Gonadoblastoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Gonadoblastoma is a benign tumor that almost exclusively involves individuals suspected of intersex disorders. This tumor comprised of underdeveloped germ cells and sex-cord stromal cells which defines the term gonadoblastoma.

Gonadoblastoma was first discovered by Dr. Scully in 1953. The association between GBY gene (GonadoBlastoma on the Y chromosome) and gonadoblastoma was made in 1986. In 1995, Tsuchiya found that the GBY gene located near the centromere of Y chromosome and contains multiple genes including Testis-specific protein Y-encoded (TSPY) gene.

Gonadoblastoma may be classified according to pathological appearance into three sub-types including classical, dissecting, and burnt-out.

The exact pathogenesis of gonadoblastoma is not fully understood. Gonadal development starts at 5 weeks of gestation and continues according to sex chromosomes. Any defects in this complicated process leads to defective gonadal development and gonadal dysgenesis and subsequently, it may be converted to gonadoblastoma in 20% to 30% of the cases.

There are no established causes for gonadoblastoma. However, there are certain risk factors that predispose to increased risk of gonadoblastoma.

Gonadoblastoma must be differentiated from other diseases that cause virilization, and primary amenorrhea and also must be differentiated pathologically from dysgerminoma, Sex-cord stromal tumors, and Sertoli-cell nodules.

The prevalence of gonadoblastoma depends on the chromosomal content, presence or absence of mosaicism, gonadal histology, and age of the patient and varies between 15,000 to 30,000 per 100,000 individuals worldwide. The incidence of gonadoblastoma varies according to the presence or absence of Y chromosomal content and age of the individual. Patients with Turner syndrome who have Y chromosomal content either completely or partially may develop gonadoblastoma with an incidence as high as 43,000 per 100,000 individuals worldwide. The incidence of gonadoblastoma among phenotypical females with XY gonadal abnormalities have been observed to be 40,000 per 100,000 individuals worldwide. Gonadoblastoma may be found at any age, but commonly presents before the age of 15 years. Since, it usually affects individuals with gonadal dysgenesis, there is no genotype–phenotype correlation. Phenotypically, it tends to affect female individuals to a greater extent.

The most potent risk factor in the development of gonadoblastoma is gonadal dysgenesis. The risk also increases with age.

There is insufficient evidence to recommend routine screening for gonadoblastoma. However, patients with XY gonadal abnormalities should be followed using sonography starting at age 2, every six months, until the gonads are removed.

Gonadoblastoma per se is a benign tumor, however, it has the capacity to convert to dysgerminoma or other more malignant germ cell tumors and produce steroids with resultant virilization. Prognosis is generally excellent after removing the tumor.

There are no established criteria for the diagnosis of gonadoblastoma. It is often found during a workup for ambiguous genitalia in infancy or sexual developmental disorder in puberty. Chromosomal analysis plays the most beneficial role in the diagnosis of conditions associated with gonadoblastoma. However, sometimes the Y chromosome materials are present in molecular level and cannot be diagnosed karyotypically. In theses individuals, molecular analysis of chromosomes using polymerase chain reaction (PCR) and/or fluorescence in situ hybridization (FISH) may be helpful.

Patients with gonadoblastoma present either during infancy with ambiguous genitalia or later with sexual developmental complaints. The hallmark of gonadoblastoma is gonadal developmental disorders.

Gonadoblastoma has no characteristic physical feature, however, any clue to the existence of an intersex disorder must raise the concern for diagnosing the coexisting gonadoblastoma.

Gonadoblastoma has no specific laboratory findings.

There are no ECG findings associated with gonadoblastoma.

An abdominal/pelvic X-ray may be helpful in the diagnosis of calcification in the gonads associated with gonadoblastoma.

There are no ultrasound findings associated with gonadoblastoma. However, an ultrasound may be helpful in the evaluation of a mass in the gonads and the exclusion of associated conditions.

There are no characteristic CT scan or MRI findings associated with gonadoblastoma. However, an imaging study may be helpful in the diagnosis of associated conditions of this disorder, which include gonadal dysgenesis, Turner syndrome, and etc.

MRI is usually not indicated for the diagnosis of gonadoblastoma.

There are no other imaging findings associated with gonadoblastoma.

There are no other diagnostic studies associated with gonadoblastoma.

The mainstay of treatment for gonadoblastoma is surgery. Hormonal replacement therapy may be considered depending on the underlying condition.

Surgery is the mainstay of treatment for gonadoblastoma. It should be removed as soon as it is diagnosed.

There are no established measures for the primary prevention of gonadoblastoma.

There are no established measures for the secondary prevention of gonadoblastoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Gonadoblastoma was first discovered by Dr. Scully in 1953. The association between GBY gene (GonadoBlastoma on the Y chromosome) and gonadoblastoma was made in 1986. In 1995, Tsuchiya found that the GBY gene located near the centromere of Y chromosome and contains multiple genes including Testis-specific protein Y-encoded (TSPY) gene.

• Gonadoblastoma was first discovered by Dr. Scully, an American pathologist, in 1953 studying the pathology of a series of tumors suspected of being dysgerminomas.^[1][2][3][4]
• This tumor is called gonadoblastoma since it looks like embryonic tissue, but in an indifferent way regarding sexual development.
• The association between GBY gene (GonadoBlastoma on Y chromosome) and gonadoblastoma was made in 1986.
• In 1995, Tsuchiya found that the GBY gene located near the centromere of Y chromosome and contains multiple genes including testis-specific protein Y-encoded (TSPY) gene.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Gonadoblastoma may be classified according to pathological appearance into three sub-types including classical, dissecting, and burnt-out.

Gonadoblastoma may be classified according to pathological characteristics into three sub-types: ^[1]

• Classical
• Dissecting
• Burnt-out

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

The exact pathogenesis of gonadoblastoma is not fully understood. Gonadal development starts at 5 weeks of gestation and continues according to sex chromosomes. Any defects in this complicated process leads to defective gonadal development and gonadal dysgenesis and subsequently, it may be converted to gonadoblastoma in 20% to 30% of the cases.

Gonadal development starts at 5 weeks of gestation and continues according to sex chromosomes. Any defects in this complicated process lead to defective gonadal development and gonadal dysgenesis.^[1][2]

• The exact pathogenesis of gonadoblastoma is not completely understood.^[3]
• Gonadoblastoma develop almost exclusively in dysgenetic gonads containing the Y chromosomal contents.
• The GBY gene locus, localized near the centromere of the Y chromosome, is hypothesized to be the culprit gene locus in the pathogenesis of gonadoblastoma.
• TSPY gene, one of the genes belonging to GBY locus, is observed to be over-expressed in the gonadoblastoma and other germ cell tumors, although its exact role is still unclear.
• There are case reports of genotypically normal women individuals with gonadoblastoma that suggests the existence of other mechanisms involving in the pathogenesis of gonadoblastoma.^[4][5]
• It is hypothesized that the genotypically normal female individuals may have the TSPY putative gene on their X chromosomes or autosomes.^[5]

Genes involved in the pathogenesis of gonadoblastoma include:^[6]

• TSPY

The following disorders are associated with the development of gonadoblastoma:

• XY gonadal dysgenesis^[7]
• Frasier syndrome^[8]
• WAGR syndrome^[9]
• Swyer syndrome^[10]
• 9p partial monosomy^[11]

• Gross pathology of tumor greatly depends on the degree of germ cells overgrowth and calcification.^[12]
• The tumor is firm and cartilaginous with a yellow to a brown-grey color.
• It may be calcified partly or almost completely.
• It may be very large, especially when accompanied by a dysgerminoma.
• Sometimes, it is hardly detectable in gross examination.

Gonadoblastoma is formed from two different types of cells:^[13]

• Larger cells resembling immature germ cells with varied degrees of atypia must be differentiated from the simultaneous invasive germ cell tumor.
• Smaller cells resembling the sex-cord stroma (granulosa or sertoli-like cells).
• Another kind of stromal cells (Leydig cells or lutein-like cells) may also exist, but their presence is not essential for the diagnosis. They tend to be present greatly after puberty.

The two essential type of cells forms a nest-like space in which, immature germ cells surrounded by sex-cord stromal cells. This nested arrangement is characteristic of gonadoblastoma.

• The nest is encircled by a basement membrane which can be hyalinized or even calcified.
• Calcification can be focal or extensive.
• Focal calcification is found in more than 80% of the individuals.
• The nodular pattern of hyalinized basement membrane encircled by stromal cells can also be present.

Gonadoblastoma may be classified pathologically into three forms:^[12][14]

• Classical form as described above.
• Burnt-out form, in which the cells regress and the remnant is calcified and forms a mulberry-shaped calcification.
• Dissecting form, which has an infiltrative and cord like pattern rather than a nested arrangement. The clinical relevance of this pathological feature is that, it should be differentiated from germinoma.^[15]

Gonadoblastoma has no specific laboratory feature, however, some immunohistochemistry staining can be positive including:^[16][17]

• TSPY
• OCT3/4
• FoxL
• SF-1
• Sox9

Germ cells may be positive for:^[18]

• SALL4
• OCT4

The sex cord cells may be positive for:

• Calretinin
• WT1
• Inhibin

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

There are no established causes for gonadoblastoma. However, there are certain risk factors that predispose to increased risk of gonadoblastoma.

There are no established causes for gonadoblastoma. However, there are certain risk factors that predispose to increased risk of gonadoblastoma. For more information on risk factors, click here.

For the WikiDoc page for this topic, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Gonadoblastoma must be differentiated from other diseases that is associated with virilization, and primary amenorrhea and also must be differentiated pathologically from dysgerminoma, Sex-cord stromal tumors, and Sertoli-cell nodules.

Gonadoblastoma must be differentiated from other diseases that cause disorders of sex development, ambiguous genitalia, virilization, and primary amenorrhea such as:^[1][2][3][4]

• 17-Hydroxylase deficiency syndrome
• Turner Syndrome
• Swyer Syndrome
• 5-Alpha-Reductase Deficiency
• Congenital adrenal hyperplasia
• Hypospadias
• Undescended testes

Gonadoblastoma must be differentiated pathologically from:

• dysgerminoma
• Sex cord stromal tumors
• Sertoli-cell nodules

Diseases		Clinical manifestations						Para-clinical findings				Gold standard	Additional findings
		Age of onset	Symptoms			Physical examination
								Lab Findings	Imaging		Immunohistopathology
			pelvic/abdominal pain or pressure	vaginal bleeding/discharge	GI dysturbance	Fever	Tenderness		CT scan/US	MRI
Gynecologic
Ovarian	Embryonal carcinoma[5][6][7][8][9]	Individuals of any age, especially young adults	+/–	+/–	_	_	_	Elevated concentration of alfa-fetoprotein (AFP)	Decreased echogenicity on the ultrasound imaging	The tumor is large, predominantly solid and unilateral with areas of necrosis and hemorrhage. There may be cystic areas that contains mucoid material.	AFP Cytokeratin (AE1/AE3) Placental-like alkaline phosphatase in 50% of the individuals. SALL4 (nuclear) in > 90% of the cases. GPC3	Biopsy	Tumor is usually a component of ovarian mixed germ cell tumors.
	Gonadoblastoma [3][4][10][11][12][13]	Individuals of any age,but more common prior to 15 years of age	+/–	+/–	_	_	_	Elevated concentration of human chorionic gonadotropin (hCG), in case of coexisting dysgerminoma	Solid mass with focal or extensive calcifications with or without ascites Mass can be complex and have a cystic component Increased echogenicity on the ultrasound imaging	Solid mass with focal or extensive calcifications with or withous ascites Mass can be complex and have a cystic component	NA	Biopsy	Tumor is bilateral in 50% of cases Focal calcification can be present in 80% of individuals
	Follicular cysts [14]	Women in reproductive age (15 -45 y/o)	+/–	–	–	–	+/–	High level of estrogen +/–	In US we may see a >3 cm simple cyst with no internal echo and with posterior acoustic enhancement	simple cyst with no internal echo or septa	NA	History/ imaging	It is associated with hyperestrogenism and endometrial hyperplasia
	Theca lutein cysts [15][16][17]	Women in reproductive age (15 -45 y/o)	+/–	–	–	–	+/–	Depends on the underlying etiology	In US we may see bilaterally enlarged ovaries with multiple cysts	Multiple bilateral cysts	Theca interna cell Hyperplasia	History/ imaging	It is associated with hydatidiform moles, choriocarcinoma, diabetes mellitus and clomiphene intake (ovulation induction)
	Serous cystadenoma/carcinoma [18][19][20][21]	>55 y/o	+/–	–	–	–	+/–	Elevated levels of serum cancer antigen-125	In US we may see simple or multiloculated cyst In serous cystadenocarcinoma we may see papillary projection inside the cyst In serous cystadenocarcinoma we may see ascites	In Serous cystadenoma we may see a simple cyst with beak sign, hypointense on T1 and hyperintense on T2 In serous cystadenocarcinoma we may see some Solid malignant components inside the cyst with intermediate signal on T1 and T2	Cyst wall consist of benign/malignant Fallopian epithelial layer Psammoma body In serous cystadenocarcinoma we may see papillary projection inside the cyst	Biopsy	Most common ovarian neoplasm
	Mucinous cystadenoma/carcinoma [22][23][24]	>55 y/o	+/–	–	–	–	+/–	Elevated levels of serum cancer antigen-125	In US we may see large simple cyst with septation In mucinous cystadenocarcinoma we may see thickened internal septation with solid components inside the cyst	Stained glass appearance due to variable signal intensity on T1 and T2 The more mucin we have, there is more intensity on T1 and less intensity on T2	Cyst wall consist of columnar endocervical epithelium We may see gelatinous mucin inside the cyst	Biopsy	It may cause pseudomyxoma peritonei
	Endometrioma [25][26][27]	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	Iron deficiency anemia Elevated levels of serum cancer antigen-125 Increased levels of interleukin 1, chemoattractant protein-1, and interferon gamma	Complex mass on US Increased Doppler flow because of increased vascularture It may present with catamenial pneumothorax, hemothorax, and lung nodules in CT scan.	hyperintensity on T1-weighted images and a hypointensity on T2-weighted images Powder burn hemorrhages	Chocolate cyst	Laparoscopy	It may cause infertility
	Teratoma [28][29][30][31]	10-30 y/o	+/–	–	–	–	+/–	High level of HCG and LDH	In US we may see cystic adnexal mass with mural components and echogenic lesion due to calcification The iceberg sign Dot-dash pattern	We may see evidence of fat components	All three germ layers cell	Biopsy	It may cause ovarian torsion May content thyroid tissue and cause hyperthyroidism In plane radiography we may see calcification due to the presence of tooth in the tumor
	Dysgerminoma [32][33]	in the second to third decade of life	+	+/–	–	–	+/–	High level of HCG and LDH Hypercalcemia	Multilobulated solid masses	We may see ovarian mass with septation which are hyperintense on T1 and hypo or isointense on T2 imaging	Sheets fried egg appearance cells	Biopsy	Same as male seminoma
	Yolk sac tumor [34][35][36]	Young children Male infants	+	–	–	–	+	High levels of AFP	In US we may see a combination of echogenic and hypoechoic components	Ovarian mass with hemorrhagic areas	Yellow appearance Hemorrhagic Schiller-Duval bodies (glomeruli like structures)	Biopsy	The other name is ovarian endodermal sinus tumor
	Fibroma [37][38][39]	>50 y/o	Pulling sensation in the groin	–	–	–	+/–	High levels of CA-125	In CT scan we may see a unilateral mass with poor contrast enhancement	Low signal intensity on T1 and T2 We may see scattered hyperintense areas due to edema or cystic degeneration	Spindle-shaped fibroblast	Biopsy	It may cause Meigs syndrome (ovarian fibroma, ascites, and hydrothorax) It may cause ovarian torsion It may cause pleural effusion
	Thecoma [40][41][42]	>50 y/o	+/–	Postmenopausal bleeding	–	–	–	High level of estrogen	In US we may see non-specific ovarian mass We may see evidence of endometrial hyperplasia due to increased level of estrogen	Hyperintense on T2 T1 intensity depends on the amount of fibrous tissue (fibrous tissue lead to hypointensity)	Lipid-laden stromal cells with pale, vaculolated cytoplasm	Biopsy	We may see endometrial cancer as e result of hyper-estrogenism We may see ovarian fibrothecoma (mixture of fibroma and thecoma)
	Granulosa cell tumor [43][44][45][46]	50-60 y/o	+	Postmenopausal bleeding	+/–	–	–	High level of estrogen and progesteron We may see inhibin, calretinin, and Ki-67 on the surface of granulosa tumor cells	In US we may see solid, cystic, or multiloculated solid and cystic mass	We may see solid, cystic, or multiloculated solid and cystic mass	Call-Exner bodies	Biopsy	In postmenopausal women may cause breast tenderness
	Sertoli-leydig cell tumor [47][48]	15 to 35 y/o	+/–	–	–	–	–	Elevated serum testosterone level Elevated alpha-fetoprotein	In US we may see unilateral Well-defined hypoechoic lesion	Low T2 signal intensity areas of high signal intensity	Lydig cells (Polygonal pink cells with eosinophilic cytoplasm Sertoli cells (clear vacuolated cytoplasm)	Biopsy	It may cause virilization symptoms and amenorrhea
	Brenner tumor [49][50]	>55 y/o	+/–	–	–	–	–	–	In US we may see hypoechoic solid mass and calcification	Hypointense on T2 because of fibrous content	Yellow/pale appearance Transitional cell tumor (resembles bladder) Coffee bean nuclei on H&E	Biopsy	Most of the times it’s an accidental finding
Krukenberg tumor [51][52]	>55 y/o	+/–	–	+/– Based on underlying malignancy	–	–	In case of metastatic GI cancers we may see iron deficiency anemia	Mostly bilateral, complex ovarian lesion In CT scan we may see evidence of concurrent malignancy in other organs	Mostly bilateral, complex ovarian lesion with solid components Internal hyperintensity on T1 and T2 weighted MR images because of mucin Evidence of concurrent malignancy in other organs	Mucin-secreting signet cell	Imaging/ biopsy	The most common primary tumor is in colon, stomach, breast, lung, and contralateral ovary Based on underlying malignancy it may cause pleural effusion
Tubal	tubo-ovarian abscess [53][54][55][56]	Young women (15-30 y/o	+	+	–	+	+	High levels of inflammatory markers Leukocytosis	In US we may see multilocular complex lesion mostly bilateral with debry inside	We may see a pelvic mass filled with fluid with thick walls hypointense in T1 and heterogeneous in T2	In abscess aspiration we may see anaerobic organisms	History/ imaging	The most common risk factors are previous PID, diabetes mellitus, intrauterine device and history of uterine surgery
	Ectopic pregnancy [57]	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	High level of BhCG Progesterone level ≤5 ng/ml	In US we may see empty uterine cavity, tubal ring sign, ring of fire sign (Doppler), extra-uterine fetal heart rate	NA	NA	History/ imaging	Any women in reproductive age presenting with abdominal pain or amenorrhea should be screened for ectopic pregnancy
	Hydrosalpinx [58][59][60]	NA	+	–	–	–	+/–	–	In US we may see tubal longitudinal folds thickening (cogwheel appearance) In CT scan we may see tubular adnexal lesion with fluid attenuation	Dilated Fallopian tube with fluid signal intensity	NA	Imaging	It is associated with endometriosis (haematosalpinx), ovulation induction, pelvic inflammatory disease, post-hysterectomy, tubal ligation, and tubal malignancy It may cause infertility
	Salpingitis [61]	Women of reproductive age	+	+	–	+	+	Leukocytosis	In US we may see , edematous and thickened endosalpingeal folds	NA	NA	History/ physical exam	It may cause infertility
	Fallopian tube carcinoma [62]	>60 y/o	+	+	+	–	+/–	High levels of CA125	US findings are non specific (complex mass on Fallopian tube We may see papillary projections	Low signal on T1 In case of hemorrhage inside the tumor we may see high signal intensity on T1 Low or of intermediate signal on T2 In case of serous fluid inside the tumor we may see high signal intensity on T2	Based on the tumor type we may have different biopsy finding	Biopsy	We may see Latzko triad (abdominal pain, vaginal discgarge, pelvic mass) It may cause pleural effusion
Uterine	Leiomyoma [63][64]	Women of reproductive age	+	+	–	–	+/–	In chronic cases, we may see mild anemia	In US we may see hypoechoic mass with calcification and cystic areas of necrosis or degeneration may	Low to intermediate signal intensity on T1 and T2 In case of necrosis inside the mass, there might be some high signal lesions on T2	Smooth muscle	Imaging	It may cause infertility
	Choriocarcinoma [65][66][67][68]	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	+	High level of B-hCG	In US we may see heterogeneous mass infiltrating myometrium Enlarged uterus Necrosis + Hemorrhage + In CT scan we may see evidence of metastasis to brain, lung and other organs	We may see an infiltrative uterine mass and thickening of uterine wall	Trophoblastic tissue origin columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels	Biopsy	It is associated with bilateral theca lutein cysts Cannonball metastases to the lungs May cause hemoptysis We may see passing of grapes like tissue from the vagina
	Leiomyosarcoma [69][70][71][72][73]	>55 y/o	+	+	–	–	+/–	In some cases we may see elevated levels of CA-125 lactate dehydrogenase	Heterogeneous mass with central low attenuation (necrosis) and calcification.	Increased uterine size Irregular central zones of low signal intensity (tumor necrosis)	We may see atypical cells, high mitotic rate, geographic areas of coagulative necrosis separated from viable neoplasm	Biopsy	In case of rapid uterine growth in post menopausal women we may suspect uterine sarcoma
	Pregnancy [74]	Women in reproductive age (15 -45 y/o)	+/−	+/−	+/−	–	–	High level of BhCG	In US we may see gestational sac, yolk sac, double bleb sign and fetal pore In CT scan we may see cystic structure filled with fluid, curvilinear enhancing structure (placenta) and fetal pore	Cystic structure filled with fluid Curvilinear enhancing structure (placenta) Fetal pore	NA	History/ laboratory findings	We do not perform CT scan and MRI in pregnancy but We may unintentionally image the pregnancy with CT scan and MRI.
Non-gynecologic
GIT	Appendiceal abscess [75]	NA	+	–	+	+/–	+	Leukocytosis	Fluid collection in the appendicular region appendicolith may be visualized.	Fluid collection in the appendicular region appendicolith may be visualized.	NA	Imaging/ history	The most common complication of acute appendicitis It may cause pleural effusion
	Appendiceal neoplasm [76][77][78][79][80]	60-70 y/o for adenocarcinoma, 30-50 y/o for carcinoid tumors	+	–	+	–	+/–	In adenocarcinoma type we may have high levels of CEA and CA 19-9 In carcinoid type we may see high levels of chromogranin A, 5-HIAA and Ki67	In CT scan we may see: Soft tissue thickening and Cystic lesion with Internal septation Wall irregularity Calcification Peri-appendiceal fat stranding	Soft tissue mass in the appendix We may see invasion to other structures	Gray/yellowi color Cystic structures with angiolymphatic invasion	Biopsy	It is associated with: MEN1 syndrome Ulcerative colitis Neurofibromatosis type 1 HNPCC Smoking It may cause pleural effusion
	Diverticular abscess [81]	>50 y/o	+	–	+	+/–	+	Leukocytosis	Ill-defined lesion with air and fluid inside Adjacent bowel loop wall thickening Smudged mesenteric fat	We may see a lesion with air and fluid inside	NA	Imaging/ history	Diverticular abscess happens in almost 30-40% of patients with diverticulitis It may cause pleural effusion
	Colorectal cancer [82][83][84][85]	>50 y/o	+	–	+	–	+/–	Anemia Positive Fecal occult blood test High levels of CEA and CA 19-9	In CT scan we may see luminal narrowing, intestinal wall thickening,intussusception, bowel obstruction, hepatic metastases, intestinal perforation,enlarged lymph nodes	We may see tumor mass and the extension of tumor to other structures We may see metastasis to the liver, lung and brain	Based on the sub-type we may have different histopathological feature (for more information click here)	Biopsy	It is associated with smoking, positive family history, processed meat, low fiber diet, lynch Syndrome and familial adenomatous polyposis They have apple core lesion on barium enema xray
Renal Bladder	Pelvic kidney [86][87]	NA	−/+ In case of sever hydronephrosis or renal stone we may have pelvic pain	–	−	−	−	−	In sonography we may see normal appearing kidney in pelvic position We may see renal calculi	We may see normal kidney structure Renal calculi	NA	Imaging	It may cause hypertension It may cause tract infection (UTI), obstruction, and renal calculi. It may be associated with RCC
	Bladder cancer [88][89][90]	≥65 y/o	+	–	–	–	–	Low red blood cell count Elevated alkaline phosphatase Positive tumor markers such as BTA, NMP, and CEA	In CT scan we may see masses protruding into the bladder lumen or asymmetric thickening of the bladder calcifications Nodal metastases	isointense compared to muscle in T1 slightly hyperintense compared to muscle in T2	Based on the sub-type we may have different histopathological feature (for more information click here)	Biopsy	It may presents with hematuria
Others	Retroperitoneal sarcoma [91][92][93][94]	40-50 y/o	+	–	+	−	−	Mild leukocytosis. It may cause hypoglycemia because of production of insulinlike substances	We may see irregular solid, semisolid, liquefactive areas and patchy necrosis on CT scan	We may see retroperitoneal involvement and degree of tumor extension We may see liver and lung metastasis	There are two types: liposarcoma and leiomyosarcoma In liposarcomas we may see background of adipocytes with scattered lipoblasts, and inflammatory cell infiltrate In leiomyosarcoma we may see smooth muscle cells	Biopsy	May cause lower extremity edema, Serous ascites we should perform chest CT scan to rule out pulmonary metastases

ABBREVIATIONS

BTA=Bladder tumor associated antigen, NMP= Nuclear matrix proteins, CEA= Carcinoembryonic antigen, US= Ultrasound, HCG= Human chorionic gonadotropin, LDH= Lactate dehydrogenase, AFP= Alpha fitoprotein, CA125= Cancer antigen 125, H&E= Hematoxylin and eosin, MRI= Magnetic resonance imaging, GI= Gastrointestinal tract, PID= Pelvic inflammatory disease, CA19-9= Carbohydrate antigen 19-9, 5HIAA= 5-hydroxyindoleacetic acid, MEN syndrome= Multiple endocrine neoplasia syndrome, HNPCC= Hereditary nonpolyposis colorectal cancer, UTI= Urinary tract infection, RCC= Renal cell carcinoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

The prevalence of gonadoblastoma depends on the chromosomal content, presence or absence of mosaicism, gonadal histology, and age of the patient and varies between 15,000 to 30,000 per 100,000 individuals worldwide. The incidence of gonadoblastoma varies according to the presence or absence of Y chromosomal content and age of the individual. Patients with Turner syndrome who have Y chromosomal content either completely or partially may develop gonadoblastoma with an incidence as high as 43,000 per 100,000 individuals worldwide. The incidence of gonadoblastoma among phenotypical females with XY gonadal abnormalities have been observed to be 40,000 per 100,000 individuals worldwide. Gonadoblastoma may be found at any age, but commonly presents before the age of 15 years. Since, it usually affects individuals with gonadal dysgenesis, there is no genotype–phenotype correlation. Phenotypically, it tends to affect female individuals to a greater extent.

• The incidence of gonadoblastoma varies according to the presence or absence of Y chromosomal content and age of the individual.^[1][2]
• The incidence of gonadoblastoma among phenotypical females with XY gonadal abnormalities have been observed to be 40,000 per 100,000 individuals worldwide.
• Patients with Turner syndrome who have Y chromosomal content either completely or partially can develop gonadoblastoma with an incidence as high as 43,000 per 100,000 individuals worldwide.

• The prevalence of gonadoblastoma depends on the chromosomal content, presence or absence of mosaicism, gonadal histology and age of the patient and varies between 15,000 to 30,000 per 100,000 individuals worldwide.^[3]

• Gonadoblastoma affects individuals of any age but commonly presents before 15 years of age.^[4]

• There is no racial predilection to gonadoblastoma.

• It commonly originated from dysgenetic gonad but has been observed in women with normal ovary and karyotypes, although rare.^[4][5]
• Since this tumor affects gonads, there is no genotype–phenotype correlations.
• The majority of affected individuals appears to be phenotypically female, however, are intersex.
• Although very uncommon, there are reports of gonadoblastoma development in phenotypically and genotypically normal men.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

The most potent risk factor in the development of gonadoblastoma is gonadal dysgenesis. The risk also increases with age.

• The most potent risk factor in the development of gonadoblastoma is gonadal dysgenesis.^[1][2]
• The risk of gonadoblastoma development increases with age. In individuals with XY gonadal abnormalities, it reaches up to 30% by the age of thirty years.
• Other risk factors include patients with Turner syndrome and having Y chromosome contents.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

There is insufficient evidence to recommend routine screening for gonadoblastoma. However, patients with XY gonadal abnormalities should be followed using sonography starting at age 2, every six months, until the gonads are removed.

• There is insufficient evidence to recommend routine screening for gonadoblastoma.
• However, patients with XY gonadal abnormalities should be followed using sonography starting at age 2, every six months, until the gonads are removed.^[1][2]
• Although very uncommon, gonadoblastoma may develop in phenotypically and genotypically normal individuals.
  • In these individuals, the affected gonads must be removed due to the risk of gonadoblastoma conversion to dysgerminoma.
  • Close monitoring with imaging studies also recommended for the contralateral gonads if it is preserved.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Gonadoblastoma per se is a benign tumor, however, it has the capacity to convert to dysgerminoma or other more malignant germ cell tumors and produce steroids with resultant virilization. Prognosis is generally excellent after removing the tumor.

• Gonadoblastoma usually develops in the first and second decades of life.^[1]
• If complicated by an invasive germ cell tumor, then prognosis depends on the staging of the tumor.^[2]
• It is usually diagnosed during a workup for sex organ developmental disorders, primary amenorrhea, and/or virilization.

• Common complications of gonadoblastoma include:^[1]
  • Dysgerminoma
  • Seminoma
  • Other gonadal malignancies

• Prognosis is generally excellent if the tumor is diagnosed and removed early.^[3]
• Depending on the presence of the coexisting germinal tumors at the time of diagnosis, the prognosis may vary.

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