What are the differences between endocervical carcinoma and squamous cell carcinoma?

Differences Between Endocervical Adenocarcinoma and Squamous Cell Carcinoma

Endocervical adenocarcinoma and squamous cell carcinoma are fundamentally distinct cervical cancers that differ in their cellular origin, epidemiology, clinical behavior, and treatment response, with adenocarcinoma generally carrying a worse prognosis despite current treatment algorithms not distinguishing between them. 1

Epidemiology and Incidence

• Squamous cell carcinoma accounts for 70-80% of cervical cancers, while adenocarcinomas represent only 10-15% 2
• The incidence of squamous cell carcinoma is decreasing in the USA, yet adenocarcinoma incidence is paradoxically increasing 1
• Patients with adenocarcinoma/adenosquamous carcinoma are significantly younger at diagnosis compared to those with squamous cell carcinoma (p = 0.007) 3

Cellular Origin and Histopathology

Squamous Cell Carcinoma

• Composed of recognizably squamous cells that vary in growth pattern or cytological morphology 2
• Classified into keratinizing and nonkeratinizing subtypes 2
• Keratinizing types are characterized by keratin pearls with infrequent mitoses 2
• Nonkeratinizing types do not form keratin pearls but may show individual cell keratinization 2

Endocervical Adenocarcinoma

• Tumor cells are not obviously mucinous and show characteristic eosinophilic cytoplasm, unlike normal endocervical mucinous epithelium 2
• The majority are architecturally well differentiated but cytologically grade 2 or 3 2
• Differential diagnosis of early invasive adenocarcinoma from adenocarcinoma in situ is significantly more difficult compared to squamous cell carcinoma 2
• Mucinous adenocarcinomas show mucin-rich cells with gastric-type features or minimal deviation type (adenoma malignum) 2

Clinical Presentation

• More adenocarcinoma patients are diagnosed asymptomatically through abnormal Pap smear findings compared to squamous cell carcinoma patients (p = 0.043) 3
• Papillary tumors on gross examination are more commonly adenocarcinomas 2
• Both can present as exophytic (growing outward) or endophytic (stromal infiltration with minimal surface growth) 2

HPV Association

• Squamous cell carcinomas and their precursors are related to HPV infection in almost all cases 2
• Endocervical adenocarcinoma of usual type is HPV-positive in nearly 90% of cases, with adenocarcinoma in situ positive in 100% 2
• HPV 18 is more common in adenocarcinomas and adenosquamous carcinomas than in squamous cell carcinomas 2
• HPV 18 DNA presence is associated with poor prognosis 2
• Rare adenocarcinoma types (clear-cell and mesonephric) appear unrelated to HPV 2

Treatment Response and Prognosis

Critical Prognostic Differences

• Adenocarcinoma/adenosquamous carcinoma patients respond significantly less to treatment compared to squamous cell carcinoma (p = 0.018) 3
• Adenocarcinoma patients have worse 5-year progression-free survival (30.0% vs. 47.6%, p = 0.044) 3
• Adenocarcinoma patients have significantly worse 5-year distant metastasis-free survival (41.5% vs. 69.9%, p = 0.005) 3
• Trends toward worse 5-year local recurrence-free survival (64.4% vs. 76.2%, p = 0.165) and overall survival (41.3% vs. 58.1%, p = 0.090) 3

Treatment Implications

• Despite these significant differences, current treatment algorithms do not distinguish between cervical squamous cell carcinoma and adenocarcinoma 1, 4
• Cervical adenocarcinoma may be more aggressive than squamous cell carcinoma, warranting more comprehensively effective treatments 3
• Prospective research directed specifically toward adenocarcinoma is limited, with most trials including insufficient numbers to generate more than hypotheses 1, 4

Patterns of Disease Spread

• Adenocarcinoma shows different patterns of recurrence and rates of metastasis compared to squamous cell carcinoma 1, 4
• The higher rate of distant metastasis in adenocarcinoma suggests more aggressive systemic behavior 3

Clinical Pitfalls

• Do not assume adenocarcinoma and squamous cell carcinoma behave similarly despite current treatment protocols treating them identically 1
• Be aware that papillary or villoglandular adenocarcinoma has good prognosis only when in pure form; underlying conventional adenocarcinoma components change behavior to usual adenocarcinoma type 2
• Clear-cell changes in squamous cell carcinoma should not be misinterpreted as clear-cell carcinoma 2
• Early invasive adenocarcinoma is more challenging to distinguish from adenocarcinoma in situ compared to squamous lesions 2