PTEN Loss and ARID1A Mutation in an HPV-positive Metastatic Adenocarcinoma Diagnosed Almost 18 yr After an Intact Cone Excision for Endocervical Adenocarcinoma In Situ.

There have been previous reports of neoplasms with the morphology of endocervical adenocarcinoma in situ (AIS) that secondarily involve the ovaries, presumably through transtubal spread, with a smaller subset metastasizing to distant sites. These ovarian metastases have been discovered up to 7 yr postexcision of the endocervical lesion, consistent with the known potential for overtly invasive cervical carcinomas to recur late after primary curative management. Herein, we present a case of a premenopausal woman with a pelvic mass classified as metastatic human papillomavirus (HPV)-associated endocervical adenocarcinoma (p16-block immunoreactive, high-risk HPV positive by in situ hybridization with PTEN loss, ARID1A, and PBRM1 mutations detected by qualitative next-generation sequencing), identified 17.7 yr (212 mo) after a fertility-sparing cone excision with negative margins for endocervical AIS [HPV-associated, p16-block immunoreactive; PTEN, and BAF250a (ARID1a) expression retained]. Our case highlights: (1) the potential for a subset of lesions with the morphology of AIS to metastasize, and the extraordinarily long timeframe (almost 18 y, the longest reported to date) during which metastases may still be identified; (2) alterations in PTEN and ARID1A may play a role in the progression of a subset of endocervical carcinomas; and (3) the need for studies to evaluate the utility of incorporating ovarian/pelvic imaging into surveillance protocols following fertility-sparing excisions or ovarian-preserving hysterectomies, during the management of endocervical adenocarcinomas, as well as the need to counsel patients about the small but real risk of delayed discovery of ovarian metastases following fertility-preserving surgeries for AIS.

Endometrial tumors with yolk sac tumor-like morphologic patterns or immunophenotypes: an expanded appraisal.

Uterine yolk sac tumors have gained increased recognition in recent years. The current study is a multi-faceted examination of yolk sac tumor-like phenotypes in endometrial tumors, based on an analysis of 3 groups of uterine tumors: Group 1: 9 endometrial tumors that had been classified as yolk sac tumor, or as having a yolk sac tumor component, were assessed with a 35-marker immunohistochemical panel, with the goal of defining their immunophenotypic spectrum; Group 2, comprised of 70 endometrial carcinomas of various histotypes, were analyzed for their expression of SALL4, Glypican-3, and AFP, to assess the specificity of these markers for yolk sac tumors relative to endometrial carcinomas; Group 3, comprised of 626 archived cases of endometrial carcinoma/carcinosarcoma, reviewed to define the frequency of yolk sac tumor-like morphology therein. Yolk sac tumor areas in the Group 1 cases were consistently immunoreactive for SALL4 and Glypican-3; variably positive for AFP (89%), Villin (89%), PLAP (78%), 34ßE12 (67%), CAM 5.2 (62.5%), EMA (56%), CD117 (50%), p16 (50%), CDX2 (44%), p53 (44% aberrant), MOC31 (37.5%), CK7 (33%), GATA3 (33%), CK5 (25%), and PAX8 (11%); and were negative for CD30, Napsin A, OCT4, estrogen, androgen, and progesterone receptors. 29 (41%) of the 70 group-2 cases expressed at least one of the 3 markers, and 96% of the positive cases was a high-grade histotype. Glypican-3, SALL4, and AFP were positive in 30, 20, and 2.8% of group-2 cases respectively; however, co-expression of any 2, or all 3 markers was uncommon (<9 and 1.4% of cases respectively). Potential yolk sac tumor-like morphology was identified in 5 (0.8%) of 626 group-3 cases, and three were ultimately deemed to be true yolk sac tumor phenotypes based on their morphologic and immunophenotypic similarity to the group 1 cases. These findings highlight the broad immunophenotypic spectrum of uterine yolk sac tumors, the potential pitfalls associated with using immunophenotypes alone to define yolk sac tumor differentiation in endometrial carcinoma, and the utility and limitations of morphologic assessment to identify yolk sac tumors at this site.

Does a p53 "Wild-type" Immunophenotype Exclude a Diagnosis of Endometrial Serous Carcinoma?

An aberrant p53 immunophenotype may be identified in several histotypes of endometrial carcinoma, and is accordingly recognized to lack diagnostic specificity in and of itself. However, based on the high frequency with which p53 aberrations have historically been identified in endometrial serous carcinoma, a mutation-type immunophenotype is considered to be highly sensitive for the histotype. Using an illustrative case study and a review of the literature, we explore a relatively routine diagnostic question: whether the negative predictive value of a wild-type p53 immunophenotype for serous carcinoma is absolute, that is, whether a p53-wild type immunophenotype is absolutely incompatible with a diagnosis of serous carcinoma. The case is an advanced stage endometrial carcinoma that was reproducibly classified by pathologists from 3 institutions as serous carcinoma based on its morphologic features. By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2. Next generation sequencing showed that there indeed was an underlying mutation in TP53 (D393fs*78, R213*). The tumor was microsatellite stable, had a low mutational burden (4 mutations per MB), and displayed no mutations in the exonuclease domain of DNA polymerase epsilon (POLE) gene. Other genomic alterations included RB1 mutation (R46fs*19), amplifications in MYST3 and CRKL, and ARID1A deletion (splice site 5125-94_5138del108). A review of the recent literature identified 5 studies in which a total of 259 cases of serous carcinoma were whole-exome sequenced. The average TP53 mutational rate in endometrial serous carcinoma was only 75% (range, 60 to 88). A total of 12 (33%) of 36 immunohistochemical studies reported a p53-aberrant rate of <80% in endometrial serous carcinoma. We discuss in detail several potential explanations that may underlie the scenario of serous carcinoma-like morphology combined with p53-wild-type immunophenotype, including analytic limitations, a nonserous histotype displaying morphologic mimicry of serous carcinoma, and true biological phenomena (including the possibility of a TP53-independent pathway of endometrial serous carcinogenesis). Ultimately, our central thematic question is provisionally answered in the negative. At present, the available data would not support a categorical conclusion that a p53 alteration is a necessary and obligate component in the genesis and/or diagnosis of endometrial serous carcinoma. On the basis of their collective experience, the authors proffer some recommendations on the use of p53 immunohistochemistry in the histotyping of endometrial carcinomas.

Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seventeen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1ß did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap with primary neoplasia. However, the expected morphology and immunophenotype of CCRCC are maintained in most gynecologic tract metastases. As such, although metastatic CCRCC and müllerian CCC may display significant overlap in pathologic features, several morphologic and immunophenotypic features are useful in their distinction.

The pathologic distinction of primary and metastatic mucinous tumors involving the ovary: A re-evaluation of algorithms based on gross features.

The problems associated with the pathologic distinction of primary ovarian mucinous tumors from their metastatic counterparts are well-recognized. Herein, we systematically evaluate a variety of gross parameters to determine the combination of features that most optimally separate primary from secondary mucinous ovarian tumors, and to address the tumor types that are most frequently associated with exceptions. 129 consecutive mucinous tumors involving the ovary formed the study set, including 61 primary mucinous tumors (16 carcinomas, 45 borderline tumors), and 68 metastatic carcinomas (21 colon; 28 appendix; 5 breast; 3 lung; 3 pancreas; 3 cervix; 1 bladder; 4 stomach). Consistent with prior studies, we found that as compared with metastases, primary ovarian mucinous tumors tend to be larger, more frequently unilateral and were more likely to be predominantly cystic and devoid of surface nodules. 41 of the 68 cases in the metastatic group showed intraperitoneal disease, as compared with only 3 of the 61 cases in the primary group (p < 0.0001). In 21% (14/68) of the metastatic group, the ovarian tumor was the first clinical indication of the primary tumor, and 82% of those cases were of gastrointestinal tract primary; this group of cases showed significantly larger tumors than ovarian tumors for patients with an established diagnosis of cancer. Receiver operating curve analyses showed that a tumor size cut off of <13 cm for metastatic disease yielded the maximal area under the curve of 0.877 (sensitivity 80%; specificity 80%); the most frequent exception to the size cut off of <13 cm for metastases was colorectal carcinoma, 30% of which were ≥13 cm. An algorithm whereby a tumor ≥13 cm is considered primary unless it displays surface nodules or bilaterality, and a tumor <13 cm is considered metastatic unless it is unilateral, correctly classified 94% (64/68) of the metastatic tumors and 98% (60/61) of the primary tumors. 3 of the 4 incorrectly classified cases in the metastatic group had intraperitoneal disease. We conclude that gross features are very useful in the distinction of primary from metastatic mucinous tumors in the ovary, and the presence of intraperitoneal disease provides additional diagnostic information. Although algorithms such as the one described herein are imperfect classifiers, they do provide baseline information on which additional findings, including microscopic features, can be added to ultimately provide the most accurate diagnostic classification.

SATB2 Expression Is Sensitive but Not Specific for Osteosarcomatous Components of Gynecologic Tract Carcinosarcomas: A Clinicopathologic Study of 60 Cases.

The novel marker special AT-rich sequence binding protein (SATB2) is highly sensitive for mesenchymal tumors with osteoblastic differentiation. However, SATB2 expression in gynecologic tract carcinosarcoma has not been previously explored. Given the potential prognostic and therapeutic implications of heterologous carcinosarcoma in the gynecologic tract, this study investigates the utility of SATB2 in identifying osteosarcomatous elements. A multi-institution database review identified consecutive cases of gynecologic tract carcinosarcoma including both heterologous and homologous types. Clinicopathologic parameters were recorded. Nuclear SATB2 immunoreactivity was scored from 1 representative whole-slide section from each case. Sixty gynecologic tract carcinosarcoma were identified (uterine corpus=47, ovary=11, fallopian tube=1, cervix=1) including 32 heterologous type (7 osteosarcoma, 3 mixed osteosarcoma/chondrosarcoma, 6 chondrosarcoma, 12 rhabdomyosarcoma, 4 mixed chondrosarcoma/rhabdomyosarcoma) and 28 homologous type. Patient ages ranged from 41 to 90 yr (average 67.9 yr). Mostly diffuse strong SATB2 positivity was present in 10/10 (100%) cases containing osteosarcoma. In these cases, SATB2 positivity was seen in malignant cells intimately associated with osteoid or bone [3/10 (30%) of these cases additionally showed patchy weak/moderate SATB2 staining in areas of nonosteogenic sarcoma elsewhere in the same tumor]. SATB2 positivity was present in 30/50 (60%) cases lacking osteosarcoma, predominantly as patchy moderate staining within undifferentiated sarcoma. No cases showed SATB2 positivity in chondrosarcoma or rhabdomyosarcoma components. SATB2 is a highly sensitive marker for osteosarcomatous differentiation in gynecologic tract carcinosarcoma, and is also highly specific when used to differentiate osteosarcoma from chondrosarcoma and rhabdomyosarcoma elements in these tumors. However, a positive SATB2 result may lack specificity for differentiating osteosarcoma from an undifferentiated sarcoma component.

Factors Predicting Pelvic Lymph Node Metastasis, Relapse, and Disease Outcome in Pattern C Endocervical Adenocarcinomas.

A pattern-based classification system has recently been proposed for invasive endocervical adenocarcinoma (EAC), which is predictive of the risk for lymph node metastases (LNM). The main utility of the system lies in separating cases with very low risk for LNM (pattern A) from those with higher risk (pattern B and C). Different growth patterns (GPs) are found in pattern C cases. The aim of the study was to evaluate the effect of GP on the behavior of pattern C EAC. By reevaluating 189 pattern C EACs, we documented 6 architectural GPs: diffuse destructive (DD), confluent (CON), extensive linear destructive (ELD), band-like lymphocytic infiltrate (BLL), solid (SOL), and micropapillary (MP). When an EAC had an appreciable second component (≤50%) the designation of a mixed EAC was used. We found 32 (17%) tumors to be DD, 23 (12%) CON, 27 (14%) ELD, 9 (5%) SOL, 7 (4%) BLL, and 7 (4%) micropapillary. A total of 84 (44%) EACs were mixed (DD+CON). All micropapillary EACs had LNM versus none of the patients with EAC with an ELD GP (P=0.002). Recurrent disease was seen in 44% of EACs with a DD GP, whereas 0% of EACs with BLL GP developed recurrent disease. Mixed (DD+CON) tumors had a significantly worse 6-year overall survival. This study demonstrated that not all pattern C EACs have an aggressive behavior. These patients should be treated with radical hysterectomy and sentinel lymph node biopsy.

Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas.

Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci. Digital H&E images from 20 gynecologic tract carcinosarcomas were reviewed by 22 gynecologic pathologists with a request to determine the presence or absence of an osteosarcomatous component. The 20 preselected cases included areas of classic heterologous osteosarcoma (malignant cells producing osteoid; n=10) and osteosarcoma mimics (malignant cells with admixed nonosteoid matrix; n=10). Interobserver agreement was evaluated and SATB2 scored on all 20 cases and compared with the original diagnoses. Moderate agreement (Fleiss' κ=0.483) was identified for the 22 raters scoring the 20 cases with a median sensitivity of 7/10 and a median specificity of 9/10 for the diagnosis of osteosarcoma. SATB2 showed 100% sensitivity (10/10) and 60% (6/10) specificity in discriminating classic osteosarcoma from osteosarcoma mimics. Utilizing negative SATB2 as a surrogate marker to exclude osteosarcoma, 73% (16/22) of the reviewers would have downgraded at least 1 case to not contain an osteosarcomatous component (range, 1-6 cases, median 1 case). Gynecologic pathologists demonstrate only a moderate level of agreement in the diagnosis of heterologous osteosarcoma based on morphologic grounds. In such instances, a negative SATB2 staining may assist in increasing accuracy in the diagnosis of an osteosarcomatous component.

Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change.

Several studies have documented phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy [NACT], but many of these studies are limited by the fact that they did not account for the baseline rate of expected phenotypic change between biopsies and resections in the absence of NACT. Herein, we assess whether the NACT-associated rate of phenotypic change is significantly different than would be expected in a control population of patients that did not receive NACT. From a pathologic database, we documented the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) phenotypes of consecutive invasive breast carcinomas (n=826), as well as the subset in which at least one of these tests was assessed in both the biopsy and resection (n=340). We then compared the rates of phenotypic change in the patients that did (n=65) and did not (n=275) receive NACT. Respectively, 49.2% and 36% of the NACT and non-NACT groups showed a biopsy-to-resection change in status for at least one biomarker (p=0.0005). The NACT and non-NACT groups showed the following respective rates of a biopsy-to-resection change in phenotype: ER (9.2% vs 2.5%, p=0.02); PR (30.7% vs 8%, p=0.000006); Her2/neu-IHC (25% vs 22.3%, p=0.7), Her2/neu-FISH (7% vs 3%, p=0.6). The direction of change in the NACT group was positive in the biopsy to negative in the resection in >70% of cases for all markers. For ER and PR, there was no statistically significant difference between cases that showed a biopsy-to-excision change in phenotype and those that were more phenotypically stable regarding a wide array of clinicopathologic variables. The average percentage of ER/PR-immunoreactive tumor cells in the pre-NACT biopsies was significantly lower in the phenotypically altered cases as compared to the phenotypically stable cases. Our findings confirm that phenotypic alterations in breast cancer occur after NACT, and that these changes are more pronounced for hormone receptors (especially PR); Significant NACT-associated alterations were not apparent for HER2/neu. A distinct pathologic profile for cases displaying a phenotypic change within the NACT group was not demonstrable. The pre-NACT levels of ER and PR may affect the likelihood of a phenotypic change. These results highlight the need for repeat testing in residual tumors after NACT.

Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria.

Previously, our international team proposed a three-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification-A tumors have well-demarcated glands lacking destructive stromal invasion or lymphovascular invasion, Pattern Classification-B tumors show localized, limited destructive invasion arising from A-type glands, and Pattern Classification-C tumors have diffuse destructive stromal invasion, significant (filling a 4 × field) confluence, or solid architecture. Twenty-four cases of Pattern Classification-A, 22 Pattern Classification-B, and 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis originally established. One H&E slide per case was reviewed by seven gynecologic pathologists, four from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near-complete (six of seven) agreement in 50%. Overall concordance was 74%. Overall kappa (agreement among pathologists) was 0.488 (moderate agreement). Pattern Classification-B has lowest kappa, and agreement was not improved by combining B+C. Six of seven reviewers had substantial agreement by weighted kappas (>0.6), with one reviewer accounting for the majority of cases under or overcalled by two tiers. Confluence filling a 4 × field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis-B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly applied by gynecologic pathologists. Further refinement of criteria should allow use of this powerful classification system to delineate which cervical adenocarcinomas can be safely treated conservatively.

New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors.

Value of PAX-8 and SF-1 Immunohistochemistry in the Distinction Between Female Adnexal Tumor of Probable Wolffian Origin and its Mimics.

Female adnexal tumors of probable wolffian origin (FATWOs) are rare. They can closely mimic endometrioid adenocarcinomas with a prominent spindle cell component and Sertoli cell tumors (SCTs). To further define their immunohistochemical profile and origin, we investigated the expression of PAX-8, PAX-2, and GATA binding protein 3 (GATA-3) (wolffian markers) and of steroidogenic factor-1 (SF-1) (sex-cord stromal marker) in FATWOs. We also studied the expression of PAX-8 and PAX-2 in endometrioid adenocarcinomas; of SF-1 in Sertoli-Leydig cell and SCTs; and of PAX-8, PAX-2, GATA-3, and SF-1 in rete ovarii-a proposed site of origin for FATWOs. A database search yielded 8 FATWOs, 18 ovarian/tubal/paraovarian endometrioid adenocarcinomas, and 8 ovarian Sertoli-Leydig cell and SCTs. Eleven cases with rete ovarii sections were included. Of the FATWOs studied, all were negative for PAX-8, PAX-2, GATA-3, and SF-1. Of the endometrioid adenocarcinomas studied, PAX-8 was positive in all and PAX-2 was positive in 57%. Of the Sertoli-Leydig cell and SCTs, all were positive for SF-1 except one. The rete ovarii were positive for PAX-8, weakly positive for SF-1, and negative for PAX-2 and GATA-3. Our study suggests that PAX-8 and SF-1 can be helpful in the distinction between FATWOs and endometrioid adenocarcinomas and SCTs, respectively. Our results do not support a Mullerian or sex-cord stromal or rete ovarii origin for FATWOs. It is curious, however, that FATWOs do not express wolffian markers-it is possibly related to their origin from a distinctive portion of the wolffian duct.

Prostate-Type Adenocarcinoma in Mature Cystic Ovarian Teratoma.

We report our experience with prostatic-type tissue in ovarian teratomas, and in particular we highlight a case of prostatic-type adenocarcinoma arising within a mature cystic ovarian teratoma in a 32-yr-old woman. On gross examination, the cyst consisted of typical features of a dermoid cyst. Closer examination revealed a single 1.5-cm solid nodule within the cyst. Microscopically, it was composed of a small cyst-like structure lined by urothelium and to one side glandular and stromal tissue consistent with prostate parenchyma. Within the prostatic-type tissue, there were malignant glands morphologically and immunohistochemically supportive of prostatic-type adenocarcinoma Gleason score 3+3=6. There were also areas consistent with high-grade prostatic intraepithelial neoplasia. Although there are several reports in the literature of benign prostatic-type tissue arising within ovarian as well as testicular teratomas, to our knowledge, prostatic-type adenocarcinoma arising in a mature ovarian teratoma is an extremely rare phenomenon, with only 1 previous report in the literature.

Tubulosquamous polyps in the vagina. Immunohistochemical comparison with ectopic prostatic tissue and Skene glands.

Two tubulosquamous polyps arising in the vagina are reported. Both were diffusely positive for GATA3 in the squamous component and focally positive for NKX3.1 in the glandular component, prostate acid phosphatase was focally positive in only 1 case in the glandular component. Both cases were negative for PAX2, PAX8, SALL4, and prostate-specific antigen. In addition, we included 3 cases of cervical squamous-lined cysts most likely representing ectopic prostatic tissue in the cervix and 1 case of paraurethral Skene-type glands to compare the immunophenotype. We analyze this immunoprofile, not previously reported. We also suggest unifying the nomenclature because vaginal Brenner tumors are most likely synonymous with tubulosquamous polyp (TSP) of the vagina. Our findings add support to the postulated origin of TSPs and cervical ectopic prostatic tissue from eutopic or misplaced Skene glands, equivalent of the prostate in the female. NKX3.1 seems a better marker to study and diagnose ectopic prostatic tissue in the cervix as well as TSPs.

Remodeling characteristics and collagen distribution in biological scaffold materials explanted from human subjects after abdominal soft tissue reconstruction: an analysis of scaffold remodeling characteristics by patient risk factors and surgical site classifications.

OBJECTIVE: The study purpose was to evaluate the associations between patient characteristics or surgical site classifications and the histologic remodeling scores of biologic meshes biopsied from abdominal soft tissue repair sites in the first attempt to generate a multivariable risk-prediction model of nonconstructive remodeling. BACKGROUND: Host characteristics and surgical site assessments may predict remodeling degree for biologic meshes used to reinforce abdominal tissue repair sites. METHODS: Biologic meshes were biopsied from the abdominal tissue repair sites of n = 40 patients during an abdominal reexploration, stained with hematoxylin and eosin, and evaluated according to a semi-quantitative scoring system for remodeling characteristics (cell types, cell infiltration, extracellular matrix deposition, scaffold degradation, fibrous encapsulation, and neovascularization) and a mean composite score. Biopsies were stained with Sirius Red and Fast Green and analyzed to determine the collagen I:III ratio. On the basis of univariate analyses between subject clinical characteristics or surgical site classification and the histologic remodeling scores, cohort variables were selected for multivariable regression models using P ≤ 0.200. RESULTS: The model selection process for cell infiltration score yielded 2 variables: age at mesh implantation and mesh classification (C statistic = 0.989). For the mean composite score, the model selection process yielded 2 variables: age at mesh implantation and mesh classification (r = 0.449). CONCLUSIONS: These preliminary results constitute the first steps in generating a risk-prediction model that predicts the patients and clinical circumstances most likely to experience nonconstructive remodeling of abdominal tissue repair sites with biologic mesh reinforcement.

Patterns of Invasion of Cervical Adenocarcinoma as Predicators of Outcome.

In this review, a recently published pattern-based risk stratification system of endocervical adenocarcinoma (EAC) is presented. This novel system evaluates the morphologic features of the tumor and establishes patterns that are associated with a particular tumor behavior. Patients with pattern A EAC do not develop lymph node metastasis, and therefore avoiding lymph node resection in these patients should be considered. These patients also have stage I tumors and conservative surgery would be beneficial to decrease morbidity. Patients with pattern B tumors rarely show metastases to lymph nodes, only if there is lymphovascular invasion, whereas those with pattern C tumors would require aggressive treatment as most lymph node or distant metastases and recurrences were noted in patients with this tumor pattern. Combining this new risk stratification system with an algorithm that surgeons and oncologists could complement to other actionable data would result in a more conservative treatment plan in patients with a new diagnosis of invasive usual-type EAC, as opposed to the current more radical treatment plan. This risk stratification model significantly improves on conventionally used factors such as histologic type, grade, and stage to help manage patients with EAC and identify those in need for aggressive surgical management versus a more conservative approach.

Differential Expression Patterns of GATA3 in Uterine Mesonephric and Nonmesonephric Lesions.

GATA binding protein 3 (GATA3) is a recently described immunohistochemical marker that has proven useful in the characterization of breast and urothelial carcinomas. However, the expression pattern of GATA3 in mesonephric proliferations is largely unknown. The aim of this study was to examine the immunohistochemical expression of GATA3 in cervicovaginal mesonephric lesions and compare it to its expression in endocervical and endometrial adenocarcinomas and cervicovaginal endometriosis. A cohort of 107 cases, including 33 cases of mesonephric lesions and 74 cases of nonmesonephric lesions, was selected for the study. Of 33 mesonephric lesions, 31 (94%) cases (16 remnants, 12 hyperplasias, and 3 adenocarcinomas) were strongly and diffusely positive in tumor cell nuclei for GATA3. The remaining 2 mesonephric carcinosarcomas showed focal nuclear staining and rare nuclear positivity, respectively. Of 36 endocervical adenocarcinomas, 33 (92%) were negative for GATA3 and the remaining revealed focal weak nuclear staining. Of 34 endometrial adenocarcinomas, 32 (94%) were negative, whereas 2 showed rare nuclear positivity. All 4 cases of endometriosis were negative. The benign endocervical epithelium and the benign endometrium in most cases lacked GATA3 expression, whereas the benign squamous epithelium in the majority exhibited nuclear basal and parabasal staining pattern. Our study demonstrates that GATA3 protein is expressed in most mesonephric lesions, regardless of them being benign or malignant. In contrast, GATA3 is absent in the majority of endometrial and endocervical adenocarcinomas. These results support that GATA3 immunostain can be a useful tool in differentiating mesonephric lesions from endocervical and endometrial adenocarcinomas.

Different staining patterns of ovarian Brenner tumor and the associated mucinous tumor.

The association of ovarian Brenner tumors and adjacent mucinous tumors is well known but not completely understood. In this study, we analyzed immunohistochemical markers on Brenner tumors and their associated mucinous tumor to explore Mullerian as well as Wolffian and germ cell derivation and determine if the mucinous component is independent or related to the Brenner tumor. Of 32 consecutive cases of Brenner tumors, 8 were identified with significant mucinous component, and 7 additional cases included foci of mucinous epithelium within the Brenner transitional nests. All Brenner tumors were diffusely positive for GATA3 and negative for Paired box gene 8, PAX2, and Sal-like protein 4. Interestingly, the areas of mucinous epithelium as well as mucinous tumors, intermixed and adjacent to the Brenner tumor, were negative for all 4 markers; however, occasional basal-like cells retained expression of GATA3. The immunoprofile of mucinous tumors associated with Brenner tumors shares the lack of Mullerian markers PAX2 and Paired box gene 8 with the Brenner tumor but differs in the expression of GATA3 only in the Brenner tumor component.

Remodeling Characteristics and Collagen Distributions of Biologic Scaffold Materials Biopsied From Postmastectomy Breast Reconstruction Sites.

OBJECTIVE: The study purpose was to evaluate the associations between patient characteristics and the histologic remodeling scores of acellular dermal matrices (ADMs) biopsied from breast reconstruction sites in the first attempt to generate a multivariable risk prediction model of nonconstructive remodeling. It was hypothesized that host characteristics and surgical site assessments predict the degree of graft remodeling for ADMs used during breast reconstruction. METHODS: The ADMs were biopsied from the breast reconstruction sites of n = 62 patients during a subsequent breast procedure, stained with hematoxylin-eosin, and evaluated according to a semi-quantitative scoring system for remodeling characteristics (cell types, cell infiltration, extracellular matrix deposition, scaffold degradation, fibrous encapsulation, and neovascularization) and a mean composite score. Biopsies were stained with Sirius Red and Fast Green, and analyzed to determine the collagen I:III ratio. Based on univariate analyses between subject clinical characteristics and the histologic remodeling scores, cohort variables were selected for multivariable regression models using a P value of 0.20 or less. RESULTS: The composite score model yielded 3 variables: pack-year history, corticosteroid use, and radiation timing (r pseudo = 0.81). The model for collagen I yielded 2 variables: corticosteroid use and reason for reoperation (r pseudo = 0.78). The model for collagen III yielded 1 variable: reason for reoperation (r pseudo = 0.35). CONCLUSIONS: These preliminary results constitute the first steps in generating a risk prediction model that predicts the patients and clinical circumstances most likely to experience nonconstructive remodeling of biologic grafts used to reconstruct the breast.

Mesonephric carcinosarcoma involving uterine cervix and vagina: report of 2 cases with immunohistochemical positivity For PAX2, PAX8, and GATA-3.

Mesonephric carcinomas are rare tumors predominantly arising in the uterine cervix from mesonephric remnants. Although the tumor has classic morphologic features, some cases can mimic Müllerian adenocarcinoma and be misdiagnosed, especially those with significant ductal pattern. Moreover, there is an overlap in immunohistochemical results with endometrial and endocervical carcinomas. In this study, we report 2 cases of mesonephric carcinosarcoma, originally diagnosed as Müllerian carcinomas, 1 presenting in the vagina; review immunohistochemical results including positivity for GATA-3, not previously reported and comment on the proposed panel of PAX8, p16, and estrogen receptors as discriminators of Müllerian adenocarcinoma (endocervical or endometrial) versus mesonephric carcinoma.