Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis

Abstract

Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

Figure 1

Cutaneous smooth muscle hamartoma contains a continuous streak of pilar smooth muscle involving mid to deep dermis and subcutis.

Figure 2

Pilar leiomyoma (here seen in the context of HLRCC syndrome) consist of dermal smooth muscle proliferation originating from pilar smooth muscle and forming coalescent nodules, often without much atypia.

Figure 3

Kidney cancer in hereditary leiomyomatosis shows an esosinophilic cells in a papillary pattern with large nuclei and prominent nuceoli (so-called renal papillary carcinoma type 2).

Figure 4

Angioleiomyoma. (a) A solid pattern. (b) Example originating from vein wall. (c) Focal atypia. (d) Examples with lipomatous components should not be confused with angiomyolipoma.

Figure 5

Mullerian leiomyoma of soft tissues shows patterns similar to uterine leiomyoma. (a) Macrotrabecular. (b) Microtrabecular. (c) Example with mildly myxoid stroma. (d) Lipoleiomyoma with a mature fatty component.

Figure 6

Mullerian leiomyomas are characterized by nuclear estrogen receptor-positivity, as seen in uterine leiomyomas. These tumors show similar WT1-positivity.

Figure 7

Peritoneal leiomyomatosis can form numerous smooth muscle nodules on the peritoneal surfaces.

Figure 8

Examples of leiomyosarcoma. (a) Example composed of uniform cells with blunt-ended nuclei with mild general atypia and high mitotic activity. (b) Focal nuclear pleomorphism is a common feature even in low-grade tumors. (c) Example with transition into a pleomorphic sarcoma (‘dedfifferentiated leiomyosarcoma’). (d) Extensively pleomorphic leiomyosarcoma, which would be difficult to recognize unless for differentiated areas elsewhere in the tumor.

Figure 9

Esophageal leiomyoma is composed of bland smooth muscle cells, some of which contain eosinophilic inclusions that are typically desmin-positive.

Figure 10

KIT-positive Cajal may colonize gastrointestinal leiomyomas, and this should not lead into confusion with a GIST.

Figure 11

Muscularis mucosae leiomyoma forms a polypoid colonic lesion immediately adjacent to the mucosa. (a) Low magnification. (b) High magnification.

Figure 12

EBV-associated smooth muscle tumor. (a) This tumor forms an eccentric intramural appendiceal mass. (b) These smooth muscle tumors are often composed of oval cells that appear less mature than typical smooth muscle cells. The tumor cells are positive for SMA but only variably positive for desmin. Nuclear positivity for Epstein–Barr virus RNA is a typical finding.