Gastric-type adenocarcinoma in situ of uterine cervix: cytological and histopathological features of two cases

Abstract

Benign, premalignant, and malignant endocervical glandular lesions occasionally show a gastric phenotype. We report 2 cases of gastric-type adenocarcinoma in situ (AIS) of the endocervix, not associated with lobular endocervical glandular hyperplasia or gastric-type adenocarcinoma. Cytologically, both showed endocervical glands with slightly enlarged nuclei, distinctive nucleoli, pseudostratified strips, and intracytoplasmic golden yellow mucin. Histologically, both lesions were situated in preexisting endocervical glands and presented columnar cells with voluminous pale eosinophilic cytoplasm and evident nuclear atypia. In case 1, the lesion was located at the mid-zone of the endocervical canal and, in case 2, at the outer endocervical canal with extension to the transformation zone and prominent intestinal metaplasia. In both, the cells showed voluminous cytoplasm containing gastric-type mucin, stained red by combined alcian blue/periodic acid-Schiff stain. Immunohistochemically, both lesions were positive for HIK1083 and p53, while negative for p16 and ER. Human papilloma virus (HPV) DNA was not detected by polymerase chain reaction. Our cases illustrate that gastric-type AIS can occur without lobular endocervical glandular hyperplasia. The lesions can occur in the outer cervical canal and present extensive intestinal differentiation. Awareness of this rare type of endocervical glandular lesion is important since they are pathogenetically different from the more common HPV-associated lesions and may become more prevalent in the HPV-eradicating era.

The developing spectrum of gastric-type cervical glandular lesions

“…Several case reports and a recently published small series have drawn attention to another potential precursor of GAS, which has been designated 'adenocarcinoma in situ of gastric-type (gAIS)'. 15,24,27,28 This uncommon form of AIS is HPV negative, displays a gastric phenotype and immunophenotype and shares many of the atypical cytological features described above for atypical LEGH. It differs from atypical LEGH architecturally in that gAIS lacks the lobular architecture with clusters of small glands surrounding a dilated duct that typifies LEGH.…”

“…28 The reported cases of gAIS have been in patients aged 25-74 (mean age 53), an older mean age than HPV-related AIS. 27,28 Most reported cases have been diagnosed following the identification of atypical glandular cells in a cervical smear in asymptomatic women; smaller numbers were incidental findings in a hysterectomy specimen or cervical excision undertaken for benign indications. gAIS is usually located at or just proximal to the transformation zone and in occasional cases, extension to the lower uterine segment and even the endometrium occurs.…”

“…10 Of the remaining small subset of non-HPV associated adenocarcinomas, the most common is so-called gastric-type adenocarcinoma (GAS), which represents the malignant end of an emerging spectrum of benign, premalignant and malignant gastric-type cervical glandular lesions, the characteristics of which have been elucidated in a series of recent publications. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] The latest edition of the World Health Organization (WHO) Classification of Tumours of the Female Genital Tract has been modified to include GAS as a subtype of mucinous adenocarcinoma of the cervix. 29 Minimal deviation adenocarcinoma (MDA) of mucinous type, also known as adenoma malignum, now denotes the rare, extremely well differentiated variant of GAS and, as discussed later, is best subsumed under the umbrella term GAS.…”

Gastric‐type endocervical adenocarcinoma and cervical cytology: Experience at a general hospital and review of the literature

“…In our four cases, we found a constellation of cytologic findings (Table 2), supported by the literature, with endocervical cells arranged in three-dimensional clusters and honeycomb sheets 7 with abundant vacuolar cytoplasm 4,16 . In patients 3-4, moderate nuclear atypia with irregular nuclear membranes was seen 18 , with either coarse chromatin and/or hyperchromatic nuclei and prominent nucleoli. Feathering or features suggestive of feathering 18 were also observed.…”

“…On cervical cytology specimens, GAS has been reported to show endocervical cells in monolayered and honeycomb sheets with well-defined cell borders, pale vacuolar and/or foamy cytoplasm, and vesicular nuclei with conspicuous nucleoli 4,5,7,16,[18][19][20] . Peripheral palisading mimicking feathering has also been reported 18 . Yellow mucin has also been reported as a diagnostic clue for endocervical glandular lesions with gastric differentiation 6 .…”