Atypical MYC rearrangement pattern of 3' deletion and 5' amplification along with independent IGH rearrangement: A case study.

A spectrum of Cellular homolog of the v-myc oncogene (cMYC) alterations such as translocation, overexpression, mutation, and amplification plays an important role in lymphomagenesis, particularly in high-grade lymphomas, and are associated with prognostic significance. Accurate identification of cMYC gene alteration is important for diagnostic, prognostic, and therapeutic implications. With the application of different FISH (fluorescence in situ hybridization) probes that helped overcome the analytical diagnostic challenges as a result of variant patterns, we report rare, concomitant, and independent gene alterations in cMYC and Immunoglobulin heavy-chain gene (IGH) with detailed characterization of its variant rearrangement. Short-term follow-up post R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy seemed to be favorable. Accumulation of many more literature studies on such cases with their therapeutic implications would lead to the categorization of these cases as a separate subclass in large B-cell lymphomas followed by molecular targeted therapy.

Indian Academy of Cytologists Guidelines for Collection, Preparation, Interpretation, and Reporting of Serous Effusion Fluid Samples.

Cytological examination plays an important role in the initial work-up of the serous cavity effusion fluids to find out the possible etiology as benign or malignant. Among malignant effusions, cytology is helpful in determining the exact type, site, and stage of the tumor. However, for reporting effusion cytology specimens, there is no consistent and reproducible reporting system. AIMS: The aim of these guidelines is to provide a standardized format for effusion cytopathology right from sample receipt to its ultimate report sign-out for implementation in all cytopathology laboratories. The Indian Academy of Cytologists in consultation with experts across the country has prepared guidelines pertaining to collection, preparation, and diagnostic categories of effusion specimens to reduce reporting variability. The guidelines are made keeping in mind the different areas of practices in India, especially low- and medium-resource settings. The guidelines are broadly divided into essential, optimal, and optional categories for best usage and appropriate allocation of the precious specimens. In referral centers or well-established setups, essential ancillary techniques can be done for accurate and final diagnosis. By adhering to and implementing these uniform guidelines, it is hoped that clinical patient care and management in India will improve and be of uniformly good quality by enabling and facilitating good laboratory practices.

Histopathological Evaluation of Inferior Alveolar Neurovascular Bundle in Cases of Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia is a painful disease that has been afflicting mankind since time immemorial. The etiology and pathophysiology have been widely studied but poorly understood. There are well-documented researches analyzing ultrastructural changes in trigeminal root specimens obtained following microvascular decompression surgery. However, there are no studies evaluating microscopic changes following peripheral neurectomy. PURPOSE: The present study examined microscopic changes in inferior alveolar neurovascular bundle in trigeminal neuralgia patients of mandibular division with no underlying cause. MATERIALS AND METHODS: The biopsy specimens were obtained from peripheral neurectomy of 11 trigeminal neuralgia patients' refractory to anti-neuralgic medications. The autopsy specimens from 10 cadavers were used as control. The specimens were subjected to histopathological examination by hematoxylin and eosin, Masson trichrome and Luxol fast blue stains. RESULTS: All biopsy specimens reported luminal occlusion of small vessels, medial degeneration and intense mononuclear inflammatory infiltrate. Focal myelin digestion chambers were observed in large and small axons. No pathological alterations of either blood vessel or nerve fibers were reported in autopsy specimens. CONCLUSION: The demyelination of inferior alveolar nerve due to pathologic vascular changes in peripheral vasculature may have a role in initiation and precipitation of trigeminal neuralgia, and hence, peripheral neurectomy has a significant role in alleviating pain.

Performance of A Convolutional Neural Network in Screening Liquid Based Cervical Cytology Smears.

CONTEXT: Cervical cancer is the second most common cancer in women. The liquid based cervical cytology (LBCC) is a useful tool of choice for screening cervical cancer. AIMS: To train a convolutional neural network (CNN) to identify abnormal foci from LBCC smears. SETTINGS AND DESIGN: We have chosen retrospective study design from archived smears of patients undergoing screening from cervical cancer by LBCC smears. MATERIALS AND METHODS: 2816 images, each of 256 × 256 pixels, were prepared from microphotographs of these LBCC smears, which included 816 "abnormal" foci (low grade or high grade squamous intraepithelial lesion) and 2000 'normal' foci (benign epithelial cells and reactive changes). The images were split into three sets, Training, Testing, and Evaluation. A convolutional neural network (CNN) was developed with the python programming language. The CNN was trained with the Training dataset; performance was assayed concurrently with the Testing dataset. Two CNN models were developed, after 20 and 10 epochs of training, respectively. The models were then run on the Evaluation dataset. STATISTICAL ANALYSIS USED: A contingency table was prepared from the original image labels and the labels predicted by the CNN. RESULTS: Combined assessment of both models yielded a sensitivity of 95.63% in detecting abnormal foci, with 79.85% specificity. The negative predictive value was high (99.19%), suggesting potential utility in screening. False positives due to overlapping cells, neutrophils, and debris was the principal difficulty met during evaluation. CONCLUSIONS: The CNN shows promise as a screening tool; however, for its use in confirmatory diagnosis, further training with a more diverse dataset will be required.

A study of BRAF mutation in colorectal carcinoma in Indian population.

CONTEXT: BRAF mutation has been extensively studied and associated with various tumors. Targeted therapeutic intervention against BRAF mutation is established modality against many such tumors. Various studies have estimated that the prevalence of BRAF mutation in colorectal carcinoma (CRC) is 5%-25%. Considering epidemiology differences from Western population and paucity of studies on BRAF mutation in CRC in Asian patients, the present study was done to study the BRAF mutation in CRC in Indian population. AIMS: The aim is to study the distribution of BRAF mutation and its correlation with the American Joint Committee on Cancer (AJCC) stage, grade, and other clinicopathological parameters in CRC. SETTINGS AND DESIGN: This was a cross-sectional study. SUBJECTS AND METHODS: Immunohistochemistry study was done using BRAFV600E monoclonal antibody (Clone VE1) for 65 consecutive cases of CRC in a tertiary care center. The results were statistically analyzed using SPSS version 2.0. RESULTS: This study found that BRAF mutation is not significantly present in CRC as only 4.6% of cases were positive for BRAFV600E mutation. However, there was statistically significant relation between increasing AJCC stage and BRAF mutation. CONCLUSIONS: This study concluded that BRAF mutation is not prevalent in Indian population with CRC. However, it is significantly related with advanced AJCC stages.

Pilot Study of an Open-source Image Analysis Software for Automated Screening of Conventional Cervical Smears.

INTRODUCTION: The Pap stained cervical smear is a screening tool for cervical cancer. Commercial systems are used for automated screening of liquid based cervical smears. However, there is no image analysis software used for conventional cervical smears. The aim of this study was to develop and test the diagnostic accuracy of a software for analysis of conventional smears. MATERIALS AND METHODS: The software was developed using Python programming language and open source libraries. It was standardized with images from Bethesda Interobserver Reproducibility Project. One hundred and thirty images from smears which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and 45 images where some abnormality has been reported, were collected from the archives of the hospital. The software was then tested on the images. RESULTS: The software was able to segregate images based on overall nuclear: cytoplasmic ratio, coefficient of variation (CV) in nuclear size, nuclear membrane irregularity, and clustering. 68.88% of abnormal images were flagged by the software, as well as 19.23% of NILM images. The major difficulties faced were segmentation of overlapping cell clusters and separation of neutrophils. CONCLUSION: The software shows potential as a screening tool for conventional cervical smears; however, further refinement in technique is required.

Clear cell sarcoma arising from paraspinal ligament of thoracic spine: Report of an unusual case.

Clear cell sarcoma (CCS) is an unusual but aggressive soft-tissue tumor with an incidence of <1% of all soft-tissue sarcomas. It was previously termed "malignant melanoma of soft parts" due to its resemblance clinically and morphologically. Normally CCS is seen in patients aged 20-40 years. A rare case of CCS of paraspinal ligament in a 5-year-old boy is being reported. Histopathology and immunohistochemistry markers confirmed the diagnosis. The present case is unique since the entity itself is rare and also due to its occurrence in a child.

Mucinous tubular and spindle cell carcinoma of kidney: A case report of an unusual tumor.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and unusual variant of renal cell carcinoma (RCC). It is important to differentiate this from the other variants particularly papillary RCC since MTSCC is generally low-grade, has low malignant potential and favorable prognosis. We are reporting a 40-year-old female presenting with right flank pain and well-circumscribed renal mass confined to the lower pole. Tumor consisted of tubules and cords separated by pale mucinous material in some areas, whereas other areas showed dense cellularity without significant mucin. The tumor cells were cuboidal or spindle and did not show significant atypical features. The patient underwent nephrectomy and is asymptomatic clinically and radiologically after 2 years.

Management of Isolated Musculocutaneous Injury: Comparing Double Fascicular Nerve Transfer With Conventional Nerve Grafting.

PURPOSE: To compare the functional outcomes of nerve grafts and nerve transfers in the management of isolated musculocutaneous nerve (MCN) injuries. METHODS: We performed a retrospective case-control study of isolated MCN injury managed at a tertiary care center. The study group was composed of 12 patients managed with double nerve transfer whereas the 8 patients in the grafted group constituted the control group. RESULTS: In the study group, stab and missile injuries constituted most cases with a denervation period ranging between 3 and 9 months. Eleven patients in this group experienced a full range of active elbow flexion whereas one had antigravity flexion of 120°. Electromyography revealed the first sign of reinnervation of biceps at 10 ± 2 weeks, compared with 20 ± 2 weeks in the grafted group. The overall trend was for patients in the study group to have earlier return of active elbow flexion and better restoration of elbow flexion strength and range of (presumably active) elbow motion than those treated with grafting, although none of these measures reached statistical significance. CONCLUSIONS: We found that distal nerve transfer was a superior method of managing isolated MCN injury compared with conventional nerve grafting.

Greater auricular nerve masquerading as lymph node.

Hansen's disease is on the verge of being eliminated from India and often missed by clinicians due to low index of suspicion. We present an unusual case in which greater auricular nerve thickening masqueraded as enlarged lymph node in the neck. The patient was referred for fine needle aspiration cytology, which revealed epithelioid cell granulomas suggestive of Hansen's disease. Further clinical examination and investigations including the skin biopsy confirmed the disease, highlighting the role of pathologist in the management of such unusual presentation of a common disease.

Renal cell carcinoma, unclassified with unique features.

Renal cell carcinoma, unclassified constitute about 3-4% of all renal carcinomas. It essentially is a tumor where more than morphological variants or subtypes are seen in a single tumor. Usually there is a mixture of 2-3 different types. However, in this particular case there were at least 5 different types of morphological patterns in a single tumor including areas of so-called rhabdoid differentiation. The patient underwent nephrectomy and has been asymptomatic for the last 3.5. years. To the best of our knowledge, this is the first case of its own kind in the published literature.

An unusual case of cavernous haemangioma of the Fallopian tube.

Fallopian tubes are one of the uncommon sites for neoplastic lesions in the female genital tract. Haemangiomas of the fallopian tubes are rare benign neoplasms that are documented as isolated case reports only. We present a rare case of incidentally detected cavernous haemangioma of the fallopian tube in a post menopausal female who underwent hysterectomy and bilateral salphingoopherectomy for dysfunctional uterine bleeding.

Primary intracranial benign fibrous histiocytoma: report of an unusual case.

Benign fibrous histiocytomas (BFH) are neoplasms of the soft tissue and bone composed of fibroblastic and histiocytic components without any nuclear pleomorphism or histological anapalsia. Primary intracranial fibrous histiocytomas are rare entities. In comparison with the malignant counterpart, BFH are more uncommon. We describe a case of a 54-year-old woman, who presented with complaints of headache, giddiness, and gait instability of six months' duration. Magnetic resonance imaging (MRI) studies revealed an extra-axial lesion in the inferior aspect of the left temporal lobe suggestive of en-plaque meningioma. Subsequent histopathological examination of the biopsy sample revealed a benign fibrous histiocytoma, with involvement of the overlying temporal bone. Immunohistochemical analysis showed positivity for vimentin and CD68, with MIB-1 labeling index (MIB-1LI) of 2%, confirming the diagnosis.

Morphometric study of nuclei and microvessels in gliomas and its correlation with grades.

INTRODUCTION: Modifications of nuclear morphology in conjunction with alteration in microvascular configuration are essential features encountered during the progression of glial tumors. In order to gain more insight into tumor biology of gliomas, objectives of the study were selected (a) to correlate morphometrically evaluated nuclear parameters [nuclear area (NA), nuclear perimeter (NP), nuclear density (ND), percentage of total nuclear area (%TNA)] and microvessel parameters [microvessel density (MVD), microvessel caliber (VC), microvessel cross sectional area (VCSA), total microvessel boundary density (TVBD), percentage of total VCSA (%TVCSA)] with WHO grading; (b) extend such correlations to the ratio parameters: ratio of MVD to ND (MDV/ND), ratio of TVBD to %TNA (TVBD/%TNA) and ratio of %TVCSA to %TNA (%TVCSA/%TNA); and (c) to correlate microvessel and ratio parameters with NP and ND. MATERIALS AND METHODS: A total of thirty gliomas managed at this institute during 2009-2012 were evaluated for various nuclear and microvessel parameters by image morphometry using a computerized digital photomicrograph system. For assessment of microvessel parameters CD34-immunostained sections were used while nuclear morphometry was performed on routine hematoxylin-eosin-stained sections. Appropriate statistical analysis was performed in correlation studies. RESULTS: All nuclear morphometric parameters showed strong positive correlation with tumor grades (r>0.7). In contrast, though all microvessel parameters exhibited positive correlation with grades, the parameters TVBD and %TVCSA showed strong positive correlation. The ratio parameters (MVD/ND) and (TVBD/%TNA) showed negative correlation with grades, whereas (%TVCSA/%TNA) did not exhibit meaningful correlation with grades. Further, while all microvessel parameters showed positive correlation with NP and ND; ratio parameters showed negative correlation with them. CONCLUSION: This study indicates that the parameters related to tumor growth (NA, NP, ND, %TNA), and angiogenesis showed increasing trend with tumor grades simultaneously; whereas the parameters related to supply of nutrients per nucleus showed decreasing trends with tumor grades, nuclear size and nuclear density. Thus, the former accounts for increased cellularity, mitosis, and vascular proliferation, while the latter culminates in tumor necrosis, all of which are essential components for grading of gliomas. The present study will therefore have a vital role as surrogate markers of grading of tumor.

A rare case of familial reactive perforating collagenosis.

A 4 year old boy presented with history of itchy raised lesions on body of 2 years duration. Though parental consanguinity was not present, his elder brother had similar complaints. Dermatological examination revealed multiple hyperpigmented papules with a central keratotic plug distributed mainly over face and extensors of upper and lower extremities. Koebnerisation was present. Skin biopsy revealed perforating collagen bundles in the upper dermis and epidermis which was confirmed by Van Gieson staining. Patient was being treated with topical retinoids and intralesional corticosteroids with minimal relief.

Utility of nuclear morphometry in predicting grades of diffusely infiltrating gliomas.

Introduction. The ability to reliably differentiate neoplastic from nonneoplastic specimen and ascertain the tumour grade of diffusely infiltrating gliomas (DIGs) is often challenging. Aims and Objective. To evaluate utility of image morphometry in identifying DIG areas and to predict tumour grade. Materials and Methods. Image morphometry was used to analyze the following nuclear features of 30 DIGs and 10 controls (CG): major axis of nucleus (MAJX), minor axis of nucleus (MINX), nuclear area (NA), nuclear perimeter (NP), nuclear roundness (NR), nuclear density (ND), and percentage of total nuclear area (%TNA). Results. Statistically significant differences in all parameters, except NR, were observed between all groups, with strong positive correlation with tumour grade (r > 0.7). The mean values were maximum for HGG and minimum for CG. For NR, the difference between CG/HGG was statistically significant, unlike CG/LGG and LGG/HGG. It was observed that NA distributions for CG were nearly Gaussian type with smaller range, while gliomas displayed erratic pattern with larger range. NA and NP exhibited strong positive correlation with ND. Conclusion. Image morphometry has immense potential in being a powerful tool to distinguish normal from neoplastic tissue and also to differentiate LGG from HGG cases, especially in tiny stereotactic biopsies.

Posterior approach for both spinal accessory nerve to suprascapular nerve and triceps branch to axillary nerve for upper plexus injuries.

Restoration of stability and movements at the shoulder joint are the 2 most important goals in the management of brachial plexus injuries. The 2 nerves that are preferentially targeted for this purpose are the suprascapular (SSN) and the axillary (AXN) nerves. These nerve transfers have conventionally been performed by the anterior approach, but recently transfers performed by posterior incisions have been gaining popularity, by virtue of being selective and located close to the target muscles. Herein, we describe the technical details of spinal accessory nerve (SAN) to SSN and triceps branch to AXN for upper plexus injuries, both performed by the posterior approach.

Correlation of histomorphologic prognostic markers and proliferative index with loss of heterozygosity 1p/19q and MGMT status in diffusely infiltrating gliomas.

BACKGROUND: Loss of heterozygosity (LOH)1p/19q, and epigenetic silencing of O(6)-methylguanine-DNAmethyltransferase (MGMT) gene, displayed promising role as predictive and prognostic markers in brain tumours. The present study correlated both with conventional histomorphologic prognostic markers and proliferative index in diffusely infiltrating gliomas (DIG). METHODS: Tissues from 45 patients were evaluated for LOH1p/19q using polymerase chain reaction based microsatellite analysis; and for MGMT using immunohistochemistry. Results were correlated with age, histologic type, WHO grade, and proliferation index. RESULTS: Mean MIB-1 LI showed significant correlation with tumour grade. MGMT-staining in grade II and IV tumours were 31.1% and 16.8%, respectively, while in DA and GBM it was 88.2% and 19.0%, respectively, which were statistically significant. Sixteen cases showed LOH 1p and/or 19q of which 10 (5 oligodendroglial, 3 GBM, AA, DA) had combined LOH; while three each showed 1p (all GBM) and 19q (2 DA and GBM) loss. In the MIB-1LI ≤ 5% and >5% groups LOH 1p and/or 19q was encountered in 6 and 10 cases, respectively. A significant inverse association was noted between LOH with MGMT. CONCLUSIONS: LOH1p/19q and MGMT shows good correlation with conventional histomorphologic and proliferation markers, and should constitute part of the optimal diagnostic workup of DIG.

Pemphigus foliaceus masquerading as IgA pemphigus and responding to dapsone.

A 14-year-old male presented with seven years history of recurrent episodes of fluid filled, itchy and eroded lesions over the body not responding to oral corticosteroids and azathioprine. Dermatological examination revealed crusted plaques and erosions in a seborrheic distribution. Histopathology of skin lesions and direct immunofluorescence were characteristic of pemphigus foliaceus. He was treated with dexamethasone pulse therapy with inadequate response. However, relapsing skin lesions revealed a circinate arrangement with a predilection to trunk and flexures. In view of clinical features suggestive of IgA pemphigus, he was started on dapsone, to which he responded dramatically in four weeks. However, repeat biopsy continued to reveal features of pemphigus foliaceus and ELISA for anti-desmoglein 1 antibodies was positive.