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2009 — December Case of the Month

Updated November 24, 2009

CLINICAL SUMMARY: LEFT THIGH  

CAP Foundation December 2009 Online Case of the Month

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

An otherwise healthy 57-year-old woman presented with a painless, palpable, firm, slightly movable mass on the medial aspect of the left thigh. Magnetic resonance imaging revealed a well-defined tumor with low signal intensity relative to the surrounding skeletal muscle on T1-weighted images and hyperintense signal relative to muscle on T2-weighted images. Received was a 8.0 x 6.8 x 4.4 cm portion of skeletal muscle containing a well-circumscribed 4.7 x 3.8 x 2.5 cm tumor with a uniform yellow-white cut surface.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2006, Case 36 and is an Intramuscular myxoma.

Criteria for Diagnosis and Comments: The diagnosis is intramuscular myxoma. This benign neoplasm was first described by Dr. Franz Enzinger in 1965. It has been described in patients aged 20 to 89 years, although most are between 40 and 70 years. Approximately two-thirds of the patients are female. Almost half the tumors are located in the thigh and range in size from 2.0 to 15.0 cm (average 5.6 cm).

Grossly, intramuscular myxomas are oval or spherical in shape and appear well-encapsulated. The cut surface is mostly solid, somewhat lobulated, and greasy. These tumors consist of three main histologic components: interstitial mucin, sparse spindle-shaped stromal cells, and fine fibrillary reticulin fibers that vary in number and distribution. Immunohistochemically, the cells are anti-vimentin immunoreactive but fail to stain for S-100 protein. The mucoid material is composed of hyaluronic acid and stains positively with alcian blue, mucicarmine, and colloidal iron.

Intramuscular myxoma is most commonly a solitary lesion. When they occur in association with fibrous dysplasia (Mazabraud's syndrome), they may be either multiple or solitary. Multiple tumors are seen in McCune-Albright syndrome and exist concurrently with polyostotic fibrous dysplasia, café-au-lait spots, and endocrine hyperfunction (most commonly precocious puberty). Rarer associations of intramuscular myxoma have been reported with the development of osteogenic sarcoma in the setting of Mazabraud's syndrome.

Extraskeletal myxoid chondrosarcoma affects adult men greater than women and is also typically found in the thigh. Local recurrence and late metastasis is characteristic. The lesions are well-circumscribed and are composed of cords and nests of cells within a myxoid stroma consisting predominantly of chondroitin sulfate. Cartilage is present in less than ten percent of the cases. Recently, chromosomal rearrangements involving 9q22, such as t(9:22)(q22;q12) have been described. These result in NR4A3 fusion genes that are present in greater than 90% of these tumors.

Low-grade fibromyxoid sarcoma is a rare malignant neoplasm that is typically situated in the deep soft tissues of adults, but may be seen in the trunk or retroperitoneum. Histologically, it consists of cellular areas with spindle-shaped cells that alternate with dense fibrous tissue and hypocellular myxoid nodules. They appear reasonably circumscribed but possess micro-infiltrative margins. Mitoses are rare and often there is swirling configuration of the tumor cells around small arcing blood vessels. By cytogenetic and molecular genetic analyses these lesions are now known to have a t(7;16) (q32-34;p11) balanced translocation which in the vast majority of cases results in a FUS/CREB3L2 fusion gene. In a subset of cases a variant FUS/CREB3L1 has been recognized.

Myxoid liposarcoma occurs most commonly in the extremities, specifically the thigh. It is more cellular than intramuscular myxoma with spindle-shaped to plump stellate cells, some of which may show mild cytologic atypia. A plexiform capillary pattern is characteristic, and well-differentiated lipoblasts help to identify this entity. Mitoses are rare in this well circumscribed/pseudo-encapsulated lesion. Soft tissue metastases may evolve.

Myxofibrosarcoma is a locally aggressive tumor and occurs predominantly in older adults. Approximately 70% are situated in the subcutis of the extremities. Histologically, low grade lesions which are in the differential diagnosis of intramuscular myxoma, are hypocellular, consisting of spindle cells within an abundant myxoid background. In comparison to intramuscular myxoma, the nuclei are usually more hyperchromatic and exhibit more cytologic atypia. Curvilinear vessels are a characteristic feature of this poorly demarcated neoplasm.

Nerve sheath myxoma tends to affect the extremities of men and women over a broad age range. It characteristically forms superficial, multilobular masses with myxoid stroma. The lesional cells are spindled, stellate, or epithelioid Schwann cells. The epithelioid Schwann cells typically have a corded arrangement or are grouped into syncytial-like aggregates. Fibrous bands surround the lobules and outer border of the lesion. This lesion is usually S100 protein and GFAP immunoreactive.

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
Which tumor is characterized by myxoid stroma that is chondroitin sulfate-rich instead of hyaluronic acid-rich and shows chromosomal rearrangements involving 9q22 resulting in NR4A3 fusion gene? A. Extraskeletal myxoid chondrosarcoma
B. Intramuscular myxoma
C. Low-grade fibromyxoid sarcoma
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Nerve sheath myxoma
Which lesion prefers the extremities and is S-100 protein immunoreactive? A. Extraskeletal myxoid chondrosarcoma
B. Intramuscular myxoma
C. Low-grade fibromyxoid sarcoma
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Nerve sheath myxoma
Which lesion may be associated with precocious puberty and fibrous dysplasia? A. Extraskeletal myxoid chondrosarcoma
B. Intramuscular myxoma
C. Low-grade fibromyxoid sarcoma
D. Myxofibrosarcoma
E. Myxoid liposarcoma
F. Nerve sheath myxoma

References

  1. Allen P. Myxoma Is Not a Single Entity: A Review of the Concept of Myxoma. Ann Diagn Pathol. 2000;4:99-123.
  2. Evans H. Low-grade Fibromyxoid Sarcoma. A Report of Twelve Cases. Am J Surg Pathol. 1993;17:595-600.
  3. Fetsch JF, Laskin WB, Miettinen M. Nerve sheath myxoma: a clinicopathologic and immunohistochemical analysis of 57 morphologically distinctive, S100 protein- and GFAP-positive, myxoid peripheral nerve sheath tumors with a predilection for the extremities and a high local recurrence rate. Am J Surg Pathol. 2005;29:1615-1624.
  4. Graadt van Roggen J, Hogendoorn P, Fletcher C. Myxoid Tumors of Soft Tissue. Histopathol. 1999;35:291-312.
  5. Hisaoka M, Hashimoto H. Extraskeletal Myxoid Chrondrosarcoma: Updated Clinicopathological and Molecular Genetic Characteristics. Pathol Internat. 2005;55:453-463.
  6. Mertens F, Fletcher CD, Antonescu CR, et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest. 2005;85(3):408-415.
  7. Lopez-Ben R, Pitt M, Jaffe K, Siegal G. Osteosarcoma in a Patient with McCune-Albright Syndrome and Mazabraud's Syndrome. Skeletal Radiol. 1999;28:522-526.
  8. Pasquier B, Barnoud R, Penc'h M. et al. Neurothekeoma. General Review Apropo of an Anatomoclinical Case with Immunohistochemical and Ultrastructural Study. Arch Anat Cytol Pathol. 1994;42:133-140.
  9. Witkin G, Guilford W, Siegal G. Osteogenic Sarcoma and Soft Tissue Myxoma in a Patient with Fibrous Dysplasia and Hemoglobins J (Baltimore) and S. Clin Orthop Relat Res. 1986;204:245-252.
  10. Weiss S, Goldblum J. Benign Soft Tissue Tumors and Pseudotumors of Miscellaneous Type in Enzinger and Weiss's Soft Tissue Tumors (4th Ed.). St. Louis, MO, Mosby; 2001:1419-1481

Author:
2006
J. Alan Long, MD
Co-Chief Resident
University of Alabama at Birmingham
Birmingham, AL

Gene P. Siegal, MD, PhD
Surgical Pathology Committee
University of Alabama at Birmingham
Birmingham, AL