Testicular Tumors

Jonathan H. Ross MD
Associate Professor of Surgery (Urology) at University Hospitals Case Western Reserve University Medical School and Chief, Division of Pediatric Urology at Rainbow Babies and Children’s Hospital

 

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I.  Introduction:

Testis tumors are rare in children compared with testis tumors occurring post-pubertally or with other genitourinary tumors in childhood such as Wilms tumor.  The incidence of testis tumor in children is only 1.6 per 1 million person-years.1  Until the last decades of the 20th century, prepubertal testis tumors were treated much the same as their adult counterparts due to a paucity of information on the behavior of the much rarer prepubertal tumors.  This approach might make sense if prepubertal tumors represented the tail end of a normally distributed incidence of tumors with age.  However, there is actually a bimodal age distribution for testis tumors with a large peak in young adults and a much smaller peak in the first 3 years of life.2  This bimodal age distribution reflects more fundamental differences between prepubertal and postpubertal testis tumors.  These differences include the typical tumor histology in each group, the malignant potential of tumors at different ages, and the molecular biological differences between prepubertal and postpubertal tumors.

The most striking difference between prepubertal and postpubertal tumors is the incidence distribution of different tumor types.  Testis tumors are generally classified by the putative cell of origin.  Germ cell tumors include seminoma, embryonal carcinoma, choriocarcinoma, yolk sac tumor, and teratoma.  Epidermoid cysts are generally considered a monodermal form of teratoma.  Stromal tumors include Leydig cell tumor, Sertoli cell tumor and juvenile granulosa cell tumor.  Gonadoblastomas, which occur almost exclusively in the setting of disorders of sexual development, contain both germ cell and stromal elements.  Mixed germ cell tumors which contain 2 or more histological types are particularly common in adolescents and adults whereas prepubertal germ cell tumors are virtually always of a single histological type.  Testicular tumors may also be classified based on their clinical behavior as benign or malignant.  Seminoma, embryonal carcinoma, choriocarcinoma and yolk sac tumors are malignant.  Teratomas are universally benign in prepubertal patients, but may behave in a malignant fashion in adolescents and adults.  Most stromal tumors are benign, though occasionally malignant behavior is seen, particularly in older patients.  The large majority of testicular tumors in adolescents and adults are malignant germ cell tumors – most commonly mixed germ cell tumors with pure seminomas occurring in older men.  In contrast, the most common germ cell tumor in children is a benign teratoma.  The most common malignant tumor in children is a yolk sac tumor, which is very rare in its pure form in post-pubertal patients.  Overall, approximately 75% of testis tumors in prepubertal patients are benign.3

Molecular biological and histological studies further support the distinct nature of prepubertal and postpubertal testis tumors.  For example, chromosome 12 abnormalities are seen in nearly all adult malignant germ cell tumors, but are not seen in prepubertal yolk sac tumors which display abnormalities in other chromosomes.4  Intratubular germ cell neoplasia (ITGCN) which is frequently seen in the testicles of men with malignant germ cell tumors, does not occur in the setting of prepubertal yolk sac tumor.5   ITGCN is also generally absent in prepubertal testicles harboring a teratoma, while 88% of testes removed for adult teratoma contain areas of ITGCN.6-8

These differences in histological distribution and clinical behavior have led to a divergence in the management strategies for prepubertal and postpubertal tumors.  In children, a testis-sparing approach is becoming more common given the high incidence of benign tumors in this population.  When a malignant tumor is identified, orchiectomy and observation with very selective use of chemotherapy has become the standard approach; retroperitoneal lymph node dissection (RPLND) and radiation therapy play a very limited role.

II. Clinical Presentation/Evaluation
The majority of testis tumors present as a palpable testicular mass detected by the patient, a parent, or by a physician on routine physical examination.  Occasionally patients will present with a hydrocele.  Therefore, in a child with a hydrocele that obscures physical examination of the testis, an ultrasound should be obtained.  Rarely, patients may present with pain.  Once a testis tumor is suspected, a thorough physical examination is undertaken.  In most cases the general examination will be normal.  Signs related to metastatic disease are uncommon in children as the most common sites – the retroperitoneum and lungs – rarely result in physical findings.  But occasionally signs of androgenization or other physical findings will be present suggesting a particular tumor type or advanced disease.  Imaging of the primary tumor almost always begins with ultrasonography.  Ultrasound distinguishes testicular from extratesticular masses and the ultrasonographic appearance of specific testis tumors has been described.9  Benign tumors tend to be well-circumscribed with sharp borders and decreased blood flow on Doppler studies.  Epidermoid cysts usually demonstrate echogenic debris within the well-defined cyst.  Yolk sac tumors tend to be more solid in appearance.  However, the ultrasonographic features, while suggestive, are not diagnostic.  When the clinical findings and ultrasound are suggestive of a benign tumor, no further evaluation is undertaken.  But in cases where malignancy is suspected a computerized tomography (CT) scan of the abdomen and pelvis is obtained to identify retroperitoneal involvement.  A chest x-ray or chest CT will identify pulmonary metastases.

 
Testis tumor markers are an important tool in the evaluation of testis tumors in children and adolescents.  Both human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) are important testis tumor serum markers in adolescents and adults.  Since yolk sac tumors do not elaborate HCG, AFP is the only important tumor marker in prepubertal patients.  AFP is elaborated by 90% of yolk sac tumors in children.  An important caveat in the use of AFP for these patients is that serum AFP levels can normally be as high as 50,000 ng/mL in the newborn dropping to approximately 300 ng/mL by 2 months of age.  AFP levels do not achieve “normal” values until nearly 1 year of age.10  Therefore, while an elevated AFP in a child over 1 year old with a testis tumor almost always reflects the presence of a yolk sac tumor, an “elevated” level in infants can occur in the setting of a benign tumor.  The post-operative status of tumor markers is also important.  Tumor marker serum levels should fall at a predictable rate based on the biological half-life of each marker (approximately 5 days for AFP and 48 hours for HCG).  Failure of the markers to decline at the expected rate reflects the likely persistence of disease.

There is no universally accepted staging system for pediatric testis tumors.  Prepubertal patients are generally staged based on the extent of local disease, the presence or absence of metastatic disease based on radiographic imaging (CT of the chest and abdomen), and the persistence or decline of elevated tumor markers post-operatively.  In the Children’s Oncology Group staging system, patients with locally confined disease, negative radiographic studies, and the expected decline in tumor markers post-operatively are designated Stage 1.  Patients with microscopically positive margins in the scrotum or spermatic cord and/or with persistently elevated tumor markers after orchiectomy, are designated stage 2.  Patients who underwent transcrotal biopsy prior to orchiectomy at a separate setting are also considered stage 2.  Stage 3 patients are those with retroperitoneal lymphadenopathy; and those with distant metastases (most commonly in the lungs) are designated stage 4. Adolescents with germ cell tumors are generally staged as adults utilizing the TNM system of the American Joint Committee on Cancer and the International Union Against Cancer.11 Because treatment options are more variably applied to post-pubertal tumors, this staging system is more complex than that employed in children.  But it is still based on the issues of local tumor extent, retroperitoneal lymph node involvement, the presence or absence of distant metastases, and the post-operative status of tumor markers.

III.  Surgical Management
While inguinal orchiectomy with early ligation of the cord has been the historical approach to testicular tumors, increasing consideration has been given to performing testis-sparing surgery for benign testicular tumors.12 Tumor excision without orchiectomy is particularly attractive in prepubertal patients because most tumors are benign in this population. An elevated AFP level in a child over 1 year of age virtually always reflects the presence of a yolk sac tumor and precludes a testis-sparing approach. However, in all infants, and in older children with a normal AFP, the likelihood of a benign tumor is considerable. This is also true in boys presenting with androgenization.  In adolescents, as in adults, a testis-sparing approach must be used very judiciously since most post-pubertal tumors are malignant.  However, in adolescents with normal tumor markers and an ultrasound appearance highly suggestive of a benign lesion, such as an epidermoid cyst, testis-sparing may be considered.

For a testis-sparing approach, the testis is delivered into the inguinal incision (the cord having been occluded with a non-crushing clamp or vessel loop), the field is draped off with towels and the tunica vaginalis is opened (see Figure). The tumor is excised or enucleated and sent for frozen section.  If a benign histology is confirmed, then the testicular defect is closed with absorbable suture and the testis is returned to the scrotum. If a malignancy is detected, or the frozen section is nondiagnostic, then an orchiectomy is performed.  Reports from small series suggest that this approach is safe and is effective in preserving testicular tissue.9,13  Valla et al reported on 83 benign lesions 2/3 of which were managed with tumor enucleation.9  With an average follow-up of 4.8 years, they saw no cases of testicular atrophy or tumor recurrence.   The lesions successfully treated with tumor enucleation included teratomas, epidermoid cysts, Sertoli cell tumors, and Leydig cell tumors.  Even when the testis appears completely replaced by tumor on ultrasound, enucleation may leave significant normal testicular tissue that was merely compressed by the benign lesion.14

IV.  Adjuvant therapy
Following excision of the primary tumor, universally benign tumors require no further evaluation or treatment.  Treatment options for potentially malignant tumors include surveillance, chemotherapy, retroperitoneal lymph node dissection (RPLND), and radiation therapy.  Virtually all germ cell tumors are sensitive to platinum-based multiagent chemotherapy which plays a major role in their management.  RPLND plays an important staging and therapeutic role for mixed germ cell tumors in adolescents, but is rarely employed in cases of prepubertal yolk sac tumor.  Radiation therapy is primarily used in treating seminoma – a very rare tumor in the pediatric population.  The specific adjuvant therapy for a given patient is dependent on tumor histology and stage.

Yolk sac tumor
Pure yolk sac tumors occur almost exclusively in infants and very young children.  Nearly all are managed with surveillance or platinum-based chemotherapy.  RPLND, which plays a central role in the staging and therapy of adults with mixed germ cell tumors, is rarely employed in children.  This is in part because prepubertal patients are less likely than adults to have metastases limited to the retroperitoneum.15  Furthermore 80% of prepubertal patients have clinical stage 1 disease and fewer than 20% will recur with no therapy beyond orchiectomy.16-21  Finally, the morbidity of RPLND is likely to be greater in children than in adolescents and adults; the feasibility of a nerve-sparing approach to RPLND in children is undefined.   In children, retroperitoneal surgery is reserved for biopsy of radiographically equivocal nodes or for resection of a persistent retroperitoneal mass following chemotherapy.   

Perhaps the greatest advance in the management of testicular cancer was the introduction of platinum-based chemotherapy.  Survival for both prepubertal and adult tumors has increased dramatically since its introduction.  Indeed, multiagent chemotherapy has become the standard therapy for virtually all metastatic prepubertal testicular malignancies.  The specific management for patients with yolk sac tumor has been defined by several multicenter clinical trials.16-21  The results of 4 major studies are summarized in the Table.  In all of these studies stage 1 tumors were managed with orchiectomy followed by surveillance.  Surveillance includes frequent physical examinations, radiographic evaluation of the chest and retroperitoneum, and serum tumor marker measurement.  Patients who developed metastatic disease were treated with 2-4 courses of multiagent platinum-based chemotherapy.  Patients who presented with locally advanced disease, metastases, or persistently elevated serum tumor markers were similarly treated with multiagent platinum-based chemotherapy.  The survival for all patients with this approach was nearly 100%.

Teratoma
While metastatic disease occurs in up to 60% of adults with teratoma, these tumors are universally benign in pre-pubertal patients.22-24   Adolescents with teratoma should undergo orchiectomy and a metastatic evaluation followed by surveillance for stage 1 disease.  Because of its benign nature, prepubertal teratoma can be managed with testis-sparing surgery.  The vast majority of prepubertal teratomas are “mature” teratomas, and for these tumors, no oncological evaluation or follow-up is necessary.  Immature teratomas are characterized by the presence of embryonal or incompletely differentiated tissue components, most commonly primitive neuroectodermal structures.4   There is some uncertainty regarding the behavior of immature teratomas.    Pediatric immature teratomas (regardless of site) generally behave in a benign fashion if completely resected, though there has been at least one case report of metastatic disease  resulting from an immature testicular teratoma in a child.25-27  Somatic malignancies may also arise in immature teratomas leading to metastatic spread.  This is exceedingly rare in children.  Furthermore, if foci of yolk sac tumor are found in an immature teratoma, then it should be treated as a yolk sac tumor.   While immature teratomas of the testis can be managed with complete tumor resection alone, consideration should be given to some clinical and radiographic follow-up in these patients.

Epidermoid cysts probably represent a monodermal variant of teratoma.  Epidermoid cysts are composed entirely of keratin-producing squamous epithelium and are universally benign in children and adults.  They can often be suspected by their typical appearance on ultrasound of a cyst filled with echogenic layered debris (corresponding to the desquamated keratin) giving an “onion-skin” appearance28.  They may be treated by tumor enucleation with no oncological evaluation or follow-up.9
 

Mixed germ cell tumor

Mixed germ cell tumors (MGCT) are vanishingly rare in pre-pubertal patients, but account for a significant proportion of testis tumors in adolescents.  Unfortunately, there is little data regarding the behavior of mixed germ cell tumors in adolescents and until further studies of adolescents with MGCT are undertaken, it seems reasonable to manage them as adults with observation, RPLND, and/or chemotherapy depending on the specific histology and stage of the disease.  Patients with stage 1 MGCT may be managed with surveillance.  The recurrence rate on surveillance is 25-30%11.  Recurrence may be prevented with a modified nerve-sparing RPLND or 2 cycles of platinum-based chemotherapy, but this “over-treats” the 70-75% of patients who do not have occult metastatic disease.  On the other hand, when recurrence occurs on surveillance, more intense therapy is required and so patients may prefer an RPLND or short course of chemotherapy up front.  Generally this dilemma is resolved by stratifying patients based on the local stage and histology of the primary tumor.  Patients with low risk disease are usually followed with frequent chest x-rays, tumor marker measurements and abdominal CT scans.  Nearly all recurrences occur within 2 years of orchiectomy and are treated with chemotherapy.  Patients at higher risk for recurrence (such as those with vascular invasion, largely embryonal cell histology, or those who are poorly compliant with therapy) generally undergo a modified nerve-sparing RPLND.  If microscopically positive nodes are found at the time of RPLND patients may elect a brief course of chemotherapy, although many with microscopic disease will be cured by the RPLND alone. 

Patients with radiographic evidence of metastatic disease at presentation or persistently elevated tumor markers following orchiectomy are treated with 3-4 cycles of chemotherapy (such as bleomycin, etoposide and cis-platinum).  The relapse rate following primary chemotherapy for metastatic disease is approximately 15%, though it may be as high as 30% for poor-risk patients.11  RPLND may be considered for patients with very limited retroperitoneal lymph node disease at presentation and normalization of tumor markers after orchiectomy.   

Some patients with MGCT treated with chemotherapy for metastatic disease will have a residual retroperitoneal mass following therapy.  If tumor markers have normalized, these residual masses should generally be resected.  40-50% of residual masses will contain only necrotic tissue and fibrosis, but 10-20% will have persistent malignancy and 40-45% will contain mature teratoma.11

 

Stromal tumors
Stromal tumors of the testis are rare in children and adolescents.  Leydig cell tumors and juvenile granulosa cell tumors are universally benign in children.1,29-32  Leydig cell tumors usually present between 5 and 10 years of age with precocious puberty.  They may be treated with orchiectomy or tumor enucleation.30,33  Contralateral tumors may occur, though they are rare in children.  Adrenal rests along the spermatic cord and in the testicular hilum may hypertrophy in patients with precocious puberty due to congenital adrenal hyperplasia (CAH) mimicking a Leydig cell tumor.  In patients with CAH the nodules are often multifocal and bilateral.34-36  The diagnosis of CAH can generally be made by demonstrating an elevated serum 17-hydroxyprogesterone level.  The nodules will usually resolve or significantly reduce in size with steroid replacement therapy for the CAH.  If this occurs, the patient may be followed with serial examinations.37  Large nodules that fail to regress may be safely enucleated.37-38  Juvenile granulosa cell tumors occur almost exclusively in the first year of life, most in the first 6 months.  They bear a light microscopic appearance similar to ovarian juvenile granulosa cell tumors.  Chromosomal mosaicism, structural abnormalities of the Y chromosome, and ambiguous genitalia are common in boys with juvenile granulosa cell tumor.39-40  Although these children should undergo a chromosomal analysis, the tumor itself  may be treated by orchiectomy or tumor enucleation with no metastatic evaluation or adjuvant therapy.31-32

While approximately 10% of adult Sertoli cell tumors are malignant, malignancy is very rare in children.29,41  While all reported cases of Sertoli cell tumors in children under 5 years of age have been benign, there have been a few cases of malignant Sertoli cell tumors in older children.39,42  Tumor excision is usually adequate treatment for infants, but a metastatic evaluation should be considered if worrisome gross or histological findings are present such as large tumor size, areas of necrosis, vascular invasion, cellular atypia, or increased mitotic activity.  Older children with Sertoli cell tumors should undergo a full metastatic evaluation.

Large-cell calcifying Sertoli cell tumors are clinically and histologically distinct tumors which occur predominantly in children and adolescents.1,43  These tumors are composed of large cells with abundant cytoplasm and varying degrees of calcification.  Approximately 1/3 of patients have an associated genetic syndrome and/or endocrine abnormality, the most common being Peutz-Jeghers syndrome and Carney’s syndrome.  Peutz-Jeghers syndrome is an autosomal dominant disorder consisting of mucocutaneous pigmentation and hamartomatous intestinal polyposis.  Features of Carney syndrome include myxomas of the skin, soft tissue, and heart; myxoid lesions of the breast; lentigines of the face and lips; cutaneous blue nevi; Cushing syndrome; pituitary adenoma; and schwannoma.  Patients and first-degree relatives of patients with large-cell calcifying Sertoli cell tumor should be screened for these potentially serious syndromes.  Whereas these tumors are occasionally malignant in adults, they have been universally benign in patients under 25 years of age.  Orchiectomy is sufficient treatment in children, but approximately ¼ of patients will have bilateral and/or multifocal disease.  A testis-sparing approach has been described for this rare tumor.44

Rarely a prepubertal patient may have a mixed or poorly differentiated stromal tumor.  Most of these behave in a benign fashion, but concern for malignancy is appropriate when a large number of mitotic figures are present, the tumor is poorly differentiated, or when local invasion is seen.29  Because orchiectomy cures most of these patients, RPLND and adjuvant therapy are probably not indicated in the absence of evidence of metastatic disease.  However, given the uncertainty regarding these tumors, postoperative evaluation and follow-up for the development of metastatic disease seems prudent.

Testicular cyst
Simple testicular cysts may be observed or, if they are growing, excised.  Cystic dysplasia of the rete testis is a benign tumor found primarily in children.45  Ultrasound typically reveals multiple small cysts arising from the testicular hilum, sometimes compressing the normal testicular parenchyma.  These tumors are universally benign and may be managed by observation, tumor excision, or orchiectomy if extensive.  Associated genitourinary anomalies, particularly renal agenesis, are common.  Therefore, patients with cystic dysplasia of the rete testis should undergo upper tract imaging.

V.  Risk factors for testicular tumors

While most testicular tumors occur sporadically, some occur in the setting of a predisposing history.  The most studied association is with undescended testicle (UDT).  The risk of testicular cancer in men with a history of UDT has historically been estimated at 10-40 fold greater than the general population.  More recent studies have found the risk of testicular cancer in a man with a history of UDT to be closer to 5-fold that of the general population.  This translates into a life-time risk for these men of 1-2%.  Whether early orchidopexy can ameliorate that risk is unclear, though a recent study suggests that it may.46  The increased risk of germ cell tumors is reflected in the finding of carcinoma in situ (CIS) in 2-4% of men with a history of cryptorchidism.47 

Testicular microlithiasis (TM) has been identified as a possible risk factor for the development of testicular cancer.  TM refers to the presence of microcalcifications, usually diffuse, within the parenchyma of the testis on ultrasound.  The association with testicular malignancies was suggested by the finding that approximately 25% of adult testes harboring cancer are found to have TM.  But the causal relationship behind this finding is unclear.  TM is found incidentally in approximately 2% of boys and men undergoing ultrasound either for testicular symptoms or as part of a screening study of asymptomatic males.48-51   Six small series with a total of 152 men (including 2 prospective studies) looked at the development of testicular cancer in testicles initially identified with TM .52-57  Three patients (1.8%) in these studies developed testicular cancer with a median follow-up of 41 months.  None of the 81 patients in the 2 prospective studies developed tumors.  There is still insufficient data to quantify the risk, if any, of testicular cancer in boys or men incidentally found to have TM.  Studies suggest that TM may be most significant when it occurs in conjunction with other risk factors for testicular cancer, such as men with infertility or a history of contralateral testicular cancer.58-59 

While rare, certain disorders of sexual development (DSD) harbor a very significant risk for the development of gonadal tumors.  Some disorders, such as complete androgen insensitivity syndrome, have an increased risk comparable to that of other patients with testicular maldescent.  But unique to patients with DSD are the risks of tumor formation in dysgenetic or streak gonads.  This risk seems to exist almost exclusively in patients with Y chromatin.60  For example, patients with Turner syndrome and any portion of a Y chromosome in their karyotype have an approximately 12% risk of tumor development; while patients with traditional Turner syndrome and a 45 XO karyotype are at no significant risk for gonadal tumors.  Similarly the gonads of patients with pure gonadal dysgenesis and Y chromatin as well as the “streak” gonad of patients with mixed gonadal dysgenesis are at a 15-30% risk for tumor development.

The tumors arising in the setting of gonadal dysgenesis are usually gonadoblastomas.  While gonadoblastomas are benign, they are prone to the development of malignant degeneration and overt malignant behavior is seen in 10% of cases.61  While most cases of malignancy occur after puberty, there have been cases reported in children as well.  Prophylactic removal of dysgenetic gonads should be undertaken early in life in patients with at-risk karyotypes.60  Gonadectomy is sufficient treatment for gonadoblastoma.  If malignant degeneration has occurred, then further therapy may be warranted.  When malignancies occur, dysgerminoma (aka seminoma when it occurs in a testis) is the most common histological type.  These tumors are very radiosensitive and the outlook for these patients is generally favorable.

VI.  Paratesticular rhabdomyosarcoma

Paratesticular rhabdomyosarcomas usually present with an enlarging painless scrotal mass.  By the time of presentation distinction from a primary testis tumor is usually not possible on physical exam, though the extratesticular nature of the tumor is usually apparent on ultrasound.  The initial management for paratesticular rhabdomyosarcomas is an inguinal excision of the tumor and testis.  Trans-scrotal biopsies of solid scrotal masses should be avoided due to the risk of seeding of the incision if the mass is indeed a rhabdomyosarcoma.  The excision should be performed just as for a testicular malignancy. 

The metastatic evaluation for paratesticular rhabdomyosarcoma includes a CT of the chest, abdomen, and pelvis.  A majority of patients will have clinical stage 1 disease.  The most common sites of metastases are the retroperitoneum and lungs.  Patients with retroperitoneal metastases undergo a modified unilateral nerve-sparing RPLND.  All patients receive chemotherapy and those with positive retroperitoneal nodes receive radiation therapy as well.  The role of staging RPLND in patients with clinical stage 1 disease is based on experience in the Intergroup Rhabdomyosarcoma Studies (IRS).62  IRS-III (from 1984-1991) required a staging unilateral RPLND for all clinical stage 1 patients.  In IRS-IV (from 1991-1997) patients with a negative CT scan did not undergo staging RPLND (and did not receive radiation to the retroperitoneum).  This approach resulted in a worrisome decrease in the percentage of patients diagnosed with metastatic disease in IRS-IV, particularly among adolescents.  Furthermore, adolescents with clinical stage 1 disease in IRS-IV had a 3-year event-free survival (EFS) of only 68% compared to a 100% survival for patients with recognized lymph node involvement (who received radiation and more intense chemotherapy)  – presumably due to under-staging and under-treatment of those stage 1 patients with occult retroperitoneal disease.  Such discrepancies were not seen in the prepubertal patients.  Based on these data, patients over 10 years of age with or without radiographic evidence of retroperitoneal disease should undergo a staging RPLND and receive radiation in addition to chemotherapy if the lymph nodes are positive.  Younger children with a normal abdominal CT may be treated with chemotherapy alone without a staging RPLND.  Overall survival rates for patients with paratesticular rhabdomyosarcoma approach 90%.62

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Study	Number of patients	Patients with stage 1 disease (%)	Recurrence rate of stage 1 tumors on surveillance alone (%)	Survival for Stage 1 tumors (%)	Survival for patients with locally advanced or metastatic disease at presentation (%)
German Cooperative Studies16	110	95	15	100	80
United Kindgdom’s Children’s Cancer Study Group19	62	68	5	100	100
Italian Cooperative Study20,a	36	72	19	100	100
U.S. Pediatric Intergroup Study17-18	94	67	17	100	100
Total	302	78	14	100	98