Association of immunohistochemical markers with premalignancy in Gonadal Dysgenesis

Research

Bonnie McCann-Crosby^1*, Sheila Gunn¹, E. O¿Brian Smith², Lefkothea Karaviti¹ and M. John Hicks³

• *
  Corresponding author: Bonnie McCann-Crosby [email protected]

Author Affiliations

¹ Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children¿s Hospital, Houston 77030, TX, USA

² Department of Pediatrics, Children¿s Nutrition Research Center, Baylor College of Medicine, Houston 77030, TX, USA

³ Department of Pathology, Baylor College of Medicine, Texas Children¿s Hospital, Houston 77030, TX, USA

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International Journal of Pediatric Endocrinology 2015, 2015:14 
doi:10.1186/s13633-015-0010-6

Published: 15 June 2015

Abstract (provisional)

Background Gonadal dysgenesis (GD) is associated with increased risk of gonadal malignancy.
Determining a patient’s risk and appropriate timing of gonadectomy is challenging,
but immunohistochemical markers (IHM) may help establish the diagnosis of malignant
germ cell tumors (GCT). Our objective was to identify the prevalence of specific IHM
expression in patients with GD and determine if the patterns of expression can help
identify malignancy versus pre-malignancy state. We evaluated the published literature
using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE)
system to provide recommendations on the predictive role of IHM in the detection of
germ cell malignancy. Methods The data for this retrospective study included karyotype,
gonadal location, external masculinization score, age at time of gonadectomy or biopsy,
microscopic description and diagnosis of gonadal tissue, and immunohistochemical staining,
including octamer binding transcription factor (OCT) 3/4, placental-like alkaline
phosphatase (PLAP), ?-catenin, alpha-fetoprotein (AFP), and stem cell factor receptor
CD117 (c-KIT). Patients with complete or partial GD who had undergone gonadectomy
or gonadal tissue biopsy were included. Results The study included 26 patients with
GD, 3 of whom had evidence of GCT (11.5 %, gonadoblastoma, dysgerminoma): 2 had Swyer
syndrome, 1 had 46,XY partial GD. One patient with XY partial GD had gonadoblastoma-like
tissue. All 4 patients (15 %) had strong expressions of 4 tumor markers (OCT 3/4,
PLAP, ?-catenin, CD117), as did 5 other patients (19 %, ages 2–14 months) without
GCT: 4 had XY GD, 1 had 46,XX GD. ?-catenin was expressed in 96 % of patients in a
cytoplasmic pattern, CD117 in 78 %, OCT 3/4 in 55 %, PLAP in 37 %, and AFP in 1 patient
(4 %). Tumor marker expression was not specific for ruling out malignancy in patients
lt;1 year. Conclusions In patients older than 1 year, expression of all three markers
(OCT 3/4, PLAP, CD117) may be instrumental in the decision-making process for gonadectomy,
even in the absence of overt germ cell malignancy. Our literature review suggests
that OCT 3/4 expression is most helpful in predicting risk of malignancy. Additional
criteria are needed to stratify risk in patients younger than 1 year of age, as these
markers are not reliable in that age group.