Cutaneous Metastasis of a Mucoepidermoid Carcinoma of the Pancreas: First Reported Case.

BACKGROUND: Mucoepidermoid pancreatic cancer is a rare entity with only 8 cases reported in the literature. On review of the literature, the authors found that cutaneous metastases in pancreatic cancer are rare and have not been associated with the mucoepidermoid subtype. The authors present the first reported case of cutaneous metastasis in a patient with mucoepidermoid carcinoma of the pancreas. CASE PRESENTATION: A 50-year old white male with a metastatic invasive poorly differentiated mucoepidermoid carcinoma of the pancreas was found to have a slow growing lesion in the skin over his left upper quadrant while undergoing active therapy. The lesion was biopsied and the pathology was consistent with pancreatic origin sharing similar morphologic features when compared with the primary pancreactectomy specimen. CONCLUSIONS: Mucoepidermoid pancreatic cancer is an exceedingly rare subtype of pancreatic cancer, with very little information regarding its diagnosis, treatment, and patterns of metastases. Here, the authors present the first reported case of cutaneous metastases of mucoepidermoid pancreatic cancer.

Benign glandular downgrowth in gastric neuroendocrine neoplasms: a potential mimic of composite tumour.

AIMS: We have observed glandular downgrowth in some gastric neuroendocrine tumours (NETs), in which nonneoplastic appearing gastric glands are admixed with submucosal neuroendocrine nests, that could potentially be confused with composite tumours. METHODS AND RESULTS: We reviewed 68 gastric NETs with at least submucosal invasion, and evaluated associations between glandular downgrowth, clinical parameters (age, gender, NET setting) and tumour characteristics (size, depth of invasion, grade). Controls included 45 duodenal NETs. Glandular downgrowth was present in 28 (41%) gastric NETs but only 2 (4.4%) duodenal NETs (P < 0.0001). It was not related to age, gender, hypergastrinemia (downgrowth present in 43% of NETs arising in autoimmune gastritis, 41% of Zollinger-Ellison syndrome, 36% of sporadic NETs), tumour size, depth of invasion, or grade. Glandular downgrowth was confined to the submucosa even though 12 (18%) gastric NETs invaded muscularis propria. Submucosal gastric glands (pyloric type in 79%, intestinal in 50%, fundic in 29%) showed metaplastic changes similar to overlying mucosa, were usually mitotically inactive (64% of cases lacked mitotic figures), were geographically restricted to the NET, and never metastasized. CONCLUSIONS: Our findings support the frequent occurrence and nonneoplastic nature of glandular downgrowth in gastric NETs, which should not be mistaken for composite tumours.

Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast is a rare type of carcinoma that has not been well studied or characterized. Of the limited number of studies reported in the literature, most are case reports. A few small retrospective series studies have been reported. METHODS: We reviewed data on 142 cases of mammary NEC recorded in the surveillance, epidemiology, and end results (SEER) database during 2003-2009 and evaluated disease incidence and patient age, sex, and race/ethnicity; clinicopathologic characteristics; and survival in comparison to invasive mammary carcinoma, not otherwise specified. We also performed univariate and multivariate analyses to identify prognostic factors in this disease. RESULTS: Review of the 142 SEER cases revealed that NEC is an aggressive variant of invasive mammary carcinoma. It generally occurred in older women (>60 years); present with larger tumor size (>20 mm), higher histologic grade, and higher clinical stage; and result in shorter overall survival and disease-specific survival than invasive mammary carcinoma, not otherwise specified (IMC-NOS). Overall survival and disease-specific survival were shorter in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was an adverse prognostic factor independent of other known prognostic factors, including age, tumor size, nodal status, histologic grade, estrogen/progesterone receptor status, and therapy. CONCLUSIONS: NEC is a rare but aggressive type of mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely clinical entity.

Viral Hepatitis B Reactivation With Delayed Cholestatic Effect Secondary to Acalabrutinib.

One significant complication of hepatitis B virus includes reactivation (HBVr) in the context of the use of immunosuppressive agents, such as corticosteroids and rituximab, among others. Limited data exist on the topic of HBVr risk in the context of tyrosine kinase inhibitors for which there is no strong guidance recommendation. We describe the clinical characteristics, diagnostic challenges, and the clinical course of a single patient with recurrent mantle cell lymphoma who developed HBVr after treatment with acalabrutinib, a Bruton tyrosine kinase inhibitor.

Oesophageal hyperkeratosis: clinicopathological associations.

AIMS: Oesophageal hyperkeratosis is rarely described. In contrast to hyperkeratosis of orolaryngeal mucosa, where its risk factors and association with squamous neoplasia are well-studied, the prevalence and clinicopathological features of oesophageal hyperkeratosis are unknown. METHODS AND RESULTS: We reviewed prospectively 1845 oesophageal biopsies and found hyperkeratosis in 37 (2.0%). Among 98 patients studied, hyperkeratosis occurred in two distinct settings: group 1 [within Barrett's oesophagus (BO)/adenocarcinoma, n = 61, 62%] and group 2 (outside BO/adenocarcinoma, n = 37, 38%). In contrast to group 1, hyperkeratosis in group 2 was more often multifocal (>3 foci in 51% versus 16%, P = 0.0001), involved mid-oesophagus (51% versus 2%, P < 0.0001), showed endoscopic leucoplakia (24% versus 3%, P = 0.003) and involved current/former alcohol users (51% versus 19%, P = 0.0012). Importantly, invasive squamous carcinoma and squamous dysplasia were seen only in group 2 (47% and 19% versus 0%, P < 0.0001). Further, 42% of group 2, but none of group 1, had benign or malignant squamous lesions of the oral cavity/larynx (P < 0.0001). CONCLUSION: Hyperkeratosis involves ~2% of oesophageal biopsies and can be divided into cases occurring within BO/adenocarcinoma and those occurring outside BO/adenocarcinoma. The former lack clinical significance, whereas the latter are associated frequently with oesophageal squamous neoplasia and squamous pathology of the head and neck region.

Optimal Combination of Pitch, Modulation Factor and Dosimetric Considerations in Treatment Planning for Total Body Irradiation Using Helical Tomotherapy.

OBJECTIVE: The aim of this study is to makethe standard total body irradiation (TBI) protocol for Helical tomotherapy© (HT) and to analyze the optimal pitch and modulation factor (MF) with respect to dose homogeneity index (HI), target dose coverage, target overdose, beam on time (BOT) and mean lung dose. MATERIALS AND METHODS: Ten patients who underwent high-dose TBI were taken for this study. For each patient, 35 dose plans were created by different combination of pitch and MF. The optimal pitch and MF were deduced using scatter plot and regression methodology based on target coverage, HI, target volume receiving 103%(V103%), 105%(V105%) and 107% (V107%) of the prescription dose and BOT. Using these optimal pitch and MF, the final dose plan was made and the planning aim and achieved dose was compared using two tailed student's t-test. Radiochromic films and ionization chambers were used to measure the delivered dose using anthropomorphic phantom on various points for the head and pelvis regions to verify the skin flash margin and its effect on skin dose. RESULTS: The optimal pitch and MF value were 0.287 and 2.4 respectively. Based on optimal pitch and MF, the mean BOT was 1692 seconds with optimal inhomogeneity (7.4%). For target, D95 and D98 were 97.09% (range:94.7-99.6%, p=0.002) and 93.9% (range:91.5-94.4%,p=0.007) respectively, and mean D2 was within 107% with SD of ±1.22% (p=0.04). The mean of PTV receiving V103, V105 and V107 was 24.48% (range=7.7-36.6%, p=0.03), 5.76% (range=1.4-12.1%, SD=±3.3%), 1.93% (range=0.1-4.6%, p=0.008) respectively. Our measurements show that the flash margin did not increase the skin dose. CONCLUSION: In our study, the optimal combination of pitch value of 0.287 and MF value of 2.4 provided acceptable plans for all patients planned for TBI in HT. The flash margin can provide adequate coverage during patient position uncertainty without increasing the skin dose.

Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate.

Commissioning and Dosimetric Results of an Indigenously Developed Intra-Vaginal Template for Interstitial Plus Intracavitary High dose Rate Image-Guided Brachytherapy of Advanced Cervix Cancer.

Aim: The goal of this study is to discuss the commissioning and dosimetric parameters achieved during the clinical implementation of an indigenously developed intracavitary (IC) plus interstitial (IS) template for high dose rate (HDR) image-guided brachytherapy (IGBT) in cancer (Ca) cervix. We want to discuss our achieved values of cumulative equi-effective doses (EQD2) for high-risk clinical target volume (HRCTV) and organ at risk (OAR) and compare it with available published results. Materials and Methods: Medanta anterior oblique/lateral oblique template has a total of 19 needles including the central tandem. For commissioning the template with needles, the indigenously made acrylic phantom was used. Oblique and straight needles were placed inside the acrylic phantom and a computed tomography (CT) scan was performed. Sixteen patients were treated in HDR IGBT using this template after external-beam radiotherapy. The IGBT plans were evaluated based on EQD2 of target coverage i.e., dose received by 98% (D98%_HRCTV), 90% (D90%_HRCTV), and 50% (D50%_HRCTV) volume of HRCTV, and dose received by 2 cc (D2cc) and 0.1 cc (D0.1cc) of OAR using linear quadratic (LQ) radiobiological model. Results: The autoradiographic in radiochromic film shows that the distance between the needle tip and the middle of the source position is 6 mm. The mean D98%_HRCTV and D90%_HRCTV was 76.8 Gy (range: 70-87.7 Gy, P < 0.01) and 84.49 Gy (range: 76.6-96.7 Gy, P < 0.01), respectively. Mean EQD2 of D2cc of the bladder, rectum, and sigmoid was 85.6 Gy (range: 77.5-99.6 Gy, P < 0.03), 74.3 Gy (range: 70.9-76.7 Gy, P < 0.05), and 58.3 Gy (range: 50.6-67.9 Gy, P = 0.01), respectively. The mean total reference air kerma at a 1 m distance is 0.489cGy (range: 0.391-0.681cGy). Conclusions: The indigenously developed template could attain satisfactory standards in terms of set parameters for commissioning and acceptable dose volume relations in our clinical use for treating the advanced Ca cervix patients who need IC + IS type of HDR IGBT. The comparative analysis with contemporary applicators was acceptable.

Metastatic nonhematopoietic neoplasms to the breast: a study of 238 cases.

The aim of this study was to review the clinicopathologic characteristics of metastatic nonhematopoietic malignancies to the breast, in order to identify salient features for practicing pathologists that are useful in distinguishing metastatic lesions from primary breast neoplasms. A total of 238 cases were identified during the period from January 2005 to January 2015. Clinicopathologic features of these cases were retrospectively reviewed. Primary tumors included melanoma (99, 42%), serous carcinoma (35, 15%), neuroendocrine neoplasm (32, 13%), sarcoma (23, 10%), and adenocarcinoma from various organs (47, 20%), and 2 others. Most metastases were unilateral (223, 94%) and unifocal (206, 87%) and were detected radiographically (167, 70%). Concurrent ipsilateral axillary metastasis occurred in 33 (14%) patients. Among 238 cases, 41 had metastatic disease to the breast concurrently or preceding the primary cancer diagnosis. Notably, in 39 (16%) cases, breast metastasis was the first clinical presentation of disease, and 16 (41%) of these cases were initially misdiagnosed as breast primaries. In contrast, with a known history of nonmammary primary tumors, only 4 of 197 (2%) cases were misdiagnosed (p < 0.0001). Metastatic tumors share many overlapping features with breast primary carcinomas. However, cases with a well-circumscribed tumor, lack of in situ component, estrogen receptor/progesterone receptor negativity, and unusual morphologic features should raise the consideration of metastatic disease. While clinical history is paramount for correct diagnosis, metastasis to the breast as the first clinical presentation is not uncommon.

Mycophenolate Mofetil: A Friend or a Foe with Post-Transplantation Cyclophosphamide and Tacrolimus Prophylaxis in HLA-Matched Donors?

Adapted from the haploidentical hematopoietic stem cell transplantation (HCT) literature, post-transplantation cyclophosphamide (PTCy) is being used increasingly with HLA-matched donors, generally with a calcineurin inhibitor, such as tacrolimus (Tac), and with or without mycophenolate mofetil (MMF). Owing to its immunosuppressive and potentially antitumor and antimicrobial properties, MMF is an attractive drug; the benefit gained when it is used with PTCy/Tac remains unclear, however. To assess this, we compared PTCy/Tac (n = 242) and PTCy/Tac/MMF (n = 144) regimens in recipients of HLA-matched donor transplantation. In multivariate analysis, the PTCy/Tac/MMF group had a significantly higher risk of grade II-IV acute graft-versus-host disease (aGVHD) (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.6 to 2.8; P < .001), and steroid-refractory/dependent aGVHD (HR, 4.8; 95% CI, 2.4 to 9.6; P < .001), yet a significantly lower risk of relapse (HR, .5; 95% CI, .3 to .9; P = .009) and better progression-free survival (PFS) (HR, .7; 95% CI, .5 to .9; P = .04). There were no differences in the risk of grade III-IV aGVHD, chronic graft-versus-host disease (cGVHD), nonrelapse mortality, or overall survival. MMF was associated with prolonged neutrophil engraftment by 2 days and an elevated risk of bacterial infection. In an exploratory stool microbiome analysis (n = 16), we noted a higher relative abundance of ß-glucuronidase-producing bacteria in the MMF group, which may have a role in the pathogenesis of MMF-related GVHD. Our data suggest that the addition of MMF to PTCy/Tac for HLA-matched donor HCT does not provide any advantage for GVHD prevention. Further studies are needed to decipher this mechanism and understand its role with PTCy-based prophylaxis.

Metastatic neuroendocrine tumour in the breast: a potential mimic of in-situ and invasive mammary carcinoma.

AIMS: The aim of this study was to review the clinicopathological characteristics of neuroendocrine tumours (NETs) metastasizing to the breast, in order to identify features that could be useful in distinguishing these metastatic lesions from primary breast neoplasms. METHODS AND RESULTS: Eighteen metastatic NETs in the breast were identified from two large hospitals over a 15-year period. Eleven (62%) tumours originated in the gastrointestinal tract, 5 (28%) originated in the lung, and the other two were of indeterminate origin. Eight (44%) cases were initially misdiagnosed as primary mammary carcinomas. In retrospect, all metastatic tumours exhibited architectural and cytological features that would suggest neuroendocrine differentiation. Immunohistochemistry can further aid in the distinction between metastatic neuroendocrine and primary mammary carcinoma. All 11 tumours from the gastrointestinal tract expressed CDX-2, 3 (60%) of five tumours from the lung expressed thyroid transcription factor-1, and only 2 (11%) of 18 showed weak oestrogen receptor positivity. Additionally, unlike primary carcinomas, the majority (82%) of metastatic NETs were negative for cytokeratin 7, and all were negative for gross cystic disease fluid protein 15 and mammoglobin. CONCLUSIONS: There is a high propensity for metastatic NETs to mimic primary breast carcinomas. Careful attention to cytological and architectural features can help to identify cases that require further immunophenotypic workup with a panel of tissue-specific antibodies. However, clinical history is paramount for optimal diagnosis.

Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges.

AIMS: The aim of this study was to review the histomorphological features of primary neuroendocrine carcinomas (NEC) of the breast, in order to identify features useful in recognition of this entity for appropriate classification. METHODS AND RESULTS: 2003 World Health Organization (WHO) classification of tumors of the breast and female genital organs defined NEC of the breast as a subtype of invasive mammary carcinoma in which >50% of the tumor cells express neuroendocrine markers. Seventy-four cases that fulfilled the WHO diagnostic criteria for NEC of the breast, excluding small cell carcinoma and low-grade solid papillary carcinoma with a predominant in-situ component, were identified between 1984 and 2008 from MD Anderson Cancer Center, and were included in the study. NECs of the breast had variable histomorphological features. The most common histologic patterns were papillary (80%) and nested (64%). Mixed growth patterns were common (59%), including admixed ductal component. The tumor cells could be polygonal, round, plasmacytoid, spindled, or with signet ring cell features. The cytoplasm could be granular, eosinophilic, clear, or finely vacuolated. These tumors frequently mimicked invasive or in situ ductal carcinoma, or invasive lobular carcinoma. CONCLUSIONS: NEC of the breast is underrecognized. Careful attention to cytologic and architectural features can help to identify cases that require further immunophenotypic confirmation for correct tumor classification.

Dosimetric Comparison of Robotic and Linear Accelerator Multi-Leaf Collimator-Based Stereotactic Radiosurgery for Arteriovenous Malformation.

PURPOSE: To investigate the dosimetric comparison of different collimators which are used in robotic radiosurgery (cyberknife-CK) and linear accelerator (LINAC) for stereotactic radiosurgery (SRS) in arteriovenous malformation (AVM). MATERIALS AND METHODS: Twenty-five AVM patients were planned in CK using FIXED cone, IRIS collimator, and multi-leaf collimator (MLC) based in LINAC. Dosimetric comparison was performed using Paddick conformity index (CIPaddick) and International Commission on Radiation Units and measurements (ICRU) homogeneity index (HIICRU), gradient score (GS), normal brain dose received by 10cc (D10cc) and critical structure (brain stem, optic chiasma, optic nerves) doses. Paired sample t-test was used for statistical analysis. RESULTS: Mean treatment volume was 3.16cc (standard deviation ± 4.91cc). No significant deviation (P =0.45, 0.237 for FIXED vs. IRIS and FIXED vs. MLC, respectively) was found in target coverage. For CIPaddick, the mean difference (MD) between FIXED- and MLC-based plans was 0.16(P = 0.001); For HIICRU, difference between FIXED and IRIS was insignificant (0.5, P = 0.823); but, when FIXED versus MLC, the deviation was 7.99% (P = 0.002). In FIXED- and MLC-based plans, significant difference was found in GS70 and GS40 (P < 0.041 and 0.005, respectively). MD between FIXED- and MLC-based plans for normal brain for 5Gy, 10Gy, 12Gy, and 20Gy were 36.08cc (P = 0.009), 7.12cc (P = 0.000), 5.84cc (P = 0.000) and 1.56cc (P = 0.000), respectively. AVM volume <0.7cc should be treated with CK FIXED and >0.7cc were treated by using FIXED or IRIS collimators. AVM volume > 1.4cc can be treated by either LINAC MLC-based SRS or CK. CONCLUSION: Our study shows CK collimator (IRIS and FIXED) could be able to treat brain AVMs in any size. Linac MLC-based SRS has some limitations in terms of conformity and low-dose spillage, and advantages like reduced treatment time and MU.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants. DESIGN: A prospective observational study. SETTING: Public healthcare system in Santa Clara County (California, USA). PARTICIPANTS: Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants. DESIGN: A prospective observational study. SETTING: A public healthcare system in Santa Clara County (CA, USA). PARTICIPANTS: Women with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.

Rosai-Dorfman disease confined to the breast.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is an uncommon, idiopathic, benign histiocytic lesion. It usually involves the cervical lymph nodes and, less commonly, extranodal sites. Involvement of the breast is rare, with only 17 cases reported in the English literature to date. Here we describe 3 new patients with extranodal Rosai-Dorfman disease in the breast. All 3 patients-aged 45, 53, and 54 years-presented with solid breast lesions that were detected on screening mammography and had no clinical history of Rosai-Dorfman disease or radiographic evidence of extramammary involvement. Initial diagnoses were accomplished by needle core biopsy in the one case and excisional biopsy in the other two. We present the histopathologic findings and follow-up of each patient and conduct a literature review of mammary Rosai-Dorfman disease with emphasis on its differential diagnosis. Because Rosai-Dorfman disease frequently mimics invasive breast carcinoma in its clinical presentation and radiographic appearance-and can mimic other benign or malignant histiocytic lesions microscopically-awareness and appropriate diagnosis of this entity are essential for proper treatment.

Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement.

Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).

Idiopathic refractory ascites after allogeneic stem cell transplantation: a previously unrecognized entity.

At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.

Nonlinear effects in asymmetric catalysis.

There is a need for the preparation of enantiomerically pure compounds for various applications. An efficient approach to achieve this goal is asymmetric catalysis. The chiral catalyst is usually prepared from a chiral auxiliary, which itself is derived from a natural product or by resolution of a racemic precursor. The use of non-enantiopure chiral auxiliaries in asymmetric catalysis seems unattractive to preparative chemists, since the anticipated enantiomeric excess (ee) of the reaction product should be proportional to the ee value of the chiral auxiliary (linearity). In fact, some deviation from linearity may arise. Such nonlinear effects can be rich in mechanistic information and can be synthetically useful (asymmetric amplification). This Review documents the advances made during the last decade in the use of nonlinear effects in the area of organometallic and organic catalysis.