EDUCATION EXHIBIT 983

Primary Neoplasms ofPeritoneal and Sub-peritoneal Origin:CT Findings1

LEARNINGOBJECTIVESFOR TEST 3After reading thisarticle and takingthe test, the reader

will be able to:

� Describe the CTfeatures of a varietyof primary peritonealneoplasms.

� Identify the perti-nent clinical and de-mographic featuresassociated with theseneoplasms.

� Discuss peritonealanatomy as it relatesto neoplastic disease.

Perry J. Pickhardt, MD ● Sanjeev Bhalla, MD

Peritoneal carcinomatosis is a common metastatic manifestation ofmany organ-based malignancies, particularly carcinomas of the gastro-intestinal tract and ovaries. Primary neoplasms of peritoneal and sub-peritoneal origin occur much less frequently than metastatic peritonealinvolvement from a known or occult primary tumor; however, theserare primary lesions (peritoneal mesothelioma, papillary serous carci-noma, desmoplastic small round cell tumor, benign and malignantmesenchymal tumors, lymphoproliferative disorders) are often firstdetected at computed tomography (CT) and should be considered inthe absence of a known or suspected organ-based malignancy. A pre-cise diagnosis based on imaging findings alone is often not possible.Furthermore, distinguishing a benign from a malignant process and aprimary from a metastatic process is also challenging. Nevertheless,CT features combined with the patient’s relevant clinical and demo-graphic data can help narrow the differential diagnosis for a peritone-um-based neoplasm in many cases. CT is useful not only for the detec-tion, characterization, and staging of primary neoplasms of peritonealand subperitoneal origin, but also for guiding biopsy for tissue diagnosis.©RSNA, 2005

Abbreviations: GIST � gastrointestinal stromal tumor, NF-1 � neurofibromatosis type 1

RadioGraphics 2005; 25:983–995 ● Published online 10.1148/rg.254045140 ● Content Codes:

1From the Department of Radiology, University of Wisconsin Medical School, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI53792 (P.J.P.); the Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (P.J.P.); and the Mallinckrodt In-stitute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.). Presented as an education exhibit at the 2003 RSNA AnnualMeeting. Received June 30, 2004; revision requested September 21 and received October 6; accepted October 7. P.J.P. is a medical consultant for Via-tronix, Inc; S.B. has no financial relationships to disclose. Address correspondence to P.J.P. (e-mail: ppickhardt@mail.radiology.wisc.edu).

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of theDepartments of the Navy or Defense.

©RSNA, 2005

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CME FEATURESee accompanying

test at http://www.rsna.org

/education/rg_cme.html

IntroductionPeritoneal carcinomatosis is a relatively commonmetastatic manifestation of a variety of organ-based malignancies, particularly of the gastroin-testinal tract and ovaries. Primary neoplasms ofperitoneal and subperitoneal origin occur muchless frequently than metastatic disease in theselocations; however, they are often first detected atcomputed tomography (CT).

In general, neoplastic involvement of the peri-toneal and subperitoneal spaces will manifest atCT as a soft-tissue process (tumorous or infiltra-tive) with or without associated fluid (ascites).Additional findings may include a cystic compo-nent or cystic necrosis, calcification, prominentcontrast material enhancement, or fat attenua-tion. However, most CT findings are nonspecific,since there are a number of nonneoplastic andbenign neoplastic peritoneal conditions that canclosely mimic malignancy (1). Even in the ab-sence of a known organ-based malignancy, anoccult gastrointestinal, ovarian, or other organ-based cancer will likely be initially favored in thesetting of findings that are suspicious for perito-neal carcinomatosis. However, primary neo-plasms of peritoneal and subperitoneal origin,albeit relatively rare, must also be considered inthis setting. Unfortunately, most of these primarytumors are malignant and often portend a poorprognosis.

In this article, we review anatomic consider-ations relating to the peritoneum and subperito-neum. We also discuss and illustrate CT tech-nique and subsequent findings in a wide spectrumof primary peritoneal neoplasms, including peri-toneal mesothelioma, papillary serous carcinoma,desmoplastic small round cell tumor, various be-nign and malignant mesenchymal tumors, andlymphoproliferative disorders (Table). We do notdiscuss desmoid tumor (fibromatosis) because itis not a true neoplasm (1).

Anatomic ConsiderationsThe visceral and parietal peritonea enclose thelarge potential space referred to as the peritonealcavity. Pathologic processes that gain access tothe peritoneal cavity can disseminate throughoutthis space by means of the relatively unrestrictedmovement of fluid and cells. Often overlooked,however, is the potential for disease extensionwithin the subperitoneal space, which lies deep tothe surface lining of the visceral and parietal peri-tonea, the omentum, and the various peritonealligaments and mesenteries (2). Furthermore, the

subperitoneal space has both intraperitoneal andextraperitoneal components that bridge the peri-toneum and retroperitoneum, allowing bidirec-tional spread of disease processes. These compo-nents help explain the dual involvement that issometimes encountered in these traditionallyseparate and distinct compartments. In this ar-ticle, we focus on entities arising primarily withinthe peritoneum and the intraperitoneal portion ofthe subperitoneal space.

CT TechniquePrior to the advent of modern cross-sectional im-aging, peritoneal disease was generally not detect-able until the process had resulted in significantdisplacement of abdominal organs or bowel ob-struction. Multidetector CT readily allows nonin-vasive evaluation of the peritoneum, but earlydetection of disease remains a diagnostic chal-lenge, particularly in the absence of peritonealfluid (ascites). In general, both orally and intrave-nously administered contrast material will in-crease the overall diagnostic accuracy of CT fordetecting peritoneal abnormalities. Soft-copy CTimage interpretation with real-time image scroll-ing has greatly enhanced the ability to reliablydetect subtle peritoneal soft tissue and distinguishit from normal bowel. Two-dimensional multipla-nar reformatted images may also be useful in se-lected cases.

Primary Peritoneal Neoplasms

MesotheliomaCystic mesotheliomaPapillary serous carcinomaDesmoplastic small round cell tumorBenign mesenchymal tumors

HemangiomaLymphangiomaLipomaNerve sheath tumorGastrointestinal stromal tumor (GIST)Leiomyomatosis peritonealis disseminata

Malignant mesenchymal tumorsLiposarcomaMalignant fibrous histiocytomaLeiomyosarcomaGISTNerve sheath tumorFibrosarcomaAngiosarcomaSynovial sarcoma

Lymphoproliferative disordersPeritoneal lymphomatosisLeukemic infiltrationGranulocytic sarcomaExtramedullary plasmacytoma

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Types of Neoplasms

MesotheliomaMalignant peritoneal mesothelioma is a rare butaggressive tumor that is derived from the perito-neal mesothelium. Although most mesotheliomasinvolve the pleural surface, approximately 30%arise solely from the peritoneum (3), and in only aminority of these cases will the patient have a his-tory of significant asbestos exposure. CT featuresof peritoneal mesothelioma range from a “dry”appearance consisting of peritoneum-basedmasses, which may be large or confluent (Fig 1),to a “wet” appearance consisting of ascites andassociated peritoneal thickening, which may benodular or diffuse (Fig 2). Scalloping of or masseffect on adjacent abdominal organs may be seen(Fig 1). Calcification is uncommon, and other

causes of extensive calcification in a peritoneum-based tumor should be considered. Unlike inpleural mesothelioma, associated calcified perito-neal plaques are not commonly encountered.

Cystic MesotheliomaCystic mesothelioma is a benign neoplasm that isderived from the peritoneal mesothelium (4).This rare tumor has a distinct female predilection.Cystic mesothelioma has no malignant potentialbut is reported to recur in 25%–50% of cases.Typically, the lesion consists of multiple grape-like clusters of mesothelium-lined cysts separatedby varying amounts of fibrous tissue. At CT, cys-tic mesothelioma appears as either a peritoneum-based multilocular cystic mass (Fig 3) or multiple

Figures 1, 2. Malignant peritoneal mesothelioma. (1) Contrast material–enhanced CT scan shows confluent peri-toneum-based masses of varying attenuation that scallop the liver. (2) Contrast-enhanced CT scan shows relativelyuniform and diffuse thickening of both the visceral and parietal (arrowheads) peritonea with associated ascites.Omental infiltration is present, but no bulky masses or loculated fluid collections are seen.

Figure 3. Cystic mesothelioma in a young woman. CT scans (a obtained cephalad to b) show a large, peritoneum-based multilocular cystic mass. Note the thin cyst walls. No prominent soft-tissue component is present.

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distinct unilocular thin-walled cysts. Involvementof the pelvic region is characteristic. Absence ofsignificant mass effect, increased attenuation, cal-cification, or a prominent soft-tissue componentare CT features that can help distinguish cysticmesothelioma from malignant metastatic diseasesuch as pseudomyxoma peritonei (5).

Papillary Serous CarcinomaPrimary papillary serous carcinoma of the perito-neum is a rare malignancy that predominantlyaffects postmenopausal women (6). Multicentricperitoneal involvement is typical, with omentalinvolvement being particularly common (Figs 4,5). Extensive calcification of omental caking ispresent in many cases and is a useful CT findingfor excluding mesothelioma. The absence of anovarian mass is critical for excluding metastaticpapillary serous ovarian carcinoma, which other-wise has a similar appearance at CT (Fig 6) and ishistologically identical to its primary peritonealcounterpart (6).

Desmoplastic Small Round Cell TumorDesmoplastic small round cell tumor is a highlyaggressive malignancy that has only recently beendescribed (7). The peritoneal cavity is the most

common site of involvement. Unlike most of theother primary peritoneal neoplasms discussed inthis article, desmoplastic small round cell tumormost often affects adolescents and young adults.The most typical CT appearance is that of mul-tiple rounded peritoneal masses (Fig 7) with orwithout ascites (6). Heterogeneous enhancementwith central low-attenuation areas is common.The omentum and paravesical regions are often

Figures 4, 5. Primary papillary serous carcinoma of the peritoneum. (4) Contrast-enhanced CT scanobtained in a middle-aged woman shows irregular soft-tissue infiltration of the omentum (arrows). Noovarian mass was present. The diagnosis was confirmed at ultrasonography-guided biopsy. (5) Contrast-enhanced CT scan obtained in a different middle-aged woman shows a solid mass involving the right as-pect of the omentum (arrow). Note the small amount of adjacent peritoneal fluid and the prominentomental vessel. As in Figure 4, no ovarian mass was present.

Figure 6. Metastatic papillary serous ovarian carci-noma. CT scan (bone window) shows densely calcifiedperitoneum-based metastases, which are considerablyhigher in attenuation than contrast material in thebowel. Primary peritoneal papillary carcinoma couldhave an identical appearance.

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involved. An infiltrative appearance with diffuseperitoneal thickening is a less common manifesta-tion (Fig 8).

Benign Mesenchymal TumorsMesenchymal tumors that arise from the intra-peritoneal portion of the subperitoneal space maybe derived from lymphatic, vascular, neuromus-cular, or fatty tissues. Malignant mesenchymaltumors outnumber benign neoplasms in mostpublished series. However, the CT findings inbenign mesenchymal neoplasms are more oftensuggestive of a specific diagnosis.

Lymphangiomas may represent either congeni-tal malformations of the lymphatic system or be-nign neoplasms (8) and typically appear as large,thin-walled, usually multiloculated cysts at CT.Mesenteric infiltration is common, and removaloften necessitates bowel resection; an omentalorigin is less commonly seen. At CT, the cystwalls are often imperceptible, but vessels may beseen coursing between locules (Figs 9, 10). Cystcontents can have an attenuation less than that ofwater due to their chylous nature, which can be akey distinguishing feature.

Figure 7. Desmoplastic small round cell tumor. Axial contrast-enhanced CT scans (a obtained cephalad tob) show multiple rounded peritoneum-based masses, which represent the most frequent manifestation of thisdisease.

Figure 8. Desmoplastic small round cell tumor.Axial contrast-enhanced CT scan shows diffuse perito-neal thickening with omental caking, findings that rep-resent a less frequent manifestation of desmoplasticsmall round cell tumor.

Figure 9. Lymphangioma. Contrast-enhanced CTscan shows a low-attenuation cystic lesion involving thegastrohepatic ligament (arrowheads). Note the vesselcoursing between locules of the lesion.

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Hemangiomas may be classified into cavern-ous, capillary, and venous types (9). Cavernoushemangiomas are the most common type to in-volve the mesentery and consist of relatively largeblood-filled sinuses lined by endothelium. Unlikecavernous hemangiomas of the liver, mesentericlesions generally lack a well-defined border. How-ever, the presence of phleboliths is highly sugges-tive of the diagnosis (Fig 11).

Lipomas arising from subperitoneal adiposetissue are generally of no clinical concern but maybe detected incidentally at CT (Fig 12). Uniformfat attenuation without a prominent soft-tissuecomponent is a pertinent feature arguing againstthe possibility of liposarcoma (10).

Nerve sheath tumors arising from the subperi-toneal space are uncommon. A mesenteric plexi-form neurofibroma in the setting of neurofibro-matosis type 1 (NF-1) likely represents the mostcommon manifestation of subperitoneal involve-ment, although retroperitoneal involvement ismuch more common. At CT, nerve sheath tu-mors often have a multifocal, branching or coales-cent appearance and may mimic low-attenuationlymphadenopathy or even a cystic lesion (Figs 13,14) (11). These tumors often bridge the retro-peritoneal and subperitoneal spaces (Figs 13, 14).

Associated nerve root lesions or other findingstypical of NF-1 can strongly suggest the diagnosis(Fig 14). Although usually benign, these tumorsmay undergo malignant degeneration.

Leiomyomatosis peritonealis disseminata is arare benign condition that primarily affectswomen of reproductive age and is associated withuterine fibroids, pregnancy, and contraceptivesteroids (12). This disease entity is characterizedby the presence of multiple subperitoneal nodulescomposed of smooth muscle cells (Fig 15).

Figure 11. Mesenteric hemangioma. Contrast-en-hanced CT scan shows a poorly circumscribed mesen-teric soft-tissue mass (arrow) with punctate calcifica-tions that represent phleboliths.

Figure 12. Mesenteric lipoma. Contrast-enhancedCT scan shows a well-circumscribed lesion with uni-form fat attenuation (arrowheads). No soft-tissue com-ponent is present.

Figure 10. Mesenteric lymphangioma. Contrast-enhanced CT scan shows a large, low-attenuationcystic lesion involving the small bowel mesentery. Notethe vessels coursing through the lesion (cf Fig 9).

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Figures 13, 14. (13) Plexiform neurofibroma in NF-1. Contrast-enhanced CT scan shows confluentlow-attenuation material surrounding the superior mesenteric and replaced right hepatic arteries, a find-ing that represents a plexiform neurofibroma. Contiguous involvement of the retroperitoneum under-scores the continuity of the retroperitoneum with the subperitoneal space. (14) Multiple neurofibromasin NF-1. Contrast-enhanced CT scan shows a prominent low-attenuation mass near the root of the mes-entery that surrounds the superior mesenteric vessels. Lymphadenopathy could also have this appear-ance; note, however, the presence of low-attenuation neurofibromas involving the paraspinal nerve roots(arrows).

Figure 15. Leiomyomatosis peritonealis dissemi-nata in a woman with acute abdominal symptomsfrom cecal volvulus. Contrast-enhanced CT scansincidentally show several enhancing peritoneum-based nodules (arrowheads in a and b). Note alsothe multiple pedunculated subserosal uterine fi-broids. Leiomyomatosis peritonealis disseminatawas proved at subsequent laparotomy for cecal vol-vulus.

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Figure 16. Mesenteric liposarcoma. Contrast-enhanced CT scans (a obtained cephalad to b) show a mesen-teric lesion (arrowheads) that is predominantly fatty but contains heterogeneous soft-tissue elements.

Figures 17, 18. Malignant fibrous histiocytoma. (17) Contrast-enhanced CT scan shows a large,heterogeneous soft-tissue mass, which is a typical appearance of peritoneal malignant fibrous his-tiocytoma. (18) Contrast-enhanced CT scan shows a relatively small mesenteric tumor (arrow-head), which is an uncommon appearance of peritoneal malignant fibrous histiocytoma.

Figure 19. Leiomyosarcoma. Axialcontrast-enhanced CT scan shows alarge, peritoneum-based soft-tissuemass with heterogeneous enhancement.

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Leiomyomatosis peritonealis disseminata mostoften represents an unexpected finding at lapa-rotomy performed for other reasons and is ofteninitially assumed to represent carcinomatosis.

Malignant Mesenchymal TumorsPrimary sarcomas of the subperitoneal space suchas liposarcoma, malignant fibrous histiocytoma,and leiomyosarcoma occur less frequently thantheir retroperitoneal counterparts (13). In somecases, extension of tumor results in involvementof both the intraperitoneal and extraperitonealportions of the subperitoneal space, with the pro-cess most often originating in the latter. Thesetumors are generally seen in adults and are typi-cally large at diagnosis.

Although liposarcoma is one of the most com-mon primary retroperitoneal malignancies, peri-toneal liposarcoma is relatively rare (14). How-ever, unlike in the other primary peritoneal sarco-mas, the CT findings can suggest this specific

diagnosis when the tumor contains areas of fatattenuation (Fig 16). Fat attenuation is less likelyto be seen in higher-grade liposarcomas, such asthe pleomorphic and round cell subtypes.

Apart from liposarcoma, the peritoneal sarco-mas largely lack any distinguishing features andgenerally manifest at CT as large, solitary masses(13). Malignant fibrous histiocytoma is reportedto be the single most common peritoneal sarcoma(Figs 17, 18) (15). Peritoneal involvement by leio-myosarcoma and GIST is most often due to meta-static spread from a primary gastrointestinal site,but primary peritoneal tumors do occur (Figs 19,20) (16). In the setting of NF-1, a large peritonealmass will most likely represent either a malignantnerve sheath tumor or a GIST, both of which occurmore frequently in these patients (Fig 21). Fibrosar-coma of the mesentery and omentum in young pa-tients can mimic inflammatory pseudotumor at

Figure 20. GIST. Contrast-enhanced CT scanshows a large, heterogeneous omentum-based mass,a finding that was believed to represent a primaryperitoneal tumor.

Figure 21. GIST complicating NF-1 in a patient who was referred for preoperative staging of “ovarian can-cer.” Contrast-enhanced CT scans show a large, heterogeneous midline abdominal mass (arrows in a) with alarge cystic component extending inferiorly (* in b). Additional findings in NF-1 include mesenchymal dyspla-sia of the lumbar spine with an associated lateral meningocele (black arrowhead in a) and multiple cutaneousneurofibromas (white arrowheads). Given the CT findings, a diagnosis of malignant nerve sheath tumor orGIST rather than ovarian primary tumor was made, and the surgical approach was altered accordingly.

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both CT and pathologic evaluation (Fig 22) (17).Angiosarcoma can arise from vascular elements ofthe subperitoneal space (Fig 23). Even synovial sar-coma can arise within the peritoneum and mayshow dystrophic calcification (Fig 24) (18).

Lymphoproliferative DisordersLymphoproliferative neoplastic disease can rarelymanifest as a primary subperitoneal process with-out additional sites of involvement at presenta-tion.

Mesenteric lymphadenopathy is a relativelycommon CT manifestation of non-Hodgkin lym-phoma. However, extensive lymphomatous infil-

Figure 22. Inflammatory fibrosarcoma in a youngpatient. CT scan shows a large, peritoneum-basedmass with heterogeneous enhancement. Differentiationfrom inflammatory pseudotumor can be difficult atboth imaging and pathologic evaluation in such cases.

Figure 23. Angiosarcoma. Axial contrast-enhancedCT scan shows a large, complex cystic or necrotic massinvolving the omentum. Angiosarcoma was subse-quently proved at pathologic evaluation.

Figure 24. Synovial sarcoma. CT scans show a complex cystic-solid mass (arrowheads in a) centered in thegastrocolic ligament between the greater curve of the stomach and the transverse colon. Tumor calcification isalso present, a finding that is unusual in peritoneal sarcomas.

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tration of the intraperitoneal portion of the sub-peritoneal space is uncommon and is referred toas peritoneal lymphomatosis (19). CT findingsconsist of omental caking, diffuse peritonealthickening, and ascites (Figs 25, 26). Associatedretroperitoneal and mesenteric adenopathy issometimes present (Fig 26).

Leukemic infiltration of the peritoneum is alsorare. As in peritoneal lymphomatosis, the CT

findings can closely mimic peritoneal carcinoma-tosis (Fig 27). Granulocytic sarcoma, sometimescalled chloroma because of its greenish hue, rep-resents a subset of extramedullary disease that isassociated with acute myeloid leukemia (20).Peritoneal involvement can manifest at CT as afocal soft-tissue mass (Fig 28) or a diffuse infiltra-tive process (Fig 29).

Figures 25, 26. Peritoneal lymphomatosis. (25) Contrast-enhanced CT scan shows omental soft-tissue infiltra-tion and ascites. No organ-based primary site was identified. Omental lymphoma was diagnosed at ultrasonography-guided biopsy. (26) Contrast-enhanced CT scan shows extensive peritoneal soft-tissue infiltration with omental cak-ing and diffuse mesenteric thickening. Note also the presence of lymphadenopathy (arrowheads).

Figure 27. Leukemic infiltration in a woman with acute lymphocytic leukemia. Contrast-enhanced CT scansshow diffuse, irregular peritoneal thickening (arrowheads) and ascites. Uterine involvement is also present (* in b).

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Figures 28, 29. Granulocytic sarcoma (chloroma). (28) Contrast-enhanced CT scan ob-tained in a patient with acute myelogenous leukemia shows extramedullary peritoneal in-volvement consisting of a focal mesenteric mass in the ileocecal region (arrow). (29) Con-trast-enhanced CT scan obtained in a different patient with acute myelogenous leukemiashows extensive and diffuse peritoneal involvement.

Figure 30. Extramedullary plasmacytomas in a patient with known multiple myeloma. Contrast-enhancedCT scans (a obtained cephalad to b) show multiple peritoneal and retroperitoneal soft-tissue masses. Renal,adrenal, and pancreatic involvement are also seen.

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Extramedullary plasmacytoma can occur eitherwith or without known underlying multiple my-eloma of the marrow space. The retroperitoneumis a more common site of extramedullary involve-ment by plasmacytoma than the peritoneum, in-volvement of which is quite rare (Fig 30). In fact,peritoneal disease in these patients is perhaps justas likely to result from myeloma-associated amy-loidosis (AL type).

ConclusionsPrimary neoplasms arising from the peritoneumand subperitoneum occur much less frequentlythan metastatic peritoneal involvement from aknown or occult primary tumor. Nevertheless,these rare primary lesions should be considered inthe absence of a known or suspected organ-basedmalignancy. CT is useful not only for detection,characterization, and staging, but also for guidingbiopsy for tissue diagnosis.

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This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician’s Recognition Award. To obtaincredit, see accompanying test at http://www.rsna.org/education/rg_cme.html.