Comparison of conventional unstained lymph nodal harvesting vs methylene blue-stained lymph nodal harvesting in colorectal specimen in staging left-sided colorectal carcinoma: a randomized controlled trial.

BACKGROUND: The management and prognosis of colorectal carcinomas (CRCs) are related to the stage of the disease, which, in turn, relies on the lymph node harvest from the surgical specimen. The guidelines recommend that at least 12 lymph nodes are required, which is not achieved in most resections. In this study, we propose a method to improve the lymph node yield in such cases. This study aimed to determine whether ex vivo injection of methylene blue into the inferior mesenteric artery or its branches improves lymph node retrieval in left-sided CRCs. METHODS: This study was conducted as a single-center, double-blinded, superiority randomized controlled trial. Patients who underwent elective surgery for left-sided CRCs with curative intent were randomized into 2 groups: stained and unstained. The sample size was calculated as 66. In all patients, details of disease stage, history of neoadjuvant therapy, and number of isolated lymph nodes were recorded. RESULTS: The mean number of lymph nodes extracted from the stained group was significantly higher than that from the unstained group (15.9 ± 5.2 vs 9.1 ± 5.7, respectively; P < .001). Among the patients who had received neoadjuvant therapy, the yield was higher in the stained group (P < .001). The yield was found to be greater in patients who had undergone upfront surgery than in those who had undergone neoadjuvant therapy, even in the stained group (100% vs 66.7%, respectively). CONCLUSION: The use of methylene blue injection into resected specimens of left-sided CRCs significantly improved the lymph node yield.

Skull Base Metastasis and Krukenberg Tumor in a Pregnant Woman: An Unusual Presentation of Metastatic Gastric Cancer.

Gastric cancer is an infrequent cause of vomiting during pregnancy. It is often diagnosed at an advanced stage due to late presentation by patients, mistaking it for gestational symptoms. We report a 24-year-old pregnant woman with gastric cancer with skull base metastasis and Krukenberg tumor on initial diagnosis. She underwent medical termination of pregnancy and best supportive care before dying of her illness.

Fatal anabolic androgenic steroid overdose in an amateur bodybuilder: a clinical and autopsy report.

Stanozolol is a synthetic anabolic-androgenic steroid commonly used by bodybuilders to increase muscle mass. However, its use can lead to serious adverse effects on the liver, including cholestasis, hepatic necrosis, and even death. In this case report, we describe a fatal case of stanozolol overdose in an otherwise healthy 35-year-old amateur bodybuilder. The patient presented with general malaise, jaundice, and a history of hematemesis after taking stanozolol tablets orally for 3 months. Upon admission, his liver function tests were significantly abnormal, and he succumbed within 48 h despite symptomatic treatment. The autopsy revealed sub-massive hepatic necrosis, focal macro-vesicular steatosis, and a cholestatic pattern of acute liver injury, with the chemical examination confirming the presence of stanozolol in the blood, liver, and kidneys. The cause of death was determined to be hepatic necrosis as a complication of stanozolol overdose. The overuse of anabolic steroids like stanozolol can cause hepatotoxicity, resulting in reversible cholestatic hepatitis or, in rare cases, fatal liver injury. The mechanism of anabolic androgenic steroid (AAS) drug-induced liver injury is obscure, but proposed mechanisms include oxidative stress and cholestasis. In this case, the recent overuse of stanozolol, a 17 alpha-alkylated (oral) AAS led to sub-massive hepatic necrosis and subsequent liver failure, proving fatal. It is imperative that healthcare providers and the public are informed about the dangers of AAS use, especially since AAS usage has increased recently due to easy online access, to prevent potentially life-threatening consequences.

Kaposiform Haemangioendothelioma of the Sublingual Gland in an Adult.

Kaposiform haemangioendotheliomas (KHE) are extremely rare, borderline malignant, locally aggressive vascular tumours. KHE is usually found in the retroperitoneum, over the extremities, the soft tissues of the trunk, mediastinum and the head and neck regions. We present a very rare case of KHE of the sublingual gland in an adult, which was not associated with Kasabach-Merritt phenomenon and was resected completely without any recurrence. To the best of our knowledge, this is the first reported case in the literature of a KHE arising from the salivary glands in an adult.

An autopsy report with a diagnostic clinical profile on fatal overdose of life-saving iron supplement.

Ferrous sulfate is a commonly prescribed drug for prophylaxis and treatment purposes, particularly in women and adolescent girls. However, its easy availability, potential toxicity at higher doses, and vague clinical presentation make it a drug of concern when evaluating a case of poisoning. We present the case of a 28-year-old female who allegedly consumed 60 ferrous sulfate (60 mg of elemental iron in 200 mg of ferrous sulfate) tablets in a suicidal attempt. She presented with gastrointestinal disturbances on the same day to a tertiary care health facility. Investigations revealed deranged liver function tests, serum iron levels ten times the normal range, and high levels of saturated transferrin. Despite treatment, she succumbed to the poisoning 4 days after the incident. Autopsy showed features of liver failure, which was confirmed by histopathology. Chemical examination detected free ferrous and chloride ions. This fatal case of adult iron toxicity highlights the different causes of death in various stages of iron toxicity, providing a wider perspective on clinical management and aiding in the determination of the cause of death during an autopsy. This article adds a rare fatal iron poisoning case in adults to the literature, emphasizing the necessity for regulating iron tablet supplementation and raising public awareness of the toxicity of iron, which could save millions of lives.

Clinicopathological Profile of Primary Hyperparathyroidism with Special Reference to Ki-67 Labelling Index.

Context: Primary hyperparathyroidism (PHPT) can occur due to a neoplastic process or hyperplasia. While the disease presentation is predominantly asymptomatic in developed countries, this is not the case yet in India. Differentiation of the type of lesion can only be done based on histomorphology but has its own challenges. Immunohistochemical markers like Ki-67 have been studied to aid in diagnosis but data on this is sparse from India. Aims: The aim of this study is to assess the clinical, biochemical and pathological profile of PHPT and to analyse the differences in immunohistochemical marker Ki-67 among the various lesions. Setting and Design: A descriptive study was carried out on 38 PHPT patients who were treated at our institute from January 2011 to March 2021. Materials and Methods: Post-surgery, the causative lesions were categorised as adenoma (31), hyperplasia (5) and carcinoma (2). Clinical, biochemical, radiological and histopathological features of all lesions were collected and analysed. Ki-67 proliferation index was calculated. The various parameters were compared across the three groups of lesions and correlated with Ki-67 index. Results: Out of 38 patients, 37 were symptomatic with skeletal symptoms being the most common followed by renal symptoms. There was no difference in clinical or biochemical parameters among the three types of lesions. Significant negative correlation was seen between serum iPTH and serum 25-OH Vitamin D levels (P0.006) The median Ki-67 index was found to be 0.40% in hyperplasia, 0.49% in adenoma and 5.84% in carcinoma. Conclusion: PHPT still presents as an overtly symptomatic disease in India. Diagnosis of the nature of lesion depends on the accurate application of morphological criteria. A high Ki-67 index was not found to be an absolute marker of carcinoma, as it was also seen in a small proportion of atypical adenomas.

Coexistence of malignancy and tuberculosis: is it double disease or double hit related to COVID-19? - Experience from a tertiary care center.

BACKGROUND: Coexistent malignancy and tuberculosis (TB) are rarely encountered. Cancer patients are a highly vulnerable subgroup during this Covid crisis. Delayed treatment for malignancy because of COVID-19 pandemic leads to higher chances to get infections. PURPOSE: The present study aimed to present the clinicopathologic profile of the patients with coexistent carcinoma and TB during the COVID-19 pandemic in a tertiary care center. MATERIALS AND METHODS: This was a retrospective study conducted during the COVID-19 pandemic between April 2020 to May 2021 in the Department of Pathology of our Institute. 11 patients with coexistent malignancy and caseous necrotizing granulomatous inflammation with Langhans giant cells and or acid-fast bacilli (AFB) positivity were included in the study. Cases of ill-defined granulomas coexistent malignancy were excluded. We studied varied clinical and histopathologic features of these cases. RESULTS: Eleven cases were reported with coexistent malignancy and tuberculosis, of which 8 were reported in 2021 and 3 cases were reported in 2020. Adenocarcinoma comprised 9 cases (81.8%) and the remaining 2 were squamous cell carcinoma (18.1%). Out of 11, 10 (90.9%) were new TB cases. Of these, 10 were extrapulmonary TB and one pulmonary TB case with cancer. Regarding chemotherapy, four patients accepted that chemotherapy was delayed because of the COVID-19 crisis. CONCLUSION: In this covid pandemic, India being the 2nd most populous country and endemic for TB, there is a higher chance of latent and active TB. The coexistence of two different pathologies is rare, even in a region with a high incidence of TB. Delayed chemotherapy in a pandemic situation leads to an increased incidence of infectious diseases such as TB.

Diagnostic utility of immunohistochemical markers alpha methyl acyl coA racemase (AMACR) and Ets related gene (ERG) in prostate cancer.

OBJECTIVES: To study the sensitivity and specificity of IHC markers AMACR and ERG in prostatic adenocarcinoma. METHODS: The study was a prospective one and samples were collected from August 2014 to June 2016. A total of 186 samples were obtained from the Department of Urology, in which 112 of these were benign prostatic hyperplasia (BPH), and 71 were prostatic adenocarcinoma. The adenocarcinoma cases were evaluated by two histopathologists, and appropriate Gleason score was given according to the modified ISUP Gleason grading system (2016). IHC markers AMACR & ERG were performed on the adenocarcinoma cases and their sensitivity and specificity were calculated. RESULTS: AMACR was a highly sensitive and specific marker for detecting prostatic carcinoma with a sensitivity and specificity of 95.8% and 96.5% respectively. ERG was a very specific marker with poor sensitivity in detecting prostate cancer. The sensitivity and specificity of ERG were 35.2% and 100% respectively. ERG expression decreased with increasing Gleason grade, PSA level, and tumour volume, which was statistically significant while the association of AMACR with Gleason grade or with tumor volume was not significant. CONCLUSION: ERG is a marker of early prostatic carcinogenesis and tumors may be positive or negative subtypes. Special histomorphologic features like perineural invasion, glomerulations, and intraluminal blue mucin were also studied. AMACR was a highly sensitive marker for detecting prostatic adenocarcinoma, while ERG was highly specific.

Vermiform Appendix and the Potential for Missed Pathologies.

Introduction The appendix is considered an appendage of little value and is often treated disdainfully, be it as part of evolutionary process, on a grossing table, under a microscope or while archiving specimens and slides. It is only recently, with data indicating its importance in gut immunity and as the origin of pseudomyxoma, that its space in a human body appears vindicated. Aim Our aim was to screen the histopathologic spectrum of appendix lesions observed in our hospital for rare, incidental or clinico-radiologically uncertain lesions that would help emphasize a necessary seriousness in its sampling. Method All appendectomy specimens over ten years were screened for diagnosis other than acute/chronic/resolving appendicitis and pseudomyxoma peritonei. Among the recorded rare diagnoses, one representative case each, based on interesting history or pathology, was selected for discussion. Observation Forty-three lesions were found to meet inclusion criteria comprising 12 varied etiologies. Among these, 25 had a normal-appearing appendix and 27 were not suspected on radiology or on clinical/surgical assessment. Histopathology comprised, among others, neoplastic entities such as (Diffuse large B-cell) lymphoma, metastasis, carcinoid as well as interesting non-neoplastic diagnoses such as pinworm infestation (in the elderly) and (post-menopausal) endometriosis. Conclusion Sampling and histopathologic assessment of the appendix should be compulsory, careful and representative. Each specimen must be treated as harboring a potential pathology, until microscopically proven otherwise because missed "rare" diagnoses could delay therapy or alter key management decisions as cancer staging.

Clinicopathologic profile of gastroenteropancreatic neuroendocrine neoplasms in a referral center of South India.

BACKGROUND: The neuroendocrine system of the gastroenteropancreatic (GEP) region gives rise to unique, heterogeneous malignancies that need a high index of suspicion to make a diagnosis owing to their indolent course. AIMS: The present study aimed to find the incidence and the differences in the morphologic and immunohistochemical profile of gastroenteropancreatic neuroendocrine tumors (GEPNET) in a referral center of South India, JIPMER, Puducherry, India. METHODS: There were 55 gastroenteropancreatic region neuroendocrine neoplasms (NEN) assessed for demographic, clinical and radiological features. Gross morphological features, histopathological features, mitotic index, Ki67 proliferation index, and immunohistochemical positivity for synaptophysin, chromogranin-A, CD-56, NSE (Neuron Specific Enolase) and pan-cytokeratin (Pan-CK) were also assessed. RESULTS: The majority were nonfunctional tumors presenting with abdominal pain, gastrointestinal bleed, vomiting, jaundice, and loss of weight and appetite. The sites of involvement according to the order of frequency were duodenum, stomach, rectum, pancreas, ileum, appendix and jejunum. The endoscopic appearance of duodenal and jejunal tumors showed polypoidal, nodular and ulceroproliferative growth. These tumors were diagnosed by preoperative biopsy; 54% of them were grade-1 neuroendocrine tumors exhibiting nesting, trabecular, cord, and solid sheet patterns. All 55 cases were synaptophysin-positive with variable positivity for chromogranin, neuron-specific enolase, CD56, and Pan-CK. Mixed adenoneuroendocrine carcinomas (MANECs) involving the duodenum and stomach comprised 7.3% of all GEPNETs. Pancreatic neuroendocrine tumors constituted 9% of all tumors; one was multifocal. Lymph node metastasis was seen in 12/55 tumors; 6/12 showed liver metastasis also. All metastasizing tumors measured less than 4 cm in size. Statistical correlation of the tumor grade, mitotic count and Ki67 index as analysed by Spearman's correlation between the paired data denoted by rs in 55 tumors showed a strong correlation between mitotic count and Ki67 index; a moderate correlation was noted between the tumor grade and Ki67 index. CONCLUSION: The clinicopathologic profile of 55 GEPNET revealed a majority to be sporadic Grade 1 tumor. Tumors that showed lymph node and liver metastasis were less than 4 cm in size. MANECs were found in the duodenum and stomach.

Identification of differentially methylated candidate genes and their biological significance in IUGR neonates by methylation EPIC array.

BACKGROUND: Intrauterine growth restriction (IUGR) is a pregnancy-associated disease manifested by decreased growth rate of fetus than the normal genetic growth potential. It is associated with increased susceptibility to metabolic diseases later in life. Although the mechanisms underlying the origin of metabolic diseases are poorly understood, DNA methylation is a crucial investigation for the identification of epigenetic changes. OBJECTIVES: To assess the degree of change of DNA methylation in IUGR neonates and compare with that of appropriate for gestational age (AGA) neonates and to explore the differentially methylated candidate genes and their biological significance. METHODS: This cohort study was conducted in the Neonatology Department of JIPMER during the period of November 2017 to December 2018. Forty each of IUGR and gestation matched AGA neonates were recruited. Umbilical cord blood samples were collected at birth. DNA was separated from the blood samples; and, using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these neonates was established. Data were expressed as mean ± standard deviation. Methylation EPIC array was performed to identify the differentially methylated candidate genes. David analysis was used to find out the functional annotation chart by KEGG pathway. RESULTS: Genomic DNA methylation varied significantly between IUGR and AGA neonates (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p value: <.01). A global shift toward hypomethylation was seen in IUGR compared with AGA, targeted to regulatory regions of the genome, and specifically promoters. Pathway analysis identified deregulation of pathways involved in metabolic diseases. Altered methylation of PTPRN2 & HLADQB1 genes leads to dysregulation of T-cells and reactive oxygen species (ROS). These changes may lead to complications later among these neonates subjected to IUGR. CONCLUSION: Our findings show significant changes in the methylation pattern of genes among IUGR and AGA babies. Steps for correcting the changes may help in reducing later complications among IUGR babies.

Neuroectodermal tumours of the sino-nasal tract: a clinicopathological study of 18 cases with a newly proposed revised classification and a brief review of literature.

AIM: Sino-nasal tract tumours constitute 3% of the head and neck malignancies. Among these tumours, neuroectodermal tumours are rare with histo-morphological and immunohistochemical overlap making them a challenge for the pathologist. We included Ewing's/PNET, olfactory neuroblastoma (OFN), mucosal malignant melanomas (MMM), Melanotic neuroectodermal tumour of infancy (MNTI), small-cell neuroendocrine carcinoma (SNEC), and the newest entity Adamantinoma like Ewing's sarcoma (ALES) as part of the neuroectodermally derived tumours of the sino-nasal tract. The last three entities were added to the existing ones, which also has been emphasized in this paper. METHODS AND RESULTS: A comprehensive analysis was done on all neuroectodermally derived tumours from 2016 to 2020. A total of 18 cases were collected, which included OFN (10 cases), SNEC (2 cases), MMM (2 cases), Ewing's/PNET (2 cases), MNTI (1 case), and ALES (1 case). The most common presentation in NE tumours was nasal obstruction (80-100%). Except for OFN, all other tumours were confined to the nasal and paranasal sinuses. 4/10 cases of OFN showed orbital extension. Cervical lymph-node metastasis was seen in 50% of cases of SNEC and MMM groups. An array of relevant immune-histochemical markers were performed. The marker expression was very subtle among the groups. On follow-up, recurrence was seen in the OFN and MMM groups in 30 and 50%, respectively. Metastasis was seen in SNEC group (100%) and OFN group (10%). CONCLUSION: As sino-nasal neuroectodermal tumours pose a diagnostic challenge and have different therapies and are prognostically different, the pathologist must be aware of the subtle morphological, immunohistochemical clues which have been dealt with in-depth in this study.

Co-infection of intestinal tuberculosis and mucormycosis in a patient with Down syndrome: a unique case report with literature review.

Mucormycosis represents several unusual opportunistic infection caused by saprophytic aseptate fungi. There is a recent rise in cases of mucormycosis due to an increase in diabetic and immunodeficient patients like patients on long-term steroids, immunomodulators due to organ transplantation, malignancies, mainly haematological malignancies, and autoimmunity. Anatomically, mucormycosis can be localised most commonly as rhino-orbito-cerebral followed by pulmonary, disseminated, cutaneous and gastrointestinal, rarest being small intestinal. Patients with Down syndrome are immunodeficient due to their impaired immune response. Disseminated tuberculosis is also common in immunodeficient patients. We report a rare case of small intestinal mucormycosis in a patient with Down syndrome with coexisting intestinal tuberculosis. Due to the invasiveness of mucormycosis, the patient succumbed to death despite providing aggressive surgical debridement and medical management.

Malakoplakia of Endometrium with Osseous Metaplasia on Evaluation of Postmenopausal Leukorrhea: A Rare Case Report.

Malakoplakia is a chronic xanthogranulomatous condition that affects the genitourinary tract reported earlier as urinary granulomas and pelvic masses. We report a different clinical manifestation of malakoplakia presenting as postmenopausal pyometra. A 64-year-old postmenopausal female presented with foul-smelling vaginal discharge with a past history of induced abortion, followed by dilatation and evacuation. On examination, abdomen was soft, vaginal examination revealed pus discharge, parous size uterus with free fornices, and pap smear ruled out malignancy. Ultrasonography revealed linear, echogenic structures in the endometrial cavity suspicious of bony spicules with fluid around. Hysteroscopy revealed congested endometrium with multiple pieces of shredded bone-like structures that were removed followed by curettage. Histopathological examination was suggestive of malakoplakia with osseous metaplasia. Retained bony spicules can cause chronic granulomatous inflammation that may become symptomatic postmenopause due to absent cyclical shedding. This is the first reported case of malakoplakia of uterus following retained bony spicules.

Gastric Candidiasis Leading to Perforation: An Unusual Presentation.

Candidal infection of the gastrointestinal tract (GIT) is rare but has recently increased due to the increased number of immunocompromised patients, injudicious use of antibacterial agents, and prolonged use of antacid drugs in immunocompetent patients. The most frequent organ involved in GIT candidiasis is the esophagus, followed by the stomach, small intestine, and large intestine. The clinical spectrum of gastric candidiasis ranges from asymptomatic to gastric perforation and even shock. This case report presents a 58-year-old immunocompetent male patient diagnosed with Candida tropicalis-induced gastric perforation peritonitis.

Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity.

OBJECTIVE: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast. MATERIAL AND METHOD: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers. RESULTS: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning. CONCLUSION: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.

De Novo Crohn's Disease Triggered After COVID-19: Is COVID-19 More Than an Infectious Disease?

Coronavirus disease 2019 (COVID-19)-associated immune dysregulation is believed to trigger the onset of various autoimmune diseases. These occur either during active COVID-19 or soon after recovery. We report ileocolonic Crohn's disease in a 35-year-old woman after her recovery from a milder form of COVID-19. She achieved remission of her symptoms with oral corticosteroids and sulfasalazine.

Effect of preoperative finasteride on perioperative blood loss during transurethral resection of the prostate and on microvessel density in patients with benign prostatic hyperplasia: An open label randomized controlled trial.

OBJECTIVE: Transurethral resection of the prostate (TURP) is a common procedure for the treatment of benign prostatic hyperplasia (BPH). Previous studies on the effect of 5-alpha reductase inhibitors on perioperative blood loss in TURP and microvessel density (MVD) in the prostate are equivocal. We evaluated whether pretreatment with finasteride for 2 weeks before surgery can reduce perioperative blood loss in TURP and MVD in the prostate. MATERIALS AND METHODS: Sixty-eight patients of BPH planned for TURP were randomized into two groups. The study group comprising 34 patients was treated with finasteride (5 mg/day) for 2 weeks and the placebo group comprising 34 patients received placebo for 2 weeks, before TURP. Blood loss was measured in terms of a reduction in the blood hemoglobin (Hb) and hematocrit (HCT) levels between preoperative values and 24 h after surgery. MVD was measured in the resected prostate tissue stained with anti-CD31 monoclonal antibody. RESULTS: The reduction of Hb and HCT in the finasteride group was significantly lower than the reduction in the placebo group (P < 0.05). The artery (P = 0.005), vein (P = 0.05), and gland (P = 0.008) densities were significantly less in the finasteride group than in the placebo group. There was no significant correlation between blood loss and MVD. CONCLUSIONS: Our study suggests a clear advantage of the preoperative use of finasteride for 2 weeks by reducing the perioperative blood loss in TURP in patients with BPH. While there is a significant reduction in MVD in the prostate on treatment with finasteride, it is not clear that this is the mechanism of reduction in blood loss in TURP.