Definition/General

Introduction:
-Cervical melanoma is an extremely rare malignant tumor arising from melanocytes in the cervical mucosa
-It represents <1% of all cervical malignancies and is classified as mucosal melanoma with typically poor prognosis.
Origin:
-Arises from melanocytes present in the cervical epithelium
-May develop de novo or from pre-existing melanocytic lesions
-Most cases are primary, but metastatic melanoma must be excluded.
Classification:
-WHO Classification categorizes as mucosal melanoma
-May be nodular, superficial spreading, or unclassified type
-Distinguished from cutaneous melanoma by location and behavior.
Epidemiology:
-Extremely rare, <0.1% of cervical cancers
-Peak incidence 50-70 years
-No racial predilection unlike cutaneous melanoma
-No association with UV exposure.

Clinical Features

Presentation:
-Abnormal vaginal bleeding
-Visible pigmented or non-pigmented cervical lesion
-Advanced cases may present with pelvic pain and mass effect.
Symptoms:
-Abnormal vaginal bleeding (most common)
-Vaginal discharge
-Visible cervical lesion (pigmented or amelanotic)
-Pelvic pain
-Dyspareunia.
Risk Factors:
-No clear risk factors identified
-Not associated with UV exposure
-No correlation with cutaneous melanoma
-Advanced age may be a factor.
Screening:
-No specific screening
-Colposcopy reveals pigmented or amelanotic lesion
-Biopsy required for diagnosis
-Staging with imaging studies.

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Gross Description

Appearance:
-Pigmented (brown to black) or amelanotic lesion
-May be polypoid, ulcerated, or flat
-Size variable from small nodules to large masses.
Characteristics:
-Size variable (few mm to >5 cm)
-Brown to black pigmentation (70% of cases)
-Some cases amelanotic
-Soft to firm consistency
-May be ulcerated.
Size Location:
-Can involve any part of cervix
-Often involves ectocervix
-May extend to vagina or endocervical canal
-Advanced cases show extensive involvement.
Multifocality:
-Usually unifocal lesion
-Satellite lesions possible
-Must distinguish from metastatic melanoma from other sites.

Microscopic Description

Histological Features:
-Malignant melanocytes with variable morphology including epithelioid, spindle cell, or mixed patterns
-Melanin pigment present in 70% of cases
-High mitotic activity.
Cellular Characteristics:
-Large cells with prominent nucleoli
-Variable morphology (epithelioid, spindle, nevoid)
-Abundant cytoplasm
-Melanin pigment may be present
-Nuclear pleomorphism.
Architectural Patterns:
-Nodular growth pattern most common
-May show junctional activity
-Pagetoid spread possible
-Invasion into stroma and vessels.
Grading Criteria:
-High-grade malignancy by definition
-Breslow thickness and Clark level not applicable for mucosal sites
-Mitotic rate important prognostic factor.

Immunohistochemistry

Positive Markers:
-S100 protein positive
-Melan-A positive
-HMB-45 positive
-SOX10 positive
-Tyrosinase positive.
Negative Markers:
-Cytokeratin negative
-EMA negative
-Desmin negative
-CD45 negative.
Diagnostic Utility:
-S100, Melan-A, and HMB-45 confirm melanocytic differentiation
-SOX10 highly sensitive for melanoma
-Essential for diagnosis of amelanotic cases.
Molecular Subtypes:
-Different molecular profile from cutaneous melanoma
-KIT mutations more common in mucosal melanomas.

Molecular/Genetic

Genetic Mutations:
-KIT mutations (10-20% of mucosal melanomas)
-NRAS mutations
-BRAF mutations less common than cutaneous melanoma
-Complex karyotype.
Molecular Markers:
-High Ki-67 proliferation index
-p53 mutations common
-Loss of CDKN2A
-Different from cutaneous melanoma molecular profile.
Prognostic Significance:
-Very poor prognosis with 5-year survival <20%
-Stage and thickness important
-Nodal and distant metastases common.
Therapeutic Targets:
-Surgery is primary treatment
-Immunotherapy (anti-PD-1, anti-CTLA-4)
-KIT inhibitors for KIT-mutated tumors
-Limited targeted options.

Differential Diagnosis

Similar Entities:
-Metastatic melanoma from other sites
-Poorly differentiated carcinoma
-Cervical sarcoma
-Blue nevus
-Pigmented squamous cell carcinoma.
Distinguishing Features:
-Primary melanoma: mucosal location, melanocyte markers+
-Metastatic: clinical history, imaging
-Carcinoma: cytokeratin+.
Diagnostic Challenges:
-Distinction from metastatic melanoma
-Recognition of amelanotic cases
-Differentiation from other poorly differentiated tumors.
Rare Variants:
-Amelanotic melanoma
-Desmoplastic melanoma
-Balloon cell melanoma
-Clear cell melanoma.

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]