Partial Molar Ectopic Pregnancy: A diagnostic challenge.

Here, we present a rare case of a primigravida who presented to us with symptoms and signs suggestive of an ectopic gestation, which turned out to be a partial mole in histopathological examination. Since it is a very rare occurrence, we would like to publish the case details in this case report.

Congenital brain tumour in a neonate: a therapeutic challenge.

A term neonate with history of ventriculomegaly in the fetal period was diagnosed with a central nervous system tumour after radiological investigations. It was confirmed as an immature teratoma after histopathological examination. He underwent left frontal craniotomy with tumour excision. Intraoperatively, massive haemorrhage (venous bleed) occurred due to the high vascularity of the tumour and led to haemodynamic instability. A massive transfusion protocol was initiated. Despite multiple transfusions and shock management, he succumbed at 2 weeks of life. This case report highlights the importance of antenatal diagnosis and fetal MRI in prognostication and also the possible role of neoadjuvant chemotherapy in reducing tumour vascularity and, hence, bleeding.

PD-L1 Expression in Colorectal Carcinoma Correlates with the Immune Microenvironment.

INTRODUCTION/BACKGROUND: Colorectal carcinoma (CRC) is a common malignancy, with its diverse clinical, pathological, and molecular features. The immune microenvironment of a tumor comprises of interplay between various cells and molecules, and has a significant role in deciding the tumor behavior and overall prognosis. PD-L1 (programmed cell death ligand-1) has been implicated in the regulation of the tumor immune microenvironment (TIME). There is limited data regarding the correlation of PD-L1 expression with immune cell profile in CRCs, especially in the Indian setting. The study aimed to assess the PD-L1 expression in CRC tumor cells and its association with TIME, mismatch repair (MMR), and various other clinicopathological parameters. METHODS: This is a hospital-based, cross-sectional observational study. PD-L1 expression was assessed at the protein level by immunohistochemistry and mRNA level by qRT-PCR. Immune cell markers (CD4, CD8, CD20, FOXP3, and CD163) were interpreted using the ImageJ Fiji platform. RESULTS: Of the 104 cases, 21% were PD-L1 positive and were more common in right-sided CRCs. PD-L1 positive cases showed significantly higher concentrations of all T-cell subsets (CD4+ , CD8+ , and FOXP3+), CD20+ B-cells, and CD163+ macrophages were noted. No statistical significance was seen between PD-L1 expression with clinical profile, pathological subtype, grade or stage, mismatch repair status (proficient vs deficient), and survival. CONCLUSIONS: The present study showed a relatively lower frequency of PD-L1 in CRC from the Eastern Indian cohort. The immune cell concentration in the present study was calculated using image analysis-based objectivised methods. Significant correlation of PD-L1 expression in tumor cells with the tumor-infiltrating immune cells indicated its crucial role in the pathobiology of CRC especially by regulating the TIME. Considering the therapeutic implication of PD-L1 in various malignancies, it may be one of the crucial therapeutic targets in a proportion of cases.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Fibrolipomatous Hamartoma Over the Left Forearm and Palm.

Introduction: Fibrolipomatous hamartomas are rare congenital benign tumors that can affect the nerves. The symptoms arise due to compression and may require surgical excision. Case Report: A man in his mid-20s suffered swelling over the volar aspect of the left forearm and hand for 4 months. He was symptomatic. A soft, non-tender swelling of size 6 × 4 cm was present over the flexor aspect of the left forearm and palm, with features suggestive of median nerve compression. Magnetic resonance imaging and electromyography were performed. Decompression of the carpal tunnel was performed with debulking of fibrofatty elements and fine dissection of the neural elements. Conclusion: This case report demonstrates a rare fibrolipomatous hamartoma encompassing the median nerve, which required surgical excision.

Diminution of Primary Cilia in the Stromal Cells at the Tumor-stromal Interface Correlates With an Aggressive Tumor Biology in the Urothelial Carcinoma of the Urinary Bladder.

BACKGROUND AND AIMS: Primary cilia (PC) are cellular organelles that regulate the cellular homeostasis. They are the seats of many oncogenic pathways and indirectly regulate the epithelial-mesenchymal transition (EMT) and extracellular matrix, both critical for the tumor microenvironment (TME). Though there are a few studies highlighting the alteration of PC in the tumor cells of various malignancies, none depict the PC in the stromal cells in the urothelial carcinoma of the urinary bladder (UC), the stromal cells being an essential component of TME. Therefore, we intend to evaluate the PC in the stromal cells at the tumor-stromal interface in UC. METHODS: Immunohistochemistry for acetylated-α-tubulin (for PC), Ki67, E-cadherin, and SNAI1 was performed in 141 cases of UC and 5 normal controls, and primary cilium: nucleus (C:N) ratio was counted in the stromal cells at the tumor-stromal interface. The C:N ratio was correlated with various clinical and histopathological parameters. RESULTS: The C:N ratio showed significant diminution from normal control (mean=0.75) to low-grade UC (mean=0.24) ( P =0.001) to high-grade UC (mean value=0.17) ( P =0.001). There was a significant diminution of the C:N ratio from the noninvasive to invasive UC ( P =0.025). The C:N ratio did not show any correlation with EMT although negatively correlated with the Ki67 index ( r =-0.32; P =0.001), and a higher ratio showed a trend with a higher recurrence-free survival ( P =0.07). CONCLUSIONS: The diminution of the PC in the stromal cells at the tumor-stromal interface is an early event and correlates with an aggressive tumor biology of UC.

C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B Fusion Negative Anaplastic Ependymoma with Lipogenic Differentiation.

Lipogenic differentiation in ependymoma is an infrequent occurrence with very few reported cases. The grading was done solely based on the histomorphology and molecular subtyping was not described in such ependymomas. New molecular classification divided ependymomas in nine different subgroups, of which supratentorial location tumor usually exhibits C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins. A 46-year-old female presented with headache and right-sided parapresis. Radilogy revealed a large intraxial left parietooccipital mass lesion, which histologically and immuohistochemically confirmed as anaplastic ependymoma with extensive lipogenic changes. The ependymal origin of the tumor was corroborated by the immunohistochemistry and ultrastructural studies. Molecular studies for C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B fusion proteins were negative. This is the first documentation of fusion negative supratentorial anaplastic ependymoma with lipogenic differentiation. This novel finding needs further reinforcement by similar studies to identify its impact on the disease outcome.

Assessment of Matrix Metalloprotease - 7 (MMP7) Immunohistochemistry in Biliary Atresia and Other Pediatric Cholestatic Liver Diseases.

Background and aims: Biliary atresia (BA) is a progressive fibro-obliterative cholangiopathy. The histopathological diagnosis is often challenging and an immunohistochemical marker is often sought as an adjunct. We evaluated MMP7 immunohistochemistry in BA and other non-BA pediatric cholestatic liver diseases. Materials and methods: MMP7 immunohistochemistry was applied in 5 age-matched normal control, 23 cases of BA and 43 cases of non-BA pediatric cholestasis including 16 cases of choledochal cyst (CC), and a multiplication score was obtained by multiplying the intensity and percentage positivity in the cholangiocytes. Results: BA showed a high mean MMP7 multiplication score which was significantly different from the normal control and other non-BA pediatric cholestatic diseases including CC (p value < 0.001). The sensitivity, specificity, positive, and negative predictive values of MMP7 immunohistochemistry were 91.3%, 93.02%, 87.5%, and 95.2% respectively. Conclusion: MMP7 immunohistochemistry may be an adjunct to histomorphology in BA.

Giant Cell Arteritis Masquerading As Migraine: A Case Report.

Giant cell arteritis, or temporal arteritis, is a chronic granulomatous vasculitis that affects large- and medium-sized arteries. An elderly male of 61 years presenting with chronic headaches for the past one year had been misdiagnosed as having migraine because of the similarity in symptoms. General examination revealed the presence of bilateral large, tortuous temporal arteries without any scalp tenderness, diminished arterial pulsations, or skin changes over the dilated arteries. A temporal artery biopsy revealed giant cell arteritis and was treated with steroids. This case report highlights the importance of considering secondary headaches, especially giant cell arteritis, in the differential diagnosis of new-onset headaches or worsening headaches in the elderly.

Expression of EZH2 and H3K27me3 predicts tumor biology of urothelial carcinoma.

Background: Enhancer of zeste homolog 2 (EZH2) is one of the major epigenetic modifiers involved in the transcriptional repression of target genes through trimethylation of H3K27 (lysine 27 residue of histone H3). Deregulated expression of both EZH2 and H3K27me3 has been implicated in the biological behavior and prognostic outcome of various malignancies. Aim: To assess the role of EZH2 and H3K27me3 in the carcinogenesis of urothelial carcinoma of urinary bladder. Materials and Methods: One hundred fifty consecutive urothelial carcinoma cases of urinary bladder (54.7% high-grade) were included in this study. Immunohistochemical analysis for EZH2 and H3K27me3 was performed on whole tissue sections. A multiplication score obtained by multiplying staining intensity and proportion of positively stained neoplastic cells was used for assessment. Results: EZH2 showed a significant correlation with the tumor grade and lamina propria invasion (p < 0.001). The cases with high EZH2 expression showed a significantly high proliferative index (Mean- 32.7%; p < 0.001). In contrast, negative and low expression of H3K27me3 was significantly more common in high-grade cases (p = 0.006). The expression of H3K27me3 was significantly associated with lamina propria (p = 0.01) and deep muscle invasion (p = 0.007). EZH2 showed a significantly higher expression in the high-grade invasive areas as compared to the high-grade non-invasive areas of the same tumor (p = 0.03). Conclusions: This study establishes an important role of the key epigenetic regulators EZH2 and H3K27me3 in the pathobiology of urothelial carcinomas. Strong expression of EZH2 and weak expression of H3K27me3 are associated with higher grade, proliferative index and invasive behavior.

Leukoreduction of red blood cell units decreases dysregulatory micro RNAs during routine storage: An observational study with In-silico analysis.

BACKGROUND: Red Blood cells (RBCs) bring about harmful consequences during storage. MicroRNA (miRNA) dysregulation in stored RBCs could represent potential biomarkers of storage lesions. Although leukoreduction prevents damage to RBCs, it is uncertain whether leukoreduction of RBCs would impact the dysregulation of miRNAs during storage. This study evaluated the potential role of miRNAs for any alteration of leukoreduced (LR) and non-leukoreduced (NLR) RBCs till 21 days of storage. STUDY DESIGN AND METHODS: In this prospective study, thirty male volunteers' blood was equally divided into leukoreduced RBCs (LR) and NLR RBC (NLR) bags and stored till Day 21 at 4-60c. Selected miRNAs were quantified on Days 0 and 21. Further, bioinformatic tools were used to analyze the selected miRNAs and their predicted target genes (mRNAs) and identify the miRNA-mRNA regulatory relationships. RESULTS: A significantly higher fold change values of three miRNAs (miR-96-5p, miR-197-3p, miR-769-3p) were observed in NLR RBCs (p < .05). A significantly higher (p < .05) expression levels of miR-150-5p and miR-197-3p were observed in NLR RBCs till 21 days of storage. Further, the correlation with mRNA quantification confirmed the regulatory role of these miRNAs upon functional pathway enrichment analysis. DISCUSSION: A higher level of dysregulation of miRNAs was observed in NLR RBCs. Validation from In-Silico analysis suggested the regulatory role of miRNAs in cell apoptosis, senescence, and RBC-related signaling pathways. This indicated that stored LR RBCs would likely have better in vivo survival and function following transfusion. However, an in vivo study of miRNA in RBCs is warranted for conclusive evidence.

Chondromyxoid Fibroma of a Rib.

Introduction: Chondromyxoid fibroma (CMF) is an uncommon bone tumor, accounting for <1% of all bone tumors. It generally affects the metaphysis of the long bone of the lower limb and seldom involves the small bones, but the involvement of the flat bones, like ribs, is infrequent. Case Report: A teenage girl complained of pain on the right side of the chest for the past 6 months, dull aching, and persistent without any diurnal variation. The chest X-ray examination showed a nodular, hyperdense lesion on the lateral chest wall near the 5-7th rib on the right side. A computed tomography scan confirmed the lesion from the sixth rib with ground-glass matrix and cortical thinning with a smooth margin, without any soft-tissue involvement. An enblock excision of the lesion was done. Histopathological studies showed a well-circumscribed tumor with reactive bone formation at the periphery with lobules of chondromyxoid tissue separated by spindle cells and stellate-shaped cells suggestive of CMF. At 1-year follow-up, she is asymptomatic without any recurrence. Conclusion: CMFs are rare benign tumors that require histopathological study to differentiate from other benign lesions of the bone. In flat tubular bones like the ribs, enblock resection is the mainstay of treatment.

Intracranial peripheral primitive neuroectodermal tumor presenting as neurosurgical emergency: A report of two cases.

Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) belongs to the family of malignant small and blue round cell tumors. It usually occurs in children and young adults with 3/4th of the cases arising from bone and 1/4 from soft tissue. Here, we present two cases of intracranial ES/pPNET who presented with mass effect. Management consists of surgical excision followed by adjuvant chemotherapy. Intracranial ES/pPNETs are highly aggressive and rare malignancies, reported to comprise of 0.03% of all intracranial tumors. The most common genetic aberration associated with ES/pPNET is chromosomal translocation t (11,12) (q24;q12). Patients with intracranial ES/pPNETs may present in acute or delayed manner. The presenting symptoms and signs depend on the location of the tumor. Intracranial pPNET although slow growing, they are highly vascular and may present as neurosurgical emergencies due to mass effect. We have presented the acute presentation of this tumor and its management.

Restoration of Altered Oncogenic and Tumor Suppressor microRNA Expression in Breast Cancer and Colorectal Cancer Cell using Epicatechin.

BACKGROUND: MicroRNAs (miRNA) are small non-coding RNAs that regulate the function of mRNA post-transcriptionally in a tissue-specific manner. miRNA expressions are heavily dysregulated in human cancer cells through various mechanisms, including epigenetic changes, karyotype abnormalities, and miRNA biogenesis defects. miRNAs may act as either oncogenes or tumor suppressors under different conditions. Epicatechin is a natural compound found in green tea which possesses antioxidant and antitumor properties. OBJECTIVE: The objective of this study is to investigate the effect of epicatechin treatment on the expression level of several oncogenic and tumor suppressor miRNAs in breast and colorectal cancer cell lines (MCF7 and HT-29) and identify its mechanism of action. METHODS: The MCF-7 and HT29 cells were treated with epicatechin for 24 hours and untreated cells were considered control cultures. miRNA was isolated and qRT-PCR was used to measure the expression profile changes of different oncogenic and tumor suppressor miRNAs. Furthermore, the mRNA expression profile was also screened at different concentrations of epicatechin. RESULTS: Our results showed several-fold changes in miRNAs expression level, which is cell line specific. Also, epicatechin at different concentrations induces biphasic changes in mRNA expression levels in both cell lines. CONCLUSION: Our findings first time demonstrated that epicatechin can reverse the expression of these miRNAs and may trigger the cytostatic effect at a lower concentration.

Holocord metastasis from supratentorial glioblastoma multiforme: an uncommon manifestation of a common tumor.

Intramedullary metastasis from primary glioblastoma multiforme (GBM) is a rare phenomenon with a poor prognosis. The rate of spinal metastasis from intracranial GBM has been variably reported to be 0.4-2%. According to a review by Lawton in 2012, there were only 42 documented cases of primary intracranial GBM with spinal metastasis. We present a unique case of early-onset symptomatic holocord metastasis of GBM in a patient approximately 2 months of detection of primary GBM.

Blastic plasmacytoid dendritic cell neoplasm: A clinicopathological diagnostic dilemma report of three cases with review of literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic neoplasm and classified under acute myeloid leukemia. Here, we describe the clinicopathological features of three cases of BPDCN: two with classical and one uncommon immunophenotype. A-35-year-old female (case 1) presented with complaint of nasal mass and generalized lymphadenopathy. Biopsy from axillary lymph node showed infiltration by cells with scant cytoplasm which were immunopositive for LCA, CD4, CD43, and ALK1. Flowcytometry showed positivity for CD45, CD4, CD33, and CD123 while negative for rest all markers. The other two cases have classical immunophenotype. In clinical practice, nasal mass with lymphadenopathy suggests natural killer T-cell/peripheral T-cell lymphoma. Again immunohistochemical positivity for CD4, CD43, and ALK while negativity for CD3 suggests anaplastic large cell lymphoma. In this case, morphology and extensive bone marrow involvement raise the suspicion. Fowcytometry positivity for HLADR, CD123, and CD33 helps in making diagnosis.

Altered Nasal Microbiome in Atrophic Rhinitis: A Novel Theory of Etiopathogenesis and Therapy.

Background: Atrophic rhinitis (AtR) is a chronic nasal condition with polygenic and polybacterial etiology. We investigated the clinical outcomes of honey therapy and the associated nasal microbiome in AtR. Methods: For eight weeks, a nonrandomized control trial using a nasal spray of 10% manuka honey and saline on the right and left sides of the nose was conducted on 19 primary AtR patients. A nasal endoscopy was performed and a mucosal biopsy were taken before and after the intervention. Five of the nineteen patients were selected for microbiome and GPR43 expression studies. Results: We used manuka honey to describe an effective prebiotic treatment for atrophic rhinitis. There were nine males and ten females with an average (±SD) age of 33.8 (±10.7) years. Endoscopic scores and clinical symptoms improved in honey-treated nasal cavities (p < 0.003). There was a significant decrease in inflammation, restoration of mucus glands, and increased expression of GPR43 in the nasal cavities with honey therapy. The nasal microbiome composition before and after treatment was documented. Particularly, short chain fatty acid (SCFA) producers were positively enriched after honey therapy and correlated with improved clinical outcomes like nasal crusting, congestion, and discharge. Conclusion: Our approach to treating AtR patients with manuka honey illustrated effective clinical outcomes such as (1) decreased fetid smell, (2) thickening of the mucosa, (3) decreased inflammation with healed mucosal ulcers, (4) increased concentration of the mucosal glands, (5) altered nasal microbiome, and (6) increased expression of SCFA receptors. These changes are consequent to resetting the nasal microbiome due to honey therapy.

Elevated expression of cholesterol transporter LRP-1 is crucially implicated in the pathobiology of glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor with a grave prognosis. The present study evaluated the expression of Cholesterol transporter [importer -Lipoprotein Receptor-related Protein-1 (LRP-1) and exporter -ATP-binding cassette transporters-1 (ABCA-1)] in GBM and their implications in tumor-biology, clinical outcome and therapeutic potentials. The mRNA and protein expression was assessed by qRT-PCR and immunohistochemistry, respectively, in 85 GBMs. For comparison, 25 lower-grade astrocytomas (IDH-mutant, grade-2/3) [LGA] 16 cases of high-grade astrocytomas (IDH-mutant, grade-4) [HGA] were also evaluated. In-vitro analysis was performed on U87MG and LN229 glioma cell line. The expression of LRP-1 (mRNA and protein) was significantly higher in GBM than LGA, HGA and normal brain (NB) [p-values 0.007, 0.003 and <0.001 for mRNA; 0.024, <0.001 and <0.001 for immunohistochemistry]. Majority of the GBMs (82.4%) showed strong immunoreactivity for LRP-1, and all tumor cases were positive while the normal brain was negative. LRP-1 immunoreactivity positively correlated with the MIB-1 labeling index (p-value-0.013). LRP-1 knockdown in-vitro was associated with decreased cell survival, proliferation, migration, invasion, and increased apoptosis. Similar effect was also demonstrated by Receptor Associated Protein (RAP), a LRP-1 inhibitory drug. The silencing of LRP-1 was also associated with decreased cholesterol level. The ABCA-1 expression was higher in GBM than LGA and NB (p-value 0.011 and <0.001), however there was no significant association with other parameters. LRP-1 showed a positive correlation with ABCA-1 and associated with decreased expression with LRP-1 knock-down in-vitro. The expression of LRP-1 and ABCA-1 didn't correlate with overall survival in GBMs. Hence, LRP-1 is crucial for the tumor cells' survival and aggressive biological behavior which is maintain through the regulation of high intracellular cholesterol import. Its expression is significantly higher in GBMs and also implicated in the regulation of ABCA-1 expression. Considering its immune-positivity only in the neoplastic cell and strong positivity in GBM it may be a useful adjunct to the diagnosis. For the first time, the present study emphasized its role as a potential therapeutic target in the form of RAP which is presently being used in other neurological diseases under clinical trials.

Pediatric-type diffuse low grade gliomas: Histomolecular profile and practical approach to their integrated diagnosis according to the WHO CNS5 classification.

Low-grade gliomas are the most common primary central nervous system (CNS) neoplasms in the pediatric age group. The majority of these tumors are circumscribed, while diffuse low-grade gliomas are relatively rare. The pediatric type diffuse low-grade gliomas (pDLGG) have a distinctly different biological behavior, molecular profile, and clinical outcome as compared to their adult counterpart. In the 5th edition of World Health Organization (WHO) CNS classification, pDLGGs are subclassified into four distinct histomolecular entities, namely, (i) diffuse astrocytoma, MYB- or MYBL1-altered, (ii) angiocentric glioma, (iii) polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and (iv) diffuse low-grade glioma, MAPK pathway-altered. Although the molecular profile, to a great extent, aligns with the morphological features, it is not specific. Many of the molecular alterations described in pDLGG have therapeutic implications with the availability of newer targeted therapies. A wide range of testing platforms are available for routine assessment of these molecular alterations in clinical laboratories, though WHO does not recommend any particular method.