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

Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

Department of Neuropathology Laboratory, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

World Health Organization Classification of Tumors of the Central Nervous System 5th Edition (WHO CNS5): What's new?

The latest fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) has been built on the prior WHO 2016 classification as well as recommendations put forward by seven updates of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT). Various new tumor types and subtypes have been recognized which are of clinical significance. Tumor groups have been restructured and the nomenclature of some tumor types has also been revised. The use of terms 'entity' and 'variant' have been replaced by 'type' and 'subtype'. Significant changes have been introduced in the grading of tumors viz. use of Arabic numerals, grading within individual tumor types and combined histological and molecular grading. The terms 'Not otherwise specified' and 'Not elsewhere classified' can now be used for all tumor types. WHO CNS5 also for the first time endorses the use of DNA methylation profiling for the diagnosis of some tumor types/subtypes. Finally, the importance of combining histology with molecular parameters is emphasized for the “layered reporting” and “integrated diagnosis”, which will provide valuable diagnostic, prognostic, and predictive information, as well as for some entities, suggest targeted therapies.

Molecular confirmation & characterization of Rickettsia conorii in north India: A report of three cases

Background & objectives: In India, spotted fever group rickettsiae (SFGR) are an underdiagnosed cause of acute febrile illness (AFI). The non-specific Weil-Felix test is the first diagnostic modality for the diagnosis of SFGR in many laboratories due to the lack of advanced diagnostic facilities in developing countries. The aim of this study was to detect SFGR using molecular methods in the patients, presenting with AFI in a tertiary care centre in north India. Methods: Consecutive patients (>14 yr of age) with AFI were enrolled over a six month period. Standard investigations for common pathogens causing AFI in India (malaria, dengue, scrub typhus, leptospirosis and enteric fever) were carried out. In patients who were negative for all of the above investigations, blood was subjected to polymerase chain reaction (PCR) targeting outer membrane protein A (ompA) gene of Rickettsia. Results: Of the 51 patients with an undiagnosed aetiology, three were positive by ompA PCR. Two of the PCR products produced good sequences and BLAST identification confirmed them as Rickettsia conorii. The sequences of R. conorii reported from south India clustered with two previously reported novel rickettsial genotypes. The study sequences clustered in a group different from that of Rickettsia spp. of the south Indian sequences reported earlier. Interpretation & conclusions: This study showed the existence of R. conorii in north India. Testing for SFGR may be included in the diagnostic workup of AFI for better disease management.

Use of eschar for the molecular diagnosis and genotypic characterisation of Orientia tsutsugamushi causing scrub typhus

Scrub typhus caused by Orientia tsutsugamushi presents as an acute febrile illness with a varied presentation from mild illness to fatal disease in the absence of appropriate antibiotic treatment. Performing polymerase chain reaction (PCR) on eschar sample acts a rapid diagnostic tool in the early stage of scrub typhus when blood is negative. A total of eight patients from whom both whole blood and eschar samples were collected and tested by nested PCR targeting 56 kDa trichostatin A (TSA) gene to detect O. tsutsugamushi DNA. All (100%) eschar samples and three whole blood samples tested positive. Genetic analysis of the 56 kDa TSA gene sequences showed that the majority were related to Karp reference strains, while one clustered with Kawasaki strain. When present, eschar should be favoured as a diagnostic sample over whole blood in the early phase of infection.

Therapy and progression – induced O6‑methylguanine‑DNA methyltransferase and mismatch repair alterations in recurrent glioblastoma multiforme.

Despite multimodality treatment protocol including surgical resection, radiotherapy, and chemotherapy in patients with glioblastoma multiforme (GBM), most suffer from treatment failure and tumor recurrence within a few months of initial surgery. The effectiveness of temozolomide (TMZ), the most commonly used chemotherapeutic agent, is largely dependent on the methylation status of the promoter of the gene O6‑methylguanine‑DNA methyltransferase (MGMT) and the integrity of the mismatch repair (MMR) system. Changes in these regulatory mechanisms at the time of recurrence may influence response to therapy. Deciphering the molecular mechanisms of resistance to these drugs may in future lead to improvised patient management. In this article, we provide an update of the spectrum of molecular changes that occur in recurrent GBMs, and thus may have an impact on patient survival and treatment response. For review, electronic search for the keywords “Recurrent GBM”, “Recurrent GBM AND MGMT” “Recurrent glioma AND MGMT”, “Recurrent GBM AND MMR” and “Recurrent glioma AND MMR”, “Recurrent GBM AND MMR” and “Recurrent glioma AND MMR” was done on PubMed and relevant citations were screened including cross‑references.

Current concepts in the pathology and genetics of gliomas.

In recent years, there has been a marked improvement in our understanding of molecular genetics of gliomas. These advancements offer hope for development of tailored therapies targeting a tumor's unique molecular profile, and may also translate into improved classification and identification of newer prognostic markers. This review focuses on the neuropathological features of different types of glial neoplasms according to the World Health Organization classification, and the recent advances in their molecular biology with emphasis on the genetic mechanisms underlying tumor progression, diagnostic and prognostic markers and potential therapeutic targets.

Cytomegalovirus pneumonia in adult acute lymphoblastic leukemia.

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in immunosuppressed patients. Though acute lymphoblastic leukemia (ALL) is an immunosuppressed state, CMV disease has been reported infrequently. We present a patient of adult B lineage ALL who was on maintenance chemotherapy and developed CMV pneumonia. Patient was managed with intravenous ganciclovir and had successful outcome. However, three weeks later patient had a relapse of ALL and died shortly after high dose chemotherapy.

Huge placental myxoid chorangioma presenting with severe antepartum hemorrhage.

A 2nd gravida presented at 27 weeks with antepartum hemorrhage. Ultrasound showed a single live fetus (parameters approximately 23 weeks) and a huge placenta with multiple cystic areas extending into the lower uterine segment; some of which showed increased vascularity on colored doppler. A diagnosis of low lying placenta with a possibility of chorangioma or a partial mole was made. The next bout of antepartum hemorrhage was severe necessitating an emergency cesarean. Histopathology of the placenta (weighing 2240 grams) revealed a myxoid chorangioma. All features in this woman are uncommonly reported in literature (large size, myxoid degeneration and severe antepartum hemorrhage necessitating a cesarean).

Multi-minicore disease: a rare form of myopathy.

BACKGROUND: Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS: A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT: During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS: Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies.

Malarial hepatopathy.

Jaundice is a common clinical presentation in severe malaria, seen in approximately 2.5% patients with falciparum infection but hepatitis is unusual. Although hepatic dysfunction is unusual and hepatic encephalopathy is almost never seen in malaria, yet, cases of hepatic dysfunction are being increasingly reported in patients with P.falciparum infection, from different parts of world. The extent of hepatocellular dysfunction varies from mild abnormalities in liver function tests to hepatic failure. Patients with hepatocellular dysfunction in malaria are more prone to develop complications, but have a favorable outcome if hepatic involvement is recognized early and managed properly. It is important to meticulously look for hepatic dysfunction in patients with severe malaria, distinguish it from fulminant hepatic failure and manage it aggressively.

HIV immunosupression and malaria: is there a correlation?

The human immunodeficiency virus (HIV) epidemic has resulted in an increase in the prevalence of many opportunistic infections and has caused re-emergence of certain diseases in the developing world. In tropical countries, immunosupression due to HIV infection has resulted in changes in the clinical presentation of endemic infections. Although the immune deficiency caused by HIV infection should presumably lead to an increased frequency of clinical malaria in areas with endemic malarial infection, like India, evidence of the association between HIV and malaria in India is scanty, with only a few studies showing a positive correlation. We hereby report a case of concurrent infection with Plasmodium falciparum malaria and human immunodeficiency virus type 1 (HIV-1) in a young male patient.

Prevalence of high--risk human papillomavirus infections in women with benign cervical cytology: a hospital based study from North India.

INTRODUCTION: Cervical cancer is the commonest cancer among Indian women. High-risk human papillomavirus (HPV) detection holds the potential to be used as a tool to identify women, at risk for subsequent development of cervical cancer. There is a pressing need for identifying prevalence of asymptomatic cervical HPV infection in the local population. OBJECTIVE: To determine the prevalence of high-risk HPV DNA in women with benign cervical cytology. MATERIALS AND METHODS: Women visiting the gynecology outpatient with varied complaints were subjected to Pap smear. Four hundred and seventy two samples were subjected to polymerase chain reaction, using consensus primers for low and high-risk HPV (types 6, 11, 16, 18, 31 and 33). The samples that were positive for HPV DNA were subsequently assessed for high-risk consensus primers, types 16, 18, 31 and 33 as well as for HPV type 16 and 18. RESULTS: One hundred and seventy four (36.8%) women tested positive for HPV DNA. Thirty nine (8.2%) of the entire cohort tested positive for high-risk HPV. Fifteen samples were positive for type 16, 22 for type 18 and two for both types 16 and 18. A statistically higher prevalence of high-risk HPV was observed in poorly educated and rural groups. No association of HPV prevalence was noted with age, parity and age at marriage. CONCLUSION: The study generates epidemiological data of prevalence of sub-clinical HPV in the women visiting a tertiary care institute as well as peripheral health centres. The data generated will be useful for laying guidelines for mass screening of HPV, treatment and prophylaxis in the local population.

Gangliogliomas: A report of five cases.

Gangliogliomas are rare tumors of the Central Nervous System. Five gangliogliomas were diagnosed out of 1560 brain tumours surgically resected out in a period of 5 years accounting for 0. 32%. We have tried to discuss in detail the pathological features of these tumours and have mentioned the clinical and radiological features associated with them. All the slides, tissue blocks and pathology reports of the surgical specimens of gangliglioma were reviewed and the clinical and radiological data reviewed. The ages of the patients ranged from 7-65 years with 4 males and 1 female. The tumors were located in the lateral ventricle (a rare site), temporal, parietal and the frontal lobes with duration of seizures varying from 1-9 years. The tumors were diagnosed by the presence of a dual population of neoplastic ganglionic and glial components. The glial components consisted of pilocytic astrocytes (l case), fibrillary astrocytes (2 cases), oligodendrocytes (1 case) and anaplastic astrocytes and oligodendrocytes (1 case). There was one-grade I GG, three-Grade II GGs and one-grade III GG. Astrocytes were the commonest glial component of GGs, either pilocytic or fibrillary. Oligodendrocytes as the glial component of GGs was seen in 2 cases one of which was anaplastic and this is a rare finding.

Mediastinal enteric duplication cyst containing aberrant pancreas.

OBJECTIVE: The purpose of the study is to report a unique association of clinical and pathological findings in a neonate. Foregut enteric duplication cysts--rare developmental anomalies that are associated with midline vertebral fusion anomalies. METHODS: We had a neonate with foregut duplication cyst who presented at birth with respiratory distress. The child also had associated communicating hydrocephalus. The patient underwent excision of the duplication cyst along with a ventriculo-peritoneal shunt. RESULT: The excised specimen revealed a duplication cyst lined by aberrant pancreatic tissue. CONCLUSION: The present case demonstrates histologically the presence of both pancreatic and gastric tissue.

Mucin-Secreting Adenocarcinoma of Kidney:A rare Histological Presentation.

A mucus producing adenomatous tumor, adenocarcinoma of the renal pelvis has been one of the rarest tumors ofthe genito-urinary tract. Presented here is a case report ofa patient who was admitted with pain and lump left loin and was operated upon. The gross morphology and histological features of the specimen were consistent with mucin-secreting adeno-carcinoma ofthe kidney.