Medical Intelligence A D E N O C A R C I N O M A OF THE RETE TESTIS: A REVIEW OF THE LITERATURE AND PRESENTATION OF A CASE WITH ASSOCIATED ASBESTOSIS SUSAN D. GISSER, M.D.,* S/iEILA NAYAK, M.D.,'~ ~IAMORU KANEKO, M.D.,:]: AND VICTOR TCIIERTKOFF, M.D.w Abstract
Although scattered reports of adenocarcinoma of the rete testis have previously appeared arm criteria for the diagnosis of this tumor have been defitted, previous cases have not been described in sufficient detail to provMe an organized account of the nature and behavior of this neoplasm. The present report describes a case followed to autopsy and provides conclusive evidence that it is of fete testis origim Previo,sly reported cases of fete testis carcinoma are reviewed attd the salient features summarized, showing that the tumor has a defiufe clinical and histolog# pattern and that the prognosis appears poor. The present case occurred in a patient with severe pulmona 9' asbestosis. This association is unique, and its significance remains speculative. A d e n o c a r c i n o m a o f tire rete testis is a rare neoplasm, o f which, by necessity, case reports have been scant)" and isolated. Earl)" authors have laid down and reiterated criteria helpftfl in nmking tire diagnosis attd in distinguishing this t u m o r front otlter testicnlar growths? '~ These sketclty reports have served to provide us with a morphologic concept o f the rete testis *Clinical Assistant l'rofessor of Patlmlog)', Temple University School of Medicine. Pathologist, Albert Einstein Medical Center, Northern Division Philadelphia, Pennsylvania. ?Resident iq l'athology, Metropolitan ttospital, New York, New York. ~+Associate l'rofessor of l'athology, The .Mount Sinai School of .Mediciqe of the City Uifiverslty of New York, New York. w of Pathology, New York Medical College. Director of Laboratories, Metropolitan Hospital, New York, New York.
carcinoma but, with incomplete clinical records and frequently b r i e f o r nonexistent follow-np, have failed to provide us with a comprehensive overview o f tlte n a t n r e attd behavior o f this malignant tumor. We Itave had the opportunity to follow a case o f a d e n o c a r c i n o m a o f the rete testis front diagnosis to the postntortem room attd ltave a t t e m p t e d in tiffs review o f tire literature to draw the loose ends together. Tire association of asbestosis with rete testis carcinoma has not been previously reported. Althongll this association might increase the suspicion that we are actuaUy dealing with a mesotbelioma o f the tunica o r metastatic adenocarcinoma or ntesothelioma from tire lung, the tnorphologic and circnmstantial featnres of tire case overwttelmhlgly s u p p o r t o n r impression tltat tltis t u m o r is indeed derived from tire rete testis. CASE R E P O R T A 73 )-ear old white male presented in November 1969 with a left scrotal mass, which he had noted two to three months earlier. He had been ill good heahlt previously. Tile only item o f ltistorical note was an 11 )'ear p e r i o d o f work, from 1924 to 1935, ill the c0al mine. Aspiration o f a hydrocele and simple orcltiectom)' were p e r f o r m e d . Tile pathology r e p o r t was adenocarcinorna o f the rete testis. T h e patient was otherwise a p p a r e n t l y in good heahh. Tire chest x-ray film could not be satisfactorily evaluated owing to the interstitial fibrosis and n o d u l a r confluent densities attributable to Iris occupational history. In Marclt 1971 the patient r e t u r n e d with a scrotal skin recnrrence. An en bloc excision o f skin and spermatic c o r d was p e r f o r m e d a n d a course o f 5-flnorouracil was given. Chest x-ray examination and general heahh had r e m a i n e d tmcltanged. Ill J a n u a r y 1972 he was hospitalized for p u h n o n a r y elnbolism and infarction, ha J a n u ary 1974 a left ingtfinal node dissection showed metastatic adenocarcinoma. T h e final admission occurred in F e b r u a r y 1974, and he died witlt p n e u m o n i a complicating pneumoconiosis and tumor. A p e r m i t was obtained for postm o r t e m exantination. PATHOLOGIC FINDINGS T h e orchiectomy specimen received by the laboratory contained a t u m o r 1.5 cm. in diam-
219
H U M A N P A T H O L O G Y - - V O L U M E 8, N U M B E R 2 eter, located at tire u p p e r pole o f tile testis, timt was firm, white, a n d honaogeneous. T h e r e was no sharp line o f demarcation from the surr o u n d i n g testicular parenchynm. T h e tunica albuginea and tunica vaginalis were studded by numerous firm wlfite nodules measuring 1 to 5 mm. in greatest dimension. Microscopically the area o f the rete was almost entirely replaced by carcinoma, yet some relatively normal a p p e a r i n g rete epithelium was demonstrable as well as some areas o f hyperplasia and varying degrees o f atypicality. In some fields hyperplastic rete epitlleliunl was seen to be continuous with neoplastic epithelium within a single efferent duct (Fig. 1). F r o m this origin t u m o r e x t e n d e d out to involve adjacent tissues. It was composed of simple tubular and dilated ah'eolus-like glandular structures, nmn)" of which contained papillary intraluminal projections. Some projections were simple but others had a somewhat glomeruloid configuration (Fig. 2). In still others, sheets o f neoplastic cells were present within glandular lumina. T h e lining cells o f the glands were cuboidal to low columnar with a b u n d a n t eosinoplfilic cytoplasm, prominent cell boundaries, a n d large r o u n d to ovoid hypercllromatic nuclei, with p r o m i n e n t eosinophilic nucleoli. Mitotic figures were numerous. T h e cells infiltrated the fibrous connective tissue o f the rete, in some areas accompanied by a m a r k e d desmoplastic reaction. Infiltration
i'8
"
March 1977
e x t e n d e d in a n d among atrophic seminiferous tubules, p r o d u c i n g minimal distortion o f their pattern. T i l e r e c u r r e n t t u m o r in the scrotal skin was c o m p o s e d of adenocarcinoma having a histologic pattern identical to that o f the original tumor. T h e ingninal lymph node metastatic t u m o r likewise had histologic features identical to those of the primary. Vascular invasion was prominent in the lymph node dissection specimen. At necropsy tbere was a 500 cc. effusion o f 9clear fluid in each pleural space 9 T h e pleura was thickened and had extensive fibrous adhesions, and dlere were multiple white firm subpleural nodules measuring 0.1 to 0.5 cm. in greatest dimension. T h e ltmgs were fixed by formalin perfusion u n d e r pressure before sections were taken. Cut sections o f the lung p a r e n c h y m a showed generalized centriacinav emt)laysema. T h e bronchi were thickened with a clmracteristic pipe stem appearance. T h e r e were multiple grayish white firm nodules t h r o u g h o u t the parenchyma, the largest one measuring 0.8 cm. in greatest dimension. Two silicomas were present, one on each side. T h e larger was ~n the right u p p e r lobe, measured 8 cm. in greatest dimension, a n d contained a p p r o x i m a t e l y 30 cc. of thick black cheesy material. Ctdtures o f the silicomas were negative for acid fast bacilli. O n microscopic examination the pleura
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MEDICAL I N T E L L I G E N C E
9
F i g u r e 2.
9
,
,
Papillary adenocarcinoma showing glomeruloid configuration. (Hematoxylin and eosin stain.
Xl00.)
showed extensive fibrosis a n d subplenral edema with dilated lymphatics. T h e aforementioned nodules showed t u m o r with a p r o m i n e n t papillary glandtflar pattern 9 T h e cells lining the glands were mostly cuboidal or low c o h u n n a r and had a b u n d a n t cytoplasm a n d large ovoid to r o u n d nuclei and p r o m i n e n t eosinophilic nucleoli. I n some areas t u m o r cells were lying free in the alveoli, giving the appearance of "tumor pnetunouia." T h e bronchi were thickened as a result of fibrosis a n d infihration of tun]or into the submucosa and the s u r r o t m d i n g lymplmtics. T h e histologic pattern of tlfis t u m o r was of papillary and t u b u l a r adenocarcinoma. T h e silicoma cavities were free of tumor. A b u n d a n t black and brown pigment was present, mostly accumulated in interstitial fibrotic nodules, in all lung sections (Fig. 3). Asbestos bodies were readily found in such areas (Fig. 4). T h e iliac, para-aortic, gastric, a n d mediastinal lymph nodes showed metastatic t u m o r having a histologic pattern similar to that of the primary. T h e liver had muhiple metastatic nodules 1 to 1.5 cm. in greatest dimension. T h e contralateral testis showed atrophy and fibrosis but no evidence of tumor. DISCUSSION A h h o u g h the concept of neoplastic change localized to the rete testis is traced to 1853, a the first g e n u i n e reports of rete carcinoma did
not appear until the middle of this century. 2 Table 1 summarizes the cases that appear to represent true rete malignant disease and indicates the data pertinent to this discussion.
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221
H U M A N I ' A T H O L O G Y - - V O I . U M E 8, NUMBER 2
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Criteria for distinguishing between rete testis carcinoma and otlmr testicular neoplasms appeared with tire first well documented r e port and were refined by later observers, n='4 T h e criteria, to be considered as a guide rather than absolute, include involvement centering o n the mediastinnm testis rather tban on the main body, lack of direct extension througll tim parietal tunica, demonstration of a transition from t u m o r througll cytologically atypical but non-neoplastic rete epithelium through normal epitlmlium, lack of histologic or lmrmonal evidence o f a teratoma, and faih, re to demonstrate any other primary tumor. Several cases previously reported as carcinoma of the fete testis have been omitted from tiffs series. These include, first, the cases not accepted as fete testis carcinomas in tim review by Schoen and Rush, = the case of Curling, a a benign1 tumor, that of Gilbert, 5 with a positive Aschheim-Zondek test, that of Laird ~; with a questionable histologic picture, and that of Frazer 2 with a positive frog test and questionable histologic findings. Additional cases considered for tiffs review as invalid include tlm third case of Willis7 o f " u n k n o w n history,"which was deleted from the latest edition o f Iris text; s tim second case of Sclmen and Rush listed by Moghe and Soni, ~ the identity of which could not be established; the two cases
222
March 1977
of Banerjea, Mehrotra, and Mangalik 9 indicated by Moghe and Soni, 1 which were incousistent with tile expected age range, came with no additional data, and apparently were never published; a n d tile case of Nair a n d Mobankumar 1~ listed by Moghe and Soni, ~ tile histologic findings in which differed markedly from tlmse of all others in the group and substantiation o f which as a fete testis carcinoma was not u n d e r taken. T h e case o f Dundon, n in which the t u m o r developed 10 )ears after orchidopexy and a p p e a r e d on review of histologic findings and course n m r e to be likely a seminoma, is also excluded here. O u r case, it is noted, previously appeared as the subject of a short report. TM T i m fete testis adenocarcinoma is a t u m o r of middle age with the youngest reported case at 30 }'ears a n d the oldest at 80. Hydrocele is a c o m m o n presenting complaint, but an isolated testictdar mass is more often the rule. Some patients manifest metastatic disease at the time of presentation, but tiffs is not usual. Metastases occur to lymph nodes, hmgs, corpus testis, skin, liver, and bone in order of decreasing, freqt,ency. Local skin recurrence has been reported in two cases in addition to - our own. T i m treatment for tim most part includeci simple orchiectomy with or without local radiation. Some patients received radiation or chemotherapy at the time of recurrence or appearance of metastases. Radiation of initiall)" present metastases appeared to be effective in one case. ~a Radiation in tire late stages of disease proved ineffective in the two cases in which it was administered, u" ~5 Methotrexate in one case, 5-fluorouracil in one, a n d a combination o f cytoxan, vincristine, actinomycin D, and a course of 5-fluorouracil in a third failed to produce a remission. O u r patient also did not r e s p o n d to 5-fluorouracil. T h e t u m o r proved to be extremely aggressive, several patieuts.dying within tim first )'ear after diagnosis. Grossly tim tumors consisted for the most part of the single main testicular mass with satellite continent nodular masses. Microscopicall)' tim pattern was of papillary and tubular adenocarcinoma similar to that described in detail in the present case report. T h e original criteria for tim diagnosis of tiffs t u m o r were met by the tumors in tiffs group in that they were centered on tim mediastinum testis, spared the parietal tunic, and had a readily denmnstrable transition zone. Also tim clinical criteria excluding teratoma and a possible other source were partially met. Invasion of testicular parenchyma was f o u n d in approximately hale
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Although scattered reports of adenocarcinoma of the rete testis have previously appeared arm criteria for the diagnosis of this tumor have been defitted, previous cases have not been described in sufficient detail to provMe an organized account of the nature and behavior of this neoplasm. The present report describes a case followed to autopsy and provides conclusive evidence that it is of fete testis origim Previo,sly reported cases of fete testis carcinoma are reviewed attd the salient features summarized, showing that the tumor has a defiufe clinical and histolog# pattern and that the prognosis appears poor. The present case occurred in a patient with severe pulmona 9' asbestosis. This association is unique, and its significance remains speculative. A d e n o c a r c i n o m a o f tire rete testis is a rare neoplasm, o f which, by necessity, case reports have been scant)" and isolated. Earl)" authors have laid down and reiterated criteria helpftfl in nmking tire diagnosis attd in distinguishing this t u m o r front otlter testicnlar growths? '~ These sketclty reports have served to provide us with a morphologic concept o f the rete testis *Clinical Assistant l'rofessor of Patlmlog)', Temple University School of Medicine. Pathologist, Albert Einstein Medical Center, Northern Division Philadelphia, Pennsylvania. ?Resident iq l'athology, Metropolitan ttospital, New York, New York. ~+Associate l'rofessor of l'athology, The .Mount Sinai School of .Mediciqe of the City Uifiverslty of New York, New York. w of Pathology, New York Medical College. Director of Laboratories, Metropolitan Hospital, New York, New York.
carcinoma but, with incomplete clinical records and frequently b r i e f o r nonexistent follow-np, have failed to provide us with a comprehensive overview o f tlte n a t n r e attd behavior o f this malignant tumor. We Itave had the opportunity to follow a case o f a d e n o c a r c i n o m a o f the rete testis front diagnosis to the postntortem room attd ltave a t t e m p t e d in tiffs review o f tire literature to draw the loose ends together. Tire association of asbestosis with rete testis carcinoma has not been previously reported. Althongll this association might increase the suspicion that we are actuaUy dealing with a mesotbelioma o f the tunica o r metastatic adenocarcinoma or ntesothelioma from tire lung, the tnorphologic and circnmstantial featnres of tire case overwttelmhlgly s u p p o r t o n r impression tltat tltis t u m o r is indeed derived from tire rete testis. CASE R E P O R T A 73 )-ear old white male presented in November 1969 with a left scrotal mass, which he had noted two to three months earlier. He had been ill good heahlt previously. Tile only item o f ltistorical note was an 11 )'ear p e r i o d o f work, from 1924 to 1935, ill the c0al mine. Aspiration o f a hydrocele and simple orcltiectom)' were p e r f o r m e d . Tile pathology r e p o r t was adenocarcinorna o f the rete testis. T h e patient was otherwise a p p a r e n t l y in good heahh. Tire chest x-ray film could not be satisfactorily evaluated owing to the interstitial fibrosis and n o d u l a r confluent densities attributable to Iris occupational history. In Marclt 1971 the patient r e t u r n e d with a scrotal skin recnrrence. An en bloc excision o f skin and spermatic c o r d was p e r f o r m e d a n d a course o f 5-flnorouracil was given. Chest x-ray examination and general heahh had r e m a i n e d tmcltanged. Ill J a n u a r y 1972 he was hospitalized for p u h n o n a r y elnbolism and infarction, ha J a n u ary 1974 a left ingtfinal node dissection showed metastatic adenocarcinoma. T h e final admission occurred in F e b r u a r y 1974, and he died witlt p n e u m o n i a complicating pneumoconiosis and tumor. A p e r m i t was obtained for postm o r t e m exantination. PATHOLOGIC FINDINGS T h e orchiectomy specimen received by the laboratory contained a t u m o r 1.5 cm. in diam-
219
H U M A N P A T H O L O G Y - - V O L U M E 8, N U M B E R 2 eter, located at tire u p p e r pole o f tile testis, timt was firm, white, a n d honaogeneous. T h e r e was no sharp line o f demarcation from the surr o u n d i n g testicular parenchynm. T h e tunica albuginea and tunica vaginalis were studded by numerous firm wlfite nodules measuring 1 to 5 mm. in greatest dimension. Microscopically the area o f the rete was almost entirely replaced by carcinoma, yet some relatively normal a p p e a r i n g rete epithelium was demonstrable as well as some areas o f hyperplasia and varying degrees o f atypicality. In some fields hyperplastic rete epitlleliunl was seen to be continuous with neoplastic epithelium within a single efferent duct (Fig. 1). F r o m this origin t u m o r e x t e n d e d out to involve adjacent tissues. It was composed of simple tubular and dilated ah'eolus-like glandular structures, nmn)" of which contained papillary intraluminal projections. Some projections were simple but others had a somewhat glomeruloid configuration (Fig. 2). In still others, sheets o f neoplastic cells were present within glandular lumina. T h e lining cells o f the glands were cuboidal to low columnar with a b u n d a n t eosinoplfilic cytoplasm, prominent cell boundaries, a n d large r o u n d to ovoid hypercllromatic nuclei, with p r o m i n e n t eosinophilic nucleoli. Mitotic figures were numerous. T h e cells infiltrated the fibrous connective tissue o f the rete, in some areas accompanied by a m a r k e d desmoplastic reaction. Infiltration
i'8
"
March 1977
e x t e n d e d in a n d among atrophic seminiferous tubules, p r o d u c i n g minimal distortion o f their pattern. T i l e r e c u r r e n t t u m o r in the scrotal skin was c o m p o s e d of adenocarcinoma having a histologic pattern identical to that o f the original tumor. T h e ingninal lymph node metastatic t u m o r likewise had histologic features identical to those of the primary. Vascular invasion was prominent in the lymph node dissection specimen. At necropsy tbere was a 500 cc. effusion o f 9clear fluid in each pleural space 9 T h e pleura was thickened and had extensive fibrous adhesions, and dlere were multiple white firm subpleural nodules measuring 0.1 to 0.5 cm. in greatest dimension. T h e ltmgs were fixed by formalin perfusion u n d e r pressure before sections were taken. Cut sections o f the lung p a r e n c h y m a showed generalized centriacinav emt)laysema. T h e bronchi were thickened with a clmracteristic pipe stem appearance. T h e r e were multiple grayish white firm nodules t h r o u g h o u t the parenchyma, the largest one measuring 0.8 cm. in greatest dimension. Two silicomas were present, one on each side. T h e larger was ~n the right u p p e r lobe, measured 8 cm. in greatest dimension, a n d contained a p p r o x i m a t e l y 30 cc. of thick black cheesy material. Ctdtures o f the silicomas were negative for acid fast bacilli. O n microscopic examination the pleura
,r
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Figure 1. Hyperplastic rete epithelium in transition to neoplastic epithelium. (ltematoxylin and eosin stain, x100.)
MEDICAL I N T E L L I G E N C E
9
F i g u r e 2.
9
,
,
Papillary adenocarcinoma showing glomeruloid configuration. (Hematoxylin and eosin stain.
Xl00.)
showed extensive fibrosis a n d subplenral edema with dilated lymphatics. T h e aforementioned nodules showed t u m o r with a p r o m i n e n t papillary glandtflar pattern 9 T h e cells lining the glands were mostly cuboidal or low c o h u n n a r and had a b u n d a n t cytoplasm a n d large ovoid to r o u n d nuclei and p r o m i n e n t eosinophilic nucleoli. I n some areas t u m o r cells were lying free in the alveoli, giving the appearance of "tumor pnetunouia." T h e bronchi were thickened as a result of fibrosis a n d infihration of tun]or into the submucosa and the s u r r o t m d i n g lymplmtics. T h e histologic pattern of tlfis t u m o r was of papillary and t u b u l a r adenocarcinoma. T h e silicoma cavities were free of tumor. A b u n d a n t black and brown pigment was present, mostly accumulated in interstitial fibrotic nodules, in all lung sections (Fig. 3). Asbestos bodies were readily found in such areas (Fig. 4). T h e iliac, para-aortic, gastric, a n d mediastinal lymph nodes showed metastatic t u m o r having a histologic pattern similar to that of the primary. T h e liver had muhiple metastatic nodules 1 to 1.5 cm. in greatest dimension. T h e contralateral testis showed atrophy and fibrosis but no evidence of tumor. DISCUSSION A h h o u g h the concept of neoplastic change localized to the rete testis is traced to 1853, a the first g e n u i n e reports of rete carcinoma did
not appear until the middle of this century. 2 Table 1 summarizes the cases that appear to represent true rete malignant disease and indicates the data pertinent to this discussion.
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221
H U M A N I ' A T H O L O G Y - - V O I . U M E 8, NUMBER 2
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Criteria for distinguishing between rete testis carcinoma and otlmr testicular neoplasms appeared with tire first well documented r e port and were refined by later observers, n='4 T h e criteria, to be considered as a guide rather than absolute, include involvement centering o n the mediastinnm testis rather tban on the main body, lack of direct extension througll tim parietal tunica, demonstration of a transition from t u m o r througll cytologically atypical but non-neoplastic rete epithelium through normal epitlmlium, lack of histologic or lmrmonal evidence o f a teratoma, and faih, re to demonstrate any other primary tumor. Several cases previously reported as carcinoma of the fete testis have been omitted from tiffs series. These include, first, the cases not accepted as fete testis carcinomas in tim review by Schoen and Rush, = the case of Curling, a a benign1 tumor, that of Gilbert, 5 with a positive Aschheim-Zondek test, that of Laird ~; with a questionable histologic picture, and that of Frazer 2 with a positive frog test and questionable histologic findings. Additional cases considered for tiffs review as invalid include tlm third case of Willis7 o f " u n k n o w n history,"which was deleted from the latest edition o f Iris text; s tim second case of Sclmen and Rush listed by Moghe and Soni, ~ the identity of which could not be established; the two cases
222
March 1977
of Banerjea, Mehrotra, and Mangalik 9 indicated by Moghe and Soni, 1 which were incousistent with tile expected age range, came with no additional data, and apparently were never published; a n d tile case of Nair a n d Mobankumar 1~ listed by Moghe and Soni, ~ tile histologic findings in which differed markedly from tlmse of all others in the group and substantiation o f which as a fete testis carcinoma was not u n d e r taken. T h e case o f Dundon, n in which the t u m o r developed 10 )ears after orchidopexy and a p p e a r e d on review of histologic findings and course n m r e to be likely a seminoma, is also excluded here. O u r case, it is noted, previously appeared as the subject of a short report. TM T i m fete testis adenocarcinoma is a t u m o r of middle age with the youngest reported case at 30 }'ears a n d the oldest at 80. Hydrocele is a c o m m o n presenting complaint, but an isolated testictdar mass is more often the rule. Some patients manifest metastatic disease at the time of presentation, but tiffs is not usual. Metastases occur to lymph nodes, hmgs, corpus testis, skin, liver, and bone in order of decreasing, freqt,ency. Local skin recurrence has been reported in two cases in addition to - our own. T i m treatment for tim most part includeci simple orchiectomy with or without local radiation. Some patients received radiation or chemotherapy at the time of recurrence or appearance of metastases. Radiation of initiall)" present metastases appeared to be effective in one case. ~a Radiation in tire late stages of disease proved ineffective in the two cases in which it was administered, u" ~5 Methotrexate in one case, 5-fluorouracil in one, a n d a combination o f cytoxan, vincristine, actinomycin D, and a course of 5-fluorouracil in a third failed to produce a remission. O u r patient also did not r e s p o n d to 5-fluorouracil. T h e t u m o r proved to be extremely aggressive, several patieuts.dying within tim first )'ear after diagnosis. Grossly tim tumors consisted for the most part of the single main testicular mass with satellite continent nodular masses. Microscopicall)' tim pattern was of papillary and tubular adenocarcinoma similar to that described in detail in the present case report. T h e original criteria for tim diagnosis of tiffs t u m o r were met by the tumors in tiffs group in that they were centered on tim mediastinum testis, spared the parietal tunic, and had a readily denmnstrable transition zone. Also tim clinical criteria excluding teratoma and a possible other source were partially met. Invasion of testicular parenchyma was f o u n d in approximately hale
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