Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Utility of GATA-3 and associated immunohistochemical markers in the differential diagnosis of poorly differentiated urothelial carcinoma.

Aims: The aims are to study the utility of GATA-3 along with panel of immunohistochemical (IHC) markers in the differential diagnosis of primary and metastatic poorly differentiated urothelial carcinoma (UC). Settings and Design: This is a prospective and retrospective observational study. Subjects and Methods: Poorly differentiated carcinomas of urinary tract and metastatic sites from January 2016 to December 2017 were subjected to a panel of four IHC markers including GATA-3, p63, Cytokeratin (CK) 7, and CK20. Additional markers such as p16, an enzyme called alpha-methylacyl-CoA racemase, CDX2, and thyroid transcription factor 1 were also done depending on the morphology and site. Statistical Analysis Used: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GATA-3 in making the diagnosis of UC were calculated. Results: Forty-five cases were included in the study and after appropriate IHC, the diagnosis was resolved as UC in 24 cases. GATA-3 was positive in 83.33% of UC; all the four markers positive in 33.33% and all negative in 4.17% of UC. However, at least one of the four markers was present in 95.83% of UC, except in sarcomatoid UC. GATA-3 had 100% specificity in differentiating from prostate adenocarcinoma. Conclusion: GATA-3 is a useful marker in the diagnosis of UC in the primary and metastatic sites with a sensitivity of 83.33%. GATA-3 along with other IHC markers in correlation with clinical and imageological features is necessary for making specific diagnosis of poorly differentiated carcinoma.

Significance of tumor-infiltrating lymphocytes in tumor regression in breast cancer: A study in a tertiary care cancer center in South India.

BACKGROUND: Tumor immunology plays a significant role in predicting tumor biology and how a tumor is going to respond to neoadjuvant chemotherapy (NACT). Tumor-infiltrating lymphocytes (TILs) are the easiest and by far the cheapest method of assessing tumor immunity. Many studies have suggested that TILs play an important role in tumor regression in breast cancer. AIM: The aim of the current study was to determine significance of TILs in tumor regression in breast cancer. MATERIALS AND METHODS: Patients with newly diagnosed and histologically proven breast cancer who were treated with both NACT and surgery in our institute were included in the study. TILs were assessed both before and after NACT, and were correlated with the relative amount of tumor regression and molecular subtypes based on the immunohistochemistry profile. RESULTS: The study included 43 specimens of carcinoma breast in females. 42 cases were diagnosed with invasive carcinoma, no special type (NST), and one with lobular carcinoma. Pathological complete remission (pCR) was noted in 6 cases, partial remission (PRe) in 12 cases, and no response in 25 cases. TILs were noted before and after NACT in all cases and were correlated with other clinicopathological parameters. CONCLUSION: The present study highlights that TILs play a vital role in tumor regression and can be included in routine reporting. It can provide an insight into tumor biology.

Granulomatous diseases of the central nervous system: Approach to diagnosis.

Diagnosis of central nervous system (CNS) granulomas is challenging. The etiology may be infectious or non-infectious. The infectious causes are due to mycobacteria, fungi, parasites and rarely bacteria. The non-infectious causes include autoimmune diseases, diseases of uncertain etiology like sarcoidosis, those associated with neoplasms and reparative processes. Histologic evaluation of type of granuloma as necrotizing, non-necrotizing, fibrotic/calcific or foreign-body type, site of CNS involvement (leptomeninges/dura, brain/spinal cord) and identification of etiologic agent on histochemistry/culture/molecular methods resolves the diagnosis in a many a patient. Correlation with clinical and imaging features, risk factors and route of spread, geographical location and travel history are important. However, diagnosis may remain unresolved despite the application of all available techniques, highlighting the need for better diagnostic techniques.

Pituitary blastoma, expanding the spectrum of newly recognized entities. A case report.

Tumors of the pituitary gland and sellar region represent about 15% of all brain tumors, with pituitary adenoma being the commonest and pituitary carcinoma being very rare. Pituitary tumors in children are even rarer. Pituitary blastoma, a pediatric adenohypophysial tumor, is a new entity described in the 2017 WHO classification of pituitary tumors. This is a very rare tumor with only 21 cases reported so far. Hence, we are reporting this unusual case seen in a 7-month-old infant who presented with a large sellar/suprasellar mass with pressure symptoms of short duration. Typically, they present between 7-24 months of age. On histopathology, a cellular tumor was seen with primitive-looking round cells with scanty cytoplasm with few well-defined gland or rosette-like structures. The immunohistochemical stains showed diffuse strong staining for synaptophysin with a very high MIB-1 index. Other markers for common round cell tumors in this age group and hormonal markers of pituitary tumors were negative with INI-1 being intact. The initial cases described by Scheithauer presented with Cushing's disease and at least focally expressed adrenocorticotrophic hormone on immunohistochemistry. However, nonfunctioning tumors are also seen, albeit rarely. These are known to be associated with DICER 1 mutations and have a poor prognosis. Hence, morphologic recognition in the right clinical context and excluding other differential diagnoses in infants help make the correct diagnosis.

Pathogenetic factors fanning the flames of COVID-19 to cause rhino-orbito-cerebral mucormycosis: An observational study.

BACKGROUND AND AIMS: Published studies on coronavirus disease 19 (COVID-19) associated rhino-orbito-cerebral mucormycosis (CAROCM) were primarily descriptive. Therefore, we aimed to identify features of COVID-19 that could predispose to CAROCM and explore the pathogenic pathways. PATIENTS AND METHODS: This retrospective hospital-based study was done during the first (March 2020 - January 2021) and the second (February 2021 - June 2021) waves of the COVID-19 pandemic. Subjects were grouped into four categories: first-wave CAROCM (n-4); second-wave CAROCM (n-27); first-wave non-mucor COVID (n-75), and second-wave non-mucor COVID (n-50). Data elements included age, gender, comorbidities, COVID-19 severity, steroid therapy, peak values of interleukin-6 (IL-6), serum ferritin and D-dimer, nadir values of absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and platelet count (Pl. C). RESULTS: Thirty-one patients of CAROCM were included. The mean (SD) age was 51.26 (11.48) years. 27 (87.1%) were aged ≥ 40 years and males. Severe COVID-19 was seen more often in the second wave than the first wave (P-0.001). CAROCM group was significantly younger (P-0.008) and showed a higher incidence of uncontrolled diabetes (P-0.001) and renal dysfunction (P-0.004) than non-mucor COVID. While IL-6, ferritin and D-dimer were significantly elevated in CAROCM than non-mucor COVID, clinical severity, ANC, ALC and Pl. C showed no significant difference. CONCLUSION: CAROCM is seen often in middle-aged diabetic males with uncontrolled hyperglycaemia, diabetic ketoacidosis, renal dysfunction and those infected by more transmissible delta variants and treated with steroids. IL-6, D-dimer, serum ferritin are more often elevated in CAROCM and might play a pathogenic role.

Sporadic Inclusion Body Myositis: A Clinicopathological Study.

BACKGROUND: Sporadic inclusion body myositis (s-IBM) is rare in India. AIM: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011. MATERIALS AND METHODS: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed. RESULTS: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1-5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57-2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies. CONCLUSIONS: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.

GATA-3 Expression in all Grades and Different Variants of Primary and Metastatic Urothelial Carcinoma.

Urothelial carcinoma has a varied and wide histological spectrum posing a diagnostic challenge in H&E examination alone. Immunohistochemical markers like GATA-3 along with other appropriate panel of IHC can be used. However, the percentage positivity and its intensity may vary in different variants and grades of primary and metastatic urothelial carcinoma. To observe the GATA-3 expression patterns in all the grades and different variants of primary and metastatic urothelial carcinomas. It is a prospective and retrospective observational study. All the clinically suspected urothelial carcinoma (UC) during January 2016 to December 2017 were included in the study. Depending on the differential diagnosis considered, immunohistochemistry (IHC) markers including CK7, CK20, p63, AMACR, CDX2, and p16 were done to differentiate UC from other primary carcinomas. The tumors confirmed as UC were analyzed further for GATA-3 expression by Chi-square test. The number of UC in the present study was 126 including 122 (bladder in 107, ureter in 7, renal pelvis in 5, and urethra in 3) primary and 4 metastatic UC (3 in lung and 1 in liver). Age of the patients ranged from 29 to 80 (mean 61.28) years with male/female ratio 4:1. GATA-3 showed positivity in 97 (79.5%) primary UC. GATA-3 was positive in all normal urothelium and non-invasive UC (100%), while it was positive in 69/94 (73.4%) invasive UC including variants. GATA-3 was positive in 35/39 LP invasive (89.74%) and 34/55 (61.81%) MP invasive UC. GATA-3 was positive in 39/40 papillary cases (97.5%) and 45/59 (76.27%) cases of non-papillary UC. GATA-3 showed strong expression in all metastatic UC (100%). GATA-3 expression was seen in 101/126 (80.15%) of UC including primary and metastatic carcinomas and hence was a useful marker in diagnosing UC. The GATA-3 positivity decreased from normal urothelium to UC; low-grade UC to high-grade UC; non-invasive to invasive UC; lamina propria invasive to muscle invasive UC; papillary to non-papillary UC.

Tissue microarray based immunohistochemical study of TLE1 in synovial sarcoma and its histologic mimics.

BACKGROUND AND AIMS: Molecular analysis is gold standard for diagnosis of synovial sarcoma (SS) but use of these ancillary techniques is limited by many practical issues like cost and limited resources. Several studies analyzed TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma and few studies disagreed. The objective of the study was to evaluate immunohistochemical expression of TLE1 in synovial sarcoma and its histological mimics. METHODS: The study included a total of 63 cases; of which 28 were synovial sarcomas (SS) and 35 its histologic mimics. A tissue microarray was constructed from these cases and subjected to TLE immunostaining. Nuclear immunoreactivity of TLE1 was graded as 0, 1+, 2+ and 3+ based on intensity and percentage of cells. RESULTS: All SS except one (27/28; 96.4%) were positive for TLE 1. These included 18 of monophasic spindle cell type (94.7%), 5 biphasic type (100%), followed by two each (100%) of poorly differentiated and calcifying type of SS. Of the other tumours 2 GISTs (50%), 2 haemangiopericytoma (66.7%), 2 schwannomas (50%) and one mesenchymal chondrosarcoma (33.3%) were positive for TLE1. CONCLUSION: TLE 1 is a highly sensitive marker with reasonable specificity for synovial sarcoma. Awareness of TLE1 expression in other tumours, is important to avoid misdiagnosis.

Primary Angiitis of Central Nervous System-Tumor-Like Mass Lesions: Report of Six Biopsy Confirmed Cases.

Tumor-like mass lesion is a rare subtype of primary angiitis of the central nervous system (ML-PACNS). This report describes six patients of histologically verified ML-PACNS. The mean age was 44.5 years (range 25-68) and four were males. Presenting symptoms headache (5), focal neurologic deficits (5), and seizures (4). On magnetic resonance imaging (MRI) the lesion was unifocal in two and multifocal in four patients. Consistent radiological findings were mass lesions with heterointense internal morphology with areas of diffusion restriction (DWI), and variable post-contrast enhancement. Pathologically vasculitis was classified as: Granulomatous in one, necrotizing in two and lymphocytic in three. There were two deaths. In conclusion patients with ML-PACNS are likely to be younger and more likely to present with seizures. MRI lesions with hetrointense internal morphology with areas of DWI was a consistent finding and may be a clue for the diagnosis of ML-PACNS.

FISH for EWSR1 in Ewing's sarcoma family of tumors: Experience from a tertiary care cancer center.

BACKGROUND: : Molecular confirmation of histologic diagnosis has become mandatory for the diagnosis of Ewing sarcoma family of tumors (ESFT). AIM: To validate the diagnosis made by morphology and immunohistochemistry (IHC) by fluorescence in-situ hybridization (FISH) for EWSR1 rearrangement on formalin fixed paraffin embedded (FFPE) tissues. Settings and design: A retrospective and prospective observational study. Material and methods: All patients who had FISH studies for EWSR1 rearrangement for small round cell tumors during 10 years period were included. Demographic, clinical and radiological details were obtained from medical records. Morphology was reviewed with IHC by CD99, FLI1 and others. FISH studies were performed using the break apart probe. Additional molecular studies and IHC were done to resolve the diagnosis in EWSR1 rearranged tumors. Final diagnosis was made by integrating clinical, morphology, IHC and molecular features. RESULTS: There were 81 patients (M: F 45:36, median age 21 years) with 32 skeletal and 49 extra skeletal tumors. CD 99 was positive in 94.52%. FISH for EWSR1 were positive in 59, negative in 13 and failed in 9. The final diagnosis was made as ESFT in 67, angiomatoid fibrous histiocytoma in 3, desmoplastic small round cell tumor in 3, myxoid chondrosarcoma in 2, unclassified in one, synovial sarcoma in 3, and one each of lymphoma and small cell neuroendocrine carcinoma. FISH was positive for ESFT in 89.83% of EWSR1 rearranged tumors. FISH validated the diagnosis made on IHC in 79.10%. FISH resolved the diagnosis in 1.49% CD99 negative tumors. CONCLUSION: FISH is a reliable ancillary technique for the diagnosis of ESFT on FFPE tissues.

Thymoma diagnosis and categorization in the current scenario: Morphological analysis based on interobserver variability.

BACKGROUND: Thymomas are not so common tumors that are encountered in day-to-day pathology reporting. The WHO system was proposed in 2015. Although, through its detailed reporting, the WHO elaborates all subtypes and morphological clinches to diagnosis, it was important to ascertain its reproducibility in our day-to-day reporting. AIMS: The aims of the study were (1) to study the interobserver agreement, concordance rates, and variability in the classification of a large number of thymomas received in our department as per the WHO 2015, (2) to correlate the WHO subtype with Masaoka-Koga stage, and (3) to study the variations in demography of thymomas in Indian patients as compared to those reported in the literature. SETTING AND DESIGN: This retrospective study was done at a tertiary care teaching hospital with huge surgical oncology patient load, also pertaining to the cardiothoracic surgeries. It is predominantly an interobserver agreement design to study the reproducibility of the WHO 2015 classification on thymic epithelial tumors. METHODS: Four pathologists have independently reviewed histopathology slides of 65 cases of thymomas and classified them into predefined categories. Kappa statistics was applied to the observations. RESULTS: There was a substantial interobserver agreement in overall classification of thymomas with a Cohen's kappa score of 0.66. A better score was achieved for the classification of Group B thymomas. The WHO subtypes correlate well with the Masaoka-Koga staging system, and this finding is statistically significant. This article also presents the clinical details of a large number of thymoma cases. CONCLUSION: The new WHO classification has good reproducibility among pathologists in thymoma reporting.

Juvenile idiopathic inflammatory myopathies: A clinicopathological study with emphasis on muscle histology.

BACKGROUND: Juvenile idiopathic inflammatory myopathies (JIIM) are rare and heterogeneous. Subtype identification is important for treatment. MATERIALS AND METHODS: Patients below 18 years diagnosed as idiopathic inflammatory myopathy (IIM) according to the Bohan and Peter criteria between January 2010 and May 2015 were evaluated with muscle biopsy in the four domains: muscle fiber, inflammation, connective tissue, and vascular, with basic panel of histochemical stains as per recommendations of the European Neuromuscular center (ENMC) workshop 2015. Immunohistochemistry with CD 31 was done to assess capillary density. RESULTS: JIIM constituted 15.25% of IIM with juvenile dermatomyositis (JDM) being the most common subgroup (24/27) followed by juvenile overlap myositis (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). Muscle biopsy in JDM was characterized by perifascicular atrophy, necrosis, degeneration, and regeneration in all and the other features included perivascular inflammation (21), lymphoid aggregates (2), mitochondrial abnormalities (9), sarcoplasmic vacuoles (6), capillary dropout (5), capillary dilatation (6), and perimysial fibrosis (14). JOM was characterized by auto-antibodies and perivascular inflammation. CONCLUSION: JIIMs were rare and JDM was the most common subtype. Muscle biopsy evaluation as per ENMC criteria characterized the subgroups.

Validation of the WHO 2016 new Gleason score of prostatic carcinoma.

CONTEXT: New Gleason Score of Prostate. AIMS: The aim of this study is to assign the patients with carcinoma prostate into new prognostic grade groups (PGGs) based on revised Gleason score (GS) and follow-up according to the WHO 2016. SUBJECTS AND METHODS: All the biopsies/resected specimens of carcinoma prostate from January 2014 to June 2016 were reviewed, and GS was done according to the WHO 2016. Accordingly, cribriform, fused, and glomeruloid glands were assigned GS 4. Thus, two groups were identified with GS 7 (3 + 4 and 4 + 3). The patients were grouped into PGGs 1-5. The number of patients with change in the prognostic group along with follow-up was calculated. RESULTS: There were 143 patients with carcinoma prostate, with a median age of 65 years. The initial GS was revised, and there was a decrease in GS 3 + 4 from 13.9% to 9% and increase in 4 + 3 from 19.6% to 23.8%. There was upgradation of PGG in 11 (7.69%) biopsies; with PGG from 1 to 2 in one; 2to 3 in eight; and 3to 4 in two. Follow-up at 2 years in 22 showed the poor prognoses in the patients who were upgraded to the higher prognostic group. CONCLUSIONS: A change in PGG according to the WHO 2016 criteria was assigned in 7.69% biopsies of carcinoma prostate, and it correlated with prognosis.

C4d as a marker of complement activation in dermatomyositis muscle tissue.

AIM: To study C4d expression as a marker of complement activation in the diagnosis of dermatomyositis. MATERIAL AND METHODS: Muscle biopsies from patients diagnosed as definite dermatomyositis (10), nonspecific myositis associated with connective tissue disease (9), necrotizing autoimmune myositis (1), inclusion body myositis (1), and normal muscle (1) according to European Neuromuscular criteria 2004 were studied for C4d expression and capillary loss on CD 34 immunohistochemistry. RESULTS: C4d was expressed in all biopsies of definite dermatomyositis in the perimysial vessels and in 3/10 endomysial capillaries corresponding to capillary loss on CD 34.C4d expression was seen in 2/3 perimysial and endomysial vessels in nonspecific myositis (2/3 overlap myositis), and 1/1 of nectrotizing autoimmune myositis.Necrotic muscle fibers in all biopsies showed positivity irrespective of the diagnosis. CONCLUSION: C4d can be used as a marker of complement activation for the diagnosis of dermatomyositis.

Idiopathic inflammatory myopathies in adults: A comparative study of Bohan and Peter and European Neuromuscular Center 2004 criteria.

BACKGROUND: Bohan and Peter criteria are widely used for the diagnosis of idiopathic inflammatory myopathies (IIMs). Recently, European Neuromuscular Center (ENMC) formulated criteria to identify subgroups of IIMs. AIM: To compare the two diagnostic criteria in adult IIMs. MATERIALS AND METHODS: This was a retrospective review of case records of histologically confirmed IIMs in adults between January 2014 and May 2015. Both the Bohan and Peter, and ENMC 2004 criteria were applied in the same group of patients to subgroup the IIMs. Muscle biopsy was evaluated in all the four domains: muscle fiber, inflammatory, connective tissue, and vascular, with the basic panel of histological stains. Sporadic inclusion body myositis (s-IBM) was diagnosed using ENMC IBM diagnostic research criteria 2011. RESULTS: During the study period, 69 patients fulfilled the ENMC criteria for IIMs including 16 patients with s-IBM. The subgrouping as per the ENMC criteria (53) was: dermatomyositis (DM) in 30; polymyositis (PM) in 2; immune-mediated necrotizing myopathy (IMNM) in 9; and nonspecific myositis (NM) in 12 patients, whereas subgrouping by the Bohan and Peter criteria was DM in 9 and PM with and without connective tissue disease (CTD) in 26 patients only. There was underdiagnosis of DM, as perifascicular atrophy is not recognized as a diagnostic histological feature, and overdiagnosis of PM with and without CTD due to poor characterization of histological features in PM by the Bohan and Peter criteria. CONCLUSIONS: Systematic evaluation of muscle biopsy according to the ENMC criteria with basic panel of histochemical stains improved the diagnostic yield of IIM significantly when compared to the Bohan and Peter criteria.

Meningiomas: Objective assessment of proliferative indices by immunohistochemistry and automated counting method.

BACKGROUND: The most reliable histological correlate of recurrence risk in meningiomas is increased mitotic activity. Proliferative index with Ki-67 immunostaining is a helpful adjunct to manual counting. However, both show considerable inter-observer variability. A new immunohistochemical method for counting mitotic figures, using antibody against the phosphohistone H3 (PHH3) protein was introduced. Similarly, a computer based automated counting for Ki-67 labelling index (LI) is available. AIMS AND OBJECTIVES: To study the use of these new techniques in the objective assessment of proliferation indices in meningiomas. MATERIALS AND METHODS: This was a retrospective study of intracranial meningiomas diagnosed during the year 2013.The hematoxylin and eosin (H and E) sections and immunohistochemistry (IHC) with Ki-67 were reviewed by two pathologists. Photomicrographs of the representative areas were subjected to Ki-67 analysis by Immunoratio (IR) software. Mean Ki-67 LI, both manual and by IR were calculated. IHC with PHH3 was performed. PHH3 positive nuclei were counted and mean values calculated. Data analysis was done using SPSS software. RESULTS: A total of 64 intracranial meningiomas were diagnosed. Evaluation on H and E, PHH3, Ki-67 LI (both manual and IR) were done in 32 cases (22 grade I and 10 grade II meningiomas). Statistically significant correlation was seen between the mitotic count in each grade and PHH3 values and also between the grade of the tumor and values of Ki-67 and PHH3. CONCLUSION: Both the techniques used in the study had advantage over, as well as, correlated well with the existing techniques and hence, can be applied to routine use.

Diagnosis of Adrenocortical Tumors by Reticulin Algorithm.

AIMS: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin-Weiss-Bisceglia (LWB) criteria for oncocytic variant. MATERIALS AND METHODS: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010-June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records. The functional status of the tumor was noted based on clinical and biochemical evaluation. The location, size, and gross appearance of the tumor were noted. The corresponding hematoxylin and eosin-stained slides were independently assessed by two pathologists applying modified Weiss criteria and LWB criteria for the oncocytic variant as applicable. Reticulin stain was performed on representative sections in all cases. All the tumors were classified according to RA, and the diagnoses made by each system were correlated. RESULTS: There were 15 ACTs in the study period. There were two adenomas including one oncocytoma which showed Weiss score (WS) of 2 and intact reticulin framework. There were 13 adrenal cortical carcinomas including two oncocytic variants with WS ranging from 4 to 7. There was disruption of reticulin and thick, irregular reticulin fibers in all tumors, irrespective of the histology. It correlated with modified Weiss and LWB criteria. CONCLUSIONS: The RA was simple, easy to apply, and correlated well with modified Weiss criteria in the diagnosis of ACTs including the oncocytic variant.

Primary leptomeningeal primitive neuroectodermal tumor: A difficult entity to diagnose.

A 25-year-old male presented with difficulty in walking, loss of vision, and seizures. A clinical possibility of craniospinal meningeal pathology was considered. On computed tomography (CT) scan and magnetic resonance imaging, there was an enhancement of leptomeninges with few ring-enhancing lesions in both frontal lobes and right frontoparietal region. He was evaluated for low backache and occipital headache 2½ years earlier and was found to have communicating hydrocephalus on CT scan. He underwent ventriculoperitoneal shunt and was followed up with CT scans. Meningeal biopsy was done in the present admission, and there was a diffusely infiltrating small round cell tumor. Immunohistochemistry was done, and the tumor cells were found to be negative for glial, mesenchymal, melanotic, and lymphoid markers. The cells were positive for neuron-specific enolase, chromogranin, and vimentin. A diagnosis of primitive neuroectodermal tumor involving the meninges was made. A possibility of primary leptomeningeal tumor extending to parenchyma was considered based on the clinical progression. Patient was treated with chemotherapy and radiotherapy. He improved partially and was stable at 3-year follow-up.

Clival giant cell tumor - A rare case report and review of literature with respect to current line of management.

Giant-cell tumor (GCT) involving the skull base is rare. Sphenoid bone is the most commonly involved bone followed by petrous temporal bone. Histopathology and radiological features of these lesions are similar to GCT involving bone elsewhere. Unlike other sites, skull base is not an ideal site for the radical surgery. Hence adjuvant treatment has pivotal role. Radiation therapy with intensity-modulated radiation therapy, stereotactic radiosurgery or chemotherapy with adriamycin are promising as described in some case reports. Bisphosphonates showed good control in local recurrence. In vitro studies with Zolendronate loaded bone cement and phase 2 trials of Denosumab showed hopeful results, may be useful in future.