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Histopathology Jan 2020Endometriosis is an extremely common condition and, in most cases, establishing a histological diagnosis is straightforward, although a variety of benign alterations may... (Review)
Review
Endometriosis is an extremely common condition and, in most cases, establishing a histological diagnosis is straightforward, although a variety of benign alterations may result in problems with interpretation. In this review, I discuss selected uncommon variants of endometriosis or benign alterations that may result in diagnostic problems. The topics covered include the contentious issue of so-called atypical endometriosis, stromal endometriosis, polypoid endometriosis, and the association of endometriosis with florid mesothelial hyperplasia. The propensity of endometriosis to undergo neoplastic transformation (especially to endometrioid and clear cell carcinoma) is well known. Selected issues relating to the various neoplasms that can arise in endometriosis are discussed, with a particular concentration on unusual variants of endometrioid carcinoma that result in a disproportionately high number of issues in referral practice. The propensity of ovarian endometrioid carcinomas to show an unexpected ('aberrant') immunophenotype with positive staining with 'intestinal' markers and negative staining with Mullerian markers is also discussed. Uncommon tumour types that may arise in endometriosis, namely seromucinous neoplasms, mesonephric-like carcinomas, and somatically derived yolk sac tumours, are also covered.
Topics: Adenocarcinoma, Clear Cell; Carcinoma, Endometrioid; Cell Transformation, Neoplastic; Endometrial Neoplasms; Endometriosis; Endometrium; Female; Humans; Hyperplasia; Precancerous Conditions
PubMed: 31846535
DOI: 10.1111/his.13970 -
Diagnostic Pathology Jul 2020Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and...
BACKGROUND
Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable.
CASE PRESENTATION
Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient.
CONCLUSIONS
Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cystadenoma, Serous; Female; Humans; Mesonephroma; Middle Aged; Ovarian Neoplasms; Ovary; Precancerous Conditions; Uterine Neoplasms
PubMed: 32693840
DOI: 10.1186/s13000-020-01012-z -
The American Journal of Surgical... Apr 2020Mesonephric carcinoma is a rare malignancy, thought to derive from Wolffian remnants. To date, no targeted molecular therapeutic options have been identified. On the...
Mesonephric carcinoma is a rare malignancy, thought to derive from Wolffian remnants. To date, no targeted molecular therapeutic options have been identified. On the basis of limited case reports, c-KIT immunohistochemical expression has been reported in female adnexal tumors of Wolffian origin, and targeted therapy with Imatinib has been attempted with mixed success. Currently, it is unclear whether c-KIT immunohistochemical expression is seen in mesonephric carcinoma, a tumor that is thought to be related to female adnexal tumors of Wolffian origin, and how this correlates with KIT mutational status. In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical expression was observed in the majority of mesonephric carcinomas (10/12 cases; 83%), no KIT mutations were detected. This cautions pathologists against the use of c-KIT immunohistochemistry as a surrogate marker for KIT-activating mutations in this setting. Consistent with previous studies, the majority of mesonephric neoplasms (10/13; 77%) harbored KRAS mutations. Additional mutations were found in CTNNB1 (2/13, 15%), TP53 (2/13, 15%), and PIK3CA (1/13, 8%).
Topics: Aged; Biomarkers, Tumor; Carcinoma; Class I Phosphatidylinositol 3-Kinases; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Genital Neoplasms, Female; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Middle Aged; Mutation; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins p21(ras); Wolffian Ducts; beta Catenin
PubMed: 31714258
DOI: 10.1097/PAS.0000000000001403 -
Radiologia Brasileira 2020Although secondary involvement of the broad ligament by malignant tumors arising elsewhere in the abdomen and pelvis is common, primary tumors in this location are rare....
Although secondary involvement of the broad ligament by malignant tumors arising elsewhere in the abdomen and pelvis is common, primary tumors in this location are rare. Tumors of the broad ligament can be of mesenchymal and mixed nature, such as leiomyoma, the most common neoplasm; epithelial tumors of Müllerian type, imposing a challenge to differentiate them from other adnexal masses; unique tumors from mesonephric origin; and tumor-like lesions. Most neoplasms in this region, whether benign or malignant, usually present clinically with vague symptoms and are often discovered during a routine gynecological examination. Suspicion of such location and knowledge of the potential range of lesions of this region may allow for planning minimally invasive surgical interventions. To be considered tumor from the broad ligament, it should not be connected with either the uterus or the ovary. Thus, the imaging approach to establish the differential diagnosis includes excluding an ovarian, uterine, or tubal origin by recognizing these separately and by rebutting imaging clues pointing to these origins. This pictorial essay reviews some of the imaging findings that may suggest such location and presents some of the possible differential diagnoses by means of illustrative confirmed cases.
PubMed: 33071380
DOI: 10.1590/0100-3984.2019.0073 -
Diagnostics (Basel, Switzerland) Aug 2021When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the...
Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma.
When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the differential diagnosis remained challenging after performing immunostaining. Considering the aggressive biological behavior and poor prognosis of uterine MLA, we believe that the accurate recognition of mesonephric-like differentiation (MLD) is important in the diagnosis of endometrial carcinoma. We aimed to investigate the clinicopathological and molecular characteristics of such cases and compared them with those of uterine MLAs. Five patients diagnosed with endometrioid carcinoma (EC) with MLD were included in this study. Histological evaluation, immunostaining, and targeted sequencing were performed. All five tumors showed typical morphological features of MLA, including densely aggregated tubular structures, deep basophilia under low-power magnification microscopy, eosinophilic intraluminal secretions, and diverse growth patterns. Immunostaining revealed moderate-to-strong nuclear immunoreactivity for estrogen and progesterone receptors in more than 50% tumor cells. The staining intensities and proportions of PAX2 and GATA3 were variable. None of the tumors harbored mutations. Considering the prognostic implications, ancillary tests, including immunostaining and targeted sequencing, should be performed to accurately differentiate between endometrial EC-MLD and uterine MLA.
PubMed: 34441384
DOI: 10.3390/diagnostics11081450 -
International Journal of Gynecological... Nov 2014Mesonephric remnants, usually located deep in the lateral cervical wall, may become hyperplastic resulting in a florid proliferation. These can be misinterpreted as...
Mesonephric remnants, usually located deep in the lateral cervical wall, may become hyperplastic resulting in a florid proliferation. These can be misinterpreted as malignant and confused with endocervical adenocarcinomas. Recent data have shown that PAX2 is diffusely expressed in mesonephric remnants and hyperplasias. PAX8 is a related transcription protein that is expressed in tissues of müllerian and wolffian origin. In this study, we have investigated the utility of an immunohistochemical panel comprising of PAX8, estrogen receptor (ER), and p16 in the differential diagnosis between mesonephric proliferations and cervical adenocarcinomas. A database search was conducted for cases of mesonephric remnants/hyperplasia/carcinoma of cervix and invasive cervical adenocarcinomas. Immunohistochemical stains for PAX8, ER, and p16 were performed using the avidin-biotin peroxidase technique on the most representative tissue. The search yielded 28 cases of mesonephric proliferations of cervix (15 mesonephric remnants, 12 mesonephric hyperplasias, and 1 mesonephric adenocarcinoma) and 16 cases of cervical adenocarcinomas (15 usual type and 1 adenoma malignum). Immunohistochemically, all the mesonephric proliferations, regardless of being benign or malignant, displayed a consistent staining pattern-diffusely and strongly positive for PAX8, negative for ER, and patchy cytoplasmic staining for p16. The usual type cervical adenocarcinomas exhibited a variable staining pattern with PAX8 and ER but all were strongly and diffusely positive for p16. The case of adenoma malignum was PAX8 positive, ER negative, and showed weak and patchy staining with p16. Our study suggests that a panel of immunohistochemical stains composed of PAX8, p16, and ER is useful in the distinction between mesonephric proliferations and cervical adenocarcinomas.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Mesonephroma; PAX8 Transcription Factor; Paired Box Transcription Factors; Receptors, Estrogen; Uterine Cervical Neoplasms
PubMed: 25272301
DOI: 10.1097/PGP.0000000000000102 -
Der Pathologe May 2021The new WHO classification of tumors of the female genitalia entails some changes, especially those of prognostic and therapeutic relevance: there is a return to the... (Review)
Review
The new WHO classification of tumors of the female genitalia entails some changes, especially those of prognostic and therapeutic relevance: there is a return to the term borderline tumor. Implants are again subdivided into noninvasive implants of the epithelial or desmoplastic type as before. Invasive extraovarian implants are classified as low-grade serous carcinoma (LGSC). Former seromucinous carcinomas are now classified as endometrioid carcinomas (seromucinous subtype). New entities of ovarian carcinomas are mesonephric-like adenocarcinoma, undifferentiated and dedifferentiated carcinoma, and mixed carcinoma. The classification of neuroendocrine neoplasms is analogous to that of pulmonary and gastrointestinal neuroendocrine neoplasms, regardless of their location. Endometrioid endometrial carcinoma can be classified into four molecular subtypes, which have significant prognostic significance. New subtypes include mucinous carcinoma of the intestinal type and mesonephric-like adenocarcinoma. Stromasarcomas of the endometrium are further subclassified based on specific molecular alterations. Adenocarcinomas (ACs) and squamous cell carcinomas (PECs) of the lower female genital tract are distinguished from HPV-associated and HPV-independent carcinomas. Block-like staining for p16 is the accepted surrogate immunohistochemical marker. Grading has not been reported for PEC. For HPV-associated AC of the cervix uteri, prognostic assessment is based on the pattern of invasion (so-called Silva pattern). Serous carcinomas in the cervix uteri are endometrial carcinomas with cervical infiltration.
Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Genitalia, Female; Humans; Ovarian Neoplasms; World Health Organization
PubMed: 33822250
DOI: 10.1007/s00292-021-00933-w -
Anticancer Research May 2021We present a case of uterine dedifferentiated mesonephric-like adenocarcinoma (MLA).
BACKGROUND/AIM
We present a case of uterine dedifferentiated mesonephric-like adenocarcinoma (MLA).
CASE REPORT
A 54-year-old woman underwent total hysterectomy for a uterine mass under the impression of a uterine sarcoma. Histologically, MLA exhibited various growth patterns including tubular and glandular architecture. Undifferentiated carcinoma (UC) displayed discohesive tumor cells without any obvious architecture. Immunohistochemically, UC was positive for epithelial markers in very few scattered tumor cells. MLA exhibited the wild-type p53 expression pattern, whereas UC showed a uniform and strong p53 immunoreactivity. Targeted sequencing analysis revealed an identical Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in both components. A pathogenic missense tumor protein 53 (TP53) mutation was detected in UC, but not in MLA.
CONCLUSION
The mutant p53 expression pattern exclusively detected in UC was concordant with the presence of missense TP53 mutation. Our observations suggested that TP53 mutation is associated with the possible transformation from MLA to UC.
Topics: Adenocarcinoma; Carcinoma; Cell Dedifferentiation; Female; Humans; Hysterectomy; Middle Aged; Sarcoma; Uterine Diseases; Wolffian Ducts
PubMed: 33952503
DOI: 10.21873/anticanres.15053 -
Journal of Endourology Case Reports 2020A 17-year-old male with Zinner syndrome, a right seminal vesicle cyst, and a solitary left kidney presented with chronic pelvic pain. Previous surgeons had attempted...
A 17-year-old male with Zinner syndrome, a right seminal vesicle cyst, and a solitary left kidney presented with chronic pelvic pain. Previous surgeons had attempted robot-assisted laparoscopic seminal vesicle cyst aspiration and transurethral resection of the ejaculatory duct. Neither surgery provided sustained symptom relief. Abdominal and pelvic MRI showed a cystic structure lodged between the prostate and bladder. The right seminal vesicle, kidney, and ureter were not observed. A robot-assisted laparoscopic seminal vesiculectomy was planned. Dissection distal to the right vas deferens and between the bladder neck and prostate revealed a cystic seminal vesicle-like structure. Attached to this was a tubular structure coursing deep to the vas deferens from the right renal fossa. This was presumed to be a dysplastic ureter. The dysplastic ureter was transected from the seminal vesicle and the seminal vesicle was marsupialized to the deep pelvis. Proximally, the dysplastic ureter was transected and left open. Histologic assessment of the specimen revealed an ∼12.1 cm tubular mesonephric remnant. The postoperative course was uncomplicated. At 6 months follow-up, the patient remains free of symptoms with preserved ejaculatory volume. Mesonephric duct abnormalities and symptoms present on a spectrum. We present a safe and effective resection of a mesonephric duct remnant from a 17-year-old male with Zinner syndrome. A robotic approach localized to the right allowed for excellent observation without compromising left-sided genitourinary anatomy. In males presenting with renal agenesis and pelvic symptoms, clinicians should be suspicious of Zinner syndrome and other mesonephric abnormalities.
PubMed: 33102726
DOI: 10.1089/cren.2020.0020 -
Applied Immunohistochemistry &... Mar 2023A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be...
A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 ( CTNNB1 ) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.
Topics: Female; Humans; Carcinoma, Endometrioid; Endometrial Neoplasms; Receptors, Progesterone; Proto-Oncogene Proteins p21(ras); Catenins; Mutation; Estrogens; Biomarkers, Tumor; beta Catenin
PubMed: 36695555
DOI: 10.1097/PAI.0000000000001102