Covid-19-Associated Mucormycosis: Histopathology of the Deadly Fungal Infection.

Introduction Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. Objective The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. Methods A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. Results The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% ( n = 26/38) of the patients had diabetes as a comorbidity, 84.2% ( n = 32/38) had a history of steroid intake, and 55.3% ( n = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% ( n = 29/38), periorbital fat/orbit 21.1% ( n = 8/38), maxillary sinus 15.8% ( n = 6/38) and ethmoid sinus 13.2% ( n = 5/38). In 76.3% ( n = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. Conclusion COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.

Primary Small Cell Neuroendocrine Carcinoma of nasopharynx with metastatic cervical lymph nodes: an exceedingly rare entity with review of literature.

Small cell neuroendocrine carcinoma of nasopharynx is extremely rare and displays aggressive nature with a poor prognosis. Neuroendocrine tumours rarely arise from the head and neck region and pose a diagnostic and management challenge. In English literature, only 16 cases of primary small cell neuroendocrine carcinoma of nasopharynx have been reported so far; and to the best of our knowledge, this is the seventeenth case and second in the younger age group. Here, we report the case of an adolescent male patient who presented with nasal blockage, repeated episodes of epistaxis and neck swellings. After proper diagnostic workup, the diagnosis of small cell neuroendocrine carcinoma of nasopharynx was made. The patient was treated with chemotherapy, followed by radiotherapy. Imaging investigation executed after the end of the treatment exhibited complete remission of the disease. The patient is kept under active surveillance with no signs of relapse at present.

Parathyroid carcinoma in a patient with primary hyperparathyroidism mimicking parathyroid adenoma.

Primary hyperparathyroidism caused by parathyroid carcinoma is extremely rare. Clinically, it is very challenging to differentiate between parathyroid carcinoma and adenoma. The correct diagnosis is made based on the histopathology of the resection specimen. This case report presents a woman in her 40s with body aches, knee joint pain, and fatigue, along with chronic kidney disease. Ultrasonography revealed a large hyperechoic lesion in the left parathyroid gland. Serum calcium, parathyroid hormone, urea, and creatinine levels were increased. The inferior parathyroid gland was surgically removed, and histopathological evaluation confirmed a diagnosis of parathyroid carcinoma. Unfortunately, many patients do not undergo complete resection due to a lack of a correct diagnosis during the initial surgery.

Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma.

Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16, DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance.

Application of international system for reporting serous fluid cytology (ISRSFC) in effusion samples-a prospective study in an oncology setting.

INTRODUCTION: Serous fluid cytology is a cost-effective procedure that can help in the diagnosis, staging, and origin of the malignancy. Recently introduced International System for Reporting Serous Fluid Cytology (ISRSFC) standardizes the reporting of serous fluid cytology in the 5 categories: Category 1: Nondiagnostic (ND), Category 2: negative for malignancy (NFM), Category 3: atypia of undetermined significance (AUS), Category 4: suspicious for malignancy (SFM), and Category 5: malignant (MAL). Here, we present our experience adopting the ISRSFC. MATERIALS AND METHODS: We implemented ISRSFC in December of 2019 at our institute and included a cohort of 555 prospective effusion samples. The pertinent surgical pathology, radiology, and clinical follow-up were also extracted to assess the risk of malignancy (ROM) and performance parameters. RESULTS: The assessment of interobserver reliability indicated substantial concordance (κ = 0.717) between the 2 investigators for serous fluid categorization. A total of 555 effusion samples were classified as follows: ND, 14 (2.5%); NFM, 394 (71%); AUS, 12 (2.2%); SFM, 13 (2.3%); and MAL, 122 (22%). The ROM for the ND, NFM, AUS, SFM, and MAL categories was 57.1%, 9.9%, 66.7%, 66.7%, and 97.2%, respectively, in peritoneal effusions and 57.1%, 7.1%, 66.7%, 100%, 100%, respectively, in pleural effusions. The ROM for NFM and MAL was 0% and 100%, respectively, in pericardial effusion. CONCLUSIONS: Application of the proposed ISRSFC can help in achieving uniformity and reproducibility in diagnoses and also help in risk stratification in cytology. ISRSFC was successfully adopted by our cytology laboratory and clinicians, with overall diagnostic performance similar to previous studies.

Programmed Death Ligand 1 Expression in Lung Adenocarcinoma: An Analysis of the Histomorphological Features.

Background: Immunotherapy is now a vital target therapy in the advanced cases of lung adenocarcinoma. The outstanding result of therapies with medications that inhibit the interaction of programmed death ligand 1 with programmed death protein 1 has revolutionarized prognostic treatment regimes. Aims: The study was undertaken with the objectives to analyze the detailed histomorphological features of adenocarcinoma lung with programmed death ligand-1 (PD-L1) expression in tumor cells and to compare the histomorphological features with PD-L1 negative group. Materials and Methods: The present study is a retrospective case series with 100 cases of non-small cell lung cancer-adenocarcinoma phenotype in which testing for PD-L1 had been done using immunohistochemistry. Detailed histomorphological analysis and comparison was performed for both the PD-L1 positive and negative phenotype. Results: Histomorphological features of 25 cases with positive PD-L1 positivity in the tumor cells and 75 cases that were negative for PD-L1 were analyzed. The most frequent pattern in the category that was PD-L1 positive was singly scattered cells or loose clusters present in 84% cases followed by solid nests that was identified in 60% cases. The presence of solid nests in the PD-L1 positive category was statistically significant (P = 0.018). Mucin was identified in 24% cases, and tumor necrosis was documented in 60% cases with PD-L1 positivity. In the cluster that was PD-L1 positive, 92% cases had moderate-to-severe nuclear pleomorphism. Conclusion: The identification of histomorphological patterns and characteristics may aid in triaging cases that have the likelihood to harbor PD-L1-positive phenotype, which has predictive and prognostic outcome.

Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study.

BACKGROUND: Diffuse gliomas in the adult population are the most common primary central nervous system (CNS) tumors. The World Health Organization incorporated isocitrate dehydrogenase (IDH) mutations and 1p/19q co-deletion with histopathological features into an "integrated diagnosis" in the revised classification of tumors of CNS. These molecular subgroups of diffuse gliomas are found to stratify patients into prognostically distinct groups better than the histological classification. The objectives of the current study were to assess the frequency of IDH mutation, ATRX expression loss, p53 overexpression, and 1p/19q co-deletion detection in adult diffuse gliomas (Grade II, III, and IV) and to correlate them with clinicopathological and histopathological features. MATERIALS AND METHODS: The current study was a tertiary care hospital-based retrospective case series of 112 cases of adult diffuse gliomas. Immunohistochemistry (IHC)-based molecular detection was performed for IDH-1, ATRX, and p53 and fluorescent in situ hybridization (FISH) was performed for 1p/19q co-deletion detection. RESULTS: IDH-1 mutation was present in 30.4% (n = 34/112) cases, ATRX expression was lost in 18% (n = 19/104) cases, p53 was mutated in 39.3% (n = 42/107) cases and 1p19q was co-deleted in 25% (n = 4/16) cases. In the IDH1 mutant cases, with retained ATRX, FISH for 1p/19q co-deletion was performed and was co-deleted in four cases. CONCLUSION: The results of the present study indicate that IHC including IDH1/2, ATRX, and p53 is useful for the molecular classification of diffuse gliomas, which could be useful for the evaluation of prognosis, especially Grade III and II. Although the immunohistochemical approach does not replace genetic testing completely, it is a practical and powerful means of assessing molecular genetic changes. IDH mutations are the established markers of better prognosis in diffuse gliomas.

Diagnostic Efficacy of BRAFV600E Immunocytochemistry in Thyroid Aspirates in Bethesda Category IV and Papillary Thyroid Carcinoma.

BACKGROUND: In papillary thyroid carcinoma (PTC), BRAFV600E is a common mutation and is associated with aggressive clinical behaviour. Immunocytochemistry (ICC) and molecular testing are recommended in the Bethesda System for Reporting Thyroid Cytopathology 2017 (TBSRTC) category III, IV and V. AIMS: The current study aimed to evaluate the diagnostic efficacy of conventional FNAC versus FNAC with BRAFV600E immunostaining in cases of TBSRTC category IV, cases of suspicious for PTC and cases of PTC. METHODS AND MATERIAL: The study included a prospective case series of 45 patients with clinically palpable thyroid nodules with TBSRTC category IV, category V (suspicious for PTC) and PTC. The corresponding histology specimens of all the 45 cases were also analyzed. Immunostaining for BRAFV600E was performed on FNAC cell blocks and their corresponding histology sections using anti-BRAF (VE1) clone (Ventana). The diagnostic efficacy of the BRAFV600E immunostaining was compared on cytological specimens with histological specimens. RESULTS: BRAFV600E immunostaining helped to improve the sensitivity of the cytology to confirm the PTC as a diagnostic aid for thyroid FNAs. Cytology alone had a sensitivity of 62.96% and a lower specificity of 60.70%. The combination of both the tests together provided 84.62% sensitivity and much higher specificity of 100%. PPV was also increased to 100% and NPV was raised 94.12%. CONCLUSIONS: The performance of BRAFV600E immunostaining on the cytological specimen is a rapid, simple and cost-effective test and could be considered in TBSRTC category IV and suspicious and malignant cases of PTC.

Longitudinal Serology of SARS-CoV-2-Infected Individuals in India: A Prospective Cohort Study.

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

Circulating free DNA as a marker of response to chemoradiation in locally advanced head and neck squamous cell carcinoma.

CONTEXT: Liquid biopsy has moved from bench to bedside as a non-invasive biomarker for early diagnosis and monitoring treatment response. OBJECTIVE: This study investigated the role of circulating free DNA (cfDNA) as a diagnostic marker in locally advanced head and neck squamous cell carcinoma (HNSCC) and in monitoring response to chemoradiation therapy. MATERIALS AND METHODS: Serum was collected from treatment naïve, histopathologically diagnosed tumors in 24 HNSCC cases and 16 normal controls. CfDNA levels were quantified using ß globin gene amplification. RESULTS: The cfDNA level was significantly elevated in HNSCC (992.67 ± 657.43 ng/mL) as compared to healthy controls (60.65 ± 30.42 ng/mL, P = <0.001). The levels of cfDNA did not significantly correlate with TNM stage, lymph node involvement and grade. In responders, percentage decrease in cfDNA levels was 9.57% and 29.66%, whereas in nonresponders percentage increase was 13.28% and 24.52% at the end of three months of follow-up. CONCLUSION: Our study adds to the evidence that cfDNA levels are significantly higher in HNSCC cases and provides some evidence that levels increase with tumor progression. CfDNA may be a promising prospective non-invasive marker to predict response in patients undergoing chemo-radiotherapy.

Increased Expression of Oct4, Nanog and CD24 Predicts Poor Response to Chemo-Radiotherapy and Unfavourable Prognosis in Locally Advanced Oral Squamous Cell Carcinoma.

BACKGROUND: Current study investigates the role of Oct4, Nanog and CD24 in locally-advanced oral squamous cell carcinoma (OSCC), to evaluate whether the expression of these markers can predict efficacy of neoadjuvant-chemo-radiotherapy and survival of patients. METHODS: Biomarker expression was evaluated in 50 homogenously treated patients of locally-advanced OSCC. RESULTS: Clinical response was complete in 30% (n=15), partial response in 46% (n=23), no response in 24% (n=12). Pathologically, 74% patents (n=37) were responders and 26% were non-responders (n=13). Biomarker-overexpression was seen in 46% cases for Oct4, 54% cases for Nanog and 58% cases for CD24. Oct4, Nanog and CD24 expression showed significant correlation with clinical and pathological response (p <0.05). Three year recurrence-free survival was 71%, overall survival was 66%. Post-treatment advanced pathological N (ypN), post treatment advanced pathological TNM (ypTNM) stage, clinical non-response, pathologic non-response, positive/high expression of all three biomarkers had a significant negative impact on recurrence-free and overall survival. CONCLUSIONS: Expressions of Oct4, Nanog and CD24 have significant association with treatment response and survival in patients with locally advanced OSCC treated with neoadjuvant chemo-radiation. Survival of these patients is significantly affected by ypN stage, ypTNM stage, expression of all three biomarkers, clinical and pathological response to neoadjuvant therapy.
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Intraoperative Comparison and Evaluation of Intrathecal Bupivacaine Combined with Clonidine versus Fentanyl in Children Undergoing Hernia Repair or Genital Surgery: A Prospective, Randomized Controlled Trial.

BACKGROUND: Nowadays, spinal anesthesia is commonly being used in infants and children for infraumblical surgeries. Intrathecal adjuvants such as clonidine and fentanyl are used with local anesthetics for additive effects. AIM: The present study aims to assess and compare the effects of adding clonidine versus fentanyl to bupivacaine intrathecally in terms of propofol consumption, hemodynamic profile, adverse events, and complications intraoperatively in pediatric patients. SETTINGS AND DESIGN: A prospective randomized controlled trial was conducted between June 2016 and October 2018 in pediatric patients aged 3-8 years undergoing hernia repair or genital surgery under spinal anesthesia after approval of the Institutional Ethical Committee (Reference No: SGRR/IEC/04/16). MATERIALS AND METHODS: Patients were randomly divided into two equal sized (n = 42) study groups, while analysis was done in (n = 40) each group. Group 1 (BC) received clonidine 1 µg/kg with 0.5% bupivacaine (heavy) and Group 2 (BF) received fentanyl 0.5 µg/kg with 0.5% bupivacaine (heavy). STATISTICAL ANALYSIS: Quantitative data were expressed in mean and standard deviation. Qualitative data were expressed in proportion and percentages. Independent t-test was applied to compare the means of quantitative data, and Chi-square test was used to compare categorical data. P < 0.05 was considered statistically significant. RESULTS: Patient characteristics regarding age, weight, and surgical time were comparable in the two groups. The maintenance dose and bolus dose of propofol consumed during surgery were less in Group 1 than that in the Group 2 and were found to be statistically insignificant. The values of hemodynamic parameters such as heart rate, systolic blood pressure, and diastolic blood pressure were less in Group 1 and were statistically significant at different time intervals. Sedation scores were comparable in both groups. Intraoperative incidence of bradycardia, systolic hypotension, and diastolic hypotension were high in Group 1, whereas the incidence of desaturation was high in Group 2. Intraoperative complications such as apnea and respiratory obstruction were high in Group 2, but were statistically insignificant. CONCLUSION: We conclude that intrathecal adjuvant fentanyl maintains a better hemodynamic profile in terms of adverse events such as bradycardia, systolic hypotension, and diastolic hypotension. Intrathecal clonidine maintains a better sedation level requiring less propofol for sedation. Complications such as apnea and respiratory obstruction can be attributed more to the deep sedation caused by bolus of propofol rather than the inherent properties of intrathecal adjuvant clonidine or fentanyl.

Comparison of Subcostal Transversus Abdominis Block with Intraperitoneal Instillation of Levobupivacaine for Pain Relief after Laparoscopic Cholecystectomy: A Prospective Study.

BACKGROUND: There are several methods employed in the management of postoperative pain after laparoscopic cholecystectomy such as conventional systemic analgesics, including paracetamol, non-steroidal anti-inflammatory drugs, systemic opioids, and thoracic epidural analgesia with all having its limitations and side effects. AIMS: The present study aims to compare ultrasound-guided subcostal transversus abdominis (STA) block with intraperitoneal instillation of levobupivacaine in reducing postoperative pain, total analgesic consumption, nausea and vomiting, and recovery time in patients after elective laparoscopic cholecystectomy. SETTINGS AND DESIGN: A prospective study was conducted between January 2017 and December 2017 in 80 patients undergoing elective laparoscopic cholecystectomy after approval of the Institutional Ethical Committee (Reference No: SGRR/IEC/05/16). MATERIALS AND METHODS: Patients were randomly divided into two equal-sized (n = 40) study groups. Group 1 patients received ultrasonography-guided STA block with 0.25% levobupivacaine both sides and Group 2 patients received 0.25% levobupivacaine through intraperitoneal route. STATISTICAL ANALYSIS: Quantitative data were expressed in mean and standard deviation. Qualitative data were expressed in proportion and percentages. Independent t-test was applied to compare the means of quantitative data and the Chi-square test was used to compare categorical data. P < 0.05 was considered to be statistically significant. Survival curve was drawn using the log-rank test for comparing two groups. RESULTS: Patient characteristics regarding age, gender, and weight were comparable in the two groups. The mean Numerical Rating Scale scores were less in Group 1 than in Group 2 in the first 6 h, which was found to be statistically significant. There was no significant difference noted in pain scores after 6 h up to 24 h in postoperative area among the two groups. Pain scores for shoulder tip pain were lower in Group 2 as compared to Group 1 in the first 24 h, which was not significant statistically. CONCLUSION: STA block is a better modality for analgesia compared to intraperitoneal instillation in patients undergoing elective laparoscopic cholecystectomy.

Cytomorphological Features of Lung Adenocarcinoma with Anaplastic Lymphoma Kinase Gene Rearrangement.

BACKGROUND: The anaplastic lymphoma kinase (ALK) gene rearrangement is a predictive and prognostic marker in pulmonary adenocarcinoma. A series of clinical and pathological features have been documented in patients who harbor this translocation. AIMS: The objectives of this study were to analyze the specific cytomorphological features of lung adenocarcinoma that harbored the ALK gene rearrangement and to compare the morphological features with the mutation-negative cases. MATERIALS AND METHODS: The study sample of 40 cases included 15 ALK-positive cases and 25 ALK-negative cases. After the diagnosis was established, testing for ALK rearrangement was on the histopathology sample. The corresponding fine-needle aspiration cytology slides were retrieved from the records and cytomorphological features were analyzed. RESULTS: A comparison of pattern between the ALK-positive and ALK-negative group revealed that the sheet-like pattern and singly scattered cells were more common in the ALK-positive group. Moderate-to-severe nuclear pleomorphism was identified in 80% of ALK-positive cases and 72% of ALK-negative cases. The presence of mucinous features and/or signet ring morphology was the most striking feature of ALK-positive cases with P value of 0.002. The presence of necrosis in the background was identified in 80% of ALK-positive cases and was statistically significant (P = 0.001). CONCLUSION: This is among the few studies from India, where a detailed analysis of the cytomorphological features of cases with ALK phenotype versus the mutation negative cases has been performed.

Detection of Anaplastic Lymphoma Kinase Gene Re-Arrangement in Non-Small Cell Lung Carcinoma in the Indian Population: Comparison of Techniques and Immunohistochemistry Clones.

OBJECTIVE: Predictive and prognostic markers have revolutionized personalized therapy in non-small cell lung carcinoma (NSCLC). Crizotinib is now approved for locally advanced or metastatic NSCLC that is anaplastic lymphoma kinase (ALK) positive by either Fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). The current study aimed to detect the incidence of ALK gene re-arrangement in the Indian population, to compare the various IHC antibodies with FISH as a gold standard, and to analyze the morphology of cases with ALK phenotype. MATERIAL AND METHOD: A case series of 614 cases of NSCLC were included. IHC for detection of ALK phenotype was compared with FISH using 5A4 clone (Labvision, USA), ALK-1(Dako, Denmark) and D5F3 clone (Ventana, USA). RESULTS: ALK gene rearrangement was evident in 4.07% of the cases. Cases with ALK phenotype had unique histomorphology with presence of mucin or signet ring cells in association with necrosis, high tumour grade and poor differentiation. Comparison of various antibody clones used in IHC revealed that the sensitivity and specificity using the D5F3 clone (100%, 100%) and 5A4 clone (87.5%, 100%) were similar while the ALK-1 clone had the lowest sensitivity and specificity (50%, 95.5%). CONCLUSION: The incidence of ALK gene rearrangement in NSCLC in the current Indian study is within the worldwide reported range of 3-5%. This is the first study from the Indian subcontinent to compare various IHC antibodies used for detection of ALK phenotype. IHC using D5F3 clone and 5A4 clone may be considered as a rapid reliable and inexpensive method for detection of ALK gene rearrangement.

Scar Endometriosis: Cytological Diagnosis.

Endometriosis occurring in a surgical scar is called incisional endometriosis. An interesting case with immunocytological confirmation is being reported. A 28-year-old female presented with a mass over anterior abdominal wall. Fine needle aspiration revealed monolayered sheets of epithelial cells and stromal fragments. A cell block was also prepared. Immunohistochemistry panel comprising of CK 7 and CD 10 was performed, which were positive in glandular and stromal component respectively. Cytodiagnosis of scar endometriosis was rendered. Scar site endometriosis is rare, occurs in 0.03-1.08% of women following obstetric or gynaecologic surgeries. It is important to include endometriosis in the differential diagnosis of anterior abdominal wall masses, if there is history of previous gynaecological surgery. This will aid in accurate diagnosis and avoid unnecessary surgery.

Rare paratesticular aggressive angiomyxoma with negative oestrogen and progesterone receptors in a male patient.

Aggressive angiomyxoma (AAM) is a rare mesenchymal myxoid tumour localised to the pelvis and/or perineum in adult females in reproductive age group. AAM is very rare in males, with <50 cases described in literature, and involves scrotum, spermatic cord and perineum. It is slow growing, with a marked tendency for local recurrence after excision, but without metastatic potential. We present a rare case of a paratesticular AAM in a man aged 53 years. Tumour cells were immunoreactive for desmin, smooth muscle actin (SMA), vimentin, CD34 and were negative for S100. Unlike AAMs in females which express oestrogen receptor (ER) and/or progesterone receptor (PR) in >90% cases, the tumour cells in our case were negative for ER and PR, suggesting that the hypothesis that these markers play a role in tumour development and pathogenesis, does not apply in males. Androgen receptor positivity was noted in 2%-5% tumour cells.

Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy.

AIMS: Programmed death-ligand 1 (PD-L1), a potential target for immune checkpoint inhibitors in various solid neoplasms, has been studied in very few cases of Gall Bladder Carcinoma (GBC). The current study aimed to evaluate PD-L1 expression at primary and metastatic sites of GBC, and its associations with standard prognostic clinicopathological parameters, as well as with overall survival. METHODS AND RESULTS: One hundred and seventy-four cases of GBC were evaluated for PD-L1 expression by the use of the SP263 clone in tissue microarrays. Clinicopathological characteristics and survival data were correlated with PD-L1 expression analysed at different cut-offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour-infiltrating lymphocytes (TILs). The mean age of patients was 49.9 years, and the male/female ratio was 1:2.9. Of the cases, 73.6% presented with stage 3/4 disease. Tumour cells expressed PD-L1 in 23.0% of cases, and TILs expressed PD-L1 in 24.1% of cases. At a cut-off of 10%, 14.9% of cases expressed PD-L1, and at a cut-off of 50%, 7.5% of cases expressed PD-L1. Significant associations were seen between tumour proportion score and histological type (P = 0.004), histological grade (P = 0.004), nuclear grade (P = 0.008), nodal metastasis (P = 0.051), higher stage (P = 0.058), and TILs (P < 0.001). Tumour size, growth pattern, the presence of necrosis and lymphovascular emboli showed no significant associations with PD-L1 in tumour cells or TILs. In synchronous paired samples from primary and metastatic lymph nodes, discordantly higher PD-L1 expression was evident in lymph nodes. Overall survival was not associated with PD-L1 expression (P = 0.546). CONCLUSION: PD-L1 does not appear to be a prognostic marker or influence survival in GBC patients. However, PD-L1 expression occurs in one of four GBCs, supporting the future possibility of immune-modulation therapy to improve the dismal overall survival.

Heterotopic pancreatic tissue associated with type 1 choledochal cyst, cystolithiasis and gall bladder stones: a rare entity with review of literature.

Choledochal cyst is a rare congenital malformation, particularly when associated with stones in cyst (cystolithiasis), gallstones and heterotopic pancreatic tissue within the cyst wall. The current case represents a 5-year-old boy with abdominal pain, pale colored stools, and jaundice. Magnetic resonance cholangiopancreatography showed a cystic lesion, arising from common bile duct with cystolithiasis and cholelithiasis. He underwent excision of choledochal cyst and gallbladder with Roux-en-Y hepaticojejunostomy. Microscopic examination showed a cyst wall composed of fibrocollagenous tissue lined by cuboidal to low columnar epithelium. The subserosal layer of cyst wall showed presence of heterotopic exocrine pancreatic tissue comprising of pancreatic acinar cells and ducts. We report the first case of heterotopic pancreatic tissue associated with choledochal cyst and cystolithiasis and cholelithiasis occurring at the same time.

Development of a New Outcome Prediction Model in Early-stage Squamous Cell Carcinoma of the Oral Cavity Based on Histopathologic Parameters With Multivariate Analysis: The Aditi-Nuzhat Lymph-node Prediction Score (ANLPS) System.

The aim of this study was to evaluate the histopathologic parameters that predict lymph node metastasis in patients with oral squamous cell carcinoma (OSCC) and to design a new assessment score on the basis of these parameters that could ultimately allow for changes in treatment decisions or aid clinicians in deciding whether there is a need for close follow-up or to perform early lymph node dissection. Histopathologic parameters of 336 cases of OSCC with stage cT1/T2 N0M0 disease were analyzed. The location of the tumor and the type of surgery used for the management of the tumor were recorded for all patients. The parameters, including T stage, grading of tumor, tumor budding, tumor thickness, depth of invasion, shape of tumor nest, lymphoid response at tumor-host interface and pattern of invasion, eosinophilic reaction, foreign-body giant cell reaction, lymphovascular invasion, and perineural invasion, were examined. Ninety-two patients had metastasis in lymph nodes. On univariate and multivariate analysis, independent variables for predicting lymph node metastasis in descending order were depth of invasion (P=0.003), pattern of invasion (P=0.007), perineural invasion (P=0.014), grade (P=0.028), lymphovascular invasion (P=0.038), lymphoid response (P=0.037), and tumor budding (P=0.039). We designed a scoring system on the basis of these statistical results and tested it. Cases with scores ranging from 7 to 11, 12 to 16, and ≥17 points showed LN metastasis in 6.4%, 22.8%, and 77.1% of cases, respectively. The difference between these 3 groups in relation to nodal metastasis was very significant (P<0.0001). A patient at low risk for lymph node metastasis (score, 7 to 11) had a 5-year survival of 93%, moderate-risk patients (score, 12 to 16) had a 5-year survival of 67%, and high-risk patients (score, 17 to 21) had a 5-year survival of 39%. The risk of lymph node metastasis in OSCC is influenced by many histologic parameters that are not routinely analyzed in pathologic reports. These significant independent factors were graded to design a scoring system that permits accurate evaluation of the risk of metastasis with accuracy independent of the traditional TNM system or isolated histologic parameters. The need for neck node dissection can be predicted depending upon the scores obtained.