Definition/General
Introduction:
Fallopian tube minimal deviation adenocarcinoma (MDA) is an extremely rare, well-differentiated variant of tubal adenocarcinoma characterized by deceptively bland cytological appearance
It represents the tubal equivalent of cervical adenoma malignum
The tumor shows minimal nuclear atypia despite invasive behavior
It accounts for less than 1% of all fallopian tube carcinomas
The bland morphology often leads to underdiagnosis or delayed diagnosis.
Origin:
Originates from the epithelial cells of the fallopian tube with retained secretory differentiation
The tumor demonstrates preserved glandular architecture with minimal cytological atypia
May arise from hyperplastic or metaplastic epithelium
The well-differentiated appearance belies the malignant nature
Deep stromal invasion is the key feature indicating malignancy.
Classification:
WHO classification includes it as a variant of well-differentiated adenocarcinoma
Grade 1 adenocarcinoma with minimal deviation from normal morphology
Must demonstrate stromal invasion to distinguish from benign conditions
May show focal areas of conventional adenocarcinoma
FIGO staging follows standard criteria
Similar to cervical adenoma malignum morphologically.
Epidemiology:
Extremely rare with fewer than 30 cases reported worldwide
Peak incidence in 4th-5th decades (younger than typical tubal carcinomas)
No specific racial predilection
May be associated with Peutz-Jeghers syndrome (similar to cervical counterpart)
No established BRCA association
Better prognosis than high-grade carcinomas
Often diagnosed at early stage.
Clinical Features
Presentation:
Subtle clinical presentation with indolent course
Mild pelvic discomfort or pressure sensation
Abnormal vaginal discharge (watery, non-bloody)
Irregular vaginal bleeding (may be minimal)
Slowly growing pelvic mass
Often asymptomatic in early stages
May be incidental finding during surgery for other indications.
Symptoms:
Mild pelvic pain or discomfort
Watery vaginal discharge (clear to white)
Minimal irregular bleeding
Feeling of pelvic fullness
No constitutional symptoms typically
Gradual onset over months to years
May be completely asymptomatic.
Risk Factors:
Peutz-Jeghers syndrome (STK11 mutations, similar to cervical MDA)
Advanced reproductive age (>35 years)
Nulliparity (possible association)
Family history of gynecological cancers
No established BRCA association
Chronic hormonal stimulation (theoretical risk)
Environmental factors (unclear role).
Screening:
No specific screening protocols due to extreme rarity
Standard gynecological examination
Genetic counseling for PJS patients
Regular surveillance in Peutz-Jeghers syndrome
Transvaginal ultrasound for pelvic mass evaluation
CA-125 levels typically normal or minimally elevated.
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Gross Description
Appearance:
Well-circumscribed, solid mass with smooth surface
Tan to yellow cut surface
Soft to firm consistency
Minimal necrosis or hemorrhage
May appear benign grossly
Cystic areas may be present
Well-demarcated margins.
Characteristics:
Homogeneous appearance on cut surface
Tan-yellow coloration
Absence of obvious malignant features
Smooth, lobulated surface
Firm consistency
Minimal calcifications
No prominent vascular pattern.
Size Location:
Size ranges from 2-6 cm (typically smaller)
May involve any part of the fallopian tube
Ampullary region commonly affected
Usually unilateral
Limited extension beyond tube at diagnosis
Confined to tube in majority of cases.
Multifocality:
Usually unifocal within the tube
Clear demarcation from normal tissue
No satellite lesions typically
Bilateral involvement rare
Minimal peritoneal involvement
Early stage at presentation.
Microscopic Description
Histological Features:
Well-formed glands with minimal architectural distortion
Bland nuclear morphology with minimal atypia
Cuboidal to low columnar epithelium
Preserved nuclear polarity
Low mitotic activity (<5 per 10 HPF)
Deep stromal invasion is key diagnostic feature
Desmoplastic stromal response may be minimal.
Cellular Characteristics:
Cuboidal to columnar cells with abundant cytoplasm
Eosinophilic to clear cytoplasm
Small, uniform nuclei with minimal enlargement
Inconspicuous nucleoli
Maintained cellular polarity
Minimal nuclear pleomorphism
Rare mitotic figures.
Architectural Patterns:
Well-formed glandular pattern predominates
Simple tubular architecture
Back-to-back glands in some areas
Minimal papillary features
Single-layered epithelium lining glands
Absence of solid areas
Infiltrative growth pattern into stroma.
Grading Criteria:
Grade 1 adenocarcinoma by definition
Architectural grade 1 (well-formed glands)
Nuclear grade 1 (minimal atypia)
Low mitotic count (<5 per 10 HPF)
Absence of necrosis
Well-differentiated appearance throughout.
Immunohistochemistry
Positive Markers:
CK7 (diffusely positive in epithelial cells)
PAX8 (nuclear, confirming müllerian origin)
CA125 (may be positive in luminal surface)
CEA (may be positive, similar to cervical MDA)
ER (positive in majority of cases)
PR (positive in 60-70%)
EMA (epithelial membrane antigen).
Negative Markers:
CK20 (negative, excludes gastrointestinal origin)
CDX2 (negative, excludes intestinal differentiation)
TTF-1 (negative, excludes lung origin)
p16 (negative to focal, unlike HPV-related tumors)
WT1 (typically negative, unlike serous carcinomas)
p63 (negative in tumor cells)
Calretinin (negative).
Diagnostic Utility:
PAX8 positivity confirms müllerian/tubal origin
CK7+/CK20- pattern supports gynecological primary
ER/PR positivity indicates hormone receptor status
CEA positivity may support MDA diagnosis
p16 negativity helps exclude HPV-related tumors
Low Ki-67 consistent with well-differentiated nature.
Molecular Subtypes:
Hormone receptor positive subtype
Low proliferation subtype (Ki-67 <10%)
p53 wild-type subtype
Microsatellite stable subtype
STK11-associated subtype (in PJS patients)
BRCA wild-type subtype.
Molecular/Genetic
Genetic Mutations:
STK11 mutations (in Peutz-Jeghers syndrome-associated cases)
TP53 mutations (rare, unlike high-grade carcinomas)
PIK3CA mutations (may be present, 10-20%)
KRAS mutations (uncommon)
CTNNB1 mutations (Wnt pathway)
PTEN alterations (rare)
BRCA1/2 mutations (no established association).
Molecular Markers:
p53 wild-type pattern (normal nuclear staining)
STK11 protein loss (in PJS-associated cases)
β-catenin expression (may show alterations)
Ki-67 proliferation index (very low, <10%)
mTOR pathway activation (in STK11-mutated cases)
PD-L1 expression (typically negative)
Microsatellite stability.
Prognostic Significance:
Better prognosis than conventional adenocarcinomas
Early stage at diagnosis (majority Stage I)
Low metastatic potential
Good response to treatment
Long-term survival (>90% 5-year survival)
Low recurrence rate
STK11 mutations may influence targeted therapy options.
Therapeutic Targets:
Hormone therapy (for ER/PR positive cases)
mTOR inhibitors (for STK11-mutated, PJS-associated cases)
PI3K inhibitors (for PIK3CA-mutated cases)
Standard chemotherapy (platinum-based for advanced cases)
Anti-angiogenic agents (limited role)
Immunotherapy (minimal role due to low TMB)
CDK4/6 inhibitors (hormone receptor positive).
Differential Diagnosis
Similar Entities:
Tubal hyperplasia (benign proliferative condition)
Adenofibroma (benign tumor with glandular component)
Well-differentiated adenocarcinoma, NOS
Endometrioid carcinoma, Grade 1
Metastatic adenocarcinoma from cervix (adenoma malignum)
Serous cystadenoma with proliferative features
Endosalpingiosis (ectopic tubal epithelium).
Distinguishing Features:
MDA vs hyperplasia: Stromal invasion, irregular glandular distribution, loss of basement membrane
MDA vs adenofibroma: Infiltrative growth, absence of fibrous stroma, cellular atypia
Primary vs metastatic: Clinical history, PAX8 positivity, site of origin
MDA vs conventional adenocarcinoma: Bland morphology, minimal atypia.
Diagnostic Challenges:
Recognizing stromal invasion in bland-appearing tumor
Distinguishing from benign conditions
Limited tissue sampling may miss invasive areas
Differentiating from metastatic cervical MDA
Assessing depth of invasion
Identifying minimal cytological atypia.
Rare Variants:
Mixed MDA and conventional adenocarcinoma
MDA with focal high-grade areas
Cystic MDA variant
MDA with mucinous differentiation
MDA with endometrioid features
MDA with clear cell areas
Multicystic MDA pattern.
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
[Unilateral/Bilateral] salpingo-oophorectomy, fallopian tube measuring [size] cm with well-circumscribed tumor
Diagnosis
Minimal deviation adenocarcinoma (adenoma malignum) of fallopian tube
Classification
Well-differentiated adenocarcinoma, minimal deviation type (Grade 1)
Histological Features
Shows well-formed glands with bland nuclear morphology and preserved cellular polarity
Minimal Deviation Features
Deceptively bland cytology with minimal nuclear atypia, low mitotic activity, deep stromal invasion
Stromal Invasion
Stromal invasion: present, Depth: [X] mm, Pattern: [infiltrative/pushing], Desmoplasia: [minimal/present]
Histological Grading
Grade 1: Well-differentiated glands, minimal nuclear atypia, low mitotic count (<5/10 HPF)
Extent of Disease
Size: [X] cm, Confined to fallopian tube, No surface involvement
Special Studies
CK7: positive, PAX8: positive (confirming müllerian origin)
ER: [positive/negative], PR: [positive/negative]
CEA: [positive/negative], p16: negative/focal
Molecular Features
p53: wild-type pattern, Ki-67: [very low, <10%], Consider STK11 testing (Peutz-Jeghers syndrome)
FIGO Staging
FIGO Stage: [IA/IB/IC] - confined to fallopian tube
Prognostic Factors
Minimal deviation adenocarcinoma (excellent prognosis), Grade 1, Early stage, Hormone receptor status: [ER/PR status]
Final Diagnosis
Primary fallopian tube minimal deviation adenocarcinoma, FIGO Stage [IA/IB/IC]