Clinicopathological Characteristics of Gastric-type Endocervical Adenocarcinoma Misdiagnosed as an Endometrial, Ovarian or Extragenital Malignancy, or Mistyped as Usual-type Endocervical Adenocarcinoma

Abstract

Background/aim: The diagnosis of gastric-type endocervical adenocarcinoma (GEA) is challenging because its differential diagnosis includes not only gynecological tumors, but also extragenital tumors.

Patients and methods: We reviewed the electronic medical records and all available slides to investigate the clinicopathological characteristics of eight misdiagnosed GEA cases.

Results: Three tumors were initially misdiagnosed as endometrial carcinoma. They displayed extensive endomyometrial involvement and complex glandular architecture, but no severe nuclear pleomorphism. Another three tumors were misclassified as usual-type endocervical adenocarcinoma because of mucin-poor, pseudoendometrioid glands, apical mitotic figures, and karyorrhectic debris. The two remaining tumors presenting as adnexal masses mimicked primary ovarian mucinous tumor and metastatic cholangiocarcinoma.

Conclusion: The varying pathological characteristics of GEA reflect the variability in clinical manifestations and its diagnostic difficulties. It is challenging to make an accurate diagnosis based solely on histological features. When suspecting GEA, clinicians should consider more comprehensively the clinicopathological context, along with immunostaining results.

Keywords: Uterus; cervix; gastric-type endocervical adenocarcinoma; misdiagnosis; mistyping.

Figure 1. Gastric-type endocervical adenocarcinoma mimicking endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) and endometrioid carcinoma. (A) At low-power magnification, a gland in the right lower corner (green arrow) shows nuclear enlargement and hyperchromasia. (B) A slightly enlarged gland (green arrow) shows loss of nuclear polarity as well as significant nuclear enlargement and pleomorphism than does the adjacent non-atypical glandular epithelium (blue arrows). Obvious cytological demarcation but without stromal invasion raises the suspicion of endometrial AH/EIN. (C) High-power view reveals atypical glandular epithelium showing enlarged nuclei with coarse chromatin and conspicuous nucleoli (green arrows). The adjacent non-atypical gland shows a single layer of inactive cuboidal epithelium with small, bland-appearing nuclei (blue arrows). (D) The pleomorphic nuclei (green arrows) partially occupies the endometrial gland. Note the cytological demarcation between atypical (upper right corner) and non-atypical (lower left corner) cells (blue arrows). (E) The tumor tissue consists predominantly of crowded glands and thin intervening stroma, resembling low-grade endometrioid carcinoma of the endometrium. (F) The invasive tumor front shows minimal inflammatory infiltrates without stromal desmoplasia. (G) There are several foci of glandular dilatation, intraluminal papillary projections, and cribriform architecture, closely similar to the features of endometrioid carcinoma. Staining method: A-G, hematoxylin and eosin staining. Original magnification: A, 100×; B, 100×; C, 400×; D, 400×; E, 40×; F, 100×; G, 100×.

Figure 2. Gastric-type endocervical adenocarcinoma mimicking usual-type endocervical adenocarcinoma and endometrial mucinous adenocarcinoma. (A) The neoplastic glands exhibit architectural complexity with papillary fronds. The papillary structures fuse to form a network of anastomosing strands of tall columnar epithelial cells. The tumor cells have hyperchromatic, elongated nuclei, most of which are basally located. The intracytoplasmic mucin is not readily identified. (B) The tumor cells have variable amounts of eosinophilic cytoplasm. Enlarged, fusiform, hyperchromatic, pseudostratified nuclei show irregular, coarse chromatin with occasional prominent nucleoli. Apical or “floating” mitoses (green arrows) as well as an atypical mitotic figure (blue arrow) are present. (C) In addition to the mitotic figures (green arrow), frequent apoptotic bodies (yellow arrows) are also noted within the epithelium. The atypical mitotic figures and apoptotic bodies are typical histological features of usualtype endocervical adenocarcinoma. (D) Low-power view reveals complex glandular proliferations involving the endometrial stroma and superficial myometrium. Crowded, branching glands resemble those of endometrial endometrioid carcinoma. A few normal endometrial glands are noted in the right lower corner. (E) The tumor cells have small, basally located nuclei with minimal-to-mild pleomorphism. Dilated glands are lined with columnar epithelial cells with abundant apical mucin. (F-H) The tumor shows varying degrees of cytological atypia: (F) a single layer of mucincontaining epithelium showing low-grade nuclear atypia, (G) significant nuclear stratification and intermediate-grade nuclear atypia in complex glandular architecture, and (H) mucin-containing epithelium high-grade nuclear atypia including loss of polarity, moderate-to-severe pleomorphism, and occasional prominent nucleoli. Staining method: A-H, hematoxylin and eosin staining. Original magnification: A, 100×; B, 400×; C, 400×; D, 40×; E, 100×; F, 400×; G, 100×; H, 400×.

Figure 3. Ovarian metastasis of gastric-type endocervical adenocarcinoma mimicking primary ovarian mucinous carcinoma and metastatic cholangiocarcinoma. (A) Low-power view of patient 7 sample shows cystically dilated glands with thin intervening stroma. (B) There are some foci showing proliferation of small well-formed glands of various shapes. (C) They are relatively evenly distributed and separated by distinct fibrous stroma. Stromal inflammatory infiltrates and desmoplastic reaction are minimal. (D) The tumor cells often show marked nuclear pleomorphism. (E) Similar to patient 7, low-power view of patient 8 sample reveals that the tumor contains cystic spaces filled with eosinophilic mucinous material and lined by mucinous epithelium. (F) Most of the lining epithelium exhibits high-grade nuclear atypia, and the intervening stroma appears similar to that of normal ovarian stroma. (G) Back-to-back arrangements of small tubular glands as well as fused and interconnected poorly formed glands and tumor cell nests in an abundant fibrous stroma raises the suspicion of metastatic cholangiocarcinoma. Staining method: A-G, hematoxylin and eosin staining. Original magnification: A, 40×; B, 40×; C, 100×; D, 400×; E, 40×; F, 200×; G, 200×.

Figure 4. Tubal intraepithelial metastasis of gastric-type endocervical adenocarcinoma (GEA). (A-B) The microscopic metastatic tumors (green arrows) involve multifocally non-fimbriated portions of the fallopian tubes. (C-D) Fimbrial involvement is also noted among the tumor cells that spread horizontally along the surface epithelium. Nuclear pleomorphism and stratification, micropapillary structure, and abrupt transition between normal tubal epithelium and tumor cells are noted. (E-F) A few tiny intraluminal tumor emboli (yellow arrows) are present. (G) There are abrupt transitions between normal tubal epithelium (blue arrow) and tumor cells (green arrow). Navy arrowheads indicate ciliated normal tubal epithelium. (H-I) Metastatic GEA exhibits (H) p53 over-expression or (I) non-block p16 immunoreactivity. The tumor cells show faint cytoplasmic p16 expression only. Staining method: A-G, hematoxylin and eosin staining; H-I, polymer method. Original magnification: A, 40×; B, 40×; C, 100×; D, 150×; E, 150×; F, 200×; G, 400×; H, 400×; I, 200×.

Figure 5. Immunophenotype of gastric-type endocervical adenocarcinoma. (A-B) Mutant p53 immunostaining pattern. Infiltrating tumor cells show (A) p53 over-expression or (B) complete absence of p53 immunoreactivity. (C) The tumor cell nuclei show uniform and strong p53 expression, whereas the adjacent non-neoplastic epithelium (blue arrows) shows patchy positivity with weak-to-strong staining intensity. (D) The tumor cells are completely negative for p53, whereas few lymphocytes (blue arrows) show weak nuclear immunoreactivity. (E) The tumor cells do not show any nuclear p16 expression except focal and weak cytoplasmic immunoreactivity. Staining method: A-E, polymer method. Original magnification: A, 40×; B, 100×; C, 200×; D, 200×; E, 150×.