Definition/General

Introduction:
-Cervical leiomyosarcoma is a rare malignant smooth muscle tumor arising from the cervical wall
-It represents <1% of all cervical malignancies and is distinguished from leiomyoma by high mitotic activity, cellular atypia, and coagulative necrosis.
Origin:
-Arises de novo from smooth muscle cells of the cervical wall or rarely from malignant transformation of pre-existing leiomyoma
-May originate from vascular smooth muscle or stromal smooth muscle.
Classification:
-WHO Classification categorizes as malignant smooth muscle tumor
-Graded using FNCLCC system
-Distinguished from other uterine sarcomas by smooth muscle differentiation.
Epidemiology:
-Extremely rare, <1% of cervical cancers
-Peak incidence 40-60 years
-Slightly more common in African American women
-No clear association with HPV infection.

Clinical Features

Presentation:
-Rapidly growing cervical mass
-Abnormal vaginal bleeding
-Pelvic pain or pressure
-Advanced cases may present with metastatic disease.
Symptoms:
-Abnormal uterine bleeding (menorrhagia, postmenopausal bleeding)
-Pelvic pain or pressure
-Rapidly enlarging cervical mass
-Dyspareunia
-Urinary or bowel symptoms.
Risk Factors:
-Prior pelvic radiation therapy (most significant)
-Tamoxifen use
-Genetic syndromes (hereditary leiomyomatosis and renal cell cancer)
-Age >40 years.
Screening:
-No specific screening
-Imaging shows heterogeneous mass with areas of necrosis
-MRI helpful for staging and surgical planning.

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Gross Description

Appearance:
-Large, lobulated, soft to firm mass with areas of hemorrhage and necrosis
-Cut surface shows heterogeneous appearance with white-tan solid areas and necrotic regions.
Characteristics:
-Size typically >5 cm
-Soft to firm consistency
-Gray-white to tan color
-Hemorrhagic and necrotic areas common
-Ill-defined borders.
Size Location:
-Usually large tumors (>5 cm) involving cervical wall
-May extend to parametrium, vagina, or corpus
-Can involve entire cervix.
Multifocality:
-Usually unifocal large mass
-May have satellite nodules
-Extension to adjacent structures common in advanced cases.

Microscopic Description

Histological Features:
-Malignant smooth muscle cells with significant nuclear atypia, high mitotic activity (>5/10 HPF), and coagulative tumor cell necrosis
-Fascicular growth pattern may be preserved.
Cellular Characteristics:
-Pleomorphic smooth muscle cells
-Enlarged, hyperchromatic nuclei with prominent nucleoli
-Abundant eosinophilic cytoplasm
-Numerous mitoses including atypical forms.
Architectural Patterns:
-Fascicular arrangement may be maintained or lost
-Areas of solid growth
-Extensive necrosis common
-Vascular invasion frequently present.
Grading Criteria:
-High-grade sarcoma
-FNCLCC grading: Grade 2-3 based on differentiation, mitoses (>20/10 HPF), and necrosis
-Most cases are high-grade.

Immunohistochemistry

Positive Markers:
-Smooth muscle actin (SMA) positive
-Desmin positive (may be focal)
-Caldesmon positive
-h-Caldesmon positive.
Negative Markers:
-CD117 (c-kit) negative
-CD34 negative
-S100 protein negative
-Cytokeratin negative
-EMA negative.
Diagnostic Utility:
-SMA and caldesmon confirm smooth muscle differentiation
-Desmin may be focal or negative in high-grade tumors
-Ki-67 typically >10%.
Molecular Subtypes:
-No specific molecular subtypes
-May have loss of tumor suppressors (RB1, TP53)
-Complex karyotype typical.

Molecular/Genetic

Genetic Mutations:
-Complex karyotype with multiple chromosomal abnormalities
-TP53 mutations common
-RB1 loss
-PTEN mutations
-Unlike leiomyomas, rarely have MED12 mutations.
Molecular Markers:
-High Ki-67 proliferation index (>10%)
-p53 overexpression or null pattern
-Loss of RB expression
-High chromosomal instability.
Prognostic Significance:
-Poor prognosis with 5-year survival <50%
-Stage, size, and grade are important prognostic factors
-Metastatic potential high.
Therapeutic Targets:
-Surgery is primary treatment
-Adjuvant chemotherapy (doxorubicin-based)
-Radiation therapy for local control
-Limited targeted therapies available.

Differential Diagnosis

Similar Entities:
-Cervical leiomyoma
-Other cervical sarcomas (rhabdomyosarcoma, fibrosarcoma)
-Poorly differentiated carcinoma
-Malignant mixed müllerian tumor.
Distinguishing Features:
-Leiomyosarcoma: high mitoses, necrosis, atypia, SMA+
-Leiomyoma: low mitoses, no necrosis, minimal atypia
-Carcinoma: cytokeratin+.
Diagnostic Challenges:
-Distinction from cellular leiomyoma
-Atypical leiomyoma vs low-grade leiomyosarcoma
-Recognition of smooth muscle differentiation in high-grade tumors.
Rare Variants:
-Epithelioid leiomyosarcoma
-Myxoid leiomyosarcoma
-Pleomorphic leiomyosarcoma
-Inflammatory leiomyosarcoma.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

[diagnosis name]

Classification

Classification: [classification system] [grade/type]

Histological Features

Shows [architectural pattern] with [nuclear features] and [mitotic activity]

Size and Extent

Size: [X] cm, extent: [local/regional/metastatic]

Margins

Margins are [involved/uninvolved] with closest margin [X] mm

Lymphovascular Invasion

Lymphovascular invasion: [present/absent]

Lymph Node Status

Lymph nodes: [X] positive out of [X] examined

Special Studies

IHC: [marker]: [result]

Molecular: [test]: [result]

[other study]: [result]

Prognostic Factors

Prognostic factors: [list factors]

Final Diagnosis

Final diagnosis: [complete diagnosis]