CROSS-SECTIONAL IMAGING FEATURES OF COMMON AND UNCOMMON PRIMARY RETROPERITONEAL TUMORS: AN EXPERIENCE AT OUR INSTITUTE – A PICTORIAL ESSAY.

Primary retroperitoneal tumors are very rare neoplasms accounting for only 0.1-0.2% of all tumors in the body. They can be either mesodermal, neurogenic, germ cell or lymphoid in origin with mesodermal tumors accounting for 80% of all primary retroperitoneal neoplasms. Cross-sectional imaging such as computed tomography and magnetic resonance imaging play a vital role in non-invasive assessment and localization of these tumors within the retroperitoneal space retroperitoneal tumors, distinctive characteristics of some of the neoplasms on imaging are helpful in narrow down the differential diagnosis.

Primary retroperitoneal tumors are very rare neoplasms accounting for only 0.1-0.2% of all tumors in the body. They can be either mesodermal, neurogenic, germ cell or lymphoid in origin with mesodermal tumors accounting for 80% of all primary retroperitoneal neoplasms. Cross-sectional imaging such as computed tomography and magnetic resonance imaging play a vital role in non-invasive assessment and localization of these tumors within the retroperitoneal space as well as for pretreatment staging. Though tissue diagnosis is required for definitive diagnosis due to the overlapping imaging features, certain key imaging features on cross-sectional imaging can help us to narrow down the differential diagnoses. Also imaging helps to guide the site of biopsy due to heterogeneous nature of these tumors. Familiarity with the key cross sectional imaging features of these heterogeneous neoplasms along with clinical and demographic data will facilitate accurate diagnosis and early management of the same.

Introduction:
Primary retroperitoneal tumors are histologically primitive tumors that arise in the retroperitoneal space which do not include the tumors originating from the retroperitoneal organs such as pancreas, adrenal glands, organs of the excretory system, ascending and descending colon or metastatic lesions. 1,2 They are very rare and account for only 0.1-0.2 % of all malignancies and 70%-80% are malignant in nature. 3,4 Primary retroperitoneal tumors are classified according to the tissue of origin in the retroperitoneal space (mesodermal, neurogenic, germ cell, sex cord and stromal, lymphoid or hematologic) 4 . Mesodermal tumors are accounting for 80% of primary retroperitoneal neoplasms, whereas neurogenic tumors are relatively less common, accounting for 10% of the primary retroperitoneal neoplasms. 3,4 Noninvasive evaluation of these tumors by computed tomography (CT) and magnetic resonance imaging (MRI) is necessary due to the variable treatment options. Both the modalities are helpful in both characterization as well as in assessing the extent of the disease and in staging. Presence of calcification within these tumors is best assessed by CT whereas MRI is helpful for the assessment of fat containing lesions and vascular invasion by these tumors due to the superior soft tissue contrast. 4 Although tissue diagnosis plays an inevitable role for the final diagnosis of these tumors and overlap in the imaging features of retroperitoneal tumors, distinctive characteristics of some of the neoplasms on imaging are helpful in narrow down the differential diagnosis.

Locating The Tumor Within The Retroperitoneal Space 2,8
Origin of a tumor/mass from a retroperitoneal organ should be excluded in order to classify that tumor/mass as a "Primary retroperitoneal mass." The following signs help to locate the mass within the retroperitoneal space [ Fig. 2]:

Beak sign:
A primary retroperitoneal mass/lesion will abut and compress the adjacent organ and form obtuse angles with that organ. Whereas, a mass originating from an organ will form acute angles with that organ thus deforming the edge of that organ into a "beak" or "claw" shape.

Phantom / Invisible organ sign:
A small retroperitoneal organ may not be visible at all if a large mass is arising from it. This is called as "phantom/invisible organ sign." Absence of this sign indicates a primary retroperitoneal pathology.

Embedded organ sign:
A mass, not originating from an adjacent hollow viscus / plastic organ (inferior vena cava) will simply compress the organ into a crescentic shape (negative embedded organ sign). In ontrast, when part of an organ appears to be embedded in the mass, it indicates that the mass is arising from that organ (positive embedded organ sign).

Mesodermal Tumors
These tumors are large at the time of presentation with involvement of adjacent structures with very high recurrence rate. Pseudocapsule may be appreciated due to compression of adjacent structures. Metastases to liver, lung, bones and brain can occur. Liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, angiosarcoma and sarcoma of perivascular cells are few of the tumors of mesodermal origin. 4

Liposarcoma
Liposarcoma is the most common sarcoma of the retroperitoneum arising from deeper soft tissue of the retroperitoneum. It is the second most common adult soft tissue sarcoma. The World Health Organization (WHO) divides liposarcomas into four subtypes: well-differentiated, myxoid, dedifferentiated, and pleomorphic. The most common subtype is well-differentiated retroperitoneal liposarcoma which shows attenuation similar to macroscopic fat on computed tomography CT. On magnetic resonance imaging (MRI), they follow the signal intensity of 215 subcutaneous fat with loss of signal on fat suppressed images. They show little or no contrast enhancement on postcontrast study reflecting the paucity of intratumoral vessels. Occasionally, thickened irregular septa, minor nodular and sclerosing components may show homogeneous enhancement. Imaging features that favor well-differentiated liposarcoma over lipoma include large lesion size (>10 cm), presence of thick septa (>2 mm), nodular and/or globular areas, nonadipose mass like areas, and a decreased percentage of fat composition (<75% fat in mass). 5 Although areas of necrosis and calcification tend to be uncommon in liposarcomas, 30% of the cases may show calcification, which is an important sign of dedifferentiation. 4

[Fig. 3]
Dedifferentiated liposarcomas show areas with attenuation and signal intensity similar to well-differentiated liposarcoma with more mass like areas of nonfatty tissue and relatively higher attenuation on CT with low T1 and high T2 signal on MRI. 5 Myxoid liposarcomas present in younger age group in comparison to well-differentiated and dedifferentiated types. On CT, they have heterogeneous hypoattenuating appearance with relatively lesser attenuation than that of muscle. A "pseudocystic" appearance is characteristic due to the homogeneous distribution of fat and soft tissue within the mass. High mucopolysaccharide contents give strikingly high T2 signal intensity on MRI along with lacy, linear / amorphous areas fat signal intensity on both T1 and T2 weighted images. Pleomorphic liposarcomas present as heterogeneous soft-tissue masses with areas of necrosis. Small foci of fat can be appreciated even in solid-appearing lesions on MRI. 4

Solitary fibrous tumor
Solitary fibrous tumors (SFTs) are very rare tumors of the retroperitoneum with only very few cases reported in the literature. Age of onset varies from 17 to 85 years with a female predilection. On cross sectional imaging, they appear as large, lobulated, round to oval shaped masses, deforming the adjacent organs. Most of the SFTs of the retroperitoneum are pseudoencapsulated / enveloped which is characteristic of these tumors. On computed tomography they are iso/hyperdense to the muscle with density increases as the cell mass increases and density decreases as the amount of collagen mass increases. They may become heterogeneous due to cystic/myxoid degeneration and necrosis. On post contrast study these tumors show three patterns of enhancement: mild (<50%), moderate (50-100%) and significant (>100%) depends on the amount of cell mass with necrosis more commonly occur in the latter. Sustained and heterogeneous enhancement maybe noted on delayed phase. Pseudoenvelope also shows variable degree of enhancement [ Fig. 4]. On MRI, they have iso-hyperintensity to muscle on T1W images with T2 signal depends on the amount of collagen (low signal), cell mass and myxoid degeneration (high signal). 9,10 Neurogenic Tumors Neurogenic tumors account for 10-20% of primary retroperitoneal tumors. They are usually benign in nature with better prognosis in comparison to sarcomas. 3,4 They can originate from (a) ganglion cell (ganglioneuromas, ganglioneuroblastomas, neuroblastomas), (b) paraganglionic system/chromaffin tissue (pheochromocytomas, paragangliomas), and (c) nerve sheath (neurilemmomas, neurofibromas, neurofibromatosis, malignant nerve sheath tumors). 4,11 Neurofibroma Neurofibromas are benign peripheral nerve sheath tumor composed of nerve sheath cells intermingled with thick collagen bundles with a small to moderate amount of myxoid degeneration accounting for about 1% of retroperitoneal tumors. 3,11 In patients with neurofibromatosis they commonly occur in deep anatomical locations. 5 Retroperitoneal neurofibromas appear as well-defined, round, hypodense, inhomogeneous solid masses on CT, seen along the expected course of the nerve. On non-contrast CT, they have attenuation values of 20-25 HU with homogeneous enhancement (30-50 HU) on contrast-enhanced CT. Centrally located nervous tissue shows T1 high and T2 low signal whereas peripherally located myxoid tissue shows T1 low and T2 high signal on MR imaging. 11 Plexiform neurofibroma is an uncommon variant of neurofibromatosis type 1 occurring along multiple nerves and their branches as an interdigitating network of fingerlike fronds. 12,13 Retroperitoneal plexiform neurofibromas appear as symmetric,bilateral parapsoas or presacral masses along the distribution of lumbosacral plexus. High lipid content, high water content within the mucinous matrix, cystic degeneration and entrapment of perineural adipose tissue are contributing to the hypodensity of these tumors 13 [Fig.5].

Paraganglioma
Paraganglia are highly vascularized specialized neural crest cells that are symmetrically distributed along the aortic axis in close association with the sympathetic chain in the neck, chest, abdomen, and pelvis. Tumors arising from these cells are called paragangliomas with the most common location being the organ of Zuckerkandl located along 216 the aorta at the level of the origin of the inferior mesenteric artery. 4,5 The rate of malignant transformation is higher in paragangliomas in comparison to pheochromocytomas. 3 On unenhanced CT, small tumors appear as wellcircumscribed, lobular or round soft tissue-attenuating homogeneous masses whereas larger tumors are heterogeneous in appearance. Fluid-fluid level can be appreciated due to hemorrhage. Intense contrast enhancement is the rule due to the hypervascular nature of these tumors 4,5 [Fig. 6]. On MRI, they exhibit variable signal intensity on T2-weighted image with signal voids can be appreciated in T1-weighted spin-echo sequences. 4

Ganglioneuroma
It is a benign neoplasm composed of ganglion cells and Schwann cells. Most common locations include posterior mediastinum, retroperitoneum, adrenal glands, head and neck soft tissues. Solitary tumors are diagnosed before 10 years of age and has a female predilection with female: male ratio of 3:1 17 .

Retroperitoneal composite malignant paraganglioma-ganglioneuroma
These are very rare tumors with only very few cases reported and few in the urinary bladder 17 . Composite paragangliomas have one of the neural components such as neuroblastoma, ganglioneuroblastoma, or typical ganglioneuroma 18 . These tumors appear as large heterogenous well defined masses showing intense enhancement with cystic areas on post contrast CT images [ Fig.7].

Germ Cell, Sex Cord And Stromal Tumors
Extragonadal germ cell tumors (EGCT) account for 1-3% of all germ cell tumors and less commonly located in the retroperitoneum second only to the most common location, the mediastinum. 5 They are usually located in or near the midline between T6 and S2 vertebrae with a midline mass more suggestive of a primary extragonadal germ cell tumor rather than of metastasis. 4

Teratoma
Teratomas represent 11% of all primary retroperitoneal tumors and is the third most common tumor in the retroperitoneum in children, after neuroblastoma and Wilms tumor 4 . They can be either mature or immature, and benign/malignant. Mature teratomas, also called as dermoid cysts, are well-differentiated tumors derived from at least two of the three germ cell layers (ectoderm, mesoderm, endoderm). Imaging features favouring mature teratoma is the presence of a fat-containing retroperitoneal cyst with mural calcifications. Wall thickening, irregular margins, and infiltration of adjacent organs are the signs of malignant transformation of mature teratomas. Immature teratomas appear as predominantly solid with coarse and ill defined areas of calcification and scattered areas of fat. Mature and immature teratomas may not be differentiated by imaging alone. 4,8 Preascral space is one of the pelvic retroperitoneal spaces with teratoma as one of the fat-containing tumors that occurs in this space. Sacrococcygeal teratomas are more common in infans and children with very few cases have been reported in adults with female:male ratio of 4:1. 14 They may grow either anterosuperiorly into the abdominopelvic cavity and/or posteroinferiorly into the gluteal region. Sacrococcygeal teratomas can occur either predominantly external or exclusively presacral without external component with later presenting late in life than with the external component. They have varied appearances on CT and MR imaging, ranging from heterogeneous solid to cystic with or without septations with areas of intratumoral fat and calcification [Fig.8]. Adult sacrococcygeal teratomas are more prone for malignancy than those occurring in children. 15.16 Lymphoid Neoplasms Lymphoma Lymphomas are accounting for 1/3 rd of all primary retroperitoneal tumors. Extranodal or para-aortic lymph nodal involvement is more common in non-Hodgkin's lymphoma (55% of cases) than Hodgkin's lymphoma. 3 Lymphomas appear as well-defined, homogeneous masses that spread between normal structures without compressing them [ Fig.9]. "Floating aorta" or "CT angiogram" sign can be appreciated on cross-sectional imaging due to anterior displacement of aorta and IVC. On MR imaging they appear as isointense on T1-weighted images and iso-to hyperintense on T2 weighted images. 4 The homogeneous appearance is the main distinguishing factor that differentiates lymphomas from other primary retroperitoneal masses, however 23% of cases may have heterogeneous appearance thus may be difficult to differentiate from other nonlipomatous primary retroperitoneal tumors.

Conclusion:-
Primary retroperitoneal neoplasms are diverse group of rare neoplasms. Though definitive diagnosis of these neoplasms done by tissue sampling, cross-sectional imaging is a vital non-invasive tool to locate these tumors within the retroperitoneal space by some key imaging features as well as for pretreatment staging. 218

Conflicts of interest:
Nil.  Axial (7a) non-contrast CT image of abdomen shows a well defined large heterogenous mass (arrows) in right retroperitoneum with compression of the IVC and the portal vein. Axial (7b) and coronal (7c) post contrast study shows heterogenous enhancement with peripheral non-enhancing cystic areas.
225 Figure 8:-Sacrococcygeal teratoma in a 27-year-old female patient. Axial T2-weighted images (8a) of the pelvis shows a round to oval shaped, heterogeneous mass lesion involving the presacral space with fluid (curved arrows) not suppressed on fat suppressed images and fat (straight arrows) suppressed on fat-suppressed images (8b). A signal void (chevrons) also noted on both T1 and T2 weighted sagittal images (8c and 8d) suggestive of calcification.
226 Figure 9:-Non-Hodgkin's lymphoma in a 56-year-old male patient. Sagittal (9a) non-contrast images of the abdomen show a large, confluent, relatively homogeneous, lobulated mass lesion involving the retroperitoneum with extension between the great vessels and spine with erosion of the vertebral bodies (9c). Right inguinal extension (arrow) is also noted in the coronal image (9b). Contrast study was not done due to the deranged renal function tests.