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Mucoepidermoid lung tumors
Mucoepidermoid lung tumors C. Axelsson, M.D., F. Burcharth, M.D., and Aa. Johansen, M.D., Copenhagen,
Denmark
Mucoepidermoid tumors of the lung are extremely uncommon, with fewer than 50 such cases having been reported. The tumors extend from the glands of the bronchial mucosa and their outlets. Like the considerably more common mucoepidermoid tumors of the salivary glands, their histology is characterized by two components: a glandular, mucoid element and an epidermoid element. Often a third component of lower differentiation is describedthe intermediary cells. The clinical findings of the tumors have been discussed. As very few cases have been reported, experience with these lesions is rather limited. There is wide variation in the estimated degree of malignancy of the tumors; as a result, it is essential to have as many case reports as possible in order to explain the conditions that surround this tumor. In this article, reference is made to 4 cases of mucoepidermoid lung tumors managed from 1964 to 1970; two of them have been briefly mentioned previously.' During this period, 2,587 patients with bronchogenic carcinoma were treated. Case reports CAS E I. (No. 83220) A 62-year-old man with subtotal atelectasis of the left lung was referred.
From the Department of Thoracic Surgery and Pathology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Received for publication Jan 8, 1973. Address for reprints: Flemming Burcharth, M.D., Ledreborg Aile 40, 2820 Gentofte, Denmark.
902
The patient had had a left-sided pneumonia at the age of 25 years and a right-sided pneumonia at the age of 40 years. Over a period of 2 years, blurring of the pleura was observed on chest roentgenography. This condition was interpreted as pleurisy sequelae. Twelve months later an infiltration was observed at the level of the left sixth segment. For 3 months prior to hospitalization the patient had intermittent fever. At the time of admission, chest roentgenography revealed a central infiltration in the left lung, with compression of the main bronchus and increasing atelectasis. The patient had no clinical symptoms apart from the fever. Investigations. Examination of the bronchial secretion yielded no tumor cells. Bronchoscopy disclosed an obliterating tumor in the left main bronchus, 3 ern. from the carina. Biopsy showed a solid carcinoma, adenomatous in part. Treatment. A left-sided thoracotomy was performed. The pleura was found to be fibrous, with atelectasis of the lung and many adhesions to the thoracic wall. Pleurectomy and pneumonectomy were carried out. Frozen section of glands and of the bronchial resection line showed that the operation was radical. On examination, the specimen was a mucoepidermoid tumor which measured 2 by 2 by 3 em. It was partly stalky, with local invasive growth into the bronchial wall. No metastases to regional lymph nodes were found. The postoperative phase was uneventful. The patient has been followed, with the most recent examination having been 2J/~ years postoperatively. He felt well and had no signs of recurrence. CASE 2. (No. 92617) A 56-year-old man had chest x-ray evidence of infiltration in the right upper lobe, extending from the hilus to the thoracic wall. Over a period of 12 months, he had had fever accompanied by a nonproductive cough. Investigations. Examination of the expectoration yielded no tumor cells. Bronchoscopy disclosed that the upper lobe bronchus on the right side was contracted to one third of its normal size and was filled with pus. However, the mucosa was normal.
Volume 65 Number 6
Mucoepidermoid lung tumors
903
June, 1973
Fig. 1. Case 2. Mucus-secreting tumor component arising from the bronchial glands. (Hematoxylin and eosin; original magnification xIOO.)
Fig. 2. Case 2. Epidermoid component of high differentiation. (Hematoxylin and eosin; original magnification x450.) It was concluded that compression had been exerted from outside. No biopsy was taken, and no examination was made of bronchial secretion. Treatment. A right-sided thoracotomy revealed partial atelectasis of the upper lobe bronchus. Frozen section showed carcinoma, probably of the epidermoid type. A lobectomy was performed, and a 2 em. area of the main bronchus was resected at the level of the outlet from the upper lobe, due to tumor infiltration. Final histologic examination showed a mucoepidermoid tumor with invasive growth into the bronchial mucosa and metastases
to the regional lymph nodes (Figs. I to 3). Therefore, it is uncertain whether the operation was radical. The postoperative phase was uncomplicated. Since then the patient has been followed, with the most recent examination having been 1 year, 8 months postoperatively. He felt completely well and showed no signs of recurrence. CASE 3. (No. 102969) A 71-year-old man was referred with infiltration of the hilus and the left upper lobe, extending to the thoracic wall. The patient had been febrile for 1 month and had had
904
Axelsson, Burcharth, Johansen
The Journal of Thoracic and Cardiovascular Surgery
Fig. 3. Case 2. Typical parakeratosis. (Hematoxylin and eosin; original magnification x450.)
Fig. 4. Case 3. Mucoepidermoid tumor of low differentiation with both extra- and intracellular mucus and pronounced invasive growth. Mainly, the epidermoid component is illustrated. (Hematoxylin and eosin; original magnification xl00.) a cough with a slightly bloody expectorant, dyspnea, and retrosternal pain. He had lost 9 kilograms of weight over the previous 6 months. Investigations. Examination of the expectoration was positive for tumor cells. Bronchoscopy revealed no abnormalities. On mediastinoscopy, the lymph nodes appeared to be normal. Treatment. A left-sided thoracotomy showed a 15 em. tumor in the upper lobe, with invasive growth into the pleura, aorta, and the pulmonary artery (Fig. 4). Frozen section revealed a small-
celled, solid carcinoma. The lesion could not be extirpated. Final histologic examination showed that it was a mucoepidermoid tumor. Postoperatively, the patient received palliative x-ray treatment. He died 5 months after the operation. No necrospy could be performed since the patient had, by will, left his body to the Institute of Normal Anatomy. CASE 4. (No. 103922) A 57-year-old man was referred with a small, round infiltration in the middle of the left lung. Prior to admission, the
Volume 65 Number 6
Mucoepidermoid lung tumors
905
June , 1973
Fig. 5. Case 4. Tumor arising from the bronchial glands. (Hematoxylin and eosin; original magnification x450.)
patient had had a nonproductive cough for about I month but had had no other symptoms. Investigations. Examination of the expectoration yielded no tumor cells . No abnormalities were demonstrated by bronchoscopy. Treatment. A left-sided thoracotomy disclosed a 3 em. tumor situated centrally in the interlobar groove, prob ably extending from the lower lobe (Fig. 5). Frozen section showed epidermoid carcinoma , and a pneumonectomy was performed. Final histologic examination revealed a mucoepidermoid tumor with local invasive growth but without met astases. The oper ation was radical. Postoperatively, the patient . developed incompensatory heart failure and died I month later from cor pulmonale. Autopsy showed cor pulmonale and hypertrophy but no signs of recurrence.
Pathology Mucoepidermoid lung tumors are described as well-defined lesions covered by normal mucosa. They are characterized by local invasive growth and rarely metastasize. Macroscopically, only one well-defined tumor (Case I) was found in this series. The other tumors were badly defined, and it was impossible, macroscopically, to distinguish between them and bronchogenic carcinomas. The tumors were firm, grayish white, and were from 2 to 15 em . in diameter. As mentioned, the tumors were charac-
terized histologically by their composition of several components. The epidermoid component occurs with varying degrees of differentiation. At times, parakeratosis and intercellular bridges are seen, but in tumors with lower differentiation these findings are not present. The mucoid component is developed from adenomatous, mucus-forming tumor cells, and the pattern may imitate glandular lum ina . The mucus is deposited both intra- and extracellularly, occasionally resembling whole lakes of mucus. Varying quantities of large, light, polygonal cells have also been described, so-called intermediary cells. They are assumed to be that component of the tumor tissue which is of lowest differentiation and, therefore, the parent cells to the other two types of tumor cells. Local invasive growth into the bronchial wall occurs frequently , with the tumor often being covered by intact mucosa. All four lesions in our series conformed in structure to the description of mucoepidermoid tumors . However, there were considerable individual differences, as shown in Table 1. All the tumors grew invasively, but in varying degrees. One tumor (Case 2) had metastasized to the regional lymph nodes, the metastases having the structure of the primary tumor. In Cases 2 and 4, the origin
The Journal of
906
Axelsson, Burcharth, Johansen
Thoracic and Cardiovascular Surgery
Table I. Pathology in four mucoepidermoid lung tumors
Case Na.
Degree Degree I Structure (pre- of dijof invasive dominant cell [erentiagrowth Metastases type)" tion +
No
E>M
>
I
High
2
+++
Yes
E=M
>
I
High
3
+++
No
M
>
E
Low
4
++
No
M >E>I
Low
I
Mucosal secretion and deposit
Scarce; intracellular Moderate; intraand extracellular Excessive; intraand extracellular Scarce; intracellular
Place of origin
Parakeratoses
Mucus glands
Yes
Mucus glands
Yes
Unknown
No
Mucus glands and outlets
Yes
'E, Epidermoid. M, Mucoid. I, Intermediary cells.
of the tumors could be localized to the mucus-secreting glands of the bronchial mucosa and their outlets (Figs. 2 and 5), but the origin of the other two tumors could not be clearly defined. The tumor in Case 3 appeared to have the lowest differentiation, as parakeratosis was not present in the epidermoid component and intercellular bridges between the cells (Fig. 4) were only occasionally present. Discussion
Mucoepidermoid lung tumors are usually included in the category of bronchial adenomas, which also encompasses the carcinoids and cylindromas. With regards to genesis, morphology, and the degree of malignancy, there are vast differences in these tumors. The term bronchial adenoma, which is more traditionally than rationally founded, should be eliminated altogether and replaced by the names of the individual tumors. The clinical symptoms do not differ from the symptoms of other malignant lung tumors and therefore do not contribute to the differential diagnosis. Preoperative diagnosis was not made in any of the cases. In the one instance (Case 1) in which a biopsy was obtained, the diagnosis was changed to mucoepidermoid tumor after re-examination of the specimen. This diagnosis is seldom suggested, because
of the infrequent occurrence of these tumors in the lung. In each case, frozen-section examination established the diagnosis of malignant tumor, predominantly based on the appearance of the epidermoid component. The final histologic examination showed that all tumors fulfilled the prescribed diagnostic criteria. The degree of tumor malignancy has been discussed: Meckstroth," Payne,' and their associates regarded the tumors as almost benign. Judging from a survey of 29 cases collected from reports, Reichle and Rosemond" arrived at a similar result. They found a protracted clinical course with slow tumor progression and no metastases. Histologically, they registered some tendency toward invasion. OzlU,H Dowling," and their associates reported the first case histories of patients with metastasizing mucoepidermoid lung tumors who died. They further discussed the occurrence of benign and malignant tumor types. Wilkins,'! Markel,' and their associates doubted the malignancy of the tumors. They considered the lesions to be benign and proposed that a possible fatal outcome was the result of chronically obstructive lung disease, caused by bronchial obstruction from growth of the tumors. Histologically, invasive growth into the bronchial wall was also seen in their cases, but there was no growth into blood vessels or lymph ducts.
Volume 65
Mucoepidermoid lung tumors
Number 6
907
June. 1973
The most recent paper is by Turnbull and associates," who have produced the largest report-twelve tumors found after investigation of 5,000 patients treated for lung cancer. All twelve tumors were highly malignant, and all patients developed metastases. Five patients had metastases on admission, while the remaining 7 developed extensive metastases during the course of the disease. In spite of intensive treatment, all the patients died. The duration of the disease, from the onset of the symptoms until death, was from 6 to 18 months-an average of 9.8 months. Only 4 patients were treated surgically by resection of the tumor; in 2 cases, it was impossible to remove all tumor tissue from the mediastinum. The mucoepidermoid tumors of the salivary glands, which have been more thoroughly investigated clinically, were originally classified into two groups: malignant and benign tumors. Through time this classification has been altered, and the tumors are now classified in three forms: high, intermediary, and low differentiated forms. The prognosis and therapy are dependent on these classifications. Of the 4 patients in this series, only 1 (Case 3) had severe symptoms. In all cases, the patients had had symptoms for only a few months before operation. However in I case (Case 1), chest x-ray films over a period of 2 years showed increasing infiltration. The tumors measured from 2 to 15 em. and can, in view of the duration of the disease, be considered to be rapidly growing lesions. Histologically, the tumors can be divided into groups of high and low differentiation (Table I). The tumor with lowest differentiation (Case 3) also grew the most actively, but it is remarkable to note that it was a tumor of high differentiation (Case 2) that metastasized (Figs. 1 to 3). In summary, it can be said that mucoepidermoid lung tumors are malignant, that they grow invasively and fairly rapidly, and that they have the ability to metastasize, irrespective of the degree of differentiation.
Therefore, the treatment must consist in immediate thoracotomy with resection as necessary, with the aid of frozen-section microscopy.
Summary Mucoepidermoid tumors are uncommon, with only 50 such cases having been reported. The degree of malignancy is still a subject of discussion. Such tumors used to be regarded as fairly benign. However, in recent years, fatal cases with metastases have been reported; latest survey reports':' show 12 cases, all of which were of a pronounced malignant nature. The 4 cases reported here all involved rapidly growing malignant tumors. The degree of differentiation varied, and it was remarkable to note that the tumor of highest differentiation had metastasized. We have concluded that mucoepidermoid lung tumors are malignant lesions that grow fairly rapidly. We believe that, irrespective of the degree of differentiation, the treatment should consist in radical resection guided by frozen section. REFERENCES
2 3 4
5 6
7
Burcharth, F., and Axelsson, C.: Bronchial Adenomas, Thorax 27: 442, 1972. Dowling, E. A., Miller, R. E., Johnson, 1. M., and Collier, F. C. D.: Mucoepidermoid Tumors of the Bronchi, Surgery 52: 600, 1962. Healey, W. Y., Perzin, K. H., and Smith, L.: Mucoepidermoid Carcinoma of Salivary Gland Origin, Cancer 26: 368, 1970. Markel, S. F., Abell, M. R., Haight, C., and French, A. J.: Neoplasms of Bronchus Commonly Designated as Adenomas, Cancer 17: 590, 1964. Meckstroth, C. Y., Davidson, H. B., and Kress, G. 0.: Mucoepidermoid Tumor of the Bronchus, Chest 40: 652, 196 I. Ozlu, C., Christopherson, W. M., and Allen, J. D., Jr.: Muco-epidermoid Tumors of the Bronchus, J. THORAc. CARDIOVASC. SURG. 42: 24, 1961. Payne, W. S., Ellis, F. H., Jr., Woolner, L. B., and Moersch, H. J.: The Surgical Treatment of Cylindroma (Adenoid Cystic Carcinoma) and Muco-epidermoid Tumors of the Bron-
908
Axelsson, Burcharth, Johansen
chus, J. THORAC. CARDIOVASC. SURG. 38: 709, 1959. 8 Reichle, F. A., and Rosemond, G. P.: Mucoepidermoid Tumors of the Bronchus, J. THORAC. CARDIOVASC. SURG. 51: 443, 1966. 9 Sniffen, R. c., So utter, L., and Robbins, L. L.: Muco-epidermoid Tumors of the Bronchus Arising From Surface Epithelium, Am. J. Patho1. 34: 671, 1958.
The Journal of Thoracic and Cardiovascular Surgery
10 Turnbull, A. D., Huvos, A. G., Goodner, J. T., and Foote, F. W.: Mucoepidermoid Tumors of Bronchial Glands, Cancer 28: 539, 1971. 1I Wilkins, E. W., Jr., Darling, R. C., Soutter, L., and Sniffen, R. C.: A Continuing Clinical Survey of Adenomas of the Trachea and Bronchus in a General Hospital, J. THORAC. CARDIOVASC. SURG. 46: 279, 1963.
Denmark
Mucoepidermoid tumors of the lung are extremely uncommon, with fewer than 50 such cases having been reported. The tumors extend from the glands of the bronchial mucosa and their outlets. Like the considerably more common mucoepidermoid tumors of the salivary glands, their histology is characterized by two components: a glandular, mucoid element and an epidermoid element. Often a third component of lower differentiation is describedthe intermediary cells. The clinical findings of the tumors have been discussed. As very few cases have been reported, experience with these lesions is rather limited. There is wide variation in the estimated degree of malignancy of the tumors; as a result, it is essential to have as many case reports as possible in order to explain the conditions that surround this tumor. In this article, reference is made to 4 cases of mucoepidermoid lung tumors managed from 1964 to 1970; two of them have been briefly mentioned previously.' During this period, 2,587 patients with bronchogenic carcinoma were treated. Case reports CAS E I. (No. 83220) A 62-year-old man with subtotal atelectasis of the left lung was referred.
From the Department of Thoracic Surgery and Pathology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Received for publication Jan 8, 1973. Address for reprints: Flemming Burcharth, M.D., Ledreborg Aile 40, 2820 Gentofte, Denmark.
902
The patient had had a left-sided pneumonia at the age of 25 years and a right-sided pneumonia at the age of 40 years. Over a period of 2 years, blurring of the pleura was observed on chest roentgenography. This condition was interpreted as pleurisy sequelae. Twelve months later an infiltration was observed at the level of the left sixth segment. For 3 months prior to hospitalization the patient had intermittent fever. At the time of admission, chest roentgenography revealed a central infiltration in the left lung, with compression of the main bronchus and increasing atelectasis. The patient had no clinical symptoms apart from the fever. Investigations. Examination of the bronchial secretion yielded no tumor cells. Bronchoscopy disclosed an obliterating tumor in the left main bronchus, 3 ern. from the carina. Biopsy showed a solid carcinoma, adenomatous in part. Treatment. A left-sided thoracotomy was performed. The pleura was found to be fibrous, with atelectasis of the lung and many adhesions to the thoracic wall. Pleurectomy and pneumonectomy were carried out. Frozen section of glands and of the bronchial resection line showed that the operation was radical. On examination, the specimen was a mucoepidermoid tumor which measured 2 by 2 by 3 em. It was partly stalky, with local invasive growth into the bronchial wall. No metastases to regional lymph nodes were found. The postoperative phase was uneventful. The patient has been followed, with the most recent examination having been 2J/~ years postoperatively. He felt well and had no signs of recurrence. CASE 2. (No. 92617) A 56-year-old man had chest x-ray evidence of infiltration in the right upper lobe, extending from the hilus to the thoracic wall. Over a period of 12 months, he had had fever accompanied by a nonproductive cough. Investigations. Examination of the expectoration yielded no tumor cells. Bronchoscopy disclosed that the upper lobe bronchus on the right side was contracted to one third of its normal size and was filled with pus. However, the mucosa was normal.
Volume 65 Number 6
Mucoepidermoid lung tumors
903
June, 1973
Fig. 1. Case 2. Mucus-secreting tumor component arising from the bronchial glands. (Hematoxylin and eosin; original magnification xIOO.)
Fig. 2. Case 2. Epidermoid component of high differentiation. (Hematoxylin and eosin; original magnification x450.) It was concluded that compression had been exerted from outside. No biopsy was taken, and no examination was made of bronchial secretion. Treatment. A right-sided thoracotomy revealed partial atelectasis of the upper lobe bronchus. Frozen section showed carcinoma, probably of the epidermoid type. A lobectomy was performed, and a 2 em. area of the main bronchus was resected at the level of the outlet from the upper lobe, due to tumor infiltration. Final histologic examination showed a mucoepidermoid tumor with invasive growth into the bronchial mucosa and metastases
to the regional lymph nodes (Figs. I to 3). Therefore, it is uncertain whether the operation was radical. The postoperative phase was uncomplicated. Since then the patient has been followed, with the most recent examination having been 1 year, 8 months postoperatively. He felt completely well and showed no signs of recurrence. CASE 3. (No. 102969) A 71-year-old man was referred with infiltration of the hilus and the left upper lobe, extending to the thoracic wall. The patient had been febrile for 1 month and had had
904
Axelsson, Burcharth, Johansen
The Journal of Thoracic and Cardiovascular Surgery
Fig. 3. Case 2. Typical parakeratosis. (Hematoxylin and eosin; original magnification x450.)
Fig. 4. Case 3. Mucoepidermoid tumor of low differentiation with both extra- and intracellular mucus and pronounced invasive growth. Mainly, the epidermoid component is illustrated. (Hematoxylin and eosin; original magnification xl00.) a cough with a slightly bloody expectorant, dyspnea, and retrosternal pain. He had lost 9 kilograms of weight over the previous 6 months. Investigations. Examination of the expectoration was positive for tumor cells. Bronchoscopy revealed no abnormalities. On mediastinoscopy, the lymph nodes appeared to be normal. Treatment. A left-sided thoracotomy showed a 15 em. tumor in the upper lobe, with invasive growth into the pleura, aorta, and the pulmonary artery (Fig. 4). Frozen section revealed a small-
celled, solid carcinoma. The lesion could not be extirpated. Final histologic examination showed that it was a mucoepidermoid tumor. Postoperatively, the patient received palliative x-ray treatment. He died 5 months after the operation. No necrospy could be performed since the patient had, by will, left his body to the Institute of Normal Anatomy. CASE 4. (No. 103922) A 57-year-old man was referred with a small, round infiltration in the middle of the left lung. Prior to admission, the
Volume 65 Number 6
Mucoepidermoid lung tumors
905
June , 1973
Fig. 5. Case 4. Tumor arising from the bronchial glands. (Hematoxylin and eosin; original magnification x450.)
patient had had a nonproductive cough for about I month but had had no other symptoms. Investigations. Examination of the expectoration yielded no tumor cells . No abnormalities were demonstrated by bronchoscopy. Treatment. A left-sided thoracotomy disclosed a 3 em. tumor situated centrally in the interlobar groove, prob ably extending from the lower lobe (Fig. 5). Frozen section showed epidermoid carcinoma , and a pneumonectomy was performed. Final histologic examination revealed a mucoepidermoid tumor with local invasive growth but without met astases. The oper ation was radical. Postoperatively, the patient . developed incompensatory heart failure and died I month later from cor pulmonale. Autopsy showed cor pulmonale and hypertrophy but no signs of recurrence.
Pathology Mucoepidermoid lung tumors are described as well-defined lesions covered by normal mucosa. They are characterized by local invasive growth and rarely metastasize. Macroscopically, only one well-defined tumor (Case I) was found in this series. The other tumors were badly defined, and it was impossible, macroscopically, to distinguish between them and bronchogenic carcinomas. The tumors were firm, grayish white, and were from 2 to 15 em . in diameter. As mentioned, the tumors were charac-
terized histologically by their composition of several components. The epidermoid component occurs with varying degrees of differentiation. At times, parakeratosis and intercellular bridges are seen, but in tumors with lower differentiation these findings are not present. The mucoid component is developed from adenomatous, mucus-forming tumor cells, and the pattern may imitate glandular lum ina . The mucus is deposited both intra- and extracellularly, occasionally resembling whole lakes of mucus. Varying quantities of large, light, polygonal cells have also been described, so-called intermediary cells. They are assumed to be that component of the tumor tissue which is of lowest differentiation and, therefore, the parent cells to the other two types of tumor cells. Local invasive growth into the bronchial wall occurs frequently , with the tumor often being covered by intact mucosa. All four lesions in our series conformed in structure to the description of mucoepidermoid tumors . However, there were considerable individual differences, as shown in Table 1. All the tumors grew invasively, but in varying degrees. One tumor (Case 2) had metastasized to the regional lymph nodes, the metastases having the structure of the primary tumor. In Cases 2 and 4, the origin
The Journal of
906
Axelsson, Burcharth, Johansen
Thoracic and Cardiovascular Surgery
Table I. Pathology in four mucoepidermoid lung tumors
Case Na.
Degree Degree I Structure (pre- of dijof invasive dominant cell [erentiagrowth Metastases type)" tion +
No
E>M
>
I
High
2
+++
Yes
E=M
>
I
High
3
+++
No
M
>
E
Low
4
++
No
M >E>I
Low
I
Mucosal secretion and deposit
Scarce; intracellular Moderate; intraand extracellular Excessive; intraand extracellular Scarce; intracellular
Place of origin
Parakeratoses
Mucus glands
Yes
Mucus glands
Yes
Unknown
No
Mucus glands and outlets
Yes
'E, Epidermoid. M, Mucoid. I, Intermediary cells.
of the tumors could be localized to the mucus-secreting glands of the bronchial mucosa and their outlets (Figs. 2 and 5), but the origin of the other two tumors could not be clearly defined. The tumor in Case 3 appeared to have the lowest differentiation, as parakeratosis was not present in the epidermoid component and intercellular bridges between the cells (Fig. 4) were only occasionally present. Discussion
Mucoepidermoid lung tumors are usually included in the category of bronchial adenomas, which also encompasses the carcinoids and cylindromas. With regards to genesis, morphology, and the degree of malignancy, there are vast differences in these tumors. The term bronchial adenoma, which is more traditionally than rationally founded, should be eliminated altogether and replaced by the names of the individual tumors. The clinical symptoms do not differ from the symptoms of other malignant lung tumors and therefore do not contribute to the differential diagnosis. Preoperative diagnosis was not made in any of the cases. In the one instance (Case 1) in which a biopsy was obtained, the diagnosis was changed to mucoepidermoid tumor after re-examination of the specimen. This diagnosis is seldom suggested, because
of the infrequent occurrence of these tumors in the lung. In each case, frozen-section examination established the diagnosis of malignant tumor, predominantly based on the appearance of the epidermoid component. The final histologic examination showed that all tumors fulfilled the prescribed diagnostic criteria. The degree of tumor malignancy has been discussed: Meckstroth," Payne,' and their associates regarded the tumors as almost benign. Judging from a survey of 29 cases collected from reports, Reichle and Rosemond" arrived at a similar result. They found a protracted clinical course with slow tumor progression and no metastases. Histologically, they registered some tendency toward invasion. OzlU,H Dowling," and their associates reported the first case histories of patients with metastasizing mucoepidermoid lung tumors who died. They further discussed the occurrence of benign and malignant tumor types. Wilkins,'! Markel,' and their associates doubted the malignancy of the tumors. They considered the lesions to be benign and proposed that a possible fatal outcome was the result of chronically obstructive lung disease, caused by bronchial obstruction from growth of the tumors. Histologically, invasive growth into the bronchial wall was also seen in their cases, but there was no growth into blood vessels or lymph ducts.
Volume 65
Mucoepidermoid lung tumors
Number 6
907
June. 1973
The most recent paper is by Turnbull and associates," who have produced the largest report-twelve tumors found after investigation of 5,000 patients treated for lung cancer. All twelve tumors were highly malignant, and all patients developed metastases. Five patients had metastases on admission, while the remaining 7 developed extensive metastases during the course of the disease. In spite of intensive treatment, all the patients died. The duration of the disease, from the onset of the symptoms until death, was from 6 to 18 months-an average of 9.8 months. Only 4 patients were treated surgically by resection of the tumor; in 2 cases, it was impossible to remove all tumor tissue from the mediastinum. The mucoepidermoid tumors of the salivary glands, which have been more thoroughly investigated clinically, were originally classified into two groups: malignant and benign tumors. Through time this classification has been altered, and the tumors are now classified in three forms: high, intermediary, and low differentiated forms. The prognosis and therapy are dependent on these classifications. Of the 4 patients in this series, only 1 (Case 3) had severe symptoms. In all cases, the patients had had symptoms for only a few months before operation. However in I case (Case 1), chest x-ray films over a period of 2 years showed increasing infiltration. The tumors measured from 2 to 15 em. and can, in view of the duration of the disease, be considered to be rapidly growing lesions. Histologically, the tumors can be divided into groups of high and low differentiation (Table I). The tumor with lowest differentiation (Case 3) also grew the most actively, but it is remarkable to note that it was a tumor of high differentiation (Case 2) that metastasized (Figs. 1 to 3). In summary, it can be said that mucoepidermoid lung tumors are malignant, that they grow invasively and fairly rapidly, and that they have the ability to metastasize, irrespective of the degree of differentiation.
Therefore, the treatment must consist in immediate thoracotomy with resection as necessary, with the aid of frozen-section microscopy.
Summary Mucoepidermoid tumors are uncommon, with only 50 such cases having been reported. The degree of malignancy is still a subject of discussion. Such tumors used to be regarded as fairly benign. However, in recent years, fatal cases with metastases have been reported; latest survey reports':' show 12 cases, all of which were of a pronounced malignant nature. The 4 cases reported here all involved rapidly growing malignant tumors. The degree of differentiation varied, and it was remarkable to note that the tumor of highest differentiation had metastasized. We have concluded that mucoepidermoid lung tumors are malignant lesions that grow fairly rapidly. We believe that, irrespective of the degree of differentiation, the treatment should consist in radical resection guided by frozen section. REFERENCES
2 3 4
5 6
7
Burcharth, F., and Axelsson, C.: Bronchial Adenomas, Thorax 27: 442, 1972. Dowling, E. A., Miller, R. E., Johnson, 1. M., and Collier, F. C. D.: Mucoepidermoid Tumors of the Bronchi, Surgery 52: 600, 1962. Healey, W. Y., Perzin, K. H., and Smith, L.: Mucoepidermoid Carcinoma of Salivary Gland Origin, Cancer 26: 368, 1970. Markel, S. F., Abell, M. R., Haight, C., and French, A. J.: Neoplasms of Bronchus Commonly Designated as Adenomas, Cancer 17: 590, 1964. Meckstroth, C. Y., Davidson, H. B., and Kress, G. 0.: Mucoepidermoid Tumor of the Bronchus, Chest 40: 652, 196 I. Ozlu, C., Christopherson, W. M., and Allen, J. D., Jr.: Muco-epidermoid Tumors of the Bronchus, J. THORAc. CARDIOVASC. SURG. 42: 24, 1961. Payne, W. S., Ellis, F. H., Jr., Woolner, L. B., and Moersch, H. J.: The Surgical Treatment of Cylindroma (Adenoid Cystic Carcinoma) and Muco-epidermoid Tumors of the Bron-
908
Axelsson, Burcharth, Johansen
chus, J. THORAC. CARDIOVASC. SURG. 38: 709, 1959. 8 Reichle, F. A., and Rosemond, G. P.: Mucoepidermoid Tumors of the Bronchus, J. THORAC. CARDIOVASC. SURG. 51: 443, 1966. 9 Sniffen, R. c., So utter, L., and Robbins, L. L.: Muco-epidermoid Tumors of the Bronchus Arising From Surface Epithelium, Am. J. Patho1. 34: 671, 1958.
The Journal of Thoracic and Cardiovascular Surgery
10 Turnbull, A. D., Huvos, A. G., Goodner, J. T., and Foote, F. W.: Mucoepidermoid Tumors of Bronchial Glands, Cancer 28: 539, 1971. 1I Wilkins, E. W., Jr., Darling, R. C., Soutter, L., and Sniffen, R. C.: A Continuing Clinical Survey of Adenomas of the Trachea and Bronchus in a General Hospital, J. THORAC. CARDIOVASC. SURG. 46: 279, 1963.