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2012 — September Case of the Month

Posted October 10, 2012

CLINICAL SUMMARY: Mediastinum  

CAP Foundation Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 45-year-old man presented with six month history of increasing cough and vague discomfort in the chest. A CT scan revealed a large anterior mediastinal mass compressing the heart. The mass was resected. The resected specimen consisted of an unencapsulated, well-circumscribed mass covered by smooth fibromembranous tissue and measuring 12.0 x 10.0 x 8.0 cm. On sectioning, the cut surfaces were yellow tan and lobulated.

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 30, and is low grade fibromyxoid sarcoma with giant collagen rosettes.

Criteria for Diagnosis and Comments:
Histologic sections of the mass show an admixture of hypocellular myxoid areas, hypercellular spindled cell areas in a collagenous background and large hyalinized collagen rosettes cuffed by a radial array of rounded cells with uniform nuclei. The spindled cells throughout the lesion are rather bland with monomorphic nuclei and form indistinct storiform patterns in some areas while in others they are arranged as fascicles. Mitotic figures are infrequent. In the myxoid areas, network of curvilinear and branching capillary sized blood vessels may be seen. These morphologic features are characteristic of low grade fibromyxoid sarcoma with giant collagen rosettes, also known as hyalinizing spindle cell tumor with giant rosettes.

Low grade fibromyxoid sarcoma (LGFMS), first described by Evans in 1987, is a relatively uncommon sarcoma characterized by a deceptively bland histologic appearance but with potential for recurrences and late metastases. A closely related tumor characterized by the additional presence of giant collagen rosettes was reported by Lane, et al., in 1997. Based on the shared clinical, morphologic, ultrastructural, immunohistochemical and cytogenetic features, hyalinizing spindle cell tumor with giant rosettes is now regarded as a variant of low grade fibromyxoid sarcoma.

Low grade fibromyxoid sarcoma occurs most commonly in young to middle aged adults and males are affected more commonly than females. The neoplasm presents typically as a slow growing painless mass in the deep soft tissues of lower extremities and less commonly in chest/axilla, shoulder region, inguinal region and neck. Other reported sites of involvement are the retroperitoneum, omentum, paravertebral region and the mediastinum.

On gross examination, LGFMS is typically well circumscribed and unencapsulated with an average size of 8.0 – 10.0 cm. On cut section, the tumor has yellow-white to tan appearance with areas of glistening that correspond to the myxoid areas. Necrosis and hemorrhage are not frequent findings.

The histologic appearance of LGFMS is characterized by low to moderate cellularity, composed of bland spindled cells with pale eosinophilic cytoplasm and small monomorphous nuclei embedded in a variably collagenous and myxoid stroma. The transition between the myxoid and fibrous areas may be abrupt or gradual. The myxoid areas contain curvilinear blood vessels. Large collagen rosettes cuffed by rounded cells as seen in the present case may be present in a significant percentage of cases.

Immunohistochemically, the cells in LGFMS stain strongly and diffusely for vimentin, and focally for muscle markers, suggestive of myofibroblastic differentiation. The cells are typically negative for β-catenin, CD34, desmin and cytokeratin. The rounded cells surrounding the collagen may be positive for S100 protein and neuron-specific enolase.

Cytogenetic studies of LGFMS including the variant with giant collagen rosettes have shown a characteristic balanced translocation involving the FUS gene on chromosome 7 and the CREBL2 gene on chromosome 16 in up to 96% of the cases. Commercial probes are available to test for the FUS gene by fluorescence in situ hybridization on formalin fixed paraffin embedded sections and can be of value in supporting the diagnosis of LGFMS.

The differential diagnosis of LGFMS includes a variety of benign and malignant soft tissue neoplasms that contain a fibrous and myxoid stroma. The most common ones are included in the master list. Desmoid tumors are typically composed of fascicles of spindled cells that have more vesicular and plumper nuclei than the cells of LGFMS. The cells are consistently positive for β-catenin. Malignant peripheral nerve sheath tumor may contain myxoid areas but the cells are typically wavy, arranged in irregular fascicles and stain for S100 protein in more than half of the cases. The myxoid zones and the curvilinear vascular pattern of LGFMS may mimic myxoid liposarcoma. Furthermore, myxoid liposarcoma may also show alteration of the FUS gene. However, myxoid liposarcoma contains lipoblasts and lacks the fibrous/collagenous component of LGFMS, features helpful in the differential diagnosis.

The most problematic differential diagnosis is between LGFMS and myxofibrosarcoma a neoplasm that belongs in the lower end of the spectrum of malignant fibrous histiocytoma. Unlike LGFMS which occurs in the deep soft tissues of young adults, myxofibrosarcoma typically occurs in the subcutaneous tissues of elderly patients. Histologically, myxofibrosarcoma is uniformly myxoid and lacks the alternating fibrous areas seen in LGFMS. Furthermore, myxofibrosarcoma invariably shows a greater degree of cytologic atypia and nuclear pleomorphism.

LGFMS with giant collagen rosettes should be differentiated from other tumors with giant collagen rosettes, in particular, schwannoma (neuroblastoma-like neurilemmoma) in which rosettes are made of core of collagen and surrounded by Schwann cells. Immunohistochemical studies with S100 protein show that both the spindled cells and those surrounding the collagen are positive for S100 protein in schwannoma whereas only the rounded cells surrounding the collagen are positive in LGFMS. In the differential diagnosis of intrathoracic LGFMS, solitary fibrous tumor should be considered in addition to other spindle cell proliferations. Alternating myxomatous and collagenous foci of LGFMS are not typical of solitary fibrous tumor. Additionally, diffuse positivity for CD34 seen in solitary fibrous tumor is not characteristic of LGFMS.

LGFMS and LGFMS with giant collagen rosettes are part of a histologic spectrum of a low grade sarcoma with bland histologic features but with a propensity for local recurrence and rarely metastasis. The treatment of choice is wide surgical excision with follow-up. Cytogenetics can be invaluable in differentiating LGFMS from other fibrous and myxoid proliferations.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which tumor exhibits consistent nuclear positivity for β-catenin? A. Desmoid tumor
B. Low grade fibromyxoid sarcoma with giant collagen rosettes
C. Malignant peripheral nerve sheath tumor
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Schwannoma
G. Solitary fibrous tumor
2. Which tumor lacks the alternating areas of myxoid and fibrous areas but is consistently positive for CD34? A. Desmoid tumor
B. Low grade fibromyxoid sarcoma with giant collagen rosettes
C. Malignant peripheral nerve sheath tumor
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Schwannoma
G. Solitary fibrous tumor
3. Which tumor is characterized by alternating areas of fibrous and myxoid zones, curvilinear blood vessels, alterations in FUS gene and absence of lipoblasts? A. Desmoid tumor
B. Low grade fibromyxoid sarcoma with giant collagen rosettes
C. Malignant peripheral nerve sheath tumor
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Schwannoma
G. Solitary fibrous tumor

References

  1. Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes. A clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol. 2000;Oct;24:(10):1353-1360.
  2. Jakowski JD, Wakely PE Jr. Primary intrathoracic low-grade fibromyxoid sarcoma. Hum Pathol. 2008;Apr;39:(4):623-628.
  3. Matsuyama A, Hisaoka M, Shimajiri S, et al. Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens. Am J Surg Pathol. 2006;Sep;30:(9):1077-1084.
  4. Reid R, de Silva MV, Paterson L, et al. Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation. Am J Surg Pathol. 2003;Sep;27:(9):1229-1236.
  5. Vernon SE, Bejarno PA, Low-grade fibromyxoid sarcoma. Arch Pathol Lab Med. 2006;Sep;130:1358-1360.
  6. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 5thed. St. Louis, MO: Mosby; 2008.
  7. Wu X, Petrovic V, Torode IP, Chow CW. Low grade fibromyxoid sarcoma: Problems in the diagnosis and management of a malignant tumor with bland histologic appearance. Pathology. 2009;Feb;41:(2):155-160.

Author:
2009
Vijaya B. Reddy, MD FCAP
Surgical Pathology Committee
Rush University Medical Center
Chicago, IL