Iris Publishers- Open access Journal of Urology & Nephrology | Primary Osteosarcoma of Testis and Para-Testicular Tissues: A Review and Update of the Literature

Authored by Anthony Kodzo Grey Venyo

Abstract

Osteosarcoma of the testis and para-testicular tissue is a terminology that refers to a malignant tumor that contains pure osteoid forming malignant cells with no skeletal origin that affect the testis or para-testicular tissues. These tumors tends to present as an intra-scrotal or testicular mass which is non-specific. It may also present in association with a hydrocele. Clinical examination may reveal a firm to hard mass in the testis or in the affected para-testicular tissue. The inguinal glands may be normal but on rare occasions there may be lymph node enlargement in advanced cases. If there is an associated hydrocele there may be clinical examination evidence of a hydrocele. The full blood count, serum urea and electrolytes and liver function tests would tend to normal unless there are un-related pathologies which would need to be investigated accordingly. Nevertheless, if there are multiple liver metastases the liver function test results may show derangement in one or more elements of the liver function tests. The serum Beta Human Chorionic gonadotrophin, alpha fetoprotein, and lactate dehydrogenase levels would tend to normal unless the osteosarcoma is associated with a synchronous Germ cell tumor which does happen occasionally. Radiology imaging could show evidence of a heterogeneous mass within the testis in the case of a testicular tumor or in an intra-scrotal area at the site of the lesion and the mass tends to be associated with calcification. Treatment tends to be radical orchidectomy for localized tumors involving the testis only, but para-testicular osteosarcomas tend to be treated by radical orchidectomy plus en bloc excision of the para-testicular tissue. If there is evidence of metastasis then adjuvant therapy can be given. Gross examination of specimens of an excised osteosarcoma of the testis would tend to show a well-circumscribed, firm, solid, whitish tan, expansile mass which had compressed the surrounding parenchyma of the testis. Microscopic examination of primary osteosarcoma of the testis specimen would tend to show sheets of pleomorphic round to spindle cells that contain prominent nucleoli, areas of osteoid and scattered areas of mineralization, high mitotic activity and atypical mitosis, osteoid and at times osteoclasts among the area of osteoid. Immunohistochemistry studies of osteosarcoma of the testis or any para-testicular structures would tend to show the tumor cells stain positively for vimentin, but the tumor cells would stain negatively for: smooth muscle actin, CD34, cytokeratin, desmin, inhibin, myo-D1, and S-100 proteins.
Keywords: Osteosarcoma; Testis; Epididymis; Tpermatic cord; Tara-testicular tissues; Vimentin; Radical orchidectomy; Spindle cells; Pleomorphic; Computed tomography scan; Magnetic resonance imaging scan; Ultrasound scan

Introduction

It has been stated that genitourinary sarcomas are not common in adults and that they had been estimated at less than 2.7% of all sarcomas. [1-2] It had also been iterated that extra-osseous paratesticular soft tissue osteosarcoma is an extremely uncommon type of malignant tumor. Hong R, et al. [3] stated that due to the rarity of para-testicular osteosarcoma; its histogenesis; treatment; and as well as its specific survival rates were not available. Osteosarcoma of the testis refers to a testicular tumor that is composed of pure osteoid forming malignant cells with no skeletal origin. Gordetsky J [4] Due to the extreme rarity of primary and metastatic osteosarcomas of the testis and the scrotal contents; it would be envisaged that majority of clinicians globally would not be familiar with the presentation; diagnosis; treatment and biological behaviour of the disease. The ensuing article on primary osteosarcoma of testis and para-testicular tissues: a review and update of the Literature is divided into two parts: (A) Overview and (B) Miscellaneous narrations; summations; and discussions related to case reports; case series; and studies related to osteosarcomas of the testis and para-testicular tissues.

Aim

To review and update the literature on primary osteosarcomas of the testis and Para testicular tissues.

Method

Internet data bases were searched including Google; Google Scholar; Yahoo and PUBMED. The search words that were used included: Primary osteosarcoma of testis; osteosarcoma of testis; primary osteosarcoma of epididymis; osteosarcoma of tunica vaginalis; osteosarcoma; osteosarcoma of tunica albuginea; osteosarcoma of the spermatic cord; para-testicular osteosarcoma; intra-scrotal osteosarcoma; and scrotal content osteosarcoma.

Result- Review and Update of Literature

Overview

Definition/general comments: Osteosarcoma of the testis refers to a tumor of the testis which is comprised of pure osteoid forming malignant tumoral cells which do not have any skeletal origin [4].

Epidemiology

• Pure primary osteosarcoma is an extremely uncommon disease [pathology outlines]
• The sporadic cases of osteosarcoma of the testis which had been reported had been reported in males whose ages had ranged between 30 years and 78 years and the mean age of the patients was 59 years [4].

Pathophysiology

• It has been postulated that osteosarcoma of the testis; usually tends to be derived from sarcomatous transformation of germ cells tumors which are also called teratomas [4].
• It had also been suggested that osteosarcoma of the testis could also develop as a component of malignant mixed sex cord / stromal tumor [4].
• It has been additionally stated that pure primary osteosarcomas of the testis without teratoma elements had been reported in which it had been indicated that the tumors could arise from primitive stromal cells of the testis or from metaplastic stromal cells [2,4-5].

Clinical features

Presentation
• Primary osteosarcoma of the testis tends to present as an intra-scrotal mass or a mass within the testis [4].

Laboratory investigations

a. Urine
• Urinalysis; urine microscopy; urine culture and sensitivity form part of the initial screening assessments of patients who have primary or metastatic intra-scrotal osteosarcomas bit generally the results would tend to be normal but if there is any evidence of urinary tract infection it would be treated with the most appropriate antibiotics based upon the antibiotic sensitivity pattern of the cultured organism and the allergy status of the patient to improve the general condition of the patient.
b. Hematology blood tests
• Full blood count and coagulation screen are routine tests that tend to be undertaken as part of the general assessment of patients who have primary intra-scrotal osteosarcoma and generally the results would tend to be normal but if there is any abnormality found it would be investigated appropriately and the most appropriate treatment would be given to improve upon the general condition of the patient.
• Full blood count and coagulation screen are routine tests that tend to be undertaken as part of the general assessment of patients who have primary intra-scrotal osteosarcoma and generally the results would tend to be normal but if there is any abnormality found it would be investigated appropriately and the most appropriate treatment would be given to improve upon the general condition of the patient.
c. Biochemistry blood tests
• Serum urea and electrolytes; blood glucose; and liver function tests are routine tests that are undertaken as part of the general assessment of patients who have primary intrascrotal osteosarcoma and most often the results would be normal but if there is any evidence of an abnormality with regard to any of the tests it would be thoroughly investigated and the an appropriate treatment would be given to improve the general condition of the patient.
• Serum Beta Human Chorionic Gonadotrophin; Alpha Fetoprotein; and Lactate Dehydrogenase (LDH) are general tests undertaken in testicular tumors to exclude Germ Cell Tumors of the testis.
d. Radiology investigations
• It has been stated that generally; radiology imaging of the scrotal contents would tend to show heterogeneous intratesticular solid mass which tends to contain calcifications [4]
e. Chest x-ray
• Chest x-ray is a general screening investigation that can be taken in the initial assessment of patients to be sure they do not have pulmonary metastases and as part of the followup assessment to exclude pulmonary metastasis. However; utilization of chest x-ray has been superseded by CT scan and MRI scan of thorax; abdomen and pelvis in the initial staging and follow-up assessment of patients who have primary intrascrotal osteosarcomas
f. Ultrasound scan
• Ultrasound scan of the scrotal contents would define the lesion in the testis or within the para-testicular area and would tend to reveal a heterogeneous mass within the testis or within the scrotum related to the site of the lesion. The size of the lesion and its relation to the surrounding structures would be shown by the ultrasound scan. Even though contrast enhanced ultrasound scan (CEUS) is not undertaken in most centres; in centres where contrast enhanced ultrasound scan is undertaken the ultrasound scan would also show contrast enhancement of the testicular or intra-scrotal lesion in addition to evidence of calcification.
• Ultrasound scan of abdomen and pelvis and renal tract could be done as part of the general assessment / staging of the tumor to ascertain if there are metastases within the abdomen and pelvis including lymph node involvement by the tumor.
• Ultrasound scan of scrotum plus abdomen and pelvis can be done as part of the regular follow-up assessment of patients who have undergone radical orchidectomy or radical orchidectomy plus en bloc excision of a para-testicular osteosarcoma to ascertain whether or not the individual has developed metastasis.
g. Computed tomography (CT) scan
• CT scan of the abdomen and pelvis and scrotal contents would show calcification in a lesion that may be in the testis; or within the scrotal lesion where the tumor is as well as a heterogenous lesion in the area of the tumor. The CT scan would demonstrate the location and size of the lesion as well as its relation to the surrounding structures; presence or absence of enlarged lymph nodes within the pelvis retroperitoneum; or para-aortic regions as well as presence or absence of metastasis within the abdomen in any of the abdominal organs. If there is any synchronous tumor elsewhere in the abdomen and pelvis the CT scan would show it.
• CT scan of thorax; abdomen; and pelvis can be undertaken as part of the initial staging of the osteosarcoma and also to illustrate that that there is no other tumor anywhere else that could constitute a primary osteosarcoma with the tumor within the scrotum being a metastatic lesion. Additionally CT Scan of thorax; abdomen; and pelvis tends be undertaken regularly as part of the follow-up assessment of patients who have undergone surgical treatment for intra-scrotal primary osteosarcomas.
h. Magnetic resonance imaging (MRI) scan
• MRI scan of the abdomen and pelvis and scrotal contents would show calcification in a lesion that may be in the testis; or within the scrotal lesion where the tumor is as well as a heterogenous lesion in the area of the tumor. The MRI scan would demonstrate the location and size of the lesion as well as its relation to the surrounding structures; presence or absence of enlarged lymph nodes within the pelvis retroperitoneum; or para-aortic regions as well as presence or absence of metastasis within the abdomen in any of the abdominal organs. If there is any synchronous tumor elsewhere in the abdomen and pelvis the MRI scan would show it.
• MRI scan of thorax; abdomen; and pelvis can be undertaken as part of the initial staging of the osteosarcoma and to illustrate that that there is no other tumor anywhere else that could constitute a primary osteosarcoma with the tumor within the scrotum being a metastatic lesion. Additionally, MRI Scan of thorax; abdomen; and pelvis tends be undertaken regularly as part of the follow-up assessment of patients who have undergone surgical treatment for intra-scrotal primary osteosarcomas.
i. Positron emission tomography (PET-CT) scan
• PET-CT scan can be done as part of the follow-up assessment of patients who have undergone treatment for intra-scrotal osteosarcomas, but this has been superseded by CT and MRI scans of thorax; abdomen and pelvis.
j. Isotope bone scan
• Isotope bone scan tends to be undertaken to confirm or negate presence of bone metastasis.
Treatment
• Treatment of primary osteosarcoma of the testis whether it is diagnosed pre-operatively from biopsy of the lesion or is being treated as a testicular tumor without knowing the type testicular would tend to be by radical orchidectomy.
• Para-testicular osteosarcoma would tend to be associated with radical orchidectomy with en bloc complete excision of the extra-testicular or para-testicular lesion.
• If there is evidence of metastasis then adjuvant chemotherapy plus or minus adjuvant chemotherapy could be given but considering that some osteosarcomas develop many years after radiotherapy has been given to organs adjacent to the site of the osteosarcoma some clinicians could prefer adjuvant chemotherapy.
a. Macroscopic features: Macroscopic examination of specimens of an excised osteosarcoma of the testis would tend to show a wellcircumscribed; firm; solid; whitish tan; expansile mass which had compressed the surrounding parenchyma of the testis [4].
b. Microscopic features
• It has been stated that microscopic examination of primary osteosarcoma of the testis specimen would tend to show sheets of pleomorphic round to spindle cells that contain prominent nucleoli [4].
• It has also been stated that microscopic examination of osteosarcoma of the testis would also show areas of osteoid and scattered areas of mineralization [4].
• Additionally, it has been documented that microscopic examination of osteosarcoma of the testis would reveal high mitotic activity and atypical mitosis [4].
• Furthermore; it has been iterated that microscopic examination of osteosarcoma of the testis would show osteoclasts among the area of osteoid [4].
c. Immunohistochemistry features
i. Positive staining: Strong cytoplasmic positivity for Vimentin [6].
ii. Negative staining
• Pan CK

• EMA
• SMA
• Desmin
• Bc12

• CD99
• CD117
• CD30
• Alfa fetoprotein
• NSE
• NF1
• S100
• PGP9.5
d. Molecular and genetics studies: It has been stated that in primary osteosarcoma of the testis; re-arrangement of p53 at 17p13 could be of importance in oncogenesis of osteosarcoma [2].
e. Prognostic factors: It has been stated that primary osteosarcomas of the testis that are confined to the testis tends to be associated a favorable prognosis [4].
f. Differential diagnoses: Some of the documented differential diagnoses include: [4]
• Metastatic osteosarcoma of testis [4].
• Sex cord / stromal tumor with sarcomatous transformation [4].
• Teratoma with sarcomatous transformation [4].
• Malignant neural tumor of testis. [4].
• Leiomyosarcoma of testis [4].
• Synovial sarcoma of testis [4].
g. Outcome
With regard to the outcome of patients who have had radical orchidectomy for osteosarcomas of the testis and radical orchidectomy plus en bloc excision of para-testicular localized primary osteosarcomas short term and medium-term survival without local recurrence and metastasis has been reported with up to 44 months survival but because few cases have been reported without long term follow-up one cannot be dogmatic about the long-term outcome of the disease. It is known that osteosarcomas can recur 11 years after an apparent complete and successful treatment it would be envisaged that unless adjuvant combination chemotherapy is utilized in the initial treatment of a localized primary intra-scrotal osteosarcoma there is the likelihood that late metastases of osteosarcoma could develop. Clinicians should be encouraged to report cases of osteosarcomas of scrotal content organs they treat in order to elucidate the biological behaviour of the disease with the knowledge that most cases of primary osteosarcomas of other organs have generally portended a poor prognosis.

Miscellaneous narrations; summations and discussions from case reports; case series; and studies related to osteosarcoma of the testis

Zukerberg LR and Young RH [7] reported the clinical and pathology features of two cases of pure sarcomas of the testis. They reported that one tumor was an osteosarcoma which was found in a 30-year-old man; and the second case was a fibrosarcoma which was found in an 86-year-old man. Both patients were treated by means of orchidectomy and high ligation of the spermatic cord and they did not receive any post-operative adjuvant therapy. Both patients were reported to be alive and well without any evidence of local recurrence or metastasis at 6 months and five and half months respectively pursuant to orchidectomy. The authors stated that majority of sarcomas of the testis do arise from a teratoma; or less commonly they tend to arise from a spermatocytic seminoma; nevertheless; their two cases and rare reported cases had shown that pure sarcomas do occur occasionally and they could be associated with a favorable prognosis. It could be argued that the two cases were reported with a short period of follow-up only and hence the long-term outcome of both patients was not available. It would also be argued that this case report is not strong enough to make any confident statement related to the outcome of osteosarcoma of the testis and some clinicians could also argue that considering that primary osteosarcomas elsewhere in the body tend to be associated with poor long-term outcome the patient who had primary osteosarcoma of the testis should have been considered for adjuvant chemotherapy to ensure his long-term survival.
Tazi H, et al. [2] reported the case of primary osteosarcoma of the testis in a 60-year-old man who was treated by means of transinguinal orchidectomy without any adjuvant therapy. The reported patient was alive and well without any evidence of local recurrence or metastasis at his 18-month post-operative follow-up. Tazi H, et al. [2] stated that 2at the time of report of their case only 3 cases of primary osteosarcoma of the testis had been reported. Tazi H, et al. [2] additionally stated that the origin of primary osteosarcoma of the testis from undifferentiated mesenchymal cells or from a malignant transformation of a pre-existing teratoma element was not clear as well as management guidelines of osteosarcoma of the testis are difficult to establish in view of the rarity of such tumors; nevertheless; in their opinion inguinal orchidectomy with careful follow-up would appear to be sufficient treatment for the tumor. Some people would argue that the case was reported with 18 months follow-up only and hence the long-term outcome would not be known and perhaps the patient should have been offered adjuvant chemotherapy with the aim of destroying any possible microscopic metastases that could develop into overt clinical metastasis in the future. Considering that there is no consensus opinion related to the treatment of primary osteosarcoma of the testis and the fact that primary osteosarcomas elsewhere generally have been associated with poor prognosis pursuant to surgical excision some people would argue that there is an urgent global need for the establishment of a multi-centre trial of different treatment options with a long-term follow-up in order to ascertain the best treatment options for localized and metastatic osteosarcomas of the testis

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