Breast cancer during pregnancy of Luminal A type overexpressed CXCL13.

Pregnancy-associated breast cancer has been increasing. In this study, we analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared their genetic profiles with those of patients with breast cancer that did not occur during pregnancy, within 1 year after childbirth nor during lactation (non-PrBC). We performed gene expression analyses of patients with PrBC and non-PrBC using microarrays and qRT-PCR. Microarray analysis showed that 355 genes were upregulated in the luminal-type PrBC group compared to those in the non-PrBC group. The C-X-C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non-PrBC group, especially in the luminal A-type (p = 0.016). This result was corroborated by the qRT-PCR analysis of microdissected cancer cells (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A-type breast carcinoma (p < 0.001). Our results provide clues for a better understanding of breast cancer pathogenesis during pregnancy.

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

BACKGROUND: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. METHODS: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. RESULTS: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. CONCLUSION: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. TRIAL REGISTRATION: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Clinical features and survival of pregnancy-associated breast cancer: a retrospective study of 203 cases in China.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is an aggressive disease, and since Chinese authority began to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. METHODS: Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled. Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. RESULTS: Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it's 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P < 0.001) as follows: in the PABC patients, Luminal B 38.4%, Triple negative breast cancer (TNBC) 30.1%, Human Epidermal Growth Factor Receptor 2 (HER-2) overexpression 15.8%, and Luminal A 10.8%; in the non-PABC patients, Luminal A 50.9%, Luminal B 20.1%, TNBC 17.4%, and HER-2 overexpression 8.0%. The 3-year disease free survival (DFS) of all PABC patients was 80.3%. The 3-year DFS of the patients in the first-pregnancy group was 78.4%, and that of the patients in the non-first-pregnancy group was 83.7% (P = 0.325). CONCLUSIONS: Our study proved that the proportion of women who developed PABC during the second or third pregnancy was extremely high relative to the newborn populations. The patients in the PABC population tended to present more luminal B and TNBC breast cancer than the non-PABC patients.

Pregnancy-induced Cushing's syndrome with an adrenocortical adenoma overexpressing LH/hCG receptors: a case report.

BACKGROUND: Pregnancy-induced Cushing's syndrome (CS) with an adrenocortical adenoma overexpressing luteinizing hormone (LH)/human choriogonadotropin (hCG) receptors (LHCGR) has been rarely reported in the literatures. This peculiar condition challenges the canonical diagnosis and management of CS. CASE PRESENTATION: A 27-year-old woman (G2P0A1) presented at 20 weeks gestational age (GA) with overt Cushingoid clinical features. Adrenocorticotropic hormone (ACTH)-independent CS was diagnosed based on undetectable ACTH and unsuppressed cortisol levels by dexamethasone. Magnetic resonance imaging (MRI) scanning without contrast revealed a left adrenal nodule while pituitary MRI scanning was normal. A conservative treatment strategy of controlling Cushingoid comorbidities was conducted. At 36 weeks GA, a caesarean operation was performed and a live female infant was delivered. At 8 weeks after parturition, our patient achieved normalization of blood pressure, blood glucose, serum potassium, and urinary cortisol level spontaneously. During non-pregnancy period, stimulation testing with exogenous hCG significantly evoked a cortisol increase. The woman underwent resection of the adrenal tumor at 6 months after parturition. Immunohistochemistry (IHC) showed the tumor tissue that stained positive for luteinizing hormone (LH)/human choriogonadotropin (hCG) receptor (LHCGR), whereas negative for both melanocortin 2 receptor (MC2R) and G protein-coupled receptor-1 (GPER-1). CONCLUSIONS: Stimulation test with exogenous hCG after parturition is necessary for the diagnosis of pregnancy-induced CS. LHCGR plays an essential role in the pathogenesis of this rare condition.

Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: Analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials.

BACKGROUND: Limited data exist on the safety of using anti-human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2-positive patients. METHODS: The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2-positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease-free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time-varying covariates to account for a guarantee-time bias. RESULTS: Ninety-two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52-2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307). CONCLUSIONS: For patients with HER2-positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.

Chemotherapy in pregnancy: exploratory study of the effects of paclitaxel on the expression of placental drug transporters.

Introduction The use of paclitaxel in pregnant cancer patients is feasible in terms of fetal safety, but little is known about the effects of paclitaxel on the placenta. Using three experimental models, we aimed to assess the effects of paclitaxel on the expression of placental drug transporters. Methods In the in vitro model (human primary trophoblast culture), trophoblasts were isolated from normal term placentas and subsequently exposed to paclitaxel. The transcriptional regulation of 84 genes encoding for drug transporters, and the protein expression of ABCB1/P-gp and ABCG2/BCRP were assessed. In the in vivo model, placental tissues isolated from pregnant cancer patients treated with paclitaxel were analyzed to assess the protein expression of ABCB1/P-gp and ABCG2/BCRP. The same parameters were assessed in extracts from human placental cotyledons perfused ex vivo with paclitaxel. Results In the in vitro model, the expression of twelve drug-transporters genes was found to be significantly down-regulated after exposure to paclitaxel, including ABCC10, SLC28A3, SLC29A2, and ATP7B (involved in the transport of taxanes, antimetabolites, and cisplatin, respectively). The protein expression of ABCB1/P-gp increased by 1.3-fold after paclitaxel administration. Finally, the protein expression of ABCB1/P-gp and ABCG2/BCRP was higher in cotyledons from mothers treated with multiple doses of paclitaxel during pregnancy than in cotyledons perfused with a single dose of paclitaxel. Discussion Paclitaxel modulates the expression of placental drug transporters involved in the disposition of various anticancer agents. Further studies will be needed to assess the impact of repeated or prolonged exposure to paclitaxel on the expression and function of placental drug transporters.

Venous thromboembolism and women's health.

The prevention and treatment of venous thromboembolism (VTE) poses distinct gender-specific challenges. Women of childbearing age are at an increased risk of VTE secondary to the transient risk factors of combined hormonal contraception (CHC) and pregnancy. Cancers specific to women are associated with a significant burden of VTE; whilst the incidence of VTE in localised breast cancer is 5 per 1000 person-years, more cases are seen due to the prevalence of breast cancer. Treatment of VTE in women can be complicated by abnormal uterine bleeding, now increasingly reported with direct oral anticoagulants (DOACs) as well as vitamin K antagonists. Divergence between international guidelines regarding the use of CHC following an oestrogen-associated VTE and appropriate withdrawal of such contraception requires clarification for clinicians. Additionally, there is uncertainty as to whether to consider such events provoked or unprovoked and, consequently, the optimal duration of treatment in these women remains unclear. During pregnancy and the puerperium, the traditional anticoagulants remain the agents of choice with no further advances in DOAC safety data, and similarly in lactation. Further studies evaluating the safety and optimal treatment strategies in these women are awaited.

Hormone-secreting adrenal tumours cause severe hypertension and high rates of poor pregnancy outcome; a UK Obstetric Surveillance System study with case control comparisons.

OBJECTIVE: To examine the management and outcomes of adrenal tumours in pregnancy. DESIGN: A national observational, cohort study over 4 years using the UK Obstetric Surveillance System (UKOSS). SETTING: Consultant-led obstetric units. PATIENTS: Women with phaeochromocytoma, primary aldosteronism or Cushing's syndrome diagnosed before or during pregnancy. METHODS: Clinical features of UKOSS cases were compared with those of women with adrenal tumours reported from 1985-2015. Nested case-control comparisons involving the UKOSS cases as well as those identified in the literature were performed for pregnancy outcome data using UKOSS controls with uncomplicated singleton (n = 2250) pregnancy and data from the Office of National Statistics (ONS). MAIN OUTCOME MEASURES: Incidence, management and frequency of adverse maternal and offspring outcomes of adrenal tumours in pregnancy. RESULTS: Fifteen pregnant women met the inclusion criteria: ten phaeochromocytoma, three primary aldosteronism and two Cushing's syndrome. All of the tumours had an incidence rate <2 per 100 000 pregnancies. Clinical symptoms were similar to those in non-pregnant women due to the hormones released. All women had severe hypertension, and in those diagnosed in pregnancy prior to conception. There was a significantly increased risk of adverse pregnancy outcomes in affected women, with increased rates of stillbirth, preterm labour and operative delivery. CONCLUSIONS: Adrenal tumours are associated with increased risks for pregnant women and their babies. Data on these tumours to inform practice are limited and international collaborative efforts are likely to be needed. TWEETABLE ABSTRACT: Study of hormone-secreting adrenal tumours in pregnancy linked with high BP and high rates of fetal morbidity.

Immunohistochemistry of p16 in nevi of pregnancy and nevoid melanomas.

BACKGROUND: Hormonal changes in pregnancy are known to alter melanocytic lesions, with some nevi noted to have increased mitotic figures and increased Ki-67 proliferation index. Additionally, cytomorphologic changes have also been noted, referred to as superficial micronodules of pregnancy. These changes may alarm the pathologist for malignancy, particularly nevoid melanoma. Immunohistochemistry for p16 has been recently utilized to distinguish benign nevi from melanoma. We assessed the use of p16 immunohistochemistry for distinguishing melanocytic nevi of pregnant patients from nevoid melanomas. METHODS: Fourteen nevomelanocytic lesions were obtained from pregnant or postpartum patients along with 20 nevoid melanomas for comparison. Immunohistochemistry with p16 was performed on each melanocytic lesion. The percentage of nuclear p16 staining of dermal melanocytes was grouped on a scale of <5%, 5% to 25%, >25% to 50%, and >50%. RESULTS: The majority of nevi from pregnant patients (81%) showed staining of >5% for p16. In contrast, the majority of nevoid melanomas (65%) had staining of <5% for p16. CONCLUSION: The application of p16 as a potential immunohistochemistry diagnostic marker to distinguish nevi from pregnant patients vs nevoid melanomas may be useful.

Cancer in pregnancy: safety and efficacy of systemic therapies.

PURPOSE OF REVIEW: Cancer in pregnancy has become increasingly frequent. It has become clear that for specific cancers under well defined circumstances, oncological treatment in pregnancy can be well tolerated and feasible for both mother and fetus. Continued critical assessment of the available literature and registration of cancer in pregnancy cases and outcomes for mother and child are necessary to work toward implementing optimal cancer treatment during pregnancy. RECENT FINDINGS: Physiologic changes in pregnancy may alter distribution and efficacy of systemic therapy. Data on systemic therapy including, chemotherapy, hormonal therapy, and targeted therapy during pregnancy are available but incomplete. Outcomes of fetuses exposed to chemotherapy in utero are generally reassuring, but new targeted therapies are mostly discouraged in pregnancy. SUMMARY: Cancer treatment during pregnancy is possible, depending on type and timing of systemic therapy and treatment modality. Available data are reassuring with a modest increase in complications such as growth restriction and preterm birth. The effect of new targeted therapies is often still unclear and therefore discouraged.

First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix.

The extracellular matrix (ECM) affects cancer cell characteristics. Its detachment from the ECM induces cell apoptosis, termed anoikis. Cancer cells can develop anoikis resistance, a necessary step for metastasis, by switching integrins, over-expressing growth factor receptors, and inducing epithelial mesenchymal transition (EMT). The placenta is a non-supportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta-induced ECM manipulations on BCCL. During experiments, BCCL (MCF-7/T47D) were cultured on placenta/BCCL-conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4 OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis-resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF-7 cells, since MCF-7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF-7 highlighted changes in the integrin, estrogen, EGFR, and TGFß pathways. Indeed, placental ECM reduced ERα, induced Smad3/JNK phosphorylation and increased integrin-α5 expression (RGD-dependent integrin) in the BCCL. Addition of RGD or TGFßR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis-resistant cells. © 2016 Wiley Periodicals, Inc.

Cystic lymphangioma of the lesser omentum in a pregnant woman: a case report and review of the literature.

OBJECTIVE: Lymphangiomas are rare benign tumors which are generally seen in pediatric population and the etiopathogenesis has not yet been understood. They occasionally occur in the head and neck or axillary region with only 5% of them being located in the abdominal or mediastinal cavity. These tumors may be asymptomatic or may cause acute abdominal symptoms due to the location and extention. In the English literature, only 4 cases of lymphangioma were reported to have occurred in the pregnancy period. Herein, we report a case of cystic lymphangioma of the lesser omentum detected incidentally on the ultrasonogram of a 21 year-old, 26-week pregnant woman. The patient was followed up uneventfully during pregnancy. Caesarean section was performed due to transverse presentation of the fetus, and the tumor was completely resected during the same session. The patient is recurrence-free after 1 year of postoperative follow-up.

Expression of G protein-coupled oestrogen receptor in melanoma and in pregnancy-associated melanoma.

BACKGROUND: The hormone sensitivity of melanoma and the role of 'classical' oestrogen receptor (ER) α and ß in tumour progression have been intensively studied with rather contradictory results. The presence of 'non-classical' G protein-coupled oestrogen receptor (GPER) has not been investigated on human melanoma tissues. OBJECTIVE: To analyse the expression of GPER, ERα and ERß in pregnancy-associated (PAM) and in non-pregnancy-associated (NPAM) melanomas in correlation with traditional prognostic markers and disease-free survival (DFS). METHODS: Receptor protein levels were tested using immunohistochemistry in 81 formalin-fixed paraffin-embedded melanoma tissues. PAMs (n = 38) were compared with age- and Breslow thickness-matched cases (n = 43) including non-pregnant women (NPAM-W) (n = 22) and men (NPAM-M) (n = 21). The association between receptor expression and DFS was analysed by uni- and multivariate Cox proportional hazards regression. RESULTS: G protein-coupled oestrogen receptor was detected both in PAMs and NPAMs. In 39 of the 41 (95.1%) GPER-positive melanomas, GPER and ERß were co-expressed. GPER/ERß-positive melanomas were significantly more common in PAM compared to NPAM (P = 0.0001) with no significant difference between genders (P = 0.4383). In PAMs, the distribution of GPER and ERß was similar (78.4% vs. 81.6%; P = 0.8504), while in NPAM, ERß was the representative ER (60.5% vs. 27.9%; P = 0.0010) without gender difference (59.1% vs. 61.9%). GPER-/ERß-positive melanomas were associated with lower Breslow thickness, lower mitotic rate and higher presence of peritumoral lymphocyte infiltration (PLI) compared to GPER-/ERß-negative cases (P = 0.0156, P = 0.0036 and P = 0.0001) predicting a better DFS (HR = 0.785, 95% CI 0.582-1.058). Despite the significantly higher frequency of GPER and ERß expression in PAM, no significant difference was found in DFS between PAM and NPAM. All but one case failed to show ERα expression. CONCLUSIONS: The presence of GPER and its simultaneous expression with ERß can serve as a new prognostic indicator in a significant subpopulation of melanoma patients.

Primary hyperparathyroidism in pregnancy - a review of literature.

Hyperparathyroidism during pregnancy is diagnosed in 0.5-1.4% women and poses a serious challenge. Symptoms of primary hyperparathyroidism (PHP), namely fatigue, lethargy and proximal muscle weakness, are unspecific and could be mistaken as complaints naturally present during pregnancy. Thus, diagnosis is usually delayed. Moreover, the complications of PHP are very common. They occur in 67% of mothers and even in up to 80% of progeny. Appropriate management is a matter of debate. According to clinical symptoms, biochemical evaluation and trimester of pregnancy an operation or conservative management should be introduced. The recognition and understanding of the illness is therefore vital. Due to the lack of unequivocal guidelines concerning pregnancy and PHP, in this review we will analyze recent findings to facilitate proper proceedings.

Dydrogesterone has no effect on uterine fibroids when used to prevent miscarriage in pregnant women with uterine fibroids.

OBJECTIVES: To analyse the effect of dydrogesterone use during pregnancy on uterine fibroids, pregnancy complications, and pregnancy outcome. MATERIAL AND METHODS: In all, 372 pregnant women with uterine fibroids who were treated at the Affiliated Provincial Hospital of Shandong University were included in this study. Thirty-three of these women received dydrogesterone and constituted the treatment group, and the 27 women who were found to have uterine fibroids during the first trimester but did not receive intervention to prevent miscarriage composed the control group. The changes in uterine fibroids before and after pregnancy and the pregnancy complications were recorded; immunohistochemistry was used to detect the expression of progesterone receptor (PR) and proliferation- and apoptosis-related proteins in the uterine fibroid tissue. RESULTS: No significant difference was observed in the change in uterine fibroid volume during pregnancy between the treatment group and the control group (p > 0.05). The percentage of uterine fibroids with red degeneration was lower in the treatment group than in the control group, but the difference was not statistically significant. No significant difference was observed in newborn weight, height, Apgar score, threatened miscarriage, or premature birth, among other characteristics, between the two groups (p > 0.05). Immunohistochemistry showed no significant difference in the expression of PR, cyclinD1, insulin-like growth factor (IGF1), or B-cell lymphoma 2 (Bcl2) between the two groups. CONCLUSIONS: The use of dydrogesterone during pregnancy has no significant effect on uterine fibroids, pregnancy progression, or pregnancy outcomes in pregnant patients with uterine fibroids.

Glycodelin expression in pregnant patients with cervical intraepithelial neoplasia: a case-control study.

We aimed to evaluate glycodelin immunostaining in pregnant women with a first diagnosis of cervical intraephitelial neoplasia (CIN) and to correlate the expression of CIN with Ki-67 and glycodelin immunostaining. A retrospective case-control study was performed including 20 patients with natural pregnancy and with first time onset of CIN occurring not later than 16 gestational weeks. The control group included 20 non-pregnant patients matched for age, parity, smoking status and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status and chronic hepatitis B and/or C. Staining for Glycodelin and for Ki-67 was expressed using a classification based on the distribution of positivity on a semi-quantitative three-point scale. An inverse relationship was observed between glycodelin immunostaining and CIN grade in pregnant patients (p = 0.01), with a significantly higher expression in CIN1 than in CIN2 and CIN3, but not in non-pregnant patients (p = 0.81). Positivity for Ki-67 was less intense in pregnant than in non-pregnant patients. A significant inverse relationship was observed between glycodelin immunostaining and Ki-67 expression (p = 0.02). We suggest that the higher expression of glycodelin in pregnancy is related to a lower proliferative activity in CIN, which is probably associated to hormonal status of pregnancy. Further clinical studies are needed to support these findings.

A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion.

BACKGROUND: Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. CASE PRESENTATION: A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm(3) in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. CONCLUSION: We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

Sclerosing Stromal Tumors With Prominent Luteinization During Pregnancy: A Report of 8 Cases Emphasizing Diagnostic Problems.

Ovarian tumors encountered during pregnancy can pose a diagnostic challenge due to an abundance of luteinized cells and other changes. We report 8 sclerosing stromal tumors with massive luteinization discovered in pregnant patients. The tumors ranged from 3.1 to 21 cm (mean=8.8 cm) in size and were typically solid and yellow; the neoplasm was bilateral in 1 case. On microscopic examination, the lutein cells, a feature of sclerosing stromal tumor, had more copious eosinophilic cytoplasm and were more numerous than is usually seen in nonpregnant patients and to varying degrees obscured the typical pseudolobular pattern. This resulted in particular diagnostic difficulty in 3 cases, especially when associated with other changes including irregular shapes of tumor cell nests, edema, and/or myxoid change. However, classic features of these tumors: ectatic vessels and admixed luteinized and nonluteinized cells were still focally evident, allowing for accurate classification. The tumors were cytologically bland and with 1 exception had rare mitoses. As sclerosing stromal tumors have been invariably benign, it is important that they not be confused with other tumors, such as steroid cell tumor, which can occasionally be malignant.

On the pathogenesis of sclerosing stromal tumor of the ovary: a neoplasm in transition.

Sclerosing stromal tumor (SST) is a distinctive benign ovarian stromal neoplasm first reported in 1973. Although its initial description supports its characterization as an ovarian stromal tumor, its exact pathogenesis remains uncertain. It is usually hormonally inactive, but occasional tumors are estrogenic or androgenic, and virilization can occur during pregnancy. We report 11 cases of SST, 6 of which were associated with another type or other types of ovarian stromal tumor. In 4 of these, a transition from thecoma of either typical or luteinized type to SST was observed. Our index case was that of a 16-yr-old girl who had a typical thecoma that underwent involutional changes in an extensive subserosal portion of the tumor with conversion to SST. In our series, 3 cases of SST underwent transformation to ovarian myxoma, one of which also contained a component of thecoma. The active SST components stained for inhibin, steroidogenic factor 1, and α-smooth muscle actin, but were negative or occasionally weakly positive for desmin.