So-Called “Inflammatory Leiomyosarcoma”: A Series of 3 Cases Providing Additional Insights into a Rare Entity

Abstract

Inflammatory leiomyosarcoma, a rare entity first described in 1995, has been characterized by smooth muscle differentiation, a near-haploid karyotype, and a surprisingly good prognosis. The morphology is similar to that of conventional leiomyosarcoma admixed with a chronic inflammatory infiltrate. Thus far, only 15 cases have been reported in the English language literature. We report the clinical and pathological features of 3 additional cases of inflammatory leiomyosarcoma. Two women (ages 64 and 25, respectively) and 1 man (age 32) presented with a thigh, ovary, and lung mass, respectively. Inflammatory symptoms, such as anorexia, fever, night sweats, abdominal pain, and diarrhea, coincided with the thigh and ovarian primaries. Immunohistochemical studies revealed diffuse positivity for desmin and poor expression for other smooth muscle and skeletal muscle markers (muscle-specific actin [0/3], alpha-smooth muscle actin 1/3 [focal], calponin [1/3], caldesmon [0/3], and myogenin [0/3]). CD68 was diffusely positive in both the histiocytes and spindle cell component in all cases. Ultrastructural evaluation of 1 case (lung primary) lacked definitive smooth muscle differentiation. Cytogenetic analysis in 1 of 2 cases that were karyotyped, identified a near-haploid karyotype, which has been reported in other cases of inflammatory leiomyosarcoma. The other case showed 2 clonal populations of cells with interstitial deletions of the short arm of chromosome 8 and the long arm of chromosome 9, respectively. The case without cytogenetic data was intimately associated with an ovarian mature teratoma. These data also suggest that inflammatory leiomyosarcoma may lack smooth muscle differentiation, characterized by diffuse immunoreactivity for desmin but lack of immunoreactivity for alpha-smooth muscle actin, calponin, and caldesmon. In addition, 2 of the 3 cases developed distant metastases to the lungs, which suggests that these lesions may have a worse prognosis than previously believed.

Transgelin is a novel marker of smooth muscle differentiation that improves diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical reappraisal of myogenic markers in 900 soft tissue tumors

“…The latter are known to show only focal expression of actin and/or h-caldesmon, yet significant reactivity for desmin. 21,22 Out of the five markers covered in this study, only h-caldesmon appears to be specific to true smooth muscle differentiation, confirming the results of previous studies. 6,7 Actin is nonspecific and is found in a subset of rhabdomyosarcomas, 23,24 and in one pleomorphic rhabdomyosarcoma in this study.…”

Inflammatory leiomyosarcoma is a distinct tumor characterized by near-haploidization, few somatic mutations, and a primitive myogenic gene expression signature

“…Including the 4 new cases presented here, there are now 10 reported inflammatory leiomyosarcomas with confirmed near-haploidization (refs 2-4 and present study), the clinical features of which seem to be distinct from those in other forms of leiomyosarcoma. First, there is a skewed sex distribution, with only one woman among the inflammatory leiomyosarcoma cases; 4 this feature was not observed in the first report of inflammatory leiomyosarcoma. 1 Second, inflammatory leiomyosarcoma patients are younger, median age 41 years (range, 18-64 years), than conventional leiomyosarcoma patients.…”

“…In six of the cases, massive reduction of the chromosome number to a hyperhaploid level (25-28 chromosomes), with or without subsequent polyploidization, was found to constitute an early step in tumorigenesis. [2][3][4] Furthermore, the copy number distribution of individual chromosomes in inflammatory leiomyosarcoma is clearly nonrandom with all six cases with a hyperhaploid origin showing retained biparental disomy for chromosomes 5 and 22, and often also for chromosomes 18, 20, and 21. 2 Nord et al 2 also performed global gene expression analysis on 3 inflammatory leiomyosarcomas and 15 leiomyosarcomas and found that these tumors have distinct transcriptional profiles, and that genes located on the disomic chromosomes are expressed at higher levels than genes on the monosomic chromosomes.…”

Genome-wide acquired uniparental disomy as well as chromosomal gains and losses in an uterine epithelioid leiomyoma

“…both chromosomes 12 with secondary duplication of the chromosome complement. The occurrence of near haploid karyotypes has been observed in a variety of solid tumors including leiomyosarcomas [7] as well as in leukemias [8]. Also, copy-number-neutral LOH affecting more or less large segments has been observed in many cancers [9].…”