Primary adenocarcinomas of the larynx By J. A. HOULE, P. JOSEPH and J. G. BATSAKIS
(Ann Arbor, Michigan) ANY FORM of malignant glandular neoplasms in the larynx must be considered unusual. Nearly all estimates place their frequency as less than i % of all laryngeal cancer (Fechner, 1975). Adenoid cystic carcinomas and adenocarcinoma comprise most of the histological types (Batsakis, 1974). Less commonly encountered are mucoepidermoid carcinomas, oncocytic carcinomas and metastatic adenocarcinomas. This report presents two cases of primary glandular malignancy; each representing one of the major histological types of laryngeal adenocarcinoma (adenoid cystic carcinoma and adenocarcinoma without special features).
Case Reports
Case 1. A 53-year-old white man was admitted to the Veteran's Administration Hospital, Ann Arbor, Michigan after an emergency tracheostomy for an acute obstruction of his airway. The patient was a chronic alcoholic and a heavy cigarette smoker for many years. In the 6 months before his admission, he had experienced progressive hoarseness, hemoptysis, dyspnea and weight loss. Direct laryngoscopic examination demonstrated a large, supraglottic tumor occluding the inlet of the larynx. Aside from this finding and a general debilitation, the patient manifested no other physical abnormality. Roentgenograms of the chest demonstrated multiple, non-calcified opacities in the lungs. Radiologic examinations of the kidneys and upper and lower gastro-intestinal tract demonstrated no intrinsic disease. However, extrinsic compression of the esophagus, at the level of the cricoid, was demonstrated. The pathological diagnosis of the tissue removed by biopsy of the supraglottic mass was adenocarcinoma. Management of the patient was confined to supportive, palliative measures and systemic chemotherapy. The patient died after 3 months of hospitalization. During this time, his pulmonary metastases increased in size and number. Pathological Examination: Necropsy was performed approximately 4 hours after death. A large, fungating, 6 cm. X5 cm. X4 cm. neoplasm filled the supraglottic space and occluded the laryngeal lumen (Figs. 1 & 2). The neoplasm had extended into the thyroid gland, adjacent soft tissues and incorporated regional lymph nodes. Numerous, bilateral metastases in the lungs were present. These ranged in size from 0-5 cm. to 2-0 cm. in diameter. No other metastases were present. Microscopic examination revealed an adenocarcinoma with variable degrees of differentiation. Origin from ductal elements was suggested by finding rudimentary "59
FIGS, I & 2.
Case 1. Large, primarily sujgraglottic adenocarcinoma occludes laryngeal lumen and extends
P
o
nT
oX
Clinical records gland formation and cellular rosettes with well denned lumina (Fig. 3). The cells possessed a relatively scant amount of cytoplasm and did not manifest secretory features. Case 2. A 52-year-old man was admitted to the University of Michigan Hospital for the evaluation of his hoarseness, dysphagia and weight loss of several months duration. He used cigarettes and alcohol in moderation and there were no other significant physical complaints. External physical examination and laboratory studies were within normal limits for his age. Direct laryngoscopy and biopsy demonstrated a neoplasm involving the right aryepiglottic fold, false cords and posterior arytenoid, and the left arytenoid and pyriform sinus. There was no apparent invasion of the wall of the pharynx. Examination of the biopsy specimen demonstrated an adenoid cystic carcinoma. A total laryngectomy and right radical neck dissection were performed. The patient has received no additional therapy and is without evidence of recurrence five and one-half years after his operation. Pathological examination: The laryngeal neoplasm measured 3-5 cm. X3 - 5 cm. X4 cm. and involved the posterior cricoid region, including the left and right arytenoids, as well as the right aryepiglottic fold, false cord and the laryngeal rim of the right pyriform sinus. Twenty lymph nodes in the neck dissection were free of metastases. Microscopic examination revealed an infiltrating neoplasm composed of small, uniform, polygonal cells arranged in a medullary pattern. Frequently, the cellular orientation assumed a pseudoglandular pattern about hyaline ground substance. Pathological diagnosis was adenoid cystic carcinoma (Fig. 4). Comment Glandular neoplasms of the upper-airway arise from seromucinous glands and minor salivary gland tissue found in the mucosa. In the larynx, the greatest concentration of these structures is found in the false cords and just inferior to the anterior commissure (Fechner, 1975). Lesser numbers are found in the aryepiglottic folds and the free portion of the epiglottis. The squamous lined portion of the cord is said to be normally devoid of glands. While histologically indistinguishable from their counterparts in the major salivary glands and minor salivary tissue of the oral cavity and paranasal sinuses, glandular neoplasms of the larynx and trachea are considerably less often encountered by the otorhinolaryngologist. Because of this relative rarity, experience with and criteria for the management of glandular malignancy of the larynx is difficult to achieve. Cady et al. (1968) could find only 17 cases (o-6%) in 2500 laryngeal malignancies. Eschwege et al. (1975) reported only 5 cases of adenoid cystic carcinomas from a collection of 1,342 cases of carcinoma of the larynx. Sessions etal. (1975) cite an incidence of o-i% in reporting 9 glandular . malignancies in a series of 888 patients with laryngeal carcinoma. Our two patients present many of the clinico-pathological features associated with primary glandular malignancies of the larynx. Laryngeal adenoid cystic carcinomas have been primarily seen in patients in the sixth or seventh decades. Most of the adenocarcinomas have occurred in patients beyond the age 1161
J. A. Houle, P. Joseph and J. G. Batsakis
FIG. 3. Case 1. Relatively poorly differentiated adenocarcinoma. (Hematoxylin and eosin, X475).
FIG. 4. Case 2. Replicated basement membrane material separates small basal type cells and imparts a pseudoglandular pattern to this adenoid cystic carcinoma of the larynx. (Hematoxylin and eosin, X485). 1162
Clinical records of 60 years. There appears to be a conspicuous male predominance in adenocarcinomas of the larynx as opposed to a nearly equal sex involvement by adenoid cystic carcinomas (Fechner, 1975). Adenocarcinomas, in contrast to adenoid cystic carcinomas, are rarely subglottic. Supraglottic and transglottic involvement are about equal. Approximately two-thirds of the adenoid cystic carcinomas are in subglottic structures (Fechner, 1975). As illustrated by the patient in Case 1, adenocarcinomas usually form large non-ulcerated masses. Adenoid cystic carcinomas manifest a less tendency to this large size. Clinical experience with adenocarcinoma and adenoid cystic carcinomas of the larynx is so meager that it is difficult to assess the effectiveness of any modality of treatment. Both carcinomas are lethal diseases, with a subjective impression that adenocarcinoma is a more rapid killer. Almost all patients with adenocarcinomas are dead within 2 years (Fechner, 1975). Widespread pulmonary and hepatic metastases are related to the outcome. Approximately one-third of the patients with adenoid cystic carcinomas eventually manifest pulmonary metastases (Fechner, 1975). The clinical course is, however more torpid with local recurrences and regional lymph node involvement. Follow-up to three or five years is not sufficient; recurrences are frequently delayed until three or five years, and there is an inverse proportion between survivors and non-survivors at 5, 10 and 15 year intervals (Eschwege et al., 1975; Sessions etal., 1975). It seems quite clear that current management of glandular malignancies of the larynx is not effective for cure in the majority of patients. Sessions et al. (1975) summarize their own experience and that of others by stating 'primary radical surgery treatment of this disease in no way appears to decrease recurrence rate or prolong survival time.' They recommend wide local excision or conservative surgery wherever feasible as the mode of primary therapy for any form of glandular malignancy of the larynx. REFERENCES J. G. (1974) Tumors of the Head and Neck: Clinical and Pathological Consideration, Williams and Wilkins Co., Baltimore, pp. 44-45. CADY, B. C, RIPPEY, J. H., and FRAZELL, E. L. (1968) Annals of Surgery, 167, 116. ESCHWEGE, F., CACHIN, Y. and MICHEAU, Ch. (1975) Canadian Journal of Otolaryngology, 4, 284. FECHNER, R. E. (1975) Canadian Journal of Otolaryngology, 4, 284. SESSIONS, D. G., MURRAY, J. P., BAUER, W. C, and OGURA, J. H. (1975) Canadian Journal of Otolaryngology, 4, 293.
BATSAKIS,
Dr. J. G. Batsakis, Dept. of Pathology, 1335 E. Catherine St., Ann Arbor, Michigan 48104.
1163
(Ann Arbor, Michigan) ANY FORM of malignant glandular neoplasms in the larynx must be considered unusual. Nearly all estimates place their frequency as less than i % of all laryngeal cancer (Fechner, 1975). Adenoid cystic carcinomas and adenocarcinoma comprise most of the histological types (Batsakis, 1974). Less commonly encountered are mucoepidermoid carcinomas, oncocytic carcinomas and metastatic adenocarcinomas. This report presents two cases of primary glandular malignancy; each representing one of the major histological types of laryngeal adenocarcinoma (adenoid cystic carcinoma and adenocarcinoma without special features).
Case Reports
Case 1. A 53-year-old white man was admitted to the Veteran's Administration Hospital, Ann Arbor, Michigan after an emergency tracheostomy for an acute obstruction of his airway. The patient was a chronic alcoholic and a heavy cigarette smoker for many years. In the 6 months before his admission, he had experienced progressive hoarseness, hemoptysis, dyspnea and weight loss. Direct laryngoscopic examination demonstrated a large, supraglottic tumor occluding the inlet of the larynx. Aside from this finding and a general debilitation, the patient manifested no other physical abnormality. Roentgenograms of the chest demonstrated multiple, non-calcified opacities in the lungs. Radiologic examinations of the kidneys and upper and lower gastro-intestinal tract demonstrated no intrinsic disease. However, extrinsic compression of the esophagus, at the level of the cricoid, was demonstrated. The pathological diagnosis of the tissue removed by biopsy of the supraglottic mass was adenocarcinoma. Management of the patient was confined to supportive, palliative measures and systemic chemotherapy. The patient died after 3 months of hospitalization. During this time, his pulmonary metastases increased in size and number. Pathological Examination: Necropsy was performed approximately 4 hours after death. A large, fungating, 6 cm. X5 cm. X4 cm. neoplasm filled the supraglottic space and occluded the laryngeal lumen (Figs. 1 & 2). The neoplasm had extended into the thyroid gland, adjacent soft tissues and incorporated regional lymph nodes. Numerous, bilateral metastases in the lungs were present. These ranged in size from 0-5 cm. to 2-0 cm. in diameter. No other metastases were present. Microscopic examination revealed an adenocarcinoma with variable degrees of differentiation. Origin from ductal elements was suggested by finding rudimentary "59
FIGS, I & 2.
Case 1. Large, primarily sujgraglottic adenocarcinoma occludes laryngeal lumen and extends
P
o
nT
oX
Clinical records gland formation and cellular rosettes with well denned lumina (Fig. 3). The cells possessed a relatively scant amount of cytoplasm and did not manifest secretory features. Case 2. A 52-year-old man was admitted to the University of Michigan Hospital for the evaluation of his hoarseness, dysphagia and weight loss of several months duration. He used cigarettes and alcohol in moderation and there were no other significant physical complaints. External physical examination and laboratory studies were within normal limits for his age. Direct laryngoscopy and biopsy demonstrated a neoplasm involving the right aryepiglottic fold, false cords and posterior arytenoid, and the left arytenoid and pyriform sinus. There was no apparent invasion of the wall of the pharynx. Examination of the biopsy specimen demonstrated an adenoid cystic carcinoma. A total laryngectomy and right radical neck dissection were performed. The patient has received no additional therapy and is without evidence of recurrence five and one-half years after his operation. Pathological examination: The laryngeal neoplasm measured 3-5 cm. X3 - 5 cm. X4 cm. and involved the posterior cricoid region, including the left and right arytenoids, as well as the right aryepiglottic fold, false cord and the laryngeal rim of the right pyriform sinus. Twenty lymph nodes in the neck dissection were free of metastases. Microscopic examination revealed an infiltrating neoplasm composed of small, uniform, polygonal cells arranged in a medullary pattern. Frequently, the cellular orientation assumed a pseudoglandular pattern about hyaline ground substance. Pathological diagnosis was adenoid cystic carcinoma (Fig. 4). Comment Glandular neoplasms of the upper-airway arise from seromucinous glands and minor salivary gland tissue found in the mucosa. In the larynx, the greatest concentration of these structures is found in the false cords and just inferior to the anterior commissure (Fechner, 1975). Lesser numbers are found in the aryepiglottic folds and the free portion of the epiglottis. The squamous lined portion of the cord is said to be normally devoid of glands. While histologically indistinguishable from their counterparts in the major salivary glands and minor salivary tissue of the oral cavity and paranasal sinuses, glandular neoplasms of the larynx and trachea are considerably less often encountered by the otorhinolaryngologist. Because of this relative rarity, experience with and criteria for the management of glandular malignancy of the larynx is difficult to achieve. Cady et al. (1968) could find only 17 cases (o-6%) in 2500 laryngeal malignancies. Eschwege et al. (1975) reported only 5 cases of adenoid cystic carcinomas from a collection of 1,342 cases of carcinoma of the larynx. Sessions etal. (1975) cite an incidence of o-i% in reporting 9 glandular . malignancies in a series of 888 patients with laryngeal carcinoma. Our two patients present many of the clinico-pathological features associated with primary glandular malignancies of the larynx. Laryngeal adenoid cystic carcinomas have been primarily seen in patients in the sixth or seventh decades. Most of the adenocarcinomas have occurred in patients beyond the age 1161
J. A. Houle, P. Joseph and J. G. Batsakis
FIG. 3. Case 1. Relatively poorly differentiated adenocarcinoma. (Hematoxylin and eosin, X475).
FIG. 4. Case 2. Replicated basement membrane material separates small basal type cells and imparts a pseudoglandular pattern to this adenoid cystic carcinoma of the larynx. (Hematoxylin and eosin, X485). 1162
Clinical records of 60 years. There appears to be a conspicuous male predominance in adenocarcinomas of the larynx as opposed to a nearly equal sex involvement by adenoid cystic carcinomas (Fechner, 1975). Adenocarcinomas, in contrast to adenoid cystic carcinomas, are rarely subglottic. Supraglottic and transglottic involvement are about equal. Approximately two-thirds of the adenoid cystic carcinomas are in subglottic structures (Fechner, 1975). As illustrated by the patient in Case 1, adenocarcinomas usually form large non-ulcerated masses. Adenoid cystic carcinomas manifest a less tendency to this large size. Clinical experience with adenocarcinoma and adenoid cystic carcinomas of the larynx is so meager that it is difficult to assess the effectiveness of any modality of treatment. Both carcinomas are lethal diseases, with a subjective impression that adenocarcinoma is a more rapid killer. Almost all patients with adenocarcinomas are dead within 2 years (Fechner, 1975). Widespread pulmonary and hepatic metastases are related to the outcome. Approximately one-third of the patients with adenoid cystic carcinomas eventually manifest pulmonary metastases (Fechner, 1975). The clinical course is, however more torpid with local recurrences and regional lymph node involvement. Follow-up to three or five years is not sufficient; recurrences are frequently delayed until three or five years, and there is an inverse proportion between survivors and non-survivors at 5, 10 and 15 year intervals (Eschwege et al., 1975; Sessions etal., 1975). It seems quite clear that current management of glandular malignancies of the larynx is not effective for cure in the majority of patients. Sessions et al. (1975) summarize their own experience and that of others by stating 'primary radical surgery treatment of this disease in no way appears to decrease recurrence rate or prolong survival time.' They recommend wide local excision or conservative surgery wherever feasible as the mode of primary therapy for any form of glandular malignancy of the larynx. REFERENCES J. G. (1974) Tumors of the Head and Neck: Clinical and Pathological Consideration, Williams and Wilkins Co., Baltimore, pp. 44-45. CADY, B. C, RIPPEY, J. H., and FRAZELL, E. L. (1968) Annals of Surgery, 167, 116. ESCHWEGE, F., CACHIN, Y. and MICHEAU, Ch. (1975) Canadian Journal of Otolaryngology, 4, 284. FECHNER, R. E. (1975) Canadian Journal of Otolaryngology, 4, 284. SESSIONS, D. G., MURRAY, J. P., BAUER, W. C, and OGURA, J. H. (1975) Canadian Journal of Otolaryngology, 4, 293.
BATSAKIS,
Dr. J. G. Batsakis, Dept. of Pathology, 1335 E. Catherine St., Ann Arbor, Michigan 48104.
1163
