International Journal of Gynecological Pathology最新文献

Endometrial carcinoma with intestinal differentiation/colorectal carcinoma-like (CRC-like) features is rare with few cases reported to date. Those described are mainly endometrioid carcinomas with intestinal differentiation. We report a case of high-grade endometrial carcinoma with serous and intestinal/CRC-like components. The gross, histologic, immunohistochemical, and molecular features are described for both components of the tumor in the initial diagnostic biopsy and subsequent resection specimen. The diagnosis of primary endometrial carcinoma with serous and CRC-like components is supported by immunohistochemical and molecular findings, as well as clinical workup. The rarity of this phenomenon poses diagnostic challenges. In addition, the literature is reviewed with specific emphasis on the molecular and pathologic features of mixed endometrial carcinomas, including those with intestinal/CRC-like features.

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis-particularly in the ovary-is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.

Using immunohistochemistry, we examined a large cohort of 135 ovarian tumors, made up of 96 low-grade serous carcinomas (LGSCs) and 39 serous borderline tumors (micropapillary variant, mSBT), with the aim of exploring their HER2 status (overexpression). We followed with comprehensive genomic analyses on this sample set from our previous study, which revealed HER2 mutation in 5% (4/75) of LGSC and 10% (3/29) of mSBT. No cases were evaluated as HER2-positive, but 6 LGSCs and 1 mSBT were scored as HER2 1+, and 2 LGSCs and 1 mSBT showed the so-called HER2 "ultra-low" phenotype. This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.

Metastasizing leiomyoma is a rare condition characterized by the development of benign-appearing smooth muscle neoplasms at extrauterine sites in patients with a history of uterine leiomyoma. These lesions occur most commonly in the lung, with the abdominopelvic and mediastinal lymph nodes being other reported sites. Malignant transformation of metastasizing leiomyoma is extremely rare, with only a few cases described in the literature. We describe a case of metastasizing leiomyoma with malignant transformation in a middle-aged Asian lady, who developed pulmonary metastatic foci 12 years after surgical excision of the original uterine leiomyomata. Molecular analysis showed a common RAB2A-PLAG1 fusion gene and identical single nucleotide variants in both tumor foci, with significantly more pronounced segmental chromosomal copy number variations in one focus showing high-grade features. A comprehensive review of the literature lends support to the hypothesis that the original leiomyomata and the metastatic foci are clonally related, with high-grade features being associated with more complex genomic signatures.

Several types of myometrial invasion in endometrioid-type endometrial adenocarcinoma (EEC) have been identified: adenomyosis-like changes; adenoma malignum; broad front, single-cell/cell clusters; and the microcystic elongated and fragmented (MELF) pattern. This study aims to investigate the effect of the MELF pattern on recurrence type and survival rate among patients with EEC. We retrospectively reviewed the records of patients diagnosed with EEC over a 10-year period from January 2011 to January 2021. Among 108 patients with EEC, 54 had recurrence (study group), and 54 did not (control group). The MELF pattern was more common in the group with recurrence than in the group without recurrence (40.7% vs. 14.8%; P=0.002). The MELF pattern was observed in 60.0% of patients with local recurrence and 29.4% of patients with extrapelvic or distant organ metastases (P=0.027). Evaluation of 5-year disease-free survival (P=0.003) and overall survival (P=0.001) rates showed that MELF positivity was associated with decreased survival. Among patients with grade I-II EEC lacking uterine-localized myometrial invasion, the MELF pattern was less common in the nonrelapsed group than in the local relapse group (10.0% vs. 60.0%; P<0.001). The MELF pattern (odds ratio=19.4, 95% CI=1.2-31.2) was a significant independent negative predictor for local recurrence. The MELF pattern was more common in patients with recurrence, especially local recurrence. This finding suggests that the MELF pattern primarily impacts direct local invasion rather than hematogenous or lymphatic spread.

Tumor budding (TB) and poorly differentiated clusters (PDCs) are well-established prognostic factors in various cancers. This study aimed to assess the independent prognostic role of these markers in endometrial carcinomas. Retrospective analysis of endometrial carcinoma resection specimens by examining traditional histologic prognostic parameters. TB and PDC were observed at 20× magnification in ten fields at the invasive front and categorized as present or absent. In addition, a count of ≥5 was stratified as "high." Clinical and follow-up details were extracted from Gynecologic Oncology records. Sixty-five endometrial carcinomas were studied and were predominantly endometrioid (n=47, 72.3%). TB was identified in 52.3% of cases, with high TB observed in 38.5%. PDC was evident in 44.6%, with high PDC seen in 29.2%. Associations were significant between the presence of TB/high TB and higher tumor grade (P < 0.001), deep myometrial invasion (P = 0.006/P = 0.002), diffuse pattern of invasion (P = 0.007/P = 0.03), microcystic elongated and fragmented pattern (P < 0.001), lymphovascular space invasion, lymph node metastasis (P=<0.001) and International Federation of Gynecology and Obstetrics stage (P = 0.000/P = 0.002). PDC/high PDC showed similar associations, and, in addition, with nonendometrioid histologic type (P = 0.02) and tumor location in a lower uterine segment (high PDC, P = 0.009). After adjusting for other significant parameters, both high TB (P = 0.03) and high PDC (P = 0.031) emerged as independent prognostic parameters for lymphovascular space invasion or Lymph node metastasis. No recorded deaths or significant events occurred, precluding commentary on overall survival status. High TB and PDC are independent predictors of Lymph node metastasis in endometrial carcinomas. Their association with the microcystic elongated and fragmented pattern makes them histologic predictors of epithelial-mesenchymal transition. Their simple application underscores their potential as valuable additional prognostic indicators for endometrial carcinomas.

This study aims to investigate the role of L1 cell adhesion molecule (L1CAM) in the prognostic assessment of endometrial cancers that have been depicted as having no specific molecular profile (NSMP) in molecular classification. This is a retrospective review of 150 patients who received the diagnosis of endometrial cancer and underwent surgery at the study center between January 2008 and January 2022. When evaluating L1CAM immunohistochemical staining, scoring was done according to the percentage of positivity in tumor cells. Accordingly, score 0 = 0%, score 1=1% to 10%, score 2 = >10% to 50% and score 3 = >50%. If the staining in tumor cells was ≥10% (scores 2 and 3), it was considered positive. The patients with L1CAM positivity had significantly more frequent lymphovascular space invasion and lymph node metastasis than patients with L1CAM negativity (P = 0.013 and P = 0.007). L1CAM expression was strongly associated with mutant p53 (P = 0.003). Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with L1CAM positivity (P = 0.001 for both). Seventy-nine patients (52.7%) were put into NSMP group. About 84.8% of them (n = 67) were L1CAM negative and 15.2% of them (n = 12) were L1CAM-positive. Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with NSMP who were positive for L1CAM (P = 0.002 and P = 0.001, respectively). This study demonstrates that L1CAM expression status may add prognostic information to endometrial cancer, particularly in the NSMP subgroup. Considering the prognostic importance of L1CAM, its use as a marker may make significant contributions to reducing prognostic heterogeneity, especially in the NSMP subgroup.

Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.