Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL.

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

Infertility knowledge and treatment beliefs among African American women in an urban community.

BACKGROUND: To assess infertility knowledge and treatment beliefs among African American women in an urban community in Atlanta, Georgia. METHODS: This was a cross sectional study at a safety net hospital. A convenience sample of a total of 158 women receiving outpatient obstetrical or gynecologic care from March-April 2017 were recruited. Infertility knowledge and treatment beliefs were assessed using a previously applied and field-tested survey from the International Fertility Decision Making Study. RESULTS: The mean infertility knowledge score was 38.15% for total subjects. Those with a higher level of education (p < 0.0001) and those with paid employment (p = 0.01) had a significantly higher level of infertility knowledge. Those who had a history of infertility therapy were significantly more likely to agree with negative treatment beliefs (p = 0.01). There was no significant difference in infertility knowledge or treatment beliefs based on age, sexuality, parity or being pregnant at the time of survey completion. CONCLUSIONS: African American women in our urban clinic setting seem to have a limited level of knowledge pertaining to infertility. Further research is needed to understand how differences in knowledge and beliefs translate into infertility care decision-making and future childbearing.

Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma--results of the UK HD3 relapse treatment strategy.

The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005, 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4-6 cycles of EPIC [etoposide, prednisolone, ifosfamide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5-year overall survival [OS] and progression-free survival from relapse was 75·8% [64·8-83·9] and 59·9% [48·3-69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19-1·18] for those with a time from end of treatment to relapse of 3-12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04-0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse. Survival outcome in children with primary refractory HL is poor.

Discrimination between benign, primary and secondary malignancies in lymph nodes from the head and neck utilising Raman spectroscopy and multivariate analysis.

BACKGROUND: The potential use of Raman spectroscopy (RS) for the detection of malignancy within lymph nodes of the head and neck was evaluated. RS measures the presence of biomolecules by the inelastic scattering of light within cells and tissues. This can be performed in vivo in real-time. METHODS: 103 lymph nodes were collected from 23 patients undergoing surgery for suspicious lymph nodes. Five pathologies, defined by consensus histopathology, were collected including reactive nodes (benign), Hodgkin's and non-Hodgkin's lymphomas, metastases from both squamous cell carcinomas and adenocarcinomas. Raman spectra were measured with 830 nm excitation from numerous positions on each biopsy. Spectral diagnostic models were constructed using principal component analysis followed by linear discriminant analysis (PCA-LDA), and by partial least squares discriminant analysis (PLS-DA) for comparison. Two-group models were constructed to distinguish between reactive and malignant nodes, and three-group models to distinguish between the benign, primary and secondary conditions. RESULTS: Results were validated using a repeated subsampling procedure. Sensitivities and specificities of 90% and 86% were obtained using PCA-LDA, and 89% and 88% using PLS-DA, for the two-group models. Both PCA-LDA and PLS-DA models were also found to be very successful at discriminating between pathologies in the three-group models achieving sensitivities and specificities of over 78% and 89% for PCA-LDA, and over 81% and 89% for PLS-DA for all three pathology groups. CONCLUSION: Raman spectroscopy and chemometric techniques can be successfully utilised in combination for discriminating between different cancerous conditions of lymph nodes from the head and neck.

Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy.

Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 × the upper limit of normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP (cyclophosphamide, vincristine, and prednisone) therapy. Central pathology revealed approximately 50% with classical features of primary MLBL. Five-year event-free survival for the stage III MLBL and non-MLBL DLBCL groups was 66% (95% confidence interval [CI], 49%-78%) and 85% (95% CI, 71%-92%), respectively (P < .001; 14%). The 5-year overall survival in the 42 MLBL patients was 73% (95% CI, 56%-84%). We conclude that MLBL in adolescent patients is associated with significantly inferior event-free survival compared with stage III non-MLBL DLBCL and can be of multiple histologies. Alternate treatment strategies should be investigated in the future taking into account both adult MLBL approaches and more recent biologic findings in adult MLBL.

Primary follicular lymphoma of the testis in children and adolescents.

This study reports 6 cases of primary follicular lymphoma of the testis (PFLT) in children and adolescents correlated with clinical presentation, pathologic features, treatment, and outcome. All 6 patients (age, 3 to 16 y; median, 4 y) had PFLT grade 3 with disease limited to the testis, completely resected and treated with 2 courses of chemotherapy (cyclophosphamide, vincristine, prednisone, doxorubicin). Event-free survival was 100% (follow-up: median, 73 mo; mean, 53 mo; range, 6 to 96 mo). In conclusion, clinical outcome in children and adolescents with PFLT is excellent with treatment including complete surgical resection and 2 courses of cyclophosphamide, vincristine, prednisone, doxorubicin.

Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (≥ 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study.

PURPOSE: Adolescents (age 15 to 21 years) compared with younger children with mature B-cell non-Hodgkin's lymphoma (NHL) have been historically considered to have an inferior prognosis. We therefore analyzed the impact of age and other diagnostic factors on the risk of treatment failure in children and adolescents treated on the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) trial. PATIENTS AND METHODS: Patients were divided by risk: group A (limited), group B (intermediate), and group C (advanced), as previously described. Prognostic factors analyzed for event-free survival (EFS) included age (< 15 v ≥ 15 years), stage (I/II v III/IV), primary site, lactate dehydrogenase (LDH), bone marrow/CNS (BM/CNS) involvement, and histology (diffuse large B-cell lymphoma v mediastinal B-cell lymphoma v Burkitt lymphoma or Burkitt-like lymphoma). RESULTS: The 3-year EFS for the whole cohort was 88% ± 1%. Age was not associated as a risk factor for increased treatment failure in either univariate analysis (P = .15) or multivariate analysis (P = .58). Increased LDH (≥ 2 × upper limit of normal [ULN] v < 2 × ULN), primary site, and BM-positive/CNS-positive disease were all independent risk factors associated with a significant increase in treatment failure rate (relative risk, 2.0; P < .001, P < .012, and P < .001, respectively). CONCLUSION: LDH level at diagnosis, mediastinal disease, and combined BM-positive/CNS-positive involvement are independent risk factors in children with mature B-cell NHL. Future studies should be developed to identify specific therapeutic strategies (immunotherapy) to overcome these risk factors and to identify the biologic basis associated with these prognostic factors in children with mature B-cell NHL.

Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation.

OBJECTIVE: Endometrial cancer is classified into: Type I estrogen-dependent endometrioid adenocarcinoma, with good prognosis and type 2 non-estrogen-dependent cancer with serous or clear cell histology and poor prognosis. Grade 3 endometrioid cancers (G3 EEC), share features of type 1 and type 2 cancer and have not been classified as either. This study compares immunohistochemistry and survival in G3 EEC and type 2 cancers. METHODS: Clinicopathological data compared with immunohistochemistry and survival in 156 consecutive patients with poor prognosis cancer-G3 EEC, uterine papillary serous (UPSC) and clear cell carcinoma (CC), sarcoma, carcinosarcoma and endometrial tumors of mixed histology. 131 (84%) datasets were complete, 25 tumors comprising sarcoma, carcinosarcoma or mixed histologies were excluded. Tissue microarray constructed and tested for estrogen receptor (ER), progesterone receptor (PR), p53 and human epidermal growth factor receptor-2 (Her-2). RESULTS: There was no significant difference in the mean age for G3 EEC (n=68) and USPC + CC (n=38), (68.01 and 67.08 respectively, p=0.697) or stage at diagnosis (p=0.384). For ER, PR, p53 and Her-2, there was no significant difference in marker positivity between G3 EEC and UPSC + CC (p=0.612, 0.132, 0.16 and 0.132 respectively). With a mean follow-up time 148 months Disease specific and recurrence-free survival between G3 EEC and USPC + CC was similar (p=0.842 and 0.863). CONCLUSION: G3 EEC and UPSC + CC share similar clinical, immunohistochemistry and poor survival. G3 EEC is better characterised as type 2 cancer and should be treated with similar adjuvant therapy to UPSC/CC.

Clinical outcome in children and adolescents with Hodgkin lymphoma after treatment with chemotherapy alone - the results of the United Kingdom HD3 national cohort trial.

PURPOSE: To assess the efficacy of a standardised hybrid chemotherapy treatment programme for Hodgkin lymphoma (HL) in a national series of children and adolescents. PATIENTS AND METHODS: The 381 assessable patients, treated between March 2000 and April 2005 in the United Kingdom Children's Cancer Study Group trial, were reviewed to evaluate overall survival (OS), disease free survival (DFS) and deaths. Protocol treatment for stages 2-4 offered a hybrid programme of ChlVbPP (chlorambucil, vinblastine, prednisolone, procarbazine) alternating with ABVcD (doxorubicin, bleomycin, vincristine, dacarbazine). Patients with stage I disease only were offered involved field radiation alone or hybrid chemotherapy. RESULTS: With a median follow up of 5.1 years (range 0.5-8.4 years), the 5 years OS and DFS for all patients was 97% and 78%, respectively. By multivariate analysis, mediastinal and stage IV disease at presentation were the only factors that affected achieving a complete response. The 5-year DFS rate for patients with stage IV disease was 55% whilst patients with mediastinal disease had a 2-fold higher risk of an event. CONCLUSIONS: This study demonstrated that multi-agent chemotherapy alone is insufficient treatment for patients with mediastinal and stage IV disease.

Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report.

PURPOSE: To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m(2) - day 1], vinblastine [6 mg/m(2) - days 1 and 8] and prednisolone [40 mg/m(2) - days 1-7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL]. PATIENTS AND METHODS: Fifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4-17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel. RESULTS: Of the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n=7] or radiotherapy [n=2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE ± 6%) and 100%, respectively. No significant early toxicity was observed. CONCLUSIONS: Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity.

Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study.

PURPOSE: The prognostic value of pathologic characteristics of childhood ALK-positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed. PATIENTS AND METHODS: All 375 patients with systemic ALK-positive ALCL included in an international trial launched by the European Intergroup for Childhood Non-Hodgkin's Lymphoma were reviewed by an international panel of pathologists based on conventional hematoxylin and eosin-stained and immunostained sections and classified according to the 2001 WHO classification. RESULTS: A small-cell (SC) or lymphohistiocytic (LH) component was observed in 114 (32%) of 361 patients, whereas ALCL of common type was diagnosed in 235 (65%) of 361 patients. Regarding the histologic subtyping of patients within the two categories of ALCL (with v without SC/LH component), the concordance between the national and international reviews was quite good, with a κ index equal to 0.67 (95% CI, 0.57 to 0.75). The presence of an SC/LH component was significantly associated with a high risk of failure (hazard ratio [HR], 2.0; 95% CI, 1.3 to 3.0; P = .002) in the multivariate analysis controlling for clinical characteristics, as well as the perivascular pattern (HR, 1.7; 95% CI, 1.1 to 2.7; P = .01), whereas CD3 positivity was significantly associated with a high risk of failure only in univariate analysis. CONCLUSION: Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment.

Gonadotropin-releasing hormone agonist increases expression of osmotic response genes in leiomyoma cells.

OBJECTIVE: To characterize hyperosmolarity-responsive genes in leiomyoma cells and determine whether gonadotropin-releasing hormone (GnRH) agonist treatment altered their expression. DESIGN: Laboratory study. SETTING: University hospital. PATIENT(S): None. INTERVENTION(S): Cell culture under hypertonic conditions and with GnRH agonist treatment, RNA isolation, and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Expression of nuclear factor of activated T cells 5 (NFAT5), aldose reductase (AR), and sodium myo-inositol transporter 1 (SMIT) messenger RNA (mRNA) in immortalized leiomyoma and patient-matched myometrial cells. RESULT(S): Leiomyoma cells had increased basal expression of NFAT5 mRNA (1.7±0.08-fold) compared with myometrial cells. The NFAT5 increased further in leiomyoma cells cultured under hyperosmolar conditions (3.0±0.46-fold at 50 mM NaCl and 3.3±0.48-fold at 100 mM NaCl). The NFAT5-regulated mRNA transcripts for AR and SMIT were increased in untreated leiomyoma cells compared with myometrial cells and further increased in leiomyoma cells exposed to osmotic stress. The NFAT5 transcripts were decreased with low-dose GnRH agonist treatment but increased with supraphysiologic doses. CONCLUSION(S): Expression of hyperosmolarity genes was increased in leiomyoma cells relative to myometrial cells. Pharmacologic concentrations of GnRH agonist decreased NFAT5 expression, suggesting that water flows out of leiomyoma cells at pharmacologic doses.

Why leiomyomas are called fibroids: the central role of extracellular matrix in symptomatic women.

Uterine leiomyomas are highly prevalent and symptomatic tumors of women in their reproductive years. The morbidity caused by these tumors is directly related to increasing size. Leiomyoma cells do not rapidly proliferate; instead, the tumors grow primarily due to excessive production of disorganized extracellular matrix (ECM). The aberrant ECM results from excessive production of collagen subtypes and proteoglycans, increased profibrotic cytokines including transforming growth factors beta1 and beta3, and decreased or disrupted matrix metalloproteinases. These alterations result in the development of an ECM that is exceptionally stable. As a result, therapeutic interventions must redirect leiomyoma cells toward extracellular matrix dissolution, rather than solely inhibiting cell proliferation. Gonadotropin-releasing hormone analogues and selective progesterone receptor modulators with demonstrated clinical efficacy provide such a change in abnormal extracellular matrix formation by leiomyoma cells, inhibiting and reversing the fibrotic process. Novel therapies using pathways distinct from gonadal hormones, including antifibrotics, retinoic acid, peroxisome-proliferator-activated receptor gamma ligands, and curcumin, provide promise for a future with improved therapeutic options for women suffering from uterine leiomyomas.

Use of F 18-fluoro-D-glucose-positron emission tomography-computed tomography to localize a hilar cell tumor of the ovary.

OBJECTIVE: To describe provocative testing and alternative imaging strategies used to localize an androgen-producing tumor in a 58-year-old woman with severe hirsutism. DESIGN: Case report. SETTING: Clinical Research Center. PATIENT(S): A 58-year-old woman who was seen for evaluation of severe hirsutism. INTERVENTION(S): Serum androgen levels were measured at baseline, 4 hours after administration of 2000 IU of hCG, and 11 days after administration of 3.75 mg of leuprolide acetate (LA). Magnetic resonance imaging and F 18-fluoro-D-glucose-positron emission tomography-computed tomography (FDG-PET/CT) were performed. MAIN OUTCOME MEASURE(S): Description of preoperative provocative testing and imaging. RESULT(S): In response to hCG, T rose from 243 to 288 ng/dL then decreased to 233 ng/dL after LA administration. The FDG-PET/CT scan demonstrated focal hypermetabolism in the right pelvis, corresponding to a soft-tissue density on the noncontrast CT scan. Magnetic resonance images were correlated with the PET/CT, and the right ovary was identified. Right salpingo-oophorectomy was performed, and final pathologic examination revealed a hilar cell tumor with ovarian cortical hyperplasia. CONCLUSION(S): This case demonstrates the utility of provocative testing in the evaluation of a patient with severe hirsutism and illustrates the value of FDG-PET/CT when traditional imaging is nondiagnostic.

Will decreasing assisted reproduction technology costs improve utilization and outcomes among minority women?

OBJECTIVE: To evaluate assisted reproduction technology (ART) usage and outcomes in minority women seeking care at enhanced access, military ART programs. DESIGN: Retrospective cohort. SETTING: Federal ART programs. PATIENT(S): Two thousand fifty women undergoing first cycle, fresh, nondonor ART from 2000 to 2005. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rate of ART use, clinical pregnancy rate, live birth rate. RESULT(S): African American women had an almost fourfold increased use of ART and Hispanic women had decreased use. Clinical pregnancy rates were significantly lower for African American women compared with white women (46.1% vs. 52.6%, relative risk [RR] 0.88; 95% confidence interval [CI], 0.78-0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74; 95% CI, 0.63-0.91). CONCLUSION(S): Economics appear to influence ART use by African American women but not Hispanic women. Despite increased use by African American women, outcomes in this group were worse when compared with Caucasian women. Improving access through decreased cost may increase use by some but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups.

Recruitment and retention of women for clinical leiomyoma trials.

BACKGROUND: Subject recruitment and retention in clinical leiomyoma trials is challenging. We evaluated strategies to increase patient enrollment and completion in leiomyoma trials. MATERIALS AND METHODS: Randomized trials for treatment of symptomatic leiomyoma published from 2000 through 2008 were evaluated and thirteen trials were selected. Subject enrollment and completion rates, recruitment methods and reasons for patient drop-out were assessed. RESULTS: Recruitment by study personnel or clinic staff during evaluation for symptomatic leiomyoma was the most common strategy for enrollment. Additional methods included local media, internet postings and physician referrals. Seven to 85% of patients enrolled after screening, with a median enrollment of 70%. Sixty-five to 100% of patients completed the study after enrollment with a median completion rate of 89%. Reasons for drop-out at the screening stage included failure to meet inclusion criteria, patient refusal and patient preference for specific treatment. Commonly reported reasons for drop-out after enrollment were refusal of treatment following randomization, adverse reaction to study intervention and non-compliance with study protocol or follow-up visits. CONCLUSION: Women with symptomatic uterine leiomyomas may be attracted to participate in leiomyoma trials, however desire for specific treatment and persistent symptoms following intervention may hinder their participation. Randomization to placebo treatment and stringent inclusion criteria appear to adversely impact accrual. A wide range of recruiting tactics is needed and media sources or direct mailings may prove particularly effective to improve subject recruitment and retention in clinical leiomyoma trials.

Fourier transform infrared spectroscopic studies of T-cell lymphoma, B-cell lymphoid and myeloid leukaemia cell lines.

This paper presents Fourier transform infrared (FT-IR) spectroscopy to characterise spectral differences that distinguish cells derived from human T-cell lymphoma, B-cell lymphoid, and myeloid leukaemia cell lines. This methodology is based on spectral measurements of major cellular biochemical constituents and multivariate spectral processing. Major spectral differences were observed in the 1800-900 cm(-1) 'fingerprint' spectral region. Bands in the averaged spectra for each cell line were assigned to major biochemical constituents including: proteins, lipids, carbohydrates and nucleic acids. Multivariate statistical analysis of the spectra was carried out to develop a classification model to discriminate the five cell types. The results show that FT-IR spectroscopy displays high sensitivity and specificity when discriminating between T-cell lymphoma, B-cell lymphoid, and myeloid leukaemia cells based on intrinsic biomolecular signatures. FT-IR spectroscopy in combination with multivariate statistical analysis provides an important insight into T-cell lymphoma, B-cell lymphoid, and myeloid leukaemia cell line identification. In conclusion, this paper demonstrates a potential for this technique to be used in developing a clinical tool for the detection and identification of haematological malignancies.

A gastrointestinal stromal tumor in a patient with multiple endocrine neoplasia type 2A and metastatic medullary thyroid cancer to the ovaries.

OBJECTIVE: To describe the first reported case of a patient with multiple endocrine neoplasia type 2A and a gastrointestinal stromal tumor, as well as the second reported case of metastatic medullary thyroid cancer to the ovary. METHODS: We present the clinical, imaging, surgical, and pathologic findings of the study patient and review the relevant literature. RESULTS: A 57-year-old woman with a clinical diagnosis of multiple endocrine neoplasia type 2A presented with a new mass in the right lower quadrant. Surgical exploration identified a 5-cm pedunculated small-bowel mass approximately 25 cm from the ileocecal junction, as well as bilaterally firm ovaries. Bilateral oophorectomy revealed medullary thyroid cancer in both ovaries and fallopian tubes. Pathology of the resected mass revealed a gastrointestinal stromal tumor of uncertain malignant potential, mitotic rate of 1/50 per high-power field, with positive staining for c-kit and smooth muscle actin and negative staining for CD34 and S-100. CONCLUSIONS: This case is the first description of a gastrointestinal stromal tumor in a patient with multiple endocrine neoplasia type 2A, potentially representing a new paraganglioma/gastrointestinal stromal tumor syndrome. This case also highlights the possibility of the ovary as a metastatic site for medullary thyroid cancer.

Ovarian response in women undergoing ovarian stimulation after myomectomy.

OBJECTIVE: To examine ovarian response in infertile women undergoing ovarian stimulation after abdominal myomectomy. DESIGN: Case report. SETTING: Academic medical research center. PATIENT(S): Four infertile women with known fibroids who had a failed assisted reproductive technology (ART) cycle followed by an abdominal myomectomy. INTERVENTION(S): Infertile women with known fibroids who had a failed ART cycle, from January 2000 to December 2006, followed by an abdominal myomectomy and a subsequent ART cycle. MAIN OUTCOME MEASURE(S): Ovarian function before (baseline) and after myomectomy was assessed by age, day 3 and day 10 FSH levels, days of stimulation, total gonadotropins used, peak E(2) level, the number of oocytes retrieved and embryos obtained, the number of high-grade embryos, and pregnancy outcome. RESULT(S): The mean age was 35 and 36 years before and after myomectomy, respectively. All subjects had uterine factor infertility. Two of these women also had tubal factor infertility, and one had endometriosis and male factor infertility. There was no difference in ovarian response before and after myomectomy. CONCLUSION(S): As expected, abdominal myomectomy did not adversely affect ovarian response in infertile women undergoing ovarian stimulation after a failed ART cycle. Larger randomized prospective studies are needed to accurately assess whether myomectomy has a negative impact on ovarian response.

Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French-American-British (FAB) international study group.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) makes up 10-20% of pediatric non-Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B-cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c-Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non-GC subtypes, and the expression of Bcl2 and c-Myc protein in a cohort of children with DLBCL treated in a uniform manner. PROCEDURE: We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c-Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600). RESULTS: Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c-Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%). CONCLUSIONS: These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease.