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Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

The experience with uterine inflammatory myofibroblastic neoplasms with an unfavorable outcome is limited. We present the clinicopathologic features of 9 such cases, including 8 inflammatory myofibroblastic tumors (IMTs) and 1 epithelioid inflammatory myofibroblastic sarcoma (EIMS). Median patient age for the IMT group was 50.5 years; the patient with EIMS was 43 years old. Patients presented with abnormal uterine bleeding, presumed fibroids, pelvic pain, arthralgia and low-grade fever, as well as an incidental finding. Median tumor size for the IMTs was 8.5 cm. The borders were either infiltrative or well-circumscribed. Histologically, IMTs were purely fascicular or myxoid or showed predominance of one or the other pattern. Seven tumors were spindled, and 1 was both spindled and epithelioid. Tumors had variable nuclear atypia, ranging from grade 1 to 3. All tumors had an inflammatory infiltrate-predominantly lymphocytic, majority had necrosis (62.5%) and none had lymphovascular invasion. 7/8 (87.5%) tumors were positive for ALK-1 by immunohistochemistry (IHC). One tumor was negative for ALK-1 by IHC but was positive for ALK fusion by fluorescence in situ hybridization and had TNS1-ALK fusion by next-generation sequencing (NGS). Three other tumors with NGS testing showed one of the following ALK-fusion partners: FN1, DCTN1, and IGFBP5. The EIMS had infiltrative borders, myxoid and hyalinized patterns, epithelioid cells, and no lymphovascular invasion. This tumor was ALK-1 positive by IHC, had ALK rearrangement by fluorescence in situ hybridization and RANBP2-ALK fusion by NGS. Extrauterine disease at time of diagnosis was noted in 2/8 (25%) of IMTs, and in the single case of EIMS. Seven patients had surgery as primary treatment, 1 patient had neoadjuvant chemotherapy and 1 patient declined treatment. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, radiotherapy or hormonal therapy. Most patients (71.4%) recurred within 24 months (mos). Two thirds of patients were alive with disease at last follow up (mean 43.6 mos). The patient with EIMS was alive with disease at 22 mos. IMT referral cases were initially diagnosed as smooth muscle tumors in 87.5% of cases; while the EIMS was diagnosed as high-grade endometrial stromal sarcoma. Lack of consideration of IMT in the differential diagnosis of smooth muscle tumors with myxoid features can result in misdiagnosis and under-utilization of targeted therapy in these patients.

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population, This work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜na

Summary Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.

Introduction: vitamin D is a fundamental biomolecule for multiple biological processes in women of childbearing age; it is also one of the most important biomarkers in reproduction. Objective: to determine the prevalence of vitamin D deficiency and insufficiency and associated factors in Colombian women between 18 and 49 years of age. Methodology: an analytical cross-sectional study; it is a secondary analysis of the Encuesta de Situación Nutricional de Colombia, of 2015. A total of 7181 women between 18 and 49 years old, of childbearing age, who were not pregnant were evaluated. Vitamin D levels were estimated through chemiluminescence immunoassay. Sociodemographic, anthropometric and frequency-of-food-consumption characteristics were evaluated. A general description of the prevalence of vitamin D insufficiency and deficiency was made for each of the variables of interest through absolute and percentage frequencies. To estimate the association between the different characteristics of interest and vitamin D insufficiency and deficiency, multivariate binomial and multinomial logistic regression models were used. Results: the prevalence of vitamin D deficiency was 23.8 % and that of insufficiency was 46.8 %; for insufficiency and deficiency the result was 70.6 %. Quartile IV of wealth (OR: 3.21; 95% CI: 2.16-4.77); abdominal obesity (OR: 1.43; IC 95 %: 1.15-1.78), and the Bogotá region (OR: 3.98; 95 % CI: 2.48-6.38) showed an association with vitamin D insufficiency and deficiency. Conclusion: a high prevalence of vitamin D insufficiency and deficiency was identified. Therefore, comprehensive interventions involving nutritional and educational components are recommended.Introducción: la vitamina D es una biomolécula fundamental para múltiples procesos biológicos de la mujer en edad fértil; es también uno de los biomarcadores más importantes para la reproducción. Objetivo: determinar la prevalencia de la deficiencia e insuficiencia de vitamina D y los factores asociados en mujeres colombianas de 18 a 49 años de edad. Metodología: estudio transversal-analítico; se trata de un análisis secundario de la Encuesta de Situación Nutricional de Colombia, del año 2015. Se evaluaron 7181 mujeres de entre 18 y 49 años, en edad fértil, que no estuvieran en embarazo. La vitamina D se estimó a través de quimiolumiscencia por inmunoensayo. Se evaluaron características sociodemográficas, antropométricas y de frecuencia de consumo de alimentos. Se realizó la descripción de la prevalencia de la insuficiencia y deficiencia de vitamina D general y por cada una de las variables de interés a través de frecuencias absolutas y porcentuales. Para estimar la asociación entre las diferentes características de interés y la insuficiencia y la deficiencia de vitamina D se utilizaron modelos de regresión logística multinomial y binomial multivariados. Resultados: la prevalencia de la deficiencia de vitamina D fue del 23,8 % y la insuficiencia del 46,8 %; entre insuficiencia y deficiencia, el resultado fue del 70,6 %; el cuartil IV de riqueza (OR: 3,21; IC 95 %: 2,16-4,77), la obesidad abdominal (OR: 1,43; IC 95 %: 1,15-1,78), y la región de Bogotá (OR: 3,98; IC 95 %: 2,48-6,38) mostraron asociación con la insuficiencia y la deficiencia de vitamina D. Conclusión: se identificó una alta prevalencia de insuficiencia y de deficiencia de vitamina D, por lo que se recomiendan intervenciones integrales en las que estén involucrados los componentes nutricional y educativo.

Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management.

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82]

Purpose: Adult granulosa cell tumor (AGCT) is characterized by the somatic FOXL2 p.C134W mutation, and recurrences have been associated with TERT promoter and KMT2D-truncating mutations. Conversely, the molecular underpinnings of the rare juvenile granulosa cell tumor (JGCT) have not been well elucidated. To this end, we applied a tumor-only integrated approach to investigate the genomic, transcriptomic, and epigenomic landscape of 31 JGCTs to identify putative oncogenic drivers. Experimental Design: Multipronged analyses of 31 JGCTs were performed utilizing a clinically validated next-generation sequencing (NGS) panel targeting 580 cancer-related genes for genomic interrogation, in addition to targeted RNA NGS for transcriptomic exploration. Genome-wide DNA methylation profiling was conducted using an Infinium Methylation EPIC array targeting 866,562 CpG methylation sites. Results: We identified frequent KMT2C-truncating mutations along with other mutated genes implicated in the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, in addition to previously reported hotspot AKT1 and DICER1 mutations. Targeted transcriptome sequencing revealed recurrent TERT rearrangements (13%) involving partners CLPTM1L or DROSHA, and differential gene expression analysis showed FGFR1 upregulation in the TERT non-rearranged JGCTs under direct promoter control. Genome-wide DNA methylation rendered a clear delineation between AGCTs and JGCTs at the epigenomic level, further supporting its diagnostic utility in distinguishing among these tumors. Conclusions: This is the largest comprehensive molecular study of JGCTs, where we further expand our current understanding of JGCT pathogenesis and demonstrate putative oncogenic drivers and TERT rearrangements in a subset of tumors. Our findings further offer insights into possible targeted therapies in a rare entity.

Background The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with aggressive diseases, such as adult T-cell leukemia/lymphoma (ATLL). However, less is known on the impact of HTLV-1 infection in non-ATLL hematologic malignancies. We aimed to investigate if HTLV-1 carriers with diffuse large B-cell lymphoma (DLBCL) have worse survival outcomes than non-HTLV-1 carriers. Materials and Methods We performed a single-center retrospective cohort study by matching HTLV-1 carriers to non-carriers based on age, sex, Ann Arbor stage, and year of diagnosis. Our outcomes of interest were overall survival (OS) and progression-free survival (PFS). The Kaplan-Meier method was used to estimate OS and PFS between carriers and non-carriers. We fitted multivariate Cox regression models to assess the mortality and recurrence/disease progression risk of HTLV-1 infection. Results A total of 188 patients, 66 with HTLV-1 infection and 122 without HTLV-1, were included in the study. HTLV-1 carriers had higher extranodal involvement than non-carriers (47% vs. 27%, P = .010). With a median follow-up of 78 months (95% CI: 41-90 months), HTLV-1 carriers had a similar 5 year OS (41% vs. 42%, P = .940) and PFS (34% vs. 32%, P = .691) compared to non-carriers. In the multivariate Cox analysis, HTLV-1 infection was not associated with worse OS (aHR: 0.98, 95% CI: 0.64-1.50) or PFS (aHR: 0.90, 95% CI: 0.60-1.34). Conclusion HTLV-1 carriers with DLBCL did not have worse survival outcomes compared to non-carriers. Our results suggest that clinicians should follow standard guidelines for DLBCL management on HTLV-1 seropositive patients.

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

Endometrial mesonephric-like carcinomas (MLCa) are uncommon with50 reported cases thus far. Previous studies have characterized the histologic, immunohistochemical, and molecular features of MLCa; however, there is limited information with respect to outcome. This single-institution study of 23 uterine MLCas characterizes the behavior of such a neoplasm. Uterine MLCas (2004-present) had review of histologic features, immunohistochemical results, molecular profile, and clinical information (stage, treatment, follow-up). The behavior of MLCa was compared with low-grade endometrioid carcinomas (ECas) and uterine serous carcinomas (USCs) treated at our institution from 2004 to present. All MLCas had a mixture of previously described architectural and cytologic features most notably ductal and/or tubular architecture (21/23), nuclei resembling those of papillary thyroid carcinoma (18/23), and at least focal intraluminal eosinophilic secretions (20/23). Immunoperoxidase studies facilitated diagnosis in 22 cases: CD10, 10/10; calretinin, 5/15; estrogen receptor (≥10% nuclei), 6/21; progesterone receptor, 1/15; GATA-3, 15/16; TTF-1, 11/16. Fourteen of 17 tested cases had a KRAS mutation (7 as the only alteration; 7 with additional mutations including PIK [n=5]; PTEN [n=2], CTNNB1 [n=1]).One case had mutations in PTEN, PIK, and CTNNB1 without KRAS; 2 cases had no detectable somatic mutation. Overall, 48% of patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage 3 or 4 disease with the following uterine risk factors:50% myometrial invasion, 20/23; lymphovascular space invasion, 16/23; cervical stromal invasion, 7/23. Twenty patients had adjuvant therapy (7 radiation only; 13 chemotherapy±radiation), whereas 3 patients had either unknown or declined therapy. Follow-up was known for 21 patients: 17 patients had recurrences or never achieved remission with the lung being the most common recurrence site (n=9); 7 patients died of disease. The median progression-free survival was 18.2 months for MLCa compared with 183 months for ECa and 67.1 months for USC. The median overall survival for MLCa was 70.6 months compared with 139.1 months for USC (median survival for ECa not reached). Uterine MLCa is uncommon with most tumors recognized by architectural heterogeneity, vesicular, overlapping nuclei with grooves, and eosinophilic luminal secretions. The typical immunoprofile includes low to absent expression of hormone receptors but at least focal expression of GATA-3 and/or TTF-1. Most tested cases had a KRAS mutation although genetic mutations typically associated with ECa are not uncommon. Compared with more commonly encountered types of ECa, MLCa is more aggressive with a tendency towards earlier and distant recurrence.

OBJECTIVE: To estimate whether gastrointestinal-type chemotherapy was associated with improved survival compared to standard gynecologic regimens for women with ovarian mucinous carcinoma. METHODS: We conducted a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers. Demographic and clinical information was abstracted from the medical records. Gastrointestinal-type chemotherapy contained 5-fluorouracil, capecitabine, irinotecan, or oxaliplatin. Gynecologic regimens included standard carboplatin or cisplatin. Bevacizumab treatment was allowed in both groups. Summary statistics were used to compare baseline characteristics; Kaplan-Meier product-limit estimator was used to compare survival outcomes. RESULTS: Fifty-two patients received either gastrointestinal-type chemotherapy (n=26; 50%) or a standard gynecologic regimen (n=26; 50%). Three-quarters of tumors were early-stage (I or II), 68% grade 1 or 2 and 88% of patients had no gross residual disease after surgery. Patients receiving gastrointestinal-type chemotherapy were more likely to receive bevacizumab (50% vs. 4%; P < .001), but there were no other differences in clinical or demographic characteristics. Unadjusted overall survival analyses showed that gastrointestinal-type chemotherapy was associated with better overall survival (HR 0.2, 95% CI 0.1–0.8), as were early stage tumors and having no gross residual disease. CONCLUSION: Gastrointestinal-type chemotherapy with or without bevacizumab was associated with improved survival and should be considered in patients with ovarian mucinous carcinoma requiring adjuvant therapy.

Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Mullerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.

The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.

Background : The use of immunosuppressive therapies in the management of non-malignant immune-mediated hematologic disorders (NMIHD) leads to an increased risk of infections. Preventive strategies, such as immunization and infectious disease (ID) screening, reduce the burden of infectious complications. However, lack of compliance to available guidelines among healthcare providers (HCP) represent a major concern. The present study was performed to assess adherence by HCP to national guidelines and recommendations for the prevention of infectious complications in patients (pts) treated for a NMIHD with the goal to identify areas where interventions can be implemented to improve awareness. Methods : We retrospectively analyzed pts diagnosed with AIHA, acquired coagulation factor deficiency (ACFD), TTP, ITP, aHUS, PNH, and antiphospholipid syndrome (APS) between January 2016 and July 2018 at an academic medical center (University of North Carolina). Pts had to have received either rituximab (RTX), eculizumab, or splenectomy. Adherence to existing strategies was assessed based on available recommendations from recognized national entities (e.g. CDC, ACIP), and clinical societies (e.g. ASH) (summarized in Table 1). Immunizations considered for analysis included: pneumococcal, meningococcal and Haemophilus influenzae vaccines ('triple vaccine' if received all together). We considered 'adherence to an immunization recommendation' when, depending on the diagnosis and treatment employed, pts received all recommended vaccines at least 2 weeks prior to therapy or 4 weeks if splenectomy. Adherence to ID screening in pts receiving RTX therapy was defined as pts screened for both hepatitis B surface antigen and total core antibodies. Influenza virus and herpes zoster (HZ) immunization rates were also analyzed. Results : 269 pts from six UNC-affiliated hospitals were included. Pts clinical characteristics are summarized in Table 2. Overall, only 6% of all evaluable pts were appropriately immunized as recommended by national guidelines (5%, 8%, and 8%, for RTX, eculizumab, and splenectomy, respectively) (Table 3). Immunization rates are summarized in Figure 1. In the eculizumab group, although 92% of HCP recommended and prescribed meningococcal immunization, only 38% (n=5/13) received both vaccines (54% either, 8% none). Likewise, although 89% (n=47/53) of pts undergoing splenectomy had received a 'triple vaccine', only 11% of pts received guideline recommended vaccines (both pneumococcal and meningococcal vaccines) and only 8% were appropriately vaccinated by receiving all indicated vaccines at least 4 weeks prior to their scheduled surgery. 68% of pts treated with RTX were appropriately screened for hepatitis B, with lower rates found in young women (screening rate: 77% age >50 vs. 58% ≤50 years, p Conclusion : To the best of our knowledge, there have been no studies conducted in the U.S. assessing adherence to infectious prevention guidelines among different NMIHD. We found that in pts with NMIHD undergoing immunotherapy or splenectomy, many pts received either incomplete recommended immunizations or the immunization was administered too close in proximity to the immunosuppressive therapy or splenectomy, both resulting in impaired immunologic response to vaccines. In addition, only two thirds of pts receiving RTX had pretreatment screening for hepatitis B infection at odds with national recommendations of 100%. Lastly, low immunization rates against influenza virus and HZ were found. Based on these results, we created infographics (supplemental figure), an "easy-to-use" pocket brochure summarizing recommendations (Table 1), and we are building immunization reminders when electronically prescribing immunotherapy, with the aim of improving HCP awareness in our health care system. Although we are unsure about other institution's compliance rate, we suspect that non-compliance to immunization is a systemic problem across the U.S. We will disseminate this data hoping to replicate this study at other academic institutions. There is an urgent need for the development of strategies to improve HCP awareness and adherence to infectious prevention guidelines! Disclosures No relevant conflicts of interest to declare.

Background Previous studies have found that healthcare-associated bacteremia (HAB) by Aeromonas species is associated with mortality. However, there is limited data on this outcome in patients with hematologic malignancies. This study aimed to identify the clinical features of patients with malignant hematologic diseases diagnosed with Aeromonas sobria bacteremia and to evaluate whether the type of bacteremia, community-acquired bacteremia (CAB) or HAB, is associated with mortality. Methods We retrospectively reviewed the clinical records of pediatric and adult patients between January 2000 and December 2017. Clinical characteristics were compared between CAB and HAB. Additionally, we stratified based on age group. Survival outcomes were assessed with Kaplan-Meier curves and a multivariate Cox regression analysis. Results A total of 37 patients (median age 24 years) were identified; 23 (62%) had HAB and 14 (38%) had CAB. Overall, the most common presenting symptom was abdominal pain (41%). Acute lymphoblastic leukemia (n = 12/15, 80%) and acute myeloid leukemia (n = 8/22, 36%) were the primary hematologic malignancies in pediatric and adult patients, respectively. CAB patients had worse overall survival (OS) rates at 30 days in all (43% versus HAB 91%, p = 0.006) and adult patients (30% versus HAB 92%, p = 0.002). Cox regression analysis found that quick Sequential Organ Failure Assessment and CAB were statistically significant factors associated with mortality. Low antimicrobial-resistant was noted, except for ciprofloxacin (n = 5/37, 14%). Conclusion Our study found a worse OS among patients with hematologic malignancies and CAB by Aeromonas sobria. Our results suggest that patients with CAB present with a worse disease severity. These findings should aid clinicians to determine the survival prognosis in this population.

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM. Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS). Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort. Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.

We present the clinicopathologic features of 15 cases of extragonadal yolk sac tumor (EGYST) detected in female patients and reviewed at our institution from 1988 to 2016. We recorded: patient age, clinical presentation, tumor location, FIGO stage (where applicable), histologic patterns including presence/absence of Schiller-Duval bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. Patients' ages ranged from 17 to 87 (median, 62) years and presentation included: abnormal uterine bleeding, 12; hematuria, 1; labial mass, 1; abdominal pain, 1. Primary sites were as follows: uterus (11), vagina (1), vulva (1), bladder (1), and peritoneum (1). Seven patients presented at FIGO stage III or IV. The following histologic patterns were observed: microcystic/reticular (7), glandular (8), solid (8), papillary (5), and hepatoid (1). An admixture of histologic patterns was present in 10 cases. Schiller-Duval bodies were seen in only 3 (23%) cases. Eight cases (46%), all uterine primaries, had associated somatic components, and 2 (15%) had a second germ cell component. In 13/14 (93%) cases, the yolk sac tumor component was either missed or misclassified as adenocarcinoma. Immunoperoxidase studies facilitated the diagnosis in all cases as follows: SALL4, 12/12; CDX2, 10/12; α fetoprotein, 7/14; glypican-3, 9/10; cytokeratin 20, 5/9 (rare cells); cytokeratin 7, 3/12 (nondiffuse); PAX8, 2/9 (variable expression). All patients received chemotherapy and all except 1 underwent surgical resection. Follow-up from 5 to 86 months was available for 13 patients: 5 died of disease, 6 are alive with disease, and 2 have no evidence of disease. EGYST arising in the female pelvis of peri/postmenopausal patients may be associated with a somatic component and represent either somatically derived YST or YST differentiation within a somatic carcinoma. EGYST in younger patients is likely a true germ cell neoplasm, and may respond to germ cell appropriate chemotherapy. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST is less clear. Awareness that the presence of glandular or microcystic patterns may lead to under-recognition or misdiagnosis of EGYST in combination with immunomarkers for germ cell and yolk sac differentiation will facilitate the diagnosis.

Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1-R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were not identified in our series, suggesting that these tumors are molecularly different from their central nervous system counterparts despite their morphologic and immunophenotypic similarities.

Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow-up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no evidence of disease. Ovarian LGSC is rare with a predilection for younger patients relative to HGSC. Most LGSC cases are associated with SBT with an MP/CP, and their invasive component usually contains a micropapillary pattern. Most patients with ovarian LGSC present with advanced-stage disease and have a short-term survival advantage over patients with HGSC (estimated 5 y survival: 62.3% vs. 43.9%). However, over a prolonged period of time, this survival advantage decreases (estimated 10 y survival: 21.2% vs. 22.7%).

Adult T-cell leukemia/lymphoma (ATLL) is a fatal disease caused by human T-cell leukemia virus type 1 (HTLV-1). We retrospectively analyzed 195 patients with ATLL (lymphomatous n = 96, acute n = 80, unfavorable chronic n = 7, chronic n = 5, smoldering n = 3, and unclassified n = 4) diagnosed between 1987 and 2016 (median age 52 years, 77% Afro-Caribbean). Hypercalcemia was associated with acute ATLL (65%, vs 23% lymphomatous) (P = .012). The median survival for patients treated with modern therapies between 2000 and 2016 was 4.1 months for acute, 10.2 months for lymphomatous, 72 months for chronic/smoldering, and not reached for unfavorable chronic type, with 4-year survival rates of 10%, 4%, 60%, and 83%, respectively. The overall response rate (ORR) after first-line multiagent chemotherapy was 78% (complete response [CR] 39%) for acute vs 67% (CR 33%) for lymphomatous ATLL. First-line zidovudine interferon-α (AZT-IFN) resulted in ORR of 56% (CR 23%) for acute (n = 43), 33% (CR 16.5%) for lymphomatous (n = 6), and 86% (CR 29%) for unfavorable chronic ATLL. The median progression-free survival (PFS) in patients with aggressive ATLL who achieved CR after AZT-IFN was 48 months vs 11 months after chemotherapy (P = .003). Allogeneic hematopoietic stem cell transplant (allo-HSCT) resulted in a PFS of 24 and 28 months in 2 patients with lymphomatous ATLL. Our results suggest high-dose AZT-IFN is a reasonable up-front option for patients with aggressive leukemic ATLL followed by chemotherapy switch in nonresponders, whereas chemotherapy should be used in lymphomatous type followed by allo-HSCT when feasible.

Whole-body attenuation correction (AC) is still challenging in combined PET/MR scanners. We describe Dixon-VIBE Deep Learning (DIVIDE), a deep-learning network that allows synthesizing pelvis pseudo-CT maps based only on the standard Dixon volumetric interpolated breath-hold examination (Dixon-VIBE) images currently acquired for AC in some commercial scanners. Methods: We propose a network that maps between the four 2-dimensional (2D) Dixon MR images (water, fat, in-phase, and out-of-phase) and their corresponding 2D CT image. In contrast to previous methods, we used transposed convolutions to learn the up-sampling parameters, we used whole 2D slices to provide context information, and we pretrained the network with brain images. Twenty-eight datasets obtained from 19 patients who underwent PET/CT and PET/MR examinations were used to evaluate the proposed method. We assessed the accuracy of the μ-maps and reconstructed PET images by performing voxel- and region-based analysis comparing the SUVs (in g/mL) obtained after AC using the Dixon-VIBE (PET(Dixon)), DIVIDE (PET(DIVIDE)), and CT-based (PET(CT)) methods. Additionally, the bias in quantification was estimated in synthetic lesions defined in the prostate, rectum, pelvis, and spine. Results: Absolute mean relative change values relative to CT AC were lower than 2% on average for the DIVIDE method in every region of interest except for bone tissue, where it was lower than 4% and 6.75 times smaller than the relative change of the Dixon method. There was an excellent voxel-by-voxel correlation between PET(CT) and PET(DIVIDE) (R(2) = 0.9998, P < 0.01). The Bland–Altman plot between PET(CT) and PET(DIVIDE) showed that the average of the differences and the variability were lower (mean PET(CT)–PET(DIVIDE) SUV, 0.0003; PET(CT)–PET(DIVIDE) SD, 0.0094; 95% confidence interval, [−0.0180,0.0188]) than the average of differences between PET(CT) and PET(Dixon) (mean PET(CT)–PET(Dixon) SUV, 0.0006; PET(CT)–PET(Dixon) SD, 0.0264; 95% confidence interval, [−0.0510,0.0524]). Statistically significant changes in PET data quantification were observed between the 2 methods in the synthetic lesions, with the largest improvement in femur and spine lesions. Conclusion: The DIVIDE method can accurately synthesize a pelvis pseudo-CT scan from standard Dixon-VIBE images, allowing for accurate AC in combined PET/MR scanners. Additionally, our implementation allows rapid pseudo-CT synthesis, making it suitable for routine applications and even allowing retrospective processing of Dixon-VIBE data.

Purpose Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is a rare subtype of ovarian or peritoneal cancer characterized by young age at diagnosis and relative resistance to chemotherapy. The purpose of this study is to report our updated experience with women diagnosed with LGSOC or LGSPC to assess the validity of our original observations. Patients and Methods Eligibility criteria for patients from our database were: stage I to IV LGSOC or LGSPC, original diagnosis before January 2012, and adequate clinical information. All patients were included in progression-free survival, overall survival, and multivariable Cox regression analyses. A subset analysis was performed among patients with stage II to IV low-grade serous carcinoma treated with primary surgery followed by platinum-based chemotherapy. Results We identified 350 eligible patients. Median progression-free survival was 28.1 months; median overall survival was 101.7 months. In the multivariable analysis, compared with women age ≤ 35 years, those diagnosed at age > 35 years had a 43% reduction in likelihood of dying (hazard ratio, 0.53; 95% CI, 0.37 to 0.74; P < .001). Having disease present at completion of primary therapy was associated with a 1.78 increased hazard of dying compared with being clinically disease free (P < .001). Similar trends were noted in the smaller patient cohort. In this cohort, women with LGSPC had a 41% decreased chance of dying (hazard ratio, 0.59; 95% CI, 0.36 to 0.98; P = .04) compared with those with LGSOC. Conclusion Women age < 35 years with low-grade serous carcinoma and those with persistent disease at completion of primary therapy have the worst outcomes. Patients with LGSPC seem to have a better prognosis than those with LGSOC.

Sentinel lymph node (SLN) sampling may provide staging information without exposing patients to risks of lymph node dissection. There is no consensus protocol for optimal pathologic handling of these specimens. This study compares 2 ultrastaging protocols of SLN in endometrial carcinoma (EC). All SLN were serially sectioned perpendicular to the long axis in 2 mm intervals and entirely submitted for routine hematoxylin and eosin (HE) processing. SLN negative by routine processing had ultrastaging (US) by one of the following: method 1 (M1), 5 HE levels at 250 μm intervals with 2 unstained slides at each level; pankeratin immunohistochemistry (IHC) performed on level 1 in cases with negative HE levels or method 2 (M2), 1 HE level + 2 unstained slides cut 250 μm into the tissue block; pankeratin IHC performed in cases with negative HE. Histologic subtype, numbers of SLN, positive SLN, non-SLN, positive non-SLN, and metastasis size were recorded. A total of 178 patients had 527 SLNs (1-16 per case; median, 2 SLN) sampled during hysterectomy for the following EC histotypes: endometrioid International Federation of Gynecology and Obstetrics grade 1/2, 117 (66%); endometrioid International Federation of Gynecology and Obstetrics grade 3, 18 (10%); serous, 20 (11%); carcinosarcoma, 11 (6%); clear cell, 9 (5%); and undifferentiated, 3 (2%). In all, 172 patients had ultrastaging: M1=65; M2=58. In total, 33 patients were SLN positive. Twenty-seven had SLN submitted for US: M1=11; M2=16. Eleven patients had additional SLN detected by US: M1=5; M2=6. Of these, 8 were patients whose SLN were only detected by US representing an increase of 32% in number of patients with positive SLN. Six patients (M1=2; M2=4) with negative SLN had a positive non-SLN. Mean size of ultrastage-detected metastasis was 0.24 mm for M1 and 0.38 mm for M2. Statistical analysis comparing M1 and M2 detected no statistically significant associations with respect to number of positive SLN detected, size of metastasis or false-negative rate and method. The methods performed similarly for both low-grade and high-grade EC. A more comprehensive US protocol had no significant advantages over a single wide interval and IHC in this study population. A pankeratin IHC stain enhances metastasis detection. Additional studies are required to further test this limited protocol as well as to evaluate the clinical significance of the low volume disease detected by ultrastaging.

Purpose The purpose of this study was to examine outcomes associated with hormonal maintenance therapy (HMT) compared with routine observation (OBS) after primary cytoreductive surgery and platinum-based chemotherapy in women with stage II to IV low-grade serous carcinoma of the ovary or peritoneum. Patients and Methods Eligibility criteria for patients from our database were: treatment with primary surgery followed by platinum-based chemotherapy, stage II to IV disease, at least 2 years of follow-up for patients who had not experienced recurrence, and adequate clinical information. The two groups were compared for progression-free survival (PFS) and overall survival, and a multivariable Cox regression analysis was performed. Subset analyses for patients who were disease free or had persistent disease were also performed. Results Between 1981 and 2013, 203 eligible patients—133 who underwent OBS and 70 who received HMT—were seen at our institution. Median PFS for patients who underwent OBS was 26.4 months, compared with 64.9 months for those who received HMT ( P < .001). No statistically significant difference in overall survival was observed between the two groups (102.7 v 115.7 months, respectively). For subgroups of women who were disease free or had persistent disease, median PFS was superior for those who received HMT (81.1 v 30.0 months; P < .001 and 38.1 v 15.2 months; P < .001, respectively). Women who received HMT had a significantly lower risk of disease progression compared with those who underwent OBS (hazard ratio, 0.44; 95% CI, 0.31 to 0.64; P < .001). Conclusion Women with stage II to IV low-grade serous carcinoma who received HMT after primary treatment had significantly longer PFS compared with women who underwent OBS. These findings warrant further investigation using a prospective trial design.

Background Strongyloides stercoralis is an intestinal nematode unique in its ability to replicate in the human host, allowing ongoing cycles of autoinfection, persisting for decades within the same host. Although usually asymptomatic, overwhelming infections can occur in Strongyloides and HTLV-1 co-infected individuals (SS/HTLV-1). Regulatory T cells (Tregs) are able to blunt specific Th2 responses necessary to control the parasite. We previously reported that peripheral blood Tregs are increased in SS/HTLV-1 and correlate with low Th2 responses. We hypothesized that Tregs are also increased at the site of infection in duodenal mucosa. Methods Paraffin embedded duodenal biopsies were obtained from 10 SS/HTLV-1 patients, 3 controls with non-parasitic chronic duodenitis, and 2 healthy controls. Immunohistochemistry was performed using monoclonal antibodies against human CD3, CD8, IgE and FoxP3. The number of cells were counted using a conventional light microscope. The number of CD3+, CD8+, FoxP3+ and IgE positive cells per 0.35 mm2 was measured using ImagePro Plus software comparing areas adjacent or distant from parasite material. Results In patients with SS/HTLV-1, T lymphocyte counts and CD8+ cells were lower in areas adjacent to the parasite compared to non-adjacent areas (CD3+: adjacent: 6.5 [Interquartile range (IQR: 2.8–12.3)]; non-adjacent: 24.5 [IQR: 20.9–34.4]; Mann-Whitney p = 0.0003; CD8+: adjacent: 4.5 [IQR: 2.3–11.8]; non-adjacent: 21 [IQR: 15.3–42.9]; Mann-Whitney p = 0.0011). Tregs cells in the intestines (FoxP3+ expressing cells) were increased in patients with SS/HTLV-1 compared with patients with chronic duodenitis (SS/HTLV-1: 1.5 [IQR: 0.7–2.3]; duodenitis controls: 0 [range 0–0.7]; healthy controls: 0; Mann-Whitney p = 0.034). There was also a trend towards fewer eosinophils adjacent to the parasites. Among SS/HTLV-1 patients the number of IgE expressing cells was increased for in areas not adjacent to the parasite compared to non-adjacent areas (ANOVA, p = 0.001). Conclusions Our data shows increased Treg cell numbers localized adjacent to the parasites in the duodenum SS/HTLV-1 patients. In addition, other T lymphocytes and IgE expressing cells were decreased adjacent to the parasites, suggesting an important role for Tregs in down-regulating local parasite effector responses., Author summary Strongyloidiasis is a parasitic infection found worldwide in warm, moist climates. In most people, Strongyloides causes a mild and chronic infection with few symptoms. However, some patients, including those infected with the Human T Lymphotrophic Virus 1 (HTLV-1), can get uncontrolled disease called hyperinfection, which can be fatal. To help determine why this infection is so serious in co-infected patients, we studied biopsies obtained from the small intestine from patients with both infections and compared them to control biopsies. The biopsies from patients with both Strongyloides and HTLV-1 had increased numbers of white blood cells in their biopsies. In particular they displayed a type of lymphocyte that downregulates immune responses. Some of them had increased numbers of cells called eosinophils in the intestines. These cells can help eliminate Strongyloides. However, they were not found near the parasite, suggesting that something near the parasite was suppressing the host response that would control infection. These studies provide more evidence that HTLV-1 suppresses the host response that controls Strongyloides and that the suppression occurs at the site of infection in the small intestines.

BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analysed by full COLD (co-amplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

ObjectiveBefore 2003, invasive endometrial stromal sarcomas (ESS) were classified into 2 categories, low-grade and high-grade ESS, according to the mitotic index. In 2003, the World Health Organization changed the definition and the diagnostic criteria. Before 2003, 20% to 35% low-grade ESS recurred, but WHO 2003–defined low-grade ESS has 10 years’ recurrence rates of less than 10%. With so few recurrences, the balance between treatment guaranteeing cure and overtreatment (“not too little” or “too much”) becomes increasingly important. However, primary treatment practices range from limited surgery only to extensive surgery combined with adjuvant chemotherapy and radiotherapy. We focused on the primary treatment of early-stage WHO 2003–defined low-grade ESS.MethodsWe evaluated the effect of different therapeutic strategies in 57 patients with International Federation of Gynecology and Obstetrics 2009 stages I to II expert-reviewed WHO 2003–defined low-grade ESS treated at a single institution between 1992 and 2007.ResultsThe patients’ median age was 43 years (range, 19–63 years). After 68 months’ median follow-up (range, 17–140 months), recurrence and mortality rates were 9% and 2%, respectively. The patients with WHO 2003–defined low-grade ESS with ovary-preserving primary surgery had a much higher recurrence rate (75%) than those without (2%; P < 0.0001). Lymphadenectomy, radical abdominal hysterectomy, and omentectomy did not influence survival. Ten patients refused chemotherapy. With univariate analysis, multiple-agent chemotherapy improved the prognosis (P = 0.02) With multivariate analysis, only ovary preservation-or-not surgery had independent prognostic value.ConclusionsIn International Federation of Gynecology and Obstetrics 2009 stage I to stage II WHO 2003–defined low-grade ESS, total abdominal hysterectomy with bilateral salpingo-oophorectomy is sufficient surgery, but ovary-preserving primary surgery increases the risk of recurrence. More extensive surgical procedures than total abdominal hysterectomy with bilateral salpingo-oophorectomy do not improve prognosis in early-stage WHO 2003–defined low-grade ESS. Chemotherapy may improve progression-free survival in early-stage low-grade ESS, but a large sample size is needed to confirm this.

The pathogenesis of orthostatic tremor (OT) remains unclear, although some evidence points to dysfunction in the brainstem or cerebellum. We used single voxel proton magnetic resonance spectroscopy (1H-MRS) (3 T) to investigate whether neurochemical changes underlie abnormal cerebellar or cortical function in OT. Fourteen OT patients and 14 healthy controls underwent 1H-MRS studies with voxels placed in midparietal gray matter and cerebellum (vermis and central white matter). Spectral analysis was analyzed using the software package LCModel (version 6.3). The absolute metabolite concentrations and ratios of total N-acetylaspartate + N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamate + glutamine to creatine were calculated. In midparietal gray matter spectra, we found a significant decrease in the absolute concentration of NAA in OT patients versus healthy controls (7.76 ± 0.25 vs 8.11 ± 0.45, P = 0.017). A similar decrease in NAA was seen in the cerebellar vermis (7.33 ± 0.61 vs 8.55 ± 1.54, P = 0.014) and cerebellar white matter (8.54 ± 0.79 vs 9.95 ± 1.57, P = 0.010). No differences in the other metabolites or their ratios were observed. Reductions in both cerebral cortical and cerebellar NAA suggest that there is neuronal damage or loss in OT, raising the intriguing question as to whether OT is a neurodegenerative disease. Along with clinical history and electrophysio0logical examination, 1H-MRS could serve as a useful diagnostic aid for OT.

Neuroendocrine carcinoma (NECa) of the endometrium is an uncommon tumor. In this study, we present the clinicopathologic features of 25 such cases. The patients ranged in age from 37 to 87 years (median, 57), and most commonly presented with vaginal bleeding. The tumors were either pure NECa (10) or mixed with other histotypes (15), most commonly endometrioid carcinoma. The NECas were large cell type (15), small cell type (4), or a mixture of both (6). NECa was under-recognized in 89% of referral/consultation cases. All tumors were positive for ≥ 1 neuroendocrine marker (chromogranin, synaptophysin, CD56). Additional immunohistochemical (IHC) studies were obtained in 18 cases, with positive results as follows: keratin cocktail (17), diffuse p16 (6), PAX-8 (6), CD117 (6), and TTF-1 (1). Mismatch repair protein expression by IHC was abnormal in 8 of 18 cases (6 MLH1/PMS2 loss; 1 MSH2/MSH6 loss; 1 MSH6 loss). According to FIGO staging, cases were distributed as follows: I (6), II (2), III (10), and IV (7). All patients underwent surgical treatment, and 20 patients received adjuvant therapy. Twelve patients died of disease (mean survival 12.3 months). Eleven patients were alive 5 to 134 months following diagnosis, including 7 who achieved a 5-year survival (3 stage I; 4 stage III). In summary, most of our endometrial NECas were large cell type, mixed with other histotypes, and under-recognized. These tumors tend to be PAX-8 negative and may be associated with microsatellite instability. The recognition of NECa may have an impact on the treatment of the patients affected by this disease. Although NECa usually has an aggressive behavior, 28% of our patients survived at least 5 years.

The assessment of prognosis is an essential part of the evaluation of all patients with liver cirrhosis. Currently continues to develop new models to optimize forecast accuracy mortality score is calculated by the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD).Compare the prognostic accuracy of hospital mortality and short-term mortality CTP, MELD and other models in patients with decompensated liver cirrhosis.Prospective descriptive study, comparison type of diagnostic test that included 84 patients. The score CTP, MELD and other models were calculated on the first day of hospitalization. The prognostic accuracy of mortality was assessed by the area under the ROC curve (AUROCs) of score CTP, MELD and other models.Hospital mortality and mortality in the short-term monitoring was 20 (23.8%) and 44 (52.4%), respectively. The AUROCs CTP, MELD, MELD Na, MESO, iMELD, RefitMELD and RefitMELD Na to predict hospital mortality was 0.4488, 0.5645, 0.5426, 0.5578, 0.5719, 0.5598 and 0.5754; and to predict short-term mortality was 0.5386, 0.5747, 0.5770, 0.5781, 0.5631, 0.5881 and 0.5693, respectively. By comparing each AUROCs of the CTP score, MELD and other models proved to be no better than the other (p0.05).This study has not shown the predictive utility of the CTP score, MELD and other models (MELD Na, MESO, iMELD, Refit Refit MELD and MELD Na) to evaluate hospital mortality or short-term mortality in a sample of patients with decompensated cirrhosis of the Hospital Cayetano Heredia.

Cardiovascular disease is one of the leading causes of death worldwide. Epicardial adipose tissue (EAT) has emerged as an independent predictor of high cardiometabolic risk. Cardiovascular MRI has proven to be a feasible and reproducible method to assess EAT quantitatively. We present a novel approach for the automated quantification of EAT using "a priori" anatomical information. We extracted a region of interest (ROI) in the end-diastolic heart phase followed by a GVF-snake algorithm to smooth it. For the EAT and endocardial boundary detection, a Law's texture filter is applied. Left and right ventricle are localized using spatial prior information. Then, thresholding is applied to quantify the cardiac muscle. For the EAT, it is differentiated from the paracardial fat by K-cosine curvature analysis. Results for 10 morbidly obese patients show no significant differences between manual and automatic quantification with a remarkable time and effort saving between them.

Cervical plasticity is partially attributed to subepithelial stromal cells. Knowing this population of cells in its variable physiologic states, with its immunophenotypic variations, will lead to better understanding of neoplastic processes related to these stromal cells. We reviewed slides of cervices from premenopausal, postmenopausal, and postpartum patients and used mesenchymal immunohistochemical stains. Results demonstrate 2 distinct subepithelial compartments, within the ectocervix and the endocervix/transformation zone. The endocervix/transformation zone has twice the number of stromal cells as the ectocervix, regardless of age. Ectocervical stromal cells are desmin+/smooth muscle actin (SMA)−, and endocervical stromal cells are desmin+/SMA−. In postpartum/premenopausal patients, the cervix has less desmin+ ectocervical and SMA− endocervical cells. In postmenopausal/prolapse patients, the cervix has no desmin+ ectocervical cells. Desmin+/SMA, calponin, caldesmon, myogenin, myoD1, CD34− cells could represent unusual myofibroblasts that should not be confused with a neoplastic process, especially if a mass is not present.

Endocervical adenocarcinomas (ECAs) uncommonly metastasize to the ovary; however, when they do they sometimes closely mimic a mucinous/endometrioid ovarian primary tumor. Here, 2 cases of mixed moderately differentiated ECA and high-grade cervical neuroendocrine carcinoma in which the ECA component metastasized to the ovary have been delineated and reported. In both cases, the primary tumor and the metastatic tumor were diffusely positive for p16 and high-risk human papillomavirus. Although similar to previously reported cases of adenocarcinoma in situ and invasive ECAs with ovarian involvement, none of the cases reported to date had concurrent neuroendocrine carcinoma with metastasis of the lower-grade component. In this respect, our cases are unique. The presence of lower uterine segment involvement in both cases and high-risk human papillomavirus positivity in the primary and metastatic tumors suggest a metastatic process, perhaps through transtubal spread, rather than independent primaries.

BACKGROUND: Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown. METHODS: Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow-up data were also analyzed. RESULTS: Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence. CONCLUSIONS: PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long-term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.

BACKGROUND: A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. METHODS: The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. RESULTS: Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). CONCLUSIONS: Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Cancer 2012;118: 3087–94. © 2011 American Cancer Society.

Summary Background & aims To assess the effect of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and anti-oxidants on the incidence of organ dysfunction and nosocomial infections in septic patients with acute lung injury or acute respiratory distress syndrome (ARDS) compared with a standard enteral diet. Methods This prospective, randomized, open-label study was performed in 11 Spanish intensive care units (ICU). Adult patients with sepsis and acute lung injury or ARDS were randomly allocated to receive either an EPA-GLA diet or a control diet. Results Of the 198 patients that were eligible, 160 were randomized and 132 were studied. Patient demographics, APACHE II and SOFA scores, and nutritional variables on admission were similar between the EPA-GLA diet and control diet groups. The EPA-GLA diet group showed a trend toward a decreased SOFA score, but it was not significant. No differences were observed in the PaO 2 /FiO 2 ratio or the days on mechanical ventilation between the groups. Incidence of infections was similar in the groups. The control group stayed longer in the ICU than the EPA-GLA diet group (16 vs. 18; p = 0.02). Conclusions A diet enriched with EPA, GLA, and anti-oxidants does not improve gas exchange or decrease the incidence of novel organ failures in critically ill septic patients with acute lung injury or ARDS. Patients treated with the EPA-GLA diet stayed in the ICU for less time, but we did not find any differences in infectious complications.

Objectives: To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1–4 endometrial endometrioid adenocarcinomas.Study Design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2–5 markers positive).Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2–4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p=0.005).Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2–4 endometrial endometrioid adenocarcinomas.

The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, P

Objective 10% of women with serous ovarian cancer have low-grade carcinomas. These patients are diagnosed at a younger age, have a longer overall survival and a lower response rate to platinum-based chemotherapy compared to women with high-grade serous ovarian carcinoma. It remains unclear if these features are similar in women with low-grade primary peritoneal cancer (PPC). To further explore this issue, a retrospective analysis of the clinical and pathologic characteristics of women with low-grade serous PPC was performed. Methods A retrospective study of 53 patients with low-grade serous PPC evaluated at a single institution from 1986 to 2009 was performed. All cases were reviewed by a gynecologic pathologist to confirm low-grade serous PPC. Results Median age at diagnosis was 51.7years (range 27.1–82.4). 46 patients (86.8%) underwent primary surgery, with optimal tumor reduction achieved in 30 patients (65.2%). 48 patients (90.6%) received chemotherapy as part of their initial treatment. At the completion of primary treatment, 66.7% of patients were noted to have persistent or progressive disease. With a median follow-up of 66.1months, the 5-year PFS was 16%, yet the 5-year OS was 69%. Conclusion To our knowledge, this is the first report of women with low-grade serous PPC. Similar to low-grade serous ovarian carcinoma, patients with low-grade serous PPC have high rates of persistent disease at the completion of primary treatment yet a long overall survival. Further study focusing specifically on low-grade serous ovarian and primary peritoneal carcinomas is needed to determine the optimal treatment of these diseases.

Fungal allergies can be detected by the skin prick test with extracts of the organisms, but not all fungi, including the basidiomycetes, are being examined. We determined the level of sensitization to basidiomycetes in allergic subjects and compared their reactivity to commercial extracts commonly used to detect allergies. Crude spore extracts of the basidiomycetes Ganoderma applanatum, Chlorophyllum molybdites, and Pleurotus ostreatus, which are known to release numerous spores, were examined along with commercial extracts on 33 subjects with asthma, allergic or non-allergic rhinitis. Overall, affected subjects showed the highest reactivity to mites (36%), followed by Ganoderma applanatum (30%), grass (27%) Chlorophyllum molybdites (12%) and Pleurotus ostreatus (12%). Allergic rhinitis patients were most reactive to mites (58%), grass (42%), Ganoderma applanatum (25%), Penicillium spp. (25%), and cat (17%). Those with asthma primarily responded to mites (44%), Ganoderma applanatum (44%), grass (33%), and Pleurotus ostreatus (22%). IgE levels correlated with positive basidiomycetes extracts. This finding, coupled with higher reactivity to basidiospores as compared to mitospores, and the similar sensitivities of patients to G. applanatum and mites, suggest that basidiomycetes are important allergen sources in the tropics.

Fifteen to thirty percent of cases with histologically confirmed CIN2-3 in cervical biopsies regress spontaneously (ie, show CIN1 or less in the follow-up cervical cone). The balance between immune-reactive cells from the host and high-risk human papillomavirus (hrHPV) genotypes may provide a biological explanation for this phenomenon. We retrospectively studied 55 cases of CIN2-3 in a cervical biopsy with subsequent cervical cone to assess whether hrHPV genotypes (by AMPLICOR and Linear Array tests) CD4, CD8, CD25, CD138 and Foxp3 cells (by quantitative immunohistochemistry) in the cervical biopsies can predict regression (defined as CIN1 or less in the follow-up cone biopsy). Eighteen percent of the CIN2-3 cases regressed (median biopsy-cervical cone time interval: 12.0 weeks, range: 5.0-34.1 weeks). HPV-16 correlated with low CD8(+) and high CD25(+). None of the regressing CIN2-3 lesions contained HPV-16. The regressing CIN2-3 lesions had lower numbers of stromal CD138(+) and higher numbers of stromal CD8(+) cells; higher stromal and intra-epithelial ratios of CD4(+)/CD25(+) cells; higher ratios of CD8(+)/CD25(+) cells and lower ratios of CD8(+)/CD4(+), CD138(+)/Foxp3(+) and CD25(+)/Foxp3(+) cells in the stroma. With multivariate survival analysis, stromal CD8(+) cell numbers, CD4(+)/CD25(+) cell ratios and CD138(+) cell numbers are found to be independent regression predictors. In conclusion, in non-HPV-16 CIN2-3 lesions, assessing stromal immune cells can be a useful prognostic indicator of regression or persistence. Modern Pathology (2010) 23, 1231-1240; doi:10.1038/modpathol.2010.109; published online 28 May 2010

Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the vulva with only 29 cases reported. We present the clinicopathologic and immunohistochemical features of 13 such cases seen in our institution over a period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean, 46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically, all the cases showed typical features of DFSP. In 1 case, myxoid changes were also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade malignant peripheral nerve sheet tumor were initially considered. All 11 cases tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were initially treated with excisional biopsy, wide local excision, or radical vulvectomy. Local recurrences occurred in 7 cases. One patient also developed distant metastases. All recurrences were treated surgically; 1 patient also received chemotherapy and radiotherapy and another received imatinib (Gleevec). Follow-up data ranging from 2 to 444 months was available for all patients. Nine patients had no evidence of disease, 2 patients were alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. DFSP affects women of a wide age range and has a propensity to recur locally. The frequent expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the findings of other investigators and supports the use of imatinib (Gleevec) in cases that are recurrent or not amenable to surgery.

Objective. This study aimed to determine the safety and feasibility of robotic radical trachelectomy and bilateral pelvic lymphadenectomy. We also describe our surgical technique. Methods. This is a retrospective review of all patients who underwent robotic radical trachelectomy and bilateral pelvic lymphadenectomy from October 2008 to May 2009. We analyzed our data to evaluate the safety and feasibility of this surgery. Results. This analysis included 4 patients with early-stage squamous cell carcinoma of the cervix. The median body mass index was 27.1 kg/m 2 (range, 22.7 to 39.1). Three patients had stage IA2 adenocarcinoma; 1 patient had stage IA1 adenocarcinoma with lymph-vascular space invasion. The median operative time was 339.5 min (range, 245 to 416). The median console time was 282.5 min (range, 217 to 338). The median estimated blood loss was 62.5 ml (range, 50 to 75). There were no conversions to laparotomy. There were no intraoperative complications. No patient required blood transfusion. The median length of hospital stay was 1.5 days (range, 1 to 2). One patient experienced a postoperative complication, transient left lower extremity sensory neuropathy. No patient had residual tumor in the trachelectomy specimen, and no patient underwent adjuvant therapy. The median number of pelvic lymph nodes removed was 20 (range, 18 to 27). The median time to a successful voiding trial was 8 days (range, 7 to 9). The median follow-up was 105 days (range, 82 to 217). There were no recurrences. Conclusion. Robotic radical trachelectomy and bilateral pelvic lymphadenectomy is feasible and safe and should be considered for patients desiring fertility-sparing surgery.

Experience with lymph node involvement (LNI) in ovarian serous tumors of low malignant potential (OSLMP) is limited, which has led to an uncertainty about the clinical significance of this phenomenon. In this study, we present the clinicopathologic features of 36 cases of OSLMP with LNI. A control group of 36 OSLMP with no LNI was established for comparison. Parameters recorded for both the study and the control group included Federation of International Gynecology and Obstetrics (FIGO) stage, microinvasion and micropapillary/ cribriform pattern in the OSLMP, invasive and noninvasive peritoneal implants, the total number of lymph nodes, the number of lymph node sites sampled and their location (pelvic, periaortic, and abdominal), and the greatest gross lymph node dimension per each site. LNI pattern (single cells, clusters, micropapillae, small papillae, papillae, glandular, and intra-glandular) and the greatest microscopic linear dimension of LNI foci were also recorded. Statistical comparisons between the study and the control group were made using the Fisher exact test and χ 2 test. The log-rank test was used to evaluate the impact of LNI on disease-free survival and overall survival. Clinical follow-up was obtained from the review of medical records and from phone calls to the attending physicians. In terms of general pathologic features, the experimental group had a significantly higher rate of invasive (P = 0.01) and noninvasive (P = 0.002) implants compared with the control group. In 22% of the cases in the study group, LNI represented the only site of extraovarian disease. The highest yield of lymph nodes with LNI was obtained from pelvic lymph nodes (90%), with a sampling of 3 to 4 sites. The average gross lymph node size range was comparable between the study (0.2 to 4.0 cm) and the control (0.2 to 4.3 cm) groups. The patients in the study group (38.5 y) were on average 10 years younger than those in the control group (49.1 y). Clinical information and follow-up were available for 86% (31) of the cases in both groups. No recurrences were seen in the control group. In the study group, 11% (4) patients are alive with recurrent disease and 6% (2) died of the disease. Histologic diagnosis of recurrences was available in 5 cases and showed low-grade serous carcinoma. Two cases recurred exclusively in the lymph nodes. Although the study group had a higher proportion of patients with disease recurrence and death disease, when the two groups were compared by looking only at FIGO stage III cases, LNI did not have a statistically significant impact on disease-free survival (P = 0.09) or the overall survival (P = 0.40). There was no relationship between the greatest linear dimension of LNI or the pattern of LNI and disease recurrence. In summary, in cases of OSLMP, LNI is associated with a higher rate of invasive and noninvasive implants, but is not an independent predictor of disease-free survival or overall survival. Women under 40 years of age and with peritoneal implants may be at particular risk for LNI. Lymphadenectomy upstages a significant proportion of patients with LNI, highlighting the need for lymph node sampling in all OSLMP cases. Grossly unremarkable lymph nodes are not at a decreased risk of LNI. The pattern and the greatest linear dimension of LNI foci were not shown to have prognostic significance.