CHAPTER X CHAPTER 4 - Cancer et environnement

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A B Fig. 4.09 Spermatocytic seminoma. A Example of G-banding on a metaphase spread. B Comparative genomic hybridization of DNA isolated from the same tumour. Note the almost complete absence of structural anomalies, while numerical changes are present. Gain of chromosome 9 is the only consistent anomaly identified. Precursor lesions Intratubular germ cell neoplasia, unclassified type (IGCNU) Definition Germ cells with abundant vacuolated cytoplasm, large, irregular nuclei and prominent nucleoli located within the seminiferous tubules. ICD-O code 9064/2 Synonyms Intratubular malignant germ cell, carcinoma in situ, intratubular preinvasive tumour, gonocytoma in situ, testicular intraepithelial neoplasia, intratubular atypical germ cells and intratubular malignant germ cells. Epidemiology Adults In adults with history of cryptorchidism intratubular germ cell neoplasia, unclassified are seen in 2-4% {345,787,887, 1010,1124,2040,2131,2222} in contrast to 0.5% in young children {501}. In infertility studies, the prevalence is about 1% {233,345,1900,2346, 2430,2943}) ranging from 0-5%. Patients with intersex syndrome, and a Y chromosome have intratubular germ cell neoplasia of the unclassified type (IGCNU) in 6-25% of cases {118,387,1831,2140, 2826}. Testes harbouring a germ cell tumour contain IGCNU in a mean of 82.4% of cases, ranging from 63 {889} -99% {346}. Since the risk of tumour development in the contralateral testis is increased about 25- 50 fold {615,1985, 2774}, some centres in Europe have initiated biopsies of the contralateral testis, with detection rates of IGCNU of 4.9-5.7% {613,2749}. IGCNU is detected in 42% of patients who presented with retroperitoneal germ cell tumours {262,555,1100} but is rarely found in patients with mediastinal tumours {997}. Several autopsy studies have shown that the incidence of IGCNU is the same as the incidence of germ cell tumours in the general population {616,891}. Children In contrast to their adult counterpart, the true incidence of prepubertal IGCNU is difficult to assess. IGCNU has only rarely been described in association with testicular maldescent, intersex states and in a very few case reports of infantile yolk sac tumour and teratoma {1134,1381, 2018,2167,2482,2483}. IGCNU is seen in association with cryptorchidism is 2–8% of patients {1381}. Four of 4 patients with gonadal dysgenesis in one series had intratubular germ cell neoplasia of the unclassified type (IGCNU) {1833} as did 3 of 12 patients with androgen insensitivity (testicular feminization) syndrome {1831}. In review of the literature Ramani et al. found IGCNU in 2 of 87 cases of different intersex states {2140}. A B Fig. 4.10 Precursor lesions of germ cell tumours. A Intratubular germ cell neoplasia (IGCNU) adjacent to normal seminiferous tubules. B Positive PLAP staining in the intratubular germ cell neoplasia (IGCNU) adjacent to normal seminiferous tubules. 228 Tumours of the testis and paratesticular tissue
A B Fig. 4.12 Comparison of morphological features of normal seminiferous tubules (left part) and intratubular germ cell neoplasia (IGCNU) in seminiferous tubules (right part). C Fig. 4.11 Precursor lesions of germ cell tumours. A Typical pattern of intratubular germ cell tumour unclassified. B PAS staining for glycogen in the malignant germ cells. C Positive PLAP staining in the malignant germ cells. The morphologic and the immunohistochemical features of normal prepubertal germ cells resemble those of IGCNU and can persist up to 8 months to one year of age {118}. Therefore, the validity of prepubertal IGCNU needs further investigation. One study found no testicular cancer in 12 of the 22 prepubertal patients, with mean 25 years follow up, who were biopsied during orchidopexy and found to have placental alkaline phosphatase (PLAP) positive atypical appearing germ cells {996}. The absence of isochromosome 12p in testicular germ cell tumours of childhood, suggests that the pathogenesis of germ cell tumours in children may be different than in adults. Clinical features The symptoms and signs are those of the associated findings, including atrophic testis, infertility, maldescended testis, overt tumour and intersex features. Macroscopy There is no grossly visible lesion specific for IGCNU. Histopathology The malignant germ cells are larger than normal spermatogonia. They have abundant clear or vacuolated cytoplasm that is rich in glycogen, as demonstrated by periodic acid-Schiff (PAS) stains. The nuclei are large, irregular and hyperchromatic with one or more large, irregular nucleoli. Mitoses, including abnormal ones, are not uncommon. The cells are usually basally located between Sertoli cells. Spermatogenesis is commonly absent, but occasionally one can see a pagetoid spread in tubules with spermatogenesis. The tubular involvement is often segmental but may be diffuse. The malignant germ cells are also seen in the rete and even in the epididymal ducts. Isolated malignant germ cells in the interstitium or lymphatics represent microinvasive disease. A lymphocytic response often accompanies both intratubular and microinvasive foci. A Fig. 4.13 Precursor lesions of germ cell tumours. A Intratubular germ cell neoplasia, unclassified. Note the large nuclei with multiple nucleoli. B Syncytiothrophoblasts in a tubule with intratubular germ cell neoplasia (IGCNU). B Immunoprofile PLAP can be demonstrated in 83-99% of intratubular germ cell neoplasia of the unclassified type (IGCNU) cases and is widely used for diagnosis {189,345,346, 888,1100,1199,1345,1615,2763}. Other markers include: CD117 (c-kit) {1191, 1302,1619,2518}, M2A {157,890}, 43-9F {889,1054,2061} and TRA-1-60 {97,151, 886}. These markers are heterogeneously expressed in IGCNU, for example: TRA-1-60 is seen in tubules adjacent to Germ cell tumours 229
Page 1 and 2: CHAPTER 4X Tumours of the of the Te
Page 3 and 4: TNM classification of germ cell tum
Page 5 and 6: Germ cell tumours P.J. Woodward A.
Page 7 and 8: senting symptom: back or abdominal
Page 9 and 10: A B Fig. 4.03 Germ cell tumours gen
Page 11: process at all {1524}. In addition,
Page 15 and 16: small tumour insufficient to produc
Page 17 and 18: A B C Fig. 4.22 Seminoma. A Pseudog
Page 19 and 20: A B Fig. 4.27 Spermatocytic seminom
Page 21 and 22: Differential diagnoses Differential
Page 23 and 24: Histologic patterns Microcystic or
Page 25 and 26: A Fig. 4.40 Yolk sac tumour. A Pleo
Page 27 and 28: Teratoma Teratomas are generally we
Page 29 and 30: A B C Fig. 4.49 Teratoma. A Teratom
Page 31 and 32: A B Fig. 4.52 Teratoma with somatic
Page 33 and 34: A B Fig. 4.59 Mixed germ cell tumou
Page 35 and 36: A B C Fig. 4.64 Leydig cell tumour.
Page 37 and 38: A Fig. 4.69 Androgen insensitivity
Page 39 and 40: tinguished from Sertoli cell nodule
Page 41 and 42: ound and have spherical, regularly
Page 43 and 44: Tumours containing both germ cell a
Page 45 and 46: Miscellaneous tumours of the testis
Page 47 and 48: Lymphoma and plasmacytoma of the te
Page 49 and 50: Tumours of collecting ducts and ret
Page 51 and 52: Tumours of paratesticular structure
Page 53 and 54: Epidemiology Nodular mesothelial hy
Page 55 and 56: A B Fig. 4.104 Papillary cystadenom
Page 57 and 58: Fig. 4.109 Desmoplastic small round
Page 59 and 60: Fig. 4.115 Leiomyosarcoma. Coronal,
Page 61 and 62: Secondary tumours C.J. Davis Defini

CHAPTER X CHAPTER 4 - Cancer et environnement

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