Serous Tubal Intraepithelial Lesions Research Articles

A Case of Hereditary Breast and Ovarian Cancer Syndrome with Serous Tubal Intraepithelial Lesions in Bilateral Fimbriae Resected by Laparoscopic Risk-reducing Salpingo-oophorectomy

A Case of Hereditary Breast and Ovarian Cancer Syndrome with Serous Tubal Intraepithelial Lesions in Bilateral Fimbriae Resected by Laparoscopic Risk-reducing Salpingo-oophorectomy

Fallopian Tube Lesions in Women at High Risk for Ovarian Cancer: A Multicenter Study.

The prognosis of women diagnosed with invasive high-grade serous ovarian carcinoma (HGSC) is poor. More information about serous tubal intraepithelial carcinoma (STIC) and serous tubal intraepithelial lesions (STIL), putative precursor lesions of HGSC, could inform prevention efforts. We conducted a multicenter study to identify risk/protective factors associated with STIC/STILs and characterize p53 signatures in the fallopian tube. The fallopian tubes and ovaries of 479 high-risk women ≥30 years of age who underwent bilateral risk-reducing salpingo-oophorectomy were reviewed for invasive cancer/STICs/STILs. Epidemiologic data was available for 400 of these women. In 105 women, extensive sampling of the tubes for STICs/STILs/p53 signatures were undertaken. Descriptive statistics were used to compare groups with and without lesions. The combined prevalence of unique tubal lesions [invasive serous cancer (n = 6) /STICs (n = 14)/STILs (n = 5)] was 6.3% and this was split equally among BRCA1 (3.0%) and BRCA2 mutation carriers (3.3%). A diagnosis of invasive cancer was associated with older age but no risk/protective factor was significantly associated with STICs/STILs. Extensive sampling identified double the number of STICs/STILs (11.9%), many p53 signatures (27.0%), and multiple lesions in 50% of the cases. Women with p53 signatures in the fimbria were older than women with signatures in the remaining tube (P = 0.03). STICs/STILs may not share the protective factors that are associated with HGSC. It is plausible that these factors are only associated with STICs that progress to HGSC. Having multiple lesions in the fimbria may be an important predictor of disease progression. Cancer Prev Res; 11(11); 697-706. ©2018 AACR.

Abstract IA16: PapGene, PapSEEK, and PapDREAming for early detection of ovarian cancer

Abstract Advances in genomic technologies are revolutionizing how we understand pathogenesis in ovarian cancer. These technologies are critical in developing innovative strategies to diagnose cancer earlier by detecting rare mutant alleles or aberrant methylation marks among a pool of normal DNA. Studies integrating these technologies provide the fundamental scientific underpinning for designing future standards of care to reduce the burden of ovarian cancer through early detection and prevention. This presentation will focus on two related topics. One is to summarize the recent research findings from the Johns Hopkins Ovarian Cancer Early Detection (JHOCD) group in deciphering the major molecular alterations involving in ovarian cancer in situ lesions (serous tubal intraepithelial carcinoma, STIC) and its precursors (including serous tubal intraepithelial lesion, STIL and so-called “p53” signatures) in fallopian tubes. The clinicopathologic and molecular studies we have done have helped define the precursor lesions in many high-grade serous carcinomas (HGSC) of the ovary, the most common and aggressive type of ovarian epithelial cancer. The other focus is to discuss the promise and challenges in applying genetic and epigenetic methods to detect ovarian HGSC. In an effort to replicate the success of cervical cancer screening, several approaches for the early detection of ovarian cancers have been proposed. JHOCD team has first reported the feasibility of using cervical cytology samples to detect ovarian carcinomas. We have extended this original study by determining whether different sample collection methods including cervical cytology specimens, uterine lavage/brush, and blood, alone or in combination with each other or serum CA-125 levels, can achieve a better sensitivity and specificity. The objective of JHOCD is to facilitate the proposed clinical studies to assess the clinical benefit in applying the aforementioned molecular diagnostics for early ovarian cancer diagnosis in high-risk women (including those carrying BRCA mutations). Citation Format: Ie-Ming Shih. PapGene, PapSEEK, and PapDREAming for early detection of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA16.

Risk reduction surgery (RRS) for tubo-ovarian cancer in an Irish gynaecological practice: an analysis of indications and outcomes.

High-grade serous carcinoma (HGSC) is the most common tubo-ovarian cancer. The fallopian tube harbours the precursor lesion: serous tubal intraepithelial carcinoma (STIC). Bilateral salpingo-oophorectomy is an effective risk-reducing surgical (RRS) strategy for breast cancer susceptibility gene mutation carriers (BRCAm). The value of RRS in those without defined genetic risk is unknown but these women represent a substantial cohort in prophylactic surgical practice. This is a retrospective review of RRS at an Irish university teaching hospital. One hundred and thirty women underwent RRS; group 1 = 46 BRCAm; group 2 = 19 BRCAm negative/65 genetic status unknown. Group 1 had one occult HGSC. Group 2 had no STIC or cancers and were older and more likely to have hysterectomy and benign pathology. Other pathologies included serous tubal intraepithelial lesions (STIL) (2), p53 signatures (2), endometriosis (6), fibroids/adenomyosis (4) and atypical endometrial hyperplasia (1). More than 60% of women undergoing RRS were BRCAm negative or untested. Counselling of high-risk women without defined germline mutations remains a challenge for gynaecologists because the likelihood of removing STIC lesions or occult invasive cancer is low. Removal of coincidental pathology may give added value to RRS in these women.

Morphologic features of fallopian tubal epithelium in pelvic high-grade serous carcinoma

Objective: To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma (HGSC), to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria. Methods: The fallopian tubes in 58 cases of pelvic HGSC (54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum) and 25 cases of pelvic non-HGSC (5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma) were collected from June 2015 to December 2016, and serially examined under light microscope (SEE-FIM protocol). Immunostaining for p53 and Ki-67 was performed to evaluate the presence of p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC) and invasive carcinoma in these fallopian tubes. Meanwhile, primary site of HGSC based on the recently proposed diagnostic criteria were also reclassified. Results: Among the study group, the frequencies of p53 signature, STIL, STIC and invasive HGSC were 27.6% (16/58), 43.1% (25/58), 36.2% (21/58) and 67.2% (39/58), respectively, while in control group, the proportions were 24.0% (6/25), 0, 0 and 8.0% (2/25), respectively. The continuum of epithelial changes in the process of serous neoplasia including p53 signature, STIL, STIC and invasive carcinoma was identified in 8 cases of pelvic HGSC. The proportions of STIL, STIC and invasive carcinomas in HGSC group were higher than that in non-HGSC group (P<0.01). About 80.0% (20/25) of STIL and 85.7% (18/21) of STIC were present unilaterally. Diagnostically, the study group contained the 17 cases of ovarian HGSC, 40 cases of tubal HGSC, and 1 case of peritoneal HGSC after reclassification of the cancer primary. Conclusions: Continuous changes of tubal epithelium including p53 signature, STIL, STIC and invasive carcinomas are identified in patients with HGSC, supporting the current understanding that the fallopian tube is likely the cellular source of the majority HGSC. STIL and STIC may be specific to pelvic HGSC and may act as a target for future research on the early detection and prevention of this disease. The newly proposed diagnostic criteria for pelvic HGSC will lead us to more accurate classification of cancer primary sites. Correct classification of HGSC may have potential impacts for cancer prevention and improve our understanding of ovarian serous carcinogenesis.

Changes in the Extracellular Matrix Are Associated With the Development of Serous Tubal Intraepithelial Carcinoma Into High-Grade Serous Carcinoma.

The identification of a marker for early progression of preinvasive lesions into invasive pelvic high-grade serous carcinoma (HGSC) may provide novel handles for innovative screening and prevention strategies. The interplay between cancer cells and the extracellular matrix (ECM) is one of the main principles in cancer development and growth, but has been largely neglected in preinvasive lesions. This is the first study addressing the involvement of the ECM in the "step-by-step" transition of normal fallopian tube epithelium into preinvasive lesions, and eventually the progression of preinvasive lesions into invasive HGSC. The expression of highly sulfated chondroitin sulfate (CS-E), a characteristic glycosaminoglycan of the cancer-associated ECM, was assessed by immunohistochemistry in a large cohort of precursor lesions of the full spectrum of HGSC development, including 97 serous tubal intraepithelial carcinomas (STICs), 27 serous tubal intraepithelial lesions, and 24 p53 signatures. In addition, the immunological reactivity in the microenvironment was evaluated. Increased stromal expression of highly sulfated CS-E was observed in 3.7%, 57.7%, and 90.6% of serous tubal intraepithelial lesions, STICs, and invasive HGSCs, respectively (P < 0.001). No or limited expression was found in p53 signatures and normal tubal epithelium (compared with STIC, P < 0.001). A gradual increase in the amount of CS-E expression between STIC and paired HGSC was demonstrated. Intense stromal CS-E expression in STIC was significantly associated with an immune infiltrate (P < 0.001). Our study showed that increased stromal CS-E expression is related to the degree of the tubal epithelium abnormality. Specific alterations in the ECM (ie, CS-E expression) occur early in pelvic HGSC development and may represent a novel biomarker of early cancer progression, useful for the identification of novel clinical strategies.

Abstract TMEM-118: ROLES OF T-LAK CELL-ORIGINATED KINASE (TOPK) AND THE MICROENVIRONMENT IN DRIVING OVARIAN CANCER PROGRESSION

Abstract Ovarian cancer (OvCa) therapy is confounded by late detection and a lack of effective therapeutics. After debulking surgery, most patients initially respond to platinum-based chemotherapeutics, however their tumors inevitably develop resistance and recur. Developing new treatments for OvCa will depend on a thorough understanding of OvCa biology. We recently identified T-LAK cell-originated kinase (TOPK), a serine-threonine kinase, as highly expressed in OvCa. A member of the cancer/testis antigen (CTA) family, TOPK is induced by mutant TP53 and is expressed in early, in situ serous tubal intraepithelial carcinoma lesions. Targeting TOPK with a small-molecule inhibitor in a mouse model of OvCa led to significant reductions in tumor burden. To better understand the interplay between TOPK and the tumor and stroma in ovarian cancer progression, we performed compartment-resolved, quantitative shotgun proteomics on microdissected tumor and stromal samples across a hypothetical progression series of ovarian cancer from in situ STIC to omental metastases. With a highly-sensitive platform, we were able to accurately quantify proteins across the progression series and confirmed expression of known tumor and stromal markers in the data set. Interestingly, we observed a conserved stromal response associated with metastasis. This signature included both genes known to play a role in cancer-associated fibroblasts, as well as proteins with no previously described roles in the tumor stroma. Many components of the signature are also representative of the previously described “mesenchymal” subgroup of ovarian cancer. In vitro and in vivo functional assays have confirmed essential roles for several of these proteins in regulating the cancer-associated fibroblast phenotype. This work establishes TOPK as a potential therapeutic target for ovarian cancer and emphasizes the importance of compartment resolved studies in understanding the individual roles of the tumor and stroma in ovarian cancer progression. Citation Format: Mark A. Eckert, Fabian Coscia, Shawn Pan, Chun-Yi Chiang, Stephanie McGregor, Ricardo Lastra, S. Diane Yamada, Matthias Mann, and Ernst Lengyel. ROLES OF T-LAK CELL-ORIGINATED KINASE (TOPK) AND THE MICROENVIRONMENT IN DRIVING OVARIAN CANCER PROGRESSION [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-118.

Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube.

There is a growing body of evidence regarding cell competition between normal and mutant mammalian cells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412 – 1.211 for p53 signature and 0.9790 (95% CI, 0.7206 – 1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations.

Serous tubal intraepithelial carcinoma lesions are common in primary peritoneal serous carcinomas

Serous tubal intraepithelial carcinoma lesions are common in primary peritoneal serous carcinomas

The morphological and immunohistochemical characteristics of changes in the fallopian tube mucosa in ovarian epithelial tumors

to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor. The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test. Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (p<0.05). There were significant differences in the incidence of STILs in patients with different histotypes of ovarian carcinomas (p<0.05). PAX2-negative SCP was detected in 75% of OSC, 60% of serous borderline tumors, and 40% of serous cystadenomas. The differences in the incidence of SCP between serous tumors of varying grade, between serous tumors and non-serous carcinomas, between OSC and non-serous carcinomas were significant (p<0.05). The investigation has shown that IHC examination should be used for the accurate diagnosis of STILs. It has also provided evidence for the pathogenetic association between STIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).

Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.

Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.

Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

Use of cervical mucus to screen for gynecological malignancies: a pilot study

High-grade malignancies are the leading cause of death from gynecological tumors. Unfortunately, no efficient screening method is available for these tumors. In this paper we report the results of a pilot study based on the frequency of TP53 mutations in these cancers. Mucus from the cervix of 32 hysterectomy specimens with no grossly visible cervical or serosal involvement were included in this study. TP53 exons 5–9 mutations were screened for mutations using single strand conformation polymorphism (SSCP). Immunostain for p53 protein was performed in all fallopian tubes and in a sample from the tumors that were identified prospectively. A total of 32 cases including 19 malignant, and 13 benign cases were included. P53 immunostain was positive in only 5 cases including 3 high grade malignant tumors and 2 precancerous lesions (serous tubal intraepithelial lesion or p53 signature) in the fallopian tubes. A TP53 mutation band pattern was detected by SSCP in 2/3 and 2/2 cases respectively. Twenty-seven cases were negative for p53 imunostain, 4 of which were positive for TP53 mutation by SSCP including 3 low-grade malignancies. The results of this study provide evidence that DNA from precursor lesions of high grade ovarian, fallopian tube and endometrial carcinomas can be detected in cervical mucus. Further studies using different markers, in preoperative setting and large scale screening studies will determine the utility of using cervical mucus to screen for gynecological malignancies.

Serous Tubal In Situ Carcinoma (STIC) in Primary Peritoneal Serous Carcinomas

Recent new data in the pathogenesis of serous pelvic cancer and the introduction of serous tubal in situ carcinoma (STIC) and its precursors have raised the question that whether all primary peritoneal cancers (PPC) are in fact of tubal origin. Therefore, the present study evaluates the frequency of STIC and its precursor lesions in cases that were diagnosed as PPC using the morphologic criteria of the most recent WHO classification. The present study evaluates immunohistochemically (Ki-67 and p53 staining) the presence of STIC and its precursor lesions (p53 signature, serous tubal intraepithelial lesion [STIL]) in the completely processed Fallopian tubes of 46 consecutive PPCs. STIC was detected in 10 patients (21.7%) and p53 signature in 9 cases (19.6%). No STIL was observed. All except 1 STIC occurred at the fimbriated end of the Fallopian tube, and a bilateral involvement was detected in 2 cases. These precursor lesions were missed during the initial routine screening. Repeated staining for p53 was negative in STIC in 2 cases. STIC and p53 signature as precursor lesions of pelvic serous cancer are detected in some but not all the cases of primary serous peritoneal cancer. There might be the 2 different carcinogenetic pathways within PPC, and further studies are required to identify the source of serous cancer in cases without an STIC lesion.

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. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The κ value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting.

N’oubliez pas les trompes ! Étude morphologique et immunohistochimique des trompes à risque génétique (mutation BRCA)

Objectives The objective of this study was to describe morphologic and immunohistochemical features of precursor tubal lesions in prophylactically removed Fallopian tubes. Patients and methods Hundred and forty-seven bilateral salpingectomies (genetic predisposition or group A: n = 57; and control group or group B: n = 90) were reviewed by two pathologists blinded to clinical data. Seven epithelial cytological and architectural features were studied to compare the degree of tubal epithelial abnormalities between the two groups. Immunohistochemical expression patterns of Ki67 and p53 were also evaluated. Results Serous tubal intraepithelial lesions (STIL) have been identified in group A with stronger expression for Ki67 and p53 (especially in BRCA 1 group) than in group B. Discussion and conclusion The current results show the importance of salpingo-oophrectomy in BRCA mutation carriers and the complete histopathological sampling of the Fallopian tubes.

Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).