Retroperitoneum

A 22-year-old man with a history of colectomy presents with abdominal pain. Physical exam shows a palpable abdominal mass, which is confirmed by a computed tomography (CT) scan that shows a 12-cm retroperitoneal lesion. The mass is excised; however, the surgeon expresses concern that adequate margins are not achieved. By immunohistochemistry, the mass is negative for CK AE1/AE3, MUC4, MDM2, and ALK1 and shows nuclear staining for beta-catenin.

Master List of Diagnoses:

  • Dedifferentiated liposarcoma
  • Desmoid fibromatosis
  • Inflammatory myofibroblastic tumor
  • Low-grade fibromyxoid sarcoma
  • Sarcomatoid carcinoma
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Archive Case and Diagnosis

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 06, and is desmoid fibromatosis of the retroperitoneum. The information provided in this case was accurate and correct at the time of publication in 2021. Any changes in terminology since the time of publication may not be reflected in this case.

Criteria for Diagnosis and Comments

Sections of the retroperitoneal mass show a bland, homogeneous, moderately cellular spindle cell neoplasm with a fibromyxoid background. The cells form long, broad fascicles, and the slender nuclei appear to aim purposefully in the same direction in a “school of fish” configuration. The blood vessels are mostly thin-walled and slightly dilated. Margins are not visible in these sections, but the tumor is poorly demarcated. The clinical, histologic, and immunohistochemical findings are most consistent with desmoid fibromatosis.

There are several forms of superficial and deep soft tissue fibromatosis. The latter, which includes abdominal desmoid tumors, are the most likely to cause patient morbidity and mortality. These are slow-growing but locally aggressive tumors that spread in an irregular fashion, making complete surgical excision difficult or impossible. Most cases recur repeatedly over time, though they do not metastasize. Deep (desmoid-type) fibromatosis generally occurs in the abdominal wall, mesentery, or retroperitoneum, but it can also arise in the shoulder/chest region.

Desmoid fibromatosis accounts for a small percentage of soft tissue tumors, and it typically occurs in the fourth or fifth decades. The median size ranges from 8 to 10 cm. It may occur sporadically (where it has a female predominance) but is also often seen in patients with Gardner syndrome (where it has a male predominance). This variant of familial adenomatous polyposis is caused by germline APC mutation and manifests as innumerable colonic adenomas (likely the reason for colectomy in this young patient), along with osteomas, Gardner-associated fibromas, and desmoid fibromatosis. Activating mutations in exon 3 of CTNNB1 (which encodes for beta-catenin) may also be found in these tumors.

The most classic immunohistochemical finding in desmoid fibromatosis is nuclear (rather than membranous) beta-catenin staining. Patchy smooth muscle actin staining can also be observed.

In addition to surgical excision, sorafenib has recently been shown to improve progression-free survival in patients with advanced tumors.

Dedifferentiated liposarcoma also occurs in the retroperitoneum. A classic component of well-differentiated liposarcoma can usually be identified. No such component was observed in the current case. The dedifferentiated component is often highly atypical but can show a variety of morphologies. MDM2 amplification is seen in these tumors and can be demonstrated by fluorescence in situ hybridization. Additionally, immunostaining for MDM2 and CDK4 is positive.

Inflammatory myofibroblastic tumor can arise anywhere in the body. In addition to a bland spindle cell proliferation, a prominent inflammatory component (including lymphocytes and plasma cells) should be evident, unlike in the current case. About half of cases are positive for ALK1 by immunohistochemistry and correspondingly show ALK1 fusions with a variety of partners.

Low-grade fibromyxoid sarcoma is a rare, slow-growing soft tissue malignancy that can reach a large size and typically arises in the extremities. In contrast to desmoid fibromatosis, it does not have a high rate of local recurrence, but it can metastasize decades after original presentation. Histologically, the fibrous and myxoid regions appear somewhat distinct, imparting a zonal appearance to the malignancy. The spindle cells are bland and may be arranged in a fascicular or storiform pattern. MUC4 immunohistochemistry is positive, and the majority show a t(7;16) FUS::CREB3L2 fusion.

Sarcomatoid carcinoma would not be expected to arise primarily in the retroperitoneum, though it could metastasize there. Histology is highly variable but generally sarcomatoid. Immunohistochemical evidence of carcinomatous differentiation would be necessary to confirm this diagnosis. The negative CK AE1/AE3 in the current case makes sarcomatoid carcinoma unlikely, though if the diagnosis were suspected, additional keratin stains should be employed

  1. Immunohistochemical positivity for which of the following markers is most consistent with desmoid fibromatosis?

    1. Beta-catenin (nuclear)
    2. CD34
    3. CK AE1/AE3
    4. MUC4
    5. Smooth muscle actin
  2. Which of the following is true regarding desmoid fibromatosis?

    1. Advanced disease does not respond to adjuvant therapy.
    2. It commonly metastasizes to the lungs.
    3. It commonly recurs following excision.
    4. It only arises in patients with familial adenomatous polyposis.
    5. It typically occurs in teenaged patients.
  3. A t(7;16) FUS::CREB3L2 fusion is most indicative of what neoplasm?

    1. Desmoid fibromatosis
    2. Inflammatory myofibroblastic tumor
    3. Low-grade fibromyxoid sarcoma
    4. Low-grade myxofibrosarcoma
    5. Synovial sarcoma

References

  1. Antonescu CR, Suurmeijer AJ, Zhang L, et al. Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement. Am J Surg Pathol. 2015;39(7):957-967.
  2. Cates JM, Stricker TP. Surgical resection margins in desmoid-type fibromatosis: a critical reassessment. Am J Surg Pathol. 2014;38(12):1707-1714.
  3. Dantey K, Schoedel K, Yergiyev O, Bartlett D, Rao UNM. Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas. Hum Pathol. 2017;66(8):86-92.
  4. Doyle LA, Möller E, Dal Cin P, Fletcher CD, Mertens F, Hornick JL. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol. 2011;35(5):733-741.
  5. Goldstein JA, Cates JM. Differential diagnostic considerations of desmoid-type fibromatosis. Adv Anat Pathol. 2015;22(4):260-266.
  6. Gounder MM, Mahoney MR, Van Tine BA, et al. Sorafenib for advanced and refractory desmoid tumors. N Engl J Med. 2018;379(25):2417-2428.

Answer Key

  1. Beta-catenin (nuclear) (a)
  2. It commonly recurs following excision (c)
  3. Low-grade fibromyxoid sarcoma (c)