Development of a cost-effective compact diode-laser-based photoacoustic sensing instrument for breast tissue diagnosis.

Significance: The photoacoustic (PA) technique, a noninvasive pump-probe technique, has found interesting applications in biomedical tissue diagnosis over the last decade. To take it a step further to clinical applications, the PA technique needs to be designed as an instrument focusing on a compact design, reducing the cost, and quickly providing a quantitative diagnosis. Aim: This work presents a design and characterization of a cost-effective, compact PA sensing instrument for biomedical tissue diagnosis. Approach: A compact laser diode case design is developed to house several laser diodes for PA excitation, and a pulsed current supply unit is also developed in-house to power the laser diodes to generate a 25 ns current pulse at a frequency of 20 kHz. After PA experimental data acquisition, the signal's frequency spectra were calculated to characterize the tissue quantitatively and correlated with their mechanobiological properties. Results: The corresponding dominant frequency peak in the PA spectral response (PASR) study was low in the fibrofatty normal breast tissue 0.26±0.03 MHz, compared to the dominant frequency peak of 1.60±0.016 MHz in the fibrocystic disease tissue, which had increased glandular and stromal elements, thereby increased tissue density. The histopathological findings correlated with the PASR results, and the fibrocystic breast disease tissue exhibited a higher dominant frequency peak and energy compared to the normal breast tissue. Conclusions: We experimented with an in vitro PASR study of fibrocystic human breast tissues and successfully differentiated different tissue types using quantitative spectral parameters peak frequency, mean frequency, and spectral energy. This gives the potential to take this technique further for cost-effective and quick clinical applications.

Dietary tannic acid attenuates elastase-induced pulmonary inflammation and emphysema in mice.

Emphysema is one of the major components of chronic obstructive pulmonary disease (COPD), which is characterised by the destruction and enlargement of air spaces, leading to airflow limitation and dyspnoea, finally progressing to oxygen dependency. The alveolar wall destruction is due to chronic inflammation, oxidative stress, apoptosis, and proteinase/anti-proteinase imbalance. So far, there has been no effective therapy for patients with COPD. We evaluated the therapeutic efficacy of tannic acid (TA), a naturally occurring plant-derived polyphenol in the murine emphysema model. In C57BL/6 J mice, we established emphysema by intratracheal instillation of elastase (EL). Then, mice were treated with TA and evaluated 1 and 21 days post-EL instillation. After 24 h, TA treatment significantly reduced EL-induced histopathological alterations, infiltrating leukocytes, and gene expression of markers of inflammation and apoptosis. Similarly, after 21 days, TA treatment suppressed the mean linear intercept, gene expression of proteinases, and increased elastic fiber contents in the lungs when compared to the EL-alone group. Furthermore, EL induced the activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB) p65 pathways in the lungs was suppressed by TA treatment. In summary, TA has the potential to mitigate EL-induced inflammation, apoptosis, proteinase/anti-proteinase imbalance, and subsequent emphysema in mice.

Giant Plexiform Schwannoma on the Medial Aspect of the Left Thigh.

Plexiform schwannoma (PS), or neurilemmoma, is an uncommon benign tumor originating from a peripheral nerve sheath. It consists of Schwann cells organized in an intricate, web-like pattern. A male farmer in his 50s from rural India sought medical attention for a painless mass on his left thigh, present for 30 years. Physical examination revealed a firm, non-tender mass with restricted mobility. Imaging, including X-ray and ultrasound, indicated a neoplastic lesion. Fine needle aspiration (FNA) cytology revealed spindle-shaped cells, prompting a provisional diagnosis of a spindle cell lesion. Surgical excision was performed successfully, with histopathological examination confirming PS. He experienced no postoperative complications, and at the one-year follow-up, the complete resolution of symptoms and normal daily activities were observed.

Presence of entry receptors and viral markers suggest a low level of placental replication of hepatitis B virus in a proportion of pregnant women infected with chronic hepatitis B.

The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host.

Haemoptysis in Askin's Tumour: Intrapulmonary Presentation of an Extrapulmonary Tumour.

Ewing's sarcoma (ES) is a small round cell sarcoma arising in the bone or soft tissue. Ewing's sarcoma/primitive neuroectodermal tumours (PNET) of the thoracopulmonary region is called Askin's tumour. The common clinical presentations described for this extrapulmonary tumour are fever, chest wall mass with or without pain, dyspnea, and cough. Very few cases of Askin's tumour have been reported with haemoptysis as the initial presentation, which is usually a presentation of intrapulmonary lesions. A 22-year-old male presented to the emergency department with complaints of haemoptysis, mild chest pain, and swelling on the right side of the chest wall. Radiological investigations showed a soft tissue mass measuring 13 cm × 11 cm × 10 cm in the right thoracic region, causing the destruction of the second rib. Histopathological examination showed the presence of a malignant small round cell tumour. Immunohistochemistry (IHC) analysis showed the tumour to be positive for CD99, NKX 2.2, and MIC2. The final diagnosis of Askin's tumour of the thoracopulmonary region was given. The case is being reported in view of the rare type of clinical presentation.

Downregulation of Lipid Phosphate Phosphatase 3 Correlates With Tumor-Infiltrating Immune Cells in Oral Cancer.

Background Sphingosine-1-phosphate (S1P) is a potent oncogenic lipid. Intracellular levels of S1P are tightly regulated by eight S1P-metabolizing enzymes. S1P synthesis is catalyzed by two sphingosine kinases, i.e., sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Five lipid phosphatases (two S1P phosphatases and lipid phosphate phosphatases (LPPs) 1, 2, and 3) reversibly convert S1P back to sphingosine. Previously, we have determined the mRNA expression profile of eight S1P-metabolizing enzymes in tumor tissues and adjacent normal tissues from oral squamous cell carcinoma (OSCC) patients. Except for SphK1, the role of S1P-metabolizing enzymes in OSCC has been poorly studied. Methods We have determined the protein expression of four S1P-metabolizing enzymes (SphK1, SphK2, sphingosine-1-phosphate phosphatase 1 (SGPP1), and lipid phosphate phosphatase 3 (LPP3)) by immunohistochemistry (IHC) in tumor tissues of 46 OSCC patients. Six subjects with non-dysplastic oral mucosa were also included in the study. The immunoreactivity score (IRS) was calculated for each protein in every subject. Further, we determined the associations of expression of S1P-metabolizing enzymes with clinicopathological features of OSCC patients. Results We demonstrate the low IRS for SphK2 and LPP3 in OSCC tumors. Importantly, expression of SphK2 and LPP3 was downregulated in malignant epithelial cells compared to non-malignant mucosa. Further, LPP3 expression negatively correlated with tumor­node­metastasis (TNM) staging of patients (r = -0.307, p = 0.043). Importantly, expression of LPP3 in tumors was found to be an independent predictor of perinodal extension (b = -0.440, p = 0.009), lymphovascular invasion (b = -0.614, p < 0.001), lymph node ratio (b = 0.336, p = 0.039), and TNM staging (b = -0.364, p = 0.030). Conclusion Taken together, our data show that expression of SphK2 and LPP3 is decreased compared to normal mucosa. Thus, the S1P signaling pathway could represent a potential therapeutic target.

Evolution of pathology teaching for MBBS students during COVID-19 pandemic lockdown: Moving from a real to a virtual classroom.

BACKGROUND: The COVID-19 pandemic lockdown has forced university hospitals to forego traditional classes and embrace online teaching platforms as the sole modality of medical education. Herein, we describe our experience of shifting from the arena of a real to a virtual classroom during the lockdown phase. Materials and. METHODS: The institutional subscription of G-suite was used for creating a virtual Google classroom. Google Calendar, Google Meet, and Google Forms were used for notification of schedules, conducting theory and practical classes, and conducting assessments, respectively. The learner-centric SNAPPS model was adapted for an interactive case-based learning (CBL) program using multimedia tools. Students' perspective on online education was assessed based on their responses to a validated questionnaire. RESULTS: The conduction of online classes, particularly the live practical classes and the CBL program got the maximum affirmative (up to 85%) responses. Students of the same batch also performed better in a test following the online CBL (77.03% vs 73.3%, P = 0.03, paired t-test statistically significant) compared to a test before it. However, access to laptops and poor Internet connectivity were significant causes of concern for nearly 40% of students. CONCLUSION: The use of virtual classroom has proved to be an efficient method for continuing teaching of Pathology to MBBS students in times of lockdown when face-to-face conventional teaching was not possible. The experience indicated that in the future a judicious mixture of traditional and online classes may be a more effective educational design for teaching Pathology to MBBS students.

An unusual case of paediatric plasmablastic lymphoma presenting with malignant effusion and the challenges in its diagnosis.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma occurring commonly in the oral mucosa and jaw of human immunodeficiency virus (HIV) positive adult males. PBL is not a common occurrence in children and a presentation with malignant effusion is rarely reported. Herein, we share our experience in the challenges confronted in the diagnosis of PBL in a 6-year-old, HIV positive boy presenting with malignant pleural and peritoneal effusions along with gum hypertrophy, lymphadenopathy and paranasal sinus mass. Amenability of pleural effusion to exfoliative cytology led to an initial cytological examination demonstrating large atypical lymphoid cells with plasmacytoid morphology and a plasmablastic variant of Burkitt lymphoma was initially considered. However immunophenotyping by flowcytometry (FCM) and a cell block immunohistochemical evaluation of the serous effusion suggested a plasma cell immunophenotype and a diagnosis of PBL was favored. A subsequent biopsy from the paranasal sinus mass confirmed the diagnosis of PBL but showed tumour cell angiocentricity on morphology and CD45 expression on immunohistochemistry (IHC), both unusual features in PBL. A CD20 negative/MUM-1 positive immunoprofile and presence of a solid tumour mass in a typical location in addition to malignant effusion substantiated the diagnosis of PBL. The patient was offered HAART (highly active antiretroviral therapy) and chemotherapy and is on follow-up. Paediatric PBL with malignant effusion is rarely reported and this case stresses the importance of use of a multimodality diagnostic approach for an accurate diagnosis.

Anti-asthmatic effects of tannic acid from Chinese natural gall nuts in a mouse model of allergic asthma.

Asthma is a chronic inflammatory disease of the airways, which is characterized by infiltration of inflammatory cells, airway hyperresponsiveness (AHR), and airway remodeling. This study aimed to explore the role and mechanism of tannic acid (TA), a naturally occurring plant-derived polyphenol, in murine asthma model. BALB/c mice were given ovalbumin (OVA) to establish an allergic asthma model. The results revealed that TA treatment significantly decreased OVA-induced AHR, inflammatory cells infiltration, and the expression of various inflammatory mediators (Th2 and Th1 cytokines, eotaxin, and total IgE). Additionally, TA treatment also attenuated increases in mucins (Muc5ac and Muc5b) expression, mucus production in airway goblet cells, mast cells infiltration, and airway remodeling induced by OVA exposure. Furthermore, OVA-induced NF-κB (nuclear factor- kappa B) activation and cell adhesion molecules expression in the lungs was suppressed by TA treatment. In conclusion, TA effectively attenuated AHR, inflammatory response, and airway remodeling in OVA-challenged asthmatic mice. Therefore, TA may be a potential therapeutic option against allergic asthma in clinical settings.

Sinonasal organising haematoma - a little known entity / Hematoma nasossinusal em organização - uma entidade pouco conhecida

Abstract Introduction: Sinonasal organising haematoma is a recently described, rare, benign inflammatory condition, which closely resembles malignancy in its clinical presentation. Objective: To describe the clinical features of organising haematoma and to review the evolution of surgical options successfully used. Methods: A retrospective review of charts of all patients with a histopathological diagnosis of sinonasal organising haematoma was performed. Results: Six (60%) of the 10 patients were male with a mean age of 47.4 years. All patients had unilateral disease with recurrent epistaxis as the presenting symptom. Maxillary sinus was the most commonly involved sinus. There was no history of trauma in any of the patients. Hypertension (80%) was the most commonly associated comorbidity. Contrast-enhanced CT scan of the paranasal sinuses showed heterogeneous sinus opacification with/without bone erosion. Histopathological examination was diagnostic. Complete endoscopic excision was done in all patients resulting in resolution of the disease. Conclusion: Awareness of this relatively new clinical entity and its evaluation and treatment is important for otolaryngologists, maxillofacial surgeons and pathologists alike. Despite the clinical picture of malignancy, histopathological features of benign disease can safely dispel such a diagnosis.

Resumo Introdução: Hematoma nasossinusal em organização é uma condição inflamatória benigna rara, recentemente descrita, que se assemelha a lesões malignas em sua apresentação clínica. Objetivo: Descrever as características clínicas do hematoma em organização e analisar a evolução das opções cirúrgicas usadas com sucesso. Método: Foi feita a revisão retrospectiva dos prontuários de todos os pacientes com diagnóstico histopatológico de hematoma nasossinusal em organização. Resultados: Seis (60%) dos 10 pacientes eram do sexo masculino, com média de 47,4 anos. Todos os pacientes apresentavam doença unilateral com epistaxe recorrente como sintoma de apresentação. O seio maxilar era o mais comumente afetado. Não havia histórico de trauma em qualquer dos pacientes. Hipertensão (80%) foi a comorbidade mais comumente associada. A tomografia computadorizada dos seios paranasais com contraste mostrou opacificação heterogênea do seio com/sem erosão óssea. O exame histopatológico foi diagnóstico. A excisão endoscópica completa foi feita em todos os pacientes, resultou na resolução da doença. Conclusão: A conscientização a respeito dessa entidade clínica relativamente nova e sua avaliação e tratamento são importantes para os otorrinolaringologistas, cirurgiões buco-maxilo-faciais e patologistas. Apesar do quadro clínico de malignidade, as características histopatológicas da doença benigna podem descartar com segurança esse diagnóstico.

Sinonasal organising haematoma - a little known entity.

INTRODUCTION: Sinonasal organising haematoma is a recently described, rare, benign inflammatory condition, which closely resembles malignancy in its clinical presentation. OBJECTIVE: To describe the clinical features of organising haematoma and to review the evolution of surgical options successfully used. METHODS: A retrospective review of charts of all patients with a histopathological diagnosis of sinonasal organising haematoma was performed. RESULTS: Six (60%) of the 10 patients were male with a mean age of 47.4 years. All patients had unilateral disease with recurrent epistaxis as the presenting symptom. Maxillary sinus was the most commonly involved sinus. There was no history of trauma in any of the patients. Hypertension (80%) was the most commonly associated comorbidity. Contrast-enhanced CT scan of the paranasal sinuses showed heterogeneous sinus opacification with/without bone erosion. Histopathological examination was diagnostic. Complete endoscopic excision was done in all patients resulting in resolution of the disease. CONCLUSION: Awareness of this relatively new clinical entity and its evaluation and treatment is important for otolaryngologists, maxillofacial surgeons and pathologists alike. Despite the clinical picture of malignancy, histopathological features of benign disease can safely dispel such a diagnosis.

Multispectral Dermatoscopic Features of Chemical Leucoderma with Pigmented Contact Dermatitis.

Chemical leukoderma is characterized by pigment loss on constant exposure to chemical agents. Its association with pigmented contact dermatitis is rare. Here, we report a 40-year-old female presenting with depigmented macule with surrounding hyperpigmentation over the upper forehead. We used a multispectral dermatoscope by which decreased pigment network was better visualized with blue light, and gray granular dots were better appreciated with yellow light. Shorter wavelengths delineate epidermal features better whereas longer wavelengths highlight dermal features in multispectral dermatoscopy.

Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India.

OBJECTIVES: Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision. This article describes the study protocol at its pre - results stage. METHODS AND ANALYSIS: PRISM-HNSCC is a bilateral observational research being conducted in Darwin, Australia and Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide local excision of the tumour followed by histopathological assessment. Tumours with clear surgical margins that satisfy the exclusion criteria will be selected for further staining of the margins with eIF4E and p53 antibodies. Results of IHC staining will be correlated with recurrences in an attempt to predict the risk of disease recurrence. Patients in Darwin will undergo intraoperative staining of the lesion with Lugol's iodine and fluorescence visualisation to delineate the excision margins while patients in Vellore will not undertake these tests. The outcomes will be analysed. ETHICS AND DISSEMINATION: The PRISM-HNSCC study was approved by the institutional ethics committees in Darwin (Human Research Ethics Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967). Outcomes will be disseminated through publications in academic journals and presentations at educational meetings and conferences. It will be presented as dissertation at the Charles Darwin University. We will communicate the study results to both participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12616000715471).

Unusual sites of metastases of carcinoma cervix.

We present a case of metastatic squamous cell carcinoma cervix with solitary bone metastases to the right tibia and multiple cutaneous metastases. A woman aged 52 years with cancer of the cervix and lung metastases, after 21 months of initial diagnosis and palliative chemotherapy presented with pain in the right knee and multiple nodular skin lesions. Bone scintigraphy revealed intense increased tracer activity in the proximal and mid shaft of the right tibia. Biopsy from the tibial lesion confirmed metastatic squamous cell carcinoma. The presentation, diagnosis and management of this rare case are discussed.

Hansen's disease: An unusual presentation.

Hansen's disease can present with varied and subtle symptoms which can be missed. A middle-aged gentleman presented with swelling of face and hands. Detailed examination and investigations confirmed borderline tuberculoid leprosy with lepra reaction. A high index of suspicion with vigilance can help to make an early diagnosis in this potentially treatable condition.

Solitary Angiokeratoma Presenting as Cutaneous Horn over the Prepuce: A Rare Appearance.

We present a case of a 47-year-old man with 4 months history of conical growth on the prepuce with a progressive increase in size. The patient had been treated for seminoma a decade ago. Histopathology of the growth showed features of angiokeratoma. It is unusual for angiokeratoma to masquerade as a cutaneous horn.

Bullous Fixed Drug Eruption Probably Induced by Paracetamol.

We report a case of a 42-year-old male who presented with second episode of bullous eruptions after ingestion of paracetamol. There were no systemic complaints. The temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous fixed drug due to paracetamol. Applying Naranjo's algorithm, a causality score of 8 was obtained and was categorized as probable reaction to paracetamol. Clinicians should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Drug alert cards could play an important role in preventing recurrences.

Role of conventional and diffusion weighted MRI in predicting treatment response after low dose radiation and chemotherapy in locally advanced carcinoma cervix.

BACKGROUND AND PURPOSE: To assess the diagnostic performance of conventional and diffusion weighted (DWI) magnetic resonance imaging (MRI) in predicting response in locally advanced cervical cancer. MATERIALS AND METHODS: Total 24 patients with stage IIB-IIIB squamous cell carcinoma cervix were treated with initial two cycles of paclitaxel and carboplatin and concurrent low dose radiotherapy prior to standard chemoradiation. Response was assessed clinically and radiologically after 3 weeks of initial treatment. Volumetric and functional parameters derived from conventional and diffusion weighted MRI, due to treatment were measured. RESULTS: Significant reduction of GTV was noted in MRI (54 cm(3) vs. 11 cm(3), p < 0.01) and DWI (44 cm(3) vs. 6 cm(3), p < 0.01, ΔADC = 0.49 × 10(-3)mm(2)/sec, p < 0.01) after treatment. Tumor volume reduction rate (TVRR) in DWI was significantly higher in pathological good responders (p = 0.03). In this group both mean post treatment apparent diffusion coefficient (ADC) value and ΔADC were significantly higher (p = 0.01 and p = 0.03). ADC was a good predictor for pathological response (area under receiver operating characteristic curve (ROC) 0.814). CONCLUSION: TVRR (DWI) and ΔADC can be used as a predictor of early pathological response. Complete response based on DWI, could be a useful predictor of long term disease control.

Adult-onset linear syringocystadenoma papilliferum over the inguinal fold: a case report with emphasis on mast cell staining pattern.

Syringocystadenoma papilliferum (SCAP) is a rare hamartoma with predominant apocrine differentiation. Clinically, presenting as solitary nodule, nodular plaque, or linear nodules, SCAP usually occurs over the head and neck region in children. Out of these three morphological presentations, the linear type is the most rare. We report herein a case of a 36-year-old man with linear SCAP over the right inguinal fold, for its rarity. Besides the typical histologic features, a marked increase in lesional mast cell concentration as compared to a control specimen obtained from an unaffected site and a strikingly raised number of spreading and degranulated mast cells were demonstrated.