Glioblastoma with Probable Intratumoral Adenocarcinoma Metastasis: A Rare Report with Review of Literature.

"Tumor-to-tumor metastasis," an uncommon phenomenon, refers to a primary tumor metastasis into another tumor, with the most frequent donor being lung carcinoma and common recipients being renal cell carcinoma and meningioma. Tumor-to-tumor metastasis occurring in gliomas is rare with less than 20 reports described so far, and that into a glioblastoma is even rarer. We report a 54-year man, diagnosed with glioblastoma, IDH-wildtype, with metastasis of an adenocarcinoma into it. On histomorphology, the glial component was composed of astrocytic cells and showed increased mitosis, microvascular proliferation, and focal necrosis. This was intermingled with an adenocarcinomatous tumor with pleomorphic epithelial cells in glands, nests, and sheets. On immunohistochemistry, the adenocarcinomatous areas were positive for AE1/AE3 and TTF1 but negative for glial markers, ruling out adenoid glioblastoma. Further cytogenetic analysis showed EGFR amplification in the glial component but not in the adenocarcinoma component, ruling out glioblastoma with true epithelial metaplasia, and supporting the diagnosis of adenocarcinoma metastasis into glioblastoma. Glioblastomas may be susceptible to intratumoral metastasis due to the proliferating leaky vascular channels, however, the short survival of patients with glioblastoma may be responsible for the rarity of this occurrence. The documentation of these tumors is important as they may be important for clinical diagnosis and further treatment and prognosis.

Indian childhood cirrhosis: a retrospective study -redefining the older myths!

AIMS: This retrospective study emphasises the need of awareness for clinicopathological attributes of Indian childhood cirrhosis (ICC) in order to enable timely diagnosis and management. METHODS: This study was done on liver archival tissue of our department from the period of January 2016 to December 2022. Of these, cases of copper overload on paediatric biopsies were retrieved. The histopathological features were scrutinised independently by three pathologists, correlating with their clinico-radiological investigations. RESULTS: Five children in infancy to middle childhood presented with features of chronic liver disease in the form of jaundice and abdominal distention, were included in the study. Characteristic firm hepatomegaly with sharp margins and transaminitis was noted in all cases. Autoimmune, viral and metabolic workup were negative in all these patients except one which showed positive autoimmunity and another whose Coomb's test was positive. Normal ceruloplasmin levels and unremarkable slit lamp examination excluded the possibility of Wilson's disease. The histological features of marked ballooning degeneration with diffuse Mallory Denk, pericellular fibrosis, absence of steatosis and panlobular copper deposits clinched the diagnosis of ICC. CONCLUSIONS: ICC once believed to be extinct has still not vanished and remains underdiagnosed in routine practice. It is a rapidly fatal disease with a debatable pattern of inheritance and controversial role of copper as etiological agent. The clinical presentation is often deceptive and lack of awareness leads to misdiagnosis. Histopathological attributes are pathognomonic and possibility of ICC should be kept in all cases of cryptogenic cirrhosis.

Glioma arising in the setting of mismatch repair deficiency-rare or are we missing it?

Germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) can be mono-allelic or biallelic, resulting in a Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD) syndrome respectively. Glioma arising in the setting of MMR deficiency is uncommon. We describe two pediatric patients with high-grade glioma (HGG) and associated MMR protein deficiency. On histomorphology both cases showed HGG with astrocytic morphology and prominent multinucleated tumor cells. On immunohistochemistry, the first case was negative for IDH1 p.R132H showed loss of ATRX and p53 positivity. The second case was positive for IDH1 p.R132H and p53, but showed retained expression of ATRX. The histomorphology in both cases and additionally IDH mutation with retained ATRX in the second case, prompted us to test for MMR protein deficiency which was carried out by immunohistochemistry (IHC). One case revealed an immunostaining pattern suggestive of CMMRD while the other was suggestive of LS. Both the cases showed good response to surgery and radio-chemotherapy in the follow-up available. Our cases highlight the importance of testing for MMR proteins by simple IHC, in the setting of appropriate clinical scenario, histopathological and immunohistochemical findings. The recognition of these tumors is extremely important to guide further treatment and prompt family screening.

Correlation of microvessel density with histopathological parameters of carcinoma breast.

BACKGROUND OBJECTIVES: Microvessel density (MVD) is a surrogate measure of tumour angiogenesis, and is well known for over two decades to identify individuals with a high risk of recurrence with greater prevision than traditional markers. This study aims to assess the utility of MVD and its correlation with the Nottingham Prognostic Index (NPI) and other routine histopathological parameters in carcinoma breast. METHODS: This two year retrospective, cross-sectional and analytical study evaluated 143 women with breast cancer presenting to rural tertiary hospital in central India. These women were graded histopathologically, the immunophenotype was determined using ER (estrogen receptor), PR (progesterone receptor), Her2 neu (human epidermal growth factor receptor 2 neu) and Ki-67 proliferation index (Kiel-67) immunohistochemical markers and anti-CD34 antibody to stain the endothelial cell clusters displaying the microvessels. The NPI was generated for each participant based on the tumour size, histologic grade and involvement of lymph node. The parameters were compared with the CD34 scores. Differential and inferential statistics, including the independent t test, analysis of variance, Pearson's correlation coefficient, Spearman's rank correlation coefficient and point biserial correlation coefficient, were used for statistical analysis. RESULTS: This study showed that CD34 values ranged from 6-36 microvessels/hpf, with 24.16±6.77 microvessels/hpf as the mean. The mean microvessel counts showed a significant positive correlation with the Bloom-Richardson histological grade, vascular invasion, LN (lymph node) positivity and NPI. However, there was no significant correlation of CD34 values with the participant's age, tumour size neither any significant association of CD34 values with the individual's immunophenotype. INTERPRETATIONS CONCLUSIONS: A positive linear correlation of the microvessel counts and the NPI scores suggest that with an increase in tumour angiogenesis, there was increased proliferative potential. Based on the significant correlation between the microvessel counts and the vascular invasion of the tumour masses in this study, it can be assumed that there will be vascular invasion if the microvessel count is higher and vice-versa. Although it is established that angiogenesis and neovascularization are required for the expansion of the solid tumour tissue, the heterogeneous nature of this entity makes it difficult for obtaining a linear correlation. Hence, it is suggested that though neovascularization permits advanced tumour spread it, however, does not guarantee it.

Varied imaging and clinical presentations of acute bacterial cerebritis.

Infectious diseases affecting the central nervous system remain an important cause of morbidity and mortality in developing countries and in immunocompromised patients. Cerebritis refers to pyogenic inflammation of the brain parenchyma that may lead to abscess formation if left untreated. Cerebritis is an uncommon diagnosis as patients are usually diagnosed at the stage of abscess formation. We present three cases of bacterial cerebritis with different clinical manifestations and varied appearances on MRI. To our knowledge, only few case reports of bacterial cerebritis have been published in the literature, and imaging findings are not fully elucidated. These cases of bacterial cerebritis add valuable information to the existing literature and would be helpful in making the appropriate diagnosis of this uncommon condition that can be medically managed if diagnosed appropriately. We recommend that cerebritis should be considered in the differential diagnosis of such lesions.

COVID-19-associated brain abscess caused by Trichosporon dohaense: A case report and review of literature.

We report the first case of Coronavirus Disease 2019 (COVID-19)-associated brain abscess caused by a rare Trichosporon species, T. dohaense. The patient was a known diabetic and had received systemic corticosteroids for the treatment of COVID-19. He underwent craniotomy and evacuation of abscess. The pus aspirate grew a basidiomycetous yeast, morphologically resembling Trichosporon species. The isolate was initially misidentified by VITEK® MS due to lack of mass spectral database of T. dohaense. Accurate identification was achieved by internal transcribed spacer-directed panfungal polymerase chain reaction. The patient had a favorable outcome following surgical intervention and antifungal therapy.

Acute haemorrhagic leukoencephalitis (AHLE) - our experience and a short review.

BACKGROUND: Acute haemorrhagic leukoencephalitis (AHLE), a rare variant of acute disseminated encephalomyelitis (ADEM), often presents differently from classical ADEM, thereby posing a diagnostic challenge to the clinician. AIM: To report AHLE, its clinic-radiological manifestations, process of diagnosis and prognosis. METHOD AND RESULTS: Eight patients presented with altered sensorium, acute focal deficits with or without seizures. Initial workup showed evidence of haemorrhagic lobar or thalamic lesions in seven patients. All patients underwent extensive evaluation for collagen vascular disease and vasculitis profile, autoimmune encephalitis panel and aquaporin-4 antibody, which were found to be normal. Cerebrospinal fluid (CSF) biochemistry and microscopy was non-contributory and CSF viral PCRs, toxoplasma antibodies, cryptococcal antigen were also negative. All patients had progressively worsening sensorium and neurological deficits. Repeat MRIs showed increase in oedema in the lesions and appearance/expansion of haemorrhage in the thalamic/hemispherical lesions. All patients received intravenous methylprednisolone (IVMP) without any benefit. Four patients underwent plasmapheresis (PLEX), one received intravenous immunoglobulin (IVIG) and one received both second line immunotherapies, without significant improvement. Brain biopsy (performed in three patients) showed inflammatory demyelination and areas of haemorrhage, thus confirming the diagnosis. Six patients succumbed in 7-30 days of the illness, despite aggressive treatment and only two survived, albeit with a significant disability. CONCLUSION: AHLE is a rare, yet very severe variant of ADEM. MRI shows lesions with haemorrhages, oedema and mass effect and histology findings reveal inflammatory infiltrates, haemorrhagic foci and fibrinoid necrosis of vessel walls. Prognosis is worse as compared to the classic ADEM, with a high mortality rate. To the best of our knowledge, this is one of the largest series of AHLE to have been reported anywhere in the world. KEYMESSAGE: Acute encephalopathy, multifocal deficits accompanied by haemorrhagic CNS demyelinating lesions with oedema and mass effect are the key features of AHLE. It is a rare, yet very severe form of ADEM with very high morbidity and mortality.

Bulimia Nervosa Leading to Squamous Cell Carcinoma of the Esophagus in a Young Adult.

Bulimia nervosa is an eating disorder which is defined as binge eating which is followed by purging and inappropriately increased concern about one's weight and body shape. We report a case of a 20 year old female who presented with a history of a dysphagia since 2 months. She had a history of binge eating disorder followed by a ritual of purging activity since six years. She also gave a history of increased concern about her weight and body shape. On endoscopy, a growth was seen on the esophagus, which upon biopsy showed features of squamous cell carcinoma.Thus, even in a young female, a simple psychological eating disorder might manifest as a malignancy. This emphasizes the need of early diagnosis and treatment of such innocent looking eating disorders to prevent serious complications in the future.

Pathogenesis of covid - 19 - Pandemonium of the pandemic in Pandora's box.

The novel disease of 2019 by name coronavirus (Covid - 19 or SARS - CoV - 2), was first detected in December of 2019 in the Seafood Market of Huanan in Wuhan region of China. In less than a month it was proclaimed as a pandemic by The World Health Organization (WHO). Now, even after a year, it still remains to be a concern as a jeopardy to the global public health. The inception of Covid-19 has been identified as the third encounter of a highly morbific coronavirus after Severe Acute Respiratory Syndrome (SARS - CoV) and Middle East Respiratory Syndrome (MERS_CoV) causing coronaviruses, in merely two decades. In this review, we illustrate the general features of coronavirus and highlight the pathogenesis of the disease, bringing forth the different theories of disease progression, which may help clinicians and other health professionals to achieve a direction for further research, therapeutic protocols and development of the vaccine for combating SARS - CoV - 2 infection.

Role of linear endosonography in the diagnosis of biopsy-negative malignant esophageal strictures: Exploring the unexplored.

BACKGROUND AND AIM: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases present with smooth stricture with repetitive negative biopsy results. We aimed to use linear endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. METHODS: We retrospectively analyzed the data from August 2017 to December 2018 of biopsy-negative esophageal strictures. All adult patients with twice-negative biopsies and with smooth overlying esophageal mucosa on endoscopy were included. Clinical, epidemiological, endoscopic, imaging, and EUS findings were noted and analyzed. RESULTS: Eighteen patients underwent EUS for suspicion of malignant esophageal stricture. Seven were excluded as they were submucosal tumors. Eleven patients showed the presence of malignancy on EUS FNA samples. Nine were males. Computed tomography showed esophageal wall thickening in eight (16-38 mm) and esophageal mass in three patients. EUS showed loss of a normal five-layered wall structure of the esophagus in all patients. Fine-needle aspiration cytology demonstrated squamous cell carcinoma (n = 4), adenocarcinoma (n = 4), poorly differentiated carcinoma (n = 2), and neuroendocrine carcinoma (n = 1). There were no complications. CONCLUSION: EUS with FNA is effective and safe for the diagnosis of biopsy-negative malignant esophageal strictures.

Draft Genome Sequences of 16 Halophilic Prokaryotes Isolated from Diverse Environments.

Halophile-specific enzymes have wide-ranging industrial and commercial applications. Despite their importance, there is a paucity of available halophile whole-genome sequences. Here, we report the draft genome sequences of 16 diverse salt-tolerant strains of bacteria and archaea isolated from a variety of high-salt environments.

p16 promoter methylation, expression, and its association with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 subtype of breast carcinoma.

OBJECTIVES: The purpose of the study is to investigate p16 protein expression and promoter methylation of p16 gene and their association with molecular subtypes based on parameter such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). MATERIALS AND METHODS: A total of 114 breast cancer tissue biopsies were collected for methylation-specific polymerase chain reaction (MSP) and immunohistochemical (IHC) analysis. RESULTS: Seven tissue microarrays were constructed. p16 protein expression was studied in 114 cases, of which 35/114 (30.7%) cases showed strong expression and the majority of them had ER-positive tumor (57.6%), and it was statistically significant (P < 0.0074). Similarly, p16 expression was reduced in the majority of PR-negative tumors (83.9%) and the association was statistically significant (P = 0.0026). p16 methylation was studied in 114 cases and was positive in 71.0% cases. CONCLUSION: High p16 protein expression was associated with ER-positive, PR-negative, and HER2-negative tumors which is associated with poor prognosis. p16 protein expression may be used as a prognostic indicator to predict treatment response to hormonal therapy.

Cytomorphological spectrum of scalp lesions in the population of a developing country: A retrospective study.

BACKGROUND: Scalp lesions are frequently encountered in clinical practice. Fine-needle aspiration cytology (FNAC) can characterize most of these lesions; however, there is little published work on cytology of scalp lesions. METHODS: Records of all the patients subjected to FNAC from January 2011 to August 2016 were retrieved from the archives of the Cytopathology section of our Institute. Out of the 71 852 cases reviewed, 896 patients, who presented with palpable scalp lesions, were included in the study. Aspirates were obtained with a 23-gauge needle attached to a 10 mL disposable plastic syringe. May-Grünwald-Giemsa stained and Pap stained slides were prepared. Special stains and immunocytochemical analysis were done when necessary. RESULTS: Out of the 896 cases of aspirates from scalp lesions, 155 (17.2%) aspirates were found to be inadequate for diagnosis. One hundred and fifty-seven (21%) out of 741 adequate aspirates showed features of inflammatory or reactive pathology comprising of abscesses (57), cystic lesions (24), tubercular lesions (16), and reactive lymphadenopathy (66). Four hundred and fifteen (56%) aspirates revealed a tumor-like etiology comprising of epidermal cyst (395), sebaceous cyst (4), dermoid cyst (1), calcinosis (7), vascular malformation (7), hematoma (5), and juvenile xanthogranulomatous lesion (1). Tumorous lesions formed 22.3% of the aspirates. Of these, 7 cases (4.2%) were of metastases to the scalp. CONCLUSION: In a developing country, FNAC is a useful and cost-effective investigation for the diagnosis of a wide spectrum of scalp lesions. It allows rapid diagnosis and permits timely intervention thereby preventing complications due to delay in diagnosis.

Role of FNAC in diagnosing lesions of hand and wrist.

BACKGROUND: Swellings in the hand and wrist are frequently encountered in clinical practice and fine needle aspiration cytology (FNAC) is used as a primary diagnostic modality in most of them. A wide spectrum of lesions can be encountered at these sites. The aim of this study was to report the prevalence and spectrum of hand and wrist lesions and evaluate the diagnostic role of FNAC. METHODS: All the patients who presented with palpable lesions in the hand or wrist between January 2011 and July 2016 were reviewed, retrospectively. RESULTS: 1312 cases were subjected to FNAC of hand and wrist swellings, of which 1136 (86.6%) cases were satisfactory. Age ranged from 5 months to 90 years with M: F = 0.7:1. 138 (12.1%) were diagnosed as inflammatory lesions, 875 (77.0%) as benign, non-neoplastic (tumor-like) lesions and 123 (10.8%) were neoplastic lesions. The inflammatory lesions included 75 cases of synovitis, 30 cases of tuberculosis, 28 cases of abscess, one case of cysticercosis, two cases of gout, and fat necrosis each. In the benign, non-neoplastic (tumor-like) lesions, the most common lesion was ganglion (775 cases). The neoplastic lesions included 78 benign lesions with the most common being giant cell tumor of tendon sheath (61 cases). There were 40 cases of mesenchymal lesions, four cases of appendageal tumors and one case of malignancy (squamous cell carcinoma). Mesenchymal lesions accounted for 3.5% (40/1136) cases. CONCLUSION: FNAC is very useful and simple investigation for early diagnosis of lesions of hand and wrist. The lesions encountered at these sites most commonly are benign.

A search for entrustable professional activities for the 1st year pathology postgraduate trainees.

INTRODUCTION: During the past decade, there has been a paradigm shift in medical education from the problem-based learning to competency-based training. This has forced a rethink on the way we evaluate the residents and finally give them the right to handle patients independently. This study makes the first attempt towards designing competency-based training program for pathology residents by formulating the entrustable professional activities (EPAs) for the 1st year pathology residents. MATERIALS AND METHODS: A questionnaire comprising 18 potential EPAs in histopathology and 12 potential EPAs in cytology were circulated among the residents of Pathology Department. The respondents were asked to grade the EPAs on a scale of 0-4 based on how important they considered that activity as EPA. The cumulative score of each EPA was divided by the number of respondents to arrive at the average score. The EPAs with an average score of 3 or more qualified to be shortlisted as consensus EPAs. RESULTS: Five activities each of histopathology and cytopathology had an average score of 3 or above and were shortlisted as EPAs for the 1st year pathology postgraduates. Each of these was also mapped to their respective competencies. CONCLUSION: There is an urgent need to restructure the postgraduate pathology curriculum in line with competency-based training. This study is the first step in this direction.

BRCA1 Promoter Methylation and Expression - Associations with ER+, PR+ and HER2+ Subtypes of Breast Carcinoma

Introduction: Considering the increasing trend in incidence rates, morbidity and mortality of breast cancer, there is an urgent need to identify and validate new biomarkers for early detection and better management. The purpose of the study was to investigate BRCA1 protein expression and promoter methylation of the BRCA1 gene and their association with molecular subtypes based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) positivity. Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation specific PCR (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. BRCA1 protein expression was reduced in 55/114 (48.2%) and in the majority of ER-negative tumors (73.3%) (p<0.001). Similarly BRCA1 expression was reduced in the majority of PR-negative tumors (69.2%) but without statistical significance (p value=0.083). BRCA1 methylation was positive in 59.6% cases. A subset regarding ER+, PR+ and HER2+ was identified which consisted of 31.6% in which an inverse relationship between BRCA1 methylation and protein expression was noted. Conclusion: Reduced expression was associated with ER and PR negative status which is linked with a poor prognosis. BRCA1 protein expression might thus be used as a prognostic indicator to predict treatment response to hormone therapy.