Definition/General
Introduction:
Cervical apocrine carcinoma is an extremely rare variant of cervical adenocarcinoma characterized by abundant eosinophilic granular cytoplasm and apocrine-type secretion
Accounts for less than 0.1% of cervical carcinomas
Shows decapitation secretion similar to breast apocrine carcinoma.
Origin:
Arises from cervical glandular epithelium with apocrine metaplasia
May originate from endocervical glands or ectopic breast-like tissue
Shows true apocrine differentiation with specific markers
HPV association uncertain due to rarity.
Classification:
WHO classification recognizes as rare adenocarcinoma variant
Must show >90% apocrine features for diagnosis
Pure apocrine carcinoma most common
Mixed apocrine-mucinous variant exists
Apocrine carcinoma in situ precursor lesion.
Epidemiology:
Extremely rare with fewer than 50 cases reported
Age range 40-70 years with median 55
No clear HPV association established
Aggressive behavior in most cases
More common in postmenopausal women.
Clinical Features
Presentation:
Abnormal vaginal bleeding (80%)
Watery discharge (50%)
Cervical mass or polyp on examination
Advanced stage at presentation (40%)
Pelvic discomfort (30%).
Symptoms:
Postmenopausal bleeding most common
Profuse watery discharge characteristic
Foul odor if necrosis present
Pelvic pain with deep invasion
Urinary symptoms if bladder involvement.
Risk Factors:
Age over 50 years
Hormonal factors possibly involved
No clear HPV association
Prior breast cancer in some cases
Hormone replacement therapy possible link.
Screening:
Pap smear shows atypical glandular cells
Apocrine features may be recognized
HPV testing often negative
Colposcopy shows glandular abnormality
Deep biopsy required for diagnosis.
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Gross Description
Appearance:
Polypoid or nodular mass
Pink to tan color
Soft to firm consistency
Granular cut surface
May have cystic areas with viscous secretion.
Characteristics:
Size 2-6 cm typically
Well-circumscribed in some cases
Infiltrative borders more common
Hemorrhage and necrosis variable
Mucoid secretion may be present.
Size Location:
Endocervical location predominant
May involve transformation zone
Deep stromal invasion common
Parametrial extension in advanced cases
Lower uterine segment involvement possible.
Multifocality:
Usually unifocal tumor
Multifocal disease rare
Skip lesions not typical
Lymph node metastases (30%)
Distant metastases to liver, lung.
Microscopic Description
Histological Features:
Abundant eosinophilic granular cytoplasm
Apical cytoplasmic snouts with decapitation secretion
Large vesicular nuclei with prominent nucleoli
Glandular and solid patterns
PAS-positive diastase-resistant granules.
Cellular Characteristics:
Large polygonal cells
Abundant granular eosinophilic cytoplasm
Round to oval nuclei
Prominent eosinophilic nucleoli
Moderate to high nuclear grade.
Architectural Patterns:
Complex glandular architecture
Solid sheets and nests
Cribriform patterns common
Papillary areas possible
Infiltrative growth into stroma.
Grading Criteria:
Usually high-grade tumors
Nuclear grade 2-3
Architectural grade variable
High mitotic rate (>10/10 HPF)
Necrosis common in high-grade tumors.
Immunohistochemistry
Positive Markers:
GCDFP-15 positive (80%)
AR (androgen receptor) positive (85%)
CK7 positive (95%)
CEA positive (70%)
GATA3 variable (50%)
PAX8 positive (60%).
Negative Markers:
CK20 negative
CDX2 negative
ER/PR usually negative
p16 often negative (HPV-independent)
Mammaglobin variable
TTF-1 negative.
Diagnostic Utility:
GCDFP-15 and AR confirm apocrine differentiation
CK7/PAX8 support gynecologic origin
Negative p16 suggests HPV-independence
GATA3 less reliable than in breast.
Molecular Subtypes:
HPV-independent pathway predominant
Hormone receptor negative phenotype
HER2 amplification rare
Androgen-driven molecular profile.
Molecular/Genetic
Genetic Mutations:
PIK3CA mutations (40%)
TP53 mutations (50%)
PTEN loss (30%)
AKT1 mutations (15%)
MAP3K1 mutations (10%).
Molecular Markers:
HPV DNA usually negative
Androgen receptor signaling active
High Ki-67 index (30-50%)
p53 overexpression common
Loss of PTEN expression.
Prognostic Significance:
Generally aggressive behavior
High stage at presentation
AR expression may predict hormone therapy response
p53 mutation associated with poor outcome.
Therapeutic Targets:
Anti-androgen therapy potential option
PI3K/AKT inhibitors under investigation
Standard chemotherapy often used
Radiation therapy for local control.
Differential Diagnosis
Similar Entities:
Metastatic breast carcinoma: ER+, mammoglobin+
Clear cell carcinoma: clear cytoplasm, hobnail cells
Mesonephric carcinoma: GATA3+, CD10+
Endometrioid carcinoma: ER+, squamous differentiation.
Distinguishing Features:
Apocrine carcinoma: GCDFP-15+, AR+, granular cytoplasm
Breast metastasis: ER+, different clinical history
Clear cell: glycogen-rich, not granular
Mesonephric: lateral cervix location.
Diagnostic Challenges:
Distinction from breast metastasis critical
Limited tissue in biopsy
Rare entity often not considered
IHC panel essential
Clinical correlation required.
Rare Variants:
Apocrine carcinoma in situ
Mixed apocrine-mucinous carcinoma
Apocrine carcinoma with neuroendocrine features
Microinvasive apocrine carcinoma.
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 apocrine carcinoma, [well/moderately/poorly] differentiated
Histological Features
Malignant glandular neoplasm with abundant eosinophilic granular cytoplasm, apical snouts, decapitation secretion, and prominent nucleoli consistent with apocrine differentiation
Tumor Size
Greatest dimension: [X] cm; Additional dimensions: [X] × [X] cm
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)
Lymphovascular Invasion
[Present/Absent]; Pattern: [focal/multifocal]
Parametrial Involvement
Right parametrium: [Involved/Not involved]; Left parametrium: [Involved/Not involved]
Lymph Nodes
Total nodes examined: [X]; Positive nodes: [X]; Largest metastatic deposit: [X] mm
Immunohistochemistry
GCDFP-15: Positive; AR: Positive; CK7: Positive; PAX8: [Positive/Negative]; p16: Negative; ER/PR: Negative
Molecular Testing
HPV ISH: Negative; Additional testing: [as indicated]
Pathological Stage
FIGO Stage (2018): [stage]; TNM Stage (8th edition): pT[X]N[X]M[X]
Additional Findings
[Background cervical changes/Other findings]