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Leiomyosarcoma-general


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Borislav A. Alexiev, M.D.

Last staff update: 5 January 2023 (update in progress)

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PubMed Search: Leiomyosarcoma soft tissue pathology

Borislav A. Alexiev, M.D.
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Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Alexiev B. Leiomyosarcoma-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissueleiomyosarcoma.html. Accessed February 3rd, 2023.
Definition / general
  • Leiomyosarcoma (LMS) is a malignant mesenchymal tumor showing smooth muscle differentiation (J Clin Oncol 2018;36:144)
Essential features
  • Fascicles of eosinophilic spindled cells with blunt ended nuclei showing variable pleomorphism (Cancer 1981;48:1022, Am J Surg Pathol 2002;26:14)
  • Immunostaining for SMA, MSA, desmin or h-caldesmon
  • Dedifferentiated areas lack expression of myogenic markers (Histopathology 2011;59:1135)
  • Clinically aggressive neoplasms with frequent local recurrences and distant metastases
ICD coding
  • ICD-O: 8890/3 - leiomyosarcoma, NOS
  • ICD-11:
    • 2B58.0 & XH7ED4 - leiomyosarcoma of retroperitoneum or peritoneum & leiomyosarcoma, NOS
    • 2B58.Y & XH7ED4 - leiomyosarcoma, other specified primary site & leiomyosarcoma, NOS
    • 2B58.Z & XH7ED4 - leiomyosarcoma, unspecified primary site & leiomyosarcoma, NOS
Epidemiology
  • Leiomyosarcoma is one of the most common subtypes of malignant mesenchymal neoplasms and represents ~10 - 20% of all newly diagnosed soft tissue sarcomas (J Clin Oncol 2018;36:144)
  • Overall incidence of leiomyosarcoma increases with age and peaks at the seventh decade of life
  • Sex predilection greatly depends on tumor location, with women comprising a clear majority of patients with retroperitoneal and inferior vena cava leiomyosarcoma and men showing a slight predominance in noncutaneous soft tissue sites
Sites
Pathophysiology
  • Leiomyosarcoma belongs to the group of soft tissue sarcomas with complex and unbalanced karyotypes, which results in severe genomic instability (J Clin Oncol 2018;36:144)
  • Some of the most common changes in leiomyosarcoma occur in the form of loss in chromosomes 10q(PTEN) and 13q (RB1) and gain at 17p (TP53)
Etiology
  • There is no definite, identifiable, causative factor for leiomyosarcoma
  • Prior history of radiotherapy, which is one of the most significant risk factors for development of soft tissue sarcomas, can also lead to the development of leiomyosarcoma (J Natl Cancer Inst 1988;80:233)
  • Patients with genetic syndromes like hereditary retinoblastoma (RB1 gene deletion) and Li-Fraumeni syndrome (mutation in the TP53 gene) can develop leiomyosarcoma, amongst other soft tissue sarcomas (J Clin Oncol 2018;36:144)
Clinical features
  • Clinical presentation of leiomyosarcoma, as with other soft tissue sarcomas, is often associated with nonspecific symptoms caused by the displacement of structures, rather than invasion, in specific anatomic locations of the primary tumor and its metastases (J Clin Oncol 2018;36:144)
Diagnosis
  • Imaging approaches include magnetic resonance imaging (MRI) in soft tissue extremity / truncal tumors and contrast enhanced computed tomography (CT) scan for retroperitoneal lesions
  • Chest and abdominal CT scans are required in the initial workup, as hematogenous spread is a frequent event in leiomyosarcoma, with the lung and liver as 2 common sites of metastases (AJR Am J Roentgenol 1988;150:615)
  • Pretreatment biopsy is mandatory in extrauterine sites, with core biopsy as the preferred technique (J Clin Oncol 2018;36:144)
  • Detailed pathologic evaluation is typically performed after complete resection
  • Fine needle aspiration is inadequate to establish a diagnosis (J Surg Oncol 2010;102:523)
Laboratory
Radiology description
  • CT findings (Radiology 1984;152:133):
    • Generally heterogeneous
    • Commonly demonstrate central low attenuation representing necrosis
    • Calcification exceedingly rare
  • MRI findings (Diagn Interv Radiol 2015;21:4):
    • T1: isointense to muscle
    • T2 non-fat suppressed: intermediate to hypointense to neighboring fat
    • T2 FS: predominantly hyperintense
Radiology images

Contributed by Borislav A. Alexiev, M.D.

MRI of right forearm

MRI of abdomen

Prognostic factors
Case reports
Treatment
  • Staging of soft tissue sarcomas, including leiomyosarcoma, is important in guiding treatment
  • Treatment is best carried out in a specialized center with expertise in sarcoma care (Surg Oncol Clin N Am 2022;31:527)
  • Treatment planning begins with a multidisciplinary review of the patient’s history, all available radiographic images and the pathologic results from biopsy
  • Treatment plan is formulated upon the input from orthopedic and general surgeons, musculoskeletal radiologists, pathologists, medical oncologists and radiation oncologists
  • Goal of treatment is to control the symptoms, decrease tumor bulk and prolong survival (J Clin Oncol 2018;36:144)
  • Surgery (Adv Surg 2015;49:107):
    • Local control of soft tissue leiomyosarcoma is usually achieved with surgical resection
    • Achieving wide surgical margins is important in preventing local recurrence
  • Radiation therapy:
    • Radiation therapy is an important additional treatment for improving rates of local control
    • Many tumors involve or are directly adjacent to vital structures and in these cases achieving a wide surgical margin is impossible
    • Radiation therapy can be delivered either preoperatively (neoadjuvant) or postoperatively (adjuvant)
      • Perioperative radiation therapy for soft tissue sarcoma is the gold standard of treatment for localized disease in extremities, trunk and head / neck region (J Clin Oncol 2018;36:144)
      • At this point, no consensus exists on the timing or benefit of perioperative radiation therapy for patients diagnosed with retroperitoneal soft tissue sarcoma
    • Radiation therapy can also be utilized as a means of palliative local control when extensive metastases have already occurred
  • Chemotherapy:
    • Leiomyosarcoma is characterized by severe genomic instability, which results in multiple genetic aberrations; as a result, leiomyosarcoma is considered moderately sensitive to chemotherapy (Sarcoma 2010;2010:506182)
    • Neoadjuvant chemotherapy can help shrink the tumor, hence improving resectability, achieving negative margins and earlier control of metastatic disease
    • Adjuvant chemotherapy after surgery significantly improves the time to local and distant recurrence and overall recurrence free survival (Lancet 1997;350:1647)
    • Chemotherapy is the first line treatment in metastatic or unresectable leiomyosarcoma
Clinical images

Images hosted on other servers:

12 cm tibial tumor

 

Oral cavity tumor

25 cm epididymis mass

Internal jugular vein

Gross description
Gross images

Contributed by Borislav A. Alexiev, M.D.

Soft tissue mass

Inferior vena cava mass

Frozen section description
  • Cellular neoplasm that is composed of intersecting fascicles of spindle cells with bright eosinophilic cytoplasm and elongated, blunt ended (cigar shaped) nuclei (Eur J Cancer 2002;38:1218, Am J Clin Pathol 2006;125:555)
  • Nuclear pleomorphism, tumor necrosis and mitotic activity
Microscopic (histologic) description
  • Classic leiomyosarcoma (Eur J Cancer 2002;38:1218, Am J Clin Pathol 2006;125:555):
    • Spindle shaped cells with plump, blunt ended nuclei and moderate to abundant, pale to brightly eosinophilic fibrillary cytoplasm
    • Cells are set in long intersecting fascicles parallel and perpendicular to the plane of section
    • Some tumors show areas with storiform or palisaded patterns
    • Moderate nuclear pleomorphism is usually noted, although pleomorphism may be focal
    • Mitotic figures, including atypical ones, are easy to find
    • Tumors usually show diffuse hypercellularity
    • Focal fibrosis, myxoid change and hyalinized hypocellular areas can be seen
    • Tumor cell necrosis is often present
    • Unusual features in soft tissue leiomyosarcoma include multinucleated osteoclast-like giant cells, granular cytoplasmic change and epithelioid morphology
  • Pleomorphic leiomyosarcoma (Am J Surg Pathol 2001;25:1030):
    • Composed of pleomorphic cells with or without abundant eosinophilic or fibrillary cytoplasm in > 66% of the maximum cut surface of the tumor, accompanied by an ordinary leiomyosarcoma fascicular area covering < 33%
    • Storiform pattern in > 50% of cases
    • Stromal hyalinization
    • Chronic inflammatory infiltrate
    • Myxofibrosarcoma-like (myxoid malignant fibrous histiocytoma-like) areas
  • Myxoid leiomyosarcoma (Am J Surg Pathol 2000;24:927):
    • Extensively myxoid stroma (> 50% of the tissue examined)
    • Tumor cells are predominantly spindled
    • 3 major histologic architectures: fascicular, reticular / microcystic and myxofibrosarcoma-like
    • Areas of conventional leiomyosarcoma are usually present at least focally
  • Dedifferentiated leiomyosarcoma (Histopathology 2011;59:1135):
    • Tumor showing features of low grade leiomyosarcoma associated with a discrete undifferentiated component lacking morphological or immunophenotypic features of myogenic differentiation
  • Histologic grade (French Federation of Cancer Centers Sarcoma Group [FNCLCC]) (J Clin Oncol 1997;15:350):
Microscopic (histologic) images

Contributed by Borislav A. Alexiev, M.D.

Intersecting fascicles

Blunt ended nuclei

Nuclear pleomorphism

Mitotic activity

Necrosis

Osteoclast-like giant cells


Pleomorphic tumor cells

Dedifferentiation

Desmin

Caldesmon

Muscle specific actin

Loss of myogenic differentiation

Cytology description
  • Leiomyosarcoma, classical variant (Diagn Cytopathol 2003;28:119):
    • Various proportions of spindle shaped, cohesive, small or large sized cells arranged in parallel alignment
    • Blunt ended nuclei
    • Cytoplasm varies from fibrillary to granular to vacuolar
  • Leiomyosarcoma, epithelioid variant:
  • Leiomyosarcoma, pleomorphic variant:
    • Variably sized and shaped cells, often including multinucleated giant cells with atypical nuclei
  • Leiomyosarcoma, myxoid variant:
    • Large amounts of background myxoid matrix containing large spindle shaped and giant cells
  • Intranuclear inclusions and mitotic figures are occasionally seen, as well as stromal fragments
Cytology images

Contributed by Taylor Bronson, M.D.

Spindle cells

Nuclear atypia

Negative stains
Molecular / cytogenetics description
  • Complex karyotypes with numerous chromosomal gains and losses (JCO Precis Oncol 2020;4:PO.20.00040)
  • Losses involving tumor suppressors TP53 (17p13.1), RB1 (13q14.2) and PTEN (10q23.31) (Am J Pathol 2010;177:2080)
  • TP53 is mutated in as many as 50% of sporadic leiomyosarcomas
  • Homozygous copy loss of CDKN2C at chromosome 1p32.3b (JCO Precis Oncol 2020;4:PO.20.00040)
    • CDKN2C null leiomyosarcoma defines a genomically distinct tumor that may have prognostic or therapeutic clinical implications, including the possible use of specific cyclin dependent kinase inhibitors
Sample pathology report


  • Right thigh mass, core biopsy:
    • Leiomyosarcoma, FNCLCC grade 2 (see comment)
    • Comment: The neoplasm is composed of cellular, intersecting fascicles of spindle cells with bright eosinophilic cytoplasm and elongated blunt ended (cigar shaped) nuclei. Moderate nuclear pleomorphism and mitotic activity (up to 13 mitoses/10 high power fields) are noted. There is focal tumor necrosis (< 5%). Immunohistochemical stains for SMA, desmin and h-caldesmon are positive in tumor cells. These pathologic findings support the diagnosis above.
    • Leiomyosarcomas of soft tissue are aggressive neoplasms with frequent local recurrence and distant metastases. The most important prognostic factors are histologic grade, tumor location and size.
Differential diagnosis
Board review style question #1


A 57 year old woman presented with a mass in the soft tissue of the left thigh. H&E stains show a tumor composed of spindle shaped cells with plump, blunt ended hyperchromatic nuclei and moderate pale to brightly eosinophilic fibrillary cytoplasm. The cells are set in long intersecting fascicles parallel and perpendicular to the plane of the section. Mitotic figures, including atypical ones, are present.

Immunohistochemical stains for h-caldesmon, SMA and desmin are positive in tumor cells, while all of the following are negative: TLE1, CD99, HMB45, MelanA, S100, SOX10, EMA and AE1 / AE3.

Which of the following is most likely the correct diagnosis?

  1. Leiomyoma
  2. Leiomyosarcoma
  3. Malignant peripheral nerve sheath tumor
  4. PEComa
  5. Synovial sarcoma (monophasic)
Board review style answer #1
B. Leiomyosarcoma

Comment Here

Reference: Leiomyosarcoma
Board review style question #2
What is the most common gene mutation in soft tissue leiomyosarcoma?

  1. EWSR1
  2. FUS
  3. NF1
  4. PLAG1
  5. TP53
Board review style answer #2
E. TP53

Comment Here

Reference: Leiomyosarcoma
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