Robert J Kurman

Johns Hopkins Medicine | JHUSOM · Department of Pathology

Background and objectives: The 9-valent human papillomavirus (9vHPV) vaccine Phase III immunogenicity study in 9- to 15-year-old boys and girls was extended to assess immunogenicity and effectiveness through 10 years after the last vaccine dose (NCT00943722). Methods: Boys (n = 301) and girls (n = 971) who received three 9vHPV vaccine doses in t...

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow‐up. Through the nationwide Pathology Registry, we identified nearly 500...

Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11,...

Population‐based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow‐up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 w...

The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed. Immunohistochemistr...

Although risk factors have been established for the development of serous carcinoma after a diagnosis of serous borderline tumor (SBT), comprising atypical proliferative serous tumor (APST) (ie, conventional SBT) and noninvasive low-grade serous carcinoma (niLGSC) (ie, micropapillary SBT), subsequent invasive carcinoma still occurs in a subset of w...

Objective: Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured f...

Women receive hormone preparations for a variety of reasons, including birth control and treatment for abnormal uterine bleeding, perimenopausal and postmenopausal symptoms, endometriosis, endometrial hyperplasia, endometrioid carcinoma, breast carcinoma, and certain types of infertility. Usually the exogenous hormone is some form of progestin, but...

Endometrial carcinoma is the 4th most common cancer for American women and the most common malignant tumor of the female genital tract. In the United States in 2015, there were 54,644 new cases and 10,096 deaths resulting from this neoplasm. Black women have a much higher rate of mortality when compared to white women. Although most endometrial car...

Most endometrial polyps appear to originate from localized overgrowth of the basalis with glands and stroma participating in the lesion. The pathogenesis of polyps has not been firmly established although molecular mechanisms have been invoked in several studies, and it is suggested that polyps originate as a monoclonal stromal overgrowth with seco...

The World Health Organization (WHO) classification of gestational trophoblastic disease (GTD) includes disorders of placental development (hydatidiform mole) and neoplasms of the trophoblast (choriocarcinoma, placental site trophoblastic tumor [PSTT], and epithelioid trophoblastic tumor [ETT]). Nonneoplastic lesions include the exaggerated placenta...

The clinical decision to perform endometrial sampling is dependent on medical history, physical examination, laboratory data, imaging studies, and patient age. Abnormal uterine bleeding (AUB) may be secondary to structural lesions including polyps, adenomyosis, leiomyoma, or malignancy and hyperplasia or nonstructural lesions including coagulopathi...

The histologic features of what constitutes “normal” endometrium change with a woman’s age, through the premenarchal, reproductive, perimenopausal, and postmenopausal years. Throughout the reproductive years, the cyclical hormonal changes of the menstrual cycle provide a continuously changing morphologic spectrum from proliferative to secretory to...

It has been well recognized since the 1970s that unopposed estrogenic stimulation leads to endometrial hyperplasia, which in turn has the potential to progress to the usual type of endometrial carcinoma, termed “endometrioid carcinoma.” More recently, another lesion designated “endometrial intraepithelial carcinoma (EIC)” has been shown to precede...

Endometritis is a persistent inflammation of the endometrial mucosa often caused by pathogens ascending into the uterine cavity. Accordingly, it may accompany pelvic inflammatory disease of the upper genital tract. Common infectious agents associated with chronic endometritis are Chlamydia, Mycoplasma/Ureaplasma, Enterococcus faecalis, Escherichia...

This chapter specifically addresses uterine bleeding resulting from alterations in the normal cyclical changes of the endometrium that are not due to structural causes. It is termed “abnormal uterine bleeding” (AUB); in the past AUB was referred to as “dysfunctional uterine bleeding” (DUB) (Fritz and Speroff, Abnormal uterine bleeding. In: Clinical...

Recognition of the features of gestational endometrium, trophoblast, and villi, as well as the pathologic changes in chorionic tissues, is an important part of endometrial biopsy interpretation. The presence of intrauterine products of conception generally excludes the diagnosis of ectopic pregnancy and can help explain other pathologic states such...

Uterine tumors other than benign polyps or carcinoma are rarely encountered in endometrial biopsies and curettings. Even submucosal leiomyomas rarely are sampled by an endometrial biopsy or curettage. The classification in Table 11.1 lists most of these other neoplasms. It has been reported that prior to a hysterectomy, the diagnosis of endometrial...

The third edition of this text entails a comprehensive review of pathophysiology, including the recognition of physiologic conditions and pathologic entities, such as polyps, endometritis, gestational trophoblastic diseases, endometrial hyperplasia, and carcinoma. It also serves as an update on the use of current terminology and ancillary tools. Th...

Since the publication of the 1/e in 1977, Blaustein's Pathology of the Female Genital Tract has consolidated its position as the leading textbook of gynecological pathology. An essential reference for all pathologists and residents, this thoroughly updated Seventh Edition includes more than 1400 illustrations in color, informative tables and 22 rev...

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 L...

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 (STILs), putative precursor lesions of HGSC could inform prevention efforts. We conducted a multicenter study to identify risk/protective fac...

(Abstracted from Sci Transl Med 2018;10:eaap8793) Although the Papanicolaou (Pap) test has dramatically decreased mortality from cervical cancer in the screened population, the test generally is unable to detect endometrial or ovarian cancers. These 2 cancers are usually diagnosed at an advanced stage when the prognosis is poor and treatment does n...

Objective: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59). Methods: A post hoc analysis of prospectively diagnosed vulvar and v...

The objective of this article was to evaluate the presence of occult metastasis after comprehensive surgical staging of clear cell ovarian carcinoma (CCC) and endometrioid ovarian carcinoma (EMCA) that appeared to be confined to the ovary at time of surgery. Between 1998 to 2016, 85 patients with CCC and EMCA were identified who were comprehensivel...

We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% c...

Since the publication of the 1/e in 1977, Blaustein's Pathology of the Female Genital Tract has consolidated its position as the leading textbook of gynecological pathology. An essential reference for all pathologists and residents, this thoroughly updated Sixth Edition includes more than 1400 illustrations in color, informative tables and 22 revis...

Gestational trophoblastic disease (GTD) encompasses a heterogeneous group of lesions with specific clinical features, morphological characteristics, and pathogenesis. The World Health Organization classification of GTD includes complete and partial hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor (PSTT), epithel...

High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fal...

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center inte...

Background: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HP...

A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefo...

PURPOSE The origin of primary mucinous ovarian carcinomas is unknown. We investigated the possible relation between mucinous ovarian tumors and Brenner tumors and teratomas to identify the cell of origin, which might provide clues for future therapies. EXPERIMENTAL PROCEDURES In total, 104 Brenner tumor-associated mucinous tumors (BAMT) and 58 tera...

Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated "atypical proliferative serous tumor (APST)" and a small...

Objective: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. Methods: This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by...

Epithelial ovarian tumors are responsive to steroid hormone stimulation and the ovarian stroma may have a direct role in this process. We evaluated immunohistochemical markers of sex-steroid differentiation and steroidogenesis (calretinin, inhibin, steroidogenic factor 1), steroid enzymes involved in hormone biosynthesis (CYP17, CYP19, HSD17β1, AKR...

Objective: Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. Methods: We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or n...

Aberration in chromosomal structure characterizes almost all cancers and has profound biological significance in tumor development. It can be facilitated by various mechanisms including overexpression of cyclin E1 and centrosome amplification. As ovarian high-grade serous carcinoma has pronounced chromosomal instability, in this study we sought to...

Mutations identified in cyst fluids and associated tumors. DOI: http://dx.doi.org/10.7554/eLife.15175.010

Primer sequences used in multiplex assay. DOI: http://dx.doi.org/10.7554/eLife.15175.011

Patient demographics. DOI: http://dx.doi.org/10.7554/eLife.15175.009

One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). As human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the...

Since our proposal of a dualistic model of epithelial ovarian carcinogenesis more than a decade ago, a large number of molecular and histopathologic studies were published that have provided important insights into the origin and molecular pathogenesis of this disease. This has required that the original model be revised and expanded to incorporate...

The recent 2014 World Health Organization (WHO) Classification of Tumours of the Female Reproductive Organs introduced a new category of ovarian neoplasm designated “seromucinous tumours”. The recognition of this distinctive group of tumors is an important addition to the classification but the term “seromucinous” has serious flaws that obscures th...

It is believed that a subset of primary ovarian mucinous tumors is derived from mature teratomas [1-5]. To confirm this, we performed microsatellite genotyping using a variety of short tandem repeat makers and analyzed allelotypes of 8 mucinous tumors (4 mucinous carcinomas, 3 atypical proliferative mucinous tumors and 1 mucinous cystadenoma) assoc...

The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atl...

The derivation of ovarian intestinal-type mucinous tumours is not well established. Some are derived from teratomas but the origin of the majority is not clear. It has been recently proposed that the non-germ cell group may be derived from Brenner tumours as the association of a mucinous tumour with a Brenner tumour is frequently observed. In order...

Ovarian cortical inclusion cysts (CICs) have been long regarded as a possible site of origin of epithelial ovarian carcinoma. It has been proposed that they develop from invagination of ovarian surface epithelium (OSE) which then undergoes metaplasia to form mullerian-type tissue and then undergoes neoplastic transformation. Recent studies have cha...

Ovarian carcinomas are heterogeneous, comprised of five different cell types: high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. High-grade serous carcinoma causes the vast majority of ovarian cancer deaths. This classification correlates with a variety of distinctive clinical, epidemiological, molecular, and beh...

Recent studies implicating the fallopian tube as the site of putative precursors of ovarian serous carcinoma, and the hypothesis that injury, inflammation, and repair of the ovarian surface epithelium at the time of ovulation, may be contributing factors to ovarian carcinogenesis, prompted us to undertake a comprehensive analysis of the immune cell...

Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this st...

Serous borderline tumor also known as atypical proliferative serous tumor (APST) is the precursor of ovarian low-grade serous carcinoma (LGSC). In this study, we correlated the morphologic and immunohistochemical phenotypes of 71 APSTs and 18 LGSCs with the mutational status of KRAS and BRAF, the most common molecular genetic changes in these neopl...

Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular character...

Objective: To describe the study population and estimate overall survival of women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years relative to the general population. Methods: The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women diagnosed with SBTs from 1978 to 2002. The histologi...

In 1976, a series of 12 cases describing a lesion that had previously not been well characterized was reported as "trophoblastic pseudotumor of the uterus." Up until that time rare reports of the lesion had classified it most often as an unusual type of sarcoma associated with pregnancy. All patients in that series were alive and well except for on...

Since our proposal of a dualistic model of epithelial ovarian carcinogenesis more than a decade ago, a large number of molecular and histopathologic studies were published that have provided important insights into the origin and molecular pathogenesis of this disease. This has required that the original model be revised and expanded to incorporate...

Ovarian cancer is associated with a high morbidity and mortality, and is the leading cause of gynecologic cancer-related death in the US. In recent years, the molecular pathophysiology of ovarian tumors has been better elucidated, allowing for the distinction of two tumor types: the more indolent type I tumors (encompassing endometrioid, clear cell...