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Association of immunohistochemical markers with premalignancy in Gonadal Dysgenesis.

McCann-Crosby B, Gunn S, Smith EO, Karaviti L, Hicks MJ - Int J Pediatr Endocrinol (2015)

Bottom Line: 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, β-catenin, CD117), as did 5 other patients (19 %, ages 2-14 months) without GCT: 4 had XY GD, 1 had 46,XX GD. β-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 %).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.

ABSTRACT

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), β-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, β-catenin, CD117), as did 5 other patients (19 %, ages 2-14 months) without GCT: 4 had XY GD, 1 had 46,XX GD. β-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 <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.

No MeSH data available.


Related in: MedlinePlus

In Situ gonadoblastoma arising within Gonadal Dysgenesis: a Several noninvasive gonadoblastoma-like nests comprised of large germ cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm and hyaline globules (H&E stain); b Nuclear immunoreactivity with OCT3/4; c CD117 (c-Kit) cytoplasmic immunoreactivity; d Placental alkaline phosphatase (PLAP) cytoplasmic immunoreactivity
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Fig3: In Situ gonadoblastoma arising within Gonadal Dysgenesis: a Several noninvasive gonadoblastoma-like nests comprised of large germ cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm and hyaline globules (H&E stain); b Nuclear immunoreactivity with OCT3/4; c CD117 (c-Kit) cytoplasmic immunoreactivity; d Placental alkaline phosphatase (PLAP) cytoplasmic immunoreactivity

Mentions: The clinical data for the 26 cases included in this study are shown in Table 1. Patient 14 had a right gonadectomy at age 12 months and a left testicular biopsy at 33 months, thus a total of 27 gonadal samples were reviewed in this study. Twenty patients had XY PGD, four patients had XX PGD, and two patients had XY CGD. The age at the time of gonadectomy or gonadal biopsy ranged from 2 months to 18 years (median, 20 months). Three patients (11.5 %) had evidence of GCT, two of whom had XY CGD and one who had XY PGD. Both of the XY CGD patients had both a GB (Fig. 1) and DG (Fig. 2), whereas the patient with XY PGD had only a GB. An additional patient with XY PGD had tissue resembling a GB (Fig. 3) and was classified as having in-situ neoplasia.Table 1


Association of immunohistochemical markers with premalignancy in Gonadal Dysgenesis.

McCann-Crosby B, Gunn S, Smith EO, Karaviti L, Hicks MJ - Int J Pediatr Endocrinol (2015)

In Situ gonadoblastoma arising within Gonadal Dysgenesis: a Several noninvasive gonadoblastoma-like nests comprised of large germ cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm and hyaline globules (H&E stain); b Nuclear immunoreactivity with OCT3/4; c CD117 (c-Kit) cytoplasmic immunoreactivity; d Placental alkaline phosphatase (PLAP) cytoplasmic immunoreactivity
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472165&req=5

Fig3: In Situ gonadoblastoma arising within Gonadal Dysgenesis: a Several noninvasive gonadoblastoma-like nests comprised of large germ cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm and hyaline globules (H&E stain); b Nuclear immunoreactivity with OCT3/4; c CD117 (c-Kit) cytoplasmic immunoreactivity; d Placental alkaline phosphatase (PLAP) cytoplasmic immunoreactivity
Mentions: The clinical data for the 26 cases included in this study are shown in Table 1. Patient 14 had a right gonadectomy at age 12 months and a left testicular biopsy at 33 months, thus a total of 27 gonadal samples were reviewed in this study. Twenty patients had XY PGD, four patients had XX PGD, and two patients had XY CGD. The age at the time of gonadectomy or gonadal biopsy ranged from 2 months to 18 years (median, 20 months). Three patients (11.5 %) had evidence of GCT, two of whom had XY CGD and one who had XY PGD. Both of the XY CGD patients had both a GB (Fig. 1) and DG (Fig. 2), whereas the patient with XY PGD had only a GB. An additional patient with XY PGD had tissue resembling a GB (Fig. 3) and was classified as having in-situ neoplasia.Table 1

Bottom Line: 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, β-catenin, CD117), as did 5 other patients (19 %, ages 2-14 months) without GCT: 4 had XY GD, 1 had 46,XX GD. β-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 %).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.

View Article: PubMed Central - PubMed

Affiliation: Division of Pediatric Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030 USA.

ABSTRACT

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), β-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, β-catenin, CD117), as did 5 other patients (19 %, ages 2-14 months) without GCT: 4 had XY GD, 1 had 46,XX GD. β-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 <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.

No MeSH data available.


Related in: MedlinePlus