Gastric type adenocarcinoma

Topic Completed: 1 August 2016

Minor changes: 2 April 2020

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PubMed Search: Gastric type adenocarcinoma cervix

Carlos Parra-Herran, M.D.
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Cite this page: Parra-Herran C. Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed May 29th, 2020.
Definition / general
  • Approximately 10% of primary endocervical adenocarcinomas are unrelated to high-risk HPV infection
  • HPV-independent adenocarcinomas include: gastric, clear cell and mesonephric
  • Minimal deviation adenocarcinoma (MDA, adenoma malignum) is part of the spectrum of adenocarcinomas with a gastric phenotype:
    • Endocervical adenocarcinoma which is mucinous and well differentiated, consisting of an endocervical glandular hyperplasia of lobular architecture resembling glands but with the characteristics of adenocarcinoma (Taiwan J Obstet Gynecol 2015;54:447)
    • Usually HPV negative (Mod Pathol 1998;11:11)
    • Diagnostic challenge due to its benign appearing histological characteristics; often missed by small cervical biopsies
    • Consider in patients presenting with heavy vaginal discharge, cystic lesion on imaging and atypical glandular cells on cytologic smear
    • May have worse prognosis due to difficulty of diagnosis or discovery at higher stage with nodal involvement
  • Rare
  • 1 - 3% of all cervical adenocarcinomas
  • Usually sporadic, but also associated with Peutz-Jeghers syndrome (rare, autosomal dominant disorder of hamartomatous polyposis in GI tract, mucocutaneous pigmentation and predisposition to benign and malignant GI, breast, ovary, cervix and testicular tumors) (Oncol Lett 2013;6:1184)
  • Associated with STK11 gene mutations (Virchows Arch 2013;462:645)
  • Not related to HPV (Int J Gynecol Pathol 2005;24:296)
  • The following have been postulated as a non-obligatory precursor lesions of gastric-type adenocarcinoma:
    • Gastric metaplasia of the endocervix (simple gastric-pyloric metaplasia, type A-tunnel clusters)
    • Lobular endocervical hyperplasia (LEGH, complex pyloric metaplasia)
      • LEGH has been documented adjacent to the tumor in 20% of gastric type adenocarcinomas, and up to 50% of minimal deviation adenocarcinomas
    • Atypical LEGH has been identified in 30% of minimal deviation adenocarcinomas
      • Characterized by LEGH with nuclear enlargement, irregular nuclear contours, loss of polarity, mitoses and intraluminal papillary projections
  • Gastric-type adenocarcinoma-in-situ (G-AIS) is the (likely) preinvasive form of gastric endocervical neoplasia
    • Cytologically abnormal (similar to atypical LEGH), but involving endocervical glands – architecturally similar to adjacent normal endocervix, and lacking the lobular architecture of atypical LEGH
Clinical features
  • Mean age at presentation is ~50 years (range 30-66)
  • History of Peutz-Jeghers syndrome is documented in a subset of patients
  • Minimal deviation adenocarcinoma:
Radiology description
  • Minimal deviation adenocarcinoma:
    • Diagnosis with MRI and ultrasonography is often difficult due to benign appearance
    • Transvaginal sonography can detect presence of multilocular cystic masses in the cervix and may aid in diagnosis
    • Ultrasound imaging with Doppler examination is more efficient and accurate
      • Minimal deviation adenocarcinoma has increased intralesional vascularity
    • MRI: multiple irregular cystic lesions, cysts arranged in floret-like manner with aggregates of small cysts resulting in a "cosmos pattern" (Int J Gynecol Cancer 2011;21:1287)
Prognostic factors
  • Gastric-type endocervical adenocarcinoma and minimal deviation adenocarcinoma have a worse prognosis and adverse outcome compared to usual-type adenocarcinoma:
    • Rate of LVI: 48%
    • Regional LN metastases: 50%
    • Ovarian metastases: 35%
    • Abdominal spread: 20%
    • > stage I at presentation: 60%
    • Fatal outcome: 39%
Case reports
  • Treatment does not significantly differ from other forms of adenocarcinoma, since this entity is relatively infrequent and only recently characterized
  • Stage I tumors at presentation are treated with complete surgical excision (trachelectomy, radical hysterectomy) and regional lymphadenectomy
  • Advanced stage tumors receive chemo-radiation therapy with subsequent consideration for surgery
  • Minimal deviation adenocarcinoma:
Gross description
Gross images

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Minimal deviation adenocarcinoma: tumor specimen

Microscopic (histologic) description
  • Histologic criteria of gastric differentiation, as defined by Kojima et al (Am J Surg Pathol 2007;31:664) are:
    • Cells with clear and/or pale eosinophilic cytoplasm
    • Distinct cell borders
    • Comprising the majority of the tumor
  • Minimal deviation adenocarcinoma is characterized by:
    • Low grade morphology
      • Minimal to absent cytologic atypia
      • Abundant apical mucin
      • Well-defined glands (claw-like pattern)
    • Stromal invasion
      • Deep haphazard gland distribution
      • Minimal to no desmoplastic reaction
    • The above changes need to be present in >90% of the tumor volume (if less, tumor is classified as gastric adenocarcinoma, NOS)
    • Well spaced, deeply invasive, branching glands lined with minimal cytological atypia and a focal stromal reaction (Pathology 1997;29:17, Mol Clin Oncol 2013;1:833)
    • Very well differentiated glands (usually endocervical type) with cystic dilation
    • Glands are variable in shape or size with irregular or claw shaped outlines with haphazard arrangement (Mol Clin Oncol 2013;1:833)
    • Often glands are close to thick walled vessels or within thickness of vessel wall (Int J Gynecol Pathol 2005;24:125)
    • May have vascular or perineural invasion
    • Rarely has endometrioid histology
  • Gastric-type adenocarcinoma NOS (GAS) displays variable range of cytologic atypia, stromal infiltration and differentiation
Microscopic (histologic) images

Gastric type, contributed by Carlos Parra-Herran, M.D.:
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Minimal deviation adenocarcinoma:
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Endocervical type

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Nonspecific type

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Endometrioid-type glands deep in cervix

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Adenocarcinoma and Related Lesions

Cytology description
  • Minimal deviation adenocarcinoma:
    • Glandular cells showing nuclear crowding and clearing with gland opening or acinar-like pattern
    • Frequent appearance of large sheets of cells with a honeycomb pattern and a palisading arrangement at the periphery
    • Individual tumor cells are monomorphic, round or oval, with nonvacuolated cytoplasm with cytoplasmic extensions or tails, prominent and displaced hyperchromatic nuclei with chromatin clumping (Taiwan J Obstet Gynecol 2015;54:447)
    • Smear background shows variable necrotic debris and neutrophils in some cases (Diagn Cytopathol 2006;34:119)
    • No pleomorphism, no/rare mitotic figures (Am J Clin Pathol 1996;105:327)
    • Yellowish-orange staining of cytoplasmic mucins by the Papanicolaou method is an important diagnostic clue to identify mucinous MDA by cytology
    • Immunostaining with HIK1083 is useful (Cancer 1999;87:245)
Positive stains
Negative stains
Molecular / cytogenetics description
Electron microscopy description
Differential diagnosis
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