Gastric type adenocarcinoma

Cervix

Adenocarcinoma

Author: Gulisa Turashvili, M.D., Ph.D.

Editor-in-Chief: Debra Zynger, M.D.

Minor changes: 19 June 2020

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

PubMed Search: Gastric type adenocarcinoma cervix [TIAB]

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Table of Contents

Cite this page: Turashvili G. Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed August 14th, 2020.

Definition / general

A subtype of human papillomavirus (HPV) negative mucinous adenocarcinoma with gastric differentiation

Essential features

Second most common subtype of endocervical adenocarcinoma
Most common subtype of non HPV associated endocervical adenocarcinoma (Am J Surg Pathol 2018;42:214)
Minimal deviation adenocarcinoma (MDA) is part of the spectrum and can be difficult to diagnose in small specimens and cytology preparations
Worse prognosis compared with HPV associated usual type endocervical adenocarcinoma

Terminology

Minimal deviation adenocarcinoma (adenoma malignum) refers to a well differentiated gastric type adenocarcinoma

ICD coding

ICD-O: 8482/3 - Mucinous adenocarcinoma, endocervical type
ICD-10: C53.0 - Malignant neoplasm of endocervix
ICD-11: 2C77.Z - Malignant neoplasms of cervix uteri, unspecified

Epidemiology

Not associated with HPV (Int J Gynecol Pathol 2005;24:296)
Second most common subtype of endocervical adenocarcinoma
Most common subtype of non HPV associated endocervical adenocarcinoma (Am J Surg Pathol 2018;42:214)
Accounts for approximately 10% of endocervical adenocarcinoma in general population and up to 25% in Japanese population (Am J Surg Pathol 2018;42:214)
Usually sporadic but can be associated with germline STK11 mutations (Peutz-Jeghers syndrome) (Oncol Lett 2013;6:1184)
Mean age at presentation is 50 years (range 30 - 66)

Sites

Endocervix

Pathophysiology

Potential nonobligatory precursor lesions of gastric type adenocarcinoma are as follows (Am J Surg Pathol 2008;32:1807, Am J Surg Pathol 2017;41:1023):
- Gastric metaplasia in type A tunnel clusters
- Lobular endocervical glandular hyperplasia (LEGH) has been identified adjacent to up to 50% of minimal deviation adenocarcinomas and 20% of gastric type adenocarcinomas
- Atypical lobular endocervical glandular hyperplasia has been identified in 30% of minimal deviation adenocarcinomas
- Gastric type adenocarcinoma in situ

Etiology

Unclear

Clinical features

Abnormal cervical cytology in asymptomatic patients
Mucoid or profuse watery vaginal discharge (Mol Clin Oncol 2013;1:833)
Vaginal bleeding
Abdominal discomfort
Barrel shaped cervix
Cervical mass
Adnexal metastases

Diagnosis

Histologic examination of tissue

Radiology description

General:
- Hypoechoic, heterogeneous mass on ultrasound examination
- Mass lesion with a high signal relative to the low signal of the cervical stroma on magnetic resonance imaging
Minimal deviation adenocarcinoma:
- Difficult to diagnose due to benign appearance
- Multilocular cystic masses on ultrasound examination, sometimes with increased intralesional vascularity on color Doppler
- Multiple irregular cystic lesions or cysts arranged in floret-like manner with aggregates of small cysts resulting in a cosmos pattern on magnetic resonance imaging (Int J Gynecol Cancer 2011;21:1287)

Radiology images

Images hosted on other servers:

Barrel shaped cervix on MRI in MDA

Ill defined cervical mass on MRI in MDA

Prognostic factors

Aggressive, chemorefractory tumor with a propensity for peritoneal and abdominal spread (Am J Surg Pathol 2007;31:664, Am J Surg Pathol 2015;39:1449, Am J Surg Pathol 2011;35:633, Int J Gynecol Cancer 2018;28:99)
Most patients present at advanced stage (II to IV) at diagnosis
Even patients presenting at stage I have a 62% 5 year disease specific survival compared with 96% for stage I HPV associated usual type endocervical adenocarcinoma (Am J Surg Pathol 2015;39:1449)
The 5 year disease specific survival for all stages is 32% (Am J Surg Pathol 2007;31:664, Am J Surg Pathol 2015;39:1449)

Case reports

33 year old woman with p16 positive minimal deviation adenocarcinoma and gastric type adenocarcinoma with Peutz-Jeghers syndrome (Int J Clin Exp Pathol 2015;8:5877)
41 and 45 year old women (Mol Clin Oncol 2013;1:833)
50 year old woman with gastric type adenocarcinoma with Lynch syndrome (Gynecol Oncol Rep 2014;10:41)
57 year old woman with minimal deviation adenocarcinoma diagnosed on Pap smear (Diagn Cytopathol 2018;46:702)
69 year old woman with uterine corpus involvement by cervical gastric type adenocarcinoma mimicking primary endometrial carcinoma (J Obstet Gynaecol Res 2019;45:1414)
71 year old woman with gastric type adenocarcinoma mimicking clear cell carcinoma post neoadjuvant chemotherapy (J Pediatr Surg 1989;24:432)

Treatment

Treatment does not significantly differ from other forms of adenocarcinoma (Gynecol Oncol 2019;153:13)
Surgical excision (trachelectomy, radical hysterectomy) and regional lymphadenectomy for stage I tumors at presentation
Neoadjuvant chemotherapy and radiotherapy for advanced stage tumors (Int J Gynecol Cancer 2018;28:99)

Gross description

In minimal deviation adenocarcinoma, the cervix may be grossly unremarkable or hypertrophic with multiple cystic lesions
Exophytic, papillary, polypoid or ulcerated mass
Induration of cervical wall
Diffuse or nodular enlargement of cervical wall
Tan to yellow, hemorrhagic, friable or mucoid cut surfaces

Gross images

Contributed by Gulisa Turashvili, M.D., Ph.D.

Radical hysterectomy for gastric type adenocarcinoma

Images hosted on other servers:

Bulging cervix in MDA

Cervical swelling without a mass in MDA

Microscopic (histologic) description

Histologic criteria of gastric differentiation defined by Kojima et al (note that all features are cytologic and not architectural) (Am J Surg Pathol 2007;31:664):
- Tumor cells with clear or pale eosinophilic and voluminous cytoplasm
- Distinct cell borders
Histologic and cytologic features further refined (Int J Gynecol Pathol 2019;38:263):
- Tumor cells usually contain tall apical mucin
- Cytoplasm can be foamy
- Nuclei are typically basally located and range from small round or ovoid to markedly enlarged and irregular with vesicular chromatin and prominent nucleoli
- Variable mitotic activity
- Intestinal differentiation may be present
- Rarely, goblet cells and Paneth-like neuroendocrine cells
- Rarely, mucin extravasation, adenocarcinoma in situ or gastric metaplasia
Architectural features range from well differentiated forms comprised of well defined glands with minimal to no desmoplastic stromal reaction (such as minimal deviation adenocarcinoma) to poorly differentiated forms comprised of infiltrating poorly formed glands, tumor nests or single cells, including goblet cells, eliciting desmoplastic stromal reaction
Minimal deviation adenocarcinoma is characterized by (Mol Clin Oncol 2013;1:833):
- Neoplastic glands of variable shape and size with irregular or claw-like outlines
- Deep cervical stromal invasion with haphazardly distributed glands and minimal to no desmoplastic reaction
- Low grade morphology with minimal to absent cytologic atypia and abundant apical mucin
- Pure minimal deviation adenocarcinoma can be underrecognized or missed due to deceptively bland morphologic appearance, although adequate sampling should allow for correct diagnosis as there is usually at least focal cytologic atypia (J Clin Pathol 2010;63:935)
Grading:
- Grading of gastric type adenocarcinomas is not recommended as even well differentiated tumors may behave aggressively (Am J Surg Pathol 2007;31:664)
- Gastric type adenocarcinomas are best regarded as inherently high grade (Surg Pathol Clin 2019;12:281)
- Well differentiated and poorly differentiated areas may be admixed
- In poorly differentiated gastric type adenocarcinomas, the tumor cells are markedly atypical with loss of the abundant cytoplasm and can grow as single cells and clusters; these tumors are called gastric type due to the pyloric gland type mucin but they are morphologically and immunophenotypically similar to pancreatobiliary adenocarcinomas (Surg Pathol Clin 2019;12:281)
There is morphologic overlap between HPV associated usual type endocervical adenocarcinoma and gastric type adenocarcinoma, with some HPV positive tumors showing limited human papillomavirus associated features and resembling gastric type adenocarcinoma (Am J Surg Pathol 2018;42:214, Am J Surg Pathol 2017;41:696)
Lymphovascular or perineural invasion may be seen

Microscopic (histologic) images

Contributed by Gulisa Turashvili, M.D., Ph.D.

Well differentiated gastric type adenocarcinoma

Poorly differentiated gastric type adenocarcinoma

Gastric type adenocarcinoma in hysterectomy

Well differentiated gastric type adenocarcinoma

Poorly differentiated gastric type adenocarcinoma

Gastric type adenocarcinoma involving fallopian tube

Cytology description

Single and crowded clusters of tumor cells (Int J Gynecol Pathol 2019;38:263)
Pale, foamy or vacuolated cytoplasm and well defined cytoplasmic borders (Int J Gynecol Pathol 2019;38:263)
Moderately pleomorphic round to oval nuclei with one or more nucleoli (Int J Gynecol Pathol 2019;38:263)
Necrotic debris an neutrophils may be seen (Diagn Cytopathol 2006;34:119)
Yellowish orange staining of cytoplasmic mucins in Pap cytology preparations is an important diagnostic clue to identify intracytoplasmic mucin on cytology (Cancer 1999;87:245)
Finding HPV negative atypical glandular cells in Pap cytology preparations should raise the possibility of gastric type adenocarcinoma
Minimal deviation adenocarcinoma:
- May be missed on cytology as differentiation from reactive endocervical cells is often not possible (Am J Clin Pathol 1996;105:327)
- Honeycombed sheets of glandular cells with abundant nonvacuolated cytoplasm, cytoplasmic extensions or tails, uniform round to oval nuclei with fine chromatin and small nucleoli, lacking significant pleomorphism and rare or no mitoses, sometimes prominent and displaced hyperchromatic nuclei with chromatin clumping (Am J Clin Pathol 1996;105:327, Taiwan J Obstet Gynecol 2015;54:447)

Cytology images

Contributed by Gulisa Turashvili, M.D., Ph.D.

Gastric type adenocarcinoma on Pap cytology

Positive stains

PAS-Alcian blue: stains neutral mucin in red or magenta (Histopathology 2007;50:843)
HIK1083: diffuse or focal (may be negative in poorly differentiated forms), can also be used in cytology (Cancer Cytopathol 1999;87:245)
MUC6: diffuse or focal, albeit not specific for gastric type adenocarcinoma
p53: aberrant (diffuse or completely absent, i.e. null) in up to 52% of cases
CEA/mCEA: diffuse or focal
CK7: usually positive
PAX8: positive in 68 - 80% of cases, can be used in distinguishing gastric type adenocarcinomas from pancreatobiliary tumors (Am J Surg Pathol 2016;40:636, Am J Surg Pathol 2018;42:989)
CAIX: usually positive
HNF-1B: often positive

Negative stains

p16: usually negative or focally positive, although up to 8.5% of cases have diffuse strong expression typical of HPV associated tumors (Am J Surg Pathol 2018;42:214, Am J Surg Pathol 2016;40:636, Int J Gynecol Pathol 2019;38:263)
Estrogen receptor
Progesterone receptor
PAX2: loss in minimal deviation adenocarcinoma
CK20 and CDX2: may be focally positive in up to 50% of cases (Am J Surg Pathol 2016;40:636, Am J Surg Pathol 2011;35:633)
CA 19-9: may be positive
CA-125: may be positive

Electron microscopy description

In minimal deviation adenocarcinoma, double immunogold staining revealed localization of HIK1083 reactive mucin to the matrix and lysozyme to the core of the mucin granules suggestive of gastric phenotypes ultrastructurally (Ultrastruct Pathol 1999;23:375)

Molecular / cytogenetics description

HPV: negative by in situ hybridization or polymerase chain reaction
STK11 mutations in minimal deviation adenocarcinoma (Lab Invest 2003;83:35)
3q gain and 1p loss (Am J Surg Pathol 2008;32:1807)
TP53 mutations in almost 50% (Am J Surg Pathol 2011;35:633)

Sample pathology report

Uterus with cervix, fallopian tubes and ovaries, radical hysterectomy and bilateral salpingo-oophorectomy:
- Cervix: invasive endocervical adenocarcinoma, gastric type (see synoptic report)
- Endometrium: proliferative
- Myometrium: leiomyomata
- Right fallopian tube: involved by adenocarcinoma
- Right parametrium: involved by adenocarcinoma
- Left fallopian tube: benign
- Left parametrium: benign
- Bilateral ovaries: benign

Differential diagnosis

Usual type endocervical adenocarcinoma:
- Typically low stage at diagnosis
- Variable mucin but usually mucin depleted, hyperchromatic nuclei with abundant apical mitoses and apoptotic debris, containing acid mucin (blue on PAS-Alcian blue stain)
- Diffusely positive for p16, positive for HPV, negative or focally positive for HIK1083 and MUC6
Intestinal (goblet cell) type endocervical adenocarcinoma:
- Prominent intestinal differentiation with goblet cells, containing acid mucin (blue on PAS-Alcian blue stain)
- Diffusely positive for p16, positive for HPV, negative or focally positive for HIK1083 and MUC6
Clear cell adenocarcinoma:
- Clear cell cytoplasm without evidence of mucinous differentiation
- Negative for CEA/mCEA
Invasive stratified mucin producing adenocarcinoma:
- Usually shows multilayered epithelium, sometimes with areas of usual type adenocarcinoma
- Diffusely positive for p16, positive for HPV
Metastatic gastric or pancreaticobiliary carcinoma:
- History of gastric or pancreaticobiliary carcinoma
Lobular endocervical glandular hyperplasia and atypical lobular glandular endocervical hyperplasia:
- Lobular proliferation of endocervical glands without irregular stromal infiltration, deep invasion into cervical wall, desmoplastic stromal reaction and cytologic atypia (Pathol Int 2005;55:412)
Diffuse laminar endocervical glandular hyperplasia:
- Lacks irregular stromal infiltration, desmoplastic stromal reaction and cytologic atypia (Am J Surg Pathol 1991;15:1123)
Tunnel clusters:
- Lobular configuration, lacking mucinous features except in 15% of type A tunnel clusters, no architectural or cytologic atypia
Florid deep glands:
- Bland inactive appearing cells lacking cytologic atypia
Microglandular hyperplasia:
- Composed of small back to back glands lined by cuboidal, columnar or flattened cells with supra or subnuclear vacuoles, bland vesicular nuclei with indistinct nucleoli, lacking mucinous features
- Negative for CEA/mCEA
Pseudoinfiltrative tubal metaplasia of the endocervix:
- Associated with in utero DES exposure (Int J Gynecol Pathol 2005;24:391)
Endocervicosis:
- Involves outer cervix and paracervical soft tissue, shows uninvolved zone of cervical wall between endocervicosis and normal endocervical glands (Int J Gynecol Pathol 2000;19:322)
Endosalpingiosis:
- Rarely presents as a mass, glands lined by ciliated tubal-type bland epithelium rather than mucinous epithelium (Am J Surg Pathol 1999;23:166)
Endocervical type adenomyoma:
- Well circumscribed, lacks cytologic and architectural atypia (APMIS 2001;109:546)

Additional references

Virchows Arch 2013;462:645, Adv Anat Pathol 2013;20:227, Am J Surg Pathol 1989;13:717, Adv Anat Pathol 2019;26:1, Methods Mol Biol 2015;1249:213, Kurman: WHO Classification of Tumours of the Female Reproductive Organs, 4th Edition, 2014

Board review style question #1

Negative HIK1083, PAX8, p16 and CEA
Positive HIK1083, PAX8, negative p16 and CEA
Positive HIK1083, PAX8, p16 and CEA
Positive HIK1083, PAX8, p16, negative CEA

Board review answer #1

B. Gastric type adenocarcinoma (shown here) is positive for PAX8 and HIK1083 and negative or focally positive for p16 and CEA.

Reference: Gastric type adenocarcinoma

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Board review style question #2

Gastric type adenocarcinomas have less favorable clinical outcomes regardless of histologic grade
Minimal deviation adenocarcinomas are well differentiated and usually have favorable prognosis
Stage matched minimal deviation adenocarcinomas clinical outcomes are not significantly different

Board review answer #2

A. Gastric type adenocarcinomas usually have a worse prognosis compared to human papillomavirus associated usual type endocervical adenocarcinomas; even well differentiated tumors may behave aggressively and thus grading of gastric type adenocarcinomas is not recommended.

Reference: Gastric type adenocarcinoma

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