Definition/General

Introduction:
-Cervical metaplastic carcinoma is a rare and aggressive variant characterized by biphasic malignant epithelial and mesenchymal-like components
-Accounts for less than 1% of cervical carcinomas
-Shows sarcomatoid transformation of epithelial carcinoma.
Origin:
-Arises from epithelial-mesenchymal transition (EMT) of carcinoma cells
-May develop from pre-existing squamous or adenocarcinoma
-Shows monoclonal origin proven by molecular studies
-HPV-associated in majority of cases.
Classification:
-WHO classification includes carcinosarcoma (malignant epithelial and mesenchymal)
-Spindle cell carcinoma (monophasic sarcomatoid)
-Matrix-producing carcinoma (with cartilage/bone)
-Mixed metaplastic variants
-Must have malignant epithelial component.
Epidemiology:
-Incidence 0.5-1% of cervical carcinomas
-Age range 40-70 years with median 55
-Worse prognosis than conventional carcinomas
-High metastatic potential (40-50%)
-Rapid progression typical.

Clinical Features

Presentation:
-Large polypoid mass (80%)
-Profuse vaginal bleeding (90%)
-Rapid growth noted by patients
-Advanced stage at presentation (60%)
-Pelvic pain from local invasion.
Symptoms:
-Heavy vaginal bleeding requiring transfusion
-Foul-smelling discharge from tumor necrosis
-Urinary symptoms from bladder compression
-Constipation from rectal involvement
-Weight loss and fatigue (30%).
Risk Factors:
-HPV infection documented in 70%
-Prior radiation therapy (10%)
-Chronic inflammation
-Immunosuppression
-Previous cervical dysplasia
-Smoking history.
Screening:
-Pap smear shows malignant cells with spindle features
-Dual population may be seen
-HPV testing positive in 70%
-Colposcopy shows friable mass
-Deep biopsy essential for diagnosis.

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Gross Description

Appearance:
-Large polypoid or fungating mass
-Heterogeneous cut surface with solid and cystic areas
-Tan-white to gray color
-Hemorrhage and necrosis prominent
-Fish-flesh appearance of sarcomatoid areas.
Characteristics:
-Size typically 5-10 cm at diagnosis
-Soft to rubbery consistency
-Myxoid or gelatinous areas (30%)
-Cartilaginous foci if heterologous elements
-Infiltrative borders.
Size Location:
-Involves entire cervix in most cases
-Parametrial extension (50%)
-Vaginal involvement (40%)
-Uterine corpus extension (25%)
-Bladder/rectum invasion in advanced cases.
Multifocality:
-Usually single large mass
-Satellite nodules rare
-Lymph node metastases (30-40%)
-Hematogenous spread to lungs/liver
-Peritoneal dissemination possible.

Microscopic Description

Histological Features:
-Biphasic pattern with epithelial and mesenchymal components
-Abrupt transition between elements
-Spindle cell areas resembling sarcoma
-Epithelial nests may be focal
-High-grade cytology throughout.
Cellular Characteristics:
-Epithelial cells show squamous or glandular differentiation
-Spindle cells with elongated nuclei
-High nuclear-cytoplasmic ratio
-Frequent mitoses (>20/10 HPF)
-Atypical mitotic figures common.
Architectural Patterns:
-Intimate mixture of carcinoma and sarcoma
-Collision pattern in some cases
-Homologous sarcoma (fibrosarcoma-like) most common
-Heterologous elements (cartilage, bone) in 20%
-Extensive necrosis.
Grading Criteria:
-All considered high-grade by definition
-Nuclear grade 3 features
-Architectural grade 3
-Mitotic rate high
-Percentage of sarcomatoid component prognostically important.

Immunohistochemistry

Positive Markers:
-Epithelial component: CK AE1/AE3+, p63+, p40+ (if squamous)
-Sarcomatoid component: Vimentin+, variable cytokeratin
-p16 positive in both components (70%)
-Smooth muscle actin variable
-Desmin in rhabdomyosarcomatous areas.
Negative Markers:
-ER/PR usually negative
-CD34 negative
-CD31 negative
-S100 negative unless neural differentiation
-HMB45 negative
-Inhibin negative.
Diagnostic Utility:
-Cytokeratin highlights epithelial component
-Vimentin confirms mesenchymal areas
-p16 supports HPV association
-Smooth muscle markers if leiomyosarcomatous
-p53 often overexpressed.
Molecular Subtypes:
-HPV-positive metaplastic carcinoma (70%)
-HPV-negative aggressive variant
-EMT phenotype with loss of E-cadherin
-Stem cell marker expression (CD44, ALDH1).

Molecular/Genetic

Genetic Mutations:
-TP53 mutations (60%)
-PIK3CA mutations (40%)
-PTEN loss (35%)
-KRAS mutations (20%)
-CTNNB1 mutations (15%)
-CDKN2A deletions (25%).
Molecular Markers:
-HPV DNA positive in 70%
-EMT markers (Snail, Twist, ZEB1)
-High Ki-67 index (>50%)
-Loss of E-cadherin
-β-catenin nuclear expression.
Prognostic Significance:
-Percentage of sarcomatoid component correlates with outcome
-Heterologous elements indicate worse prognosis
-p53 overexpression poor prognostic factor
-High proliferation index adverse.
Therapeutic Targets:
-Aggressive multimodal therapy required
-Neoadjuvant chemotherapy considered
-Radiation resistance common
-Targeted therapy under investigation
-Immunotherapy for PDL1-positive cases.

Differential Diagnosis

Similar Entities:
-Malignant mixed Müllerian tumor (MMMT): older age, corpus location
-Leiomyosarcoma: pure spindle cells, desmin+
-Endometrial stromal sarcoma: CD10+, ER+
-GIST: CD117+, DOG1+.
Distinguishing Features:
-Metaplastic carcinoma: epithelial component present, p16+
-Pure sarcomas: no epithelial differentiation
-Carcinoma with pseudosarcomatous stroma: benign spindle cells
-Radiation-induced sarcoma: history important.
Diagnostic Challenges:
-Small biopsy may sample only one component
-Extensive sampling required
-IHC essential to identify epithelial elements
-Distinction from collision tumors
-Recognition of EMT.
Rare Variants:
-Adenosquamous carcinoma with sarcomatoid transformation
-Neuroendocrine carcinoma with sarcomatoid features
-Metaplastic carcinoma with melanoma differentiation
-Osteoclast-like giant cell variant.

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

Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection, received [fresh/in formalin]

Diagnosis

Cervical metaplastic carcinoma (carcinosarcoma) with [homologous/heterologous] sarcomatous elements

Histological Features

Biphasic tumor with malignant epithelial component ([X]%) showing [squamous/glandular] differentiation and sarcomatoid component ([X]%) with [specify type] features

Heterologous Elements

[Present/Absent]; If present: [chondrosarcoma/osteosarcoma/rhabdomyosarcoma]

Tumor Size

Greatest dimension: [X] cm; Additional dimensions: [X] × [X] cm; Gross tumor volume: [X] cm³

Depth of Invasion

Full thickness cervical wall invasion; Extension beyond cervix: [Present/Absent]

Margins

Ectocervical margin: [Negative/Positive] ([X] mm); Endocervical margin: [Negative/Positive] ([X] mm); Parametrial margins: [Negative/Positive]

Lymphovascular Invasion

[Present, extensive/Present, focal/Not identified]; Both components present in emboli: [Yes/No]

Parametrial Involvement

Right parametrium: [Involved/Not involved]; Left parametrium: [Involved/Not involved]; Pattern: [direct extension/lymphovascular]

Lymph Nodes

Total nodes examined: [X]; Positive nodes: [X]; Component in metastases: [epithelial/sarcomatoid/both]

Immunohistochemistry

Epithelial component: Pan-CK+, p63/p40+ (if squamous); Sarcomatoid component: Vimentin+, CK focal+; p16: Positive in both components

Molecular Testing

HPV ISH: [Positive/Negative]; Additional markers: [as indicated]

Pathological Stage

FIGO Stage (2018): [stage]; TNM Stage (8th edition): pT[X]N[X]M[X]

Additional Findings

[Background cervical dysplasia/Other findings]