Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

choriocarcinomas more often spread primarily hematogenously. Thus lung metastases are more common with nonseminomas, but retroperitoneal, mediastinal, and neck involvement is more common with seminomas (Fig. 13.8).

Testicular lymphatics drain alongside the testicular arteries and veins into nodes close to the renal hila and eventually into para-aortic nodes. Left sentinel nodes are located close to the renal hilum; on the right these nodes are paracaval in location, inferior to the renal vessels. Tumors involving the epididymis drain into the iliac nodes. Right-sided tumors tend to spread more often to the left para-aortic nodes than vice versa. Drainage occurs to other sites, such as to inguinal and iliac nodes, if the usual lymphatic drainage pathways become obstructed.

With metastasis, left renal vein and inferior vena caval invasion are not uncommon and are detected by imaging (Fig. 13.9). An endovascular biopsy is diagnostic. These tumors can result in a life-threatening malignant pulmonary embolus.

The results of a prospective multicenter study of extraperitoneal lymph node involvement by testicular tumors are listed in Table 13.7. Although this study is now dated, it does provide relative sensitivities of various tests. Nodal involvement by tumor is not identified by CT directly; rather, enlarged lymph nodes in the

presence of known tumor suggest metastases. In general, as the diameter of a lymph node increases, the likelihood of metastasis increases almost continuously. Ultrasonography is not accurate in detecting extraperitoneal lymph node involvement.

When associated with germ cell tumors, laminar calcifications suggest extension beyond the tunica albuginea (77). An occasional “burned-out” germ cell tumor develops curvilinear calcifications, similar to those seen with a Sertoli cell tumor.

Currently chest and abdominopelvic CT are part of staging these tumors. A negative study, however, has limited significance. Imaging cannot differentiate reliably between stage I (tumor confined to testis) and stage II (spread to regional nodes), and thus retroperitoneal lymph node dissection is necessary.

Magnetic resonance imaging has a limited role in the staging of germ cell tumors. Tumor signal intensity is similar to that of normal tunica albuginea,and invasion cannot be readily determined. In evaluating extraperitoneal lymph node invasion, MRI is similar to CT; namely, lymph node size is used as the primary criterion.

Preliminary studies suggest that FDG-PET appears to have a role in staging metastatic testicular germ cell tumors by detecting increased carbohydrate metabolism of malig-

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Figure 13.9. Metastatic testicular carcinoma. Inferior vena cavagram reveals a tumor thrombi in the inferior vena cava (arrows) and occlusion of the left common iliac vein. Retroperitoneal adenopathy and lung metastases were also present. (Courtesy of David Waldman, M.D., University of Rochester.)

nant cells. Both primary seminomas and malignant teratomas reveal avid uptake. Normal tissue uptake is found in differentiated teratomas and in necrotic tissue.

L-(1–11C)tyrosine PET imaging in men with retroperitoneal metastatic nonseminoma testicular germ cell tumors did not detect most tumors (78); in fact, even with large, inhomoge-

Table 13.7. Retroperitoneal lymph node involvement by testicular tumors*

* Final diagnosis was based on histology of resected retroperitoneal lymph nodes.

Source: Adapted from Bussar-Maatz and Weissbach (76).

neous tumors identified by CT, PET revealed decreased uptake at the site.

Lymphography has been used in the past to evaluate extraperitoneal lymph node involvement. With advances in CT, however, lymphography currently is rarely employed for this purpose; CT, especially multislice, provides additional information about tumor invasion.

Follow-Up

The current primary role of FDG-PET is in men with elevated serum tumor markers and no tumor identified by conventional imaging; keep in mind that FDG-PET is also positive in a setting of postoperative inflammation (79). False-negative studies also occur. The FDG-PET scans are more accurate than CT in detecting residual tumor when performed several weeks or later after chemotherapy.

In evaluating local recurrence after orchiectomy for testicular neoplasms, 67% of US-detected focal tumors and 27% of heterogeneous changes consisted of cancer (80).

Seminoma

Seminoma is the most common germ cell tumor. Histologically, most seminomas are solid tumors composed of sheets of uniform large tumor cells having an overall superimposed fibrous structure, with an anaplastic appearance found in a minority. Some contain a lymphocytic infiltrate. These tumors vary from a small nodule to diffuse infiltration and testicular enlargement. An occasional one is associated with testicular microlithiasis.

Peak incidence occurs in the fourth and fifth decades of life. It is rare under the age of 10 years and over the age of 60 years. A minority of patients have detectable tumor markers b- human chorionic gonadotropin (b-hCG), lactate dehydrogenase, and placental alkaline phosphatase. In most patients with a seminoma at least one of these three markers is elevated. Elevated serum lactate dehydrogenase levels correlate with seminoma invasive status, metastatic status, and poor outcome, while serum b-hCG levels correlate only with metastatic status; most seminomas produce small amounts of hCG, and an elevated serum level reflects an increase in tumor volume and thus suggests metastases. Placental alkaline phosphatase has the highest

sensitivity for detecting metastatic disease. A pure seminoma does not result in elevated a- fetoprotein levels, and the presence of this tumor marker should suggest a nonseminomatous or mixed tumor.

Some of these tumors first manifest by their metastases. The anaplastic variety appears to be more aggressive than a more typical seminoma.

Ultrasonography reveals most seminomas as focal, solid, and well-circumscribed hypoechoic tumors. Most other germ cell tumors do not have a clearly defined tumor margin. A minority of seminomas contain hypoechoic regions. Cystic or hyperechoic regions are not seen and, if present, should suggest another diagnosis. Larger tumors tend to be hypervascular, a finding evident with Doppler US (Fig. 13.10).

Seminomas are isointense to normal tissue on T1and mostly hypointense and relatively homogeneous on T2-weighted MR images. They tend to be homogeneous, and regions of increased signal intensity presumably represent either bleeding or calcifications. They enhance less than normal testicular tissue.

Initial seminoma therapy is orchidectomy. Radiotherapy and chemotherapy for pos-

Figure 13.10. Testicular seminoma. Transverse Doppler image of the left testis. Note hypervascular hypoechoic mass (arrows) occupying most of the testis. Residular normal testicular tissue is present anteriorly (arrowhead). (Courtesy of Deborah Rubens MD, University of Rochester.)

ADVANCED IMAGING OF THE ABDOMEN

torchidectomy relapse of stage I and IIA disease achieves long-term cure rates of 85% or more; relapse-free rates are predicted by tumor size, age, and small vessel invasion.

Seminoma patients require long-term posttherapy follow-up, including a search for radio- therapy-related secondary cancers years later. Thus a review of men treated at the Institut Claudius Regaud for stages I and II testicular seminoma found an overall second nongerm cell cancer in 11% (81); the Standardized Incidence Ratio was significantly increased in men treated with supraplus infradiaphragmatic radiation, but not in those treated with infradiaphragmatic radiation only. Also, the incidence of second cancers increased with the duration of follow-up.

Spermatocytic Seminoma

Whether a spermatocytic seminoma is a variant of a seminoma or a separate entity is debatable. Histologically, cells resemble maturing spermatogonia. This is a rare testicular neoplasm occurring only in adults and developing only in descended testes. The vast majority are benign, although an occasional one is associated with a testicular sarcoma.

Nonseminoma

In the United States, embryonal cell carcinoma, yolk sac tumor, teratoma, and choriocarcinoma are considered nonseminomatous germ cell tumors. British authors prefer to lump nonseminomatous germ cell tumors under malignant teratomas. A number of these tumors contain more than one cell type and these are known as mixed germ cell tumors. Histologically, nonseminomatous germ cell tumors have a heterogeneous appearance. They are prone to hemorrhage and necrosis. An elevated serum a-fetoprotein level should suggest a nonseminoma.

Magnetic resonance imaging reveals most of these tumors to be more heterogeneous than seminomas with all sequences. They contain regions of high and low signal intensity both with T1and T2-weighted images. Because of their MRI heterogeneity, most, but not all, of these tumors can be differentiated from seminomatous tumors.

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Embryonal Cell Carcinoma: An embryonal cell carcinoma is a highly malignant undifferentiated tumor occurring either by itself or as part of a mixed germ cell tumor. A rare embryonal cell carcinoma undergoes differentiation to a peripheral neurectodermal tumor. These tumors occur after puberty, with a peak in young men. They invade readily. Metastases are common at the time of initial diagnosis. Embryonal cell carcinomas are associated with elevated a-fetoprotein levels and about half have elevated b-hCG levels.

Ultrasonography can reveal cysts, calcifications, or areas of hemorrhage. These tumors tend to be hypoechoic.

Yolk Sac Tumors: A yolk sac tumor, or endodermal sinus tumor, predominates in childhood, representing an embryonal adenocarcinoma of the prepubertal testis. It is the most common testicular neoplasm in infants. In adult men this tumor tends to be part of a mixed germ cell tumor. An occasional one occurs in other body parts. Most infants with a yolk sac tumor have elevated a-fetoprotein levels.

A yolk sac tumor occasionally is associated with testicular microlithiasis. The US appearance varies from heterogeneous to homogeneous. Some tumors contain cystic regions. This tumor is not as well marginated as a seminoma and tends to invade adjacent structures.

Teratoma: Primary testicular teratomas contain several germ cell layers and are classified into mature and immature types, with the latter (teratocarcinoma, teratosarcoma, or teratoma with malignant transformation) containing undifferentiated tissue from germ cell layers and having undergone malignant transformation.

Teratomas have two peak incidences: one in infancy and early childhood and another in young men. In the very young they tend to be mature and benign. About half of prepubertal boys with a testicular teratoma have an elevated a-fetoprotein level. Most postpubertal teratomas are malignant. Of interest is that any element in a teratoma can metastasize. A majority of malignant testicular teratomas present with metastatic disease. Occasionally a metastasis contains other subtypes of nonseminomatous germ cell tumors, such as a sarcoma, adenocarcinoma, or even a neuroectodermal tumor.

Pretherapy, most teratomas have an inhomogeneous appearance and contain both solid and

cystic components. A cystic region should not be confused with a benign cyst. Some contain calcifications; the presence of bone or cartilage indicates maturity. A capsule is seen as a hypointense band in the periphery. A PET scan suggests a malignant teratoma in presence of increased tumor uptake.

Choriocarcinoma: A choriocarcinoma is the least common testicular malignancy. Histologically, this tumor contains two cell types: syncytiotrophoblasts and cytotrophoblasts. Most choriocarcinomas are part of a mixed germ cell tumor. An occasional choriocarcinoma is extraperitoneal in origin.

This is a highly malignant tumor occurring mostly in the second and third decades of life. Metastasis is via both lymphatic and hematogenous routes, and at times metastases manifest before a primary tumor is detected. These tumors are associated with elevated b-hCG levels produced by syncytiotrophoblasts; a- fetoprotein levels are not elevated in pure choriocarcinomas.

Hemorrhage and necrosis are common imaging findings.

Mixed Germ Cell Tumor: A mixed germ cell tumor contains several germ cell elements, with the most common combination being an embryonal cell carcinoma and teratoma elements (teratocarcinoma). The embryonal carcinomatous component often represents more than 50% of the tumor mass. These tumors often contain both solid and cystic components and have an overall inhomogeneous appearance.

A gonadoblastoma consists of a mixture of a germ cell tumor and a stromal tumor. Most occur in a setting of cryptorchidism and other congenital abnormalities.

Only about half of mixed germ cell tumors have a homogeneous appearance; many contain cystic degeneration, hemorrhage, or necrosis, and, as a result, the US appearance varies considerably. An imaging appearance of a necrotic tumor containing multilocular cysts is common.

An FDG-PET scan of retroperitoneal metastases often reveals heterogeneous, increased glucose metabolism prior to chemotherapy, reverting to normal FDG uptake after chemotherapy.

Therapy/Follow-Up of Nonseminomas:

Chemotherapy is curative in most individuals with nonseminomatous tumors.

Imaging studies generally do not play a major role in the follow-up of nonseminoma and mixed germ cell tumors because adequate serum markers are available (a-fetoprotein and b-hCG). Persistent elevation of tumor markers after orchidectomy suggests residual tumor. Although increased levels usually signify tumor progression, they are not specific to tumor type. Elevated a-fetoprotein levels occur with hepatocellular carcinomas, some gastrointestinal neoplasms, bronchial carcinomas, and some benign liver disorders, while b-hCG levels are elevated with some gastrointestinal, liver, pancreatic, and urogenital neoplasms. At times elevated b-hCG levels result in gynecomastia. Negative tumor marker levels are of less significance and are seen even with metastatic disease.

Imaging is useful after orchidectomy primarily to detect metastases. A tumor developing after chemotherapy is not necessarily a recurrence; some of these are mature teratomas. Computed tomography is often employed to detect residual tumor after chemotherapy of relapsing nonseminomatous testicular tumors. Among men treated by salvage chemotherapy, CT does not reliably differentiate tumor, scarring, and necrosis (82); CT does, however, provide guidance for lymphadenectomy, which is often considered.

Among men with clinical stage I (T1) nonseminomatous germ cell testicular tumors treated by orchiectomy alone, 74% remained disease-free when followed for a median of 11 years (83); relapses are mostly in those with predominantly embryonal carcinomas and tumors showing vascular invasion, and the authors suggest management by surveillance alone after orchiectomy in this select population with clinical stage I tumors, normal serum markers, and neither predominant embryonal carcinoma nor vascular invasion.

The growing teratoma syndrome is applied to nonseminoma testicular germ cell tumors, which, after chemotherapy, continue to enlarge in a setting of normal tumor markers. Residual tumor resection is associated with a good prognosis. Nevertheless, this issue is complex, illustrated by the following: An orchiectomy in a 21-year-old man with a left testicular tumor and extraperitoneal lymph node metastases revealed a mixed germ cell tumor containing immature teratoma, embryonal carcinoma, and

ADVANCED IMAGING OF THE ABDOMEN

seminoma components (84); after chemotherapy, a-fetoprotein levels declined, but over the next 8 years he underwent several paraaortic tumor resections for enlarged nodes, with the last one yielding adenocarcinoma within parts of a mature teratoma. The authors concluded that the malignant potential of these tumors cannot be evaluated from its maturation and any residual tumor should be resected.

Among extraperitoneal tumors detected by CT after chemotherapy for nonseminomatous testicular cancers, at resection 47% consisted of benign tissue and 53% were either mature teratomas or residual cancer (85); a small residual tumor size and reduction in size after chemotherapy are predictors of benign histology.

An occasional man successfully treated for a nonseminomatous germ cell tumor develops lymphoma years later.

Sex Cord and Stromal Tumors

The nongerm cell tumors include Leydig cell tumor, Sertoli cell tumor, and granulosa cell tumor. Most are benign. Combinations of several of these tumors also occur; these are simply called stromal tumors. Hormone secretion is common.

Leydig Cell Tumors.

Stromal (interstitial) Leydig cells produce androgen necessary for spermatogenesis. A Leydig cell tumor is the most common stromal tumor. It is a tumor of adults, with only a minority developing prepuberty. In the elderly these tumors tend toward malignancy, with the more malignant ones becoming hemorrhagic and necrotic. In some adults, only metastasis establishes their malignant nature.

A common presentation is a painless tumor or testicular enlargement. Some young boys develop precocious puberty, while young men tend towards gynecomastia and infertility. Serum testosterone levels are normal or low. An occasional malignant Leydig cell tumor is associated with high progesterone levels. A Leydig cell tumor can develop in a cryptorchid testis.

Leydig cell tumors are well marginated, encapsulated, solid, and relatively homoge-

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neous, although some larger ones develop cysts and necrosis. Most are similar in appearance to germ cell tumors. Ultrasonography findings vary and range from hypoto hyperechoic. They tend to be isointense on T1and hypointense on T2-weighted images, an appearance similar to germ cell tumors (Fig. 13.11). Some malignant Leydig cell tumors have foci of increased signal intensity both on T1and T2-weighted images, thus mimicking nonseminomatous germ cell tumors.

Sertoli Cell Tumors

Sertoli cells line the tubule basement membrane. Most Sertoli cell tumors are benign. Their prevalence is increased in tuberous sclerosis and Peutz-Jeghers syndrome. Some of these tumors calcify and some are bilateral.

One variant is a large-cell calcifying Sertoli cell tumor found mostly in boys. Usually benign, it has distinctive microscopic features and contains multifocal and curvilinear calcifications identifiable by imaging. This tumor is one of the components in Carney’s

complex (which includes cardiac and skin myxomas, myxoid mammary fibroadenomas, skin pigmentation, adrenocortical abnormalities, pituitary adenoma, and testicular tumors such as large-cell calcifying Sertoli cell tumor).

Granulosa Cell Tumor

Granulosa cell and theca tumors are rare in males. Two peaks occur: one during the first month of life and the other one in late adulthood. Their imaging appearance is similar to that of other stromal tumors.

Carcinoid

A primary testicular carcinoid is exceedingly rare. Carcinoid metastases to testes are more common.

Metastatic to Testes

Metastatic spread to the scrotum is by spermatic cord, lymphatics, or, least often, via a hematoge-