Ann 0101 Rhinal LaryngoI99:1990
PATHOLOGY CONSULTATION
HISTOPATHOLOGIC GRADING OF SALIVARY GLAND NEOPLASMS: III. ADENOID CYSTIC CARCINOMAS JOHN G. BATSAKIS, MD MARIO A. LUNA, MD
ADEL EL-NAGGAR, MD, PHD HOUSTON, TEXAS
Histopathologic grading of adenoid cystic carcinomas can provide valuable prognostic information, particularly when the presence or absence of a solid growth architecture is noted. Other growth patterns, exemplified by a tubuloductal or cribriform-cylindromatous differentiation, are associated with a more protracted biologic course and less rapid mortality. A three-tiered grading system based on the three growth patterns of the carcinoma is presented.
If histopathologic grading of adenoid cystic carcinoma is less controversial than the grading of other salivary carcinomas, it may be that certain cytomorphologic features of the carcinoma are not completely aleatory to size, site, clinical stage, and completeness of resection of the neoplasm.
adenoid cystic carcinomas reported by Eby et al. 4 Patients without solid-type carcinomas had a prolonged course with survival for many years in spite of recurrences and metastases. Morinaga et al" have also shown that the prognosis of adenoid cystic carcinoma with a solid pattern is worse than that without in respect to 5- and lO-year survival rates. At 15 years, however, there was no difference between the two groups. The effect of a solid pattern on cumulative survival rates is also seen in data presented by Szanto et al. 6 Dividing their adenoid cystic carcinomas into three grades based on the presence and preponderance of a solid component, these authors found cumulative survival rates at 15 years of 39% (no solid), 26% (less than 30% solid), and 5 % (preponderantly solid). The carcinomas with a preponderantly solid architecture were larger, recurred frequently, and killed their hosts within 4 years. A solid cellular pattern negatively affected the survival period of adenoid cystic carcinomas of the maxillary sinus in the analysis reported by Buffoli et aLII The preponderantly solid carcinomas were also associated with a higher T stage than nonsolid carcinomas.
That a solid growth architecture in an adenoid cystic carcinoma imparts a more serious prognosis than any other architecture was first suggested a half century ago. I The validity of the observation has been underscored in subsequent studies and in the event has placed the solid adenoid cystic carcinoma (see Figure, A) at the histologically defined high-grade end of the neoplasm's light microscopic spectrum. 2-9 At the opposite or low-grade end of the spectrum is the tubular or tubuloductal adenoid cystic carcinoma (see Figure; B,C). The "classic" or cribriform-cylindromatous pattern lies between. These three cytoarchitectures form the basis of nearly every grading scheme for adenoid cystic carcinoma. Mode of invasion (broad front or pushing versus diffuse or tentacular), perineurial invasion, mitotic activity, necrosis, and cellular and nuclear pleomorphism are additional findings often incorporated in the grading of the carcinoma. 10
The incidence of lymphatic (noncontiguous involvement) metastases to regional lymph nodes from adenoid cystic carcinomas is known to be low. When present, the metastases have a dramatically adverse effect on survival. Stell et aP2 have indicated that such metastases occur more often in poorly differentiated (solid) adenoid cystic carcinomas. They also state that site and stage are not significant predictors of the probability of the metastases.
Eneroth et al,2.3 in dealing with adenoid cystic carcinoma at two different sites, the palate and submandibular gland, demonstrated that the solid form of the carcinoma was associated with a high mortality and, especially, a considerably shorter survival time than cribriform carcinomas. Using determinate survival statistics, Eneroth et al ' found a 17 % survival at 5 years and no survivors at 10 years for patients with solid adenoid cystic carcinomas of the palate. Cribriform carcinomas manifested 100 % and 62 % survival at 5 and 10 years, respectively. A fulminating course with early recurrence, metastasis, and a fatal outcome within 3 years of therapy also characterized the behavior of solid
In 1978, Perzin et al? described and introduced to surgical pathologists what they believed to be the most differentiated form of adenoid cystic carcinoma - the tubular pattern. Classifying 62 carcinomas according to their predominant histologic pat-
From the University of Texas M. D. Anderson Cancer Center, Houston, Texas. REPRINTS - John G. Batsakis, MD, Dept of Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
1007
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
1008
Batsakis et al, Pathology Consultation
_,>:I.
..
...,.
Adenoid cystic carcinomas. A) Solid form, manifesting no differentiation, central necrosis, mitoses, and cellular or nuclear pleomorphism (H & E, original x200). B) Tubular form, manifesting small ductal lumens and rather banal cytomorphology (H & E, original x200). C) Tubuloductal form, with tentacular invasion and invasion of small nerve (upper left) (H & E, original x60). D) Manifesting preponderantly solid growth pattern but with areas of cribriform differentiation (H & E, original x60). This coexistence of patterns is common, with assigned grade based on dominant pattern in carcinoma.
tern (tubular, cribriform, or solid), these investigators found a recurrence rate of 59 % with carcinomas demonstrating a preponderantly tubular pattern, as compared to 89 % for the cribriform lesions and 100 % for solid carcinomas. Of patients who died of their malignancy, those with tubular carcinomas had the longest course (average 9 years before death, in contrast to 8 years for cribriform and 5 years for solid carcinomas). Chilla et a1 8 . 9 have subsequently confirmed the distinctly favorable course exhibited by tubular adenoid cystic carcinomas. The foregoing suggests that histopathologic grading of adenoid cystic carcinoma has prognostic implications, especially as it relates to the carcinoma's two extremes of differentiation - tubular and solid. However, the greater importance of the clinical stage and its often linear relationship with the grade have prompted Spiro et a1'3-IS to reserve judgment of the impact of histologic appearance on prognosis.
The three grades of adenoid cystic carcinoma proposed in the Table represent a composite of criteria used by several other proponents of grading. Data reported by Caselitz et al " give an immunohistologic profile of the three basic cytoarchitectural patterns of the grades that, in turn, supports the reserve cell hypothesis of the histogenesis of the carcinomas. 1 7 Histologic grading should ideally be prospective, be applied to carcinomas presenting in a single anatomic region or salivary gland that are similarly staged, and be reproducible. Since the three basic growth patterns of adenoid cystic carcinoma are uncommon in a pure form, the assigned numeric grade has reflected the dominant pattern (see Figure, D). This subjective evaluation may suffice for carcinomas with tubular and cribriform-cylindromatous architectures, but the repeated demonstrations of poor patient outcome associated with a solid pattern require a more objective assessment. Szanto
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
Batsakis et al, Pathology Consultation
1009
THREE GRADES OF ADENOID CYSTIC CARCINOMA AND THEIR HlSTOCYTOLOGIC CHARACTERISTICS
Grade 1
Grade 2
Often circumscribed and usually smaller than other grades; may manifest capsule
May be deceptively circumscribed and, on rare occasions, encapsulated, particularly in major salivary glands Infiltrative growth is usual; more perineurial invasion than grade 1
Pushing, blunt, or diffuse infiltrative growth; perineurial invasion of small nerves can be present Definite tubular or ductal architecture; can simulate ductal monomorphic adenoma or terminal duct adenocarcinoma; cytologically banal; no or very rare mitoses Stromal changes usually not conspicuous; hyalinization not common; no necrosis Rarely present in pure form; usually coexists with cribriforrn-cylindromatous pattern
Cribriform and cylindromatous architecture; few to rare mitoses; cytologically less banal than grade 1; polymorphism and pleomorphism of cells mild to moderate Stromal changes usually prominent and may be striking; excessive hyalinization may obscure carcinoma; focal necrosis may be present Can present in pure form; if coexisting with tubular form, tubules exhibit more atypia than seen in usual grade 1
et al" and Greiner et al " have elected a 30 % solid component to signify a high-grade adenoid cystic carcinoma in their grading proposals. It is possible, however, that any measurable solid component in an otherwise cribriform or tubular adenoid cystic carcinoma portends a worse prognosis and shorter survival periods. While the impact of a solid architecture on patient outcome is strong, there is considerably less certainty of the significance of histologic evidence of perineurial invasion as it relates to survival. An absence of correlation has been reported by most investigators of the problem. 4-6.18-20 In none of the
Grade 3 Never circumscribed or encapsulated Infiltrative growth, nearly always diffuse; perineurial invasion readily identified Solid sheets and nests of atypical basaloid cells; "undifferentiated" appearance; mitoses easily found Variable stromal induction; necrosis easily found and may be comedo type Rarely present in pure form, and if so, may not be recognizable as adenoid cystic carcinoma; most often coexistswith grade 2 phenotype
studies, however, has the size of the invaded nerve been given. It may be that small nerve invasion, found in any of the three grades, does not carry the stigma of probable therapeutic failure seen in patients with preoperative facial nerve dysfunction. In view of the data derived from other grading systems for adenoid cystic carcinoma, it may be that the most important derivative of grading will be to identify those carcinomas with a rapidly progressive and lethal course. Other patients will manifest the traditionally accepted high morbidity and delayed mortality regardless of the level of differentiation or clinical stage.
REFERENCES 1. Patey DH, Thackray AC. The treatment of parotid tumors in the light of a pathological study of parotidectomy material. Br J Surg 1958;45:477-87.
11. Buffoli A, Olivetti L, Micheletti E, Facchetti F, Moretti R. Degree of malignancy of maxillary sinus cylindromas in relation to histologic characteristics. Tumori 1982;68: 127-31.
2. Eneroth C-M, Hjertman L, Moberger G. Adenoid cystic carcinoma of the palate. Acta Otolaryngol (Stockh) 1968;66: 248-60.
12. Stell PM, Cruickshank AH, Stoney PJ, McCormick MS. Lymph node metastases in adenoid cystic carcinoma. Am J Otolaryngol 1985;6:433-6.
3. Eneroth C-M, Hjertman L, Moberger G. Malignant tumors of the submandibular gland. Acta Otolaryngol (Stockh) 1967;64:514-36.
13. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg 1974;128:512-20.
4. Eby LS, Johnson DS, Baker HW. Adenoid cystic carcinoma of the head and neck. Cancer 1972;29: 1160-8.
14. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83.
5. Morinaga S, Nakajima T, Shimosato Y, Saitoh H, Ebihara S, Ono I. Histologic factors influencing prognosis of adenoid cystic carcinoma of the head and neck. Jpn J Clin OncoI1986;16: 29-40.
15. Spiro RH, Armstrong J, Harrison L, Geller NL, Lin S-Y, Strong EW. Carcinoma of major salivary glands. Recent trends. Arch Otolaryngol Head Neck Surg 1989;115:316-21.
6. Szanto PA, Luna MA, Tortoledo E, White RA. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 1984;54:1062-9. 7. Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinoma arising in salivary glands: a correlation of histologic features and clinical course. Cancer 1978;42:265-82. 8. Chilla R, Schroth R, Eysholdt V, Droese M. Adenoid cystic carcinoma of the head and neck. Controllable and uncontrollable factors in treatment and prognosis. ORL J Otorhinolaryngol Retat Spec 1980;42:346-67. 9. Chilla R, Schroth R, Eysholdt V, Droese M. Uber die therapeutische Beeinflusbarkeit adenoidzystischer Karzinome. HNO 1981;29: 118-23. 10. Santucci M, Bondi R. Histologic-prognostic correlations in adenoid cystic carcinoma of major and minor salivary glands of the oral cavity. Tumori 1986;72:293-300.
16. Caselitz J, Schulze I, Seifert G. Adenoid cystic carcinoma of the salivary glands: an immunohistochemical study. J Oral Pathoi 1986;15:308-18. 17. Batsakis JG, Reqezi JA, Luna MA, El-Naggar A. Histogenesis of salivary gland neoplasms: a postulate with prognostic implications. J Laryngol Otol 1989;103:939-44. 18. Greiner TC, Robinson RA, Maves MD. Adenoid cystic carcinoma. A clinicopathologic study with flow cytometric analysis. Am J Clin Pathol 1989;92:711-20. 19. Nascimento AG, Amaral ALP, Prado LAF, Kligerman J, Silveira TRP. Adenoid cystic carcinoma of salivary glands. A study of 61 cases with clinicopathologic correlation. Cancer 1986; 57:312-9. 20. Matsuba HM, Spector GJ, Thawley SE, Simpson JR, Mauney M, Pikul FJ. Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns. Cancer 1986;57:519-24.
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
PATHOLOGY CONSULTATION
HISTOPATHOLOGIC GRADING OF SALIVARY GLAND NEOPLASMS: III. ADENOID CYSTIC CARCINOMAS JOHN G. BATSAKIS, MD MARIO A. LUNA, MD
ADEL EL-NAGGAR, MD, PHD HOUSTON, TEXAS
Histopathologic grading of adenoid cystic carcinomas can provide valuable prognostic information, particularly when the presence or absence of a solid growth architecture is noted. Other growth patterns, exemplified by a tubuloductal or cribriform-cylindromatous differentiation, are associated with a more protracted biologic course and less rapid mortality. A three-tiered grading system based on the three growth patterns of the carcinoma is presented.
If histopathologic grading of adenoid cystic carcinoma is less controversial than the grading of other salivary carcinomas, it may be that certain cytomorphologic features of the carcinoma are not completely aleatory to size, site, clinical stage, and completeness of resection of the neoplasm.
adenoid cystic carcinomas reported by Eby et al. 4 Patients without solid-type carcinomas had a prolonged course with survival for many years in spite of recurrences and metastases. Morinaga et al" have also shown that the prognosis of adenoid cystic carcinoma with a solid pattern is worse than that without in respect to 5- and lO-year survival rates. At 15 years, however, there was no difference between the two groups. The effect of a solid pattern on cumulative survival rates is also seen in data presented by Szanto et al. 6 Dividing their adenoid cystic carcinomas into three grades based on the presence and preponderance of a solid component, these authors found cumulative survival rates at 15 years of 39% (no solid), 26% (less than 30% solid), and 5 % (preponderantly solid). The carcinomas with a preponderantly solid architecture were larger, recurred frequently, and killed their hosts within 4 years. A solid cellular pattern negatively affected the survival period of adenoid cystic carcinomas of the maxillary sinus in the analysis reported by Buffoli et aLII The preponderantly solid carcinomas were also associated with a higher T stage than nonsolid carcinomas.
That a solid growth architecture in an adenoid cystic carcinoma imparts a more serious prognosis than any other architecture was first suggested a half century ago. I The validity of the observation has been underscored in subsequent studies and in the event has placed the solid adenoid cystic carcinoma (see Figure, A) at the histologically defined high-grade end of the neoplasm's light microscopic spectrum. 2-9 At the opposite or low-grade end of the spectrum is the tubular or tubuloductal adenoid cystic carcinoma (see Figure; B,C). The "classic" or cribriform-cylindromatous pattern lies between. These three cytoarchitectures form the basis of nearly every grading scheme for adenoid cystic carcinoma. Mode of invasion (broad front or pushing versus diffuse or tentacular), perineurial invasion, mitotic activity, necrosis, and cellular and nuclear pleomorphism are additional findings often incorporated in the grading of the carcinoma. 10
The incidence of lymphatic (noncontiguous involvement) metastases to regional lymph nodes from adenoid cystic carcinomas is known to be low. When present, the metastases have a dramatically adverse effect on survival. Stell et aP2 have indicated that such metastases occur more often in poorly differentiated (solid) adenoid cystic carcinomas. They also state that site and stage are not significant predictors of the probability of the metastases.
Eneroth et al,2.3 in dealing with adenoid cystic carcinoma at two different sites, the palate and submandibular gland, demonstrated that the solid form of the carcinoma was associated with a high mortality and, especially, a considerably shorter survival time than cribriform carcinomas. Using determinate survival statistics, Eneroth et al ' found a 17 % survival at 5 years and no survivors at 10 years for patients with solid adenoid cystic carcinomas of the palate. Cribriform carcinomas manifested 100 % and 62 % survival at 5 and 10 years, respectively. A fulminating course with early recurrence, metastasis, and a fatal outcome within 3 years of therapy also characterized the behavior of solid
In 1978, Perzin et al? described and introduced to surgical pathologists what they believed to be the most differentiated form of adenoid cystic carcinoma - the tubular pattern. Classifying 62 carcinomas according to their predominant histologic pat-
From the University of Texas M. D. Anderson Cancer Center, Houston, Texas. REPRINTS - John G. Batsakis, MD, Dept of Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
1007
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
1008
Batsakis et al, Pathology Consultation
_,>:I.
..
...,.
Adenoid cystic carcinomas. A) Solid form, manifesting no differentiation, central necrosis, mitoses, and cellular or nuclear pleomorphism (H & E, original x200). B) Tubular form, manifesting small ductal lumens and rather banal cytomorphology (H & E, original x200). C) Tubuloductal form, with tentacular invasion and invasion of small nerve (upper left) (H & E, original x60). D) Manifesting preponderantly solid growth pattern but with areas of cribriform differentiation (H & E, original x60). This coexistence of patterns is common, with assigned grade based on dominant pattern in carcinoma.
tern (tubular, cribriform, or solid), these investigators found a recurrence rate of 59 % with carcinomas demonstrating a preponderantly tubular pattern, as compared to 89 % for the cribriform lesions and 100 % for solid carcinomas. Of patients who died of their malignancy, those with tubular carcinomas had the longest course (average 9 years before death, in contrast to 8 years for cribriform and 5 years for solid carcinomas). Chilla et a1 8 . 9 have subsequently confirmed the distinctly favorable course exhibited by tubular adenoid cystic carcinomas. The foregoing suggests that histopathologic grading of adenoid cystic carcinoma has prognostic implications, especially as it relates to the carcinoma's two extremes of differentiation - tubular and solid. However, the greater importance of the clinical stage and its often linear relationship with the grade have prompted Spiro et a1'3-IS to reserve judgment of the impact of histologic appearance on prognosis.
The three grades of adenoid cystic carcinoma proposed in the Table represent a composite of criteria used by several other proponents of grading. Data reported by Caselitz et al " give an immunohistologic profile of the three basic cytoarchitectural patterns of the grades that, in turn, supports the reserve cell hypothesis of the histogenesis of the carcinomas. 1 7 Histologic grading should ideally be prospective, be applied to carcinomas presenting in a single anatomic region or salivary gland that are similarly staged, and be reproducible. Since the three basic growth patterns of adenoid cystic carcinoma are uncommon in a pure form, the assigned numeric grade has reflected the dominant pattern (see Figure, D). This subjective evaluation may suffice for carcinomas with tubular and cribriform-cylindromatous architectures, but the repeated demonstrations of poor patient outcome associated with a solid pattern require a more objective assessment. Szanto
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
Batsakis et al, Pathology Consultation
1009
THREE GRADES OF ADENOID CYSTIC CARCINOMA AND THEIR HlSTOCYTOLOGIC CHARACTERISTICS
Grade 1
Grade 2
Often circumscribed and usually smaller than other grades; may manifest capsule
May be deceptively circumscribed and, on rare occasions, encapsulated, particularly in major salivary glands Infiltrative growth is usual; more perineurial invasion than grade 1
Pushing, blunt, or diffuse infiltrative growth; perineurial invasion of small nerves can be present Definite tubular or ductal architecture; can simulate ductal monomorphic adenoma or terminal duct adenocarcinoma; cytologically banal; no or very rare mitoses Stromal changes usually not conspicuous; hyalinization not common; no necrosis Rarely present in pure form; usually coexists with cribriforrn-cylindromatous pattern
Cribriform and cylindromatous architecture; few to rare mitoses; cytologically less banal than grade 1; polymorphism and pleomorphism of cells mild to moderate Stromal changes usually prominent and may be striking; excessive hyalinization may obscure carcinoma; focal necrosis may be present Can present in pure form; if coexisting with tubular form, tubules exhibit more atypia than seen in usual grade 1
et al" and Greiner et al " have elected a 30 % solid component to signify a high-grade adenoid cystic carcinoma in their grading proposals. It is possible, however, that any measurable solid component in an otherwise cribriform or tubular adenoid cystic carcinoma portends a worse prognosis and shorter survival periods. While the impact of a solid architecture on patient outcome is strong, there is considerably less certainty of the significance of histologic evidence of perineurial invasion as it relates to survival. An absence of correlation has been reported by most investigators of the problem. 4-6.18-20 In none of the
Grade 3 Never circumscribed or encapsulated Infiltrative growth, nearly always diffuse; perineurial invasion readily identified Solid sheets and nests of atypical basaloid cells; "undifferentiated" appearance; mitoses easily found Variable stromal induction; necrosis easily found and may be comedo type Rarely present in pure form, and if so, may not be recognizable as adenoid cystic carcinoma; most often coexistswith grade 2 phenotype
studies, however, has the size of the invaded nerve been given. It may be that small nerve invasion, found in any of the three grades, does not carry the stigma of probable therapeutic failure seen in patients with preoperative facial nerve dysfunction. In view of the data derived from other grading systems for adenoid cystic carcinoma, it may be that the most important derivative of grading will be to identify those carcinomas with a rapidly progressive and lethal course. Other patients will manifest the traditionally accepted high morbidity and delayed mortality regardless of the level of differentiation or clinical stage.
REFERENCES 1. Patey DH, Thackray AC. The treatment of parotid tumors in the light of a pathological study of parotidectomy material. Br J Surg 1958;45:477-87.
11. Buffoli A, Olivetti L, Micheletti E, Facchetti F, Moretti R. Degree of malignancy of maxillary sinus cylindromas in relation to histologic characteristics. Tumori 1982;68: 127-31.
2. Eneroth C-M, Hjertman L, Moberger G. Adenoid cystic carcinoma of the palate. Acta Otolaryngol (Stockh) 1968;66: 248-60.
12. Stell PM, Cruickshank AH, Stoney PJ, McCormick MS. Lymph node metastases in adenoid cystic carcinoma. Am J Otolaryngol 1985;6:433-6.
3. Eneroth C-M, Hjertman L, Moberger G. Malignant tumors of the submandibular gland. Acta Otolaryngol (Stockh) 1967;64:514-36.
13. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg 1974;128:512-20.
4. Eby LS, Johnson DS, Baker HW. Adenoid cystic carcinoma of the head and neck. Cancer 1972;29: 1160-8.
14. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83.
5. Morinaga S, Nakajima T, Shimosato Y, Saitoh H, Ebihara S, Ono I. Histologic factors influencing prognosis of adenoid cystic carcinoma of the head and neck. Jpn J Clin OncoI1986;16: 29-40.
15. Spiro RH, Armstrong J, Harrison L, Geller NL, Lin S-Y, Strong EW. Carcinoma of major salivary glands. Recent trends. Arch Otolaryngol Head Neck Surg 1989;115:316-21.
6. Szanto PA, Luna MA, Tortoledo E, White RA. Histologic grading of adenoid cystic carcinoma of the salivary glands. Cancer 1984;54:1062-9. 7. Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinoma arising in salivary glands: a correlation of histologic features and clinical course. Cancer 1978;42:265-82. 8. Chilla R, Schroth R, Eysholdt V, Droese M. Adenoid cystic carcinoma of the head and neck. Controllable and uncontrollable factors in treatment and prognosis. ORL J Otorhinolaryngol Retat Spec 1980;42:346-67. 9. Chilla R, Schroth R, Eysholdt V, Droese M. Uber die therapeutische Beeinflusbarkeit adenoidzystischer Karzinome. HNO 1981;29: 118-23. 10. Santucci M, Bondi R. Histologic-prognostic correlations in adenoid cystic carcinoma of major and minor salivary glands of the oral cavity. Tumori 1986;72:293-300.
16. Caselitz J, Schulze I, Seifert G. Adenoid cystic carcinoma of the salivary glands: an immunohistochemical study. J Oral Pathoi 1986;15:308-18. 17. Batsakis JG, Reqezi JA, Luna MA, El-Naggar A. Histogenesis of salivary gland neoplasms: a postulate with prognostic implications. J Laryngol Otol 1989;103:939-44. 18. Greiner TC, Robinson RA, Maves MD. Adenoid cystic carcinoma. A clinicopathologic study with flow cytometric analysis. Am J Clin Pathol 1989;92:711-20. 19. Nascimento AG, Amaral ALP, Prado LAF, Kligerman J, Silveira TRP. Adenoid cystic carcinoma of salivary glands. A study of 61 cases with clinicopathologic correlation. Cancer 1986; 57:312-9. 20. Matsuba HM, Spector GJ, Thawley SE, Simpson JR, Mauney M, Pikul FJ. Adenoid cystic salivary gland carcinoma. A histopathologic review of treatment failure patterns. Cancer 1986;57:519-24.
Downloaded from aor.sagepub.com at The University of Iowa Libraries on June 24, 2015
