Histopathology of the Host Cornea Following Penetrating Keratoplasty.

INTRODUCTION: To study the ultra-structural changes in the diseased corneal cells by histopathology, electron microscopy, and immunohistochemistry using conventional antisera and monoclonal antibodies with the ultimate goal of justifying pre-treatment and post-treatment advice and, if necessary, modifying the post-operative treatment for improved graft survival. METHODS: Thirty cases registered for penetrating keratoplasty were worked up for routine systemic and ophthalmic criteria. A full-thickness diseased cornea was subjected to histopathology after suitable staining and fixation, including electron microscopic and immunohistochemical studies where possible. RESULTS: The ages ranged from four to 60 years. The majority (26%) were in the age group of 31-40 years. The most frequent causes of corneal pathology that underwent keratoplasty include post-traumatic corneal scarring (40%), followed by pseudophakic bullous keratopathy (16.7%). In almost all cases, the histopathology confirmed the existing clinical diagnosis. Histopathology helped to confirm one doubtful case of Fuchs' dystrophy and to contradict one clinical diagnosis of pseudophakic bullous keratopathy, which turned out to be epithelization of the anterior chamber. CONCLUSION: The results underline the significance of the histopathological study of these corneal conditions to increase the post-surgical survival of the corneal graft.

Study of angiogenesis in invasive breast carcinoma by morphometry and immunohistochemistry.

Background: Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma. Methods: Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated. Results: The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels. Conclusions: In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.

Application of International association for the study of lung cancer/American Thoracic Society/European Respiratory Society criteria for the diagnosis of lung carcinomas on small biopsies: A tertiary care center experience.

BACKGROUND: The new IASLC/ATS/ERS classification provides standardized terminology for lung cancer diagnosis in small biopsies and cytology specimens. OBJECTIVES: The aim was to study the feasibility of the guidelines using one marker for adenocarcinoma (ADC) and one for squamous cell carcinoma (SQCC) in non-small cell lung carcinomas (NSCLCs). SUBJECT AND METHODS: In this study, we reviewed all the formalin-fixed paraffin-embedded tissue blocks diagnosed as lung carcinoma between July 2016 and December 2017. Cases were labeled as SCLC, ADC, SQCC, NSCLC favor ADC, NSCLC favor SQCC, NSCLC-not otherwise specified (NOS), and NSCLC-NOS possible adeno-SQCC (ADSQCC) as per IASLC/ATS/ERS 2011 guidelines. A three-step approach incorporating morphology, immunohistochemistry (IHC), and molecular analysis was used. RESULTS: One hundred and nine cases were included. Six of the 109 cases were SCLC and 1 case was of large-cell neuroendocrine type. Of the remaining 102, 51 were diagnosed based on their classical histomorphology into SQCC (8) and ADC (43). Remaining 51 cases required IHC/special stains for categorization. The panel comprised anti-CK7, anti-thyroid transcription factor-1 (TTF-1), and anti-p63. Twenty-nine were positive for anti-TTF-1 and thus labeled as NSCLC favor ADC. Fifteen were labeled as NSCLC favor SQCC as they were highlighted by anti-p63. Four cases showed reaction to both the antibodies in different sets of tumor cells and thus were classified as NSCLC-NOS, possible ADSQCC. Remaining 3 cases did not show reaction to any of the antibodies and hence were labeled NSCLC-NOS. CONCLUSION: The need for every laboratory to use minimal tissue for ancillary tests to diagnose lung carcinoma on small biopsies is reemphasized. Tissue from small biopsies needs to be preserved not only for the diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, in this era of personalized medicine.

Osteoclastic variant of anaplastic thyroid carcinoma: A case report of rare entity.

Anaplastic thyroid carcinoma (ATC) is a rare, highly malignant thyroid tumor with dismal prognosis. Osteoclastic giant cell variant of ATC is extremely rare and is characterized by the presence of a large number of multinucleated giant cells resembling osteoclasts. We report here this unusual variant in a 67-year-old female with a history of long-standing goiter of 13 years duration. Histologically, many multinucleated osteoclast-like giant cells were seen accompanying the malignant spindle cell component. Despite extensive sampling, no evidence of differentiated thyroid malignancy could be elucidated.

Evaluation of cases of membranoproliferative glomerulonephritis according to newer classification: A retrospective record-based study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) has traditionally been classified on electron microscopy (EM) into different types based on the location of the immune complexes. Sethi et al. subsequently suggested a more relevant etiology-based and clinically useful classification based on immunofluorescence. METHODS: In this retrospective study, 18 diagnosed cases of MPGN over a one-year period for which direct immunofluorescence (DIF) study results were available, were selected. Cases without archived records of immunofluorescence photographs/reports were excluded. Histological diagnosis of MPGN was confirmed and DIF results were analyzed with reference to antibodies to IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. RESULTS: Evaluation of cases revealed 8 males and 10 females with age range from 11 to 66 years. Fifteen cases presented with nephrotic syndrome. On evaluation, 88.89% cases (16/18) were immune complex mediated while two (11.11%) were of complement mediated type of MPGN. Among immune complex-mediated cases, a single case of monoclonal gammopathy associated or light chain mediated MPGN was present. CONCLUSION: The classification described by Sethi et al. is easy to use since it relies on DIF instead of EM which is not readily available. Most of the cases were immune complex mediated whereas incidence of complement mediated MPGN, that is, C3 glomerulopathy was low (11.11%). Application of the new classification allows more relevant categorization of cases based on etiology and without the requirement of EM.

Invasive cutaneous mucormycosis in a preterm neonate presenting as a vesicobullous lesion.

Mucormycosis is a relatively rare fungal infection seen in immunocompromised patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates have been reported in literature. It is an aggressive disease with a mortality rate of around 64% in neonates, so a high index of suspicion is essential for rapid diagnosis and definitive treatment with broad-spectrum antifungals such as Amphotericin B. We present a case of a premature infant born at 25 weeks of gestation who developed vesicobullous lesions all over the body on day 5 of life. Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain.

Medical renal disease in tumor nephrectomies: The silent killer.

In tumor nephrectomy specimens, the evaluation of the normal renal parenchyma is often overlooked. A patient with both end-stage renal diseases (ESRDs) with a renal cell carcinoma is more likely to die of the ESRD rather than cancer. At the time of nephrectomy, a pathologist has a large amount of tissue available to him to comment upon the presence of disease in the nonneoplastic kidney. Hence, this study was undertaken with the idea of characterizing disease in the nonneoplastic kidney at the time of tumor nephrectomy. A two-year retrospective study was carried out on all tumor nephrectomies and partial nephrectomies. Glomerular, tubulointerstitial, and vascular compartments were evaluated for abnormalities. Twenty-four cases were included in the study. A total of 17 cases showed abnormalities in the nonneoplastic renal parenchyma. In the glomeruli, two cases showed IgA nephropathy, one case showed segmental sclerosis, and one case showed the presence of cellular crescents. A single case showed diabetic glomerulosclerosis. Interstitial fibrosis and tubular atrophy were noted in seven cases. Fifteen cases showed intimal sclerosis and medial hypertrophy and six cases showed nodular hyalinosis. Tumor nephrectomy specimens may very often show the presence of various nonneoplastic diseases. Hypertensive and diabetic renal disease are the major contributors, although primary glomerular diseases may also be present. At the time of the evaluation of a renal tumor on nephrectomy specimen, the status of the nonneoplastic kidney may become as an important predictor of clinical outcome as the tumor itself.

Primary Cutaneous B-cell Lymphomas: Case Report of Two Cases.

Primary cutaneous lymphomas are a unique, heterogeneous group of lymphoproliferative disorders which have a primary cutaneous manifestation in the absence of systemic involvement of lymph nodes, bone marrow, or visceral organs at the time of diagnosis. Among the primary cutaneous lymphomas, B-cell lymphoma is much less common and accounts for 20%-25% of cases. Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) are aggressive neoplasms with poor prognosis. Early and accurate diagnosis is required as these patients respond well to systemic anthracycline-based chemotherapy (R-CHOP). In this article, we report two cases of PCDLBCL, other which presented with rapidly enlarging skin nodules and were diagnosed based on clinical features, histomorphology, and characteristic immunohistochemical expression. Both the patients were treated with systemic chemotherapy and responded well. During the 6 months' follow-up period, the lesions regressed. The patients are symptom free with no evidence of disease relapse or dissemination to extracutaneous sites.

Sclerosing Mediastinitis Presenting as Complete Heart Block.

Sclerosing Mediastinitis (SM) is a rare condition which is characterized by the presence of dense fibrosis which infiltrates and encroaches upon various structures in the mediastinal cavity. Depending on the extent and the predominant organ of involvement, the patient presents with symptomatology of dysphagia, superior vena cava compression syndrome or dyspnoea. However, the involvement of the heart is rarely seen. Aetiologies of SM are several, with infections being the most common. We discuss a case of SM involving the oesophagus, descending aorta, hilum of lungs and the heart secondary to mucormycosis in an immunocompetent male.

Analysis of epithelial-cadherin and human epidermal growth factor receptor 2/ expression in gastric carcinoma using immunohistochemistry.

CONTEXT: Gastric adenocarcinoma (GAC) is a common malignancy with high mortality-rate. Analysis of molecular markers could form a foundation for the future use of targeted therapies to reduce morbidity and mortality. AIMS: To find the prevalence and relation of epithelial cadherin (E-cadherin) and human epidermal growth factor receptor 2 (HER-2/neu) protein expression with histological type and grade of GAC using immunohistochemistry (IHC). MATERIALS AND METHODS: A total of 100 cases of GAC diagnosed over a 2 year period were studied. Expression of E-cadherin and HER-2/neu was analyzed by IHC in relation to the histological type and grade. RESULTS: Of the 100 cases of GAC studied, 11 revealed a loss of E-cadherin and over-expression of HER-2/neu was seen in 17 cases. Loss of E-cadherin was seen in 50% of signet ring-cell carcinomas but only in 8% of tubular and none of papillary and mucin-secreting GAC (P = 0.003). Of all the cases of tubular GAC with loss of E-cadherin expression, majority (71.4%) were Grade III (P = 0.04). Of all the tubular GAC cases with an over-expression of HER-2/neu, 20% and 67% were Grade I and II GAC respectively while only 13% were Grade III (P < 0.001). CONCLUSIONS: Although poorly-differentiated tumors show loss of E-cadherin, better-differentiated tumors over-express HER-2/neu protein. Signet ring-cell carcinoma is more likely to exhibit a loss of E-cadherin protein. Targeted therapy toward HER-2/neu in GAC should be considered. Novel therapy to block E-cadherin down-regulation is justified.

Burkittts lymphoma revisited: series of three cases with varied clinical presentation.

Burkitt's lymphoma is a form of non-Hodgkin's B-cell lymphoma with more than one identifiable variant. This tumour was first noted in Africans. The sporadic form most commonly presents with abdominal lymph node involvement. This tumour predominently affects children and is probably the fastest growing tumours in humans, with exuberant proliferation. We here in report on three patients from our experience both adult and children who presented with varied clinical features.

Emerging organisms in a tertiary healthcare set up.

BACKGROUND: One-tenth of all infectious diseases are attributable to emerging organisms. As emerging organisms sporadically affect a relatively small percentage of population they are not studied at large. This study was aimed at studying the characteristics of emerging organisms encountered from various clinical samples in an apex tertiary care multispeciality teaching and research hospital. METHODS: 16,918 positive isolates obtained from 66,323 culture samples processed in the clinical microbiology lab of an apex multispeciality hospital during 2011-2012 were included after a pilot study. Both manual and automated systems were used for identification and antimicrobial susceptibility. The frequency of isolation, sources, referring centers, resistance and susceptibility profiles, phenotypic characteristics and number of reports in PubMed were studied. RESULTS: Out of 16,918 isolates, 13,498 (79.78%) were Gram negative bacteria, 3254 (19.23%) were Gram positive bacteria and 166 (0.98%) were yeasts. A total of 483 (2.85%, 95% CI 2.6%-3.1%) emerging organisms including 116 (0.69%, 95% CI 0.57%-0.81%) emerging species were identified comprising 54 genera. CONCLUSION: Emerging organisms are likely to evade routine identification or be disregarded as non-contributory. Astute efforts directed at identification of emerging isolates, decisions by clinical microbiologists and treating physicians and containment of infection are required.

Gastric teratoma-unusual cause of neonatal obstructive jaundice: a case report.

The gastric teratoma is a very rare tumour that usually presents as an abdominal mass, gastrointestinal bleeding with/without features of gastric outlet obstruction. We report a rare case of immature gastric teratoma in a two months old female child who presented with abdominal lump and jaundice. The presentation was a diagnostic challenge and a dilemma, added by the fine needle aspiration cytology (FNAC) suggestive of small round cell tumor, favouring diagnosis of Wilms tumor over Neuroblastoma. Intra-operatively the tumor was found compressing upon the common bile duct (CBD). Final histopathological examination (HPE) revealed immature gastric teratoma Grade III. We wish to highlight this unusual presentation of gastric teratoma manifesting with obstructive jaundice and fallacy of FNAC in the diagnosis of teratomas.

Unusual autopsy finding in a case of metastatic teratocarcinoma.

An unusual autopsy finding was seen in a young case of metastatic teratocarcinoma of the right testis. The patient presented with features of myocardial ischemia and died of sudden cardiac arrest. At autopsy, the lungs were studded with variably sized metastatic nodules composed of glistening hyaline cartilage. Examination of the coronary arteries revealed complete occlusion of the left anterior descending and left circumflex artery lumina by tumor emboli composed of glistening white chondromyxoid material. Histopathology confirmed the presence of mature hyaline cartilage and chondromyxoid material in tumor emboli. The individual died due to severe coronary insufficiency and sudden cardiac arrest secondary to complete luminal occlusion of the left anterior descending and left circumflex artery lumina by tumor emboli composed of hyaline cartilage.