IgG4-related Lymphadenopathy: A Comparative Study of 41 Cases Reveals Distinctive Histopathologic Features

ola Kala shared this article with you from Inoreader IgG4-related Lymphadenopathy: A Comparative Study of 41 Cases Reveals Distinctive Histopathologic Features Μέσω The American Journal of Surgical Pathology - Current Issue Lymphadenopathy is common in patients with immunoglobulin G4-related disease (IgG4-RD). However, the described histopathologic features of IgG4-related lymphadenopathy have been shown to be largely nonspecific. In an attempt to identify features specific for nodal IgG4-RD we examined the histopathologic features of lymph nodes from 41 patients with established IgG4-RD, with comparison to 60 lymph nodes from patients without known or subsequent development of IgG4-RD. An increase in immunoglobulin (Ig) G4-positive plasma cells >100/HPF and IgG4/IgG ratio >40% was identified in 51% of IgG4-RD cases and 20% of control cases . Localization of increased IgG4-positive plasma cells and IgG4/IgG ratio to extrafollicular zones was highly associated with IgG4-RD, particularly when identified in regions of nodal fibrosis (P View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters

ola Kala shared this article with you from Inoreader Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters Μέσω The American Journal of Surgical Pathology - Current Issue Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus an d a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma shou ld be considered in patients with a shunt who present with new ascites. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Histopathologic Characterization of Bladder Perivascular Epithelioid Cell Neoplasms (PEComa): A Series of 11 Cases With a Subset Having: TFE3: Rearrangements

ola Kala shared this article with you from Inoreader Histopathologic Characterization of Bladder Perivascular Epithelioid Cell Neoplasms (PEComa): A Series of 11 Cases With a Subset Having: TFE3: Rearrangements Μέσω The American Journal of Surgical Pathology - Current Issue Perivascular epithelioid cell neoplasms (PEComas) of the bladder are extremely rare, with ~30 case reports. A subset of PEComas contain TFE3 gene rearrangement, however, the distinct histomorphologic features of these translocation tumors has not been fully explored in bladder PEComas. In our series, 11 cases of bladder PEComas were collected, including 1 internal and 10 consults, with 1 case previously reported. There was a female predominance (9 female, 2 male) with a mean age of 44.2 years (24 to 61 y). In only 1 of the 10 consult cases was PEComa considered in the differential diagnosis. In 10 of 11 cases, prominent epithelioi d features were noted, with the final case having focal epithelioid morphology. Mitotic rate was increased in 2 of 11 cases, and 2 of 11 cases had cytological atypia. Two cases were malignant, with invasion into perivesicle tissue in 1 case, and metastases to lungs and brain followed by death in the other case. Immunohistochemically, there was strong, and diffuse staining for cathepsin K in 10/11 cases with the 1 negative case restained on a previously stained slide. HMB-45 was diffusely positive in 8/11 cases, while melan-A was present in only 1/10 cases. Muscle markers were variably expressed with positivity for both smooth muscle actin in 6/10 cases and desmin in 3/10 cases. Keratin AE1/3 was uniformly negative (0/11). In 5/8 cases where TFE3 was rearranged by fluorescence in situ hybridization, the morphology had a predominantly epithelioid, nested architecture. Overall, bladder PEComas are particularly difficult to diagnose given their rarity, are predominantly epithelioid and do not always express melanocytic markers. Diagnosis in the bladder requires a combination of morphologic characterization, exclusion of other diagnostic possibilities, positive Cathepsin K staining, variable melanocytic marker expression, with some cases showing a TFE3 gene rearrangement. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Postchemotherapy Histiocyte-rich Pseudotumor Mimicking Residual Lymphoma: A Report of 11 Cases Correlating Clinicopathologic and Radiologic Findings

ola Kala shared this article with you from Inoreader Postchemotherapy Histiocyte-rich Pseudotumor Mimicking Residual Lymphoma: A Report of 11 Cases Correlating Clinicopathologic and Radiologic Findings Μέσω The American Journal of Surgical Pathology - Current Issue Postchemotherapy histiocyte-rich pseudotumor is a rare event in lymphoma patients and can cause elevated metabolic activity on positron emission tomography-computed tomography scan mimicking residual tumor. Here, we reported 11 lymphoma cases showing mass-like lesions with increased fluorodeoxyglucose uptake after chemotherapy. These postchemotherapy lesions occurred in various anatomic sites including spleen, mediastinum, lymph node, and other tissue locations, concerning for refractory or residual lymphoma. Their median size was 2.7 cm (range, 1.4 to 7.7 cm) and the median standardized uptake value on positron emission tomogr aphy-computed tomography was 10.6 (range, 5.2 to 13.8). Histologic examination of these lesions demonstrated reactive changes mainly composed of histiocyte-rich proliferation without viable lymphoma. Fat necrosis, cholesterol cleft, and calcium deposit were also commonly observed. After biopsies, 3 patients received additional chemotherapy, 2 had stem cell transplant with adjuvant chemotherapy or radiation, 1 had surgical excision, and the remaining 5 patients did not receive any further treatment. Follow-up imaging studies showed the resolved or decreased fluorodeoxyglucose activities in all patients including those without additional treatments, consistent with benign/reactive nature of these pseudotumor lesions. This study illustrates postchemotherapy mass-like lesions with elevated metabolic activity do not always represent residual disease and provides awareness of correlation between radiologic and histologic features of these lesions to avoid misinterpretation and overtreatme nt of lymphoma patients after chemotherapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma

ola Kala shared this article with you from Inoreader DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma Μέσω The American Journal of Surgical Pathology - Current Issue Myxoid liposarcoma is a malignant adipogenic neoplasm characterized by prominent arborizing capillaries, occasional lipoblasts, and primitive-appearing spindle cells in a myxoid background. A recurrent translocation in myxoid liposarcoma results in an oncoprotein consisting of full-length DDIT3 (CHOP) fused to an N-terminal segment of either FUS (TLS) or, less often, EWSR1. Here, we explore the diagnostic significance of DDIT3 expression in myxoid liposarcoma using a mouse monoclonal antibody recognizing an epitope in the N-terminal region. Studying a total of 300 tumors, we find diffuse, moderate-to-strong nuclear-localized an ti-DDIT3 immunoreactivity in all 46 cases of myxoid liposarcoma representing 36 unique tumors, including 6 cases with high-grade (round cell) morphology. DDIT3 immunohistochemistry also highlighted a distinctive vasculocentric growth pattern in 7 myxoid liposarcomas treated with neoadjuvant radiation. In contrast, the vast majority of other examined lipomatous and myxoid neoplasms exhibited no DDIT3 expression; limited, weak immunoreactivity in View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clear Cell Adenocarcinoma in Men: A Series of 15 Cases

ola Kala shared this article with you from Inoreader Clear Cell Adenocarcinoma in Men: A Series of 15 Cases Μέσω The American Journal of Surgical Pathology - Current Issue Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The me an time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Phase I Basket Study of Taselisib, an Isoform-Selective PI3K Inhibitor, in Patients with PIK3CA-Mutant Cancers

Cancer shared this article with you from Inoreader Phase I Basket Study of Taselisib, an Isoform-Selective PI3K Inhibitor, in Patients with PIK3CA-Mutant Cancers Via Clinical Cancer Research recent ... Purpose: Somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), which encodes the p110α catalytic subunit of PI3K, are found in multiple human cancers. While recurrent mutations in PIK3CA helical, regulatory, and kinase domains lead to constitutive PI3K pathway activation, other mutations remain uncharacterized. To further evaluate their clinical actionability, we designed a basket study for patients with PIK3CA-mutant cancers with the isoform-specific PI3K inhibitor taselisib. Patients and Methods: Patients were enrolled on the basis of local PIK3CA mutation testing into one of 11 histology-specific cohorts and treated with taselisib at 6 or 4 mg daily until progression. Tumor DNA from baseline and progression (when available) was sequenced using a next-generation sequencing panel. Exploratory analyses correlating genomic alterations with treatment outcomes were performed. Results: A total of 166 patients with PIK3CA-mutant cancers were enrolled. The confirmed response rate was 9%. Activity varied by tumor type and mutant allele, with confirmed responses observed in head and neck squamous (15.4%), cervical (10%), and other cancers, plus in tumors containing helical domain mutations. Genomic analyses identified mutations potentially associated with resistance to PI3K inhibition upfront (TP53 and PTEN) and postprogression through reactivation of the PI3K pathway (PTEN, STK11, and PIK3R1). Higher rates of dose modification occurred at higher doses of taselisib, indicating a narrow therapeutic index. Conclusions: Taselisib had limited activity in the tumor types tested and is no longer in development. This genome-driven study improves understanding of the activity, limitations, and resistance mechanisms of using PI3K inhibitors as monotherapy to target PIK3CA-mutant tumors. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer

Cancer shared this article with you from Inoreader A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer Via Clinical Cancer Research recent ... Purpose: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC). Patients and Methods: This study enrolled premenopausal women with HR+, HER2– ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. Results: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2– ABC. See related commentary by Clark et al., p. 371 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response

Cancer shared this article with you from Inoreader Sequential Prostate Magnetic Resonance Imaging in Newly Diagnosed High-risk Prostate Cancer Treated with Neoadjuvant Enzalutamide is Predictive of Therapeutic Response Via Clinical Cancer Research recent ... Purpose: For high-risk prostate cancer, standard treatment options include radical prostatectomy (RP) or radiotherapy plus androgen deprivation therapy (ADT). Despite definitive therapy, many patients will have disease recurrence. Imaging has the potential to better define characteristics of response and resistance. In this study, we evaluated prostate multiparametric MRI (mpMRI) before and after neoadjuvant enzalutamide plus ADT. Patients and Methods: Men with localized intermediate- or high-risk prostate cancer underwent a baseline mpMRI and mpMRI-targeted biopsy followed by a second mpMRI after 6 months of enzalutamide and ADT prior to RP. Specimens were sectioned in the same plane as mpMRI using patient-specific 3D-printed molds to permit mpMRI-targeted biopsies to be compared with the same lesion from the RP. Specimens were analyzed for imaging and histologic correlates of response. Results: Of 39 patients enrolled, 36 completed imaging and RP. Most patients (92%) had high-risk disease. Fifty-eight lesions were detected on baseline mpMRI, of which 40 (69%) remained measurable at 6-month follow-up imaging. Fifty-five of 59 lesions (93%) demonstrated >50% volume reduction on posttreatment mpMRI. Three of 59 lesions (5%) demonstrated growth in size at follow-up imaging, with two lesions increasing more than 3-fold in volume. On whole-mount pathology, 15 patients demonstrated minimal residual disease (MRD) of <0.05 cc or pathologic complete response. Low initial mpMRI relative tumor burden was most predictive of MRD on final pathology. Conclusions: Low relative lesion volume at baseline mpMRI was predictive of pathologic response. A subset of patients had limited response. Selection of patients based on these metrics may improve outcomes in high-risk disease. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Early Response to First-Line Anti-PD-1 Treatment in Hodgkin Lymphoma: A PET-Based Analysis from the Prospective, Randomized Phase II NIVAHL Trial

Cancer shared this article with you from Inoreader Early Response to First-Line Anti-PD-1 Treatment in Hodgkin Lymphoma: A PET-Based Analysis from the Prospective, Randomized Phase II NIVAHL Trial Via Clinical Cancer Research recent ... Purpose: A primary analysis of the ongoing NIVAHL trial demonstrated unexpectedly high interim complete response rates to nivolumab-based first-line treatment in early-stage unfavorable Hodgkin lymphoma. However, biomarkers such as metabolic tumor volume (MTV) or total lesion glycolysis (TLG) and their change under treatment (MTV and TLG), measured on PET, might provide additional relevant information for response assessment in this setting. Hence, the current analysis aimed to investigate early response to checkpoint inhibitor therapy beyond conventional criteria. Patients and Methods: NIVAHL is a prospective, randomized phase II trial that recruited between April 2017 and October 2018. Patients in arms A and B were assessed for early treatment response after two courses of doxorubicin, vinblastine, and dacarbazine with two concomitant nivolumab infusions per cycle (2 x N-AVD) and 4 x nivolumab, respectively. In the current analysis, we included all 59 individuals with PET images available to the central review panel for quantitative analysis before April 30, 2019. Results: At interim restaging, we determined a mean MTV and TLG of –99.8% each in arm A after 2 x N-AVD, compared with –91.4% and –91.9%, respectively, for treatment group B undergoing 4 x nivolumab. This high decrease in MTV and TLG was observed regardless of the initial lymphoma burden. Conclusions: Our study showed that nivolumab-based first-line treatment leads to rapid, near-complete reduction of tumor metabolism in early-stage unfavorable Hodgkin lymphoma. Thus, PET-derived biomarkers might allow reduction or even omission of chemotherapy and radiotherapy. Furthermore, MTV and TLG could be also used to optimize immune checkpoint-targeting treatments in other cancers. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors

Cancer shared this article with you from Inoreader OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors Via Clinical Cancer Research recent ... Purpose: This phase I/IIa study (NCT02737475) evaluated the safety and activity of BMS-986178, a fully human OX40 agonist IgG1 mAb, ± nivolumab and/or ipilimumab in patients with advanced solid tumors. Patients and Methods: Patients (with non–small cell lung, renal cell, bladder, other advanced cancers) received BMS-986178 (20–320 mg) ± nivolumab (240–480 mg) and/or ipilimumab (1–3 mg/kg). The primary endpoint was safety. Additional endpoints included immunogenicity, pharmacodynamics, pharmacokinetics, and antitumor activity per RECIST version 1.1. Results: Twenty patients received BMS-986178 monotherapy, and 145 received combination therapy in various regimens (including two patients receiving nivolumab monotherapy). With a follow-up of 1.1 to 103.6 weeks, the most common (≥5%) treatment-related adverse events (TRAEs) included fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. Overall, grade 3–4 TRAEs occurred in one of 20 patients (5%) receiving BMS-986178 monotherapy, six of 79 (8%) receiving BMS-986178 plus nivolumab, zero of two receiving nivolumab monotherapy, six of 41 (15%) receiving BMS-986178 plus ipilimumab, and three of 23 (13%) receiving BMS-986178 plus nivolumab plus ipilimumab. No deaths occurred. No dose-limiting toxicities were observed with monotherapy, and the MTD was not reached in either the monotherapy or the combination escalation cohorts. No objective responses were seen with BMS-986178 alone; objective response rates ranged from 0% to 13% across combination therapy cohorts. Conclusions: In this study, BMS-986178 ± nivolumab and/or ipilimumab appeared to have a manageable safety profile, but no clear efficacy signal was observed above that expected for nivolumab and/or ipilimumab. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.