Definition/General

Introduction:
-Cervical tubular carcinoma is a rare variant of cervical adenocarcinoma characterized by well-formed tubular structures with minimal mucin production
-Accounts for less than 2% of cervical adenocarcinomas
-Shows orderly tubular architecture similar to breast tubular carcinoma.
Origin:
-Arises from endocervical glandular epithelium with unique differentiation pattern
-Characterized by tubular glands lined by single layer of epithelial cells
-Shows minimal intraluminal mucin distinguishing from mucinous carcinoma
-Generally HPV-associated malignancy.
Classification:
-WHO classification recognizes it as distinct adenocarcinoma variant
-Pure tubular pattern (80%)
-Mixed tubular-mucinous (15%)
-Tubular with solid areas (5%)
-Must have >90% tubular architecture for diagnosis.
Epidemiology:
-Rare with incidence 0.5-2% of cervical adenocarcinomas
-Age range 30-60 years with median age 45
-HPV association in 80-90% cases
-Better prognosis than conventional adenocarcinoma
-More common in Asian populations.

Clinical Features

Presentation:
-Abnormal vaginal bleeding (75%)
-Watery discharge (40%)
-Cervical mass or induration on examination
-Deep cervical infiltration common
-Often presents at locally advanced stage.
Symptoms:
-Postcoital bleeding most common symptom
-Intermenstrual bleeding (60%)
-Watery or mucoid discharge
-Pelvic pain with parametrial involvement
-Urinary symptoms if bladder involvement.
Risk Factors:
-High-risk HPV infection (80-90%)
-HPV type 18 most common
-Age 30-50 years
-Oral contraceptive use >5 years
-Multiple sexual partners
-Immunosuppression.
Screening:
-Pap smear sensitivity low (40-50%)
-Atypical glandular cells (AGC) on cytology
-HPV testing positive in 80-90%
-Colposcopy may show barrel cervix
-Deep cone biopsy often required.

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Gross Description

Appearance:
-Firm, indurated mass with ill-defined borders
-White-gray cut surface with fibrous texture
-Minimal mucin production
-Hemorrhage and necrosis less common than mucinous type.
Characteristics:
-Size 1-5 cm typically
-Rock-hard consistency due to desmoplasia
-White to tan coloration
-Infiltrative borders without encapsulation
-Gritty texture on sectioning.
Size Location:
-Endocervical origin in 90%
-Deep stromal invasion characteristic
-Parametrial extension in 30-40%
-Lower uterine segment involvement possible
-Vaginal fornix extension in advanced cases.
Multifocality:
-Usually unifocal primary tumor
-Skip lesions rare
-Associated with AIS in 20-30%
-Lymphovascular invasion common (50%)
-Perineural invasion in 25%.

Microscopic Description

Histological Features:
-Well-formed tubular glands with open lumina
-Single layer of epithelium lining tubules
-Minimal intraluminal mucin (<10% of cells)
-Marked desmoplastic response
-Infiltrative growth pattern between cervical smooth muscle.
Cellular Characteristics:
-Cuboidal to low columnar cells
-Eosinophilic cytoplasm with apical snouts
-Round to oval nuclei with minimal atypia
-Low mitotic rate (2-5/10 HPF)
-Absence of goblet cells.
Architectural Patterns:
-Angular tubular glands (90%)
-Open lumina without mucin lakes
-Haphazard infiltrative pattern
-Prominent desmoplasia (70%)
-Focal solid areas (<10%).
Grading Criteria:
-Well-differentiated: >90% tubular, minimal atypia
-Moderately differentiated: 50-90% tubular, moderate atypia
-Nuclear grade 1-2 typical
-Architectural grade 1 by definition.

Immunohistochemistry

Positive Markers:
-p16 diffuse positive (85%)
-CK7 positive (95%)
-PAX8 positive (90%)
-CEA positive (80%)
-CA125 positive (60%)
-ER negative to weak (70%).
Negative Markers:
-CK20 negative (95%)
-CDX2 negative (90%)
-TTF-1 negative
-GATA3 negative
-Mammoglobin negative
-GCDFP-15 negative.
Diagnostic Utility:
-p16/CK7/PAX8 panel confirms cervical origin
-Negative mammoglobin/GATA3 excludes breast primary
-CEA positivity supports glandular differentiation
-Ki-67 low (10-20%).
Molecular Subtypes:
-HPV-associated tubular type most common
-HPV-independent rare (<10%)
-Mixed tubular-mucinous shows hybrid features
-Microinvasive tubular variant exists.

Molecular/Genetic

Genetic Mutations:
-HPV integration in 85% (HPV 18 > HPV 16)
-PIK3CA mutations (35%)
-KRAS mutations (15%)
-PTEN loss (20%)
-ARID1A mutations (10%).
Molecular Markers:
-High-risk HPV DNA positive (85%)
-p16 overexpression correlates with HPV
-Low Ki-67 index (10-20%)
-Microsatellite stable
-HER2 negative (95%).
Prognostic Significance:
-Intermediate prognosis between well and poorly differentiated
-5-year survival 70-80% for early stage
-Depth of invasion critical factor
-Lymph node status most important
-HPV status may influence outcome.
Therapeutic Targets:
-Surgery preferred for early stage
-Radical hysterectomy with lymphadenectomy
-Adjuvant therapy for high-risk features
-Chemoradiation for advanced stage
-Anti-angiogenic agents under study.

Differential Diagnosis

Similar Entities:
-Metastatic breast carcinoma: tubular/invasive ductal type
-Endometrial adenocarcinoma: direct extension
-Mesonephric carcinoma: tubular pattern
-Minimal deviation adenocarcinoma: well-differentiated glands.
Distinguishing Features:
-Cervical tubular: p16+, PAX8+, HPV+
-Breast metastasis: GATA3+, mammoglobin+, ER+
-Endometrial: ER+/PR+, different location
-Mesonephric: GATA3+, CD10+, calretinin+.
Diagnostic Challenges:
-Small biopsy interpretation difficult
-Distinction from benign tubular metaplasia
-Recognition of minimal mucin
-Assessment of invasion depth
-Exclusion of metastasis critical.
Rare Variants:
-Microinvasive tubular carcinoma (<3mm invasion)
-Mixed tubular-mucinous carcinoma
-Tubular carcinoma with solid areas
-Multifocal tubular carcinoma
-Tubular carcinoma in pregnancy.

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 tubular carcinoma, well to moderately differentiated

Histological Features

Well-formed tubular glands (>90% of tumor) with minimal intraluminal mucin, single layer epithelium, marked desmoplastic stroma

Tumor Size

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

Depth of Invasion

Depth of stromal invasion: [X] mm; Cervical wall thickness: [X] mm; Percentage of wall invasion: [X]%

Margins

Ectocervical margin: [Negative/Positive] ([X] mm); Endocervical margin: [Negative/Positive] ([X] mm); Deep stromal margin: [Negative/Positive] ([X] mm); Vaginal cuff margin: [Negative/Positive] ([X] mm)

Lymphovascular Invasion

[Present/Absent]; If present: [focal (<5 foci)/multifocal (≥5 foci)]; Vessel type: [lymphatic/blood vessel/both]

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]; Largest metastatic deposit: [X] mm; Extranodal extension: [Present/Absent]

Immunohistochemistry

p16: Diffuse positive; CK7: Positive; PAX8: Positive; CEA: Positive; Mammoglobin: Negative; GATA3: Negative

Molecular Testing

HPV ISH: Positive (type [X]); Additional testing: [as indicated]

Pathological Stage

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

Additional Findings

[Adenocarcinoma in situ/Endometriosis/Nabothian cysts/Other findings]