Selection of Representative Histologic Slides in Interobserver Reproducibility Studies: Insights from Expert Review for Ovarian Carcinoma Subtype Classification.

Background: Observer studies in pathology often utilize a limited number of representative slides per case, selected and reported in a nonstandardized manner. Reference diagnoses are commonly assumed to be generalizable to all slides of a case. We examined these issues in the context of pathologist concordance for histologic subtype classification of ovarian carcinomas (OCs).

Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging.

Context.—: Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined.

Objective.

Clinical Decision Support for Ovarian Carcinoma Subtype Classification: A Pilot Observer Study With Pathology Trainees.

Context.—: Clinical decision support (CDS) systems could assist less experienced pathologists with certain diagnostic tasks for which subspecialty training or extensive experience is typically needed. The effect of decision support on pathologist performance for such diagnostic tasks has not been examined.

High-grade Pelvic Serous Carcinoma Within the Fallopian Tube Lumen: Real or Artifact?

Tumor cells are occasionally observed in the lumen in histologic sections of the fallopian tube from women with gynecologic cancer. There is some evidence that this finding may be important in endometrial cancer, but its significance is unknown in women with extrauterine pelvic serous carcinomas (tubo-ovarian high-grade serous carcinoma). Fallopian tube sections from 213 women with extrauterine pelvic serous carcinoma were reviewed, and luminal tumor cells were correlated with clinical and pathologic features.

Lymphatic Invasion in the Fallopian Tube is a Late Event in the Progression of Pelvic Serous Carcinoma and Correlates With Distant Metastasis.

The majority of extrauterine high-grade serous carcinomas are believed to arise in the fallopian tube as serous tubal intraepithelial carcinomas. The primary mode of metastasis is intraperitoneal, and patients usually present with peritoneal carcinomatosis. Although the tubes have a rich lymphatic network, tubal lymphatic invasion is observed in only a minority of cases.

Intratumoral Heterogeneity Accounts for Apparent Progression of Noninvasive Serous Tumors to Invasive Low-grade Serous Carcinoma: A Study of 30 Low-grade Serous Tumors of the Ovary in 18 Patients With Peritoneal Carcinomatosis.

Noninvasive ovarian low-grade serous tumors [atypical proliferative serous tumor (APST)/serous borderline tumor] appear to progress to invasive low-grade serous carcinoma (LGSC) at a low but regular rate. The underlying biology of this phenomenon is unknown. We studied 18 patients with 30 ovarian tumors (12 bilateral), including APST, noninvasive LGSC and invasive LGSC, who also had low-grade serous carcinomatosis.

Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma.

Background: Ovarian carcinoma is highly dependent on the ubiquitin proteasome system (UPS), but its clinical response to treatment with the proteasome inhibitor bortezomib has been disappointing. This has driven exploration of alternate approaches to target the UPS in ovarian cancer. Recently, proteasome inhibitors targeting the 19S regulatory particle-associated RPN13 protein have been described, such as RA190.

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium.

Non-Neoplastic Conditions of the Ovaries in Grossly Normal Adnexa: A Clinicopathologic Study of 403 Completely Embedded Cases.

Most non-neoplastic lesions of the ovaries have not been comprehensively examined in the contemporary literature. We evaluated completely embedded ovaries from 403 unselected, consecutive patients who had grossly normal adnexa. These included prophylactic specimens in high-risk women with BRCA mutations (38 women) and women with a personal history of breast cancer or a family history of breast and/or ovarian cancer (79 women).

Incidental Serous Tubal Intraepithelial Carcinoma and Non-Neoplastic Conditions of the Fallopian Tubes in Grossly Normal Adnexa: A Clinicopathologic Study of 388 Completely Embedded Cases.

Serous tubal intraepithelial carcinoma (STIC), the putative precursor of the majority of extrauterine high-grade serous carcinomas, has been reported in both high-risk women (those with a germline BRCA mutation, a personal history of breast carcinoma, and/or family history of breast or ovarian carcinoma) and average risk women from the general population. We reviewed grossly normal adnexal specimens from 388 consecutive, unselected women undergoing surgery, including those with germline BRCA mutation (37 patients), personal history of breast cancer or family history of breast/ovarian cancer (74 patients), endometrial cancer (175 patients), and a variety of other conditions (102 patients). Among 111 high-risk cases and 277 non-high-risk cases, 3 STICs were identified (0.

Pseudoxanthomatous salpingitis as an ex vivo model of fallopian tube serous carcinogenesis: a clinicopathologic study of 49 cases.

Iron is a well-documented carcinogen based on both animal models and observational studies in humans. There are limited published data on pseudoxanthomatous salpingitis, an uncommon condition characterized by the accumulation of histiocytes containing iron and iron-related compounds-lipofuscin and hemosiderin-in the lamina propria of the fallopian tube. The clinical and pathologic features of 49 consecutive cases were evaluated.

Serous tubal intraepithelial carcinoma localizes to the tubal-peritoneal junction: a pivotal clue to the site of origin of extrauterine high-grade serous carcinoma (ovarian cancer).

Recent data suggest that intraepithelial carcinoma of the fallopian tube [serous tubal intraepithelial carcinoma (STIC)] is the precursor of high-grade extrauterine serous carcinoma. A more specific location for the origin of this lesion is suggested by the recently described junction between the fallopian tubal epithelium and the peritoneum [tubal-peritoneal junction (TPJ)]. Fallopian tubes from 202 patients with advanced-stage high-grade extrauterine serous carcinoma or carcinosarcoma were evaluated histologically as were 124 prophylactic salpingo-oophorectomy specimens.

Distribution and case-fatality ratios by cell-type for ovarian carcinomas: a 22-year series of 562 patients with uniform current histological classification.

Background: Ovarian carcinoma is comprised of several different cell types reflecting different clinicopathologic features. Pathologic criteria for distinguishing cell types have evolved, and therefore non-contemporary literature on ovarian cancer may have limited current relevance. A new dualistic model of pathogenesis that distinguishes type I (endometrioid, mucinous, clear cell and low grade serous carcinomas) from type II (high grade serous carcinomas and carcinosarcomas) tumors has become widely accepted.

Ovarian Brenner tumour: a morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium.

Background: Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium.

Aim And Methods: We hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal junction which, when embedded in the ovary as Walthard cell nests, may progress to BTs. The aim of this study was to validate this hypothesis by a morphologic and immunohistochemical (IHC) analysis.

The presence of mucosal iron in the fallopian tube supports the "incessant menstruation hypothesis" for ovarian carcinoma.

The incessant ovulation hypothesis for the etiology of ovarian carcinoma has been accepted for decades, but recent evidence strongly implicates the fallopian tube mucosa as the source of most high-grade "ovarian serous carcinomas." Menstrual reflux through the tubes, a normal phenomenon, is a putative source of tubal mucosal exposure to carcinogens. We searched for histologic evidence of deposition of iron, a well-recognized carcinogen, in the fallopian tubes in 196 women with advanced-stage high-grade pelvic serous carcinomas in comparison with 370 controls.

The pathogenesis of atypical proliferative Brenner tumor: an immunohistochemical and molecular genetic analysis.

Brenner tumors are ovarian tumors, usually benign, containing epithelium that resembles transitional epithelium. As with other epithelial tumors there exist frankly malignant tumors and tumors that display greater proliferation than the benign Brenner tumors but lack destructive infiltrative growth, and these have been designated 'atypical proliferative' (borderline) Brenner tumors. There have been no well-documented cases of atypical proliferative Brenner tumors that have exhibited malignant behavior.

Transitional cell carcinoma of the ovary is related to high-grade serous carcinoma and is distinct from malignant brenner tumor.

Transitional cell tumors of the ovary include benign, borderline (atypically proliferating), and malignant Brenner tumors (BT), as well as transitional cell carcinoma (TCC). Some TCCs could conceivably be examples of malignant BT where the benign component has been overgrown. Our objectives were: (A) compare the immunophenotypes of BT and TCC and (B) examine a large cohort of ovarian carcinomas for cases with the immunophenotype of BT and transitional features but lacking a benign BT component.

Validation of an algorithm for the diagnosis of serous tubal intraepithelial carcinoma.

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose.

Survival rates for international federation of gynecology and obstetrics stage III ovarian carcinoma by cell type: a study of 262 unselected patients with uniform pathologic review.

Objective: Published data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate.

Methods: An unselected series of 262 International Federation of Gynecology and Obstetrics stage III ovarian carcinomas was studied.

"Primary peritoneal" high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer.

Objective: Primary peritoneal high-grade serous carcinoma is thought to arise from the peritoneum, but recent data suggest that the fallopian tube may be an occult source of many of these tumors. This study was performed to evaluate this hypothesis in an unselected series of cases.

Methods: Fallopian tubes from 51 consecutive cases meeting the GOG criteria for primary peritoneal high-grade serous carcinoma, FIGO stages II-IV, were analyzed.

The fallopian tube-peritoneal junction: a potential site of carcinogenesis.

Junctions between different types of epithelia are hot spots for carcinogenesis, but the junction of the peritoneal mesothelium with the fallopian tubal epithelium, the tubal-peritoneal junction, has not been characterized earlier. A total of 613 junctional foci in 228 fallopian tube specimens from 182 patients who underwent surgery for a variety of indications, including 27 risk-reducing salpingo-oophorectomy specimens, were studied. Edema, congestion, and dilated lymphatic channels were commonly present.

Mucinous metaplasia of the fallopian tube: a diagnostic pitfall mimicking metastasis.

Interpretation of the mucinous change in the fallopian tubes has been difficult because several reports consider this mucinous change as a metastasis from a mucinous tumor. To clarify this issue, we decided to retrospectively review salpingectomies from 3 institutions looking for mucinous change in the fallopian tubes and documented the clinical history of these patients. Twenty-three cases of fallopian tubes with mucinous changes were found, including 11 patients without evidence of malignancy, 4 patients with mucinous ovarian tumors, 5 patients with nonmucinous gynecologic tumors, 2 patients with mucinous appendiceal neoplasm, and 1 patient with colon carcinoma.

Upstaging pathologic stage I ovarian carcinoma based on dense adhesions is not warranted: a clinicopathologic study of 84 patients originally classified as FIGO stage II.

Background: FIGO stage II ovarian cancer comprises 8% of ovarian cancers. It is a common but not universal practice to upstage densely adherent pathologic stage I tumors to stage II. FIGO guidelines are not clear, and data supporting this practice are sparse.

The relationship between papillary infarction and microinvasion in ovarian atypical proliferative ("borderline") serous and seromucinous tumors.

Papillary infarction is commonly observed in ovarian atypical proliferative serous and seromucinous tumors (APST/APSMT), but there are no published data on its significance. This study characterizes the features associated with papillary infarcts and microinvasion to further understand these phenomena. From consecutive hospital-based cases, 32 APST/APSMT in 26 patients (6 bilateral) were reviewed and evaluated for papillary infarcts, microinvasion (<5 mm), and other histologic features.

Differences in tumor type in low-stage versus high-stage ovarian carcinomas.

Although there are recognized differences in the type of ovarian carcinomas between those tumors diagnosed at low versus high stage, there is a lack of data on stage distribution of ovarian carcinomas diagnosed according to the current histopathologic criteria from large population-based cohorts. We reviewed full slide sets of 1009 cases of 2555 patients diagnosed with ovarian carcinoma that were referred to the British Columbia Cancer Agency over a 16-year period (1984 to 2000). On the basis of the reviewed cases we extrapolated the distribution of tumor type in low-stage (I/II) and high-stage (III/IV) tumors.