Definition/General

Introduction:
-Cervical minimal deviation adenocarcinoma (adenoma malignum) is a rare, extremely well-differentiated mucinous adenocarcinoma that closely mimics benign endocervical glands
-It has association with Peutz-Jeghers syndrome and STK11 mutations.
Origin:
-Arises from endocervical glandular epithelium with minimal morphologic deviation from normal
-Shows deep invasion despite bland cytology
-May be associated with STK11 germline mutations.
Classification:
-WHO Classification recognizes minimal deviation adenocarcinoma as distinct entity
-Also known as adenoma malignum
-Extremely well-differentiated mucinous type.
Epidemiology:
-Peak incidence 30-50 years
-Represents <1% of cervical adenocarcinomas
-Association with Peutz-Jeghers syndrome (15-20% of cases)
-Often HPV-independent
-Poor prognosis due to late diagnosis.

Clinical Features

Presentation:
-Profuse watery vaginal discharge
-May have minimal or no bleeding
-Often normal-appearing cervix
-Late-stage presentation common.
Symptoms:
-Profuse watery vaginal discharge (hallmark)
-Minimal vaginal bleeding
-Pelvic pain in advanced cases
-May be asymptomatic initially
-Constitutional symptoms late.
Risk Factors:
-Peutz-Jeghers syndrome (STK11 mutations)
-Family history of PJS
-Mucocutaneous pigmentation
-Gastrointestinal polyposis
-Usually HPV-independent.
Screening:
-Standard screening often negative
-Cytology frequently normal
-High index of suspicion needed
-Deep endocervical sampling essential
-MRI helpful for assessment.

Master Cervical Minimal Deviation Adenocarcinoma Pathology with RxDx

Access 100+ pathology videos and expert guidance with the RxDx app

Gross Description

Appearance:
-Often grossly normal cervix
-May show cervical enlargement or induration
-Yellow, mucinous discharge possible
-Difficult to identify grossly.
Characteristics:
-Cervix may appear normal or enlarged
-Firm consistency on palpation
-Mucinous material may be present
-No obvious mass lesion.
Size Location:
-Deep endocervical involvement
-May extend into lower uterine segment
-Parametrial involvement possible
-Difficult to assess extent grossly.
Multifocality:
-Often multifocal deep glands
-Extensive involvement of endocervix
-Skip lesions possible
-May involve entire endocervical canal.

Microscopic Description

Histological Features:
-Irregular, angulated glands with minimal cytologic atypia
-Glands extend deep into stroma beyond normal limit
-Bland cytology despite invasive behavior.
Cellular Characteristics:
-Tall columnar cells with minimal atypia
-Abundant mucin production
-Low nuclear grade
-Rare mitoses
-Cytology closely resembles normal endocervix.
Architectural Patterns:
-Irregular, angulated glands
-Cribriform pattern possible
-Back-to-back arrangement
-Glands extending >7mm from surface
-Desmoplastic stroma variable.
Grading Criteria:
-Well-differentiated by definition
-Minimal cytologic atypia
-Low mitotic rate
-Diagnosis based on architectural features and depth.

Immunohistochemistry

Positive Markers:
-CEA positive
-HIK1083 positive
-p16 usually negative (HPV-independent)
-CK7 positive
-PAX8 positive
-Mucin stains positive.
Negative Markers:
-p16 negative or patchy
-CK20 negative
-TTF-1 negative
-Estrogen receptor variable
-Progesterone receptor variable.
Diagnostic Utility:
-CEA and HIK1083 help distinguish from normal glands
-p16 negativity suggests HPV-independent pathway
-STK11 loss in PJS-associated cases.
Molecular Subtypes:
-HPV-independent adenocarcinoma
-Peutz-Jeghers syndrome-associated vs sporadic.

Molecular/Genetic

Genetic Mutations:
-STK11 mutations (germline in PJS, somatic in sporadic)
-KRAS mutations common
-PIK3CA mutations
-GNAS mutations
-Usually HPV-negative.
Molecular Markers:
-STK11 loss of function
-KRAS activation
-mTOR pathway activation
-Usually HPV DNA negative
-Low tumor mutational burden.
Prognostic Significance:
-Poor prognosis due to late diagnosis and advanced stage
-Deep invasion despite bland morphology
-High metastatic potential.
Therapeutic Targets:
-mTOR inhibitors (STK11 pathway)
-MEK inhibitors (KRAS pathway)
-Limited targeted options
-Standard chemotherapy often ineffective.

Differential Diagnosis

Similar Entities:
-Normal endocervical glands
-Tunnel clusters
-Endocervical hyperplasia
-Nabothian cysts
-Lobular endocervical glandular hyperplasia.
Distinguishing Features:
-MDA: Irregular glands, >7mm depth, CEA+
-Normal glands: Regular, <7mm depth, CEA-
-Tunnel clusters: Dilated glands, no atypia.
Diagnostic Challenges:
-Bland cytology mimics benign
-Assessment of invasion depth
-Recognition of architectural abnormalities
-Adequate sampling essential.
Rare Variants:
-Minimal deviation with focal conventional adenocarcinoma
-Mixed minimal deviation and villoglandular
-Gastric-type minimal deviation.

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]