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Primary malignant melanomas of the lung and adrenal
Primary Malignant Melanomas of the Lung and Adrenal PER H. B. CARSTENS, ME),* JAMES G. KUHNS, ME),t AND CYRUS GHAZI, MD t Malignant melanoma originating outside the skin, juxtacutaneous mucous membranes, eyes, and leptomeninges is a very rare neoplasm. Two such primary visceral malignant melanomas from the lung and adrenal are described in detail. HUM PATHOL 15:910--914, 1984. Malignant melanoma originating outside the skin, s q u a m o u s m u c o u s m e m b r a n e s , eyes, a n d lept o m e n i n g e s is very rare. It is difficult to p r o v e that a visceral m a l i g n a n t m e l a n o m a is a p r i m a r y lesion, because m a l i g n a n t m e l a n o m a s in the m o r e c o m m o n locations m a y metastasize widely. Metastases f r o m the m o r e c o m m o n p r i m a r y s o u r c e s m u s t t h e r e f o r e be c o n v i n c i n g l y e x c l u d e d 9 T h i s can be a c h i e v e d o n l y rarely, and, even then, the p r o b l e m o f s p o n t a n e o u s regression in a c u t a n e o u s m a l i g n a n t m e l a n o m a remains. 1 T w o cases o f m a l i g n a n t m e l a n o m a , c o n s i d e r e d to be p r i m a r y in the l u n g a n d in the adrenal, are presented.
REPORT OF TWO CASES
Case 2. A 32-year-old black woman was admitted with a three-week history of pain in the left flank; she had had a spontaneous abortion four weeks previously. She had experienced recurrent discomfort in the left flank for several years, with a 4.5-kg weight loss during the preceding year. Intravenous pyelography showed inferior displacement of the left kidney by a large mass. Arteriography demonstrated a relatively avascular mass, fed primarily by the left adrenal and left renal arteries, in the retroperitoneum. The patient underwent left nephroadrenalectomy. No extension of the tumor to neighboring organs or other tumor masses were encountered during the operation. A tentative diagnosis of primary malignant melanoma of the adrenal was made. A search for a p r i m a r y t u m o r in the more common locations was unsuccessful. The patient subsequently moved to Georgia, where she died seven months afterward with widespread metastatic disease to the liver and hmgs as evidenced by radiography. Prior to death, the patient had received chemotherapy and radiotherapy to the left hip area after histologic confirmation of malignant melanoma in a biopsy specimen from this area. No p r i m a r y t u m o r had a p p e a r e d in m o r e 9common locations at the time of death. A request for autopsy was denied.
Case 1. A 29-year-old white woman was admitted for evaluation of a lung mass that lind been identified on a routine chest radiograph four weeks previously. The patient underwent right upper lobectomy, and a tumor occupying the right u p p e r lobe was found. A diagnosis of primary malignant melanoma in the lung was rendered. The patient was carefully screened for evidence of a primary malignant melanoma in the more common locations, i.e., skin, eyes, leptomeninges, and squamous mucous membranes, but without success. However, she reported ha~5ng had a mole removed from the right scapular area approximately six years prior to the current admission. The mole had been present for 13 years without change. A f t e r t h o r a c o t o m y , i m m u n o t h e r a p y and chemotherapy were begun. During the course of treatment radiographic evidence of metastases to the left tenth and 12th ribs, left iliac bone, and the proximal portion of the left femur developed. At the same time multiple skin metastases and progressive lung disease were discovered. The patient died one month later. Autopsy showed multiple small metastases in the lungs, heart, liver, both adrenals, kidneys, ovaries, sigmoid colon, dura, cerebellum, corpus striatum, skin, and the bones of the skull. No other primary tumor was observed, and no lesions were discovered in the nose, nasopharynx, urethra, vagina, anus, or rectum.
MATERIALSAND METHODS T i s s u e f o r light microscopic e x a m i n a t i o n f r o m both cases was fixed in f o r m a l i n a n d e m b e d d e d in p a r a f f i n . Sections w e r e s t a i n e d with h e m a t o x y l i n e o s i n a n d f o r m e l a n i n by t h e F o n t a n a - M a s s o n method. F o r electron microscopic e x a m i n a t i o n tissue was fixed in 10 p e r cent f o r m a l i n (case 2) or retrieved f r o m p a r a f f i n blocks (case 1). T i s s u e f r o m both cases was postfixed in o s m i u m tetroxide, processed roufinely f o r electron microscopy, a n d e x a m i n e d in an electron microscope.
PATHOLOGIC FINDINGS
Received August 23, 1983, from the Departments of Pathology,* University of Louisville School of Medicine, tNortonKosair-Children's Hospital and :~Suburban ttospital, Louisville. Kentucky. Revision accepted for publication October 27, 1983. Address correspondence and reprint requests to Dr. Carstens: Department of Pathology, .University of Louisville, Louisville, KY 40292.
910
Case 1. T h e r i g h t l o b e c t o m y s p e c i m e n c o n tained a large p a r a b r o n c h i a l t u m o r m e a s u r i n g 4 x 2.5 x 2 cm. T h e t u m o r w a s c o m p o s e d o f elongated, 'poorly d i f f e r e n t i a t e d neoplastic cells, which in s o m e areas r e s e m b l e d spindle cells (fig. 1). Most o f the cells h a d p r o m i n e n t nucleoli. T h e reaction with FontanaMasson stain f o r m e l a n i n was positive. I n o n e portion o f the t u m o r j u n c t i o n a l activity with s q u a m o u s m e t a plasia was o b s e r v e d in the overlying bronchial m u c o s a (fig. 2). T h e p a r a b r o n c h i a l l y m p h n o d e s a n d the resection line were f r e e o f t u m o r . Electron microscopic studies o f p a r a f f i n - e m b e d d e d , F o n t a n a - M a s s o n - p o s itive a r e a s d e m o n s t r a t e d t h e c h a r a c t e r i s t i c crossh a t c h e d a p p e a r a n c e o f p r e m e l a n o s o m e s (fig. 3). T h e
MALIGNANT MELANOMA OF LUNG AND ADRENAL (Carstens et al.]
FIGURE 1 (top). Case 1. Lung tumor composed of spindle cells. ~ FIGURE 2 (bottom]. Case 1. Bronchial mucosa demonstrating junctional activity and squamous metaplasia.
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FIGURE 3. Case t. Lung tumor with numerous premelanosomes and melanosomes. (x 25,000.) Inset, premelanosome. (x 76,000.]
slide of the elevated, hairy mole removed from tile patient's back six years previously was reviewed. It was cut for margins; several sections were examined and found to represent an intradermal nevus without junctional activity. Light microscopic examination at the time of autopsy showed the tumors in the various locations to be identical to the hmg tumor diagnosed earlier. Case 2. T h e removed tumor measured 14 • 9 • 5 cm in greatest dimension, and the weight, including the kidney, was 650 g. The mass appeared to be well encapsulated, with a smooth, glistening outer surface. On sectioning, large areas of necrosis and hemorrhage were found, but at tile periphery of the tumor viable tissue, dark brown to black, was noticed. At one pole of the specimen, closely related to the capsule, a narrow rim of grayish yellow tissue was grossly identifiable as a remnant of the left adrenal. The tumor appeared to be closely attached to the kidney but had not penetrated the capsule. Light microscopic examination o f multiple sections of the tumor showed the individual cells to be of variable sizes and shapes. Some formed nests and others solid masses, and in some areas the cells were spindly and had a sarcomatous appearance (fig. 4). Most of the cells had irregular nuclei, with prominent chromatin and nucleoli. Many abnormal mitotic figures were noticed, and m u h i n u c l e a t e d giant cells were also encountered. Vascular invasion was present. In some of
the sections normal adrenal cortical tissue was observed close to tile capsule. A large amount of brown pigment was seen in. sections stained with hematoxylin-eosin. The same areas were positive on FontanaM a s s o n staining. Electron microscopic examination d e m o n s t r a t e d cytoplasmic m e m b r a n e - b o u n d structures with cross-hatched filaments characteristic of a premelanosome (fig. 5). DISCUSSION A review of tile current literature revealed eight reported cases of primary malignant melanoma in the lung2-9; criteria for the diagnoses in these cases included the presence of melanin in a tumor histologically consistent with melanoma involving the respiratory epithelium, the absence of a current or previous p r i m a r y m e l a n o m a elsewhere, and no previously resected p i g m e n t e d skin lesion of unknown type3 ~ If autopsy to rule out a primary lesion elsewhere is included in the criteria, the field is limited to five cases. 3,4,7-9 I f we f u r t h e r m o r e require junctional changes, with invasion of intact bronchial mucosa by malignant melanoma cells with obvious m a l i g n a n t m e l a n o m a b e n e a t h , only one case remains, s O f the eight previously reported cases, four were in women2,4,6,7 and four in men ~,5,8,9 (age range, 33 912
MALIGNANTMELANOMA OF LUNG AND ADRENAL [Carstens et al.]
FIGURE 4 (top]. Case 2. Adrenal tumor composed of spindle cells. FIGURE 5 [bottom]. Case 2. Adrenal tumor with many premelanosomes and glycogen particles. ( x 1~,000.] Inset, premelanosome. [ x 76,000.]
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to 71 years). F o u r o f t h e t u m o r s w e r e in the left l u n g 3,4,5,8 a n d t h r e e in the right,2,6,9 a n d o n e ext e n d e d d o w n w a r d f r o m the carina in both the left and right main stem bronchi. 7 T w o were in the main stem bronchus,3, 7 o n e in the u p p e r lobe, 4 a n d five in the lower 10be.2,5,6,8,9 Six o f the eight t u m o r s were located centrally.. ~-8 Five o f the eight patients died within 11/2 years a f t e r diagnosis,3,4, 7-9 b u t two patients survived m o r e t h a n ten years a f t e r p n e u m o n e c t o m y a n d lobectomy. 5,6 O u r case 1 fulfills all o f these criteria, except for the m o l e r e m o v e d six years previously. T h e mole h a d , h o w e v e r , b e e n p r e s e n t f o r 13 y e a r s w i t h o u t c h a n g e a n d was f o u n d to be an i n t r a d e r m a l nevus without j u n c t i o n a l changes. F u r t h e r m o r e , the lack o f a n o t h e r p r i m a r y t u m o r at the time o f diagnosis o f the malignant m e l a n o m a in the lung, the j u n c t i o n a l changes in the b r o n c h u s , and the s u b s e q u e n t develo p m e n t o f multiple u n i f o r m , small widespread metastases strong.ly s u p p o r t the classification o f the lung t u m o r as a p r i m a r y t u m o r . We were unable to locate any r e f e r e n c e s to the presence o f melanocytes in n o r m a l lungs. However, it is not surprising to find a malignant m e l a n o m a in the lung, given that the respiratory tract develops as a d o w n g r o w t h f r o m the primitive f o r e g u t s o m e w h e r e between the p h a r y n x a n d the esophagus, two sites at which malignant m e l a n o m a s are k n o w n to occur. A review o f the c u r r e n t literature revealed t h r e e p r i m a r y m a l i g n a n t m e l a n o m a s in the a d r e n a l . 11-13 Many have e x p r e s s e d great reluctance to accept malignant m e l a n o m a s as p r i m a r y in the a d r e n a l because o f the f r e q u e n c y o f metastases to this organl4A 5 f r o m the m o r e c o m m o n p r i m a r y sources, such as the skin and eye. Criteria should include the presence o f a p r i m a r y malignant m e l a n o m a in only one o f the adrenals, n o p r i o r o r c u r r e n t m a l i g n a n t m e l a n o m a s elsewhere, n o removal o f p i g m e n t e d skin o r eye lesions, and, preferably, exclusion by autopsy o f the presence o f a h i d d e n p r i m a r y lesion. T h e t h r e e previously r e p o r t e d p r i m a r y m a l i g n a n t m e l a n o m a s o f the a d r e n a l were all large, cystic, a n d necrotic d a r k b r o w n o r black tumors. T w o o f the patients died after a y e a r with w i d e s p r e a d small metastases.11,12 N o follow-up i n f o r m a t i o n was available for the third patient.~3 O u r case 2 fulfills these criteria, except that autopsy was not p e r f o r m e d . W h e n the malignant mela n o m a was discovered in the left adrenal, a careful clinical search was initiated for a p r i m a r y t u m o r in
914
the m o r e c o m m o n locations, b u t without success. T h e patient died a f t e r seven m o n t h s with p r o v e d wides p r e a d metastatic malignant m e l a n o m a , w i t h n o primary t u m o r having a p p e a r e d . W e have not been able to find any c u r r e n t references to the presence o f melanocytes in the adrenal, a l t h o u g h this p h e n o m e n o n was m e n t i o n e d in the past. 16 Since the p h e o c h r o m o c y t e s in the medulla o f the adrenal, like the melanocytes, are considered to be d e r i v e d f r o m the neural crest, the presence o f melanocytes, a n d t h e r e f o r e o f a malignant melanoma, in the a d r e n a l would seem reasonable. Acknowledgments. T h e authors thank Cathie Caple, Lucille O. Chann, and Charlie D. Foreman for expert technical assistance and tile Department of Pathology, University of Kentucky, for making slides available (case I).
REFERENCES 1. Das Gupta T, Bowden L, Berg JW: Malignant melanoma of unknown primary origin. Surg Gynecol Obstet 117:341, 1963 2. Allen MS, Drash EC: Primary melanoma of the lung. Cancer 21:154, 1968 3. Gephardt GN: Malignant melanoma of the bronchus. Hv.xi PATIIOL12:671, 1981 4. Jensen OA, EgedorfJ: Primary malignant melanoma of the lung. Scand J Respir Dis 48:127, 1967 5. Reed RJ, Kent EM: Solitary pulmonary melanomas. Two case reports. J Thorac Cardiovasc Surg 48:226, 1964 6. Reid JD, Mehta V: Melanoma of the lower respiratory tract. Cancer 19:627, 1966 7. Robertson AJ, Sinclair DJM, Sutton PP, et al: Primary melanocarcinoma of the lower respiratory tract. Thorax 35:158, 1980 8. Salm R: A primary malignant melanoma of the bronchus. J Pathol Bact 85:121, 1963 9. Waher P, Fernandes.C, Florange W: Melanome malin primitif pulmonaire. Ann Anat Pathol 17:91, 1972 10. Carter D, EgglestonJC: Tumors of the lower respiratory tract. In Atlas of Tumor Pathology, series 2, fascicle 17. Washington, DC, Armed Forces Institute of Pathology, 1979, p 220 11. Dick JC, Ritchie GM, Thompson H: Histological differentiation between phaeochromocytoma and melanoma of the supradrenal gland. J Clin Pathol 8:89, 1955 12. Kniseley RM, Baggenstoss AH: Primary melanoma of the adrenal gland. Arch Pathol 42:345, 1946 13. Sasidharan K, Babu AS, Pandey AP, et ah Primary'melanoma of tile adrenal gland: a case report. J Urol 117:663, 1977 14. Das Gupta T, Brasfield R: Metastatic melanoma. A clinicopathological study. Cancer 17:1323, 1964 15. Willis RA: The Spread of Tumors in the Human Body. St. Louis, CV Mosby Co, 1952, p 202 16. Bourne GH: The Mammalian Adrenal Gland. Oxford, Oxford University Press, 1949, p 200
REPORT OF TWO CASES
Case 2. A 32-year-old black woman was admitted with a three-week history of pain in the left flank; she had had a spontaneous abortion four weeks previously. She had experienced recurrent discomfort in the left flank for several years, with a 4.5-kg weight loss during the preceding year. Intravenous pyelography showed inferior displacement of the left kidney by a large mass. Arteriography demonstrated a relatively avascular mass, fed primarily by the left adrenal and left renal arteries, in the retroperitoneum. The patient underwent left nephroadrenalectomy. No extension of the tumor to neighboring organs or other tumor masses were encountered during the operation. A tentative diagnosis of primary malignant melanoma of the adrenal was made. A search for a p r i m a r y t u m o r in the more common locations was unsuccessful. The patient subsequently moved to Georgia, where she died seven months afterward with widespread metastatic disease to the liver and hmgs as evidenced by radiography. Prior to death, the patient had received chemotherapy and radiotherapy to the left hip area after histologic confirmation of malignant melanoma in a biopsy specimen from this area. No p r i m a r y t u m o r had a p p e a r e d in m o r e 9common locations at the time of death. A request for autopsy was denied.
Case 1. A 29-year-old white woman was admitted for evaluation of a lung mass that lind been identified on a routine chest radiograph four weeks previously. The patient underwent right upper lobectomy, and a tumor occupying the right u p p e r lobe was found. A diagnosis of primary malignant melanoma in the lung was rendered. The patient was carefully screened for evidence of a primary malignant melanoma in the more common locations, i.e., skin, eyes, leptomeninges, and squamous mucous membranes, but without success. However, she reported ha~5ng had a mole removed from the right scapular area approximately six years prior to the current admission. The mole had been present for 13 years without change. A f t e r t h o r a c o t o m y , i m m u n o t h e r a p y and chemotherapy were begun. During the course of treatment radiographic evidence of metastases to the left tenth and 12th ribs, left iliac bone, and the proximal portion of the left femur developed. At the same time multiple skin metastases and progressive lung disease were discovered. The patient died one month later. Autopsy showed multiple small metastases in the lungs, heart, liver, both adrenals, kidneys, ovaries, sigmoid colon, dura, cerebellum, corpus striatum, skin, and the bones of the skull. No other primary tumor was observed, and no lesions were discovered in the nose, nasopharynx, urethra, vagina, anus, or rectum.
MATERIALSAND METHODS T i s s u e f o r light microscopic e x a m i n a t i o n f r o m both cases was fixed in f o r m a l i n a n d e m b e d d e d in p a r a f f i n . Sections w e r e s t a i n e d with h e m a t o x y l i n e o s i n a n d f o r m e l a n i n by t h e F o n t a n a - M a s s o n method. F o r electron microscopic e x a m i n a t i o n tissue was fixed in 10 p e r cent f o r m a l i n (case 2) or retrieved f r o m p a r a f f i n blocks (case 1). T i s s u e f r o m both cases was postfixed in o s m i u m tetroxide, processed roufinely f o r electron microscopy, a n d e x a m i n e d in an electron microscope.
PATHOLOGIC FINDINGS
Received August 23, 1983, from the Departments of Pathology,* University of Louisville School of Medicine, tNortonKosair-Children's Hospital and :~Suburban ttospital, Louisville. Kentucky. Revision accepted for publication October 27, 1983. Address correspondence and reprint requests to Dr. Carstens: Department of Pathology, .University of Louisville, Louisville, KY 40292.
910
Case 1. T h e r i g h t l o b e c t o m y s p e c i m e n c o n tained a large p a r a b r o n c h i a l t u m o r m e a s u r i n g 4 x 2.5 x 2 cm. T h e t u m o r w a s c o m p o s e d o f elongated, 'poorly d i f f e r e n t i a t e d neoplastic cells, which in s o m e areas r e s e m b l e d spindle cells (fig. 1). Most o f the cells h a d p r o m i n e n t nucleoli. T h e reaction with FontanaMasson stain f o r m e l a n i n was positive. I n o n e portion o f the t u m o r j u n c t i o n a l activity with s q u a m o u s m e t a plasia was o b s e r v e d in the overlying bronchial m u c o s a (fig. 2). T h e p a r a b r o n c h i a l l y m p h n o d e s a n d the resection line were f r e e o f t u m o r . Electron microscopic studies o f p a r a f f i n - e m b e d d e d , F o n t a n a - M a s s o n - p o s itive a r e a s d e m o n s t r a t e d t h e c h a r a c t e r i s t i c crossh a t c h e d a p p e a r a n c e o f p r e m e l a n o s o m e s (fig. 3). T h e
MALIGNANT MELANOMA OF LUNG AND ADRENAL (Carstens et al.]
FIGURE 1 (top). Case 1. Lung tumor composed of spindle cells. ~ FIGURE 2 (bottom]. Case 1. Bronchial mucosa demonstrating junctional activity and squamous metaplasia.
911
HUMAN PATHOLOGY
Volume 15, No. 10 (October 1984]
FIGURE 3. Case t. Lung tumor with numerous premelanosomes and melanosomes. (x 25,000.) Inset, premelanosome. (x 76,000.]
slide of the elevated, hairy mole removed from tile patient's back six years previously was reviewed. It was cut for margins; several sections were examined and found to represent an intradermal nevus without junctional activity. Light microscopic examination at the time of autopsy showed the tumors in the various locations to be identical to the hmg tumor diagnosed earlier. Case 2. T h e removed tumor measured 14 • 9 • 5 cm in greatest dimension, and the weight, including the kidney, was 650 g. The mass appeared to be well encapsulated, with a smooth, glistening outer surface. On sectioning, large areas of necrosis and hemorrhage were found, but at tile periphery of the tumor viable tissue, dark brown to black, was noticed. At one pole of the specimen, closely related to the capsule, a narrow rim of grayish yellow tissue was grossly identifiable as a remnant of the left adrenal. The tumor appeared to be closely attached to the kidney but had not penetrated the capsule. Light microscopic examination o f multiple sections of the tumor showed the individual cells to be of variable sizes and shapes. Some formed nests and others solid masses, and in some areas the cells were spindly and had a sarcomatous appearance (fig. 4). Most of the cells had irregular nuclei, with prominent chromatin and nucleoli. Many abnormal mitotic figures were noticed, and m u h i n u c l e a t e d giant cells were also encountered. Vascular invasion was present. In some of
the sections normal adrenal cortical tissue was observed close to tile capsule. A large amount of brown pigment was seen in. sections stained with hematoxylin-eosin. The same areas were positive on FontanaM a s s o n staining. Electron microscopic examination d e m o n s t r a t e d cytoplasmic m e m b r a n e - b o u n d structures with cross-hatched filaments characteristic of a premelanosome (fig. 5). DISCUSSION A review of tile current literature revealed eight reported cases of primary malignant melanoma in the lung2-9; criteria for the diagnoses in these cases included the presence of melanin in a tumor histologically consistent with melanoma involving the respiratory epithelium, the absence of a current or previous p r i m a r y m e l a n o m a elsewhere, and no previously resected p i g m e n t e d skin lesion of unknown type3 ~ If autopsy to rule out a primary lesion elsewhere is included in the criteria, the field is limited to five cases. 3,4,7-9 I f we f u r t h e r m o r e require junctional changes, with invasion of intact bronchial mucosa by malignant melanoma cells with obvious m a l i g n a n t m e l a n o m a b e n e a t h , only one case remains, s O f the eight previously reported cases, four were in women2,4,6,7 and four in men ~,5,8,9 (age range, 33 912
MALIGNANTMELANOMA OF LUNG AND ADRENAL [Carstens et al.]
FIGURE 4 (top]. Case 2. Adrenal tumor composed of spindle cells. FIGURE 5 [bottom]. Case 2. Adrenal tumor with many premelanosomes and glycogen particles. ( x 1~,000.] Inset, premelanosome. [ x 76,000.]
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to 71 years). F o u r o f t h e t u m o r s w e r e in the left l u n g 3,4,5,8 a n d t h r e e in the right,2,6,9 a n d o n e ext e n d e d d o w n w a r d f r o m the carina in both the left and right main stem bronchi. 7 T w o were in the main stem bronchus,3, 7 o n e in the u p p e r lobe, 4 a n d five in the lower 10be.2,5,6,8,9 Six o f the eight t u m o r s were located centrally.. ~-8 Five o f the eight patients died within 11/2 years a f t e r diagnosis,3,4, 7-9 b u t two patients survived m o r e t h a n ten years a f t e r p n e u m o n e c t o m y a n d lobectomy. 5,6 O u r case 1 fulfills all o f these criteria, except for the m o l e r e m o v e d six years previously. T h e mole h a d , h o w e v e r , b e e n p r e s e n t f o r 13 y e a r s w i t h o u t c h a n g e a n d was f o u n d to be an i n t r a d e r m a l nevus without j u n c t i o n a l changes. F u r t h e r m o r e , the lack o f a n o t h e r p r i m a r y t u m o r at the time o f diagnosis o f the malignant m e l a n o m a in the lung, the j u n c t i o n a l changes in the b r o n c h u s , and the s u b s e q u e n t develo p m e n t o f multiple u n i f o r m , small widespread metastases strong.ly s u p p o r t the classification o f the lung t u m o r as a p r i m a r y t u m o r . We were unable to locate any r e f e r e n c e s to the presence o f melanocytes in n o r m a l lungs. However, it is not surprising to find a malignant m e l a n o m a in the lung, given that the respiratory tract develops as a d o w n g r o w t h f r o m the primitive f o r e g u t s o m e w h e r e between the p h a r y n x a n d the esophagus, two sites at which malignant m e l a n o m a s are k n o w n to occur. A review o f the c u r r e n t literature revealed t h r e e p r i m a r y m a l i g n a n t m e l a n o m a s in the a d r e n a l . 11-13 Many have e x p r e s s e d great reluctance to accept malignant m e l a n o m a s as p r i m a r y in the a d r e n a l because o f the f r e q u e n c y o f metastases to this organl4A 5 f r o m the m o r e c o m m o n p r i m a r y sources, such as the skin and eye. Criteria should include the presence o f a p r i m a r y malignant m e l a n o m a in only one o f the adrenals, n o p r i o r o r c u r r e n t m a l i g n a n t m e l a n o m a s elsewhere, n o removal o f p i g m e n t e d skin o r eye lesions, and, preferably, exclusion by autopsy o f the presence o f a h i d d e n p r i m a r y lesion. T h e t h r e e previously r e p o r t e d p r i m a r y m a l i g n a n t m e l a n o m a s o f the a d r e n a l were all large, cystic, a n d necrotic d a r k b r o w n o r black tumors. T w o o f the patients died after a y e a r with w i d e s p r e a d small metastases.11,12 N o follow-up i n f o r m a t i o n was available for the third patient.~3 O u r case 2 fulfills these criteria, except that autopsy was not p e r f o r m e d . W h e n the malignant mela n o m a was discovered in the left adrenal, a careful clinical search was initiated for a p r i m a r y t u m o r in
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the m o r e c o m m o n locations, b u t without success. T h e patient died a f t e r seven m o n t h s with p r o v e d wides p r e a d metastatic malignant m e l a n o m a , w i t h n o primary t u m o r having a p p e a r e d . W e have not been able to find any c u r r e n t references to the presence o f melanocytes in the adrenal, a l t h o u g h this p h e n o m e n o n was m e n t i o n e d in the past. 16 Since the p h e o c h r o m o c y t e s in the medulla o f the adrenal, like the melanocytes, are considered to be d e r i v e d f r o m the neural crest, the presence o f melanocytes, a n d t h e r e f o r e o f a malignant melanoma, in the a d r e n a l would seem reasonable. Acknowledgments. T h e authors thank Cathie Caple, Lucille O. Chann, and Charlie D. Foreman for expert technical assistance and tile Department of Pathology, University of Kentucky, for making slides available (case I).
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