This is the malignant counterpart of the leiomyoma. In spite of this, it is distinctly uncommon for this tumor to arise from a leiomyoma. In addition to the usual morphological criteria of smooth muscle cells, a combination of nuclear atypia, cellularity, and mitotic figures all combine to make the diagnosis. Like leiomyomas, they occur in all locations in the soft tissue and in virtually all organs. The majority of these tumors in the soft tissue occur in the thigh.
Pathogenesis Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ALTERATIONS
Loss of 13q14-q21 and gain of 5p14-pter in the progression of leiomyosarcoma.
Wang R, Titley JC, Lu YJ, Summersgill BM, Bridge JA, Fisher C, Shipley J.
Molecular Cytogenetics, Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Mod Pathol. 2003 Aug;16(8):778-85. Abstract quote
Leiomyosarcomas of soft tissues are an aggressive group of tumors with a high incidence of recurrence. Little is known about the molecular genetic changes associated with clinical outcome.
Therefore, we studied 28 leiomyosarcoma samples of similar grade using comparative genomic hybridization and DNA flow cytometry and identified a difference in survival time associated with ploidy status and the number of chromosomal aberrations. The average survival time was shown to decrease with increase in chromosomal aberrations identified using comparative genomic hybridization. The average survival time was shorter in the near-tetraploid group than in the diploid and triploid group. Gain of 5p14-pter was significantly more common in near-tetraploid tumors. The survival time of patients with near-tetraploidy together with gain of 5p14-pter was reduced, and 50% died within the 1st year. Furthermore, loss of 13q14-q21 was significantly more frequent in the <5-year than in the >5-year survival group (P =.01).
These results suggest that 13q14-q21 loss and 5p14-pter gain at diagnosis could be used to identify patients with leiomyosarcoma who are likely to have a shorter survival time and who might benefit from early treatment intensification.
Gene expression analysis of human soft tissue leiomyosarcomas.
Ren B, Ping Yu Y, Jing L, Liu L, Michalopoulos GK, Luo JH, Rao UN.
Hum Pathol. 2003 Jun;34(6):549-58 Abstract quote
Leiomyosarcoma of the somatic soft tissue is a rare malignant mesenchymal neoplasm that metastasizes to other organs in a subset of cases. Much remains to be learned about the mechanisms underlying the development of aggressive behavior of this tumor. It has been difficult to predict the clinical behavior of leiomyosarcomas using the morphology-based grading system, even though tumor size and histological grade have correlated with biologic behavior in some studies.
In this study we analyzed the gene expression patterns of 35 samples of mesenchymal origin, including 11 cases of leiomyosarcomas of different histological grades arising in soft tissue and the retroperitoneum, using the Affymetrix U133a chips, which contain more than 22,000 genes and expression sequence tags (ESTs).
We identified a set of genes whose expression was commonly altered in all leiomyosarcoma samples. In addition, we identified specific gene expression patterns in several subsets of the tumor. We used these alterations of gene expression to subclassify the leiomyosarcomas into 3 groups. Interestingly, the grouping of these samples correlated well with tumor differentiation and clinical aggressiveness. The analysis identified 92 genes that distinguish low-grade, well-differentiated leiomyosarcomas from less well-differentiated, high-grade, and metastatic leiomyosarcoma. Thesse alterations of gene expression appear to be correlated with the clinical behavior and histological grade of the tumor.
The striking differences in terms of gene expression pattern among leiomyosarcomas of different differentiation status and clinical aggressiveness imply that several genetic abnormalities are responsible for the genesis and progression of this tumor.
CHARACTERIZATION General VARIANTS GALLBLADDER
- Polypoid leiomyosarcoma of the gallbladder: study of a case associated with adenomyomatous hyperplasia.
Perez-Montiel D, Mucientes F, Spencer L, Klaassen R, Suster S.
Department of Pathology, Division of Anatomic Pathology, The Ohio State University, Columbus, USA.
Ann Diagn Pathol. 2004 Dec;8(6):358-63. Abstract quote
A case of polypoid leiomyosarcoma of the gallbladder arising in association with pre-existing adenomyomatous hyperplasia is described. The patient, a 34-year-old woman with symptoms of cholelithiasis, underwent a cholecystectomy for gallstones. The resected specimen showed, in addition to multiple stones, a large, rubbery, broad-based polypoid mass in the fundus.
Histologic examination showed a malignant spindle cell proliferation with immunophenotypic features of smooth muscle differentiation. The base of the lesion showed features of adenomyomatous hyperplasia.
The possible relationships of this lesion with adenomyomatous hyperplasia and other stromal lesions of the gallbladder are reviewed.
HEAD AND NECK
Sinonasal smooth muscle cell tumors: a clinicopathologic and immunohistochemical analysis of 12 cases with emphasis on the low-grade end of the spectrum.
Huang HY, Antonescu CR.
Department of Pathology, Chang Gung Memorial Hospital, Kaoshiung Medical Center, Niao-Sung, Kaoshiung Hsien, Taiwan.
Arch Pathol Lab Med 2003 Mar;127(3):297-304 Abstract quote
CONTEXT: Smooth muscle tumors (SMTs) of the sinonasal tracts are very rare mesenchymal neoplasms, and the literature includes very limited data correlating histologic parameters with clinical outcome. As the behavior of SMTs is site-dependent, defining applicable criteria to distinguish among low-grade leiomyosarcoma, SMT of uncertain malignant potential (SMTUMP), and cellular leiomyoma is sometimes difficult and arbitrary.
OBJECTIVE: To correlate the clinicopathologic features of 12 well-differentiated sinonasal SMTs with MIB-1 index and clinical outcomes so as to better classify this group of tumors.
DESIGN: Twelve cases of sporadic well-differentiated SMTs arising from the sinonasal tract were retrieved from both institutions. High-grade leiomyosarcomas were excluded from this analysis. The histologic parameters assessed included circumscription, mucosal ulceration, cellularity, nuclear atypia, mitotic count, necrosis, and destruction of adjacent bony structures. The histologic classification of these tumors was based on the guidelines for SMTs of deep soft tissues, using greater than 4 mitotic figures (MF)/10 high-power fields (HPF) to separate SMTUMP from leiomyosarcoma and the presence of 1 to 4 MF/10 HPF to distinguish between leiomyoma and SMTUMP. Immunostaining of MIB-1 index was performed in 7 cases with available material.
RESULTS: This study showed a 1:1.5 male-female ratio and a mean age of 40 years (range, 20-67 years). The most frequent symptoms were nasal stuffiness and/or epistaxis. The tumors involved nasal cavity in 8 cases (67%), paranasal sinus alone in 2 cases (16.5%), and both nasal cavity and paranasal sinuses in 2 cases (16.5%). The tumors ranged in size from 0.3 to 5.5 cm (mean, 2 cm) and were classified as follows: 7 leiomyomas, 2 SMTUMPs, and 3 low-grade leiomyosarcomas. All 7 leiomyomas, 1 SMTUMP, and 1 leiomyosarcoma originated from vessel walls. Bone involvement was seen in both the SMTUMPs (1 of 2) and leiomyosarcomas (2 of 3). Focal infiltrative growth was observed only in the 3 leiomyosarcomas, 1 of which also showed microscopic coagulative tumor necrosis. Mitotic figures ranged from 0 to 10 (mean, 2.3), with absence of mitosis in all 7 leiomyomas, 1 to 4 MF/10 HPF in the 2 SMTUMPs, and more than 4 MF/10 HPF in the 3 low-grade leiomyosarcomas. The MIB-1 index was low (<or=5%) in both leiomyoma and SMTUMP groups, while the leiomyosarcomas showed a higher (>or=15%) proliferative index. All 12 patients were treated by surgical excision, and only 1 patient with leiomyosarcoma received postoperative radiation. In all 12 tumors, there was neither local recurrence nor distant metastasis after an average of 93 months of follow-up (range, 4-221 months).
CONCLUSION: Well-differentiated sinonasal SMTs are rare and occur in adults with a slight female predilection. The lesions confined within the nasal cavity were more common than those involving a single paranasal sinus or both nasal cavity and paranasal sinuses. Despite variations in location, clinical manifestation, histologic features, and MIB-1 index, these tumors appear to follow a favorable course. Complete surgical excision appears to provide adequate treatment for these patients.
Leiomyosarcoma of the head and neck: a clinicopathological study.
Montgomery E, Goldblum JR, Fisher C.
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA, The Cleveland Clinic Foundation, Cleveland, OH, USA, The Royal Marsden NHS Trust, London, UK.
Histopathology 2002 Jun;40(6):518-25 Abstract quote
Leiomyosarcoma of the head and neck: a clinicopathological study
Aims: The behaviour of leiomyosarcoma is site-related and there are few data on such tumours located in the head and neck. We studied the clinicopathological features of these lesions.
Methods and results: Cases diagnosed as leiomyosarcoma of the head and neck were retrieved from the archives of three institutions. Immunohistochemistry was performed and follow-up information was obtained. There were seven men and six women, aged 21-73 years, and lesions involved the neck (n=3), maxilla (n=4), buccal area (n=3), and maxillary sinus, nose, and pharynx (n=1 each). Tumours ranged from 10 to 80 mm. All tumours showed at least focally typical histological features of leiomyosarcoma with perpendicularly arranged fascicles of smooth muscle cells with blunt-ended nuclei, eosinophilic cytoplasm and paranuclear vacuoles. They expressed muscle-specific actin (8/9), smooth muscle actin (7/9), and desmin (10/12). Follow-up information was available on nine patients. All had surgery, with radiation and/or chemotherapy in seven. Three (27%) recurred at 6-24 months; in one case twice. Five (56%) had metastases, including the three with prior recurrences at 1-128 months. Five (including two who received adjuvant therapy) were disease-free at a median of 47 months, one was alive with metastatic disease at 24 months), and three were dead of disease (median 13 months).
Conclusions: Head and neck leiomyosarcomas are rare and aggressive neoplasms which metastasize. Adjuvant therapy has limited effect.
Leiomyosarcoma of the Kidney: A Clinicopathologic Study
Deyrup, Andrea T MD, PHD*; Montgomery, Elizabeth MD†; Fisher, Cyril MD, DSC‡
From the *Department of Pathology, University of Chicago, Chicago, IL; †Department of Pathology, Johns Hopkins University, Baltimore, MD; and ‡Department of Histopathology, Royal Marsden Hospital, London, United Kingdom.
The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 178-182 Abstract quote
Leiomyosarcoma of kidney is a rare lesion for which limited data are available. Cases coded as leiomyosarcoma of the kidney from three institutions were reviewed.
These cases comprised 3 men and 7 women, 40 to 75 years of age. Immunohistochemistry was performed where possible and clinical follow-up information was obtained. On immunohistochemical staining, 6 of 6 tumors expressed smooth muscle actin, desmin, calponin, and h-caldesmon, and epithelial membrane antigen was positive in 1 of 5. Tumors were negative for cytokeratin and S-100 protein. Follow-up information was available for 9 patients. Two patients had metastases at diagnosis, four developed metastases, and two had recurrent disease. Five of 9 died of disease. Two patients were alive with no evidence of disease after 19 and 60 months, and 2 patients were alive with disease after 48 months and 56 months.
Comparing outcome with tumor grade, the one patient with grade 1 tumor was alive with no evidence of disease; of 5 patients with grade 2 tumor, 2 died of disease, 1 was alive with no evidence of disease, 1 was alive with disease, and 1 was alive with extensive disease; all 3 grade 3 patients died of disease.
In summary, the majority of renal leiomyosarcomas are intermediate or high grade with correspondingly poor prognosis.
- Smooth Muscle Tumors of the Ovary: A Clinicopathologic Study of 54 Cases Emphasizing Prognostic Criteria, Histologic Variants, and Differential Diagnosis.
Lerwill MF, Sung R, Oliva E, Prat J, Young RH.
From the *James Homer Wright Pathology Laboratories of the Massachusetts General Hospital and the Department of Pathology, Harvard Medical School, Boston, MA; and the daggerDepartment of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
Am J Surg Pathol. 2004 Nov;28(11):1436-1451. Abstract quote
We studied 54 ovarian smooth muscle tumors with an emphasis on histologic criteria for malignancy. Twenty-two leiomyomas were identified, including 7 typical, 11 cellular, 2 mitotically active, 1 with bizarre nuclei, and 1 myxoid. Follow-up ranging from 12 to 240 months (mean, 77.6 months) was available for 14 patients; all were alive with no evidence of disease.
Of 26 leiomyosarcomas, including 2 myxoid leiomyosarcomas, most were readily diagnosed by the presence of at least two of the following: moderate or severe cytologic atypia, mitotic rate >/=10 mitotic figures per 10 high power fields, and tumor cell necrosis. Some cytologically atypical tumors demonstrated lesser mitotic activity of 5 to 9 mitotic figures per 10 high power fields, in the absence of tumor cell necrosis. Sixty percent of these were clinically malignant, supporting a diagnosis of leiomyosarcoma in such tumors. Follow-up was available for 21 patients. Seventy-one percent developed recurrent disease at a mean of 19 months, and 62% died of their disease at a mean of 24 months. Four tumors were deemed of uncertain malignant potential, and two that were stage II both recurred in the pelvis. One case of ovarian intravenous leiomyomatosis had a benign outcome at 42 months, as did one case of ovarian leiomyoma with leiomyomatosis peritonealis disseminata at 180 months.
Overall, ovarian smooth muscle tumors encompass the same varied histologic spectrum as their uterine counterparts. The main tumors in the differential diagnosis are those in the fibroma/thecoma category, spindle cell carcinomas, and metastatic gastrointestinal stromal tumors.
Leiomyosarcoma of the Paratesticular Region A Clinicopathologic Study Cyril Fisher, M.D.; John R. Goldblum, M.D.; Jonathan I. Epstein, M.D.; Elizabeth Montgomery, M.D.
From the Departments of Pathology, the Royal Marsden NHS Trust, London, U.K. (C.F.); Johns Hopkins Hospital, Baltimore, Maryland (E.M., J.I.E.); and Cleveland Clinic Foundation, Cleveland, Ohio (J.R.G.), U.S.A.
Am J Surg Pathol 2001;25:1143-1149 Abstract quoteThe behavior of leiomyosarcoma (LMS) is site related, but there are limited data on such tumors presenting in the paratesticular region. Cases diagnosed as LMS of the paratesticular region from the files of three institutions were reviewed. Immunohistochemistry was performed in cases with available blocks, and follow-up information was obtained. From 31 cases originally diagnosed as LMS, 24 were retained after review. These were from men aged 34–86 years (mean 62 years; median 64 years) and involved the testicular tunica (10), spermatic cord (10), scrotal subcutis and dartos muscles (1 each), and the epididymis (1). Tumors ranged in size from 2–9 cm (mean 5 cm; median 4 cm). On immunohistochemical staining they expressed muscle-specific actin (13 of 14), smooth muscle actin (10 of 10), desmin (16 of 17), and CD34 (3 of 9); all of the latter three were strongly desmin-positive. Focal reactivity for cytokeratin (3 of 8) and S-100 protein (1 of 8) was seen. Follow-up information was available in 14 patients. Four (29%) had recurrences, in one case four times. Metastases to lymph nodes, lungs, or liver were seen in four patients (29%), of whom two had prior recurrences. Ten were alive with no evidence of disease (ANED), and four were dead of disease (DOD). Comparing outcome with tumor grade, all seven patients with grade 1 tumors (of whom two had recurrences) and all three with grade 2 tumors were ANED, whereas all four patients with grade 3 tumors were DOD.
In summary, paratesticular LMSs are rare neoplasms. The majority in this site are low-grade, although high-grade lesions behave aggressively.
- Leiomyosarcoma of the penis presenting as a cutaneous lesion.
Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.
- J Cutan Pathol. 2008 Jun;35(6):585-7. Abstract quote
We report a case of a 68-year-old man with cutaneous leiomyosarcoma of the penis.
Leiomyosarcoma of the penis is an extremely rare neoplasm that usually presents in middle to old age, and to our knowledge only approximately 30 cases have been reported in the literature to date.
This is an important diagnosis in the differential diagnosis of cutaneous spindle cell neoplasms of the male genital tract.
Leiomyosarcoma of the penis: a clinicopathologic study of 14 cases with review of the literature and discussion of the differential diagnosis.
Fetsch JF, Davis Jr CJ, Miettinen M, Sesterhenn IA.
Departments of Soft Tissue and dagger Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, DC.
Am J Surg Pathol. 2004 Jan; 28(1): 115-25. Abstract quote
SUMMARY: Primary leiomyosarcomas of the penis are very rare. To date, less than 30 have been documented in the English language literature.
In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 14 cases retrieved from our files. The patients ranged in age from 43 to 62 years (mean age, 51 years) at the time of initial surgical resection. The tumors involved the prepuce (n = 1), prepuce and distal shaft (n = 1), circumcision scar line (n = 2), circumcision scar line and distal shaft (n = 1), shaft (n = 5), base of the penis (n = 3), and penis, not otherwise specified (n = 1). The lesions ranged in size from 0.5 to 6.0 cm (median size, 1.5 cm) in greatest dimension. Nine tumors were superficially located, two were of indeterminate depth, and three were deep-seated. The superficial tumors were relatively asymptomatic, and seven were reportedly present for 1 year to more than 20 years (median duration, 5 years) before medical attention was sought. In contrast, one deep-seated lesion caused dysuria and difficulty voiding, prompting the patient to seek a clinical opinion within only a few months of the apparent onset.
Histologically, all tumors contained smooth muscle cells with both cytologic atypia and mitotic activity. Immunohistochemical studies were available for nine tumors, and immunoreactivity for desmin was present in all instances. All patients were initially treated with a local procedure. Follow-up information is available for 9 of the 14 patients (64%), with a median follow-up interval of 12 years 11 months. Three patients had multiple (two to four) local recurrences. Two of these patients were ultimately treated with a wide local excision or partial penectomy, and both were alive and well at last follow-up. In contrast, one patient, who had four local recurrences and refused a penectomy, developed a distant metastasis 10 months after the fourth recurrence.
The best predictors of outcome are tumor depth and tumor size. Superficial leiomyosarcomas of the penis are optimally managed by wide local excision whenever this is technically feasible. Tumors with a deep-seated component may require more aggressive intervention to ensure complete removal.
Leiomyosarcoma of urinary bladder following cyclophosphamide therapy: report of two cases.Tanguay C, Harvey I, Houde M, Srigley JR, Tetu B.Departments of Pathology, CHUQ (CT, IH, BT), Hotel-Dieu de Quebec, Laval University.
Mod Pathol 2003 May;16(5):512-4 Abstract quote
Leiomyosarcoma of urinary bladder is rare, although it is the most common mesenchymal tumor in adults. We report two cases of this tumor following cyclophosphamide therapy.
The first case is from a 53-year-old man with Wegener's granulomatosis treated for 6 years with cyclophosphamide. He presented with painless hematuria, and the initial biopsy of the bladder tumor revealed a malignant spindle cell neoplasm. A final diagnosis of leiomyosarcoma was made on radical cystoprostatectomy. The second example is from a 21-year-old man who had received cyclophosphamide in early infancy for a bilateral retinoblastoma. He also presented with painless hematuria, and a bladder tumor was resected transurethrally and diagnosed as leiomyosarcoma. He underwent partial cystectomy two months later.
Cyclophosphamide, when used for a neoplastic or non-neoplastic condition, is associated with an increased risk of developing bladder cancer. The distribution of histologic subtypes differs from that seen in spontaneous bladder tumors. A review of the literature shows an increased proportion of squamous cell carcinomas and sarcomas, especially leiomyosarcomas in cyclophosphamide exposed patients. Acrolein, a cytotoxic metabolite of cyclophosphamide excreted in urine, is regarded as the most likely causative agent.
Ann Diagn Pathol. 2005 Oct;9(5):259-66. Abstract quote
We describe 3 cases of leiomyosarcoma of the inferior vena cava (IVC) and review the literature describing clinicopathologic features of 211 cases and the outcome. Of these, 74% of the cases affected women with median age of 52 years.
The most common symptoms were abdominal pain or mass (57%), Budd-Chiari syndrome (17%), and deep vein thrombosis (4%). The most frequent site of tumor origin is the middle segment of the IVC (33%). Tumor size ranged from 2 to 38 cm (mean, 12 cm). Of the tumors with an assigned grade, 46% were high grade, 17% were intermediate grade, and 36% were low grade.
Of all patients, 47% underwent complete resection, 24% had complete resection with preoperative or postoperative chemotherapy and/or radiation, and 5% had palliative surgery. Tumor recurrence occurred in 40% of the patients (11% had local recurrence and 29% had metastasis). Perioperative mortality occurred in 4% of the cases. Of those patients who died, 42% died of the disease, 2% died of other causes, 26% were alive and free of the disease, 14% were alive with recurrent disease, and 11% were lost to follow-up. Tumors involving level 2 of the IVC have the best prognosis and tumors of level 1 have the worse prognosis.
Although there is no standardized criteria for the grading of extrauterine leiomyosarcoma, we propose to grade based on mitotic activity as follows: high grade, 10 or more mitoses per 10 high-power field (HPF); intermediate grade, 5 to 9 mitoses per 10 HPF; and low grade, 1 to 4 mitoses per 10 HPF.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Smooth muscle morphology by light microscopy Intersecting fascicles of spindle cells with abundant eosinophilic cytoplasm, centrally located, cigar-shaped or blunt ended nuclei Immunohistochemical evidence of smooth muscle differentiation Strong cytoplasmic positivity for desmin and/or alpha-smooth muscle actin Myxoid stroma Comprises at least 50% of the tumor by microscopic examination Mitoses At least 1 MF per 10 high power fields GIANT CELLS
Malignant gastrointestinal leiomyosarcoma and gastrointestinal stromal tumor with prominent osteoclast-like giant cells.
Insabato L, Di Vizio D, Ciancia G, Pettinato G, Tornillo L, Terracciano L.
Dipartimento di Anatomia Patologica, Facolta di Medicina, Universita Federico II, Napoli, Italy.
Arch Pathol Lab Med. 2004 Apr;128(4):440-3. Abstract quote
CONTEXT: One case of leiomyosarcoma and one case of gastrointestinal stromal tumor with prominent osteoclast-like giant cells have so far been reported in the digestive tract.
OBJECTIVE: To ascertain the clinicopathologic features and biologic behavior of these tumors, we report 3 additional cases of leiomyosarcoma of the gastrointestinal tract and one malignant gastrointestinal stromal tumor.
DESIGN: Histologic and immunohistochemical examinations were performed. Clinical and follow-up data were recorded, and the literature was reviewed.
RESULTS: The age of the patients ranged from 50 to 68 years (mean, 62 years). One of the lesions arose in the stomach, one in the ileum, and 2 in the colon. Three tumors showed a strong positivity for muscle actin and desmin and were diagnosed as leiomyosarcomas, 2 of them showing spindle cells and 1 of them showing epithelioid cells. The fourth tumor reacted strongly positive for c-Kit (CD117) and vimentin, and it was diagnosed as an epithelioid malignant gastrointestinal stromal tumor. All tumors were characterized by numerous osteoclast-like giant cells that were unevenly distributed and that, using immunohistochemistry, reacted strongly with CD68.
CONCLUSIONS: Malignant stromal tumors with osteoclast-like giant cells of the gastrointestinal tract are rare entities, are more commonly of a myogenic origin such as leiomyosarcoma, and seem to have an aggressive behavior.
Myxoid Leiomyosarcoma of Soft Tissue, an Underrecognized Variant Brian P. Rubin, M.D., Ph.D.; Christopher D. M. Fletcher, M.D., FRCPath
From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.
Am J Surg Pathol 2000;24:927-936 Abstract quoteMyxoid leiomyosarcoma is an uncommon tumor which, although previously well described in the uterus, is recognized to a lesser extent at other sites. We describe 18 cases of soft tissue leiomyosarcoma in which myxoid stroma occupied >50% of the tissue examined. Patients ranged in age from 22 to 84 years old (median, 57.5 yrs) and female patients outnumbered male patients 14 to 4. Tumor locations included the limbs (6 cases), female external genitalia (4 cases), head and neck region (3 cases), chest (2 cases), nipple, paratesticular soft tissue, and perineum (one case each). The tumors had a grossly gelatinous appearance and adopted three major histologic architectures: fascicular, reticular/microcystic, and ``myxofibrosarcoma-like.'' The tumor cells were predominantly spindled in all cases with typical features of smooth muscle differentiation; there was a mixture of spindle and epithelioid cells in one case. No cases with pure epithelioid cytology were seen. All tumors displayed immunoreactivity for smooth muscle markers (smooth muscle actin 16/17, desmin 8/18) and, in addition, four cases were positive for keratin CAM 5.2 and three for epithelial membrane antigen. The tumors had a tendency to be morphologically lower grade (9 tumors were grade I, 8 were grade II, and only 1 was grade III). Follow up was available in 13 patients with a duration of 8 months to 41 years (median, 39 mos), and revealed local recurrences (often repeated) in five cases and metastases in two cases. There were three tumor-related deaths, of which two were the result of uncontrolled local disease. The differential diagnosis of myxoid leiomyosarcoma is broad and encompasses both benign and malignant lesions.
Accurate diagnosis is critical because therapies may differ widely for entities in the differential diagnosis of myxoid leiomyosarcoma.
Leiomyosarcoma of Somatic Soft Tissues A Tumor of Vascular Origin With Multivariate Analysis of Outcome in 42 Cases Gelareh Farshid, M.B.B.S. ; Malcolm Pradhan, M.B.B.S. , Ph.D. ; John Goldblum, M.D. ; Sharon W. Weiss, M.D.
From the Division of Tissue Pathology, Institute of Medical and Veterinary Science (G.F.), Department of Health Informatics (M.P.), University of Adelaide, South Australia; the Department of Pathology (J.G.), Cleveland Clinic Foundation, Cleveland, Ohio; and the Department of Pathology and Laboratory Medicine (S.W.W.), Emory University Hospital, Atlanta, Georgia, U.S.A.
Am J Surg Pathol 2002;26:14-24 Abstract quoteLeiomyosarcomas of the somatic soft tissues (SST) are rare compared with their retroperitoneal and cutaneous counterparts and, therefore, have not been extensively studied. We have analyzed the clinicopathologic features of 42 SST leiomyosarcomas referred in consultation to determine what factors affect outcome. Cutaneous, visceral, retroperitoneal, uterine, gastrointestinal, and major vessel leiomyosarcomas were excluded. By definition all lesions possessed at least focal cytologic atypia and mitotic activity, although the latter varied from <1/10 high power fields to 66/10 high power fields. The patients (21 females and 21 males) ranged in age from 26 to 86 years (mean 60 years); tumors developed in the lower (n = 28) or upper extremity (n = 11) and trunk (n = 3). Most arose in deep (n = 27) as opposed to superficial (n = 15) soft tissue; 39 arose from a small vein. During the follow-up period (mean 47 months, range 9–162 months), 3 of 38 (8%) patients developed local recurrence and 17 of 38 metastasized (45%) mostly to the lungs. In a univariate analysis age >62 years, size >4 cm, extensive necrosis, modified updated French Federation of Cancer Centers (FFCC) grade, and whether the tumor had been “disrupted” by a previous incisional biopsy or incomplete excision were significantly correlated with metastasis. AJCC stage also approached significance (p = 0.096) but could not be reliably tested because of the sparseness of the data. In multivariate analyses the logistic regression model that best predicted metastasis at 36 months incorporated the effects of age, FFCC grade, and disruption and had a sensitivity of 94.1% and a specificity of 95.2%. Disruption was the only significant risk factor for metastasis in a multivariate analysis (relative risk 2.70; p = 0.0001) but was strongly correlated with large size and deep location. Other parameters did not improve the predictive power of the model significantly.
We concluded that the majority of SST leiomyosarcomas are actually of vascular origin, an observation that has clinical and possibly biologic ramifications. Our histologic definition of leiomyosarcoma to include atypia and any level of mitotic activity appears warranted by the biologic outcome in our cases. The risk of metastasis can be calculated from a model incorporating age, FFCC grade, and disruption. Because disruption correlates with size and depth, it could represent a surrogate as opposed to causal marker for metastasis. Nevertheless, in view of their vascular origin, the possibility that tumor disruption may facilitate or promote access to the bloodstream merits further study.
Calponin and h-caldesmon expression in atypical fibroxanthoma and superficial leiomyosarcoma.Sakamoto A, Oda Y, Yamamoto H, Oshiro Y, Miyajima K, Itakura E, Tamiya S, Honda Y, Ishihara A, Iwamoto Y, Tsuneyoshi M.
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Virchows Arch 2002 Apr;440(4):404-9 Abstract quote
To evaluate smooth muscle differentiation, myogenic markers [desmin, alpha-smooth muscle actin (SMA), and muscle-specific actin (HHF35)] have been widely used. Calponin and h-caldesmon, which are cytoskeleton-associated actin-binding proteins, have been reported to be more specific myogenic markers, especially since myofibroblasts express a small amount of h-caldesmon. Atypical fibroxanthoma (AFX) occurs in the sun-exposed skin of the elderly and follows a benign clinical course. Histologically, AFX, which is a pleomorphic spindle cell tumor and considered to be a superficial variant of malignant fibrous histiocytoma, also mimics leiomyosarcoma. AFX has been thought to differentiate along pathways with fibrohistiocytic and myofibroblastic phenotypes. AFX ( n=10), superficial leiomyosarcoma (S-LMS) ( n=17) and benign fibrous histiocytoma (BFH) ( n=17) were analyzed for myofibroblastic and smooth muscle differentiation immunohistochemically from the viewpoint of comparison. AFX and BFH showed immunoreactivities respectively for calponin (3/10, 11/17), desmin (3/10, 1/17), SMA (3/10, 13/17), and HHF35 (1/10, 5/17), but failed to express h-caldesmon (0/10, 0/17). S-LMS had a high immunoreactive rate of calponin (17/17), desmin (13/17), SMA (16/17), and HHF35 (16/17), while also expressing caldesmon (11/17).
The results reveal that AFX and BFH have immunoreactivities for several myogenic markers, with myofibroblastic differentiation (calponin: +/-, h-caldesmon: -), but without the smooth muscle differentiation seen in S-LMS (calponin:+, h-caldesmon: +/-). In addition, calponin and h-caldesmon are considered to be useful markers for distinguishing AFX from S-LMS.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Myxoid tumors Malignant tumors which must be excluded include a myxofibrosarcoma (myxoid MFH), myxoid liposarcoma, and extraskeletal myxoid chondrosarcoma. In these latter cases, cytogenetics may be helpful.
Myxoid chondrosarcomas show t(9;22)(q22;q12).
Retroperitoneal Leiomyomas A Clinicopathologic and Immunohistochemical Study of 56 Cases With a Comparison to Retroperitoneal Leiomyosarcomas Edina Paal, M.D. ; Markku Miettinen, M.D. , Ph.D.
From the Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC, U.S.A.
Am J Surg Pathol 2001;25:1355-1363 Abstract quoteMost retroperitoneal smooth muscle tumors are believed to be malignant, and leiomyomas are considered very rare. This study was undertaken to determine the clinicopathologic features and long-term follow-up of 56 tumors diagnosed as retroperitoneal leiomyomas (LM) or smooth muscle tumors with an uncertain malignant potential (SMTUMP) in an effort to correlate their behavior and clinicopathologic features. These tumors were compared with a series of 11 cases of retroperitoneal leiomyosarcomas (excluding gastrointestinal stromal tumors). Histologic slides and immunohistochemistry for SMA, desmin, S-100 protein, HMB45, CD34, C-KIT, estrogen (ER) and progesterone (PR) receptor proteins, and MIB-1 were analyzed. All tumors diagnosed as LM and all but one SMTUMP were well-differentiated smooth muscle tumors that lacked atypia and coagulative necrosis. There was <1 mitosis per 50 high power field (HPF) in 38 tumors; no tumor had >3 mitoses/50 HPF. Most tumors had a striking resemblance to uterine smooth muscle tumors with common hyaline change and trabecular patterns. There were 51 females and 5 males ranging in age from 25 to 79 years (mean 45 years, median 43 years). These tumors were typically large, with a mean size of 16.2 cm and weight of 1600 g. Immunohistochemically, all 35 tumors studied were positive for -SMA, 30 of 35 tumors were positive for desmin, and all were negative for CD117, S100 protein, and HMB45 and all but one for CD34. Steroid receptors were commonly present: ER in 20 of 29 cases and PR in 26 of 31 cases in the tumors of female patients. MIB-1 score was <2% in all of 28 cases. Long-term follow-up (mean 140 months) did not reveal metastases, but two patients had local recurrence; however, neither patient with recurrence demonstrated disease progression in follow-up. By contrast, all 11 leiomyosarcomas had at least mild atypia, and all were ER and PR negative. All cases had MIB-1-positive nuclei, but only four had >10% nuclei positive. Four patients died of disease, four were alive with recurrence, and three had no evidence of disease.
A group of benign leiomyomas can be identified among retroperitoneal smooth muscle tumors. Most of these tumors resemble uterine leiomyomas by histology and positive hormone receptors, and they seem to have a good long-term prognosis with a small potential for local recurrence.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Outcome Number of Patients (13 patients) No evidence of disease 7 Local recurrences and metastases 5 Tumor related deaths 3 (2 were uncontrolled local disease) Metastasis 2 GENERAL
Childhood leiomyosarcoma: a report from the soft tissue sarcoma Italian Cooperative Group. Ferrari A, Bisogno G, Casanova M, Meazza C, Cecchetto G, Mancini MA, Zanetti I, Alaggio R, Ninfo V, Carli M.
Pediatric Oncology Unit, Istituto Nazionale Tumori, Milano, Italy.
Ann Oncol 2001 Aug;12(8):1163-8 Abstract quoteBACKGROUND: Only a few reports on the clinical features and management of childhood leiomyosarcoma are available. To contribute additional information on the management of this rare tumor, we report on a series of 16 pediatric patients treated from 1982 to 1998 by the Soft Tissue Sarcoma Italian Cooperative Group. PATIENTS AND METHODS: Primary surgery was conservative in all but two patients, and consisted of biopsy--three cases, non-radical excision--four, and radical resection--nine (involving a primary re-excision in 4 of 9). In two cases secondary radical surgery was performed after primary chemotherapy. Chemotherapy was administered to 9 of 16 patients, radiotherapy to three. RESULTS: After a median follow-up of seven years (range 3-18), the five-year event-free survival (EFS) and overall survival were 56.3% and 72.9%, respectively; 12 of 16 patients were alive (nine of them in continuos complete remission). Univariate analysis was performed to compare EFS according to different subgroups: size represented the most significant prognostic factor.
CONCLUSIONS: Complete surgical resection is the mainstay of treatment for leiomyosarcoma. The role of both adjuvant chemotherapy and radiotherapy has yet to be established, and awaits cooperative multicentric studies.
Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma
Athanasios C Tsiatis1, Megan E Herceg2, Vicki L Keedy3, Jennifer L Halpern2, Ginger E Holt2, Herbert S Schwartz2 and Justin M M Cates4
1Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
2Department of Orthopaedics and Rehabilitation, Vanderbilt Orthopaedic Institute, Nashville, TN, USA
3Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
4Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
Correspondence: Dr JMM Cates, MD, PhD, Department of Pathology, Medical Center North C-3321, Vanderbilt University Medical Center, 1161 21st Ave South, Nashville, TN 37232, USA.
Modern Pathology (2009) 22, 1432–1438 Abstract quote
The biological potential of soft tissue leiomyosarcoma is difficult to predict using current standard prognostic parameters, and control of systemic disease is challenging with current chemotherapeutic protocols. Additional prognostic markers and alternative treatment options are very much required. Previous studies implicate upregulation of the oncogenic nuclear transcription factor c-Myc with aggressive behavior of many solid tumors. Therefore, this oncoprotein was evaluated as a prognostic marker for overall and metastasis-free survival in leiomyosarcoma.
Immunohistochemical stains for c-Myc were performed on 28 cases of leiomyosarcoma occurring in the deep somatic soft tissues. Comparisons of Kaplan–Meier survival curves stratified by c-Myc status and conventional prognostic factors (histological grade, tumor size, and tumor stage) were evaluated using standard univariate statistical methods. A subsequent multivariate survival analysis was carried out according to the Cox proportional hazards regression model adjusting for potential confounding prognostic factors. A total of 15 cases (54%) were positive for nuclear c-Myc expression. Patients with c-Myc-positive tumors had significantly shorter metastasis-free survival intervals compared with those with c-Myc-negative tumors (median, 9 months vs. >94 months; P=0.014). c-Myc positivity also correlated with decreased overall survival (median, 23 months vs. >94 months; P=0.017).
Histological grade was the only other prognostic marker predictive of poor outcome in the univariate analyses. In the multivariate survival analysis, only c-Myc status reached statistical significance, suggesting that it is an important and independent predictor of prognosis in leiomyosarcoma.
Detection of nuclear c-Myc in leiomyosarcoma predicts decreased overall and metastasis-free survival, independent of standard prognostic variables, tumor size, histological grade, and TNM stage. The expression of this oncoprotein may represent a useful prognostic marker and potential therapeutic target in leiomyosarcoma.
TREATMENT Wide excision
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