Case 5 -

Leiomyoma Scott Kilpatrick

Clinical History: The patient is a 43-year-old female with a large retroperitoneal mass. She underwent resection of the mass and a hysterectomy. The hysterectomy revealed adenomyosis and a single 1.5 cm subserosal leiomyoma. Diagnosis: Leiomyoma. Leiomyoma (LM) of deep soft tissue usually arises in young to middle aged adults; there is no sex predilection. [1] The extremities represent the most common anatomic location, followed by the pelvis and retroperitoneum. Diagnosis of the latter is dependent upon such tumors being clearly distinct from the uterus. [2] Painless soft tissue swelling is the most common clinical compliant. Intra-abdominal tumors may be associated with intestinal obstruction and/or urinary symptoms. LM of deep soft tissue are typically well-circumscribed lesions, ranging from small tumors (2 cm) to huge abdominal masses, measuring up to 37 cm in greatest dimension. [3] They are typically composed of well-differentiated and mature smooth muscle cells, containing ovoid to blunt-ended, cigar-shaped nuclei and abundant tapering eosinophilic cytoplasm, arranged in interlacing fascicles and bundles, often intersecting at perpendicular angles. Significant nuclear pleomorphism is not present, although some nuclei may appear enlarged with a smudgy chromatin pattern (ancient change). By definition, mitotic activity is scant with usually fewer than 1 mitosis per 50 high power fields. [1, 2] Degenerative changes, most prominent centrally within the lesion, may include extensive hyalinization, dystrophic microcalcifications, and myxoid areas. As expected, the tumor cells show at least focal positivity for actin, smooth muscle actin, and desmin. S-100 protein is typically negative. Intra-abdominal and retroperitoneal LM are frequently positive for estrogen and progesterone receptors, while those that arise in the deep somatic soft tissues of the extremities and trunk do not express these markers. [2, 3] Complete excision of LM usually results in cure. Local recurrence is rarely observed. Obviously, the most important differential diagnosis is leiomyosarcoma (LMS). LMS involving deep soft tissues generally occurs in middle aged to older adults. The most common anatomic site is the retroperitoneum, and some intra-abdominal forms arise from large blood vessels, principally the inferior vena cava. [4] When LMS arises within the retroperitoneum, women are more commonly affected than men. In other sites, this female predilection is not observed. [5] Most patients present with soft tissue swelling or mass effect. Morphologically, LMS may appear deceptively circumscribed. Fascicles and bundles of well-demarcated smooth muscle cells intersect at perpendicular angles. Less frequent patterns include storiform arrangements, hemangiopericytoma-liked vascular patterns, nuclear palisading (mimicking nerve sheath tumors), and myxoid change. Degenerative changes, similar to those seen in LM, are often observed in large lesions. Nuclear pleomorphism is variable, ranging from minimal to marked, indistinguishable from so-called malignant fibrous histiocytoma. In low grade tumors, mitotic figures, may be scarce but tend to be easily found in higher grade examples. Unusual cytomorphologic features include epithelioid cytology, granular cytoplasmic changes, extensive cytoplasmic vacuolation, and abundant osteoclast-like giant cells. Immunohistochemically, LMS generally express one or more markers of smooth muscle differentiation, including actin, smooth muscle actin, desmin, or h-caldesmon. Less frequently, focal positivity may be observed with S-100 protein, CD117, cytokeratin (rarely diffuse), and EMA. Cytogenetic analyses of LMS have revealed complex karyotypic changes, but no specific chromosomal abnormality has yet been identified. [6] Adverse prognostic indicators include localization within the retroperitoneum and large tumor size (>10 cm). In the extremities, older age (>62 years), FNCLCC grade 3, tumor size >4 cm, localization in deep soft tissues, and disruption portend a worse clinical outcome. [5] Small superficially-located tumors arising within the extremities are more amenable to surgical resection and, therefore, less likely to recur locally. The distinction between low grade LMS and LM may be very difficult. Based on solid data and reported biologic outcome, most regard the presence of atypia and any level of mitotic activity as diagnostic of LMS. [1, 5] Among retroperitoneal tumors, estrogen and progesterone receptor studies may be very helpful, as LM are typically positive but LMS are usually negative. By light microscopy, high grade, pleomorphic LMS may be indistinguishable from so-called malignant fibrous histiocytoma. To establish the diagnosis of pleomorphic LMS, I require the presence, at least focally, of definite leiomyosarcomatous fascicles and positivity for one or more muscle markers (e.g. actin, smooth muscle actin, or desmin). [7] Kilpatrick SE, Mentzel T, Fletcher CDM. Leiomyoma of deep soft tissue: clinicopathologic analysis of a series. Am J Surg Pathol 1994;18:576-582. Billings SD, Folpe AL, Weiss SW. Do leiomyomas of deep soft tissue exist? An analysis of highly differentiated smooth muscle tumors of deep soft tissue supporting two distinct subtypes. Am J Surg Pathol 2001;25:1134-1142. Paal E, Miettinen M. Retroperitoneal leiomyomas: a clinicopathologic and immunohistochemical study of 56 cases with a comparison to retroperitoneal leiomyosarcomas. Am J Surg Pathol 2001;25:1355-1363. Hines OJ, Nelson S, Quinones-Baldrich WJ, et al. Leiomyosarcoma of the inferior vena cava: prognosis and comparison with leiomyosarcoma of other anatomic sites. Cancer 1999;85:1077-1083. Farshid G, Pradham M, Goldblum J, et al. Leiomyosarcoma of somatic soft tissues: a tumor of vascular origin with multivariate analysis of outcome in 42 cases. Am J Surg Pathol 2002;26:14-24. Mandahl N, Fletcher CD, Dal Cin P, et al. Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group. Cancer Genet Cytogenet 2000;116:66-73. Oda Y, Miyajima K, Kawaguchi K, et al. Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma. Am J Surg Pathol 2001;25:1030-1038.