Serous Carcinoma Mimicking Primary Urothelial Carcinoma on Clinical Evaluation and Pathology: A Potential Diagnostic Pitfall.
In contrast to this "typical" scenario, we have identified 5 patients who were originally considered to have primary bladder carcinoma based on imaging, symptomatic findings, and initial histopathologic review. Variations on this scenario have previously been reported in isolated case reports or small case series. (6,7) We also identified a subset of serous carcinoma implants within the bladder wall that showed morphologic overlap with urothelial carcinoma. Given the potential clinical and morphologic overlap in the diagnosis between serous carcinoma involving the bladder wall and urothelial carcinoma of the bladder, we performed a panel of immunohistochemical stains to determine the frequency of immunoreactivity in serous carcinoma implants. This study expands upon the reported features of tubo-ovarian and endometrial serous carcinoma in this clinical setting, including morphologic mimics of urothelial carcinoma, and describes a panel of immunohistochemical stains that can be useful in the differential diagnosis.
MATERIALS AND METHODS
Histopathologic Review and Patient Outcomes
This study was approved by the institutional review board at each institution. We performed a surgical pathology database search for all bladder specimens obtained during the years 2001 to 2015 and substratified that report to identify cases containing the term serous carcinoma. Reports were manually screened to identify cases in which tissues were obtained concurrent with resection for known ovarian, fallopian tube, or uterine primary carcinoma. Twenty-two cases of high-grade serous carcinoma involving the bladder wall were identified that included both local peritoneal resection of the exterior bladder wall and transurethral resection specimens to sample the luminal bladder surface. Material from 2 patients was unavailable for review, and those patients were excluded from further study.
Hematoxylin-eosin-stained slides from the 20 cases with available material were rereviewed by 3 genitourinary pathologists and a gynecologic pathologist. Bladder specimens were characterized for extent of carcinoma involvement of the bladder wall, morphologic features, and presence of urothelial colonization.
Clinical records for all patients were reviewed. Information collected included age at procedure, prior medical history, presurgical imaging, operative notes, pathology reports, postoperative therapies, and survival.
Prior immunohistochemical stains, when available, were reviewed. All cases were additionally restained for cytokeratin 7 (CK7; 1:1500; Abcam, Cambridge, Massachusetts); GATA3 (1:300; Cell Marque Rocklin, California), PAX8 (1:300; Cell Marque), uroplakin II (UPII; prediluted; Biocare Medical, Concord, California), p63 (1:600; Biocare Medical), and WT1 (1:10; Leica Microsystems, Buffalo Grove, Illinois). In brief, 4-[micro]m sections were obtained from formalin-fixed, paraffin-embedded material. Antigen retrieval was performed using Cell Conditioning I (Ventana Medical Systems, Tucson, Arizona) for 40 to 72 minutes at 95[degrees]C, with range dependent upon epitope. Slides were incubated with primary antibody for 1 hour at 37[degrees]C, followed by application of secondary UltraMap (Vexcel Imaging, Graz, Austria) antibodyhorseradish peroxidase conjugate and incubation of slides with 3,3'-diaminobenzidine. Slides were counterstained with hematoxylin, rinsed, dehydrated with alcohol and xylene, and coverslipped. The UPII antibody was developed using Fast Red chromogen. Stains were scored by 2 pathologists (D.E.H. and O.F.). For each antibody, cancer cells were categorized as negative, weakly positive ([1.sup.+]), or strongly positive ([2.sup.+]-[3.sup.+]) and as present in a focal or diffuse pattern. Appropriate positive and negative controls were used.
Clinicopathologic Features of Women With Serous Carcinoma Involvement of the Bladder Wall
We identified 20 patients with a final diagnosis of serous carcinoma involving the bladder (Table 1). Mean patient age was 63 years, although some patients presented as young as 44 years. Fifteen patients (75%) had a known history of tuboovarian or uterine serous carcinoma. Three of the 20 patients (15%) had a history of serous carcinoma at least 1 year prior but which presented as a primary bladder carcinoma on clinical evaluation, and 2 patients (10%) had no precedent gynecologic history and presented with a large, regional mass that involved the full thickness of the bladder wall. Five patients (25%) had precedent breast cancer, and 1 patient (5%) subsequently developed breast cancer.
Imaging results were available for 17 of the 20 patients (85%) performed at the time of bladder involvement and showed a bladder-predominant mass in 2 patients (10%), a uterine or adnexal primary mass in 3 patients (15%), and extensive pelvic involvement in 12 patients (60%). Urine cytology was requested in 5 patients (25%) and showed atypical cells in 1 patient and malignant cells in a second. Papanicolaou tests showed the presence of adenocarcinoma in 2 of 13 patients (15%) in which it was performed.
In the 15 of 20 patients (75%) with a suspected high-grade serous carcinoma, surgery included removal of bladder implants in addition to resection of the primary lesion. The remaining 5 patients (25%) were presumed to have a likely primary bladder carcinoma and underwent transurethral resection (1 patient), partial cystectomy (1 patient), or pelvic exenteration (3 patients).
Morphology of Serous Carcinoma Involving the Bladder Wall
We rereviewed all hematoxylin-eosin slides from the 20 patients in the study to determine the spectrum of morphologic findings of serous carcinoma involving the bladder wall (Table 2). In 13 cases (65%), classic serous carcinoma morphology, including micropapillary, papillary, solid with slitlike spaces, cribriform, or glandular architecture; psammoma bodies; marked desmoplasia; nuclear pleomorphism; and prominent nucleoli were present in a subset of cases and did not pose a diagnostic dilemma (Figure 1, A through D). In addition, those cases typically showed minimal peritoneal involvement.
Carcinomas that penetrated deeper into the bladder wall, however, showed more-variable features that could potentially be misinterpreted as urothelial carcinoma variants in the context of limited clinical information or a clinical impression of a primary bladder cancer, including features that overlapped with urothelial carcinoma variants. Those features included solid growth with basaloid features (3 of 20 patients; 15%), squamouslike differentiation (2 patients; 10%), bland nests (2 patients; 10%), spindled/sarcomatoid change (2 patients; 10%), and syncytial growth with inflammation (1 patient; 5%). Both basaloid and syncytial growth patterns occur in serous carcinoma and can thus show morphologic overlap with poorly differentiated urothelial carcinoma and a lymphoepithelioma-like carcinoma appearance, respectively. Four of the 20 cases (20%) showed these variant morphologies of serous carcinoma. The basaloid appearance was notable for irregular sheets of basophilic cells with peripheral palisading that were associated with a desmoplastic stromal background (Figure 2, A and B). Brisk mitotic activity and prominent nucleoli were appreciated at higher magnification, although psammoma bodies were absent in these cases. One case showed a more-epithelioid appearance (Figure 2, C and D). A syncytial growth pattern was evident in one case, which extended to immediately underlie the surface urothelium (Figure 2, E and F). The carcinoma cells contained a syncytial growth pattern, with carcinoma cells containing vesicular nuclei and prominent nucleoli that could readily mimic a lymphoepithelioma-like carcinoma; however, the prominent inflammatory infiltrate in that patient consisted of neutrophils, rather than lymphocytes and plasma cells.
Several unusual patterns were also evident that could readily mimic an urothelial carcinoma in that location. A subset of cases showed small- to medium-sized epithelial nests with only mild to moderate nuclear pleomorphism infiltrating the full thickness of the bladder wall (Figure 3, A and B). An early suggestion of desmosomes in these cases may give the appearance of squamous differentiation. In addition, one case was also notable for exceptionally bland morphology, which is unusual in the setting of metastatic serous carcinoma (Figure 3, C and D). Two cases also showed a spindled/sarcomatoid appearance that could mimic a sarcomatoid carcinoma of the bladder (Figure 3, E and F).
We also identified 2 of the 20 cases (10%) with surface colonization of the urothelium by serous carcinoma. In both cases, those carcinomas showed exophytic lesions that resembled high-grade papillary urothelial carcinoma with the presence of thin, fibrovascular cores and overlying neoplastic cells (Figure 4, A and B). Two additional cases that were clinically considered a primary bladder carcinoma contained diagnostic comments related to the surface urothelium, including the presence of urothelial atypia (Figure 4, C) and a possible papillary lesion (Figure 4, D). Each of these 2 latter cases was ultimately benign and were either marked reactive atypia or a tangential section.
Analysis of an Immunohistochemical Panel for CK7, WT1, UPII, p63, GATA3, and PAX8 in the Differential Diagnosis
We next applied a panel of immunohistochemical stains to 17 cases in which blocks were still available (Table 3). We selected CK7, WT1, UPII, p63, GATA3, and PAX8, which would allow for a likely distinction between urothelial carcinoma and serous carcinoma when combined. Individually, CK7, p63, GATA3, WT1, and PAX8 have been reported in each of these entities. UPII has recently been described and has not yet been applied in this setting, to our knowledge. In conventional serous carcinoma with micropapillary or cribriform features, the anticipated immunostaining pattern was present, including diffuse CK7, WT1, and PAX8 immunoreactivity and negative immunostaining for UPII, p63, and GATA3 (Figure 5, A through D). However, a subset of cases showed variations in this anticipated antibody profile that could confound the diagnosis. Basaloid morphology was more likely to show patchy CK7 staining (Figure 5, E), and nested and spindled morphology could show focal GATA3 immunoreactivity (Figure 5, F). Two cases, one of classic cribriform architecture and one with nested architecture, showed expression of p63 (Figure 5, G and H). One case of serous carcinoma even showed focal, strong immunoreactivity for UPII, although findings from the other urothelial markers, which included p63 and GATA3, were negative, and the morphology was consistent with classic serous carcinoma (Figure 6, A through D). UPII has not previously been described in serous carcinoma, and this represents one of the first reports of that finding; however, most prior studies on UPII have primarily focused on its sensitivity in identifying urothelial carcinoma. (8-10) Use of this panel of immunohistochemical stains confirmed serous carcinoma as the diagnosis in all cases, despite occasional aberrant staining patterns.
Both bladder and serous carcinoma occur most frequently in patients in the sixth decade and older, although a broad age range may be seen. (11,12) Advanced-stage bladder cancer presents with transmural involvement of the bladder wall and may show regional extensions into adjacent organs, including the colon, prostate, uterus, vaginal wall, and occasionally, adnexal structures. (13-15) By contrast, serous carcinoma arising in the gynecologic tract typically shows a complex adnexal and/or uterine mass that may be associated with pelvic carcinomatosis and regional implants, including to the bladder peritoneal surface. (12,16,17) Given those unique presentations, the clinical impression derived from imaging, serum and urine analyses, and clinical examination readily distinguishes those 2 entities in most patients, which in turn, informs histopathologic diagnosis if tissue analysis is undertaken before surgical intervention. However, significant diagnostic conundrums associated with areas of clinicopathologic overlap between those entities may occasionally occur. (7,15,18,19) We identified 5 patients whose clinical presentation resulted in a differential diagnosis of bladder carcinoma. Review of those and additional cases identified a spectrum of clinical, morphologic, and immunohistochemical features that could lead to an erroneous diagnosis and improper patient treatment. We review the diagnostic pitfalls of serous carcinoma involvement of the bladder wall and discuss approaches to avoid misdiagnosis of a potential mimicker of bladder carcinoma.
Most patients with serous carcinoma involving the bladder wall will undergo excision of the peritoneal bladder wall implant(s) concurrent with surgical staging of the primary gynecologic carcinoma. The 2 situations identified as clinical confounders in this study include the presence of a large mass that involves pelvic structures and extends through the full thickness of the bladder wall, and a secondary development of a bladder mass at a time remote from the original serous carcinoma resection with clinical findings suspicious for a new bladder cancer primary. For example, low CA 125 levels, absence of a clear-cut adnexal primary carcinoma, clinical assumption of serous carcinoma remission, presence of gross hematuria, and a cystoscopically identified luminal bladder mass were all clinical findings in different patients that resulted in a heightened suspicion of a separate bladder cancer process.
Review of morphologic features associated with serous carcinoma involving the bladder wall identified additional histopathologic features that could also pose a diagnostic dilemma in the setting of bladder wall involvement by serous carcinoma. Of the 20 cases evaluated, conventional serous carcinoma features were present in most and included either micropapillary or cribriform architecture, psammomatous calcification, marked desmoplasia, and prominent nucleoli. (11,20) Micropapillary architecture, however, may also be seen in the context of urothelial carcinoma, (21) which represents the most common morphologic overlap between these 2 entities and may present a diagnostic challenge in the setting of large, transmural masses or an absence of known serous carcinoma. However, the presence of psammomatous calcification is exceedingly rare in the micropapillary variant of urothelial carcinoma and, if seen, should, therefore, increase the suspicion for a primary gynecologic carcinoma.
A subset of cases deviated from conventional serous carcinoma morphology and resulted in diagnostic challenges, especially because urothelial carcinoma can itself demonstrate a broad spectrum of morphologic findings in the context of variant histology. (22) Specifically, morphology that demonstrated nested growth patterns with or without squamouslike foci, spindled/sarcomatoid growth, basaloid morphology, and syncytial growth patterns were all potential mimickers of conventional or variant urothelial carcinoma. Rereview of those cases identified morphologic features that should warrant caution in the diagnosis, including the presence of dense desmoplasia and absence of surface involvement in most cases.
One unusual aspect of 2 cases was the ability of serous carcinoma to colonize the urothelial lining of the bladder and result in exophytic lesions that resembled high-grade papillary urothelial carcinoma, a finding that has not previously, to our knowledge, been reported in the literature. Fortunately, neither of those 2 cases affected the patients who were considered to have de novo bladder cancer at clinical evaluation. The ability of carcinomas to colonize the urothelium is not unique to this study and is known to occur in colonic adenocarcinoma and other metastatic lesions to the bladder, which can mimic both papillary and flat, high-grade urothelial lesions. Cytologic evaluation can also lead to confusion regarding the presence of an in situ bladder lesion; for example, in their study of the cytology of metastatic lesions in the bladder, Edgerton et al (6) found that 1 of 3 adenocarcinoma diagnoses (33%) in a series of 4677 urine specimens from female patients originated from the ovary, rather than the bladder. In instances in which a known prior history of serous carcinoma has been reported, however, the presence of putative, in situ lesion should still be viewed with caution and not be considered "diagnostic" of a new urothelial carcinoma.
Given the potential for serous carcinoma to morphologically mimic urothelial carcinoma, we tested a directed panel of antibodies to determine their utility in distinguishing serous and urothelial carcinoma. We selected CK7, WT1, UPII, p63, GATA3, and PAX8 because they are readily available in most laboratories and could be used to address the differential diagnosis. We opted not to use p53 immunohistochemical stain because it has been reported to be immunoreactive in both serous and urothelial carcinoma. Use of this panel could correctly identify the diagnosis in all cases we evaluated, despite occasional outliers. Conventional serous carcinoma most commonly showed diffuse CK7, WT1, and PAX8 expression and absence of p63 and GATA3. CK7 immunoreactivity was present in all carcinomas evaluated, although a subset of cases showed patchy CK7 immunostaining, especially in more basaloid phenotypes. No case was CK7 immunonegative. WT1 and PAX8 immunoreactivity rates were in line with a prior study that evaluated immunohistochemical markers in micropapillary carcinomas of unknown origin, with WT1 positivity in 91% of cases and PAX8 positivity in 100% of cases reported in ovarian carcinomas. (23) In our analysis, all ovarian serous carcinomas showed immunoreactivity for both WT1 and PAX8, although some cases showed more focal and/or weak staining. WT1, for example, has been proposed to be reduced in serous carcinomas after administration of chemotherapy, (24) although most other studies show equivalent expression of WT1 and other immunohistochemical markers before and after chemotherapy in serous carcinoma specimens. (25,26) Least useful was PAX8, which showed the greatest variability in staining patterns and which has also been reported in both urothelial and serous carcinomas. (27,28)
Most serous carcinomas interrogated in this study were immunonegative for p63 and GATA3, which represent 2 major immunohistochemical markers expressed in many urothelial carcinomas. In reported series, p63 is expressed in up to 83% of primary urothelial carcinomas and is frequently negative in many serous carcinomas. (29) However, mixed data regarding p63 status in serous carcinoma has been reported. Whereas some studies have shown that p63 expression may occur in malignant serous carcinomas of the ovary, (30) other studies have suggested that p63 immunoreactivity may actually decrease with malignant progression in serous lesions. (31) In our analysis, only 2 of 17 immunostained cases (12%) of serous carcinoma demonstrated focal p63 expression--one nonproblematic case associated with conventional serous morphology and diffuse WT1 expression, and one more-challenging case that demonstrated nests of carcinoma cells reminiscent of urothelial carcinoma. This latter case also demonstrated diffuse WT1 expression and absence of UPII.
GATA3 expression has been reported in up to 78% of urothelial carcinomas, (32) including the micropapillary variant of urothelial carcinoma (33) but is typically negative in primary ovarian carcinoma. (34) We identified 2 of 17 serous carcinomas (12%) involving the bladder wall that showed focal, weak immunoreactivity for GATA3, including one case of spindled/sarcomatoid morphology and one case containing nests of carcinoma cells. Both cases were diffusely positive for WT1.
Finally, 1 of 17 immunostained cases (6%) of serous carcinoma showed focal, strong immunoreactivity for UPII, which has not previously been reported, to our knowledge. This case showed UPII expression specifically in regions that resembled conventional serous carcinoma, including features such as micropapillary architecture, desmoplasia, and psammomatous calcifications. Additional studies that further expand the number of cases analyzed in serous carcinoma may be useful to determine the frequency of UPII immunoreactivity in this setting.
In summary, we identified a set of diagnostically challenging cases of serous carcinoma of the gynecologic tract involving the bladder. Whereas many clinical scenarios may not pose a diagnostic dilemma, cases occurring after presumed remission of the primary serous carcinoma or clinical findings suspicious for a bladder cancer may confound the differential diagnosis. A subset of serous carcinomas involving the bladder wall may also demonstrate histologic features not classic for serous carcinoma, including morphologic overlap with urothelial carcinoma variants and surface colonization of the urothelium. Awareness of the prior clinical history and a high index of suspicion for secondary involvement of the bladder by serous carcinoma will help direct additional workup to confirm the diagnosis, including immunohistochemical stains for CK7, WT1, UPII, PAX8, p63, and GATA3.
(1.) Ramalingam P. Morphologic, immunophenotypic, and molecular features of epithelial ovarian cancer. Oncology (Williston Park). 2016;30(2):166-176.
(2.) Al-Agha OM, Blake Gilks C. High-grade serous carcinoma involving fallopian tube, ovary and peritoneum. Surg Pathol Clin. 2011;4(1):375-396.
(3.) Iyer RB, Balachandran A, Devine CE. PET/CTand cross sectional imaging of gynecologic malignancy. Cancer Imaging. 2007;7(spec A):S130-138.
(4.) Micco M, Sala E, Lakhman Y, Hricak H, Vargas HA. Role of imaging in the pretreatment evaluation of common gynecological cancers. Womens Health (Lond). 2014;10(3):299-321.
(5.) Saida T, Tanaka YO, Matsumoto K, Satoh T, Yoshikawa H, Minami M. Revised FIGO staging system for cancer of the ovary, fallopian tube, and peritoneum: important implications for radiologists. Jpn J Radiol. 2016;34(2): 117-124.
(6.) Edgerton ME, Hoda RS, Gupta PK. Cytologic diagnosis of metastatic ovarian adenocarcinoma in the urinary bladder: a case report and review of the literature. Diagn Cytopathol. 1999;20(3):156-159.
(7.) Young RH, Scully RE. Urothelial and ovarian carcinomas of identical cell types: problems in interpretation: a report of three cases and review of the literature. Int J Gynecol Pathol. 1988;7(3):197-211.
(8.) Leivo MZ, Elson PJ, Tacha DE, Delahunt B, Hansel DE. A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma. Pathology. 2016;48(6):543-549.
(9.) Hoang LL, Tacha DE, Qi W, et al. A newly developed uroplakin II antibody with increased sensitivity in urothelial carcinoma of the bladder. Arch Pathol Lab Med. 2014;138(7):943-949.
(10.) Hoang LL, Tacha D, Bremer RE, Haas TS, Cheng L. Uroplakin II (UPII), GATA3, and p40 are highly sensitive markers for the differential diagnosis of invasive urothelial carcinoma. Appl Immunohistochem Mol Morphol. 2015; 23(10):711-716.
(11.) Kurman RJ, Carcangiu ML, Herrington CS, Young RH, eds. WHO Classification of Tumours of Female Reproductive Organs. 4th ed. Lyon, France: IARC Press; 2014. World Health Organization Classification of Tumours; vol 6.
(12.) Kurman RJ. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma. Ann Oncol. 2013;24(suppl 10):x16-21.
(13.) Andriole GL, Garnick MB, Richie JP. Unusual behavior of low-grade, lowstage transitional cell carcinoma of bladder. Urology. 1985;25(5):524-526.
(14.) Kardar AH, Lindstedt EM, Tulbah AM, Bazarbashi SN, al Suhaibani HS. Metastatic transitional cell carcinoma of the ovary from superficial bladder tumour. Scand J Urol Nephrol. 1998;32(1):73-76.
(15.) Lee M, Jung YW, Kim SW, Kim SH, Kim YT. Metastasis to the ovaries from transitional cell carcinoma of the bladder and renal pelvis: a report of two cases. J Gynecol Oncol. 2010;21(1):59-61.
(16.) Bennett JA, Oliva E. Pathology of the adnexal mass. Clin Obstet Gynecol. 2015;58(1):3-27.
(17.) Shih Ie M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164(5):15111518.
(18.) Kadiri H, Jahid A, Zouaidia F, et al. Transitional cell carcinomas in the bladder and ovary: unusual primary association or metastatic lesions? Taiwan J Obstet Gynecol. 2010;49(3):373-376.
(19.) Raspollini MR, Paglierani M, Taddei GL. Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature. Appl Immunohistochem Mol Morphol. 2009;17(2): 178-183.
(20.) Soslow RA. Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol. 2008;27(2):161-174.
(21.) Amin MB, Ro JY, el-Sharkawy T, et al. Micropapillary variant of transitional cell carcinoma of the urinary bladder. Histologic pattern resembling ovarian papillary serous carcinoma. Am J Surg Pathol. 1994;18(12):1224-1232.
(22.) Paner GP, Annaiah C, Gulmann C, et al. Immunohistochemical evaluation of novel and traditional markers associated with urothelial differentiation in a spectrum of variants of urothelial carcinoma of the urinary bladder. Hum Pathol. 2014;45(7):1473-1482.
(23.) Lotan TL, Ye H, Melamed J, Wu XR, Shih Ie M, Epstein JI. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am J Surg Pathol. 2009;33(7):1037-1041.
(24.) Chew I, Soslow RA, Park KJ. Morphologic changes in ovarian carcinoma after neoadjuvant chemotherapy: report of a case showing extensive clear cell changes mimicking clear cell carcinoma. Int J Gynecol Pathol. 2009;28(5):442446.
(25.) Miller K, Price JH, Dobbs SP, McClelland RH, Kennedy K, McCluggage WG. An immunohistochemical and morphological analysis of post-chemotherapy ovarian carcinoma. J Clin Pathol. 2008;61(5):652-657.
(26.) Wang Y, Wang Y, Zheng W. Cytologic changes of ovarian epithelial cancer induced by neoadjuvant chemotherapy. Int J Clin Exp Pathol. 2013;6(10):21212128.
(27.) Laury AR, Perets R, Piao H, et al. A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol. 2011;35(6):816-826.
(28.) Tacha D, Zhou D, Cheng L. Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol. 2011;19(4):293-299.
(29.) Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI. Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma. Am J Surg Pathol. 2007;31(8):1246-1255.
(30.) Cai Y, Zhai JJ, Feng BB, Duan XZ, He XJ. Expression of glucose transporter protein 1 and p63 in serous ovarian tumor. J Obstet Gynaecol Res. 2014;40(7): 1925-1930.
(31.) Poli Neto OB, Candido Dos Reis FJ, Zambelli Ramalho LN, Nogueira AA, de Andrade JM. p63 expression in epithelial ovarian tumors. Int J Gynecol Cancer. 2006;16(1):152-155.
(32.) Clark BZ, Beriwal S, Dabbs DJ, Bhargava R. Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract, and other cytokeratin 7positive carcinomas. Am J Clin Pathol. 2014;142(1):64-71.
(33.) Liang Y, Heitzman J, Kamat AM, Dinney CP, Czerniak B, Guo CC. Differential expression of GATA-3 in urothelial carcinoma variants. Hum Pathol. 2014;45(7):1466-1472.
(34.) Espinosa I, Gallardo A, D'Angelo E, Mozos A, Lerma E, Prat J. Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and GATA3 for distinguishing independent primary tumors from metastases. Int J Gynecol Pathol. 2015;34(3):257-265.
Leili Mirsadraei, MD; Alexey Hodkoff, MD; Karra Jones, MD, PhD; Ahmed Shabaik, MD; A. Karim Kader, MD; Cheryl C. Saenz, MD; Rodolfo Montironi, MD; David E. Tacha, PhD; Oluwole Fadare, MD; Donna E. Hansel, MD, PhD
Accepted for publication April 21, 2017.
Published as an Early Online Release August 10, 2017.
From the Departments of Pathology (Drs Mirsadraei, Hodkoff, Jones, Shabaik, Fadare, and Hansel), Urology (Drs Kader and Hansel), and Reproductive Medicine (Dr Saenz), University of California, San Diego; the Department of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region, Ancona, Italy (Dr Montironi); and the Department of Research and Development, Biocare Medical, Concord, California (Dr Tacha).
Dr Tacha is an employee, minor shareholder, and chief scientific officer of Biocare Medical. The other authors have no relevant financial interest in the products or companies described in this article.
Presented as a poster at the 31st Annual Meeting of the International Academy of Pathology and the 28th Annual Congress of the European Society of Pathology; September 29, 201 6; Cologne, Germany.
Reprints: Donna E. Hansel, MD, PhD, Department of Pathology, University of California, San Diego, 9500 Gilman Dr, MC 0612, La Jolla, CA 92093 (email: firstname.lastname@example.org).
Caption: Figure 1. For most patients with serous carcinoma involving the bladder wall, the tumor shows classic features of serous carcinoma on hematoxylineosin including micropapillary architecture (A), psammomatous calcification and background desmoplasia (B), cribriform growth and high nuclear grade (C), and prominent nucleoli (D) (original magnifications 3200 [A through C] and X400 [D]).
Caption: Figure 2. A subset of cases showed less-common features of serous carcinoma on hematoxylin-eosin, such as basaloid (A and B) and epithelioid morphology (C and D). E and F, One case showed syncytial growth of cancer cells and dense neutrophilic infiltrate (original magnifications X100 [A, C, and E] and X400 [B, D, and F]).
Caption: Figure 3. Several potential mimickers of urothelial carcinoma were identified with hematoxylin-eosin stain. A and B, Several cases showed small- to medium-sized nests of infiltrating carcinoma with only mild nuclear atypia. C and D, Another subset of cases showed sheetlike growth with exceptionally bland nuclear features. E and F, Sarcomatoid growth was present in 2 cases (original magnifications X100 [A, C, and E] and X400 [B, D, and F]) .
Caption: Figure 4. Mimickers of in situ urothelial carcinoma with hematoxylin-eosin stain. A and B, Two cases with in situ colonization of the urothelium by serous carcinoma resembled papillary neoplasms. Two additional cases were initially considered to have atypical urothelium at original case sign out but which were, instead, consistent with reactive atypia (C) and tangential sectioning mimicking a papillary neoplasm (D) (original magnifications X200 [A, B, and D] and X400 [C]).
Caption: Figure 5. Immunohistochemical staining patterns in cases with classic serous carcinoma morphology (top panel) or variant morphology (bottom panel). Classic serous carcinoma (A) showed diffuse CK7 (B) and WT1 (C) immunostaining patterns, immunoreactivity for PAX8 (D), and frequently an absence of GATA3 and p63. In contrast, a subset of cases with variant morphology (eg, basaloid, nested, sarcomatoid) showed focal staining of GATA3 and p63. E, Basaloid carcinoma with patchy CK7 stain. F, Carcinoma with small nests and bland nuclear features showing focal GATA3 immunoreactivity. G and H, p63 immunoreactivity in invasive nests and peritoneal surface serous carcinoma (hematoxylin- eosin, original magnification X100 [A]; original magnifications X100 [B] and X200 [E]; original magnification X100 [C]; original magnification X100 [D]; original magnification X200 [F]; original magnifications X200 [G] and X400 [H]).
Caption: Figure 6. Uroplakin II (UPII) immunostaining. A and B, The UPII findings were negative in all cases, with the exception of one case of classic serous carcinoma with micropapillary features. C and D, That case was negative for GAT A3 [C] and p63 [D] (original magnification X200 [A and B]; original magnification X200 [C]; original magnification X200 [D]).
Table 1. Patient Demographics and Clinical History at Time of Bladder Involvement, n = 20 Clinical Feature Findings Age, y Mean (median) 62.8 (64) Range 44-80 Presenting symptoms at time of bladder lesion Gross hematuria, No. (%) 2 (10) Uterine enlargement and/or dysmenorrhea, 2 (10) No. (%) Abdominal fullness, early satiety, No. (%) 7 (35) Abdominal/pelvic pain, No. (%) 3 (15) Incidental, No. (%) 3 (15) Unknown, No. (%) 3 (15) Known precedent/concurrent uterine or ovarian primary Yes, No. (%) 15 (75) No, No. (%) 5 (25) Precedent chemotherapy Yes, No. (%) 4 (20) No, No. (%) 16 (80) CA 125 U/mL serum levels Mean (median) 1086 (265) Range 18-7029 Imaging Bladder predominant mass, No. (%) 2 (10) Uterus or adnexa predominant mass, 3 (15) No. (%) Large, diffuse pelvic mass, No. (%) 12 (60) Unknown, No. (%) 3 (15) Urine cytology Not performed, No. (%) 15 (75) Negative, No. (%) 3 (15) Atypical, No. (%) 1 (5) Positive for malignant cells, No. (%) 1 (5) Papanicolaou test Not performed, No. (%) 7 (35) Negative, No. (%) 11 (55) Adenocarcinoma, No. (%) 2 (10) Table 2. Pathologic Findings Associated With Bladder Involvement by Serous Carcinoma, n = 20 Histopathologic Feature Findings Bladder specimen Biopsy, No. (%) 14 (70) Partial cystectomy, transurethral resection, 3 (15) No. (%) Pelvic exenteration, No. (%) 3 (15) Extent of bladder wall involvement Peritoneal surface only, No. (%) 13 (65) Full thickness (muscularis propria and 7 (35) lamina propria), No. (%) Morphology of bladder lesion Micropapillary and cribriform (classic 10 (50) serous), No. (%) Solid with basaloid features, No. (%) 3 (15) Squamous-like features, No. (%) 2 (10) Bland nests, No. (%) 2 (10) Spindled/sarcomatoid, No. (%) 2 (10) Syncytial growth with inflammation, 1 (5) No. (%) Psammoma bodies Yes, No. (%) 9 (45) No, No. (%) 11 (55) Marked desmoplasia Yes, No. (%) 16 (80) No, No. (%) 4 (20) Prominent nucleoli Yes, No. (%) 17 (85) No, No. (%) 3 (15) Surface colonization Yes, No. (%) 2 (10) No, No. (%) 18 (90) Known or presumed primary site of serous carcinoma Tubo-ovarian, No. (%) 17 (85) Uterus, No. (%) 3 (15) Serous carcinoma grade Low grade, No. (%) 2 (10) High grade, No. (%) 18 (90) Table 3. Immunohistochemical Characterization of Serous Carcinoma Within the Bladder Case No. Histology CK7 WT-1 UPII p63 GATA3 PAX8 1 Micropapillary D, S F, W Neg Neg Neg D, S 2 Micropapillary D, S F, S F, S Neg Neg D, S 3 Micropapillary D, S D, S Neg Neg Neg F, S 4 Micropapillary D, S D, S Neg Neg Neg F, S 5 Basaloid F, S D, S Neg Neg Neg F, W 6 Micropapillary D, S D, S Neg Neg Neg D, S 7 Cribriform D, S D, S Neg F, S Neg F, W 8 Cribriform D, S D, S Neg Neg Neg D, S 9 Nests D, S D, S Neg Neg Neg F, S 10 Cribriform D, S D, S Neg Neg Neg D, S 11 Basaloid D, S D, S Neg Neg Neg F, S 12 Micropapillary D, S F, S Neg Neg Neg F, S 13 Basaloid F, S D, S Neg Neg Neg D, S 14 Nests F, S D, S Neg F, W F, W F, S 15 Spindled D, S D, S Neg Neg F, W F, S 16 Micropapillary D, S D, S Neg Neg Neg D, S 17 Micropapillary D, S D, S Neg Neg Neg D, S Abbreviations: D, diffuse; F, focal; Neg, negative; S, strong ([2.sup.+]-[3.sup.+] staining); W, weak ([1.sup.+] staining).
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|Title Annotation:||Original Articles|
|Author:||Mirsadraei, Leili; Hodkoff, Alexey; Jones, Karra; Shabaik, Ahmed; Kader, A. Karim; Saenz, Cheryl C.;|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Feb 1, 2018|
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