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Anticancer Research Oct 2023The expression of L1 cell adhesion molecule (L1CAM) in uterine mesonephric-like adenocarcinoma (MLA) remains understudied. Our aim was to explore the L1CAM expression in...
BACKGROUND/AIM
The expression of L1 cell adhesion molecule (L1CAM) in uterine mesonephric-like adenocarcinoma (MLA) remains understudied. Our aim was to explore the L1CAM expression in uterine MLA, delving into its clinicopathological implications and prognostic significance.
PATIENTS AND METHODS
We conducted L1CAM immunostaining in MLA, endometrioid carcinoma (EC), and serous carcinoma (SC), compared L1CAM expression across these histological types, and probed the relationship between L1CAM expression and the clinicopathological features and outcomes of patients with MLA.
RESULTS
High L1CAM expression was evident in 15 of 28 MLA cases (53.6%). This rate surpassed that of EC (7.5%) but was less than that of SC (78.9%). A high L1CAM expression correlated with initial distant metastasis, advanced initial stage, lung metastasis, and the recurrence of MLA. L1CAM-high MLA exhibited worse disease-free and overall survival than L1CAM-low MLA.
CONCLUSION
L1CAM over-expression was observed in more than half of the MLA cases, and was associated with aggressive clinicopathological traits and adverse outcomes in patients with uterine MLA.
Topics: Female; Humans; Prognosis; Neural Cell Adhesion Molecule L1; Endometrial Neoplasms; Biomarkers, Tumor; Carcinoma, Endometrioid; Adenocarcinoma
PubMed: 37772557
DOI: 10.21873/anticanres.16650 -
The Journal of Pathology Jun 2024Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping...
Mesonephric adenocarcinomas (MAs) and mesonephric-like adenocarcinomas (MLAs) are rare, aggressive neoplasms that arise in the gynecologic tract and show overlapping morphologic, immunohistochemical, and molecular features. While MAs occur in the cervix and are thought to arise from mesonephric remnants, MLAs occur in the endometrium and ovary and are believed to originate from transdifferentiation of Müllerian lesions. Both MAs and MLAs show a variety of architectural patterns, exhibit frequent expression of GATA3 by immunohistochemistry, and harbor KRAS mutations. In a recent article published in The Journal of Pathology, Kommoss and colleagues used DNA methylation profiling to extend these similarities and showed that MLAs and MAs cluster together based on their epigenetic signatures and are epigenetically distinct from other Müllerian adenocarcinomas. They also showed that MLAs and MAs harbor a high number of global copy number alterations. This study provides evidence that MLAs more closely resemble MAs than Müllerian carcinomas on an epigenetic level. As a result, the authors argue that MLA should be renamed 'mesonephric-type adenocarcinoma.' Further research is needed to establish the relationship between these two entities, their etiology, and pathogenesis. © 2024 The Pathological Society of Great Britain and Ireland.
Topics: Humans; Adenocarcinoma; Female; Epigenesis, Genetic; Uterine Cervical Neoplasms; DNA Methylation; Mullerian Ducts; Mesonephroma; Biomarkers, Tumor; Epigenome
PubMed: 38593211
DOI: 10.1002/path.6285 -
International Journal of Gynecological... Sep 2023Mesonephric neoplasms of the lower female genital tract are rare. To date, there are scarce reports of benign biphasic vaginal mesonephric lesions, and none have...
Mesonephric neoplasms of the lower female genital tract are rare. To date, there are scarce reports of benign biphasic vaginal mesonephric lesions, and none have included immunohistochemical and/or molecular analysis. A biphasic neoplasm of mesonephric-type was incidentally identified in the vaginal submucosal tissue of a 55-yr-old woman who underwent a right salpingo-oophorectomy for an ovarian cyst. The well-circumscribed, 5 mm nodule exhibited white-tan, firm homogenous cut surfaces. Microscopic examination showed a lobular arrangement of glands with columnar to the cuboidal epithelium and intraluminal eosinophilic secretions, embedded within a myofibromatous stroma. Cytologic atypia and mitotic activity were absent. Immunohistochemical staining for PAX8 and GATA3 demonstrated diffuse expression in the glandular epithelium, CD10 exhibited a patchy luminal expression pattern, while TTF1, ER, PR, p16, and NKX3.1 were negative. Desmin highlighted a subset of the stromal cells, but myogenin was negative. Whole exome sequencing demonstrated variants of unknown significance in multiple genes including PIK3R1 and NFIA . The morphologic and immunohistochemical profiles are consistent with a benign mesonephric neoplasm. This is the first report describing the immunohistochemical and whole exome sequencing results for a benign biphasic vaginal mesonephric neoplasm. To the best of our knowledge, benign mesonephric adenomyofibroma has not been previously reported in this anatomic location.
Topics: Female; Humans; Epithelium; Neoplasms, Glandular and Epithelial; Ovarian Cysts; Salpingo-oophorectomy
PubMed: 36811844
DOI: 10.1097/PGP.0000000000000945 -
Cancer Reports (Hoboken, N.J.) Jan 2024Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of...
Identification of characteristics and construction of nomogram to predict the survival probability of mesonephric carcinoma patients: A population-based analysis and a case report.
BACKGROUND
Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines.
OBJECTIVE
To summarize the characteristics and construct an external-validated nomogram to predict the survival of MC patients.
METHOD
Sixty-four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan-Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3-to-8-year survival probability of MC patients, which were evaluated by C-index, ROC curves, DCA curves, and calibration plots.
RESULTS
The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C-index, ROC curves, DCA curves, and calibration plots.
CONCLUSION
Sufficient regional lymph nodes examined, and applying radiotherapy in high-risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow-up.
Topics: Humans; Nomograms; Databases, Factual; Lymph Nodes; Carcinoma
PubMed: 38030392
DOI: 10.1002/cnr2.1940 -
The American Journal of Surgical... Jun 2024Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically...
Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.
PubMed: 38919071
DOI: 10.1097/PAS.0000000000002237 -
International Journal of Gynecological... Feb 2024Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort.
INTRODUCTION
Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort.
METHODS
Forty-one carcinosarcomas were identified from a cohort of 973 endometrial carcinomas diagnosed in 2016. We assessed immunostaining and sequencing data and undertook expert pathology reviews of these cases as well as all subsequently diagnosed (post-2016) carcinosarcomas of no specific molecular profile (NSMP) molecular subtype (n=3) from our institutions.
RESULTS
In the 2016 cohort, 37 of the 41 carcinosarcomas (91.2%) were p53abn, 2 (4.9%) were NSMP, and 1 each (2.4%) were POLEmut and mismatch repair deficiency molecular subtypes, respectively. Of the 4 non-p53abn tumors on review, both NSMP tumors were corded and hyalinized (CHEC) pattern endometrioid carcinoma, the mismatch repair deficiency tumor was a grade 1 endometrioid carcinoma with reactive stromal proliferation, and the POLEmut tumor was grade 3 endometrioid carcinoma with spindle cell growth, that is, none were confirmed to be carcinosarcoma on review. We found 11 additional cases among the 37 p53abn tumors that were not confirmed to be carcinosarcoma on the review (3 undifferentiated or dedifferentiated carcinomas, 5 carcinomas with CHEC features, 2 carcinomas showing prominent reactive spindle cell stroma, and 1 adenosarcoma). In the review of institutional cases reported as NSMP carcinosarcoma after 2016, 3 were identified (1 adenosarcoma and 2 mesonephric-like adenocarcinoma on review).
CONCLUSION
In this series, all confirmed endometrial carcinosarcomas were p53abn. The finding of any other molecular subtype in a carcinosarcoma warrants pathology review to exclude mimics.
PubMed: 38303106
DOI: 10.1097/PGP.0000000000001010 -
Indian Journal of Pathology &... Jun 2024Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological...
Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.
PubMed: 38847204
DOI: 10.4103/ijpm.ijpm_518_23 -
The American Journal of Surgical... May 2024Trichorhinophalangeal syndrome type 1 (TRPS1) is a new reportedly sensitive and specific immunohistochemical marker for carcinomas of breast origin, including...
Trichorhinophalangeal syndrome type 1 (TRPS1) is a new reportedly sensitive and specific immunohistochemical marker for carcinomas of breast origin, including triple-negative (estrogen receptor, progesterone receptor, and HER2) tumors. In our practice, we have observed a subset of cases of nonmammary carcinomas that are positive for TRPS1, with higher frequency in cytology effusion samples with metastatic gynecologic malignancies. This study aimed to evaluate the expression of TRPS1 in a large tissue cohort of Müllerian carcinomas. We retrospectively retrieved 105 cases of formalin-fixed paraffin-embedded gynecologic tumors from our surgical pathology archives. Cases corresponded to tumors of tubo-ovarian (17 high-grade serous carcinomas, 3 low-grade serous carcinomas, 2 clear cell carcinomas, and 8 endometrioid adenocarcinomas), endometrial (25 endometrioid adenocarcinomas, 8 serous carcinomas, 6 clear cell carcinomas, 12 carcinosarcomas, 1 dedifferentiated carcinoma, and 1 mesonephric-like adenocarcinoma), cervical (6 human papillomavirus [HPV]-associated squamous cell carcinomas [SCCs], 11 HPV-associated endocervical adenocarcinomas, and 2 HPV-independent gastric-type endocervical adenocarcinomas), and vulvar (2 HPV-independent SCCs and 1 HPV-associated SCC) origins. Immunohistochemistry for TRPS1 was performed in whole tissue sections and assessed for positivity (≥5% of nuclear labeling), distribution (focal: 5% to 49%, diffuse: 50% to 100%), and intensity (1+, 2+, 3+) in tumor cells. Positive TRPS1 staining was observed in 51.4% (54/105) of cases. Most tumors (64.8%) demonstrated diffuse labeling, while focal in 35.2%. Among positive cases, the intensity was predominantly 1+ (57.4%), followed by 2+ (33.3%) and 3+ (9.2%). Tumors with a high percentage of positivity overall consisted of tubo-ovarian (70%) and endometrial carcinomas (58.4%). TRPS1 immunostain is often expressed in gynecologic carcinomas. Awareness of this phenomenon is crucial when evaluating challenging cases in which the differential diagnosis includes a malignancy of breast origin, to avoid misclassification of the primary site.
Topics: Female; Humans; Carcinoma, Endometrioid; Papillomavirus Infections; Retrospective Studies; Biomarkers, Tumor; Uterine Cervical Neoplasms; Genital Neoplasms, Female; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Repressor Proteins
PubMed: 38357982
DOI: 10.1097/PAS.0000000000002193 -
International Journal of Gynecological... May 2024Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor...
Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.
Topics: Female; Humans; Carcinoma, Endometrioid; Mesonephros; Uterus; Adenocarcinoma; Biomarkers, Tumor; Endometrial Neoplasms
PubMed: 37566876
DOI: 10.1097/PGP.0000000000000976 -
Histopathology Jun 2024Decreased oestrogen receptor (ER) expression is a marker of poor prognosis in endometrial carcinomas (EC) of no specific molecular profile (NSMP), but the optimal...
AIMS
Decreased oestrogen receptor (ER) expression is a marker of poor prognosis in endometrial carcinomas (EC) of no specific molecular profile (NSMP), but the optimal cut-off to separate high-risk 'low ER' versus low-risk 'high ER' expression has not been defined. Here we characterised the distribution of ER staining in a cohort of ECs.
METHODS AND RESULTS
Biopsy specimens from 120 cases of NSMP EC were stained for ER and assigned an Allred score. In 66 additional cases ER staining of matched biopsy and hysterectomy were compared. Twelve of 120 tumours had an Allred score of 0-3, including three endometrioid carcinomas (EEA) (one G1, two G3), four clear cell carcinomas (CCC), two mesonephric-like adenocarcinoma (MLA) and one each of: gastric-type adenocarcinoma, carcinosarcoma and endometrial carcinoma NOS. Three had Allred scores of 4-5: two MLA and one high-grade carcinoma with yolk sac differentiation. Five had Allred scores of 6: four EEA (one G1, one G2, two G3) and one mixed clear cell and endometrioid carcinoma. The remaining 100 tumours with Allred scores ≥ 7 were all EEA (66 G1, 28 G2, five G3 and one grade unknown). Comparing the biopsy versus hysterectomy ER staining (n = 66), the results were within a single Allred score point, except two cases with strong diffuse expression in the biopsy (Allred 8) and moderate expression in the hysterectomy (Allred 5).
CONCLUSIONS
Most NSMP ECs (> 80%) show high ER expression (Allred score ≥ 7). All non-endometrioid carcinomas and a few endometrioid carcinomas had lower ER expression (Allred score ≤ 6) or were completely negative.
PubMed: 38890776
DOI: 10.1111/his.15241