seminoma in klinefelter's syndrome with 47 xxy, 15s+ karyotype

Download Seminoma in Klinefelter's syndrome with 47 XXY, 15s+ karyotype

Post on 06-Jun-2016




5 download

Embed Size (px)




    A 32-year-old man was found to have seminoma of the right testis which had been subjected to orchiopexy for cryptorchism 14 years earlier. The left testis was small and firm, and the patient was further studied for hypogonadism. Chromosome analysis revealed a karyotype of 47, XXY, 15s+ with an extra X chromosome and enlarged and fluorescent satellites on chromosome 1 5 . The satellites were also found in the mother as well as in two sisters and one brother out of his four siblings. Endocrine studies, histological pictures of the biopsied left testis and dermatoglyphic analysis were compatible with Klinefelter's syn- drome. To our knowledge this is the first reported case of seminoma associated with the syndrome. Several implications are discussed for the rare occurrence of a germinal cell tumor in Klinefelter's syndrome.

    Cancer 39:2041-2047, 1977.

    ARIOUS NEOPLASTIC LESIONS H A V E BEEN RE- V ported to occur in patients with Klinefel- ter's syndrome. 2,18,21 In particular, the high in- cidence of male breast cancer in patients with the syndrome has been emphasized. l 1 Regard- ing the testis as the site of tumor development, however, only occasional cases of benign tumors have been reported. '*' The present paper de- scribes a case of seminoma in a testis of Klinefel- ter's syndrome after orchiopexy. In addition to an extra X chromosome, there were intensively fluorescent materials on satellites of autosome 15 (47, XXY, 15s+).


    K.T. was 32 years old when he was first seen in May 1971, at the Department of Urology, Bokutoh

    From the Ikpartment of Urology, Bokutoh General Hos- pital, Tokyo Metropolitan Government, 4-23-15 Kotobashi, Sumidaku, Tokyo 130.

    Address for reprints: Koichiro Isurugi, Department of Urology, The Liniversity of Tokyo Branch Hospital, Mejirodai, Bunkyo-ku, Tokyo 112.

    * Department of Cytogenetics. Medical Research In- stitute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, 'Tokyo I 13, Japan.

    The authors are grateful to Miss Y. Hayashida, Depart- ment of Legal Medicine, the University of Tokyo School of Medicine, for her kind co-operation in blood group and haptoglobin studies, to Dr. K. Harada, Department of Legal Medicine, Kyorin University School of Medicine for eryth- rocyte enzyme analyses, and to Dr. S. Nanko, Department of Human Genetics and Criminology, Institute of Brain Re- search, University of Tokyo School of Medicine for derma- toglyphic analysis performed in the present study.

    Accepted for publication August 26, 1976.

    General Hospital for an enlargement of the right scrota1 content. He was born on January 16, 1939, a t full term after uneventful pregnancy as the first child for the parents who were unrelated and healthy with- out any known hereditary diseases. No abnormality of the external genitalia was noticed by the parents and physical growth and mental development were said to be normal until puberty except that the patient suf- fered from bronchial asthma in childhood. At the age of 18 (1957), the patient noticed that the right testis was located in the inguinal region and received or- chiopexy in a hospital. At this time it was pointed out by the physician that the bilateral testes were small but the patient received no further examination. He stated that development of the secondary sexual char- acteristics had been normal and he had not received any medication before.

    At the time of his first visit to our hospital in 1971, the external genitalia were underdeveloped with a small, phimotic penis and the left testis which was small and firm. The prostate was also small on palpa- tion. A female type distribution of the pubic hair was noted. There was no gynecomastia. The right testis was enlarged symmetrically to a hen-egg sized hard tumor. The height was 158.3 cm, the arm span 151.0 cm, and the body weight 54 kg. Blood counts, blood chemistries, liver function studies and the erythrocyte sedimentation rate were all within normal limits. The chest and skull films and excretory urograms were also normal.

    The right testicular tumor (6.6 X 4.4 X3.8 cm) was removed on May 18, 1971, and the pathological diag- nosis was pure seminoma (Fig. 1). The patient post- operatively received a total of 9000 rads of irradiation. The patient was observed carefully for more than three years without any sign of tumor recurrence or metastasis. Subsequently, for the evaluation of hy- pogonadism, biopsy of the left testis and chromosome

    204 1

  • 2042 CANCER May 1977 Vol. 39

    analysis were performed in July 1975. Histologically, the left testis showed mostly hyalinized seminiferous tubules buried in markedly hyperplastic Leydig cells, a finding compatible with Klinefelters syndrome (Fig. 2) .

    Chromosome analysis has been made in cells de- rived from lymphocyte cultures of the patient, and the presence of an extra C group chromosome and an unusually large satellite on the short arm of one of the D group chromosomes were found in the cells ana- lyzed (Fig. 3). The results of chromosome counts and

    FIG. 1. Histological picture of seminoma of the right testis which was removed in 1971. Tumor cells with large nuclei with lymphocytic infiltration are noted.

    analyses in the patient together with those in the family are shown in Table 1 . Blood smears examined for drumsticks were found to be chromatin-positive (2.8%). Using the quinacrine fluorescence (Q-band- ing) technique, the extra C group chromosome was clearly identified as an X and the chromosome having a large satellite was found to be chromosome 15 (Fig. 4 ) . The karyotype of the patient can thus be desig- nated 47, XXY, 1 5 s f .

    The large satellite fluoresced brilliantly and dis- tinctly in the metaphase plate. A corresponding fluo-

    FIG. 2. Histological picture of the hiopsied left testis. Atrophic or mostly hyalinized semi- niferous tubules and markedly hyperplastic Leydig cells.


    FIG. 3. The karyotype of the pro- positus (47, XXY, 15s+) with the unusually enlarged satellite (arrow) on autosome 15.

    rescent particle was present in many interphase nu- clei, as shown in Fig. 4. The satellite was darkly stained with the C-banding technique (Fig. 5).

    In order to clarify the significance of the presence of this fluorescent satellite, chromosome analysis was performed on both parents and four siblings (two brothers and two sisters) by the use of lymphocyte cultures. In addition, the chromosomes of a 7-year- old boy who is a son of one of the two brothers were also studied, since the boy had been noted to have the right testis undescended in the inguinal region. They showed apparently normal karyotypes. With the Q- banding technique, the fluorescent satellite on one of


    the chromosome 15 was observed in cells of the mother (Fig. 6), and three members of the siblings, while no such fluorescent satellite was found in the father, in one of the two brothers and in the boy with undescendent testis. (Table I ) . These results may indicate that there is no direct correlation between the clinical conditions of the patient and the presence of the unusually large satellite.

    Blood groups, erythrocyte enzyme variants, hap- toglobin types and group specific components were studied in the proband and the parents. The results are shown in Tables 2 and 3, and indicate that all genetic expressions were compatible with inheritance

    FIG. 4. Q-band staining of the metaphase chromosomes of the propositus showing brightly fluo- rescent portions of the Y and 15 (arrow) chromosomes. An inter- phase nucleus (bottom left) shows corresponding fluorescent spots.

  • 2044 CANCER May 1977 Vol. 39

    from the parents. From the finding of Xg blood type it can be seen that at least one of the two X chromo- somes in the proband was of maternal origin.

    Dermatoglyphic analysis revealed a total finger ridge count(TRC) of 118 in the proband. The mean T R C of normal Japanese male and female controls were 151.3 & 46.1 (SD) and 142.2 st 44.8, respec- tively. I' There were third interdigital loops and hy- pothenar distal loops bilaterally. In hallucal areas, a tibia1 loop on the left and a distal loop with ridge count over 20 on the right were observed. The max- imal d d angle on the left was 37' and on the right 34". No simian line or thenar pattern was found. The finding of a low TRC is considered as compatible with Klinefelter's syndrome.

    Endocrine studies performed in July 1975, showed

    FIG. 5. C-band patterns of the metaphase chromosome spread in the propositus showing the darkly stained satellite on the 15 chromo- some (arrow).

    elevated basal levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deter- mined by radioimmunoassay." Serum LH was 257.9 ng (LER 907)/ml and FSH was 1219 ng (LER 907)/ml. Normal ranges for adult men (16-39 years of age) in our laboratories are 10-45 ng/ml for LH and 40-180 ng/ml for FSH. lo Exaggerated increases of both LH and FSH levels were observed in response to a n intravenous injection of synthetic luteinizing hormone-releasing hormone (LH-RH, 100 rg), i.e., after 30 minutes of the injection serum LH and FSH levels were increased at 1203.1 and 2138.7 ng/ml, respectively. The serum testosterone level also deter- mined by radioimmunoassay was 133.7 ng/dl, which was decreased compared with normal adult men.'

    Since September 1975; the patient has been receiv-

    FIG. 6. Q-band patterns of a metaphase preparation in the mother of the propositus. Note the brilliantly fluorescent satellite (ar- row) and the corre


View more >