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Malignant degeneration of pleomorphic adenoma—Clinical implications
Malignant Degeneration of Pleomorphic Adenoma-Clinical Implications SIGSBEE W. DUCK, MD, AND FRED M. S. McCONNEL,
MD
Introduction: The incidence of carcinoma arising in a pleomorphic adenoma is reportedly between 1.4% and 6.3%. Malignant degeneration is often associated with a prolonged history of untreated or recurrent pleomorphic adenoma. Materials and Methods: Two patients with malignant parotid carcinoma that arose from benign pleomorphic adenoma are reviewed. Results: Both patients exhibited a prolonged history of pleomorphic adenoma apparently persistent after initial inadequate surgery. Surgeries were performed 37 and 12 years before development of malignancy. Discussion: The phenomenon of malignant carcinoma arising from benign pleomorphic adenoma is an important issue. The occurrence of these malignant carcinomas emphasizes that aggressive treatment of primary and recurrent mixed tumors is necessary. Copyright 0 1993 by W.B. Saunders Company
The occurrence of carcinoma arising from a pleomorphic adenoma is uncommon, with an incidence reported between 1.4% to 6.3%’ However, the occurrence of carcinomas in pleomorphic adenomas with the passage of time is another reason for complete removal of the pleomorphic adenoma at the time of original surgery. In the treatment of pleomorphic adenomas, simple lumpectomies have fallen into disfavor in comparison with superficial parotidectomies. Simple lumpectomies are reported to be associated with an unacceptably high recurrence rate.’ However, the clinical question remains, if when a superficial parotidectomy is inadequate in its deep margins, is the only other option a total parotidectomy? CASE HISTORIES Case No. 1 A 63-year-old woman presented with a chief complaint of a mass in the right side of the neck. The patient had a benign mixed tumor removed
From St Joseph Hospital, Atlanta, GA, and the Department of Surgery, Emory University, Atlanta, GA. Presented at the Triological Society-Southern tion, Sea Island, GA, January 17, 1992. Address reprint requests to Fred M. S. McConnel, 180 Blackland Dr, Atlanta, GA 30342. Copyright 0 1993 by W.B. Saunders Company 0196-0709/93/l 403-0005$5.00/O
SecMD,
American Journal of Otolaryngology,
from the right parotid gland some 37 years previously. The type of prior parotid surgery could not be determined. The patient had no problems until she developed fullness in the right side of her neck 3 months before presentation. A neck biopsy was performed at another institution, which was read as poorly differentiated large cell carcinoma. A computed tomography scan was obtained, which showed a large mass in the parapharyngeal space, possibly involving the deep lobe of the parotid with multiple metastatic nodes in the right side of the neck. Multiple endoscopy with biopsies of the nasopharynx, tonsil, base of tongue, and pyriform sinuses were performed in a workup to rule out other sources of the neck metastasis. All biopsies were negative. The patient underwent a right radical neck dissection and total parotidectomy. The patient seemed to have a remaining superficial lobe of the parotid gland, therefore a total narotidectomy with facial nerve preservation was p&formed. Microscopic findings were a poorly differentiated adenocarcinoma arising in a pleomorphic adenoma (Figs 1, 2, 3, and 4). The poorly differentiated adenocarcinoma evolves into areas showing a large cell undifferentiated carcinoma pattern. Nearly all lymph nodes in the anterior and posterior cervical triangle along with the jugular chain showed bulky metastatic poorly differentiated adenocarcinoma. The lymph nodes were totally replaced by tumor. Vascular and lymphatic invasion were observed. The midjugular vein showed tumor invading through the wall and showed a polypoid tumor within the lumen. The patient did well postoperatively, with no facial weakness. Irradiation therapy was administered to the parotid and neck. The natient progressed to haie distal metastatic diseaie in several months.
Vol 14, No 3 (May-June),
1993: pp 175-178
175
176
DUCK AND McCONNEL
cinema expleomorphic adenoma and primary “malignant mixed tumors.” In the literature, these terms have been used interchangeably or lumped as the same entity.3-” According to Tortoledo et a1,7 carcinoma expleomorphic adenoma is an epithelial malignancy in which the remnants of a mixed tumor matrix can be identified. The true malignant mixed tumor is rare in contrast to the expleomorphic adenoma. This tumor requires a biphasic heterologous tissue composition, consisting of a definable carcinoma in a histologically malignant sarcoma. Therefore, a pleomorphic adenoma may transform into a true malignant mixed tumor, a noninvasive carcinoma (in-situ), or a carcinoma expleomorphic adenoma (low or high grade). In the literature, many times “true malignant mixed tumors” are grouped with the carcinoma expleomorphic adenomas histologically as well as when determining survival rates.8 True “malignant mixed tumors” have a
Fig 1. Residual hyalinized area of pleomorphic adenoma on the right, with areas of infiltrating poorly differentiated adenocarcinoma of the left, with lymphocytic stromal reaction.
Case
No. 2
A 4%year-old white man presented with a mass in the left parotid. He had reported a marked increase in the size of the mass over the previous 6 months, and numbness in the left temporal area. The parotid surgery had been performed some 12 years previously for a reportedly benign mixed tumor. The type of initial surgery was not documented. On physical exam the patient had a 2.5 X 2 cm mass in the left parotid gland. There also was a 2 cm x 3 cm node in the left upper neck. A left total parotidectomy and left neck dissection were performed. The facial nerve was sacrificed and a sural nerve graft was used for reconstruction. Pathology showed a poorly differentiated carcinoma in a pleomorphic adenoma of the superficial deep lobe. Metastatic carcinoma was found in 28 of 36 lymph nodes examined in the neck dissection. The patient had postoperative irradiation. Three months later he was noted to have a metastatic lesion in the lung.
DISCUSSION When considering malignant mixed tumors the distinction should be made between car-
Fig 2. Areas of hyalinired stroma containing benignappearing spindle cells conristent with residual pleomorphic adenoma, with a mixture of cribriform and papillary tumor representing adenocarcinoma.
MALIGNANT DEGENERATION OF PLEOMORPHIC ADENOMA
177
months, whereas superficial parotidectomies had a recurrence time of 7.7 years.’ Fitzpatrick and Theriaultll found a 54% rate of successful surgical treatment of malignant tumors after initial surgery. This series consisted of a retrospective review of 403 patients with malignant tumors who were followed up for 10 years. Theriault and FitzpatrickI’ reported a series of 271 patients with parotid carcinomas observed over a 20-year period. They noted a 46% success rate of primary surgical treatment for malignant tumors. Residual disease was left in 15% of patients, and recurrence appeared later in 38.5%. No time frame was given for the time to recurrences. Patients treated with combined therapy had a recurrence rate of 22% compared with 62% for those treated by surgery alone.” More specifically, in a retrospective review of 2,211 cases at M. D. Anderson by Stephens et a1,13 11 cases of “malignant mixed tumors” were reviewed. Of these cases, four patients fulfilled the histological criteria for preexist-
Pig 3. Poorly differentiated adenocarcinoma, with a few small foci residual hyalinized pleomorphic adenoma.
poorer prognosis than carcinoma expleomorphic adenoma.7 A combined survival rate as reported by Whitten et al,’ is approximately 25% at 10 years. Patey et al,’ state that at least 50% of the parotid gland carcinomas arise from benign mixed pleomorphic adenomas, and stress that proper initial treatment can reduce the incidence of this tumor. Patey et al have also shown the presence of fingerlike projections of the tumor passing through the capsule. These pseudo-pods are felt to be the most probable reason for recurrence. Conley and Clairmontl’ have proposed the possibility of a multicentric origin of benign mixed tumors. However, most investigators feel that with the exception of capsular rupture with implantation, the most likely cause of recurrence is inadequate removal of the tumor at the time of primary treatment. This trend is observed when the recurrences after lumpectomy are compared with superficial parotidectomy. Simple lumpectomies were noted to have an average recurrence time of IO
Fig 4. A nerve with edema, showing perineural and intraneural infiltration by adenocarcinoma and adjacent unremarkable parotid tissue.
178
ing benign mixed tumors, or carcinoma developing in a previously existing benign mixed tumor. The time between initial treatment and recurrence varied from 10 to 50 years. Two of the four patients with histological evidence of pleomorphic adenoma had recurrences of their benign tumors over a 17-year period. This review does histologically separate carcinoma developing in previous benign mixed tumors from initial malignant mixed tumors. As we have noted, other series do not make this distinction, and it is difficult to interpret their results. However, a true “malignant mixed tumor” seems to have a more serious outcome with the series we reviewed reporting a 0% to 50% survival rate. Patients with carcinomas developing in previous pleomorphic adenomas had survival rates reported between 25% and 50%.7*14 With the occurrence of malignancy in expleomorphic adenomas, the best treatment is complete removal at the time of initial surgery, No less than a superficial parotidectomy should be performed in the treatment of these lesions. If the tumor is against the nerve, or if a superficial parotidectomy does not provide an adequate margin of normal tissue around the benign mixed tumor, then a near-total parotidectomy is indicated. An initial treatment sacrifice of the facial nerve is not indicated in most cases, unless the procedure cannot be technically performed with preservation of the nerve with an adequate margin of normal tissue. When performing a near-total parotidectomy, lumpectomies of the deep lobe should be discouraged, as should lumpectomies of the superficial lobe, because they have been shown to have a high rate of recurrence. The treatment plan for a carcinoma expleomorphic adenoma should include (if the mass is confined to the parotid gland] a total parotidectomy. If the lymph nodes are present, a radical neck dissection is indicated. If the tumor is in the deep lobe of the parotid, a neck dissection in many cases can facilitate a total
DUCK AND McCONNEL
parotidectomy and assure exposure of the internal carotid artery. If problems with exposure occur, the surgeon should not hesitate to perform a partial mandibulectomy or mandibulotomy to extirpate the entire deep lobe of the parotid gland. The best treatment for carcinoma expleomorphic adenoma is aggressive initial treatment. We recommend radiation therapy in essentially all cases, particularly those with clinically and histologically extensive neck disease. REFERENCES 1. Yoav PT, et al: View from beneath: Pathology in focus, true malignant mixed tumours of the parotid gland. J Laryngol Otol 104:360-361, 1990 2. Maran AG, Mackenzie IJ, Stanley RE: Recurrent pleomorphic adenomas of the parotid gland. Arch Otolaryngol 110:167-171, 1984 3. Whitten J, Hybert F, Hansen HS: Treatment of malignant tumors in parotid glands. Cancer 65:2515-2520,
1990 4. Spiro RH, Huvos AG, Stong EW: Malignant
mixed of salivary origin, a clinicopathological study of 146 cases. Cancer 39:388-396, 1977 5. Gerughty TM, Scofield HH, Brown FM, et al: Malignant mixed tumours of salivary gland origin. Cancer 24:
tumors
471-486,1969 6. Saksela E, Tarkkanen J, Kohonen A: The malignancy of mixed tumours of the salivary gland. A clinicopathological analysis of 70 cases. ACTA Otolaryngol 70:62-70,
1970 7. Tortoledo
ME, Luna MA, Batsakis JG: Carcinomas expleomorphic adenoma and malignant mixed tumours. Arch Otoktryngol 110:172-178, 1984 8. Whitten J, Hybert F, Hansen HS: Treatment of malignant mixed tumours of salivary origin, a clinicopathological study of 146 cases. Cancer 39:388-396, 1977 9. Patey DH, Thackray AC, Keeling DH: Malignant disease of the parotid. Br J Cancer 19:172-737, 1965 10. Conley J, Clairmont AA: Facial nerve in recurrent pleomorphic adenomas. Arch Otolaryngol 105:247-251,
1979 11. Fitzpatrick
PJ, Theriault C: Malignant salivary gland tumors. J Rad Oncol Biophys 12:1743-1747, 1986 12.Theriault C, Fitzpatrick PJ: Malignant parotid tumours-Prognostic factors and optimum treatment. Am J Clin Oncol 9:510-516, 1986 13. Stephens J, Batsakis JG, Luna MA, et al: True malignant mixed tumours (carcinosarcoma] of salivary alands. Oral Surg Oral Med Oral Path01 61:597-602, 1986 14. Batsakis JG: Tumours of the head and neck, in Clinical and Pathological Considerations, (ed 2). Baltimore, MD, Williams and Wilkins, pp. 26-30.
MD
Introduction: The incidence of carcinoma arising in a pleomorphic adenoma is reportedly between 1.4% and 6.3%. Malignant degeneration is often associated with a prolonged history of untreated or recurrent pleomorphic adenoma. Materials and Methods: Two patients with malignant parotid carcinoma that arose from benign pleomorphic adenoma are reviewed. Results: Both patients exhibited a prolonged history of pleomorphic adenoma apparently persistent after initial inadequate surgery. Surgeries were performed 37 and 12 years before development of malignancy. Discussion: The phenomenon of malignant carcinoma arising from benign pleomorphic adenoma is an important issue. The occurrence of these malignant carcinomas emphasizes that aggressive treatment of primary and recurrent mixed tumors is necessary. Copyright 0 1993 by W.B. Saunders Company
The occurrence of carcinoma arising from a pleomorphic adenoma is uncommon, with an incidence reported between 1.4% to 6.3%’ However, the occurrence of carcinomas in pleomorphic adenomas with the passage of time is another reason for complete removal of the pleomorphic adenoma at the time of original surgery. In the treatment of pleomorphic adenomas, simple lumpectomies have fallen into disfavor in comparison with superficial parotidectomies. Simple lumpectomies are reported to be associated with an unacceptably high recurrence rate.’ However, the clinical question remains, if when a superficial parotidectomy is inadequate in its deep margins, is the only other option a total parotidectomy? CASE HISTORIES Case No. 1 A 63-year-old woman presented with a chief complaint of a mass in the right side of the neck. The patient had a benign mixed tumor removed
From St Joseph Hospital, Atlanta, GA, and the Department of Surgery, Emory University, Atlanta, GA. Presented at the Triological Society-Southern tion, Sea Island, GA, January 17, 1992. Address reprint requests to Fred M. S. McConnel, 180 Blackland Dr, Atlanta, GA 30342. Copyright 0 1993 by W.B. Saunders Company 0196-0709/93/l 403-0005$5.00/O
SecMD,
American Journal of Otolaryngology,
from the right parotid gland some 37 years previously. The type of prior parotid surgery could not be determined. The patient had no problems until she developed fullness in the right side of her neck 3 months before presentation. A neck biopsy was performed at another institution, which was read as poorly differentiated large cell carcinoma. A computed tomography scan was obtained, which showed a large mass in the parapharyngeal space, possibly involving the deep lobe of the parotid with multiple metastatic nodes in the right side of the neck. Multiple endoscopy with biopsies of the nasopharynx, tonsil, base of tongue, and pyriform sinuses were performed in a workup to rule out other sources of the neck metastasis. All biopsies were negative. The patient underwent a right radical neck dissection and total parotidectomy. The patient seemed to have a remaining superficial lobe of the parotid gland, therefore a total narotidectomy with facial nerve preservation was p&formed. Microscopic findings were a poorly differentiated adenocarcinoma arising in a pleomorphic adenoma (Figs 1, 2, 3, and 4). The poorly differentiated adenocarcinoma evolves into areas showing a large cell undifferentiated carcinoma pattern. Nearly all lymph nodes in the anterior and posterior cervical triangle along with the jugular chain showed bulky metastatic poorly differentiated adenocarcinoma. The lymph nodes were totally replaced by tumor. Vascular and lymphatic invasion were observed. The midjugular vein showed tumor invading through the wall and showed a polypoid tumor within the lumen. The patient did well postoperatively, with no facial weakness. Irradiation therapy was administered to the parotid and neck. The natient progressed to haie distal metastatic diseaie in several months.
Vol 14, No 3 (May-June),
1993: pp 175-178
175
176
DUCK AND McCONNEL
cinema expleomorphic adenoma and primary “malignant mixed tumors.” In the literature, these terms have been used interchangeably or lumped as the same entity.3-” According to Tortoledo et a1,7 carcinoma expleomorphic adenoma is an epithelial malignancy in which the remnants of a mixed tumor matrix can be identified. The true malignant mixed tumor is rare in contrast to the expleomorphic adenoma. This tumor requires a biphasic heterologous tissue composition, consisting of a definable carcinoma in a histologically malignant sarcoma. Therefore, a pleomorphic adenoma may transform into a true malignant mixed tumor, a noninvasive carcinoma (in-situ), or a carcinoma expleomorphic adenoma (low or high grade). In the literature, many times “true malignant mixed tumors” are grouped with the carcinoma expleomorphic adenomas histologically as well as when determining survival rates.8 True “malignant mixed tumors” have a
Fig 1. Residual hyalinized area of pleomorphic adenoma on the right, with areas of infiltrating poorly differentiated adenocarcinoma of the left, with lymphocytic stromal reaction.
Case
No. 2
A 4%year-old white man presented with a mass in the left parotid. He had reported a marked increase in the size of the mass over the previous 6 months, and numbness in the left temporal area. The parotid surgery had been performed some 12 years previously for a reportedly benign mixed tumor. The type of initial surgery was not documented. On physical exam the patient had a 2.5 X 2 cm mass in the left parotid gland. There also was a 2 cm x 3 cm node in the left upper neck. A left total parotidectomy and left neck dissection were performed. The facial nerve was sacrificed and a sural nerve graft was used for reconstruction. Pathology showed a poorly differentiated carcinoma in a pleomorphic adenoma of the superficial deep lobe. Metastatic carcinoma was found in 28 of 36 lymph nodes examined in the neck dissection. The patient had postoperative irradiation. Three months later he was noted to have a metastatic lesion in the lung.
DISCUSSION When considering malignant mixed tumors the distinction should be made between car-
Fig 2. Areas of hyalinired stroma containing benignappearing spindle cells conristent with residual pleomorphic adenoma, with a mixture of cribriform and papillary tumor representing adenocarcinoma.
MALIGNANT DEGENERATION OF PLEOMORPHIC ADENOMA
177
months, whereas superficial parotidectomies had a recurrence time of 7.7 years.’ Fitzpatrick and Theriaultll found a 54% rate of successful surgical treatment of malignant tumors after initial surgery. This series consisted of a retrospective review of 403 patients with malignant tumors who were followed up for 10 years. Theriault and FitzpatrickI’ reported a series of 271 patients with parotid carcinomas observed over a 20-year period. They noted a 46% success rate of primary surgical treatment for malignant tumors. Residual disease was left in 15% of patients, and recurrence appeared later in 38.5%. No time frame was given for the time to recurrences. Patients treated with combined therapy had a recurrence rate of 22% compared with 62% for those treated by surgery alone.” More specifically, in a retrospective review of 2,211 cases at M. D. Anderson by Stephens et a1,13 11 cases of “malignant mixed tumors” were reviewed. Of these cases, four patients fulfilled the histological criteria for preexist-
Pig 3. Poorly differentiated adenocarcinoma, with a few small foci residual hyalinized pleomorphic adenoma.
poorer prognosis than carcinoma expleomorphic adenoma.7 A combined survival rate as reported by Whitten et al,’ is approximately 25% at 10 years. Patey et al,’ state that at least 50% of the parotid gland carcinomas arise from benign mixed pleomorphic adenomas, and stress that proper initial treatment can reduce the incidence of this tumor. Patey et al have also shown the presence of fingerlike projections of the tumor passing through the capsule. These pseudo-pods are felt to be the most probable reason for recurrence. Conley and Clairmontl’ have proposed the possibility of a multicentric origin of benign mixed tumors. However, most investigators feel that with the exception of capsular rupture with implantation, the most likely cause of recurrence is inadequate removal of the tumor at the time of primary treatment. This trend is observed when the recurrences after lumpectomy are compared with superficial parotidectomy. Simple lumpectomies were noted to have an average recurrence time of IO
Fig 4. A nerve with edema, showing perineural and intraneural infiltration by adenocarcinoma and adjacent unremarkable parotid tissue.
178
ing benign mixed tumors, or carcinoma developing in a previously existing benign mixed tumor. The time between initial treatment and recurrence varied from 10 to 50 years. Two of the four patients with histological evidence of pleomorphic adenoma had recurrences of their benign tumors over a 17-year period. This review does histologically separate carcinoma developing in previous benign mixed tumors from initial malignant mixed tumors. As we have noted, other series do not make this distinction, and it is difficult to interpret their results. However, a true “malignant mixed tumor” seems to have a more serious outcome with the series we reviewed reporting a 0% to 50% survival rate. Patients with carcinomas developing in previous pleomorphic adenomas had survival rates reported between 25% and 50%.7*14 With the occurrence of malignancy in expleomorphic adenomas, the best treatment is complete removal at the time of initial surgery, No less than a superficial parotidectomy should be performed in the treatment of these lesions. If the tumor is against the nerve, or if a superficial parotidectomy does not provide an adequate margin of normal tissue around the benign mixed tumor, then a near-total parotidectomy is indicated. An initial treatment sacrifice of the facial nerve is not indicated in most cases, unless the procedure cannot be technically performed with preservation of the nerve with an adequate margin of normal tissue. When performing a near-total parotidectomy, lumpectomies of the deep lobe should be discouraged, as should lumpectomies of the superficial lobe, because they have been shown to have a high rate of recurrence. The treatment plan for a carcinoma expleomorphic adenoma should include (if the mass is confined to the parotid gland] a total parotidectomy. If the lymph nodes are present, a radical neck dissection is indicated. If the tumor is in the deep lobe of the parotid, a neck dissection in many cases can facilitate a total
DUCK AND McCONNEL
parotidectomy and assure exposure of the internal carotid artery. If problems with exposure occur, the surgeon should not hesitate to perform a partial mandibulectomy or mandibulotomy to extirpate the entire deep lobe of the parotid gland. The best treatment for carcinoma expleomorphic adenoma is aggressive initial treatment. We recommend radiation therapy in essentially all cases, particularly those with clinically and histologically extensive neck disease. REFERENCES 1. Yoav PT, et al: View from beneath: Pathology in focus, true malignant mixed tumours of the parotid gland. J Laryngol Otol 104:360-361, 1990 2. Maran AG, Mackenzie IJ, Stanley RE: Recurrent pleomorphic adenomas of the parotid gland. Arch Otolaryngol 110:167-171, 1984 3. Whitten J, Hybert F, Hansen HS: Treatment of malignant tumors in parotid glands. Cancer 65:2515-2520,
1990 4. Spiro RH, Huvos AG, Stong EW: Malignant
mixed of salivary origin, a clinicopathological study of 146 cases. Cancer 39:388-396, 1977 5. Gerughty TM, Scofield HH, Brown FM, et al: Malignant mixed tumours of salivary gland origin. Cancer 24:
tumors
471-486,1969 6. Saksela E, Tarkkanen J, Kohonen A: The malignancy of mixed tumours of the salivary gland. A clinicopathological analysis of 70 cases. ACTA Otolaryngol 70:62-70,
1970 7. Tortoledo
ME, Luna MA, Batsakis JG: Carcinomas expleomorphic adenoma and malignant mixed tumours. Arch Otoktryngol 110:172-178, 1984 8. Whitten J, Hybert F, Hansen HS: Treatment of malignant mixed tumours of salivary origin, a clinicopathological study of 146 cases. Cancer 39:388-396, 1977 9. Patey DH, Thackray AC, Keeling DH: Malignant disease of the parotid. Br J Cancer 19:172-737, 1965 10. Conley J, Clairmont AA: Facial nerve in recurrent pleomorphic adenomas. Arch Otolaryngol 105:247-251,
1979 11. Fitzpatrick
PJ, Theriault C: Malignant salivary gland tumors. J Rad Oncol Biophys 12:1743-1747, 1986 12.Theriault C, Fitzpatrick PJ: Malignant parotid tumours-Prognostic factors and optimum treatment. Am J Clin Oncol 9:510-516, 1986 13. Stephens J, Batsakis JG, Luna MA, et al: True malignant mixed tumours (carcinosarcoma] of salivary alands. Oral Surg Oral Med Oral Path01 61:597-602, 1986 14. Batsakis JG: Tumours of the head and neck, in Clinical and Pathological Considerations, (ed 2). Baltimore, MD, Williams and Wilkins, pp. 26-30.