Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs.

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against "self". In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients' life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.

Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center.

BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.

Clinical characteristics, prognostic factors, and long-term outcomes associated with epithelial malignancies of the thymus: A 20-year single-institution experience.

BACKGROUND: Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long-term outcomes in these tumors. AIMS: This review aims to describe disease features of thymomas and thymic carcinomas and to report clinical differences among thymoma histological subtypes. METHODS AND RESULTS: A retrospective chart review was performed at the University of Florida Shands Hospital, a tertiary care academic medical center in Gainesville, Florida, USA. The review included clinical data of adults with thymic epithelial tumors diagnosed between 2001 and 2021. Significant associations among demographics, histology, stage, and outcomes were investigated. Thymoma subgroup analysis was performed using histological subtype and sex. Forty patients with thymoma and seven patients with thymic carcinoma were included in the final analysis. Among those with thymomas, patients with subtype B1, B2, or B3 tumors were younger, had larger tumors, and presented with higher stage disease when compared to those with subtypes A or AB. Tumor recurrence was most common in subtype B2 and B3 tumors (50.0% and 16.7% vs. 0%; p < .01). However, there was no significant difference in overall survival between histologic subtypes. Compared to females, males with thymomas had superior overall survival (103.0 vs. 62.9 months; p = .021) despite presenting with larger tumors (9.8 vs. 5.8 cm; p = .041). Concomitant myasthenia gravis was associated with increased recurrence but not worsened mortality. Compared to thymomas, patients with thymic carcinoma presented with higher-stage disease and had poorer 5-year survival (50.0% vs. 93.1%; p < .01). CONCLUSION: This study affirmed pathologic stage and resectability as prognostic factors for thymic epithelial tumors. New findings include inferior overall survival in female patients and higher recurrence rates in those with thymomas and concomitant myasthenia gravis.

Immunological signature of patients with thymic epithelial tumors and Good syndrome.

Background: Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity. Methods: In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD). We analyzed the immunophenotype from peripheral blood of these patients focusing on selected immune cell subsets (CD4+T cells, CD8+T cells, T regulatory cells, NK cells, B-cells, monocytes, eosinophils, basophils, neutrophils) and serum levels of cytokines, chemokines and growth factors. Results: We observed higher number of leucocytes, in particular lymphocytes, B lymphopenia and lower number of T regulatory cells in TET patients with associated AD compared to TET patients without AD. In the group of TET patients with AD, we also observed increased serum levels of IL-15, VEGF, IP-10, GM-CSF, IL-6, and MIP-1α. Thus, we identified considerable differences in the lymphocyte profiles of TET patients with and without ADs, in particular a reduction in the numbers of B lymphocytes and T-regulatory cells in the former, as well as differences in the serum levels of various immune modulators. Conclusions: Although the pathogenic mechanisms are still unclear, our results add new knowledge to better understand the disease, suggesting the need of surveilling the immunophenotype of TET patients to ameliorate their clinical management.

A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.

Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg = 0.71), endometrioid (rg = 0.48), and high-grade serous (rg = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.

Lifetime ovulations and epithelial ovarian cancer risk and survival: A systematic review and meta-analysis.

OBJECTIVE: To assess the relationship between lifetime ovulatory years (LOY) and Epithelial ovarian cancer (EOC) risk and survival. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Relevant studies were identified from PubMed, MEDLINE, and Embase through December 31, 2021 combining the following search: [("ovulation" or "ovulation cycles" or "ovulatory age" or "ovulatory cycles") and ("ovarian cancer" or "ovarian neoplasms") and ("humans" and "female")]. Reference lists of identified articles were searched for additional studies. Studies were excluded from consideration if they were not a published, peer-review article; not in English; lacked data on effect sizes; had data included in another publication; or were a review article, cross-sectional study, or case report. Two independent investigators screened abstracts and full texts for eligibility, extracted study-level data, and assigned study quality. Disagreements between abstractors were discussed and resolved by consensus. RESULTS: Thirty-one reports were included in the qualitative review of LOY and EOC risk, inclusive of 24 studies with sufficient data to be included in the meta-analysis. Women with the highest level of LOY had 2.26 times higher odds of EOC than women with the lowest level of LOY (95% CI 1.94-2.83). LOY was associated with risk of serous (pooled OR 2.31, 95% CI 1.60-3.33) and endometrioid tumors (pooled OR 3.05, 95% CI 2.08-4.45) but not mucinous disease (pooled OR 1.52, 95% CI 0.87-2.64). There were only four studies examining the LOY-survival association, which precluded a quantitative assessment; however, three of the published studies reported worse outcome with greater LOY. CONCLUSION: LOY is a risk factor for specific EOC histotypes and may also influences EOC survival. Standard definitions of LOY, participant-level data, and larger sample size will enable more precise quantitation of the LOY-EOC association, which can inform EOC risk assessment models.

Efficacy of dexamethasone in the management of malignant small bowel obstruction in advanced epithelial ovarian cancer.

INTRODUCTION: Malignant small bowel obstruction (MSBO) occurs in up to 50% of women with advanced epithelial ovarian cancer (EOC) causing symptom burden and distress to women and their families, particularly in the terminal stages of the disease. Corticosteroids are used to promote symptom resolution in malignant small bowel obstruction (MSBO) related to EOC, with little published data on their efficacy, optimal dosing and duration of treatment. OBJECTIVE: To evaluate the efficacy of dexamethasone in achieving symptom control in women with advanced EOC presenting with MSBO, assess dexamethasone dosing and efficacy over subsequent presentations, and examine differences in dexamethasone responsiveness between platinum-resistant and platinum-sensitive patient. METHODS: This is a retrospective cohort study of women presenting with MSBO due to advanced EOC over a 12-year period from January 2005 to December 2016 in a single tertiary hospital. RESULTS: Ninety-one women with MSBO were administered dexamethasone over 154 admissions with 89% of women initially achieving partial or complete symptom control. Dexamethasone responsiveness did not change with recurrent admissions, and platinum responsive patients were more likely to respond to dexamethasone than platinum-resistant patients (OR 3.6 [95%CI 1.1 to 12.2, p = 0.04]). A total of 15.6% of patients required additional measures to control symptoms of MSBO, and 44.8% had adequate symptom resolution to allow them to remain on or commence further treatment for EOC. CONCLUSION: Dexamethasone therapy is a useful adjunctive therapy in the management of symptoms associated with MSBO in women with EOC.

The Coexistence of Two Different Epithelial Ovarian Tumors: A Rare Case.

BACKGROUND: Epithelial tumors are the most common subgroup and are seen in 60-70% of all ovarian tumors. Serous cystadenoma and mucinous cystadenoma are the most common benign epithelial tumors. Serous cystadenomas are ovarian tumors with the highest bilateral incidence. The coexistence of tumors with different histopathology in the ovaries is extremely rare and has only been reported in a few cases in the literature. We present a case of bilateral ovarian tumor that was diagnosed as serous and mucinous cystadenoma after laparoscopic surgery. CASE REPORT: A 45-year-old female patient was admitted to our center with swelling in the pelvic region and pain in the left lumbar region. US imaging showed a cystic lesion in the right adnexal area, 4x2 cm in size, well-circumscribed, containing a few thin septa, and a low echo fluid content. A cystic lesion with 6x4cm sized multilocular, well-circumscribed, slightly high echo fluid content was observed in the left adnexal area. On CT, a complex cystic lesion measuring 6x4cm was observed in the left adnexal area, pushing the left ureter laterally and causing the hydroureter. In addition, a 4x2 cm cystic lesion was observed in the right adnexal area and hydroureter was observed on the right side proximal to this lesion. Both lesions were removed by surgery. On histopathologic examination, the left-sided cystic lesion was diagnosed as mucinous cystadenoma, and the right-sided cystic lesion was diagnosed as serous cystadenoma. CONCLUSION: The coexistence of different ovarian tumor subtypes is rare. In this article, we presented a case in which serous and mucinous cystadenoma lesions were seen together for the fourth time in the literature, according to our knowledge.

Relationship between ascites volume and clinical outcomes in epithelial ovarian cancer.

OBJECTIVE: Ascites is a tumor microenvironment, ascites and massive ascites-induce compression could promote the progression of epithelial ovarian cancer (EOC); however, the impact of ascites volume on clinical outcomes has not been studied extensively. We aimed to investigate the association between ascites volume and clinical outcomes especially platinum resistance in EOC. METHODS: We retrospectively evaluated a total of 546 EOC patients with respect to the amount of ascites, clinicopathologic factors, and survival. Using the threshold of 1500 ml to classify patients into small- and large-volume ascites groups, we analyzed the correlation between ascites volume and clinicopathological factors, including platinum-free interval (PFI), and prognosis. RESULTS: Patients with large volume ascites were more likely to present with later stage disease, primary platinum-resistant (PPR) cancer, and suboptimal cytoreduction. Prolonged PFI was associated with decreased ascites volume. The large-volume ascites group showed worse progression-free survival (PFS) and overall survival (OS). An increase in ascites volume was associated with an increased risk of disease recurrence (hazard ratio [HR] = 1.115, 95% confidence interval [CI]: 1.035-1.200) and death (HR = 1.213, 95% CI: 1.090-1.350). CONCLUSIONS: Ascites was an independent predictor of PFS and OS in EOC patients. A large volume of ascites predicated a shortened PFI, an increased incidence of PPR and suboptimal cytoreduction. Thus, the volume of ascites is a simply available clinical parameter, which could be used to evaluate the prognosis and platinum resistance of EOC patients early, it contributes to formulate individualized treatment plan and improve the outcome of EOC patients.

Double trouble: Extrauterine epithelioid trophoblastic tumor with uterine choriocarcinoma - An autopsy report.

Gestational trophoblastic tumors (GTTs) include choriocarcinoma, epithelioid trophoblastic tumor, and placental site trophoblastic tumor. The occurrence of mixed GTT is rare. We report such a case in a 24-year-old woman who presented with menorrhagia since 2 months and obstetric history of two abortions, one of which was a molar pregnancy. She was undergoing evaluation for carcinoma cervix and treatment for pulmonary tuberculosis from another hospital when she was admitted at our institute for further workup and treatment. However, she succumbed and an autopsy was performed. Histologic evaluation after the autopsy revealed uterine choriocarcinoma with metastatic epithelioid trophoblastic tumor (ETT) in the lung and spleen.

Cerebellar Hypermetabolism in a Case of Paraneoplastic Cerebellar Syndrome With the Primary Lymphoepithelial Carcinoma in Tonsil.

A 70-year-old man with cerebellar syndromes was clinically diagnosed as paraneoplastic cerebellar degeneration and underwent whole-body F-FDG PET/CT imaging for screening primary tumor. Intensely elevated tracer uptake in both cerebellar hemispheres was revealed, whereas no abnormality was found in MRI. Increased tracer uptake and swelling of the left tonsil and a cervical lymph node were found at the same time, suggesting neoplasm in tonsil with lymph node metastasis. Pathological examination demonstrated lymphoepithelial carcinoma of the left tonsil.

A case of brain metastasis of a thymic carcinoma with a review of the literature.

Thymic epithelial tumors (TET) are rare lesions. The brain metastases of these tumors are even rarer. We report a case of brain metastases in a known patient with a thymic carcinoma diagnosed in October 2016. She was a 73-year-old woman who presented with headache, nausea, and right hemiplegia. Brain MRI revealed five lesions (1 insular, 1 frontal and 2 left temporal, 1 right parafalcine). These lesions were initially treated using two stereotactic radiosurgery gamma knives. A macroscopically complete excision of the left frontal lesion was subsequently performed without any complications with a good evolution of the neurological symptoms postoperatively. Immunohistochemical examination was compatible with metastatic thymic carcinoma. The patient died 14 months after the initial diagnosis. A review of the literature in English has reported another 45 TET cases with brain metastases.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Atypical Thymoma With Rhabdomyomatous Differentiation.

Thymic epithelial neoplasms with foci of rhabdomyomatous differentiation are rare. A case is presented of a primary thymic epithelial neoplasm showing the features of an atypical spindle cell thymoma that contained foci of bland-appearing rhabdomyomatous cells. The histologic and immunohistochemical features of this tumor are discussed along with a review of the literature and the comments from the AMR members to the case.

Useful computed tomography features for differentiating between focal atelectasis and pleural dissemination on preoperative evaluations of thymic epithelial tumors.

PURPOSE: Distinguishing between focal atelectasis (FA) and pleural dissemination (PD) is important for determining the optimal therapeutic strategy for thymic epithelial tumors (TET). This study aimed to identify useful computed tomography (CT) features for distinguishing between these two conditions. MATERIALS AND METHODS: We retrospectively analyzed preoperative CT images of 27 TET, which included 40 PD and 40 FA lesions. Two radiologists independently interpreted the pleural lesions without knowing the final diagnosis. The CT images were evaluated to assess the lesion location, size, and shape, presence of a spinous shadow and ground glass opacities (GGO) near to the lesion, and the shortest distance from the lesion to the nearest peripheral pulmonary artery (PA). RESULTS: FA lesions tended to occur on the dorsal side (90%, P = 0.024); have shorter major and minor axes (P < 0.001), a triangular shape (43%, P = 0.002), a spinous shadow (45%, P = 0.001) and GGO (28%, P = 0.006); and be close to a peripheral PA (P = 0.007). Ninety percent of PD lesions were located in the left thorax, and all of them were ipsilateral to the tumor (both P < 0.001). The 9 examined factors exhibited sensitivity, specificity, positive predictive, and negative predictive values of 85%, 95%, 94%, and 86%, respectively, for diagnosing FA (when ≥3 factors were present), and 90%, 48%, 63%, and 83%, respectively, for diagnosing PD (when ≥4 factors were present). CONCLUSION: The site, size, and shape of a lesion; the presence of a spinous shadow/GGO; and the distance to the nearest PA are useful for distinguishing between PD and FA.

Concomitant venous thromboembolism at the time of primary EOC diagnosis: Perioperative outcomes and survival analyses.

OBJECTIVE: To compare outcomes among women with epithelial ovarian cancer (EOC) undergoing primary surgery who present without venous thromboembolism (VTE) versus with VTE and placement of inferior vena cava (IVC) filter. METHODS: Women who underwent primary surgery for EOC between 1/2/2003 and 12/30/2011 were identified. Patient characteristics were retrospectively abstracted, including diagnosis of VTE within 30days prior to surgery and placement of IVC filter. Associations with overall survival (OS) were evaluated using Cox proportional hazards models. RESULTS: A total of 843 patients met inclusion criteria; 817 patients (Group 1) did not have VTE at the time of EOC diagnosis and 26 patients (Group 2) had a VTE and IVC placement within 30days prior to surgery. Group 2 had worse performance status, lower albumin, and more likely to have clear cell histology. Groups 1 and 2 were similar in terms of perioperative outcomes. Mortality within 90days of surgery was 6.4% in Group 1 versus 11.5% in Group 2 (p=0.24). Although median OS for group 1 was much higher than group 2, 56.6m versus 25.7m, in this cohort this difference did not reach statistical significance (adjusted HR 1.39, 95% CI 0.85-2.29, p=0.19). CONCLUSIONS: Patients with VTE diagnosed at the time of EOC diagnosis have poor outcomes. This may reflect more aggressive tumor biology, worse overall health of the patient following VTE, or may reflect worse survival secondary to the VTE. Patients must be carefully selected for surgery in the setting of VTE.

Cytological Features of the Large Cell Variant of Small Cell Ovarian Carcinoma in Young Patients with Hypercalcemia: Histological Findings and Review of the Literature.

OBJECTIVE: To present the cytological features of a very rare and lethal ovarian neoplasm occurring in the young. STUDY DESIGN: We reviewed the cytological findings as they presented in touch imprints obtained from an ovarian mass sent to our department for frozen section investigation. RESULTS: Smears were highly cellular. The cells were of intermediate size with a moderate amount of microvacuolated, pale, or eosinophilic cytoplasm with indistinct cell borders. The nuclei were of round or oval shape with mild to moderate atypia and indistinct nucleoli. CONCLUSIONS: The diagnosis of small cell carcinoma of the ovary can be challenging even histologically. Cytology can be an invaluable adjunct to hematoxylin-eosin sections both pre- or intraoperatively. Although it is a very rare occurrence and cytological results are almost absent in the literature, our case can make cytopathologists more acquainted with the cytological features of this rare tumor entity especially in association with a characteristic clinical profile. Furthermore, the cytological features of small cell carcinoma of the ovary, large cell variant, have only rarely been described in the literature.

Functional not chronologic age: Frailty index predicts outcomes in advanced ovarian cancer.

OBJECTIVES: To assess the impact of frailty as measured by a frailty deficit index (FI) on outcomes in advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Women with Stage IIIC/IV EOC who underwent PDS between 1/1/2003-12/31/2011 were included. Medical records were reviewed for patient characteristics and outcomes. The FI includes 30 items scored at 0, 0.5 or 1 and is calculated by summing across all the item scores and dividing by the total. Frailty was defined as a FI ≥0.15. Associations were assessed using logistic regression and Cox proportional hazards regression. RESULTS: Of the 535 studied, 78% had stage IIIC disease and mean (SD) age was 64.3 (11.3) years. Median FI was 0.08, and 131 patients (24.5%) were considered frail with FI ≥0.15. Compared to non-frail patients, frail patients were more likely to have an Accordion grade 3+ complication (28.2 vs. 18.8%; odds ratio (OR): 1.70, 95% CI: 1.08-2.68) and more likely to die within 90days of surgery (16.0 vs. 5.2%; OR: 3.48, 95% CI: 1.83-6.61). After adjusting for known risk factors, these associations remained significant, adjusted OR (aOR): 1.62, 95% CI: 1.00-2.62; aOR: 2.60, 95% CI 1.32-5.10; and aOR: 0.57, 95% CI 0.34-0.97, respectively. Overall survival (OS) for the entire cohort was 39.6months (m). OS was shorter in the frail versus non-frail (median 26.5 vs 44.9m, p<0.001). Frailty was independently associated with death (adjusted hazard ratio: 1.52, 95% CI: 1.21-1.92) after adjusting for known risk factors. CONCLUSIONS: Frailty is a common finding in patients with EOC and is independently associated with worse surgical outcomes and poorer OS. Routine assessments of frailty can be incorporated into patient counseling and decision-making for the EOC patient beyond simple reliance on single factors such as age.

Malignant Bowel Obstruction in Relapsed Ovarian Cancer With Peritoneal Carcinomatosis: An Occlusive State.

OBJECTIVE: The aim of this study was to describe the clinical and oncological outcomes of women with malignant bowel obstruction (MBO) for relapsed ovarian cancer and peritoneal carcinomatosis. METHODS: A retrospective cohort study was performed in all consecutive patients admitted at Instituto Valenciano de Oncología, Valencia, Spain, between July 2013 and July 2016 with MBO for relapsed ovarian cancer and peritoneal carcinomatosis. All patients underwent the same protocol of conservative management. Surgical treatment was indicated only in selected cases. RESULTS: There were a total of 22 patients presenting 59 episodes of MBO; 17 (77.2%) of those patients presented more than 1 episode of MBO. All patients had serous epithelial ovarian cancer; 18 (81.8%) were high grade, and 4 (18.2%) low-grade tumors. The median (range) number of episodes per patient was 3 (range, 1-7) with a mean length of hospitalization of 13 (SD, 13.6) days. The median time interval between episodes of MBO (54 episodes in 17 patients) was 17 days (range, 1-727 days). Twenty of 22 patients died with a median overall survival time from the first episode of MBO of 95 days (95% confidence interval, 49-124 days). CONCLUSIONS: Patients with MBO due to relapsed epithelial ovarian cancer in the peritoneal carcinomatosis setting have a short life expectancy, presenting a median of 3 episodes of MBO until death, with a short time interval between episodes. These findings show that bowel obstruction can represent a constant status over time until death.

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

BACKGROUND: Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. CASE PRESENTATION: A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. CONCLUSIONS: Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.