A Curious Case of Morphologically Deceptive Pediatric B-Lymphoblastic Leukemia with Granular "Blebbed" Blasts and DLBCL-Like Biopsy Findings.

Background: B-cell acute lymphoblastic leukemia is known for heterogeneous blast morphology. Cytoplasmic granules and blebs have both been described, but not together, in lymphoblasts. Case presentation: A 7-year-old boy presented with fever, abdominal distension for 3 weeks, with hepatosplenomegaly. Investigations revealed pancytopenia, peripheral smear showing 21% blasts of varying size, displaying cytoplasmic blebbing and granulation. Marrow aspirate was hemodilute, 10% cells showed dim to moderate expression of CD45, CD10, CD19, HLA-DR confirming B-ALL. Megakaryocytic markers (CD41, CD61) were negative. Marrow biopsy showed a focus of large atypical cells displaying increased nuclear-cytoplasmic ratio, vesicular nuclear chromatin and macronucleoli, reminiscent of diffuse large B-cell lymphoma, cells strongly expressing PAX5, CD19, CD20, and bcl-2.The child was put on standard induction therapy. No blasts were detected in subsequent peripheral smears. Conclusion: To the best of our knowledge, this is the first case of pediatric B-ALL displaying granular "blebbed" blasts.

Supernumerary Remnant Vas Deferens Like Wolffian-Derivatives in a Young Child With Abdominal Cocoon Syndrome-A Clinicopathological Novelty.

The abdominal cocoon syndrome is a rare cause of recurring intestinal obstruction in children. It refers to encasement of the small bowel by a fibrocollagenous membrane forming a cocoon. We report a nine year old male presenting with abdominal pain, distension, bilious vomiting and inability to pass stool and flatus for two days. In view of a persistently increasing bilious nasogastric output, an urgent exploratory laparotomy was performed. The small bowel loops were matted together forming a cocoon densely adherent to the parietal peritoneum with supra-colic fibrous bands. The bands histologically displayed multiple ductal remnants with epithelium resembling that of ductus deferens. These structures showed immunopositivity for pan-cytokeratin and basal CD10.Workup for tuberculosis and other etiological causes was unremarkable. This is the first documented case of abdominal cocoon in a pediatric subject associated with supernumerary wolffian remnants.

Mammary Fibrocystic Change in a Pre-Pubertal child- A Case Report with a Histopathological Perspective.

BACKGROUND: Fibrocystic change in the breast is one of the entities under the spectrum of benign breast disease. It occurs primarily in females of the reproductive age group. Though the exact etiology is unknown, estrogen-progesterone imbalance is possibly one of the causative factors. Its occurrence in the pediatric age group is infrequent and is hitherto unreported in the pre-pubertal age group. Case report: We present the case of a 2-year-old female presenting with an ill -defined lump approximately 4 cm in diameter, with an unremarkable hormonal status for the age. Histopathology revealed fibrocystic change in the resected tissue. Conclusion: Fibrocystic breast change in children may represent an exaggeration of the normal developmental involution process.

Exploring the pH dependent aqueous speciation of metal complexes through UV-Vis spectroscopy.

Coordination chemistry is a major component of the undergraduate inorganic chemistry curriculum and yet the presentation of the material can be cumbersome due to the limitations of the course typically being taught in one semester. Also, because of the large scope of this branch of chemistry encompassing all of the elements, the course design has not been standardized. These factors result in some important coordination chemistry themes being given insufficient development. Herein we propose a novel activity to formally introduce metal complex aqueous speciation in a holistic active-learning manner that includes a lecture component and hands-on experience. This topic has real world relevance and contextualizes many important coordination concepts. It would extend student comprehension about the intricate factors that affect metal complexation in an aqueous solution environment by focusing on the influence of pH. The activity explores the pH dependent speciation of the well-characterized interaction between Fe(III) and 2,3-dihydroxynapthalene-6-sulfonate and reveals the colorful changes in species throughout the pH range of 0 to 13. Students learn how to generate speciation plots and to understand the ultraviolet-visible (UV-Vis) electronic absorption spectroscopy of transition metal compounds to be able to analyze the source of color that they observe. Assessment of the activity was conducted with 24 students who completed a Likert scale survey and responded to open-ended questions. The activity was then applied in actual course settings in which student comprehension was quantitatively evaluated. The activity can be easily adapted to students of different stages of academic development from elementary to college students.

Sickle cell disease presenting in the third trimester of pregnancy: Delayed detection heralding a public health problem?

We report the case of a 22-year-old primigravida detected as having sickle cell disease (SCD), initially presenting in the third trimester (30th week) of pregnancy. The patient came to our center with a complaint of severe lower limb pain. The peripheral smear showed marked anisopoikilocytosis, numerous leptocytes, sickle cells, and target cells. High-performance liquid chromatography corroborated the diagnosis of SCD, showing a significant peak in the sickle window. The patient was conservatively managed and delivered a healthy baby through normal vaginal delivery. Delayed presentation of SCD in the third trimester of pregnancy is unusual. This report aims to bring attention to the possible causes of such a lag in detection. We also suggest measures to refine the antenatal healthcare screening at multiple levels, with regard to the detection of sickle cell hemoglobinopathy.

Exploring titanium(IV) chemical proximity to iron(III) to elucidate a function for Ti(IV) in the human body.

Despite its natural abundance and widespread use as food, paint additive, and in bone implants, no specific biological function of titanium is known in the human body. High concentrations of Ti(IV) could result in cellular toxicity, however, the absence of Ti toxicity in the blood of patients with titanium bone implants indicates the presence of one or more biological mechanisms to mitigate toxicity. Similar to Fe(III), Ti(IV) in blood binds to the iron transport protein serum transferrin (sTf), which gives credence to the possibility of its cellular uptake mechanism by transferrin-directed endocytosis. However, once inside the cell, how sTf bound Ti(IV) is released into the cytoplasm, utilized, or stored remain largely unknown. To explain the molecular mechanisms involved in Ti use in cells we have drawn parallels with those for Fe(III). Based on its chemical similarities with Fe(III), we compare the biological coordination chemistry of Fe(III) and Ti(IV) and hypothesize that Ti(IV) can bind to similar intracellular biomolecules. The comparable ligand affinity profiles suggest that at high Ti(IV) concentrations, Ti(IV) could compete with Fe(III) to bind to biomolecules and would inhibit Fe bioavailability. At the typical Ti concentrations in the body, Ti might exist as a labile pool of Ti(IV) in cells, similar to Fe. Ti could exhibit different types of properties that would determine its cellular functions. We predict some of these functions to mimic those of Fe in the cell and others to be specific to Ti. Bone and cellular speciation and localization studies hint toward various intracellular targets of Ti like phosphoproteins, DNA, ribonucleotide reductase, and ferritin. However, to decipher the exact mechanisms of how Ti might mediate these roles, development of innovative and more sensitive methods are required to track this difficult to trace metal in vivo.

Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?

Intravascular papillary endothelial hyperplasia (Masson's tumor) is a reactive vascular lesion of obscure etiopathogenesis, often seen in the head and neck. Its presentation as a scalp swelling, however, is extremely uncommon. We describe the first report in an adult, being treated for bipolar illness. A young male presented with a right frontotemporal scalp swelling since 3 weeks. He was also being treated for bipolar illness with olanzapine. Examination revealed a soft, non-pulsatile swelling. After inconclusive aspiration results, a complete excision was performed. Histopathology revealed proliferating endothelial cells arranged as papillary fronds confined to vessel lumina, devoid of atypia, accompanied by thrombosed vessels facilitating a diagnosis of Masson's tumor. The patient is free of recurrence five months after surgery. Further studies on a possible effect of olanzapine on vascular proliferation in experimental in vivo and in vitro models would definitely aid in elucidating clinical relevance, if any.

Acantholytic Squamous Cell Carcinoma: a Diagnostic Pitfall on Cytology.

Acantholytic squamous cell carcinoma is an infrequent subtype of squamous cell carcinoma. This tumour variant being rare in itself has been rarely described at the penile location, thus leading to a limitation on information of pathological and immunohistochemical findings and prognosis. Clinical observations indicate an aggressive biologic behaviour. The cytological features on fine-needle aspiration cytology samples have rarely been described in literature. It is imperative for pathologists to be aware of the cytological features so as to allow the distinction of this variant from conventional squamous carcinoma. Here, we explore an intriguing case of a metastatic tumour to inguinal lymph node with the primary lesion at the penis which constituted a diagnostic challenge on cytological examination.

Hearts don't lie: Cardiac tuberculosis diagnosed on fine-needle aspiration cytology.

Cardiac involvement in tuberculosis is relatively rare when compared to other organs and often involves the pericardium leading to constrictive pericarditis. Myocardial tuberculoma is exceedingly rare and only seldom cases have yet been reported. Our report is of a case diagnosed on fine-needle aspiration cytology.

Erythrophagocytosis in a patient with B-cell acute lymphoblastic leukemia with t(12;21) (p13.2; q22.1); ETV6-RUNX1: Case report and review of the literature.

Erythrophagocytosis (EP) is extremely rare in de novo acute lymphoblastic leukemia (ALL). We document a rare case, which in addition, showed extensive blast vacuolization. A detailed literature review has also been incorporated with the aim of unraveling the prognostic import of our morphological observations if any. A five-year-old male presented with fever and progressive pallor for 1 month. He had hepatosplenomegaly and bicytopenia. Peripheral smear examination showed 43% blasts. Nuclear and cytoplasmic vacuolations were seen in 75% blasts and EP in 4% blasts. The blasts showed block positivity on periodic acid-Schiff (PAS) stain. Marrow aspirate smears showed 58% blasts displaying a similar morphology. Flow cytometry showed features of a common acute lymphoblastic leukemia antigen (CALLA) positive B-cell ALL with aberrant, dim CD 33 expression in 53.4% of the gated blasts. Fluorescence in situ hybridization showed translocation (12; 21) (p13;q22). The patient responded well to standard induction therapy. To conclude, EP is rarely seen in de novo ALL and is associated with a favorable translocation, t(12;21).

A Case of Premenopausal Uterine Leiomyoma, Non-cirrhotic Portal Fibrosis, Hepatic Koch's, a PET Gone Astray-Morphology Antidotes a Confounding Concoction.

Uterine leiomyoma with hepatic vasculopathy, specifically non-cirrhotic portal fibrosis (NCPF), has hitherto been undescribed. NCPF is characterized by elevated portal pressure sans cirrhosis and has previously not been described in association with a gynecological pathology. We report the case of a female under evaluation for a heterogeneously enhancing intrauterine mass with multiple hepatic lesions with increased uptake of fluorodeoxyglucose on positron emission analysis. Fibroscan values were increased. Histopathologic evaluations revealed a leiomyoma with liver tissue showing tubercular granulomas, thin wispy fibrotic strands, and rounded portal tracts pointed to NCPF. No evidence of malignancy was seen. Metabolic imaging may be unreliable to distinguish between benign and malignant uterine pathology and granulomatous and malignant hepatic lesions. Elastography may also be ineffective in diagnosing the etiology of liver fibrosis. Histopathological analysis hence remains essential despite noninvasive tests. Further research is required on females afflicted with NCPF to exclude a hormonal link.

Filariasis presenting with bicytopenia, progressive splenomegaly and acute renal failure: An unusual case report.

Extra-lymphatic manifestation of filariasis, especially as acute renal failure, is uncommon and may be clinically unsuspected. We document the case of a 60 year old elderly male who presented with bilateral pedal oedema, fatigue and abdominal distension. Investigations revealed severe anaemia, splenomegaly and acute renal failure. Bone marrow aspiration was performed to evaluate the clinical suspicion of malignancy. Out of eight smears examined, microfilaria (Brugia malayi) were identified in two. This presentation was devoid of peripheral eosinophilia. The patient was commenced on a regimen of diethylcarbamazine, on which he made a good recovery. The incidence of extra-lymphatic filariasis is largely unknown and sparsely reported. Such a presentation should be kept in mind by both clinicians and pathologists as it is potentially treatable.

Life After Death.

OBJECTIVES: To test the performance characteristics of 69 primary immunohistochemistry antibodies after expiration and compare with fresh primary antibodies wherever possible. METHODS: A total of 69 expired primary antibodies were evaluated for specificity, background staining, and intensity. An optimal staining result corresponded to a semiquantitatively scored 2+ or 3+ intensity, with intact specificity devoid of moderate or strong background staining. Any deviation from a normal staining pattern was also considered to be a suboptimal result. RESULTS: Nearly half of the antibodies studied showed an optimally positive staining result after expiration (34/69, 49.2%). Overall, 10.1% (7/69) of antibodies could be compared with fresh primary antibodies of the same clone with equivalent results. Eight of 69 (11.6%) expired antibodies showed splotchy or granular staining. CONCLUSIONS: Evidence from this study and previous work point to maintained functionality of a fair number of primary immunohistochemical antibodies after expiration. Decisions about the use of such reagents should be guided by a thorough assessment of functionality by the pathologist rather than a manufacturer-specified deadline. Quality maintenance should imply a sensible balance between histopathologic performance and economics.

Chronic Liver Disease Presenting as Immune Hemolytic Anemia: The Challenges of Diagnosis in the Critically Ill in a Resource-Limited Health Care Setting.

Immune hemolytic anemia is very rarely associated with chronic liver disease. Diagnosis is often complicated in critically ill patients, where an etiological diagnosis can be elusive, especially in routine health care settings. A 48-year-old man presented with jaundice for three months. Ultrasonography showed features of chronic liver disease. Fibroscan showed increased parenchymal stiffness suggesting cirrhosis. Investigations revealed immune hemolytic anemia and thrombocytopenia. A percutaneous liver biopsy was not performed due to worsening thrombocytopenia. Isolated protein C deficiency and portal vein thrombosis were noted in subsequent testing. The patient eventually succumbed to illness. Coagulopathy such as protein C and D-dimer elevation discovered in subsequent rounds of testing may be misleading in rapidly deteriorating patients, emphasizing the need for timely coagulation workup and imaging. Despite comprehensive testing, lack of liver biopsy, as seen herein, may hamper clinical management. Training residents in the skill of transjugular liver biopsy is necessary to manage critical patients at secondary health care facilities.

Papanicolaou-Stained Cytosmear Preparations in the Evaluation of Leucocytospermia: A Tertiary Centre Experience and Assessment of Utility.

Objectives Leucocytospermia is a rare cause of infertility with a variable incidence in infertile men. In many andrology laboratories, semen analysis is primarily centered on analyzing basic parameters (sperm count, motility, and viability). We examined the role of cytomorphological analysis on Papanicolaou (PAP)-stained smears in the work up of male infertility, with special reference to leukocytospermia and assessed the morphological features of sperms in these cases. Materials and Methods All cases signed out as "leukocytospermia" between November 2017 and January 2018 were evaluated. Cases showing pus cells (≥ 1/5hpf) on cytosmear evaluation were also analyzed. Parameters obtained on modified Neubauer's chamber, wet mount preparations, and autoanalyzer SQA-IIC-P (Medical Electronic Systems, Israel) were tabulated. PAP-stained smears were examined to assess morphological defects and other findings, if any. Results Out of 348 semen samples, 6 (1.72%) were diagnosed as leukocytospermia, all displaying pus cells on cytomorphological evaluation. Five cases having white blood cells < 1 × 10 9 /L were analyzed, which displayed the presence of pus cells (≥ 1/5 hpf) on cytosmear preparations (1.43%). Nine cases (81.8%) showed reduced motile sperm concentration, functional sperm concentration, and sperm motility index. Morphological evaluation of the PAP-stained smears showed mid-piece defects in 18.1% cases. Conclusion Diligent cytomorphological evaluation of semen is essential to diagnose leukocytospermia, assess morphological defects, and serve as a quality control measure.

Duodenal strongyloidiasis - Our 15-year histopathological experience at a tertiary gastrointestinal centre.

In order to emphasise the importance of histopathology in the clinically unsuspected diagnosis of duodenal strongyloidiasis, we report six cases diagnosed on duodenal biopsies identified from the database over a period of 15 years, and clinical, endoscopic and histopathological findings were analysed retrospectively. Four were elderly males and the remainder young females. Only one patient had an underlying immunocompromised state. Three presented with cholestatic jaundice and simulated hepatobiliary malignancy. In all cases, endoscopy provided non-specific findings. Only one case showed a predominant eosinophilic infiltrate. Eggs, larvae and adult forms of strongyloides were seen in crypts and showed intense basophilic staining on HE stain. It is concluded that since mostly undetected clinically, duodenal biopsy serves as the first step in the diagnosis of strongyloidiasis. Hepatobiliary manifestations, though very infrequent, should raise the suspicion for strongyloidiasis and thus necessitate the need for duodenal biopsy.

Iron Chelator Transmetalative Approach to Inhibit Human Ribonucleotide Reductase.

Efforts directed at curtailing the bioavailability of intracellular iron could lead to the development of broad-spectrum anticancer drugs given the metal's role in cancer proliferation and metastasis. Human ribonucleotide reductase (RNR), the key enzyme responsible for synthesizing the building blocks of DNA replication and repair, depends on Fe binding at its R2 subunit to activate the catalytic R1 subunit. This work explores an intracellular iron chelator transmetalative approach to inhibit RNR using the titanium(IV) chemical transferrin mimetic (cTfm) compounds Ti(HBED) and Ti(Deferasirox)2. Whole-cell EPR studies reveal that the compounds can effectively attenuate RNR activity though seemingly causing different changes to the labile iron pool that may account for differences in their potency against cells. Studies of Ti(IV) interactions with the adenosine nucleotide family at pH 7.4 reveal strong metal binding and extensive phosphate hydrolysis, which suggest the capacity of the metal to disturb the nucleotide substrate pool of the RNR enzyme. By decreasing intracellular Fe bioavailability and altering the nucleotide substrate pool, the Ti cTfm compounds could inhibit the activity of the R1 and R2 subunits of RNR. The compounds arrest the cell cycle in the S phase, indicating suppressed DNA replication, and induce apoptotic cell death. Cotreatment cell viability studies with cisplatin and Ti(Deferasirox)2 reveal a promising synergism between the compounds that is likely owed to their distinct but complementary effect on DNA replication.

Finish before the start: Analyzing preanalytical sample errors in a tertiary care hematology laboratory.

AIMS: (a) To evaluate the types and frequencies of preanalytical errors occurring in a tertiary care hematology diagnostic center and (b) To evaluate differences if any, across groups [outpatient data (OPD) vs inpatient data (IPD), type of test requested [complete blood count (CBC) vs coagulation] and laboratory (routine vs emergency). SETTINGS AND DESIGN: A prospective study was conducted over a period of nine months (August 2017-April 2018) to address the above objectives. All samples received in the clinical hematology division of our institute were included in the analysis. MATERIALS AND METHODS: Categories of preanalytical errors were defined. This included insufficient, clotted, diluted, and lipemic samples. Clerical errors such as wrong/absent sample labeling, requisition form-sample mismatch, and wrong vacutainer selection were also documented. IPD and OPD data, as well as data pertaining to samples sent for different tests [complete blood count (CBC)/coagulation] and in the routine and emergency laboratories, were segregated. STATISTICAL ANALYSIS USED: All errors in each category were recorded as numbers and corresponding percentages (proportions). The two-tailed z-test was applied to assess the significance of the difference in proportions across all groups. Statistical significance was kept at P < 0.05. RESULTS: A total of 189,104 samples were received in the clinical hematology laboratory during the aforementioned period, out of which preanalytical errors were found in 4052 (2.14%) samples. Inadequate sample quantity (ISQ) comprised the bulk of preanalytical errors in our laboratory (1.11% of total samples) followed by sample clots (0.88%). There was no significant difference in the error frequencies in OPD and IPD (P = 0.1031). The proportion of errors was higher in routine vis-à -vis emergency samples and also in samples sent for coagulation analysis vis-à -vis CBC.

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity.

Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.