Gastric type adenocarcinoma

Cervix
Carcinoma
Gastric type adenocarcinoma

Author: Carlos Parra-Herran, M.D.

Topic Completed: 1 August 2016

Revised: 7 January 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed Search: Gastric type adenocarcinoma cervix

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Table of Contents

Cite this page: Parra-Herran C. Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed January 24th, 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

Epidemiology

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)

Pathophysiology

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:
- Mucoid vaginal discharge
- Irregular or "contact" vaginal bleeding (Kaohsiung J Med Sci 2012;28:161)

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

33 year old woman with p16+ minimal deviation adenocarcinoma (Int J Clin Exp Pathol 2015;8:5877)
41 year old woman with Peutz-Jegher syndrome and unusual admixture of neoplastic and metaplastic genital tract lesions (Gynecol Oncol 2004;92:337)
41 and 45 year old women (Mol Clin Oncol 2013;1:833)
46 year old woman with rare case of adenoma malignum and large cystic tumor (Gynecol Oncol 2002;84:339)
55 year old woman with minimal deviation adenocarcinoma of the cervix and high grade cervical squamous intraepithelial lesion (Eur J Gynaecol Oncol 2010;31:227)

Treatment

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:
- Surgical excision is the standard treatment (World J Surg Oncol 2013;11:168, Zhonghua Zhong Liu Za Zhi 2008;30:772)

Gross description

Minimal deviation adenocarcinoma:
- Usually grossly normal
- May have cervical hypertrophy with multiple cystic lesions (Kaohsiung J Med Sci 2012;28:161)

Gross images

Images hosted on other servers:

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.:

Minimal deviation adenocarcinoma:

Endocervical type

Nonspecific type

Endometrioid-type glands deep in cervix

Images hosted on other servers:

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

PAS-Alcian blue: Neutral mucin staining pattern (red staining)
MUC6: >90% (expression can be focal)
HIK1083: >90% (expression can be focal)
p53: Abnormal expression (overexpressed) in 45% of GAS
PAX2: Loss in MDA
mCEA: 100% (expression can be focal)
Minimal deviation adenocarcinoma:
- HIK1083 (available as latex agglutination test) (Gynecol Oncol 1999;75:345)
- p53 (Med Hypotheses 2013;80:643)
- CEA (variable)

Negative stains

p16 (not overexpressed), ER, PR, CDX2
Minimal deviation adenocarcinoma: CA125 (Med Hypotheses 2013;80:643)

Molecular / cytogenetics description

Minimal deviation adenocarcinoma: often mutations in STK11 gene (Lab Invest 2003;83:35)

Electron microscopy description

Minimal deviation adenocarcinoma: may have gastric phenotype (Ultrastruct Pathol 1999;23:375)

Differential diagnosis

Usual type endocervical adenocarcinoma: Mucin depletion, hyperchromasia and abundant apical mitoses, lack of pyloric-type mucinous differentiation, acid mucin staining (dark purple staining with PAS-Alcian blue stain), p16 overexpression, HPV detection by ISH, MUC6/HIK1083 negative
Intestinal (goblet cell) type endocervical adenocarcinoma: Intestinal (goblet cell) mucinous phenotype instead of gastric (pyloric), acid mucin staining (dark purple staining with PAS-Alcian blue stain), p16 overexpression, HPV detection by ISH, MUC6/HIK1083 negative
Clear cell adenocarcinoma: Clear cell cytoplasm without evidence of mucinous differentiation, mCEA negative
Adenofibroma: may extend throughout cervix and into upper vagina wall; has dense periglandular fibrosis (Int J Gynecol Cancer 1995;5:236)
Diffuse laminar endocervical glandular hyperplasia: no irregular stromal infiltration, no desmoplastic stromal response, no focal malignant cytologic features (Am J Surg Pathol 1991;15:1123)
Endocervical type adenomyoma: see APMIS 2001;109:546
Endocervicosis: outer cervix and paracervical connective tissue, presence of uninvolved zone of cervical wall between endocervicosis and normal endocervical glands (Int J Gynecol Pathol 2000;19:322)
Endosalpingiosis: rarely presents as a mass (Am J Surg Pathol 1999;23:166)
Florid deep glands: bland inactive appearing cells
Lobular endocervical glandular hyperplasia: noninvasive proliferation of endocervical glandular cells in lobular arrangement without any irregular stromal infiltration, desmoplasia or focal malignant features (Pathol Int 2005 Jul;55:412)
Microglandular hyperplasia: different morphology; CEA negative
Pseudoinfiltrative tubal metaplasia of the endocervix associated with in utero DES exposure: see Int J Gynecol Pathol 2005;24:391
Tunnel clusters: little variation in size, shape and depth of glands

Additional references

Am J Surg Pathol 2015;39:1449, Am J Surg Pathol 2007;31:664, Adv Anat Pathol 2013;20:227, Histopathology 2007;50:843, Pathol Int 2005;55:412