Cervix

Benign / nonneoplastic epithelial lesions

Lobular endocervical glandular hyperplasia



Last author update: 10 January 2023
Last staff update: 10 January 2023

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PubMed Search: Lobular endocervical glandular hyperplasia

Adam Lechner, B.M.
Carlos Parra-Herran, M.D.
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Cite this page: Lechner A, Parra-Herran C. Lobular endocervical glandular hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixlobularendocerv.html. Accessed February 6th, 2023.
Definition / general
  • Rare lesion of the cervix characterized by a proliferation of discrete lobules of small, round glands showing gastric type differentiation
Essential features
  • Benign (though frequent association with underlying malignancy poses a challenge for management)
  • Involves the upper endocervical canal of predominantly perimenopausal women
  • Not related to high risk HPV infection
  • Well differentiated (minimal deviation type) gastric type adenocarcinoma is the primary differential diagnosis of this lesion
  • Immunohistochemical profile: HIK1083+, MUC6+, PAX2+ (retained), CEA-, ER-, PR-
  • Atypical cytologic and architectural features are associated with progression to malignancy (known as atypical LEGH; now classified as a form of adenocarcinoma in situ, gastric type)
Terminology
  • Lobular endocervical glandular hyperplasia (LEGH) is part of the benign spectrum of gastric type epithelium in the uterine cervix
  • Atypical LEGH is now considered to be a form of gastric type adenocarcinoma in situ (gAIS)
  • Minimal deviation adenocarcinoma (MDA), also known as adenoma malignum:
    • Malignant lesion, now referred to as HPV independent endocervical adenocarcinoma, gastric type; it is part of the differential diagnosis of LEGH
ICD coding
  • ICD-10: N88.9 - noninflammatory disorder of cervix uteri, unspecified
Epidemiology
Sites
  • Located in the upper part of the endocervical canal (rather than at the transformation zone) and usually confined to the inner half of the cervix (Minerva Chir 1989;44:1107)
Pathophysiology
Etiology
  • Association with Peutz-Jeghers syndrome (due to germline STK11 / LKB1 mutations) has been reported (Pathol Int 2011;61:369, Ann Oncol 2012;23:2990)
  • May be associated with the recently described synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN FGT) (Histopathology 2009;54:184)
  • LEGH and other gastric type cervical glandular lesions are not associated with persistent infection by high risk HPV
Diagrams / tables

Images hosted on other servers:
Gastric type cervical lesion spectrum

Gastric type cervical lesion spectrum

Proposed management algorithm

Proposed management algorithm

Clinical features
  • Often incidental in hysterectomy or cervical loop electrosurgical excision specimens (LEEP)
  • Up to half of cases present with symptoms suggestive of MDA (Am J Surg Pathol 1999;23:886):
    • Watery / mucoid vaginal discharge
    • Cervical mass
Diagnosis
  • Constellation of features on MRI and Pap smear can yield reasonably high suspicion; however, histologic evaluation remains necessary for definitive diagnosis and exclusion of occult malignant disease
Radiology description
  • Multiple large cysts encircling a smaller, central solid component in the upper cervix; termed the cosmos pattern (referring to the flower, Cosmos bipinnatus)
  • Gastric type adenocarcinomas, including MDA, tend to present instead as predominantly solid lesions; however, some may display overlapping features (Abdom Imaging 2015;40:459)
  • Observing a hypointense cosmos pattern lesion relative to the surrounding cervical stroma on T1 weighted imaging gave a specificity of 95% for gastric type, mucin positive lesions in one series (J Obstet Gynaecol Res 2021;47:745)
Radiology images

Images hosted on other servers:
LEGH with cosmos pattern LEGH with cosmos pattern LEGH with cosmos pattern

LEGH with cosmos pattern

Prognostic factors
Case reports
Treatment
  • Pure LEGH without atypical features, diagnosed on hysterectomy, is considered benign and requires no additional treatment / follow up
  • If diagnosed on biopsy, cervical LEEP or conization, conduct may vary:
    • Hysterectomy may be preferred to confirm absence of coexisting MDA or gAIS; however, deferral for fertility preservation is an alternative option (Adv Anat Pathol 2013;20:227)
    • Symptomatic presentation (discharge / cervical mass) warrants cautious management, which should include at least close follow up with diagnostic imaging and further sampling
    • Diagnosis on biopsy should prompt consideration for cervical loop electrosurgical excision or conization
  • Diagnostic algorithm with retrospective validation has been proposed for managing patients with multicystic, gastric mucin positive lesions identified on MRI and cervical Pap smear (Int J Gynecol Cancer 2011;21:1287, J Obstet Gynaecol Res 2016;42:1588)
Gross description
  • Cut surface displays variably sized cystic spaces within a thickened, fibrotic cervical wall
  • Typically confined to the inner half of the cervix, in the superior aspect near the internal os
  • Reference: Adv Anat Pathol 2013;20:227
Microscopic (histologic) description
  • Well demarcated lesion with lobular / acinar architecture composed of a central crypt, sometimes with cystic dilation, surrounded by smaller, round shaped glands and cysts arranged in a floret-like pattern
    • Most cases are confined to the inner third of the cervical wall; however, larger cystic lesions may be seen deeper within the cervical wall
  • Central and peripheral glands are lined by columnar cells with pale eosinophilic cytoplasm and basally oriented, small nuclei with bland morphology
    • Focal intestinal metaplasia may be observed, especially within the central glands
  • May have, at most, mild nuclear atypia
  • No desmoplasia, no irregularly shaped glands, no mitotic figures, no squamous differentiation
  • Atypical LEGH, now regarded as a form of gastric type AIS, is defined as architecturally consistent with LEGH but with ≥ 4 of the following features (Mod Pathol 2004;17:962):
    • Nuclear enlargement
    • Irregular nuclear contours
    • Distinct nucleoli and coarse chromatin
    • Loss of polarity
    • Mitotic figures (occasional)
    • Apoptotic bodies or luminal nuclear debris
    • Intraluminal papillary projections
Microscopic (histologic) images

Contributed by Carlos Parra-Herran, M.D.
Densely packed glands

Densely packed glands

Round mucinous glands

Round mucinous glands

Lobulated / floret-like appearance

Lobulated / floret-like appearance

Glands lined by benign columnar cells

Glands lined by benign columnar cells

PAS - Alcian blue stain PAS - Alcian blue stain

PAS - Alcian blue stain



Contributed by @MirunaPopescu13 on Twitter
Lobular endocervical glandular hyperplasia

Lobular endocervical glandular hyperplasia

Cytology description
  • High columnar mucinous cells with smooth nuclear contours, no atypia and no / rare mitotic figures
  • Monolayered sheets, no glandular complexity, no loss of polarity
  • Extracellular or intracellular golden yellow mucin on Papanicolaou stain, reflecting gastric type differentiation (Diagn Cytopathol 2002;27:80)
  • Intranuclear cytoplasmic inclusions usually are present; less likely in MDA (Diagn Cytopathol 2008;36:535)
  • PAS shows neutral mucin filling entire cytoplasm
Cytology images

Images hosted on other servers:
LEGH and MDA

LEGH and MDA

Positive stains
Negative stains
Molecular / cytogenetics description
  • Up to 58% harbor mutually exclusive mutations in GNAS, STK11 or KRAS (8, 2, and 1 out of 19, respectively) (Am J Surg Pathol 2014;38:370)
  • Whole exome sequencing in 3 cases of pure LEGH demonstrated a lack of known carcinogenic mutations, supporting a hypothesis of metaplasia (Oncol Lett 2019;18:2592)
    • Driver mutations may therefore only occur in late lesions (i.e., atypical or MDA associated LEGH)
  • Atypical LEGH shares molecular alterations with MDA, including 3q gain and 1p loss (Mod Pathol 2004;17:962)
  • HPV negative (Int J Gynecol Pathol 2005;24:296)
Sample pathology report
  • Uterus, hysterectomy:
    • Cervix with lobular endocervical glandular hyperplasia

  • Cervix, loop electrosurgical excision:
    • Lobular endocervical glandular hyperplasia (see comment)
    • Comment: Lesion appears completely excised; margins are negative.

  • Cervix, biopsy:
    • Gastric type glandular proliferation, favor lobular endocervical glandular hyperplasia (see comment)
    • Comment: The epithelial proliferation has a lobular configuration. The epithelial cells have a gastric phenotype, which includes tall pale to foamy mucinous cytoplasm, as well as neutral type mucin on PAS - Alcian blue stain, positive HIK1083 and negative ER / PR. PAX2 is normal (retained). By itself, LEGH is considered benign but it is associated with other gastric type proliferations in the cervix, including gastric type adenocarcinoma. Consideration for excisional sampling or at least close monitoring and imaging to exclude the presence of a cervical mass is recommended.
Differential diagnosis
Board review style question #1

A 40 year old woman presents with watery vaginal discharge and is found to have a multicystic, cervical lesion on MRI. The lesion (shown above) displays well defined lobules of endocervical glands lined by columnar cells with eosinophilic cytoplasm and small, bland nuclei. Immunostain for HIK1083 and MUC6 is positive. PAS staining shows pale red cytoplasm in lesional cells. Desmoplastic response is not seen. Which of the following distinguishes this lesion from gastric type endocervical adenocarcinoma?

  1. Absence of haphazard growth
  2. HIK1038 / MUC6 positivity
  3. Lack of association with high risk HPV infection
  4. Pale red cytoplasmic staining on PAS
Board review style answer #1
A. Absence of haphazard growth. Like lobular endocervical glandular hyperplasia (LEGH), very well differentiated forms of gastric type endocervical adenocarcinoma (formerly known as minimal deviation endocervical adenocarcinoma) are characterized by well differentiated endocervical glands that express gastric type mucin, which stains pale red (neutral) on PAS and is positive for HIK1083 and MUC6. Diagnosis of malignancy is reached when glands with the previously described features infiltrate the cervical stroma haphazardly, unlike LEGH, which has a distinct floret-like lobulated configuration. Haphazard growth in adenocarcinoma is often associated with at least focal desmoplastic response and cytologic atypia. None of the glandular lesions with gastric type differentiation of the cervix are associated with HPV infection.

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Reference: Lobular endocervical glandular hyperplasia
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