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Estrogen receptor assay in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of salivary gland origin
Estrogen receptor assay in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of salivary gland origin An immunohistochemical study Arthur S. Miller, DMD,a Grace G. Hartman, MD,a Sow-Yeh Chen, BMD, PhD,a Pamela R. Edmonds, MD,b Signe A. Brightman, MD,b and Robert D. Harwick, MD,C Philadelphia, Pa. TEMPLE
UNIVERSITY
SCHOOL
OF MEDICINE
AND
MEDICAL
COLLEGE
OF PENNSYLVANIA
An apparent relationship between breast cancer and salivary gland cancer has been observed, and there is one report in the literature that describes estrogen receptors in normal salivary gland and salivary gland cancers. With the use of a monoclonal antibody against estrogen receptor protein and the avidin-biotin immunoperoxidase procedure, we were unable to demonstrate estrogen receptors in formalin-fixed paraffin-embedded sections of either polymorphous low-grade adenocarcinoma or adenoid cystic carcinoma of salivary gland origin. (ORAL SURC ORAL MED &AL PATHOL 1994;7736-40)
Certain salivary gland tumors are remarkably similar histologically to adenocarcinomas of the breast. For example, the polymorphous low-grade adenocarcinoma (PLGA) of minor salivary gland origin has microscopic features that mimic those of infiltrating lobular carcinoma of the breast.lm7 In addition, the majority of reported cases of PLGA have been in females, Adenoid cystic carcinomas (ACC) of salivary gland origin are indistinguishable histologically from ACC of the breast and vulva.*, 9 Over the past 25 years, a number of reports have appeared in the literature of a possible association between salivary gland cancer and breast cancer; these reports are based primarily on clinical observations and tumor registry data.‘O-I4 One article analyzes estrogen receptors (ER) in normal salivary gland and salivary gland carcinoma.15 The authors reported that eight of nine salivary gland tumors in women had ER levels that would be considered hormone-dependent in breast carcinoma. Four of these reported cases were ACC; three in females and one in a male. The purpose of this study was to determine, with the use of immunohistochemistry, if ER can be identified in formalin-fixed paraffin-embedded tumor cells of PLGA and ACC and to compare the immunoperoxidase reaction with known samples of infiltrating lobular carcinoma of the breast. Positive results might suggest that endogenous estrogen could influence the development of some salivary gland tumors. =Department of Pathology, Temple University School of Medicine. bDepartment of Pathology, Medical College of Pennsylvania. =Department of Surgery, Temple University School of Medicine. Copyright @ 1994 by Mosby-Year Book, Inc. 0030-4220/93/$1.00 + .I0 7/14/48701
36
MATERIAL AND METHODS
Cases coded as PLGA and ACC were identified and retrieved from the files of the Oral Pathology Laboratory, Temple University School of Medicine, and the section of Surgical Pathology, Temple University Hospital (TUH). Slides were reviewed to confirm the diagnoses. Five PLGA of minor salivary gland origin yielded sufficient paraffin-embedded tissue for immunohistochemical sections. Five cases of ACC were selected, four of minor salivary gland origin and one from sublingual gland. Immunocytochemical assay for the identification of human ER was performed on each block of formalinfixed, paraffin-embedded study tissue. Sensitivity of the procedure was established by comparing similarly prepared known cases of infiltrating lobular carcinoma of the breast from the files of TUH. Positive control tissue was from infiltrating lobular carcinoma of the breast used regularly as a control in evaluating breast tumors at the Medical College of Pennsylvania (MCP). All breast tissues were processed concurrently with the salivary gland tumors in batches with current surgical cases from MCP. Adjacent sections of each specimen provided negative controls. The ABBOTT ER-ICA monoclonal system (Abbott Laboratories, Diagnostics Division, Abbott Park, Ill.) was used. It uses a sensitive peroxidase antiperoxidase technique for visualization of ER through the use of a monoclonal antibody directed specifically against the ER protein. 16-‘* Diaminobenzidine is used as a chromogenic agent. This assay is based on direct antigenic recognition rather than on steroid binding activity. Comparable results are achieved with these two techniques. l9 Reddish-brown nuclear immunoreactivity is scored
Miller
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume
77. Number
et al.
37
1
Fig. 1. Expressionof ER shownby brown nuclearstainingof sectionof infiltrating lobular carcinomaof breast. (Immunostaining;original magnificationX 132.) Table I Tumor
Type
Age
Infiltrating lobular adenocarcinoma of the breast TUH-Control: 1 66 TUHControl2 62 MCP-Control Polymorphous low-grade adenocarcinoma 78 Case 1 Case 2 59 Case 3 Unknown Case 4 82 83 Case 5 Adenoid cystic carcinoma 31 Case 6 Case I 72 65 Case 8 Case 9 64 53 Case 10
Sex
Immunoreactivity to ER
Site
F F F
Breast Breast Breast
4+ 4+ 4f
F M F F F
Hard palate Soft palate Hard palate Mandibular vestibule Hard palate
0 0 0 0 0
M M F F M
Ventral tongue Nasal cavity Hard palate/ridge Buccal mucosa Sublingual gland
0 0 0 0 0
Scoring for immunoreactivity: 0 = negative; I+ = spotty staining; 2+ = up to 25% of tumor than 50% of tumor cells positive.20
as described by Regezi et al.*O This semiquantitative method usesa scale of 0 to 4+. Score of 0 indicates that the tissue is negative or nonreactive; 1+ = spotty staining; 2+ = up to 25% of tumor cells positive; 3+ = 25% to 50% of tumor cells positive; 4+ indicates that more than 50% of the tumor cell nuclei show positive reactions. RESULTS
Five casesof PLGA and five casesof ACC were retrieved from TUH files (Table I). Eight were of mi-
cells positive;
3+ = 25% to 50% of tumor
cells positive;
4+ = more
nor salivary gland origin, one casearosein the sublingual gland and one casein the nasal cavity. These lesions were compared with similarly fixed and prepared sectionsof infiltrating lobular carcinoma of the breast. Patients ranged from 37 years to 83 years. In one instance the patient’s age was not recorded. Six of the ten total caseswere females, four were males. With the use of the semiquantitative method of Regezi et a1,20two of the coauthors scoredthe two infiltrating lobular breast carcinomas from the TUH
38
Miller
et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY January 1994
Fig. 2. Sectionof PGLA with immunoperoxidase stain with specificmonoclonalantibody againstestrogen receptor.No tumor cellswere positive.A, Hematoxylin-eosinstain; original magnificationX 132.B, Immunostaining;original magnificationX 132.)
collection and the lobular breast carcinoma control provided by MCP as 4+ with over 50% of tumor nuclei staining (Fig. 1). All the remaining salivary gland tumor tissues were essentially negative for nuclear staining for ER (Figs. 2 and 3). Minor salivary gland acini and ducts adjacent to tumor elements did not exhibit reactivity. Dl!XUSSlON
The relationship of salivary gland cancer and breast cancer has intrigued investigators over the years as apparent correlations between the two have been observed and reported.10-‘4 Berg et al.‘O reported an
eightfold increase in breast cancer in patients with known cancersof major salivary glands. Dunn et a1.,12 with data from the California Tumor Registry, felt the eightfold risk to be an overestimate but did find the number of breast cancers in women with known salivary cancers to be twice the number expected. Abbey et a1.,14 with data from the Virginia Tumor Registry reported a four-to-fivefold increased risk. Prior and Waterhouse,13 with data from the Birmingham Regional Cancer Registry (England), reported an association between salivary gland and breast cancer and suggested other hormone-dependent sites are also at risk. Moertel and Elveback’ 1 could find no association
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 77, Number 1
Miller
et al.
39
Fig. 3. Section of ACC with immunoperoxidase stain with specificmonoclonalantibody againstestrogen receptor.No tumor cellswerepositive.A, Hematoxylin-eosinstain; original magnificationX 132.B, Immunostaining;original magnificationX 132.)
between breast cancer and salivary gland cancer in 297 women studied at the Mayo Clinic. Other parallels exist. The PLGA of salivary gland origin has microscopic features that have been reported as similar to those of infiltrating lobular carcinoma of the breast.” 2 Strands of tumor cells, often one cell in width (Indian file pattern) are loosely dispersed in a fibrous stroma. In most casesthe tumor cells are small and uniform with little pleomorphism. It is clear that the majority of reported casesof PLGA
have occurred in females,3-6,I5 and that ACC of salivary gland origin is more prevalent in females.6*l5 PLGA has been evaluated ultrastructurally21-23 and subjected to a variety of immunohistochemical procedures.6,20,24These studies have concluded that the tumor cellsexhibit markers for myoepithelial cells and luminal epithelial cells, and are probably ultimately derived from pluripotential reserve cells. PLGA casesalso show a considerable range of tumor heterogeneity as well as variation in their organiza-
40
Miller
et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY January 1994
tion.2’-23 This variation in differentiation characteristics probably accounts for the histologic diversity observed by many pathologists.23 Dimery et a1.15suggested the possibility that estrogen may act as a promoting factor for some salivary gland neoplasms. These suggestions were based on their study in which eight of nine salivary gland tumors had ER levels that would be considered hormone-dependent in breast carcinoma. Their study differed considerably from ours. They used fresh tissue obtained at surgery, which was then frozen in liquid nitrogen. The frozen tissue was pulverized, centrifuged, and the ER in the supernatant was determined by adding various concentrations of tritiated estradiol. The radioactivity was determined in a scintillation counter. Results of the immunohistochemical staining for ER in our laboratories were negative in each instance. We were unable to demonstrate ER with the use of the avidin-biotin immunoperoxidase procedure on formalin-fixed paraffin-embedded sections of PLGA or ACC. Further studies may be necessary to determine if salivary gland tumors indeed may be influenced by sex steroid hormone levels. REFERENCES I.
Freedman PD, Lumerman H. Lobular carcinoma of intraoral minor salivary gland origin: report of twelve cases. ORAL SURC ORAL
MED
ORAL
PATHOL
1983;56:157-65.
2. Batsakis JG, Pinkston GR, Luna MA, Byers RM, Sciubba JJ, Tillery GW. Adenocarcinoma of the oral cavity: a clinicopathologic study of terminal duct carcinoma. J Laryngol Otol 1983;97:825-35. 3. Evans HL, Batsakis JG. Polymorphous low-grade adenocarcinoma of minor salivary glands: a study of 14 cases of a distinctive neoplasm. Cancer 1984;53:935-42. 4. Frierson HF, Mills SE, Garland TA. Terminal duct carcinoma of minor glands: a nonpapillary subtype of polymorphous lowgrade adenocarcinoma. Am J Clin Path01 1985;84:8-14. 5. Aberle AM, Abrams AM, Bowe R, Melrose RJ, Handlers JP. Lobular (polymorphous low-grade) carcinoma of minor salivary glands: a clinicopathologic study of twenty cases. ORAL SURC
ORAL
MED
ORAL
PATHOL
1985;60:387-95.
6. Wenig BM, Gnepp DR. Polymorphous low-grade adenocarcinoma of minor salivary glands. In: Surgical pathology of the salivary glands, Vol. 25, In: Ellis GL, Auclair PL, Gnepp DR, ed. Major problems in pathology. Philadelphia: WB Saunders, 1991:390-411. I. Kumar V, Cotran RS, Robbins SL. Basic pathology, 5th ed. Philadelphia: WB Saunders, 1992:636-9. 8. Ro JY, Silva EG, Gallagher HS. Adenoid cystic carcinoma of the breast, Hum Path01 1987;18:1216-81.
9. Abrao FS, Marques AF, Marzionn F, Abrao MS, Junqueira LC, Torloni H. Adenoid cystic carcinoma of Bartholin’s gland: review of the literature and report of two cases, J Surg Oncol 1985;30: 132-7. 10. Berg JW, Hutter RV, Foote FW. The unique association hetween salivary gland cancer and breast cancer. JAMA 1968;204:77 l-4. Il. Moertel CG, Elveback LR. The association between salivary gland cancer and breast cancer. JAMA 1969;2 10:306-8. 12. Dunn J, Bragg K, Sautter C, Gardipee C. Breast cancer risk following a major salivary gland carcinoma. Cancer 1972;29:1343-6. 13. Prior P, Waterhouse JAH. Second primary cancers in patients withtumoursofthesalivaryglands. Br JCancer 1977;36:362-7. 14. Abbey LM, Schwab BH, Landau GC, Perkins ER. Incidence of second primary breast cancer among patients with a first primary salivary gland tumor. Cancer 1984;54:1439-42. 15. Dimery IW, Jones LA, Verjan RP, Raymond AK, Goepfert H, Hong WK. Estrogen receptors in normal salivary gland and salivary gland carcinoma. Arch Otolaryngol Head Neck Surg 1987;113:1082-5. 16. Shintaku IP, Said JW. Detection of estrogen receptors with monoclonal antibodies in routinely processed formalin-fixed paraffin sections of breast carcinoma. Am J Clin Path01 1987;87:161-7. 17. Anderson J, Orntoft T, Poulsen HS. Semiquantitative estrogen receptor assay in formalin-fixed paraffin sections of human breast cancer using monoclonal antibodies. Br J Cancer 1986;53:691-4. 18. Masood S. Immunocytochemical localization of estrogen and progesterone receptor in imprint preparations of breast carcinomas Cancer 1992;70:2109-14. 19. King WJ, DeSombre ER, Jensen EV, Greene GL. Comparison of immunocytochemical and steroid-binding assays for estrogen receptor in human breast tumors. Cancer Res 1985;45:293-304. 20. Regezi JA, Zarbo RJ, Stewart JCB, Courtney RM. Polymorphous low-grade adenocarcinoma of minor salivary gland: a comparative histologic and immunohistochemical study. ORAL SLRG
ORAL
MED
ORAL
PATHOL
1991;71:469-75.
21. Nicolatou 0, Kakarantza-Angelopoulou E, Angelopoulos AP, Anagnostopoulou S. Polymorphous low-grade adenocarcinoma of the palate: report of a case with electon microscopy. J Oral Maxillofac Surg 1988;46:1008-13. 22. Dardick I, van Nostrand AWP. Polymorphous low-grade adenocarcinoma: a case report with ultrastructural findings. OR.AI.
SURG
ORAL
MED
ORAL
PATHOL
1988;66:459-65.
23. Norberg LE, Burford-Mason AP, Dardick I. entiation and morphologic heterogeniety in low-grade adenocarcinoma of minor salivary Path01 Med 199 I ;20:373-9. 24. Gnepp DR, Chen JC, Warren C. Polymorphous enocarcinoma of minor salivary gland origin: tochemical and clinicopathologic study. Am 1988;12:461-8. Reprint requests. Arthur S. Miller, DMD Temple University School Oral Pathology Section 3223 N. Broad Street Philadelphia, PA 19140
of Medicine
Cellular differpolymorphous gland. J Oral low-gradeadan immunohisJ Surg Pathol
UNIVERSITY
SCHOOL
OF MEDICINE
AND
MEDICAL
COLLEGE
OF PENNSYLVANIA
An apparent relationship between breast cancer and salivary gland cancer has been observed, and there is one report in the literature that describes estrogen receptors in normal salivary gland and salivary gland cancers. With the use of a monoclonal antibody against estrogen receptor protein and the avidin-biotin immunoperoxidase procedure, we were unable to demonstrate estrogen receptors in formalin-fixed paraffin-embedded sections of either polymorphous low-grade adenocarcinoma or adenoid cystic carcinoma of salivary gland origin. (ORAL SURC ORAL MED &AL PATHOL 1994;7736-40)
Certain salivary gland tumors are remarkably similar histologically to adenocarcinomas of the breast. For example, the polymorphous low-grade adenocarcinoma (PLGA) of minor salivary gland origin has microscopic features that mimic those of infiltrating lobular carcinoma of the breast.lm7 In addition, the majority of reported cases of PLGA have been in females, Adenoid cystic carcinomas (ACC) of salivary gland origin are indistinguishable histologically from ACC of the breast and vulva.*, 9 Over the past 25 years, a number of reports have appeared in the literature of a possible association between salivary gland cancer and breast cancer; these reports are based primarily on clinical observations and tumor registry data.‘O-I4 One article analyzes estrogen receptors (ER) in normal salivary gland and salivary gland carcinoma.15 The authors reported that eight of nine salivary gland tumors in women had ER levels that would be considered hormone-dependent in breast carcinoma. Four of these reported cases were ACC; three in females and one in a male. The purpose of this study was to determine, with the use of immunohistochemistry, if ER can be identified in formalin-fixed paraffin-embedded tumor cells of PLGA and ACC and to compare the immunoperoxidase reaction with known samples of infiltrating lobular carcinoma of the breast. Positive results might suggest that endogenous estrogen could influence the development of some salivary gland tumors. =Department of Pathology, Temple University School of Medicine. bDepartment of Pathology, Medical College of Pennsylvania. =Department of Surgery, Temple University School of Medicine. Copyright @ 1994 by Mosby-Year Book, Inc. 0030-4220/93/$1.00 + .I0 7/14/48701
36
MATERIAL AND METHODS
Cases coded as PLGA and ACC were identified and retrieved from the files of the Oral Pathology Laboratory, Temple University School of Medicine, and the section of Surgical Pathology, Temple University Hospital (TUH). Slides were reviewed to confirm the diagnoses. Five PLGA of minor salivary gland origin yielded sufficient paraffin-embedded tissue for immunohistochemical sections. Five cases of ACC were selected, four of minor salivary gland origin and one from sublingual gland. Immunocytochemical assay for the identification of human ER was performed on each block of formalinfixed, paraffin-embedded study tissue. Sensitivity of the procedure was established by comparing similarly prepared known cases of infiltrating lobular carcinoma of the breast from the files of TUH. Positive control tissue was from infiltrating lobular carcinoma of the breast used regularly as a control in evaluating breast tumors at the Medical College of Pennsylvania (MCP). All breast tissues were processed concurrently with the salivary gland tumors in batches with current surgical cases from MCP. Adjacent sections of each specimen provided negative controls. The ABBOTT ER-ICA monoclonal system (Abbott Laboratories, Diagnostics Division, Abbott Park, Ill.) was used. It uses a sensitive peroxidase antiperoxidase technique for visualization of ER through the use of a monoclonal antibody directed specifically against the ER protein. 16-‘* Diaminobenzidine is used as a chromogenic agent. This assay is based on direct antigenic recognition rather than on steroid binding activity. Comparable results are achieved with these two techniques. l9 Reddish-brown nuclear immunoreactivity is scored
Miller
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume
77. Number
et al.
37
1
Fig. 1. Expressionof ER shownby brown nuclearstainingof sectionof infiltrating lobular carcinomaof breast. (Immunostaining;original magnificationX 132.) Table I Tumor
Type
Age
Infiltrating lobular adenocarcinoma of the breast TUH-Control: 1 66 TUHControl2 62 MCP-Control Polymorphous low-grade adenocarcinoma 78 Case 1 Case 2 59 Case 3 Unknown Case 4 82 83 Case 5 Adenoid cystic carcinoma 31 Case 6 Case I 72 65 Case 8 Case 9 64 53 Case 10
Sex
Immunoreactivity to ER
Site
F F F
Breast Breast Breast
4+ 4+ 4f
F M F F F
Hard palate Soft palate Hard palate Mandibular vestibule Hard palate
0 0 0 0 0
M M F F M
Ventral tongue Nasal cavity Hard palate/ridge Buccal mucosa Sublingual gland
0 0 0 0 0
Scoring for immunoreactivity: 0 = negative; I+ = spotty staining; 2+ = up to 25% of tumor than 50% of tumor cells positive.20
as described by Regezi et al.*O This semiquantitative method usesa scale of 0 to 4+. Score of 0 indicates that the tissue is negative or nonreactive; 1+ = spotty staining; 2+ = up to 25% of tumor cells positive; 3+ = 25% to 50% of tumor cells positive; 4+ indicates that more than 50% of the tumor cell nuclei show positive reactions. RESULTS
Five casesof PLGA and five casesof ACC were retrieved from TUH files (Table I). Eight were of mi-
cells positive;
3+ = 25% to 50% of tumor
cells positive;
4+ = more
nor salivary gland origin, one casearosein the sublingual gland and one casein the nasal cavity. These lesions were compared with similarly fixed and prepared sectionsof infiltrating lobular carcinoma of the breast. Patients ranged from 37 years to 83 years. In one instance the patient’s age was not recorded. Six of the ten total caseswere females, four were males. With the use of the semiquantitative method of Regezi et a1,20two of the coauthors scoredthe two infiltrating lobular breast carcinomas from the TUH
38
Miller
et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY January 1994
Fig. 2. Sectionof PGLA with immunoperoxidase stain with specificmonoclonalantibody againstestrogen receptor.No tumor cellswere positive.A, Hematoxylin-eosinstain; original magnificationX 132.B, Immunostaining;original magnificationX 132.)
collection and the lobular breast carcinoma control provided by MCP as 4+ with over 50% of tumor nuclei staining (Fig. 1). All the remaining salivary gland tumor tissues were essentially negative for nuclear staining for ER (Figs. 2 and 3). Minor salivary gland acini and ducts adjacent to tumor elements did not exhibit reactivity. Dl!XUSSlON
The relationship of salivary gland cancer and breast cancer has intrigued investigators over the years as apparent correlations between the two have been observed and reported.10-‘4 Berg et al.‘O reported an
eightfold increase in breast cancer in patients with known cancersof major salivary glands. Dunn et a1.,12 with data from the California Tumor Registry, felt the eightfold risk to be an overestimate but did find the number of breast cancers in women with known salivary cancers to be twice the number expected. Abbey et a1.,14 with data from the Virginia Tumor Registry reported a four-to-fivefold increased risk. Prior and Waterhouse,13 with data from the Birmingham Regional Cancer Registry (England), reported an association between salivary gland and breast cancer and suggested other hormone-dependent sites are also at risk. Moertel and Elveback’ 1 could find no association
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY Volume 77, Number 1
Miller
et al.
39
Fig. 3. Section of ACC with immunoperoxidase stain with specificmonoclonalantibody againstestrogen receptor.No tumor cellswerepositive.A, Hematoxylin-eosinstain; original magnificationX 132.B, Immunostaining;original magnificationX 132.)
between breast cancer and salivary gland cancer in 297 women studied at the Mayo Clinic. Other parallels exist. The PLGA of salivary gland origin has microscopic features that have been reported as similar to those of infiltrating lobular carcinoma of the breast.” 2 Strands of tumor cells, often one cell in width (Indian file pattern) are loosely dispersed in a fibrous stroma. In most casesthe tumor cells are small and uniform with little pleomorphism. It is clear that the majority of reported casesof PLGA
have occurred in females,3-6,I5 and that ACC of salivary gland origin is more prevalent in females.6*l5 PLGA has been evaluated ultrastructurally21-23 and subjected to a variety of immunohistochemical procedures.6,20,24These studies have concluded that the tumor cellsexhibit markers for myoepithelial cells and luminal epithelial cells, and are probably ultimately derived from pluripotential reserve cells. PLGA casesalso show a considerable range of tumor heterogeneity as well as variation in their organiza-
40
Miller
et al.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY January 1994
tion.2’-23 This variation in differentiation characteristics probably accounts for the histologic diversity observed by many pathologists.23 Dimery et a1.15suggested the possibility that estrogen may act as a promoting factor for some salivary gland neoplasms. These suggestions were based on their study in which eight of nine salivary gland tumors had ER levels that would be considered hormone-dependent in breast carcinoma. Their study differed considerably from ours. They used fresh tissue obtained at surgery, which was then frozen in liquid nitrogen. The frozen tissue was pulverized, centrifuged, and the ER in the supernatant was determined by adding various concentrations of tritiated estradiol. The radioactivity was determined in a scintillation counter. Results of the immunohistochemical staining for ER in our laboratories were negative in each instance. We were unable to demonstrate ER with the use of the avidin-biotin immunoperoxidase procedure on formalin-fixed paraffin-embedded sections of PLGA or ACC. Further studies may be necessary to determine if salivary gland tumors indeed may be influenced by sex steroid hormone levels. REFERENCES I.
Freedman PD, Lumerman H. Lobular carcinoma of intraoral minor salivary gland origin: report of twelve cases. ORAL SURC ORAL
MED
ORAL
PATHOL
1983;56:157-65.
2. Batsakis JG, Pinkston GR, Luna MA, Byers RM, Sciubba JJ, Tillery GW. Adenocarcinoma of the oral cavity: a clinicopathologic study of terminal duct carcinoma. J Laryngol Otol 1983;97:825-35. 3. Evans HL, Batsakis JG. Polymorphous low-grade adenocarcinoma of minor salivary glands: a study of 14 cases of a distinctive neoplasm. Cancer 1984;53:935-42. 4. Frierson HF, Mills SE, Garland TA. Terminal duct carcinoma of minor glands: a nonpapillary subtype of polymorphous lowgrade adenocarcinoma. Am J Clin Path01 1985;84:8-14. 5. Aberle AM, Abrams AM, Bowe R, Melrose RJ, Handlers JP. Lobular (polymorphous low-grade) carcinoma of minor salivary glands: a clinicopathologic study of twenty cases. ORAL SURC
ORAL
MED
ORAL
PATHOL
1985;60:387-95.
6. Wenig BM, Gnepp DR. Polymorphous low-grade adenocarcinoma of minor salivary glands. In: Surgical pathology of the salivary glands, Vol. 25, In: Ellis GL, Auclair PL, Gnepp DR, ed. Major problems in pathology. Philadelphia: WB Saunders, 1991:390-411. I. Kumar V, Cotran RS, Robbins SL. Basic pathology, 5th ed. Philadelphia: WB Saunders, 1992:636-9. 8. Ro JY, Silva EG, Gallagher HS. Adenoid cystic carcinoma of the breast, Hum Path01 1987;18:1216-81.
9. Abrao FS, Marques AF, Marzionn F, Abrao MS, Junqueira LC, Torloni H. Adenoid cystic carcinoma of Bartholin’s gland: review of the literature and report of two cases, J Surg Oncol 1985;30: 132-7. 10. Berg JW, Hutter RV, Foote FW. The unique association hetween salivary gland cancer and breast cancer. JAMA 1968;204:77 l-4. Il. Moertel CG, Elveback LR. The association between salivary gland cancer and breast cancer. JAMA 1969;2 10:306-8. 12. Dunn J, Bragg K, Sautter C, Gardipee C. Breast cancer risk following a major salivary gland carcinoma. Cancer 1972;29:1343-6. 13. Prior P, Waterhouse JAH. Second primary cancers in patients withtumoursofthesalivaryglands. Br JCancer 1977;36:362-7. 14. Abbey LM, Schwab BH, Landau GC, Perkins ER. Incidence of second primary breast cancer among patients with a first primary salivary gland tumor. Cancer 1984;54:1439-42. 15. Dimery IW, Jones LA, Verjan RP, Raymond AK, Goepfert H, Hong WK. Estrogen receptors in normal salivary gland and salivary gland carcinoma. Arch Otolaryngol Head Neck Surg 1987;113:1082-5. 16. Shintaku IP, Said JW. Detection of estrogen receptors with monoclonal antibodies in routinely processed formalin-fixed paraffin sections of breast carcinoma. Am J Clin Path01 1987;87:161-7. 17. Anderson J, Orntoft T, Poulsen HS. Semiquantitative estrogen receptor assay in formalin-fixed paraffin sections of human breast cancer using monoclonal antibodies. Br J Cancer 1986;53:691-4. 18. Masood S. Immunocytochemical localization of estrogen and progesterone receptor in imprint preparations of breast carcinomas Cancer 1992;70:2109-14. 19. King WJ, DeSombre ER, Jensen EV, Greene GL. Comparison of immunocytochemical and steroid-binding assays for estrogen receptor in human breast tumors. Cancer Res 1985;45:293-304. 20. Regezi JA, Zarbo RJ, Stewart JCB, Courtney RM. Polymorphous low-grade adenocarcinoma of minor salivary gland: a comparative histologic and immunohistochemical study. ORAL SLRG
ORAL
MED
ORAL
PATHOL
1991;71:469-75.
21. Nicolatou 0, Kakarantza-Angelopoulou E, Angelopoulos AP, Anagnostopoulou S. Polymorphous low-grade adenocarcinoma of the palate: report of a case with electon microscopy. J Oral Maxillofac Surg 1988;46:1008-13. 22. Dardick I, van Nostrand AWP. Polymorphous low-grade adenocarcinoma: a case report with ultrastructural findings. OR.AI.
SURG
ORAL
MED
ORAL
PATHOL
1988;66:459-65.
23. Norberg LE, Burford-Mason AP, Dardick I. entiation and morphologic heterogeniety in low-grade adenocarcinoma of minor salivary Path01 Med 199 I ;20:373-9. 24. Gnepp DR, Chen JC, Warren C. Polymorphous enocarcinoma of minor salivary gland origin: tochemical and clinicopathologic study. Am 1988;12:461-8. Reprint requests. Arthur S. Miller, DMD Temple University School Oral Pathology Section 3223 N. Broad Street Philadelphia, PA 19140
of Medicine
Cellular differpolymorphous gland. J Oral low-gradeadan immunohisJ Surg Pathol