case report: carcinoma in-situ of the testis diagnosed on semen cytology

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Clinical Radiology (1989) 40, 323-324 Case Report: Carcinoma In-situ of the Testis Diagnosed on Semen Cytology G. C. W. HOWARD, T. B. HARGREAVE* and M. A. McINTYRE~ Departments of Radiation Oncology, * Urology and ~Pathology, Western General Hospital, Crewe Road South, Edinburgh, UK The case is reported of a patient who presented to an infertility clinic following extensive treatment for testicular teratoma. An incidental finding on semen analysis was of abnormal cells suggestive of carcinoma in-situ. This diag- nosis was later confirmed by biopsy of the remaining testicle. Radiotherapy will be given to the testis to ablate the germinal epithelium while sparing Leydig cell function. Carcinoma in-situ of the testis has aroused increasing interest since it was first recognised as a pathological entity (Skakkebaek, 1972). It is estimated that at 5 years following diagnosis, in excess of 50% of patients with this condition will have progressed to invasive testicular tumours (Berthelsen et al., 1982; Hargreave, 1986). The diagnosis of carcinoma in-situ of the testis is usually made on a testicular biopsy, although pre-malignant cells may be seen in the semen of affected patients (Giwercman et al_, 1988). Opinions vary as to when biopsy is indicated, and what treatment is most appropriate once the diagno- sis is made. The benefit of diagnosing the pre-malignant stage of what is both a chemosensitive and radiosensitive tumour is open to question. There would appear to be no advantage in making this diagnosis unless treatment is given in the pre-invasive stage. This case history contains some unusual features and highlights some of the problems of making the diagnosis and difficulties of further management. CASE REPORT A 37-year-old male presented to the infertility clinic for investigation. Nine years previously, whilst abroad, a trans-scrotal biopsy of a lump in the left testis had been performed. The pathology was reported as showing a malignant testicular teratoma. He subsequently underwent an inguinal orchidectomy, partial scrotectomy and block dissection of the ipsilateral inguinal nodes. There was no evidence of spermatic cord involvement, nodal or distant metastatic disease. Further treatment was undertaken in the USA where a retroperito- neai lymph node dissection was performed. Metastatic disease was found in two of 38 lymph nodes removed. Post-operative chemo therapy was planned but never given due to the development of serum hepatitis. Follow-up has been sporadic due to the patient's extensive travelling, but when last investigated he was considered to be disease-free. Following the retroperitoneal surgery the patient was able to achieve an erection and could produce a semen specimen with the aid of a valsalva manoeuvre. Semen produced by this method was mixed with urine. When the patient subsequently presented to the infertility clinic, a semen specimen was examined. A low sperm count and reduced motility was noted. In addition, flocculation was seen to be abnormal. On cytological examination (Fig. 1) abnormal cells with large hyperchro- matic nuclei were seen which were considered to be carcinoma in-situ cells, even in view of the abnormal method of production of the specimen. Subsequently, a testicular biopsy was performed under direct vision. A representative section (Fig, 2) demonstrated positive staining with placental alkaline phosphatase and appearances consistent with the diagnosis of carcinoma in-situ. DISCUSSION This case demonstrates a number of unusual features. Both chemotherapy and radiotherapy at low dosage (yon Fig. 1 Semen cytology. Many spermatozoa and some spermatids are seen. Also present are cells with large hyperchromatic nuclei and minimal cytoplasm. Fig. 2 - Testicular biopsy stained using immunoperoxidase for placental alkaline phosphatase. The seminiferous tubule is lined by cells with large nuclei, prominent nucleoli and granular cytoplasmic staining, x 128.

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Page 1: Case report: Carcinoma in-situ of the testis diagnosed on semen cytology

Clinical Radiology (1989) 40, 323-324

Case Report: Carcinoma In-situ of the Testis Diagnosed on Semen Cytology G. C. W . H O W A R D , T. B. H A R G R E A V E * a n d M . A. M c I N T Y R E ~

Departments of Radiation Oncology, * Urology and ~ Pathology, Western General Hospital, Crewe Road South, Edinburgh, UK

The case is reported of a patient who presented to an infertility clinic following extensive treatment for testicular teratoma. An incidental finding on semen analysis was of abnormal cells suggestive of carcinoma in-situ. This diag- nosis was later confirmed by biopsy of the remaining testicle. Radiotherapy will be given to the testis to ablate the germinal epithelium while sparing Leydig cell function.

C a r c i n o m a in - s i t u o f t h e tes t i s h a s a r o u s e d i n c r e a s i n g i n t e r e s t s ince i t was f i rs t r e c o g n i s e d as a p a t h o l o g i c a l e n t i t y ( S k a k k e b a e k , 1972). I t is e s t i m a t e d t h a t a t 5 yea r s f o l l o w i n g d i a g n o s i s , in excess o f 50% o f p a t i e n t s w i t h th i s c o n d i t i o n will h a v e p r o g r e s s e d to i n v a s i v e t e s t i c u l a r t u m o u r s ( B e r t h e l s e n et al., 1982; H a r g r e a v e , 1986). T h e d i a g n o s i s o f c a r c i n o m a i n - s i t u o f t he tes t is is u s u a l l y m a d e o n a t e s t i c u l a r b iopsy , a l t h o u g h p r e - m a l i g n a n t cells m a y be seen in the s e m e n o f a f fec ted p a t i e n t s ( G i w e r c m a n et al_, 1988). O p i n i o n s v a r y as to w h e n b i o p s y is i n d i c a t e d , a n d w h a t t r e a t m e n t is m o s t a p p r o p r i a t e o n c e the d i a g n o - sis is m a d e . T h e bene f i t o f d i a g n o s i n g the p r e - m a l i g n a n t s t age o f w h a t is b o t h a c h e m o s e n s i t i v e a n d r a d i o s e n s i t i v e t u m o u r is o p e n to q u e s t i o n . T h e r e w o u l d a p p e a r to be n o a d v a n t a g e in m a k i n g th i s d i a g n o s i s un less t r e a t m e n t is g iven in the p r e - i n v a s i v e s tage .

T h i s case h i s t o r y c o n t a i n s s o m e u n u s u a l f e a t u r e s a n d h i g h l i g h t s s o m e o f the p r o b l e m s o f m a k i n g the d i a g n o s i s a n d dif f icul t ies o f f u r t h e r m a n a g e m e n t .

C A S E R E P O R T

A 37-year-old male presented to the infertility clinic for investigation. Nine years previously, whilst abroad, a trans-scrotal biopsy of a lump in the left testis had been performed. The pathology was reported as showing a malignant testicular teratoma. He subsequently underwent an inguinal orchidectomy, partial scrotectomy and block dissection of the ipsilateral inguinal nodes. There was no evidence of spermatic cord involvement, nodal or distant metastatic disease.

Further treatment was undertaken in the USA where a retroperito- neai lymph node dissection was performed. Metastatic disease was found in two of 38 lymph nodes removed. Post-operative chemo therapy was planned but never given due to the development of serum hepatitis. Follow-up has been sporadic due to the patient's extensive travelling, but when last investigated he was considered to be disease-free.

Following the retroperitoneal surgery the patient was able to achieve an erection and could produce a semen specimen with the aid of a valsalva manoeuvre. Semen produced by this method was mixed with urine. When the patient subsequently presented to the infertility clinic, a semen specimen was examined. A low sperm count and reduced motility was noted. In addition, flocculation was seen to be abnormal. On cytological examination (Fig. 1) abnormal cells with large hyperchro- matic nuclei were seen which were considered to be carcinoma in-situ cells, even in view of the abnormal method of production of the specimen.

Subsequently, a testicular biopsy was performed under direct vision. A representative section (Fig, 2) demonstrated positive staining with placental alkaline phosphatase and appearances consistent with the diagnosis of carcinoma in-situ.

D I S C U S S I O N

T h i s case d e m o n s t r a t e s a n u m b e r o f u n u s u a l f ea tu res . B o t h c h e m o t h e r a p y a n d r a d i o t h e r a p y a t low d o s a g e ( y o n

Fig. 1 Semen cytology. Many spermatozoa and some spermatids are seen. Also present are cells with large hyperchromatic nuclei and minimal cytoplasm.

Fig. 2 - Testicular biopsy stained using immunoperoxidase for placental alkaline phosphatase. The seminiferous tubule is lined by cells with large nuclei, prominent nucleoli and granular cytoplasmic staining, x 128.

Page 2: Case report: Carcinoma in-situ of the testis diagnosed on semen cytology

324 CLINICAL RADIOLOGY

de r M a a s e et al., 1987) h a v e b e e n r e p o r t e d to e r a d i c a t e c a r c i n o m a in -s i tu o f the test is . U n d e r d i f f e ren t c i r c u m - s t a n c e s t h e p a t i e n t m i g h t h a v e r ece ived s u c h t r e a t m e n t s b u t d id n o t in th is case. T h e m e t h o d o f p r o d u c t i o n o f the s e m e n s p e c i m e n was e x t r e m e l y a b n o r m a l a n d m i g h t be e x p e c t e d to p r o d u c e a b n o r m a l c y t o l o g i c a l a p p e a r a n c e s . S u b s e q u e n t b iopsy , h o w e v e r , c o n f i r m e d t h a t the sus- p i c i o u s cells seen in t h e s e m e n were p r e - m a l i g n a n t . F u r t h e r t r e a t m e n t in th i s case wil l be l ow d o s e r a d i o - t h e r a p y (20 G y in 10 f r a c t i o n s in 12 d a y s ) to the r e m a i n i n g test is . T h i s will be g iven as 4 M V X - r a y s f r o m a s ingle a n t e r i o r f ield w i t h 1 c m t h i c k n e s s o f b o l u s o v e r the s c r o t u m . T h i s s h o u l d e r a d i c a t e t h e c h a n g e s o f c a r c i n o m a in - s i t u w h i l s t s p a r i n g L e y d i g cell f u n c t i o n , t h u s a v o i d i n g l o n g - t e r m h o r m o n a l r e p l a c e m e n t .

T h e p l ace o f t e s t i cu l a r b i o p s y o f t he c o n t r a l a t e r a l tes t is in p a t i e n t s w i t h i nvas ive t e s t i c u l a r t u m o u r s is c o n t r o v e r - sial. I t is p r o b a b l y o f l i m i t e d v a l u e i f u s e d o n a r o u t i n e bas i s as o n l y a r o u n d 5 % will p r o v e to be pos i t ive . I t is pos s ib l e , h o w e v e r , to de f ine a h i g h - r i s k g r o u p , w h i c h s h o u l d d e t e r m i n e 80% o f cases. P a t i e n t s in th is g r o u p are t h o s e w i t h sma l l a t r o p h i c ( < 12 ml) , o r c r y p t o r c h i d tes tes ( B e r t h e l s e n , 1982). T h e r e m a y be a ro le f o r r o u t i n e s e m e n c y t o l o g y in th is g r o u p o f p a t i e n t s . O n c e d i a g n o s e d , t he m o s t a p p r o p r i a t e t r e a t m e n t is still a c o n t r o v e r s i a l issue. C lea r ly , t he tox ic i ty o f c h e m o t h e r a p y is n o t a c c e p t a b l e .

L o w dose r a d i o t h e r a p y w o u l d a p p e a r to be s u i t a b l e a n d i n d e e d h a s b e e n r o u t i n e l y u sed p r o p h y l a c t i c a l l y in s o m e c e n t r e s ( R e a d , 1987).

Acknowledgements. The authors wish to thank Professor N.E. Skakkebaek for reviewing the pathology and Mrs McParland for performing the semen analysis.

REFERENCES

Berthelsen, JG, Skakkebaek, NE, vonder Maase, H, Sorensen, BL & Morgensen, P (1982). Screening for carcinoma in-situ of the contralateral testis in patients with germinal testicular cancer. British Medical Journal, 285, 1683-1686.

Giwercman, A, Marks, A & Skakkebaek NE (1988). Carcinoma in-situ germ cells exfoliated from seminiferous epithelium into seminal fluid. Lancet, i, 530.

Hargreave, TB (1986). Carcinoma in-situ of the testis. British Medical Journal, 293, 1389 1390.

Read, G (1987), Carcinoma in-situ of the contralateral testis. British Medtcal Journal, 294, 121.

Skakkebaek NE (1972). Possible carcinoma in situ of the testis. Lancet, ii, 516.

vonder Maase, H, Berthelsen, JG, Jacobsen, GK, Hald, T, Rorth, M, Christopherson, IS et al. (1985). Carcinoma in-situ of the testis eradicated by chemotherapy. Lancet, i, 98.

vonder Maase, H, Giwercman, A, Muller, J & Skakkebaek, NE (1987). Management of carcinoma in-situ of the testis. International Journal o f Andrology, 10, 209--220.

Book Reviews

Ultrasound of the Prostate. By M. D. Rifkin, Raven Press, New York, 1988, 303 pp., $99.00.

Prostate ultrasound is not new, but has only relatively recently become popular as evidenced by numerous papers in the journals and the proliferation of available equipment, mainly related to probe design. It is a procedure as often as not performed by our clinical colleagues and it was the urologists who first engendered interest in prostate ultrasound in the UK. Despite all the work that has been done to explain the changes in echo pattern seen in various disease states, there is still no consensus of opinion as to what means what. This book is one of the first to be produced concentrating on prostate ultrasound, the first I 'm sure of many. The first half of the book is a description of prostate anatomy, it's correlation with ultrasound images, biopsy techniques and a review of scanners and probes. These sections are well-illustrated by both pictures and line drawings. The reader will know by the end of it what the normal prostate looks like and how best to image it. The second half of the book deals with prostate pathology, cancer taking the lions share. There is a chapter on the pathogenesis, staging classification and the modes of spread of prostate cancer. The chapter describing the ultrasound appearances is as well done as it can be with available knowledge. The illustrations are of good quality and the reader will appreciate that biopsy of an abnormal area is the only definite way to diagnose small cancers of the prostate. There is a chapter on benign hypertrophy and one on inflammatory disease. The chapter on the prostatic urethra is rather superficial.

This is a book for the imager, radiologist or urologist, who is embarking on providing a prostate ultrasound service and who hasn't the recent literature to refer to. I do not think that those already involved in this modality will benefit from this book. As time passes and more is known about the ultrasound of this small, but troublesome gland, future editions will be of more value.

D. Rickards

Imaging in Clinical Practice. By A. G. Chalmers, J. H. McKillop and P. J. A. Robinson, Edward Arnold, London, 1988, 330 pp., £16.95.

This book is aimed principally at clinicians of all grades, from consultants requiring a refresher course on current imaging to juniors seeking instruction for post-graduate examinations. The text is well written and easy to follow but the quality of some of the limited number of illustrations is rather disappointing. Candidates for MRCP and FRCR will still have to resort to other sources to see suitable examples of examination cases.

The opening chapter gives a short introduction to each family of imaging tests, and a useful summary of radiation dosimetry and risk assessment. Subsequently each organ system is approached in turn, giving firstly a description of imaging tests and then their application to common clinical problems. The final chapter is devoted to oncology and suggests imaging strategies for the common turnouts. The book closes with a pot-pourri of subjects including a detailed description of the radiology of AIDS.

There is particularly good coverage of scintigraphic studies and a realistic appreciation of the strengths and limitations of barium studies and excretion urography. It was good to see the dismissal of several outdated techniques, e.g. intravenous cholangiography, although others, e.g. fluoroscopy for hilar dance, have slipped through the net. The sections covering neuroradiological topics could have stressed thc primacy of CT and MRI (where available), relegated plain radiography and dispatched epidural venography to the archives.

This book provides a good introduction to modern imaging for junior clinicians but cannot be recommended as the sole source in preparation for MRCP or FRCS. I felt that a more dogmatic approach to the use and abuses of imaging tests would have been helpful to clinicians and radiologists alike.

N. R. Moore