The use of fine-needle aspiration in the diagnosis of metastatic pulmonary adenoid cystic carcinoma MARTHA BISHOP PITMAN, MD, MARK E. SHERMAN, MD, and W. STEPHEN BLACK-SCHAFFER, MD, Boston, Massachusetts, and Baltimore, Maryland
Nine patients with a history of adenoid cystic carcinoma (ACC) arising In the head and neck and In whom transthoracic fine-needle aspiration (FNA) was performed to Investigate pulmonary lesions are described. FNA yielded a definitive diagnosis of metastatic ACC In all cases. In six of the nine patients, the pulmonary metastases were asymptomatic. Lung lesions were discovered up to 19 years after primary tumor presentation, and In two, pulmonary spread was the only evidence of recurrent disease. On the basis of the FNAdiagnosis, these two patients were treated surgically for their Isolated pUlmonary metastases, and are disease free at 107 and 139 months. Six of the nine patients received radiation or chemotherapy; one Initially refused treatment. Thoracotomy was avoided In these patients on the basis of the FNA diagnosis. All are alive with disease at 25 to 246 months. The metastatic tumors were Indistinguishable cytologically from two primary pulmonary ACCs that were available for comparison. Our experience suggests FNA Is a useful tool In the diagnosis of ACC In pulmonary material-one which obviates the need for thoracotomy with Its associated morbidity. (OTOLARVNGOL HEAD NECK SURG 1991;104:441.)
Pulmonary metastases develop in more than 40% of patients with ACC arising in the head and neck region. 1.2 Such metastases may develop as late as 30 years after initial diagnosis and frequently represent the only indication of recurrent disease." Hence, pathologic examination to exclude primary lung carcinoma or benign disease of the lung is essential before treatment. We present nine patients with ACC in whom transthoracic FNA was successfully used to confirm the presence of pulmonary metastases.
tially diagnosed by FNA, were available for morphologic comparison. Three additional cases of metastatic pulmonary ACC diagnosed by FNA were found in the cytopathology files of the Johns Hopkins Hospital. FNA was performed using small-gauge needles with radiologic guidance. Specimens were prepared as smears, cytospins, or millipore filters, fixed in 95% ethanol or air-dried, and stained by the Papanicolaou or Diff Quik methods, respectively. All cytologic and histologic slides and clinical records were reviewed.
METHODS
RESULTS Clinical Data
Six patients with metastatic ACC who underwent pulmonary FNA were identified by review of the cytopathology records of all patients with histologically confirmed ACC diagnosed at the Massachusetts General Hospital. Two cases of ACC primary in the lung, ini-
From the Department of Pathology (Drs. Pitman and Black-Schaffer), Massachusetts General Hospital. Harvard Medical School, and the Department of Pathology (Dr. Sherman), The Johns Hopkins Hospital. Received for publication June 4, 1990: accepted Nov. 21, 1990. Reprint requests: Martha Bishop Pitman, MD, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114.
13/1126911
The patients with metastatic ACC were six women and three men who ranged in age from 27 to 74 years at presentation, with a median age of 37 years (Table I. patients I through 9). Of these nine patients, seven had primary salivary gland neoplasms (5 major, 2 minor), one had a maxillary sinus tumor, and one had a tracheal neoplasm. Seven patients were without pulmonary symptoms, and radiologic abnormalities on chest x-ray films were the only evidence of metastases. In two of the seven, metastases were discovered at initial presentation, and in five, distant spread was identified during 2 to 19 years of followup. The pulmonary metastases selected for biopsy were contralateral to the ....1
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Table 1. Clinical patient data Patient
no.
Sexlage
M/70
Primary tumor slle
Symptoms of lung tumor
Treatment of primarytumor
ASX, CXR for met workup ASX, CSR for met workup Dry cough and dysphonia, 9 yrs post primary ASX, fol/ow-up CXR at 7 yrs ASX, follow-up CXR at 3 yrs ASX, follow-up CXR at 2 yrs ASX, follow-up CXR at 2 yrs ASX, follow-up CXR at 5 yrs SOB and chest pain at 19 yrs
Surgery (curettage
2
F/32
3
F/34
4
F/41
5
F/34
Upper trachea Right parotid gland Left submandibular gland Left maxi 1lary sinus Soft palate
6
F/74
Soft palate
7
M/27
8
M/37
9
F/40
10
F/58
11
F/67
Left parotid gland Right parotid gland Right submandibular gland Right lower lobe of lung Left lower lobe of lung
ASX, routine CXR
2 yr history of wheezing
FNAs"e of lung
Treatment of lung tumor
LLL
Rads
Rads
LLL
Rads, chemo
Surgery, rads
RUL
Surgery, rads
Surgery, rads
RML
Surgery
Surgery, rads
LLL
Rads
Surgery, rads (to tumor 1 yr later) Surgery, rads
RLL
Chemo
LUL
Chemo
Surgery, rads
RLL
Surgery
LUL
Chemo after initial refusal Rads, chemo
Surgery (right lower 10bectomy) Surgery (left upper lobectomy), rads
RLL
(See treatment of primary tumor)
LUL
(See treatment of primary tumor)
only)
FNA, Fine-needle aspiration: ASX, asymptomatic; CXR, chest x-ray; met, metastatic; LLL, left lower lobe; fads, radiation therapy; onemo, chemotherapy; RUL, right upper lobe, RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; SOB, shortness of breath.
Table 2. Clinical followup Time to
recurrence (mol
Total time followup (mol
Yes'
N/A'
25
2
No
N/A
36
3
N/A N/A
139
5
No No Yes
39
130
6
Yes
12
60
7
No
N/A
30
8
No
N/A
72
9
Yes
216
No No
N/A N/A
Patient no.
4
10 11
Recurrence of primary tumor
107
246
31 19t
'Primary exophytic tumor removed by curettage only. tDied of other causes at 19 months
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Disease status Metastatic disease Metastatic disease Disease free Disease free Metastatic disease Metastatic disease Metastatic disease Metastatic disease Metastatic disease Disease free Disease freet
Volume 104 Number 4
Metastatic pulmonary adenoid cystic carcinoma
April 1991
~
Fig . 1. Large fragments of tissuerevea l a characteristic cohesive . three -dimensiona l sieve-like pattern (papanicolaou stain; original magnificat ion x 50.)
Fig. 2. Spaces filled with hyaline basement membrane material are surrounded by small. basalold cells with uniform nuclei. inconspicuous nucleon. no nuclear molding. and little cytoplasm (papanicolaou stain; original magnification x 500.)
primary tumor in two of the six cases in which laterality of the primary was well defined. Recurrent primary tumors, which became evident up to 18 years after presentation, developed in four patients.
Pulmonary metastases were the only evidence of disease in two patients (patients 3 and 4) . Patient 3 underwent lobectomy and received postoperative radiation therapy to treat positive bronchial margins, and patient
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A
.,
B Fig. 3. A. Hyaline material partially covered by epithelium (o"ow) (papanicolaou stain; original magnification x 313.) B. Free hyaline globules (o"ow), characteristic of ACC (papanicolaou stain; original magnification x 500.)
4 underwent wedge resection of two separate nodules. The other seven patients received palliative radiation and / or chemotherapy. These seven patients are alive with metastatic disease at 25 to 246 months and patients 3 and 4 are alive and disease-free at 107 and 139 months after initial diagnosis, respectively. Both patients with primary pulmonary ACC (patients 10 and II) were treated with surgery on the basis of the FNA diagnosis. Histology of the resection specimens of these cases and the two resections of metastatic
ACC confirmed the FNA diagnosis. Patient II had peribronchial lymph node metastases and therefore received postoperative radiation therapy. The two patients with primary pulmonary ACC are clinically diseasefree at 19 and 31 months. Cytomorphology. The FNA specimens of all nine cases of metastatic ACC were cellular and cytologically similar. Large fragments of tissue revealed a cohesive, three-dimensional sieve-like pattern (Fig. I). Small tissue fragments best illustrated the basaloid cells with
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Volume 104 Number 4 April 1991
Metastatic pulmonary adenoid cystic carcinoma
..as
Fig. 4. The cytomorphology recapitulates the hlstomorphology of small. uniform cells forming trabeculae and cribriform spaces filled with transparent to cyanophilic material (Papanicolaou stain; original magnification x 125.)
bland, rather uniform, homogeneous nuclei, inconspicuous nucleoli, no nuclear molding, and little cytoplasm. surrounding cystic spaces , many of which were filled with transparent to cyanophilic hyaline basement membrane material (Fig. 2). Occasionally this material was only partially covered by epithelium (Fig. 3, A), and was infrequently present as isolated globules (Fig. 3, B, arrow). The background was free of necrosis and inflammation in all cases. Single cells were few in number and mitoses were absent. These features were identical to those observed in the two cases of primary pulmonary ACC, and recapitulate the histomorphologic picture (Fig. 4).
Comment The lung is the most common site of metastases in patients with ACC of the head and neck, 1-4 but because distant spread may occur after a long disease-free intervaI,3-6 pathologic examination of pulmonary lesions is necessary before treatment. Our experience suggests that FNA is an effective procedure for the pathologic confirmation of pulmonary metastases in patients with ACC. FNA yielded a definitive diagnosis of ACC in all patients in this series. In seven of the nine patients with metastases, the pulmonary disease was asymptomatic. Lung metastases developed up to 19 years after initial
presentation, and in five patients, were the only indication of recurrent disease at the time of FNA. In all cases, the pathologic material was sufficient to render a specific diagnosis of ACC and exclude primary lung tumors and non-neoplastic disease. On-site rapid evaluation of pulmonary FNAs, as is performed for all of our patients, helps ensure adequacy of the biopsy with the smallest number of needle passes, decreasing the risk of pneumothorax and other potential complications associated with core needle and open lung biopsies. 7.8 None of our patients experienced biopsy-related complications. On the basis of cytologic diagnosis, seven patients were treated with radiation or chemotherapy, and thoracotomy was averted. The remaining two patients underwent resection of their pulmonary lesions and are alive, disease-free, at 19 and 24 months after surgery. Patients in whom isolated pulmonary metastases of ACC develop are typically asymptomatic and tend to live many years after diagnosis.":" In the absence of extrathoracic metastases and recurrent primary disease, resection of pulmonary metastases has gained favor over the past few years with various types of primary malignancies. 11-13 Studies evaluating the operability of metastatic disease have suggested that resection may be especially indicated for tumors with slow growth rate. 14 ACC is characteristically a slowly growing neo-
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plasm, \-\0 and resection of pulmonary metastases may improve long-term survival. Primary tracheal or bronchial ACC, if completely resected, has a favorable long-term prognosis. 15.16 Both patients with primary pulmonary ACC in this series (patients 10 and II) were treated by lobectomy and were clinically disease-free at 31 and 19 months of followup, respectively. FNA was of use in this setting in establishing a definitive preoperative diagnosis and thereby assisting the frozen section pathologist in the appropriate evaluation of surgical resection margins. The accuracy of FNA cytology in the diagnosis of ACC has been well documented":": however, experience with the cytologic diagnosis of ACC in respiratory material is limited.":" Our findings suggest that the cytologic appearance of ACC in aspirated pulmonary tissue is highly characteristic and should permit a definitive diagnosis in nearly all cases. Microscopically, primary and metastatic pulmonary ACC are indistinguishable from ACC arising in other sites.":":":" The small uniform cells of ACC are easily distinguished from the large, usually pleomorphic cells of non-small cell carcinomas of the lung. 26 Unlike small cell undifferentiated carcinoma, ACC displays a uniform, finely granular nuclear chromatin pattern and lacks nuclear molding, crush artifact, and necrosis. Carcinoid tumors generally exhibit greater loss of cohesion and more cytoplasm" than ACe. Unlike carcinoid tumors, ACC does not show immunohistochemical evidence of neuroendocrine differentiation. In all of our cases, the distinctive cribriform pattern and characteristic globules of basement membrane material were easily discerned. We reviewed the histopathology of several primary pulmonary adenoid cystic carcinomas, including the two diagnosed by FNA included in this study, in addition to more than 20 cases of tracheal ACC, and failed to identify a single case in which the tumor extended to the epithelial surface. Despite narrowing and distortion of the bronchial and tracheal lumen by invasive tumor, the epithelial layer and basement membrane appeared intact in all cases, indicating that ACC is unlikely to shed malignant cells and, thus, also unlikely to be diagnosed in exfoliated material. 27 Our experience demonstrates that FNA is an accurate means of establishing a definitive diagnosis of metastatic pulmonary ACC that may obviate the need for thoracotomy with its associated morbidity. We wish to thank Dr. Hermes Grillo for his review and critical appraisal of this manuscript, and Ms. Christine Peters for her expert assistance in preparation of the manuscript.
REFERENCES 1. Marsh WL, Allen MS. Adenoid cystic carcinoma: biologic behavior in 38 patients. Cancer 1979;43:1463-73. 2. Conley J, Dingman D. Adenoid cystic carcinoma in the head and neck (cylindroma). Arch Otolaryngol 1974;100:81-90. 3. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83. 4. Moran Jl, Becker SM, Brady LW, et al. Adenoid cystic carcinoma, a clinicopathologic study. Cancer 1961;14:1235-50. 5. Osborn DA. Morphology and the natural history of cribriform adenocarcinoma (adenoid cystic carcinoma). J Clin Pathol 1977;30:195-205. 6. Ampil FL, Misra RP. Factors influencing survival of patients with adenoid cystic carcinoma of the salivary glands. J Oral Maxillofac Surg 1987;45:1005-10. 7. Nordenstrom BE. Technical aspects of obtaining cellular material from lesions deep in the lung: a radiologist's view and description of the screw-needle sampling technique. Acta Cytol 1984; 28:233-42. 8. Ray JF, Lawton BR, Myers WO, et al. Open pulmonary biopsy: nineteen-year experience with 4 I6 consecutive operations. Chest 1976;69:43-7. 9. Mountain CF, Khalil KG, Hennes KE, Frazier OH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer 1978;41:833-40. 10. Lampe I, Zatzkin H. Pulmonary metastases of pseudoadenomatous basal-cell carcinoma (mucous and salivary gland tumor). Radiology 1948;53:379-85. II. Mountain CF, Khalil KG, Hennes KE, Frazier OH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer 1978;41:833-40. 12. Morrow CE, Vassilopoulos PP, Girage TB. Surgical resection for metastatic neoplasms of the lung: experience at the University of Minnesota Hospitals. Cancer 1980;45:2981-5. 13. Mountain CF, McMurtrey MJ, Hennes KE. Surgery for pulmonary metastases: a 20-year experience. Ann Thorac Surg 1984;38:323-30. 14. Joseph WL. Prognostic significance of tumor doubling time in evaluating operability in pulmonary metastatic disease. J Thorac Cardiovasc Surg 1974;61:23-32. 15. Conlan AA. Payne WS, Woolner LB. Sanderson DR. Adenoid cystic carcinoma and mucoepidermoid carcinoma of the bronchus. 1 Thorac Cardiovasc Surg 1978;76:369-77. 16. Grillo HC, Mathisen OJ. Primary tracheal tumors: treatment and results. Ann Thorac Surg 1990;49:69-77. 17. Eneroth CM, Zajicek J. Aspiration biopsy of salivary gland: IV. Morphologic studies on smears and histologic sections from 45 cases of ACe. Acta Cytol 1969;13:59-63. 18. Frable WI, Goplerud DR. Adenoid cystic carcinoma of Bartholin's gland: diagnosis by aspiration biopsy. Acta Cytol 1975;19:152-3. 19. Geisinger KR. Reynolds GO, Vance RP, McGuirt WF. Adenoid cystic carcinoma arising in a pleomorphic adenoma of the parotid gland: an aspiration cytology and ultrastructural study. Acta Cytol 1985;29:511. 20. Malberger E, Gidal-On M. Adenoid cystic carcinoma of the orbit diagnosed by means of aspirative cytology. Ophthalmologica (Base\) 1985;190:125-7. 21. Plafker J, Nosher IL. Fine needle aspiration of liver with metastatic adenoid cystic carcinoma. Acta Cytol 1983;27: 323-5.
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Metastatic pulmonary adenoid cystic carcinoma
April 1991
22. Smith RC, Amy RW. Adenoid cystic carcinoma metastatic to • the lung: report of a case diagnosed by fine needle aspiration biopsy cytology. Acta Cytol 1985;29:533-4. 23. Anderson RI, Iohnston WW, Szpak CA. Fine needle aspiration of adenoid cystic carcinoma metastatic to the lung: cytologic features and differential diagnosis. Acta Cytol 1985;29:527-32.• 24. Lawrence IB, Mazur MT. Adenoid cystic carcinoma: a comparative pathologic study of tumor in salivary gland, breast, lung and cervix. Hum Pathol 1982;13:916-24.
447
25. Zaloudek C, Oertel YC, Orenstein JM. Adenoid cystic carcinoma of the breast. Am J Clin Pathol 1984;81:297-307. 26. Szyfelbein WM, Ross JS. Carcinoids, atypical carcinoids and small-cell carcinomas of the lung: differential diagnosis of fine needle aspiration biopsy specimens. Diag Cytopathol 1988;4: 1-8. 27. Lozowski MS, Mishriki Y, Solitare GB. Cytopathologic features of adenoid cystic carcinoma: case report and literature review. Acta Cytol 1982;27:317-22.
AVAILABU NOWI The FIVE-YEAR (\981-1985) CUMULATIVE INDEX TO OTOLARYNGOLOGY-HEAD AND NECK SURGERY can be purchased from the Publisher for $36.00. This comprehensive, 84-page reference guide is a current presentation of all topics included in the Journal from January 1981 through December 1985 (volumes 8993)-the past 5 volumes. It incorporates complete references to over 570 original articles, abstracts, case reports, letters, editorials, and CME articles. It features 1,473 Subject Headings, under which there are 3,284 references. Each subject entry lists the complete article title, author(s), volume, page, and year of publication. In addition, it includes 2,188 Author Entries, which list contributors, along with their respective titles, author-to-author referral, volume, page, and publication date. To purchase, call or write: Mosby-Year Book, Inc., 11830 Westline Industrial Dr., St. Louis, Missouri 63146-3318, or telephone FREE 1-800-325-4177, extension 4531, Journal Fulfillment (in Missouri call collect at 314-872-8370, extension 4531, Journal Fulfillment). Please reference book code number 2606-4 when placing your order. PREPAYMENT REQUIRED. Make checks payable to Mosby-Year Book, Inc.; (all payments must be in U.S. funds drawn on a U.S. bank). Price: $36.00 in the U.S., $38.50 international (price includes mailing charges).
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Nine patients with a history of adenoid cystic carcinoma (ACC) arising In the head and neck and In whom transthoracic fine-needle aspiration (FNA) was performed to Investigate pulmonary lesions are described. FNA yielded a definitive diagnosis of metastatic ACC In all cases. In six of the nine patients, the pulmonary metastases were asymptomatic. Lung lesions were discovered up to 19 years after primary tumor presentation, and In two, pulmonary spread was the only evidence of recurrent disease. On the basis of the FNAdiagnosis, these two patients were treated surgically for their Isolated pUlmonary metastases, and are disease free at 107 and 139 months. Six of the nine patients received radiation or chemotherapy; one Initially refused treatment. Thoracotomy was avoided In these patients on the basis of the FNA diagnosis. All are alive with disease at 25 to 246 months. The metastatic tumors were Indistinguishable cytologically from two primary pulmonary ACCs that were available for comparison. Our experience suggests FNA Is a useful tool In the diagnosis of ACC In pulmonary material-one which obviates the need for thoracotomy with Its associated morbidity. (OTOLARVNGOL HEAD NECK SURG 1991;104:441.)
Pulmonary metastases develop in more than 40% of patients with ACC arising in the head and neck region. 1.2 Such metastases may develop as late as 30 years after initial diagnosis and frequently represent the only indication of recurrent disease." Hence, pathologic examination to exclude primary lung carcinoma or benign disease of the lung is essential before treatment. We present nine patients with ACC in whom transthoracic FNA was successfully used to confirm the presence of pulmonary metastases.
tially diagnosed by FNA, were available for morphologic comparison. Three additional cases of metastatic pulmonary ACC diagnosed by FNA were found in the cytopathology files of the Johns Hopkins Hospital. FNA was performed using small-gauge needles with radiologic guidance. Specimens were prepared as smears, cytospins, or millipore filters, fixed in 95% ethanol or air-dried, and stained by the Papanicolaou or Diff Quik methods, respectively. All cytologic and histologic slides and clinical records were reviewed.
METHODS
RESULTS Clinical Data
Six patients with metastatic ACC who underwent pulmonary FNA were identified by review of the cytopathology records of all patients with histologically confirmed ACC diagnosed at the Massachusetts General Hospital. Two cases of ACC primary in the lung, ini-
From the Department of Pathology (Drs. Pitman and Black-Schaffer), Massachusetts General Hospital. Harvard Medical School, and the Department of Pathology (Dr. Sherman), The Johns Hopkins Hospital. Received for publication June 4, 1990: accepted Nov. 21, 1990. Reprint requests: Martha Bishop Pitman, MD, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114.
13/1126911
The patients with metastatic ACC were six women and three men who ranged in age from 27 to 74 years at presentation, with a median age of 37 years (Table I. patients I through 9). Of these nine patients, seven had primary salivary gland neoplasms (5 major, 2 minor), one had a maxillary sinus tumor, and one had a tracheal neoplasm. Seven patients were without pulmonary symptoms, and radiologic abnormalities on chest x-ray films were the only evidence of metastases. In two of the seven, metastases were discovered at initial presentation, and in five, distant spread was identified during 2 to 19 years of followup. The pulmonary metastases selected for biopsy were contralateral to the ....1
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OtolaryngologyHead and Neck Surgery
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Table 1. Clinical patient data Patient
no.
Sexlage
M/70
Primary tumor slle
Symptoms of lung tumor
Treatment of primarytumor
ASX, CXR for met workup ASX, CSR for met workup Dry cough and dysphonia, 9 yrs post primary ASX, fol/ow-up CXR at 7 yrs ASX, follow-up CXR at 3 yrs ASX, follow-up CXR at 2 yrs ASX, follow-up CXR at 2 yrs ASX, follow-up CXR at 5 yrs SOB and chest pain at 19 yrs
Surgery (curettage
2
F/32
3
F/34
4
F/41
5
F/34
Upper trachea Right parotid gland Left submandibular gland Left maxi 1lary sinus Soft palate
6
F/74
Soft palate
7
M/27
8
M/37
9
F/40
10
F/58
11
F/67
Left parotid gland Right parotid gland Right submandibular gland Right lower lobe of lung Left lower lobe of lung
ASX, routine CXR
2 yr history of wheezing
FNAs"e of lung
Treatment of lung tumor
LLL
Rads
Rads
LLL
Rads, chemo
Surgery, rads
RUL
Surgery, rads
Surgery, rads
RML
Surgery
Surgery, rads
LLL
Rads
Surgery, rads (to tumor 1 yr later) Surgery, rads
RLL
Chemo
LUL
Chemo
Surgery, rads
RLL
Surgery
LUL
Chemo after initial refusal Rads, chemo
Surgery (right lower 10bectomy) Surgery (left upper lobectomy), rads
RLL
(See treatment of primary tumor)
LUL
(See treatment of primary tumor)
only)
FNA, Fine-needle aspiration: ASX, asymptomatic; CXR, chest x-ray; met, metastatic; LLL, left lower lobe; fads, radiation therapy; onemo, chemotherapy; RUL, right upper lobe, RML, right middle lobe; RLL, right lower lobe; LUL, left upper lobe; SOB, shortness of breath.
Table 2. Clinical followup Time to
recurrence (mol
Total time followup (mol
Yes'
N/A'
25
2
No
N/A
36
3
N/A N/A
139
5
No No Yes
39
130
6
Yes
12
60
7
No
N/A
30
8
No
N/A
72
9
Yes
216
No No
N/A N/A
Patient no.
4
10 11
Recurrence of primary tumor
107
246
31 19t
'Primary exophytic tumor removed by curettage only. tDied of other causes at 19 months
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Disease status Metastatic disease Metastatic disease Disease free Disease free Metastatic disease Metastatic disease Metastatic disease Metastatic disease Metastatic disease Disease free Disease freet
Volume 104 Number 4
Metastatic pulmonary adenoid cystic carcinoma
April 1991
~
Fig . 1. Large fragments of tissuerevea l a characteristic cohesive . three -dimensiona l sieve-like pattern (papanicolaou stain; original magnificat ion x 50.)
Fig. 2. Spaces filled with hyaline basement membrane material are surrounded by small. basalold cells with uniform nuclei. inconspicuous nucleon. no nuclear molding. and little cytoplasm (papanicolaou stain; original magnification x 500.)
primary tumor in two of the six cases in which laterality of the primary was well defined. Recurrent primary tumors, which became evident up to 18 years after presentation, developed in four patients.
Pulmonary metastases were the only evidence of disease in two patients (patients 3 and 4) . Patient 3 underwent lobectomy and received postoperative radiation therapy to treat positive bronchial margins, and patient
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A
.,
B Fig. 3. A. Hyaline material partially covered by epithelium (o"ow) (papanicolaou stain; original magnification x 313.) B. Free hyaline globules (o"ow), characteristic of ACC (papanicolaou stain; original magnification x 500.)
4 underwent wedge resection of two separate nodules. The other seven patients received palliative radiation and / or chemotherapy. These seven patients are alive with metastatic disease at 25 to 246 months and patients 3 and 4 are alive and disease-free at 107 and 139 months after initial diagnosis, respectively. Both patients with primary pulmonary ACC (patients 10 and II) were treated with surgery on the basis of the FNA diagnosis. Histology of the resection specimens of these cases and the two resections of metastatic
ACC confirmed the FNA diagnosis. Patient II had peribronchial lymph node metastases and therefore received postoperative radiation therapy. The two patients with primary pulmonary ACC are clinically diseasefree at 19 and 31 months. Cytomorphology. The FNA specimens of all nine cases of metastatic ACC were cellular and cytologically similar. Large fragments of tissue revealed a cohesive, three-dimensional sieve-like pattern (Fig. I). Small tissue fragments best illustrated the basaloid cells with
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Volume 104 Number 4 April 1991
Metastatic pulmonary adenoid cystic carcinoma
..as
Fig. 4. The cytomorphology recapitulates the hlstomorphology of small. uniform cells forming trabeculae and cribriform spaces filled with transparent to cyanophilic material (Papanicolaou stain; original magnification x 125.)
bland, rather uniform, homogeneous nuclei, inconspicuous nucleoli, no nuclear molding, and little cytoplasm. surrounding cystic spaces , many of which were filled with transparent to cyanophilic hyaline basement membrane material (Fig. 2). Occasionally this material was only partially covered by epithelium (Fig. 3, A), and was infrequently present as isolated globules (Fig. 3, B, arrow). The background was free of necrosis and inflammation in all cases. Single cells were few in number and mitoses were absent. These features were identical to those observed in the two cases of primary pulmonary ACC, and recapitulate the histomorphologic picture (Fig. 4).
Comment The lung is the most common site of metastases in patients with ACC of the head and neck, 1-4 but because distant spread may occur after a long disease-free intervaI,3-6 pathologic examination of pulmonary lesions is necessary before treatment. Our experience suggests that FNA is an effective procedure for the pathologic confirmation of pulmonary metastases in patients with ACC. FNA yielded a definitive diagnosis of ACC in all patients in this series. In seven of the nine patients with metastases, the pulmonary disease was asymptomatic. Lung metastases developed up to 19 years after initial
presentation, and in five patients, were the only indication of recurrent disease at the time of FNA. In all cases, the pathologic material was sufficient to render a specific diagnosis of ACC and exclude primary lung tumors and non-neoplastic disease. On-site rapid evaluation of pulmonary FNAs, as is performed for all of our patients, helps ensure adequacy of the biopsy with the smallest number of needle passes, decreasing the risk of pneumothorax and other potential complications associated with core needle and open lung biopsies. 7.8 None of our patients experienced biopsy-related complications. On the basis of cytologic diagnosis, seven patients were treated with radiation or chemotherapy, and thoracotomy was averted. The remaining two patients underwent resection of their pulmonary lesions and are alive, disease-free, at 19 and 24 months after surgery. Patients in whom isolated pulmonary metastases of ACC develop are typically asymptomatic and tend to live many years after diagnosis.":" In the absence of extrathoracic metastases and recurrent primary disease, resection of pulmonary metastases has gained favor over the past few years with various types of primary malignancies. 11-13 Studies evaluating the operability of metastatic disease have suggested that resection may be especially indicated for tumors with slow growth rate. 14 ACC is characteristically a slowly growing neo-
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446
OtolaryngologyHead and Neck Surgery
PmAAN at oJ.
plasm, \-\0 and resection of pulmonary metastases may improve long-term survival. Primary tracheal or bronchial ACC, if completely resected, has a favorable long-term prognosis. 15.16 Both patients with primary pulmonary ACC in this series (patients 10 and II) were treated by lobectomy and were clinically disease-free at 31 and 19 months of followup, respectively. FNA was of use in this setting in establishing a definitive preoperative diagnosis and thereby assisting the frozen section pathologist in the appropriate evaluation of surgical resection margins. The accuracy of FNA cytology in the diagnosis of ACC has been well documented":": however, experience with the cytologic diagnosis of ACC in respiratory material is limited.":" Our findings suggest that the cytologic appearance of ACC in aspirated pulmonary tissue is highly characteristic and should permit a definitive diagnosis in nearly all cases. Microscopically, primary and metastatic pulmonary ACC are indistinguishable from ACC arising in other sites.":":":" The small uniform cells of ACC are easily distinguished from the large, usually pleomorphic cells of non-small cell carcinomas of the lung. 26 Unlike small cell undifferentiated carcinoma, ACC displays a uniform, finely granular nuclear chromatin pattern and lacks nuclear molding, crush artifact, and necrosis. Carcinoid tumors generally exhibit greater loss of cohesion and more cytoplasm" than ACe. Unlike carcinoid tumors, ACC does not show immunohistochemical evidence of neuroendocrine differentiation. In all of our cases, the distinctive cribriform pattern and characteristic globules of basement membrane material were easily discerned. We reviewed the histopathology of several primary pulmonary adenoid cystic carcinomas, including the two diagnosed by FNA included in this study, in addition to more than 20 cases of tracheal ACC, and failed to identify a single case in which the tumor extended to the epithelial surface. Despite narrowing and distortion of the bronchial and tracheal lumen by invasive tumor, the epithelial layer and basement membrane appeared intact in all cases, indicating that ACC is unlikely to shed malignant cells and, thus, also unlikely to be diagnosed in exfoliated material. 27 Our experience demonstrates that FNA is an accurate means of establishing a definitive diagnosis of metastatic pulmonary ACC that may obviate the need for thoracotomy with its associated morbidity. We wish to thank Dr. Hermes Grillo for his review and critical appraisal of this manuscript, and Ms. Christine Peters for her expert assistance in preparation of the manuscript.
REFERENCES 1. Marsh WL, Allen MS. Adenoid cystic carcinoma: biologic behavior in 38 patients. Cancer 1979;43:1463-73. 2. Conley J, Dingman D. Adenoid cystic carcinoma in the head and neck (cylindroma). Arch Otolaryngol 1974;100:81-90. 3. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83. 4. Moran Jl, Becker SM, Brady LW, et al. Adenoid cystic carcinoma, a clinicopathologic study. Cancer 1961;14:1235-50. 5. Osborn DA. Morphology and the natural history of cribriform adenocarcinoma (adenoid cystic carcinoma). J Clin Pathol 1977;30:195-205. 6. Ampil FL, Misra RP. Factors influencing survival of patients with adenoid cystic carcinoma of the salivary glands. J Oral Maxillofac Surg 1987;45:1005-10. 7. Nordenstrom BE. Technical aspects of obtaining cellular material from lesions deep in the lung: a radiologist's view and description of the screw-needle sampling technique. Acta Cytol 1984; 28:233-42. 8. Ray JF, Lawton BR, Myers WO, et al. Open pulmonary biopsy: nineteen-year experience with 4 I6 consecutive operations. Chest 1976;69:43-7. 9. Mountain CF, Khalil KG, Hennes KE, Frazier OH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer 1978;41:833-40. 10. Lampe I, Zatzkin H. Pulmonary metastases of pseudoadenomatous basal-cell carcinoma (mucous and salivary gland tumor). Radiology 1948;53:379-85. II. Mountain CF, Khalil KG, Hennes KE, Frazier OH. The contribution of surgery to the management of carcinomatous pulmonary metastases. Cancer 1978;41:833-40. 12. Morrow CE, Vassilopoulos PP, Girage TB. Surgical resection for metastatic neoplasms of the lung: experience at the University of Minnesota Hospitals. Cancer 1980;45:2981-5. 13. Mountain CF, McMurtrey MJ, Hennes KE. Surgery for pulmonary metastases: a 20-year experience. Ann Thorac Surg 1984;38:323-30. 14. Joseph WL. Prognostic significance of tumor doubling time in evaluating operability in pulmonary metastatic disease. J Thorac Cardiovasc Surg 1974;61:23-32. 15. Conlan AA. Payne WS, Woolner LB. Sanderson DR. Adenoid cystic carcinoma and mucoepidermoid carcinoma of the bronchus. 1 Thorac Cardiovasc Surg 1978;76:369-77. 16. Grillo HC, Mathisen OJ. Primary tracheal tumors: treatment and results. Ann Thorac Surg 1990;49:69-77. 17. Eneroth CM, Zajicek J. Aspiration biopsy of salivary gland: IV. Morphologic studies on smears and histologic sections from 45 cases of ACe. Acta Cytol 1969;13:59-63. 18. Frable WI, Goplerud DR. Adenoid cystic carcinoma of Bartholin's gland: diagnosis by aspiration biopsy. Acta Cytol 1975;19:152-3. 19. Geisinger KR. Reynolds GO, Vance RP, McGuirt WF. Adenoid cystic carcinoma arising in a pleomorphic adenoma of the parotid gland: an aspiration cytology and ultrastructural study. Acta Cytol 1985;29:511. 20. Malberger E, Gidal-On M. Adenoid cystic carcinoma of the orbit diagnosed by means of aspirative cytology. Ophthalmologica (Base\) 1985;190:125-7. 21. Plafker J, Nosher IL. Fine needle aspiration of liver with metastatic adenoid cystic carcinoma. Acta Cytol 1983;27: 323-5.
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Volume 104 Number 4
Metastatic pulmonary adenoid cystic carcinoma
April 1991
22. Smith RC, Amy RW. Adenoid cystic carcinoma metastatic to • the lung: report of a case diagnosed by fine needle aspiration biopsy cytology. Acta Cytol 1985;29:533-4. 23. Anderson RI, Iohnston WW, Szpak CA. Fine needle aspiration of adenoid cystic carcinoma metastatic to the lung: cytologic features and differential diagnosis. Acta Cytol 1985;29:527-32.• 24. Lawrence IB, Mazur MT. Adenoid cystic carcinoma: a comparative pathologic study of tumor in salivary gland, breast, lung and cervix. Hum Pathol 1982;13:916-24.
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25. Zaloudek C, Oertel YC, Orenstein JM. Adenoid cystic carcinoma of the breast. Am J Clin Pathol 1984;81:297-307. 26. Szyfelbein WM, Ross JS. Carcinoids, atypical carcinoids and small-cell carcinomas of the lung: differential diagnosis of fine needle aspiration biopsy specimens. Diag Cytopathol 1988;4: 1-8. 27. Lozowski MS, Mishriki Y, Solitare GB. Cytopathologic features of adenoid cystic carcinoma: case report and literature review. Acta Cytol 1982;27:317-22.
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