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A supply of plant micronutrients (some of which are metals) is necessary to regulate many plant processes; their excess, however, can have detrimental consequences and can hamper plant growth, physiology and metabolism.Artemisia annua is an important crop plant used in the treatment of malaria. In this investigation, the physio‐biochemical mechanisms involved in exogenous hydrogen sulphide‐mediated (H2S) alleviation of copper (Cu) stress in A. annua were assessed..Two different levels of Cu (20, 40 mg·kg−1), one H2S treatment (200 µm) and their combinations were introduced while one set of plants was retained as control.Results showed that the presence of excess Cu in the soil reduced growth and biomass, photosynthetic parameters, chlorophyll content and fluorescence, gas exchange parameters and induced antioxidant enzyme activity. Copper stress enhanced the production of thiobarbituric acid reactive substances (TBARS) and increased Cu content in both roots and shoots of affected plants. Exogenous application of H2S restored the physio‐biochemical characteristics of Cu‐treated A. annua plants by reducing lipid peroxidation and enhancing the activity of antioxidant enzymes in Cu‐stressed plants as compared with the controls.Hydrogen sulphide also reduced the Cu content in different plant parts, increased photosynthetic efficiency, trichome density, average area of trichomes and artemisinin content. Therefore, our results provide a comprehensive assessment of the defensive role of H2S in Cu‐stressed A. annua. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral smear examination is a simple and cost-effective test that is routinely performed while monitoring patients diagnosed with COVID-19. We sought to summarize the peripheral blood morphologic findings in patients with COVID-19 infection., Methods: A systematic review was conducted using a standardized keyword search on Medline database (PubMed), med RXIV, Google Scholar, EMBASE, and SCOPUS for studies discussing peripheral blood smear or morphologic blood findings in patients diagnosed with COVID-19., Results: A total of 28 studies were included in the review. Normocytic normochromic anemia was the most frequently encountered red blood cell finding. Neutrophilia was seen in most of the studies. A variety of morphological changes were observed in neutrophils, including pyknotic nuclei, variable shapes, toxic granules, and cytoplasmic vacuolization. Hyposegmented neutrophils, pseudo-Pegler Huet forms, and hypogranular forms were common findings reported by many studies. Lymphopenia was reported by most studies. Lymphocytes showed numerous morphological changes, including reactive forms, Downey forms, increased large granular lymphocytes, and plasmacytoid cells. The presence of giant platelets was seen frequently., Conclusions: The peripheral blood in COVID-19 shows a spectrum of findings, mostly reactive changes in neutrophils, monocytes, lymphocytes, and platelets. Increased neutrophil/lymphocyte ratio and higher neutrophil counts have been associated with poor prognosis, which potentially could help triage patients, but this needs to be confirmed in larger studies., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Extramedullary hematopoiesis (EMH)-the proliferation of hematopoietic progenitors outside of the bone marrow (BM) is a well-known phenomenon in myeloproliferative neoplasms (MPN). Abundant literature describes EMH at various body sites in cases of MPN, and some studies showed the presence of cytogenetic changes associated with MPN in the EMH tissues. We present a case of an 80-year-old female, with a history of MPN, presenting with mediastinal adenopathy. The transbronchial fine-needle aspiration (FNA) of the mediastinal lymph node showed EMH with atypical megakaryocytes and del(13q) demonstrated by fluorescence in situ hybridization. The subsequent BM biopsy demonstrated myelofibrosis with atypical megakaryocytes harboring the same cytogenetic abnormality. Our case highlights the capability of FNA cytology for providing accurate morphologic, immunohistochemical, and cytogenetic diagnosis of clonal EMH., (© 2021 Wiley Periodicals LLC.)

Preoperative fine needle aspiration diagnosis and cyto-histologic correlation of primary pulmonary mucoepidermoid carcinoma have rarely been described in detail in the literature. A 26-year old male presented at our institution with cough, bloody sputum, and a 4.3 cm left lower lobe lung mass. He was accurately diagnosed with pulmonary mucoepidermoid carcinoma on preoperative aspiration cytology. The patient subsequently proceeded to left lower lobectomy, confirming the diagnosis. In this article, we present a detailed report of primary pulmonary mucoepidermoid carcinoma describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: According to the Clinical Laboratory Improvement Amendments 1988 regulations, 5-year retrospective review (5YRR) of normal Papanicolaou tests in patients with a newly diagnosed high grade squamous intraepithelial lesion or above (HSIL+) is mandatory. Since this mandate has been in place, a multitude of changes have taken place in the screening and management guidelines of cervical cancer. The aim of this study is to assess the role of this mandate in our laboratory and to investigate the lessons learned., Material and Methods: The cytopathology electronic database and institutional quality assurance records at Loyola University Medical Center were searched from January 2009 to December 2019 to identify all Papanicolaou tests diagnosed as new "HSIL and above" (HSIL+). Major discrepancy (2+) was defined as initial negative diagnosis changed to HSIL+., Results: A total of 153,083 Papanicolaou tests were performed during this period; out of these, 1452 (0.94%) were diagnosed as HSIL+. A total of 695 HSIL+ Papanicolaou tests had a negative prior Papanicolaou and in 615 of 695 there was agreement with the initial negative diagnosis. In 61 Papanicolaou tests, the initial diagnosis was changed from negative and they were reclassified on review as 3 HSIL, 9 ASC-H, 7 AGC, and 42 ASCUS or LSIL. Major discrepancy rate was calculated as 3 of 695 (0.43%). None required an amended report., Conclusions: It is important to revisit the 5YRR as a method of implementing the quality indicators in gynecologic cytology so that the process retains its value without overburdening cytology laboratories and personnel., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The Paris System (TPS) for Reporting Urinary Cytology (UCyto) was published in 2016, but to date, no study addressing the unsatisfactory (UNSAT) category has been published. We aimed to identify the negative predictive value (NPV) for UNSAT UCyto after the implementation of TPS at our institution., Method: For the period from January 1, 2017, to December 31, 2019, we identified all cases with UNSAT diagnosis on UCyto specimens and available cytologic and/or surgical pathology follow-up within 6 months from the UNSAT diagnosis. Cases were deemed true negative (TN) if the follow-up was "negative for high-grade urothelial carcinoma" (NHGUC). Information regarding previous medical history, clinical indications, and specimen type were tabulated and analyzed., Results: From 6348 UCyto specimens, there were 230 (3.6%) UNSAT diagnoses made on 209 patients (112 [53.6%] men and 97 [46.4%] women) with a median age of 64 years. Of these, 116 UCyto specimens from 106 patients, which had cytologic and/or surgical pathology follow-up within 6 months, were further studied. Most UNSAT UCyto specimens were bladder washing/barbotage (BW/BB), and the most common indication for UCyto was cancer surveillance. The main cause of UNSAT UCyto was low cellularity. There were 5 false-negative (FN) results for high-grade urothelial carcinoma (HGUC), which corresponds to an overall NPV of 84.4%. NPV was highest for patients with UCyto for hematuria, and for patients with BW/BB as UCyto specimen type., Conclusions: Our results show that UNSAT diagnoses have a lower NPV than that typical of NHGUC diagnoses, and should be managed accordingly., (Published by Elsevier Inc.)

Background: Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor characterized by WWTR1-CAMTA1, t (1:3) (p36;q25) translocation in 90% of cases. Without prior EHE history, it can mimic other malignant effusions. Recently, CAMTA1 was published as an excellent immunohistochemical surrogate marker for molecular testing for WWTR1-CAMTA1 fusion in surgical specimens., Methods: A 6-year retrospective search using our computer system was performed for cases diagnosed as EHE on effusion cytology and surgical specimens. The clinical presentation, cytologic findings and immunohistochemical stain results, including CAMTA1 were reviewed., Results: Four pleural and one peritoneal effusions were identified. The median age was 52 years with a female to male ratio of 3:2. Most patients presented with pulmonary symptoms. The cytologic features were non-specific easily mimicking other malignancies; especially in the absence of known prior malignancy. This was exemplified by one of our cases which was initially misdiagnosed as adenocarcinoma. Intracytoplasmic erythrocytes were present only on the cell blocks but not on cytology. The cytology cell blocks from patients with prior EHE confirmed on surgical biopsies stained positive for vascular markers (CD31, ERG) and CAMTA1., Conclusion: The features of EHE in effusion are non-specific and a diagnostic pitfall in cytology. In the absence of prior EHE diagnosis, inclusion of this entity in the differential diagnoses and application of immunohistochemical stain panels will be prudent in avoiding a misdiagnosis. However, in cases with prior EHE diagnosis, CAMTA1 could serve as diagnostic marker; especially on limited cytology material. Additional studies will be helpful in supporting our results., (© 2020 Wiley Periodicals LLC.)

Introduction: Various types of contaminants can be encountered in cytologic specimens. This study describes a vegetable material that we encountered in ileal conduit urine specimens. We aim to describe the cytomorphology and the source of origin of this vegetable material., Material and Methods: The cytology database for the past 5 years (January 2015-April 2020) was searched for ileal conduit urine cytology specimens with a reported vegetable contaminant. The details of the ostomy procedure and device used were recorded. Histologic sections were prepared from the ostomy devices as well as from guar beans and seeds., Results: A total of 17 urinary specimens from 8 patients were identified that showed the presence of a vegetable contaminant. All the patients were using Coloplast (Minneapolis, MN) SenSura Mio ostomy device. The urine cytology showed presence of polygonal thick-walled cells with a dark brown/orange core with irregular outlines. Similar cells were also seen in the histologic sections prepared from the ostomy adhesive and the guar seed and bean., Conclusions: Guar gum is a naturally occurring hydrocolloid that is used in ostomy wafer adhesives. Correct identification and familiarity with the cytomorphology of the guar cells in samples of ileal conduit urine is essential to avoid a potential diagnostic pitfall when evaluating urine cytology specimens from these diversion specimens., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

A premature infant male was born at 30 weeks' gestation with severe coagulopathy and thrombocytopenia. Over the first days of his life, the patient developed evidence of immune hyperactivation with adenopathy, hepatosplenomegaly, and elevated ferritin. Although the patient met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH), flow cytometric based assays were not consistent with primary HLH. A lymph node and bone marrow biopsy eventually revealed the presence of anaplastic lymphoma kinase+anaplastic large cell lymphoma. To our knowledge, this is the earliest presentation of a lymphoma, and expands the known timeframe of lymphomagenesis.

Objectives: To define the clinicopathologic features of extranodal marginal zone lymphoma (EMZL) of the central nervous system (CNS), including cases arising in CNS parenchyma, which have been reported only rarely., Methods: Twelve cases of CNS EMZL were identified, including 5 based in CNS parenchyma and 7 nonparenchymal cases arising in dura or choroid plexus., Results: Histologically, parenchymal cases were perivascular infiltrates without a dominant lymphoid mass, whereas nonparenchymal cases were masses of small lymphocytes. Plasma cells were a larger component of the infiltrate in parenchymal cases (median, 30%; range, 20%-50%) than nonparenchymal cases (median, 0%; range, 0%-5%; P < .001), and plasma cells were clonal by immunohistochemistry in 4 of 5 parenchymal vs 1 of 7 nonparenchymal cases (P = .07). Fluorescence in situ hybridization for MALT1 rearrangement was positive in 1 of 3 parenchymal and none of 3 nonparenchymal cases. Chromosomal microarray was abnormal in 5 of 7 cases (71%), with chromosome 6/6q alterations identified in 3 cases. No patients with parenchymal disease but all 6 (100%) with nonparenchymal disease achieved complete remission., Conclusions: This case series, the first to include multiple parenchymal cases, clarifies the spectrum of clinical, pathologic, and genetic findings in CNS EMZL and suggests that parenchymal-based lesions may show less favorable prognosis than dural-based disease., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mammary ductal carcinoma in situ (DCIS) is classically treated by combinations of excision, radiation, and endocrine therapy, based upon the specific needs of individual patients. Estrogen receptor (ER) status is generally assessed by immunohistochemistry (IHC) in newly diagnosed cases of DCIS, and endocrine therapy in this setting is thought to be chemopreventive. The potential impact of androgens on mammary carcinogenesis has been studied in recent years, and several authors have proposed androgen receptor (AR) IHC testing and targeted antiandrogenic therapy in patients with locally advanced or metastatic triple-negative invasive breast cancer (ie, negative for ER and progesterone receptor and HER-2). Very little has been published on AR in DCIS. We report results of AR IHC on archival tissue blocks from 221 adult female patients, each of whom underwent definitive breast resection of DCIS. Of the 221 cases, 72 (33%) were shown to express AR in their DCIS at or above the 10% threshold often used for invasive carcinoma. AR expression was seen in all grades of DCIS. Of the 72 positive AR cases, 21 (29%) were ER negative, corresponding to 10% (21/221) of all patients. The majority of the AR-positive cases were high grade, and the most common histologic subtype in this subset was a solid growth pattern with apocrine features. Early data from clinical trials evaluating AR antagonists in invasive/metastatic triple-negative breast cancer suggest that some patients may benefit from androgen blockade. IHC testing and potential clinical trials of AR antagonists for chemoprevention in patients with AR-positive and ER-negative DCIS could be considered.

Background: Follicular lymphoma (FL) is heterogeneous. Although FL Grade 3B (FL3B) is treated as aggressive FL (aggFL), an optimal approach to FL Grade 3A (FL3A) remains unclear because few data exist on clinical outcomes on the basis of subclassification of FL Grade 3 (FL3) since the introduction of rituximab. We report outcomes of FL3 in the rituximab era., Patients and Methods: We identified and analyzed a retrospective cohort of 53 patients with FL3A, 3B, and FL Grade 3 with areas of diffuse large B-cell lymphoma (DLBCL). They were divided into 2 groups: aggFL (n = 21) included patients with FL3B (n = 10) and FL3 (A or B) with concomitant DLBCL (n = 11); indolent lymphoma (n = 32) included only FL3A., Results: Baseline characteristics did not differ between the groups. rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was initial treatment in 15 (79%) of patients with aggFL and 21 (72%) of those with FL3A; rituximab was included in initial therapy in 18 (95%) and 24 (83%), respectively. Comparing aggFL and FL3A, 5-year overall survival was 90% versus 79% (P = .97) and 5-year progression-free survival (PFS) 44% versus 34% (P = .75), respectively., Conclusion: We conclude that outcomes for FL3, primarily treated with R-CHOP, do not differ between FL3A and aggFL (FL3B and FL3/DLBCL). The aggFL group showed a plateau in PFS confirming these should be treated with curative intent. FL3A patients, mainly managed with R-CHOP, also show an apparent plateau in PFS. Although longer follow-up and confirmation in other data sets is required, this indicates potential undertreatment of FL3A with less aggressive regimens often used for indolent lymphoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations., Methods: A computerized archival search was performed for cases of non-chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data. Bone marrow biopsy specimens were stained with monoclonal antibody CAL2, and the percentage of stained megakaryocytes was calculated. In select cases, double immunofluorescence staining was done with CAL2 and each of the following: CD61, myeloperoxidase, CD34, and glycophorin A., Results: We studied 38 bone marrow biopsy specimens of non-CML MPNs (primary myelofibrosis, n = 21; essential thrombocythemia, n = 15; and n = 2 post-polycythemia vera myelofibrosis) from 31 patients. All eight bone marrow biopsy specimens from patients with mutant CALR showed strong cytoplasmic staining of the megakaryocytes (83.5%; range, 50%-98%; median, 87%) with the CAL2 antibody. Double immunofluorescence staining of the small mononuclear cells seen in CALR mutant cases revealed them to be myeloid blasts., Conclusions: Immunohistochemistry in routinely processed bone marrow biopsy specimens for mutated CALR is feasible and accurately identifies mutated cases, including rare cases with additional driver mutations., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Establishment of accurate axillary lymph node status is of essential importance in determining both prognosis and the potential need for adjuvant therapy in patients with invasive breast cancer. Axillary lymph node heterotopias can in some cases result in overdiagnosis of metastatic disease. Nodal endosalpingiosis is perhaps the least commonly reported type of axially lymph node heterotopia. We herein illustrate a case in which second opinion pathologic interpretation combined with ancillary immunohistochemical studies allowed for a specific diagnosis of axillary nodal müllerian-type inclusions, confirming ypN0 staging and resulting in appropriate disease management and prognostication.

Background: Four and a half LIM domain protein-2 (FHL2) is part of the focal adhesion structures modulating cell motility. FHL2 may translocate into the nucleus serving as a transcriptional cofactor binding several transcription factors. Overexpression of FHL2 has been linked to cancer progression in various neoplasias. The aim of the present study was to determine, whether FHL2's function as nuclear cofactor plays a prognostic role in invading tumor cells of sporadic and HNPCC-associated colorectal cancer (CRC)., Design: Immunohistochemical staining intensity of nuclear FHL2 was quantified by Remmele score analysing 47 sporadic and 42 HNPCC-associated colorectal cancers. Analysis was restricted to carcinoma cells of the tumoral invasion front., Results: Confocal microscopy detected nuclear expression of FHL2 in colon cancer cells and absence of nuclear FHL2 signal in normal colon enterocytes. In colon cancer, nuclear FHL2 expression was predominantly observed in low-differentiated, often mucinous tumor areas. 42.55% of sporadic and 54.76% of HNPCC-associated CRC showed enhanced (Remmele score 6-12) nuclear FHL2 expression in the carcinoma cells of the tumoral advancing edge. Enhanced nuclear FHL2 expression was significantly linked to lymphatic metastasis in sporadic CRC (p=0.0197) and almost reached significance in HNPCC-associated CRC (p=0.0545). In contrast, nuclear FHL2 expression was neither associated with hematogenic metastasis in sporadic (p=0.7087) nor in HNPCC-associated colorectal cancer (p=0.3007)., Conclusions: We recently demonstrated that enhanced nuclear FHL2 expression in tumor stroma of sporadic colon cancer is associated with lymphatic metastasis. The results of the present study indicate a synergistic effect of nuclear cofactor FHL2 in tumor cells as well as in peritumoral stroma cells promoting lymphatic metastasis in sporadic CRC. As HNPCC-associated tumors did not show a significant association between tumoral nuclear FHL2 expression and lymphatic metastasis we speculate, that the intensive lymphocytic immune response in HNPCC precludes a direct contact of tumor cells and stromal cells resulting in reduced lymphatic spread., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

As the use of single donor apheresis platelets and plateletpheresis procedures done steadily increases in India, the plateletpheresis donors are at an increased risk of postpheresis anemia and thrombocytopenia. This study was planned in order to evaluate the effect of plateletpheresis on the hematological parameters in the local donor population and to evaluate the possibility of following the 2day deferral for repeat plateletpheresis. A total of 60 plateletpheresis procedures performed over a period of 1year with CS 3000 Plus Baxter Fenwal were evaluated. All the post-donation hematological parameters showed a significant decrease from the pre-donation values (p<0.001). Post-donation hemoglobin <12g, which is defined by WHO as anemia irrespective of the gender occurred in 25% (n=15) of the donors. The post-donation platelet count was less than 100×10(9)/L in 16.6% (n=10) of the procedure. The ability of these donors to serve as repeat plateletpheresis donor after 2days as recommended by AABB needs to be evaluated by further studies done post donation. Keeping in view the hematological profile of our donor population we recommend that donors who already have a low or borderline pre-donation platelet count and hemoglobin should be assessed and monitored post-donation for decrements in these parameters. While serving as repeat donors, their pre donation hemoglobin and platelet counts should be tested again., (Copyright © 2013 Elsevier Ltd. All rights reserved.)