic cells usually are arranged in large monolayers or sheets with a "honeycomb" appearance, and the nucleoli are prominent. After we started this review, we have performed aspirations on three additional patients (two HIV positive) with similar cytologic findings. As the swelling disappeared and the cytologic diagnosis of "benign lymphoepithelial cyst" was made, surgical excision was deemed unnecessary. Hence, we do riot have "tissue confirmation" in these three cases. We believe that when a diagnosis of lymphoepithelial cyst is made on an FNA, the possibility of HIV infection should be ruled out.
Fourteen cases of surgically excised lymphoepitheUal cysts (13 from the parotid gland and 1 from the submandibular gland) were reviewed for diagnostic histologic features. They showed squamous epithelium-lined cysts within lymph nodes. Lymphocytes, histiocytes, and plasma cells were found in the walls of the cysts. Multinucleated giant cells were present in four cases. The five patients tested for human immunodeficiency virus (HIV) infection were positive, both by enzyme-linked immunosorbent assay (ELISA) and Western Blot. Fine-needle aspiration (FNA) was performed on five cases (two were confirmed histologically). Diff-Quik®-stained smears showed a proteinaceous background and a mixed population of lymphocytes, histiocytes, plasma cells, and metaplastic squamous cells. When the above cytologic findings are present on fine-needle aspiration of a major salivary gland lesion, the diagnosis of lymphoepithelial cyst should be considered. (Key words: Fine-needle aspiration; Lymphoepithelial cyst; Salivary glands) Am J Clin Pathol 1990;93:39-43
Department of Pathology, The George Washington University Medical Center, Washington, D.C.
LESIONS OF THE PAROTID GLAND are easily noticed and are a source of concern for both the patient and the physician. Also, anxiety mounts as the patient awaits surgery and the subsequent pathology report to learn the diagnosis. The cause and course of the lymphoepithelial lesion have been studied intensively. Another lesion that has generated controversy about its histogenesis is the cystic intraparotid lesion. Bernier and Bhaskar introduced the term "lymphoepithelial cyst" to stress that this lesion is not an embryologic remnant. 2,3 Lymphoepithelial cysts are considered distinct entities from the lymphoepithelial lesions.1 In the past six years an increasing number of lymphoepithelial cysts have been diagnosed at The George Washington University Medical Center. The purpose of this study is to identify histologic and cytologic features useful in the diagnosis of the lymphoepithelial cyst.
Results
Patients and Methods Our surgical pathology files were reviewed, and all cases of lymphoepithelial cyst and lymphoepithelial lesion were retrieved from February 1968 to July 1988. Nineteen of
Received February 28, 1989; accepted for publication March 28, 1989. Address reprint requests to Dr. Oertel: Cytopathology Service, Room 2221-South, The George Washington University Medical Center, 901 23rd Street, NW, Washington, D.C. 20037.
39
Fourteen lymphoepithelial cysts were diagnosed in 11 patients (see Table 1). Thirteen cases occurred within the past six years. Two of the patients were women and nine were men. Three had bilateral lesions. Their ages ranged from 29 to 58 years. Five patients were tested for evidence of human immunodeficiency virus (HIV) infection (enzyme-linked immunosorbent assay [ELISA] and Western Blot procedures), and they showed positive results. Six patients (including four HIV-positive patients) had varying degrees of lymphadenopathy. The sexual preferences of most of our patients were not recorded except for one homosexual man who was infected with HIV. There was no known history of intravenous drug abuse among the patients. There were five cases of lymphoepithelial lesion diagnosed in four patients (see Table 2). All of the cases occurred between 1975 and 1982. Two patients were men and two were women. One patient had bilateral lesions.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
these entities (14 lymphoepithelial cysts and 5 lymphoepithelial lesions) were diagnosed in 15 patients. The clinical information was obtained from the medical records at the hospital and from private physicians' offices. The surgical pathology slides and smears from fine-needle aspirations (FNAs) were reviewed by both authors. Special stains for mycobacteria, fungi, and spirochetes (Fite, Gomori methenamine silver, Warthin-Starry) were performed on all cases with multinucleated giant cells. The diagnosis of lymphoepithelial cyst was made when epithelial-lined cysts were observed in a lymph node, adjacent to or embedded in a major salivary gland. A lymphoepithelial lesion was diagnosed when partial or complete replacement of the salivary gland by lymphohistiocytic infiltrate with islands of epimyoepithelial cells was observed and when gross or microscopic evidence of an epithelial-lined cyst was absent.
ELLIOTT AND OERTEL
40
A.J.C.P. • January 1990
Table 1. Lymphoepithelial Cysts Patient
Sex
Age (years)
HIV Tests
Date of Surgery
Location
Bilateral
1 2 3 4 5 6 7 8 9 10 11
F M F M M M M M M M M
58 32 32 46 43 46 31 40 44 36 29
ND ND ND + ND ND + ND + + +
02-27-68 01-19-82 07-23-82 07-17-87 09-08-87 03-04-88 03-30-88 07-21-87 10-09-87 06-27-85 04-03-87
Right parotid Right parotid Right parotid Left submandibular Left parotid Right parotid Left parotid Right parotid Left parotid Right parotid Right parotid
No No Yes No Yes No No No No Yes No
Comment
Contralateral lesion excised 4-22-83 Contralateral lesion excised 5-4-88
Contralateral lesion excised 8-13-85
ND = not done ; + = positive.
Gross and Microscopic Findings Lymphoepithelial Cysts. The parotid gland was involved in 13 cases. A single case involved the submandibular gland. The cysts varied in size from 0.5 to 4.5 cm and occurred on both sides. A contralateral cyst occurred in three patients within a year. The cysts were mostly single, but multiple small cysts were present in two cases. The cysts contained yellow to brown nonviscous fluid. The inner lining of the walls was gray and had multiple small nodules covered by a smooth membrane. The cyst walls were of variable thickness. In the thicker parts, the cut surfaces were grayish-white. Histologic examination revealed keratinaceous debris and serous proteinaceous material in the lumen. The walls of the cysts were lined by metaplastic squamous epithelium (Fig. 1) and occasionally by cuboidal epithelial cells infiltrated by mature lymphocytes. A lymphohistiocytic infiltrate underlay the epithelial layer. Follicular lymphoid hyperplasia (Fig. 2) with prominent plasma cell prolifer-
ation was present in eleven of the fourteen cases. Multinucleated giant cells (Fig. 3) with abundant eosinophilic cytoplasm were found in four cases. They were seen in the lumen of the cyst, or just below the epithelial lining, or surrounding invaginations of the epithelial lining, or among the lymphohistiocytic infiltrate. Special stains for mycobacteria, fungi, and spirochetes (Fite, GMS, Warthin-Starry) were negative. Remnants of salivary gland parenchyma and metaplastic duct epithelium were found trapped within the lymphohistiocytic infiltrate. The cyst and the trapped parenchymal components were partially, and in some cases completely, surrounded by lymph nodal tissue (recognized as such by the presence of a fibrous capsule and marginal sinuses). In two cases there was lymphocytic infiltrate around interlobar ducts away from the cyst. In one case some sections showed extensive lymphohistiocytic infiltrate of the salivary gland parenchyma and epimyoepithelial islands identical to the histologic findings in the lymphoepithelial lesion, whereas other sections showed an epithelial-lined cyst; hence, we classified it as a cyst. Fine-needle aspirations were performed on 2 of the 14 cases of lymphoepithelial cysts before surgery. The cytologic findings included a proteinaceous background with a mixture of small and large lymphocytes (some with "nuclear clearing" [Fig. 4], others with degenerative changes) and clumps of lymphoid cells and "lymphoid
Table 2. Lymphoepithelial Lesions Patient
Sex
Age (years)
HIV Tests
Date of Surgery
Location
Bilateral
Comment
1 2 3 4
F F M M
64 38 30 68
ND ND ND ND
11-10-75 03-07-77 06-24-81 03-09-82
Left parotid Left parotid Left parotid Right parotid
Yes No No No
Contralateral lesion excised 11-13-76
ND = not done.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Their ages ranged from 30 to 68 years. No history of intravenous drug abuse, homosexual preference, or lymphadenopathy was recorded. Both female patients gave a history of Sjogren's syndrome and Raynaud's phenomenon. None of the patients had been tested for evidence of HIV infection.
•**
v-.
•j%'^*'-l
FIG. 1 (upper, left). Wall of lymphoepithelial cyst lined by metaplastic squamous cells. Note the lymphoid infiltrate in the wall. Hematoxylin and eosin (X400). FIG. 2 (lower, left). Wall of lymphoepithelial cyst with follicular hyperplasia. Pale area represents germinal center. Hematoxylin and eosin (X100). FIG. 3 (upper, right). Wall of lymphoepithelial cyst. Multinucleated giant cells mixed with lymphocytes. Hematoxylin and eosin (X200). FIG. 4 (lower, right). FNA of lymphoepithelial cyst. Proteinaceous background, lymphocytes with nuclear clearing (arrow) and cholesterol crystals. Diff-Quik® (X200).
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
«•""»> 'J
ELLIOTT AND OERTEL
42
Discussion Within the past six years, ten patients with 13 lymphoepithelial cysts have been diagnosed at our institution.
In all our cases, the cysts were within a lymph node. This finding suggests that a salivary gland inclusion within a lymph node is a prerequisite for the development of a lymphoepithelial cyst and also supports Bhaskar and Bernier's hypothesis about their origin. 23 Five patients tested for HIV infection had positive results; the other six were not tested. Plasma cell proliferation and follicular hyperplasia were present in 11 of 14 cases. Clonal expansion of B-cells with associated polyclonal gammopathy occurs in some viral infections, including HIV infection.6 The atrophy of the surrounding salivary gland parenchyma with lymphocytic infiltration of the ductal epithelium suggests cell-mediated immune destruction of the ductal epithelial cells. Destruction of virally infected cells, as the body's response to viral replication, has been described previously for many viruses and recently for HIV infection.912 Although no viral agent has been etiologically linked to the lymphoepithelial cyst, the Epstein-Barr (EBV) virus is thought to replicate in salivary gland parenchyma. 78 None of the HIV-positive patients was leukopenic or had an opportunistic infection at the time of presentation. This suggests that these patients probably had generated
FIG. 5 (left). FNA of lymphoepithelial cyst. Stacks of cholesterol crystals in an inflammatory background. Diff-Quik® (X200). FIG. 6 (right). FNA of lymphoepithelial cyst. Tingible-body macrophage (thick arrow) surrounded by degenerated acinar cells. Metaplastic squamous epithelial cells (thin arrow), and a multinucleated histiocyte. Diff-Quik® (X400).
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
tangles." Dispersed among the lymphocytes were cholesterol crystals (Figs. 4 and 5), hemosiderin-laden and tingible-body macrophages, squamous metaplastic cells (singly and in small clusters), multinucleated histiocytes, and degenerated acinar cells from salivary gland parenchyma (Fig. 6). A few capillaries were found in one case. Lymphoepithelial Lesions. The specimens from the five cases of lymphoepithelial lesions were lobulated and graytan. No cysts were identified on sectioning. A contralateral lesion occurred in one patient within a year. All the cases lacked a cystic component, grossly and/ or microscopically. The salivary gland parenchyma was infiltrated by mature lymphocytes mixed with histiocytes. Acinar atrophy and ductal epithelial metaplasia were present. The destruction of the ductal epithelial cells was associated with obliteration of the lumina. Scattered among the lymphocytes were epimyoepithelial islands. The histologic findings varied in severity in each case. No fine-needle aspirations of these lesions were performed.
A.J.C.P. • January 1990
Vol. 93 • No. I
43
LYMPHOEPITHELIAL CYSTS References
1. Batsakis JG. Tumors of the head and neck: clinical and pathological considerations. 2nd ed. Baltimore: Williams and Wilkins, 1979: 105-117. 2. Bernier JL, Bhaskar SN. Lymphoepithelial lesions of salivary glands. Histogenesis and classification based on 186 cases. Cancer 1958; 11: 1156-1179. 3. Bhaskar SN, Bernier JL. Histogenesis of branchial cysts. A report of 468 cases. Am J Pathol 1959;35:407-423. 4. Couderc U, D'Agay MF, Danon F, Harzic M, Brocheriou C, Clauvel JP. Sicca complex and infection with human immunodeficiency virus. Arch Intern Med 1987;147:898-901. 5. Gordon JJ, Golbus J, Kurtides ES. Chronic lymphadenopathy and Sjogren's syndrome in a homosexual man. N Engl J Med 1984;311:1441-1442. 6. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983;309:453-458. 7. Morgan DG, Niederman JC, Miller G, Smith HW, Dowaliby JM. Site of Epstein-Barr virus replication in the oropharynx. Lancet 1979;2:1154-1157. 8. Niederman JC, Miller G, Pearson HA, Pagano JS, Dowaliby JM. Infectious mononucleosis: Epstein-Barr virus shedding in saliva and the oropharynx. N Engl J Med 1976;294:1355-1359. 9. Plata F, Autran B, Martins LP, et al. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature 1987;328:348-351. 10. Smith FB, Rajdeo H, Panesar N, Bhuta K, Stahl R. Benign lymphoepithelial lesion of the parotid gland in intravenous drug users. Arch Pathol Lab Med 1988;112:742-745. 11. Ulirsch RC, Jaffe ES. Sjogren's syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Pathol 1987;18:1063-1068. Acknowledgments. The authors thank Frank Janotta, M.D., for pro- 12. Weinhold KJ, Lyerly HK., Matthews TJ, et al. Cellular anti-gpl20 viding histologic sections fromfiveof the cases. They would also like to cytolytic reactivities in HIV-1 seropositive individuals. Lancet thank Violet Jamison and Troy Tortorella for typing the manuscript. 1988;1:902-904.
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
an immune response to virally infected ductal epithelial cells. A similar response may account for the sicca complex and lymphoepithelial lesion reported in some HIVinfected patients. 4,5,10 " Fine-needle aspirates of two lymphoepithelial cysts showed a proteinaceous background with small and large lymphocytes, lymphoid tangles, hemosiderin-laden macrophages, squamous metaplastic cells, cholesterol crystals, multinucleated histiocytes, and salivary gland acinar cells. Warthin's tumors have to be considered in the differential diagnosis because some smears may show similar cytologic findings as described above. Also, the small clumps of metaplastic squamous cells can mimic or vaguely resemble the oncocytic cells found in Warthin's tumors. However, oncocytic cells usually are arranged in large monolayers or sheets with a "honeycomb" appearance, and the nucleoli are prominent. After we started this review, we have performed aspirations on three additional patients (two HIV positive) with similar cytologic findings. As the swelling disappeared and the cytologic diagnosis of "benign lymphoepithelial cyst" was made, surgical excision was deemed unnecessary. Hence, we do riot have "tissue confirmation" in these three cases. We believe that when a diagnosis of lymphoepithelial cyst is made on an FNA, the possibility of HIV infection should be ruled out.
