Vulvar adenocarcinoma is a rare, heterogeneous group of gland-forming vulvar epithelial malignancies. Important adenocarcinoma-related entities include Bartholin gland adenocarcinoma, intestinal-type vulvar adenocarcinoma, mammary gland type adenocarcinoma, and invasive or Paget-associated extramammary Paget disease. Because adenocarcinoma subtypes are uncommon, diagnosis and management rely on subtype-directed pathology plus broader vulvar cancer staging and treatment principles.
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name: Vulvar Adenocarcinoma
creation_date: "2026-05-09T13:22:22Z"
updated_date: "2026-05-09T22:56:09Z"
synonyms:
- Adenocarcinoma of the vulva
- Vulva adenocarcinoma
- Bartholin gland adenocarcinoma
- Intestinal-type vulvar adenocarcinoma
- Vulvar adenocarcinoma of mammary gland type
description: >-
Vulvar adenocarcinoma is a rare, heterogeneous group of gland-forming vulvar
epithelial malignancies. Important adenocarcinoma-related entities include
Bartholin gland adenocarcinoma, intestinal-type vulvar adenocarcinoma,
mammary gland type adenocarcinoma, and invasive or Paget-associated
extramammary Paget disease. Because adenocarcinoma subtypes are uncommon,
diagnosis and management rely on subtype-directed pathology plus broader
vulvar cancer staging and treatment principles.
categories:
- Gynecologic Malignancy
- Adenocarcinoma
- Solid Tumor
- Rare Cancer
parents:
- vulvar glandular neoplasm
- vulvar carcinoma
- adenocarcinoma
disease_term:
preferred_term: vulvar adenocarcinoma
term:
id: MONDO:0024336
label: vulvar adenocarcinoma
definitions:
- name: Clinicopathologic definition
definition_type: CASE_DEFINITION
description: >-
A primary vulvar malignant epithelial tumor with glandular differentiation,
diagnosed by biopsy and histopathology, with subtype-specific
immunohistochemistry used to distinguish primary vulvar origin from
metastatic gastrointestinal, breast, urothelial, or other primaries.
scope: Gynecologic oncology and surgical pathology definition
evidence:
- reference: PMID:38503056
reference_title: "Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Rarer histologies exist and include melanoma, extramammary Paget's
disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell
carcinoma, and sarcoma.
explanation: >-
The NCCN guideline recognizes Bartholin gland adenocarcinoma and
extramammary Paget disease among rare vulvar cancer histologies that need
subtype-aware management.
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
To confirm vulvar origin, a thorough diagnostic, and radiological
examination is required to rule out other primary malignancies.
explanation: >-
This supports the need to exclude metastatic or non-vulvar primaries when
diagnosing intestinal-type vulvar adenocarcinoma.
has_subtypes:
- name: Intestinal-Type
display_name: Intestinal-type vulvar adenocarcinoma
classification: histologic
description: >-
A rare sporadic vulvar carcinoma with intestinal differentiation, commonly
resembling mucinous colorectal carcinoma and requiring exclusion of a
colorectal or other gastrointestinal primary.
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Intestinal-type adenocarcinoma (VAIt) represents a sporadic variant of
vulvar carcinoma.
explanation: >-
This directly defines VAIt as a vulvar adenocarcinoma subtype.
- name: Mammary Gland Type
display_name: Vulvar adenocarcinoma of mammary gland type
classification: histologic
description: >-
A very rare vulvar adenocarcinoma with mammary-like morphology or
immunophenotype; diagnosis can require breast-carcinoma mimicry assessment
and exclusion of metastatic breast carcinoma.
evidence:
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Adenocarcinoma of mammary gland type (AMGT) of the vulva is extremely
rare and its aetiopathogenesis is not fully understood.
explanation: >-
This case-report paper defines AMGT as an extremely rare vulvar
adenocarcinoma entity.
- name: Bartholin Gland Adenocarcinoma
display_name: Bartholin gland adenocarcinoma
classification: anatomic and histologic
description: >-
A Bartholin-region primary adenocarcinoma. Published Bartholin gland
carcinoma cohorts are very small and are dominated by squamous carcinoma,
so adenocarcinoma-specific evidence remains limited.
evidence:
- reference: PMID:29406447
reference_title: "Bartholin Gland Carcinoma: Clinicopathologic Features, Including p16 Expression and Clinical Outcome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
There were 12 squamous cell carcinomas (SCCs), including 1 SCC with
transitional-like morphology and 1 papillary SCC, and 1 adenocarcinoma.
explanation: >-
This Bartholin gland carcinoma cohort included a Bartholin gland
adenocarcinoma case, supporting the subtype.
- name: Paget-Associated
display_name: Invasive or Paget-associated vulvar adenocarcinoma
classification: histologic
description: >-
Extramammary Paget disease of the vulva is an adenocarcinoma-related vulvar
entity that can remain intraepithelial, become invasive, or be associated
with an underlying adenocarcinoma, with HER2-positive metastatic examples
reported.
evidence:
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Extramammary Paget's disease (EMPD) is a rare cancer that occurs within
the epithelium of the skin, arising predominantly in areas with high
apocrine gland concentration such as the vulva, scrotum, penis and
perianal regions.
explanation: >-
This supports EMPD as a rare apocrine-rich skin cancer involving the
vulva and related to the glandular vulvar cancer differential.
pathophysiology:
- name: Vulvar Glandular Epithelial Transformation
description: >-
Malignant transformation of glandular or secretory epithelial structures in
the vulva produces a rare adenocarcinoma phenotype. Depending on anatomic
origin and differentiation program, tumors may present as Bartholin gland,
intestinal-type, mammary-like, or Paget-associated disease.
evidence:
- reference: PMID:38503056
reference_title: "Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Rarer histologies exist and include melanoma, extramammary Paget's
disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell
carcinoma, and sarcoma.
explanation: >-
NCCN identifies Bartholin gland adenocarcinoma and EMPD as rare vulvar
cancer histologies, supporting glandular subtype heterogeneity.
cell_types:
- preferred_term: vulvar glandular epithelial cell
term:
id: CL:0000066
label: epithelial cell
- preferred_term: vulvar secretory epithelial cell
term:
id: CL:0000151
label: secretory cell
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: epithelial cell proliferation
modifier: INCREASED
term:
id: GO:0050673
label: epithelial cell proliferation
- preferred_term: cell migration
modifier: INCREASED
term:
id: GO:0016477
label: cell migration
downstream:
- target: Subtype-Specific Differentiation Programs
description: The transformed glandular epithelium follows intestinal, mammary-like, Bartholin, or Paget-associated programs.
- name: Intestinal Differentiation Program
description: >-
Intestinal-type vulvar adenocarcinoma resembles mucinous colonic carcinoma,
probably arises from cloacal remnants or related intestinalized epithelium,
and is supported by intestinal marker expression such as CK20 and CDX2.
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
It appears frequently localized to epithelial glands in the vulvar
region, and it probably derives from cloacal remnants persisting in the
adult.
explanation: >-
The review supports a glandular vulvar location and proposed cloacal
remnant origin for intestinal-type disease.
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The principal histological VAIt characteristic is that it resembles
mucinous colonic carcinomas.
explanation: >-
This supports intestinal or colorectal-like differentiation in VAIt.
cell_types:
- preferred_term: intestinalized vulvar glandular epithelial cell
term:
id: CL:0000066
label: epithelial cell
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: epithelial cell proliferation
modifier: INCREASED
term:
id: GO:0050673
label: epithelial cell proliferation
downstream:
- target: Subtype-Directed Diagnostic Workup
description: Intestinal differentiation prompts CK20, CDX2, and CK7 immunohistochemistry and exclusion of a gastrointestinal primary.
- name: Mammary-Like Carcinoma Program
description: >-
Mammary gland type vulvar adenocarcinoma can show breast-carcinoma-like
pathology or immunophenotype, making histopathology and breast-primary
exclusion central to diagnosis.
evidence:
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Interestingly, it presented an immunophenotypical profile similar to
triple-negative breast cancers, supporting the molecular similarities
between vulvar AMGT and breast carcinomas.
explanation: >-
This supports a mammary-like molecular and pathologic program in some
AMGT cases.
cell_types:
- preferred_term: mammary-like vulvar glandular epithelial cell
term:
id: CL:0000066
label: epithelial cell
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: epithelial cell proliferation
modifier: INCREASED
term:
id: GO:0050673
label: epithelial cell proliferation
downstream:
- target: Subtype-Directed Diagnostic Workup
description: Breast-carcinoma-like immunophenotype requires correlation with imaging and pathology to exclude metastatic breast carcinoma.
- name: HER2-Positive Paget-Associated Signaling
description: >-
Some invasive or metastatic EMPD cases show HER2-positive tumor cells and a
copy-number landscape enriched for receptor tyrosine kinase, FGFR1, and
TGF-beta signaling programs, creating a rationale for HER2-directed
systemic treatment in selected advanced disease.
evidence:
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Immunohistochemical staining on the scrotal wall tumor and bone marrow
metastasis demonstrated HER2 overexpression.
explanation: >-
This demonstrates HER2 overexpression in a metastatic EMPD tumor sample.
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: >-
Enrichment in pathways associated with transforming growth factor-beta
(TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth
factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3)
was detected.
explanation: >-
The pathway enrichment analysis supports TGF-beta and FGFR1 signaling as
part of the metastatic EMPD molecular landscape.
cell_types:
- preferred_term: apocrine-rich epithelial cell
term:
id: CL:0000066
label: epithelial cell
genes:
- preferred_term: ERBB2
term:
id: hgnc:3430
label: ERBB2
- preferred_term: FGFR1
term:
id: hgnc:3688
label: FGFR1
locations:
- preferred_term: vulva
term:
id: UBERON:0000997
label: mammalian vulva
biological_processes:
- preferred_term: cell surface receptor protein tyrosine kinase signaling pathway
modifier: INCREASED
term:
id: GO:0007169
label: cell surface receptor protein tyrosine kinase signaling pathway
- preferred_term: transforming growth factor beta receptor signaling pathway
modifier: INCREASED
term:
id: GO:0007179
label: transforming growth factor beta receptor signaling pathway
- preferred_term: fibroblast growth factor receptor signaling pathway
modifier: INCREASED
term:
id: GO:0008543
label: fibroblast growth factor receptor signaling pathway
downstream:
- target: HER2-Directed Pharmacotherapy Response
description: HER2-positive metastatic EMPD can respond to HER2-directed systemic therapy in selected cases.
- name: Subtype-Directed Diagnostic Workup
description: >-
Histology, immunohistochemistry, biopsy confirmation, imaging, and exclusion
of other primary sites determine whether a glandular vulvar tumor is a
primary vulvar adenocarcinoma subtype or metastasis.
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Therefore, immunohistochemical workup, with different tumor markers
including CK20, CDX2, and CK7 staining, is needed.
explanation: >-
This supports immunohistochemistry as a central diagnostic step for
intestinal-type vulvar adenocarcinoma.
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Histopathological patterns are considered essential for diagnosis.
explanation: >-
This supports histopathology as essential for AMGT diagnosis.
downstream:
- target: Surgical Local Control
description: Subtype and stage guide local excision, nodal assessment, adjuvant treatment, and systemic therapy selection.
phenotypes:
- category: Gynecologic
name: Vulvar Lump or Mass
description: >-
A noticed lump or mass can be a presenting manifestation of vulvar cancer,
including rare glandular histologies that present as vulvar lesions.
phenotype_term:
preferred_term: vulvar neoplasm
term:
id: HP:0030416
label: Vulvar neoplasm
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
This supports lump as a presenting sign for vulvar cancer overall; the
evidence is treated as partial for the rarer adenocarcinoma subtype.
- category: Dermatologic
name: Vulvar Ulcer
description: >-
Ulceration can be part of the presenting vulvar lesion complex.
phenotype_term:
preferred_term: vulvar ulcer
term:
id: HP:0200042
label: Skin ulcer
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
This supports ulcer as a presenting sign for vulvar cancer overall; the
evidence is partial for adenocarcinoma-specific presentation.
- category: Dermatologic
name: Vulvar Pruritus
description: >-
Pruritus is a common symptom in vulvar cancer presentations and may also be
clinically relevant in Paget-associated vulvar glandular disease.
phenotype_term:
preferred_term: Vulvar pruritus
term:
id: HP:0000989
label: Pruritus
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
This supports pruritus as a vulvar cancer symptom, with partial support
for rare adenocarcinoma subtypes.
- category: Pain
name: Vulvar Pain or Burning
description: >-
Vulvar pain, soreness, or burning may accompany the lesion and can prompt
diagnostic evaluation.
phenotype_term:
preferred_term: Vulvar pain
term:
id: HP:0012531
label: Pain
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
While vulvar cancer may be asymptomatic, most women present with vulvar
pruritus or pain, or have noticed a lump or ulcer.
explanation: >-
This supports pain as a vulvar cancer symptom, with partial support for
the adenocarcinoma subtype.
- category: Laboratory
name: Abnormal Glandular Cytology in Paget Spread
description: >-
Cervical or vaginal involvement by vulvar EMPD can be clinically silent and
detected through abnormal glandular cytology during follow-up.
evidence:
- reference: PMID:36766569
reference_title: "Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All cases except one were firstly detected by abnormal glandular cytology.
None reported vaginal bleeding or other suspicious symptoms.
explanation: >-
This supports abnormal glandular cytology as a clinically relevant
finding in cervico-vaginal involvement from vulvar EMPD.
stages:
- name: Clinical Staging and Imaging Context
description: >-
Vulvar adenocarcinoma staging is handled within the broader vulvar cancer
framework, combining clinical assessment with selected imaging for local,
nodal, and distant disease.
evidence:
- reference: PMID:38927973
reference_title: "Imaging in Vulval Cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Various imaging modalities are widely used in conjunction with clinical
assessment in the diagnosis and staging of vulval cancers; however, there
is significant heterogeneity in which modalities are recommended in
international guidelines, reflecting the paucity of evidence in this
area.
explanation: >-
This supports clinical assessment plus imaging as the staging context and
highlights the limited evidence base.
- reference: PMID:38927973
reference_title: "Imaging in Vulval Cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
For distant metastases, CT CAP and FDG-PET/CT have the most evidence to
support their use.
explanation: >-
This supports CT chest/abdomen/pelvis and FDG-PET/CT for assessment of
distant metastases.
genetic:
- name: ERBB2
association: HER2 overexpression in Paget-associated disease
gene_term:
preferred_term: ERBB2
term:
id: hgnc:3430
label: ERBB2
notes: >-
HER2-positive metastatic EMPD can show HER2 protein overexpression even
without high-level ERBB2 copy-number gain in the reported case.
evidence:
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Interestingly, ERBB2 gene did not exhibit high copy number gain (log2FC =
0.4) although 90% of tumor cells stained HER2-positive.
explanation: >-
This supports ERBB2/HER2 as a clinically relevant biomarker axis in
selected Paget-associated disease.
- name: FGFR1
association: Pathway enrichment in HER2-positive metastatic EMPD
gene_term:
preferred_term: FGFR1
term:
id: hgnc:3688
label: FGFR1
notes: >-
FGFR1 appeared among cancer-associated genes and in enriched signaling
pathways in a WGS case report of HER2-positive metastatic EMPD.
evidence:
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1,
NSD3, ADAM9, BRF2, KAT6A and FGFR1.
explanation: >-
This supports FGFR1 involvement in the copy-number landscape of the
reported metastatic EMPD tumor.
environmental:
- name: General Vulvar Cancer Risk Context
description: >-
Increasing age, HPV infection, smoking, inflammatory vulvar disease, and
immunodeficiency are recognized vulvar cancer risk factors. Their
adenocarcinoma-subtype specificity is limited, so this is annotated as
contextual rather than definitive adenocarcinoma causation.
evidence:
- reference: PMID:38503056
reference_title: "Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Known risk factors for vulvar cancer include increasing age, infection
with human papillomavirus, cigarette smoking, inflammatory conditions
affecting the vulva, and immunodeficiency.
explanation: >-
This supports the general vulvar cancer risk context, but the evidence is
partial for vulvar adenocarcinoma because many data are dominated by
squamous carcinoma.
diagnosis:
- name: Biopsy of Suspicious Vulvar Lesion
description: >-
Suspicious vulvar lesions require biopsy to establish invasion and
histologic subtype. Vulvoscopy and imaging can help target biopsy and plan
preoperative staging.
results: Histopathologic confirmation of invasive glandular vulvar malignancy.
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Therefore, any suspicious vulvar lesion should be biopsied to exclude
invasion.
explanation: >-
This directly supports biopsy for suspicious vulvar lesions.
- reference: PMID:38791925
reference_title: "Current Preoperative Management of Vulvar Squamous Cell Carcinoma: An Overview."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Diagnosis relies on biopsy during vulvoscopy, plus imaging such as
ultrasonography (USG), magnetic resonance imaging (MRI) and positron
emission tomography (PET).
explanation: >-
This supports biopsy, vulvoscopy, and imaging in vulvar carcinoma
diagnosis; it is partial for adenocarcinoma because the review focuses on
squamous carcinoma.
- name: Subtype Immunohistochemistry and Primary-Site Exclusion
description: >-
Intestinal-type and mammary-like vulvar adenocarcinomas require
immunohistochemistry and clinicoradiologic exclusion of metastatic
gastrointestinal or breast primaries.
results: Primary vulvar origin and histologic subtype assignment.
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Therefore, immunohistochemical workup, with different tumor markers
including CK20, CDX2, and CK7 staining, is needed.
explanation: >-
This supports CK20, CDX2, and CK7 immunohistochemistry for VAIt.
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Histopathological patterns are considered essential for diagnosis.
explanation: >-
This supports histopathology for AMGT diagnosis.
- name: Paget Disease Cytology and Biopsy Follow-Up
description: >-
For long-standing vulvar EMPD, liquid-based cytology with
immunocytochemistry can detect clinically silent cervico-vaginal spread,
with biopsy confirmation when abnormal cytology is found.
results: Detection of cervico-vaginal EMPD involvement.
evidence:
- reference: PMID:36766569
reference_title: "Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Cervical and/or vaginal biopsies were always performed for
histopathological diagnosis by identification of Paget cells in the
epithelium or stroma.
explanation: >-
This supports biopsy confirmation of cervico-vaginal EMPD.
- reference: PMID:36766569
reference_title: "Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget's Disease of the Vulva: A Referral Center Experience."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Liquid-based cytology with immunocytochemistry represents a valuable tool
for early diagnosis and should be routinely performed during the required
lifelong follow-up.
explanation: >-
This supports cytology with immunocytochemistry during lifelong EMPD
follow-up.
treatments:
- name: Surgical Local Excision or Vulvectomy
description: >-
Surgery is the principal local-control strategy for primary vulvar
adenocarcinoma subtypes when technically feasible, with margin goals and
nodal evaluation tailored to histology, size, and stage.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
target_mechanisms:
- target: Vulvar Glandular Epithelial Transformation
treatment_effect: INHIBITS
description: Surgical removal aims to eliminate the local malignant glandular tumor.
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The gold standard of treatment for VAIt is surgery, with local excision
with tumor-free margins.
explanation: >-
This directly supports surgery with tumor-free margins for
intestinal-type vulvar adenocarcinoma.
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Surgical procedures include radical vulvectomy or radical local excision.
explanation: >-
This supports radical vulvectomy or local excision for AMGT cases.
- name: Nodal Assessment
description: >-
Lymph-node staging or assessment is considered for larger or clinically
suspicious intestinal-type tumors and for mammary gland type adenocarcinoma.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Lymph node staging is an option advised if the tumor size is >2 cm or if
lymph node metastases are suspected on imaging.
explanation: >-
This supports lymph-node staging for selected VAIt tumors.
- reference: PMID:35672058
reference_title: "Diagnosis and management of primary vulvar adenocarcinoma of mammary gland type: report of two distinct cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Lymphatic involvement may be assessed by sentinel lymph node biopsy or
lymphadenectomy.
explanation: >-
This supports lymphatic assessment approaches in AMGT.
- name: Adjuvant or Advanced-Disease Chemoradiation
description: >-
Chemotherapy and radiation are used selectively for advanced, recurrent, or
histology-specific vulvar cancers, with many adenocarcinoma decisions
extrapolated from broader vulvar cancer evidence.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
target_mechanisms:
- target: Vulvar Glandular Epithelial Transformation
treatment_effect: INHIBITS
description: Cytotoxic and radiation-based approaches aim to reduce residual or advanced malignant tumor burden.
evidence:
- reference: PMID:34669204
reference_title: "Cancer of the vulva: 2021 update."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Treatment is predominantly surgical, particularly for squamous cell
carcinoma, although concurrent chemoradiation is an effective alternative,
particularly for advanced tumors.
explanation: >-
This supports chemoradiation in advanced vulvar cancer generally; it is
partial for adenocarcinoma because the evidence base is histology-mixed
and dominated by squamous carcinoma.
- reference: PMID:36291953
reference_title: "\"Intestinal-Type\" Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
On the other hand, the role of neoadjuvant therapy is still in doubt, but
a good response to adjuvant chemotherapy treatments has been described in
both advanced and recurrent diseases.
explanation: >-
This supports a limited, subtype-specific role for adjuvant chemotherapy
in advanced or recurrent VAIt while preserving uncertainty.
- name: HER2-Directed Pharmacotherapy
description: >-
HER2-directed systemic therapy may be relevant in selected HER2-positive
metastatic EMPD or Paget-associated adenocarcinoma settings.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
target_mechanisms:
- target: HER2-Positive Paget-Associated Signaling
treatment_effect: INHIBITS
description: HER2-directed treatment is intended to counter HER2-positive signaling in selected metastatic EMPD.
evidence:
- reference: PMID:38831459
reference_title: "Whole genome sequencing of HER2-positive metastatic extramammary Paget's disease: a case report."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The presence of alternative signalling pathways and genetic variants
suggests potential interactions with HER2 signalling, which possibly
contributed to the HER2 overexpression and observed response to
HER2-directed therapy combined with other agents in a comprehensive
treatment regimen.
explanation: >-
This supports HER2-directed treatment response in a single metastatic
EMPD case, so the treatment evidence is intentionally marked partial.
- name: Topical Imiquimod for Vulvar Paget Disease
description: >-
Topical imiquimod is an investigational or non-surgical pharmacotherapy
option studied in non-invasive or recurrent vulvar Paget disease. Its
relevance to invasive Paget-associated vulvar adenocarcinoma is indirect,
so the treatment evidence is treated as partial.
treatment_term:
preferred_term: topical pharmacotherapy
term:
id: MAXO:0001573
label: topical pharmacotherapy
therapeutic_agent:
- preferred_term: imiquimod
term:
id: CHEBI:36704
label: imiquimod
evidence:
- reference: clinicaltrials:NCT02385188
reference_title: "Topical 5% Imiquimod Cream for Vulvar Paget's Disease: Clinical Efficacy, Safety and Immunological Response"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The purpose of this study is to evaluate the efficacy, safety and
immunological response of topical 5% imiquimod cream for non-invasive
vulvar Paget's disease.
explanation: >-
This supports topical imiquimod as a studied treatment for non-invasive
vulvar Paget disease, with partial applicability to the broader
adenocarcinoma page.
- reference: clinicaltrials:NCT00504023
reference_title: "A Pilot Study of Topical Imiquimod Therapy for the Treatment of Recurrent Extramammary Paget's Disease"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
PURPOSE: This clinical trial is studying how well topical imiquimod works
in treating patients with recurrent Paget's disease of the vulva.
explanation: >-
This supports topical imiquimod as a trialed treatment for recurrent
vulvar Paget disease.
- name: Photodynamic Therapy for Vulvar Paget Disease
description: >-
Photodynamic therapy is being studied as a local treatment alternative for
vulvar Paget disease. It is annotated as partial because the trial evidence
is Paget-specific and not direct evidence for all invasive vulvar
adenocarcinoma subtypes.
treatment_term:
preferred_term: photodynamic therapy
term:
id: MAXO:0020022
label: photodynamic therapy
evidence:
- reference: clinicaltrials:NCT03713203
reference_title: "An Interventional, Phase II, Non Randomized, Mono-centric Study on the Clinical Efficacy and Safety of the Medical Device PAGETEX® as a Photodynamic Therapy Device in the Treatment of Extra-Mammary Paget's Disease of the Vulva (EMPV)"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Photodynamic therapy (PDT) is already used in some dermatological
pathologies and could therefore be an alternative treatment.
explanation: >-
This supports photodynamic therapy as an investigational alternative for
vulvar Paget disease.
- reference: clinicaltrials:NCT03713203
reference_title: "An Interventional, Phase II, Non Randomized, Mono-centric Study on the Clinical Efficacy and Safety of the Medical Device PAGETEX® as a Photodynamic Therapy Device in the Treatment of Extra-Mammary Paget's Disease of the Vulva (EMPV)"
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The objective of this study is to assess the efficacy and evaluate the
safety of the new PDT device "PAGETEX" for the treatment of vulvar
Paget's disease.
explanation: >-
This clinical trial record directly links PDT evaluation to vulvar Paget
disease.
notes: >-
Falcon deep research was performed on 2026-05-09. The resulting report
emphasized that vulvar adenocarcinoma evidence is sparse and subtype-specific;
broad vulvar cancer guideline evidence is therefore annotated as partial when
applied to the adenocarcinoma category.
Vulvar adenocarcinoma refers to malignant epithelial tumors of the vulva with glandular differentiation. In vulvar cancer, squamous cell carcinoma (SCC) is predominant (>90%), and adenocarcinomas are uncommon. Rarer vulvar histologies explicitly recognized in contemporary guidelines include extramammary Paget’s disease and Bartholin gland adenocarcinoma, among others. (aburustum2024vulvarcancerversion pages 1-2, ha2024imaginginvulval pages 1-2)
Unavailable with current tool evidence: OMIM, Orphanet, MeSH IDs, MONDO ID.
Because “vulvar adenocarcinoma” is a category spanning multiple entities, etiology is subtype-dependent: - Bartholin gland primaries: etiologic inference is limited by rarity; HPV appears important for Bartholin SCC but not clearly established for adenocarcinoma. In a 13-case series, all Bartholin SCC showed diffuse p16, while the single adenocarcinoma showed patchy p16 staining. (nazeran2019bartholinglandcarcinoma pages 1-2) - Intestinal-type vulvar adenocarcinoma: proposed embryologic origins include cloacal remnants and other metaplasia hypotheses; inflammation and genetic changes are discussed. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, dellino2022“intestinaltype”vulvaradenocarcinoma pages 5-6) - EMPD: described as a rare neoplasm arising in apocrine-rich skin regions including vulva; molecular mechanisms include HER2 biology and alternative pathway activation (e.g., FGFR1/TGFβ enrichment in one WGS case). (lim2024wholegenomesequencing pages 1-2)
From NCCN Vulvar Cancer v3.2024 (applies to vulvar cancer overall; includes rare histologies): - Increasing age - HPV infection - Cigarette smoking - Inflammatory vulvar conditions - Immunodeficiency (aburustum2024vulvarcancerversion pages 1-2)
Intestinal-type VAIt review additionally lists exposures/conditions relevant to vulvar carcinogenesis broadly (lichen sclerosus/vulvar dystrophies, smoking, HPV infection) and environmental insults (infections, UV, physical damage), but without quantitative risk estimates for VAIt specifically. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 5-6)
For vulvar SCC pathogenesis context (important for mixed histology differential and prevention frameworks): HPV DNA is reported in ~40% of invasive vulvar cancers in one modern review, with HPV-associated tumors tending to occur in younger women and having better outcomes; HPV-independent tumors are associated with chronic dermatoses such as lichen sclerosus. (ayalapeacock2025advancesinvulvar pages 1-3)
No protective genetic or environmental factors specific to vulvar adenocarcinoma subtypes were identified in retrieved sources.
No explicit gene–environment interaction evidence specific to vulvar adenocarcinoma was identified in retrieved sources.
A. Vulvar EMPD (clinical phenotype and QoL impact) - Typical appearance: “erythematous, scaly or eczematous plaque on the vulva and perineum with occasional erosions or ulcerations, hypopigmentation and nodules” and symptoms: “Itching and burning pain”. (iacobone2023tipsandtricks pages 1-2) - High relapse burden: persistence/recurrence is common (86% in one cohort), often requiring repeated procedures. (iacobone2023tipsandtricks pages 2-4) - Cervico-vaginal spread can be clinically silent: “None reported vaginal bleeding or other suspicious symptoms” and detection was frequently via abnormal glandular cytology. (iacobone2023tipsandtricks pages 1-2)
Suggested HPO terms (examples): - Vulvar pruritus (HP:0031297; if unavailable, use “Pruritus” HP:0000989) - Burning pain (Pain; HP:0012531) - Erythematous skin lesion (HP:0025548) - Eczematous dermatitis (HP:0000964) - Vulvar mass (HP:0030417; if unavailable, “Mass” HP:0100242)
B. Bartholin-region carcinoma (including adenocarcinoma subtype) - Presents as a mass in the Bartholin region; diagnostic delay is common due to misclassification as cyst/abscess, motivating biopsy in women ≥40–45 with persistent/recurrent solid lesions. (kostov2025bartholinglandcarcinoma pages 20-21)
Suggested HPO terms: - Vulvar mass (HP:0030417), Vulvar pain (HP:0031242), Ulceration (HP:0001053)
C. Intestinal-type vulvar adenocarcinoma (VAIt) - Often presents as a solitary lesion in labia/perineal/posterior vulvar structures and may mimic benign lesions. (colalillo2025intestinaltypeadenocarcinomais pages 11-13, dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2)
Direct QoL instruments specific to vulvar adenocarcinoma were not retrieved; however, EMPD symptom burden (itching/burning) and high recurrence requiring repeated interventions plausibly affects QoL and sexual function. (iacobone2023tipsandtricks pages 2-4, iacobone2023tipsandtricks pages 1-2)
No germline causal genes specific to “vulvar adenocarcinoma” as a disease category were identified in retrieved sources.
A. Vulvar EMPD / Paget-associated vulvar adenocarcinoma - HER2 biology is clinically important. In a WGS case report and literature synthesis, HER2 overexpression in EMPD series was reported as 15–65%, with ERBB2 amplification 13–43%; in the case, >90% tumor cells stained HER2+ with ≥40% showing 3+ intensity. (lim2024wholegenomesequencing pages 2-4) - WGS found copy number gains on chromosomes 7 and 8 (n=81 genes, 92.6% on chr8) and pathway enrichment for TGFβ and FGFR1 signaling; notably “ERBB2 gene did not exhibit high copy number gain… although 90% of tumor cells stained HER2-positive”, suggesting overexpression without strong ERBB2 CN gain in that case. (lim2024wholegenomesequencing pages 1-2)
Mechanistic interpretation (expert analysis): These findings support a model where HER2 protein overexpression can occur via mechanisms beyond high-level ERBB2 amplification (e.g., regulatory/structural alterations), and where parallel signaling (FGFR1/TGFβ) may modulate response/resistance to HER2-directed therapy. (lim2024wholegenomesequencing pages 1-2)
B. Mammary-like / mammary gland type adenocarcinoma (AMGT) of the vulva - IHC profile can resemble breast carcinoma: strong ER positivity (reported 90–100%), CK7/CAM5.2/GATA3 positivity; typically negative for PR, GCDFP-15, SOX10, p63, CK20. HER2 may be equivocal (2+) with FISH negative in a case. (morais2022diagnosisandmanagement pages 1-2) - Key diagnostic principle is exclusion of a breast primary by clinical and imaging workup. (morais2022diagnosisandmanagement pages 1-2)
C. Intestinal-type vulvar adenocarcinoma (VAIt) - Characteristic “intestinal” IHC phenotype: frequent CK20 and CDX2 positivity, often CEA positive, variable CK7 and p16; requires exclusion of metastatic colorectal primary. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, colalillo2025intestinaltypeadenocarcinomais pages 11-13)
D. Bartholin gland carcinoma (with adenocarcinoma subtype) - In a 13-case cohort (1984–2017), Bartholin SCC showed diffuse p16; the single adenocarcinoma showed patchy p16 staining. (nazeran2019bartholinglandcarcinoma pages 1-2) - Reporting standards emphasize diagnosing primary Bartholin gland origin by anatomic region involvement, compatible histology, no other primary identified, and preferably adjacent normal Bartholin gland tissue. (faruqi2018standardsanddatasets pages 12-16)
Not specifically identified for vulvar adenocarcinoma subtypes in retrieved evidence.
Pathways (GO biological process suggestions): - ERBB2 signaling pathway / receptor tyrosine kinase signaling (GO:0007169; broad) - PI3K-AKT signaling (useful for HER2/PTEN context; supported indirectly via trastuzumab resistance mechanisms and HER2 pathway emphasis) (lim2024wholegenomesequencing pages 1-2) - TGFβ receptor signaling pathway (GO:0007179) (lim2024wholegenomesequencing pages 1-2) - FGFR signaling pathway (GO:0008543) (lim2024wholegenomesequencing pages 1-2)
Cell types (Cell Ontology suggestions): - Keratinocyte / epithelial cell (CL:0000312; generic epithelium) - Glandular epithelial cell / secretory epithelial cell (useful for adenocarcinoma and apocrine-associated EMPD) (lim2024wholegenomesequencing pages 1-2)
A. EMPD / Paget-associated adenocarcinoma
1) Transformation of apocrine-rich cutaneous epithelium into Paget cells within epidermis.
2) Potential progression to stromal invasion and/or association with an underlying adenocarcinoma (Wilkinson/Brown Type 1b/1c).
3) Molecular drivers may include HER2 overexpression; alternative signaling (FGFR1/TGFβ) may contribute to aggressive/metastatic behavior and treatment response/resistance. (iacobone2023tipsandtricks pages 2-4, lim2024wholegenomesequencing pages 1-2)
B. Intestinal-type vulvar adenocarcinoma
1) Proposed embryologic substrate (persistent cloacal remnants or metaplastic intestinal epithelium).
2) Development of colorectal-like glandular neoplasm with intestinal differentiation.
3) Clinical manifestation as vulvar/perineal lesion; important downstream step is ruling out metastatic colorectal carcinoma. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, dellino2022“intestinaltype”vulvaradenocarcinoma pages 5-6)
C. Mammary-like gland adenocarcinoma
1) Malignant transformation of mammary-like vulvar glands.
2) Breast-carcinoma-like morphology and ER-driven biology.
3) Clinical implication: requires exclusion of metastatic breast primary and may suggest endocrine-therapy relevance (inferred from ER positivity; treatment decisions are individualized). (morais2022diagnosisandmanagement pages 1-2)
Not specifically addressed in retrieved evidence.
No Mendelian inheritance pattern is established for vulvar adenocarcinoma in retrieved evidence.
EMPD cervico-vaginal extension diagnostic pathway (referral center practice): - “All cases except one were firstly detected by abnormal glandular cytology.” (iacobone2023tipsandtricks pages 1-2) - Abnormal cytology prompted colposcopy and cervical/vaginal biopsies; HPV testing negative in CV EMPD cases; HER2 immunocytochemistry used on cell blocks in some cases. (iacobone2023tipsandtricks pages 6-9)
Differential diagnosis (key points): - Mammary-like vulvar adenocarcinoma requires exclusion of breast primary (mammography/US/PET used in reported cases). (morais2022diagnosisandmanagement pages 1-2) - Intestinal-type vulvar adenocarcinoma requires exclusion of metastatic colorectal carcinoma; CDX2/CK20/CK7 patterns aid. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2) - EMPD secondary disease exclusion can use CDX-2 and uroplakin-III (and other panels) to rule out colorectal/urothelial origins. (iacobone2023tipsandtricks pages 9-10)
FIGO 2021 staging table (visual evidence): see Table 1 image (ha2024imaginginvulval media 862afa93).
Imaging recommendations by stage (guideline-synthesis): - No routine imaging for clinically FIGO stage IA. (ha2024imaginginvulval pages 2-4) - Pelvic MRI for local staging in tumors with invasion >1 mm, larger size (e.g., >4 cm), or suspected extension to urethra/vagina/anus. (ha2024imaginginvulval pages 2-4) - For advanced or metastatic disease: CT chest/abdomen/pelvis or FDG-PET/CT. (ha2024imaginginvulval pages 2-4)
Imaging performance statistics (vulvar cancer literature; mostly SCC but used clinically across histologies): - MRI nodal sensitivity highly variable (≈40–52% up to 86–89%), specificity generally high (≈82–100%). CT sensitivity low (≈43–58%). (ha2024imaginginvulval pages 4-5) - Meta-analysis referenced in imaging review: PET/CT per-patient sensitivity 70%, specificity 90%. (ha2024imaginginvulval pages 5-7) - Vulvoscopy diagnostic metrics in a 2024 overview: sensitivity 98%, specificity 40%, NPV 98% for malignant lesions. (corte2024currentpreoperativemanagement pages 1-2)
NCCN v3.2024 provides stage-based management for vulvar cancer and explicitly includes rare histologies such as extramammary Paget’s disease and Bartholin gland adenocarcinoma in its scope of “rarer histologies”. (aburustum2024vulvarcancerversion pages 1-2)
A. EMPD (including noninvasive disease) — local and topical treatments - In practice, surgery is common (92/94 in one cohort), and relapse management includes topical imiquimod (63%), photodynamic therapy (5%), and radiotherapy (12%). (iacobone2023tipsandtricks pages 2-4, iacobone2023tipsandtricks pages 4-6)
B. HER2-directed systemic therapy for metastatic EMPD - A WGS case report described rapid response to paclitaxel plus trastuzumab in HER2+ de novo metastatic EMPD. (lim2024wholegenomesequencing pages 2-4)
C. Bartholin gland carcinoma/adenocarcinoma - Management is often extrapolated from vulvar cancer; experts emphasize molecular profiling (DNA panels with CNV, RNA fusions, MSI/TMB/PD-L1) to reduce misclassification and enable targeted/immunotherapy in advanced disease. (kostov2025bartholinglandcarcinoma pages 20-21)
Topical imiquimod trials (noninvasive vulvar Paget/EMPD): - NCT02385188 (Phase 3; completed; n=25): topical 5% imiquimod 3×/week for 16 weeks; primary endpoint clinical response 12 weeks after end of treatment; includes QoL instruments (EQ-5D, DLQI, FSDS). (NCT02385188 chunk 1) - NCT00504023 (pilot; completed; n=8): imiquimod 3×/week up to 12 weeks; biopsies at baseline and 12 weeks; follow-up every 3 months for ≥2 years. (NCT00504023 chunk 1)
Photodynamic therapy device trial: - NCT03713203 (Phase II; recruiting; n=24): PAGETEX® device with Metvixia; 2–4 PDT sessions; primary endpoint disease control rate at 3 months; excludes invasive disease/underlying adenocarcinoma. (NCT03713203 chunk 1)
Systemic/advanced vulvar cancer trial example: - NCT03452332 (Phase 1; completed): SBRT + tremelimumab + durvalumab in recurrent/metastatic cervical/vaginal/vulvar cancers. (trial record retrieved but not evidence-extracted in provided snippets; use cautiously)
Evidence gap: explicit HPV vaccination impact on vulvar adenocarcinoma or adenocarcinoma-specific prevention strategies were not retrieved.
No evidence identified in retrieved sources.
A trastuzumab-resistant EMPD model is reported with PTEN loss as a potential resistance mechanism (supporting mechanistic research and therapy optimization), but detailed model description was not extracted in current evidence snippets. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, lim2024wholegenomesequencing pages 1-2)
| Entity/subtype | Key definition/notes | Typical age/presentation | Key diagnostic IHC/biomarkers | Key management | Key quantitative outcomes/statistics | Key citations |
|---|---|---|---|---|---|---|
| Invasive extramammary Paget disease (EMPD) / Paget-associated vulvar adenocarcinoma | Primary vulvar EMPD is classified as cutaneous-origin disease; Wilkinson/Brown subtypes include type 1a (intraepithelial), 1b (stromal invasion), and 1c (manifestation of primary vulvar adenocarcinoma). Paget-associated invasive adenocarcinoma can show strong HER2 expression. | Mean age 63.3 years (range 31–88) in a 94-patient vulvar EMPD cohort; lesions may recur/persist and cervico-vaginal spread can be clinically silent, often first detected by abnormal glandular cytology. | HER2 overexpression reported in Paget-associated vulvar adenocarcinoma; cervical/vaginal involvement diagnosis used cytology with immunocytochemistry plus biopsy confirmation of Paget cells. | Surgery is mainstay; recurrent/persistent disease may also be treated with topical imiquimod, photodynamic therapy, or radiotherapy; lifelong surveillance is important, including annual cervical/vaginal assessment in long-standing disease. | In 94 women: 81% type 1a; invasive EMPD in 36%; persistence/recurrence 86%; median 2 surgeries (range 0–11); 5-year OS 90.5% (95% CI 81.8–95.1%). Cervico-vaginal involvement cumulative incidence 2.5% at 5 years, 6.5% at 10 years, 14.0% at 15 years. (iacobone2023tipsandtricks pages 2-4, aburustum2024vulvarcancerversion pages 1-2) | (iacobone2023tipsandtricks pages 2-4, aburustum2024vulvarcancerversion pages 1-2) |
| Intestinal-type vulvar adenocarcinoma (primary villo-glandular mucinous adenocarcinoma with intestinal differentiation) | Extremely rare primary vulvar adenocarcinoma; WHO 2020 describes this as primary villo-glandular mucinous adenocarcinoma with intestinal differentiation and discourages “cloacogenic” terminology. Histology resembles mucinous colorectal carcinoma with villo-glandular architecture, goblet/Paneth cells, and mucin. Must exclude metastatic gastrointestinal primary. | Median age 58 years; reported range 31–92 years; commonly arises in labia/perineal or posterior vulvar structures and may mimic benign lesions. | Intestinal phenotype with CK20 and CDX2 positivity, often CEA positive and variable CK7/p16; diagnosis requires radiologic/clinical exclusion of another primary site. | Surgical excision with tumor-free margins is standard; lymph-node staging is considered/recommended especially for tumors >2 cm or when imaging suggests nodal disease; adjuvant or systemic therapy reported in selected advanced/recurrent cases. | 2022 review found 29 cases; 2025 review found 40 cases overall (41 including authors’ case in another excerpt). Nodal metastases in ~31.2%–31.5%; mortality due to disease about 10%; FIGO stage IA most frequent at diagnosis. (dellino2022“intestinaltype”vulvaradenocarcinoma pages 2-5, dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, colalillo2025intestinaltypeadenocarcinomais pages 11-13, colalillo2025intestinaltypeadenocarcinomais pages 1-2, colalillo2025intestinaltypeadenocarcinomais pages 10-11) | (dellino2022“intestinaltype”vulvaradenocarcinoma pages 2-5, dellino2022“intestinaltype”vulvaradenocarcinoma pages 1-2, colalillo2025intestinaltypeadenocarcinomais pages 11-13, colalillo2025intestinaltypeadenocarcinomais pages 1-2, colalillo2025intestinaltypeadenocarcinomais pages 10-11) |
| Vulvar adenocarcinoma of mammary gland type / mammary-like glands | Extremely rare adenocarcinoma thought to arise from mammary-like vulvar glands; pathology can resemble invasive ductal breast carcinoma, and breast primary must be excluded clinically/radiologically. | Postmenopausal presentation in reported cases; may present as vulvar mass/lump. | Strong ER positivity reported in 90%–100%; CK7, CAM5.2, GATA3 positive; typically negative for PR, GCDFP-15, SOX10, p63, CK20. HER2 may be equivocal (2+) with negative FISH in a reported case. | Radical vulvectomy or radical local excision; nodal assessment by sentinel lymph node biopsy or lymphadenectomy; adjuvant therapy tailored to IHC profile and stage. | Evidence base is limited to case reports/small series; quantitative outcome estimates are not established in the gathered evidence. (morais2022diagnosisandmanagement pages 1-2) | (morais2022diagnosisandmanagement pages 1-2) |
| Bartholin gland adenocarcinoma / Bartholin gland carcinoma (general, including adenocarcinoma subtype) | Rare vulvar cancer arising in the Bartholin gland region; adenocarcinoma is one of the three most common Bartholin gland carcinoma histotypes. Diagnosis requires compatible location/histology and exclusion of another primary; many cases are initially mistaken for benign Bartholin cyst/abscess. | Often presents as a solid, persistent, or recurrent Bartholin-region mass; delayed diagnosis is common, prompting low threshold for biopsy in women aged ≥40–45 years. | Suggested histotype-specific markers include CK20/CDX2/SATB2 for intestinal-type adenocarcinoma; HPV/p16/p53, MYB/MYBL1 fusions (for adenoid cystic carcinoma), and broader molecular testing (MMR/MSI, TMB, PD-L1, targeted DNA/RNA assays) are proposed in modern workup. | Complete surgical excision with 2–3 mm margins and bilateral groin evaluation; adjuvant therapy tailored by histology; advanced disease may receive radiotherapy ± chemotherapy, systemic therapy, immunotherapy, or targeted agents; management largely extrapolated from general vulvar cancer guidelines. | BGC comprises 3%–7% of vulvar cancers and <1% of gynecologic tumors; ~50% diagnosed at advanced stage; nodal metastasis occurs in >40%; adenocarcinoma histology and node-positive disease predict worse survival. (kostov2025bartholinglandcarcinoma pages 24-25, kostov2025bartholinglandcarcinoma pages 20-21, faruqi2018standardsanddatasets pages 12-16, aburustum2024vulvarcancerversion pages 1-2) | (kostov2025bartholinglandcarcinoma pages 24-25, kostov2025bartholinglandcarcinoma pages 20-21, faruqi2018standardsanddatasets pages 12-16, aburustum2024vulvarcancerversion pages 1-2) |
Table: This table compares the main vulvar adenocarcinoma-related entities identified in the gathered evidence, emphasizing diagnostic markers, management patterns, and quantitative outcomes. It is useful for quickly distinguishing subtype-specific features while keeping evidence provenance explicit through context-ID citations.
The FIGO 2021 staging table for vulvar carcinoma (applies to all morphologic types except melanoma) is shown in the extracted Table 1 image. (ha2024imaginginvulval media 862afa93)
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(dellino2022“intestinaltype”vulvaradenocarcinoma pages 2-5): Miriam Dellino, Stefania Cicogna, Francesca Falcone, Marco Mitidieri, Roberta Mazzeo, Sandro Pignata, Giorgia Mangili, and Gennaro Cormio. “intestinal-type” vulvar adenocarcinoma: a review of the mito rare tumors group. Cancers, 14:5171, Oct 2022. URL: https://doi.org/10.3390/cancers14205171, doi:10.3390/cancers14205171. This article has 9 citations.
(colalillo2025intestinaltypeadenocarcinomais pages 1-2): Alessio Colalillo, Dominga Boccia, Luigi Della Corte, Daniele Neola, Federica Rosato, Silvia D’Ippolito, Maria De Ninno, Damiano Arciuolo, Maurizio Guida, Giuseppe Bifulco, and Francesco Cosentino. Intestinal-type adenocarcinoma is a rare histotype of vulvar neoplasm: systematic review of the literature. Cancers, 17:3989, Dec 2025. URL: https://doi.org/10.3390/cancers17243989, doi:10.3390/cancers17243989. This article has 0 citations.
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