Post on 21-Jun-2020
Riunione Gruppo Italiano Chirurgia Oncologica PediatricaGenova 18 Settembre 2009
IL “TUMOR RISK” NEI PAZIENTI CON DIFETTI DELLA DIFFERENZIAZIONE SESSUALE (DSD):INTRATUBULAR GERM CELL NEOPLASIA UNCLASSIFIED (IGCNU) IN UN CASO DI DEFICIT DEL MIF (Mϋllerian Inhibiting Factor).
Massimiliano Silveri Dipartimento Chirurgia Pediatrica Ospedale Pediatrico “Bambino Gesù” ‐ Palidoro
Francesca Diomedi‐Camassei Dipartimento Laboratori ‐ Servizio Anatomia‐Istologia Patologica
1 mese (1985) ernia inguinale dx
utero – gonadi rudimentali
SIN: gonade primordiale
biopsie gonadiche
DX: testicolo tubuli prividi lume
DIAGNOSI ENDOCRINOLOGICA: DEFICIT DEL MIF (Mϋllerian Inhibiting Factor)
CARIOTIPO NORMALE: 46 XY
18 mesi (1987) asportazione gonade sinno residui mϋllerianinuova biopsia gonade dx (no referto)
9 anni (1994) posizionamento protesi sin
24 anni (2009) sospetta ernia inguinale dx diretta
ECOGRAFIA
RMN ADDOME/PELVI
ESAME LIQUIDO SEMINALE: AZOOSPERMIA
sospetto OVOTESTIS
sospetto residuo mulleriano
INTERVENTO 1
1.LAPAROSCOPIA (no residui mϋlleriani)
2.BIOPSIA TESTICOLARE (a funicolo clampato)
3. CISTOSCOPIA non identificabili utricolo prostatico e sbocchi vescicole seminali
ISTOLOGIA ESTEMPORANEA:“Ipotrofia testicolare. Scarsa focale spermatogenesi”
ISTOLOGIA DEFINITIVA:“Ipoplasia testicolare sede di neoplasia intratubulare a cellule germinali, non classificata (IGCNU)”
A
B
C
A‐B‐C: tubuli piccoli con membranabasale ispessita (atrofici) rivestitida grosse cellule germinali neopl.
Colorazione ematossilina‐eosina 10 X
Colorazione immunoistochimica per fosfatasi alcalina placentare (PLAP)Ingrandimento 20 X
Positivita’ marroneNuclei controcolorati in bluette
L’enzima è presente nelle cellule germinali neoplastiche
IGCNU (Intratubular Germ Cell Neoplasia, Unclassified)
Skakkebaek NE. “Possible carcinoma in situ of the undescended testis”, Lancet 1992
TIN. Testicular Intraepithelial Neoplasia. It is defined as the presence of malignant germcells within the seminiferous tubules
At 5 years about 50 % of patients with a testicular biopsy positive for IGCNU havedeveloped invasive germ cell tumors and only a small fraction remain free of invasivetumors by 7 years
Orchiectomy is the treatment of choice in patients with unilateral IGCNU, and low‐dose radiation is efficacious in patients with bilateral IGCNU (although sterility is certain).
INTERVENTO 2
ORCHIFUNICOLECTOMIA DX
ISTOLOGIA DEFINITIVA
“neoplasia intratubulare a cellule germinali, non classificata (IGCNU) con focale estensione extratubulare”
Rx torace: NLTC LFN: NL
“Specific subgroups of DSD patients are prone to the developmentOf a germ cell tumor (GCT).
Their individual risk profile can be estimated by combining knowledge on the specific gonadal differentiation patterns present in patients,and detailed histological and genetic diagnostic investigations”.
Cools M, Loojienga HJ. “Disorders of sex development: update on genetic background, terminology and risk for the development of germ cell Tumors”. World J Pediatr 2009; 5(2): 93‐102
RISK CONDITION RISK (%) PROPOSED MANAGEMENT NUMBER OF STUDIES
HIGH GD (Y+), intra‐abdominal 15‐35 Gonadectomy 12
PAIS, non‐scrotal 15 Gonadectomy 3
Frasier syndrome (Y+) 60 Gonadectomy 1
Danys‐Drash (Y+) 40 Gonadectomy 1INTERMEDIATE Turner (Y+) 12 Gonadectomy 11
17β‐HSD 28 Strict follow‐up; biopsy? 2LOW CAIS 0.8 Biopsy/in case of CIS: irradiation or
gonadectomy3
Ovotesticular DSD 3 Removal of testicular tissue if possible in case of female GID (Gender IDentity)
3
Turner (Y‐) 1 None 11UNKNOWN 5° reductase deficiency 0 Unknown 1
Leydig cell hypoplasia 0 Unknown 1
GD (Y+), scrotal ? Biopsy; in case of CIS: irradiation
0
PAIS, scrotal gonads ? Biopsy; in case of CIS: irradiation
0
From: Cools M, Leendert HJ. “Disorders of sex development: update on the genetic background, terminology and riskfor the development of germ cell tumors”. World J Pediatr Vol 5 No 2; May 15, 2009
INCIDENCE OF GCT IN DSD PATIENTS
GD: gonadal dysgenesis; PAIS: partial androgen insensitivity syndrome; CAIS: complete androgen insensitivity syndrome; CIS: carcinoma in situ
Grazie per l’attenzione !
Sede di Palidoro