Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India.

Manas Kumar BeheraBackground and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61-3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan-Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression ( p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

Early detection of cutaneous complications of insulin therapy in type 1 and type 2 diabetes mellitus.

BACKGROUND: Subcutaneous insulin therapy is associated with important injection site complications, which can influence insulin pharmacokinetics resulting in glycemic fluctuations above and below target levels for blood glucose. OBJECTIVE: Our objective was to assess the prevalence and risk factors of cutaneous complications including insulin derived amyloidosis in insulin-injecting diabetes patients and to study the role of ultrasonography (in comparison to gel-assisted palpation) in early diagnosis of lipohypertrophy (LH). METHODS: This was a cross-sectional study conducted at a tertiary care center in India, wherein 500 patients injecting insulin for ≥2 years were randomly enrolled and evaluated for the presence of cutaneous complications of insulin therapy through clinical examination, ultrasonography and punch biopsy of skin. RESULTS: Clinical examination detected LH in 44.6% of patients. Ultrasonography diagnosed additional 13.4% of patients with LH which were missed on clinical examination. Incorrect rotation of sites (P < 0.001) and insulin syringe reusage for more than five times (P < 0.001) significantly increased the risk of LH. Skin biopsy was performed in 100 cases, out of which two patients showed apple green birefringence and its association with insulin was confirmed by positive staining with anti insulin antibody in these two patients. CONCLUSION: Improper rotation of sites and reuse of needles were the leading causes of LH in Indian diabetic patients. Ultrasonography is more objective and reliable method of detecting LH. Insulin-derived amyloidosis may be a more common complication of insulin therapy than previously thought.

Epithelial-myoepithelial carcinoma at the base of the tongue presented with metastatic disease in the absence of myoepithelial anaplasia.

Epithelial-myoepithelial carcinoma (EMC) is a biphasic low-grade malignant tumor that shows ductal structures lined by the ductal cells with surrounding myoepithelial cells. EMC is most commonly reported in the parotid gland followed by other major and minor salivary glands. EMC of the tongue is an extremely uncommon tumor, with only five previously published case reports. We herein report the sixth case of EMC of the tongue. A 40-year-old female who had throat pain, dysphagia, and right earache for 3 years showed a 4 cm × 4 cm nodular tumor at the base of her tongue. Histopathological and immunohistochemical features were diagnostic of EMC with cervical lymph node metastasis. The metastatic behavior of EMC of the tongue in the absence of myoepithelial anaplasia or high-grade histological features is unusual and reported in this case report for the first time.

Distribution of various histopathological types of ovarian tumors: A study of 212 cases from a tertiary care center of Eastern Uttar Pradesh.

BACKGROUND: Ovarian tumors are one of the leading cancers in females with variable pathological types. This study describes the distribution, clinical and pathological details of various histopathological types of ovarian tumors in a tertiary care hospital in North India. MATERIALS AND METHODS: A retrospective data of 3 years were collected for ovarian tumors submitted to the pathology department of a tertiary care hospital. Data were classified according to the latest World Health Organization (WHO) Classification into epithelial tumors, germ cell tumors, sex cord-stromal tumors, and others. RESULTS: A total of 212 cases of ovarian tumors were studied, 186 were unilateral and 26 were bilateral. Resection specimen, part of specimen, and block review formed 80.2%, 15.1%, 4.7%, respectively. Epithelial tumors formed the majority in 71.7% of cases followed by germ cell tumors (22.2%), sex cord-stromal tumors (3.8%) and others (2.3%). Maximum number of cases in the respective groups occurred in the age groups 31-40, 21-30, 51-60, and 41-50 years, respectively. Overall, benign tumors were 63.7%, malignant tumors were 31.1%, and borderline were 5.2%. The most common histopathological type of benign and malignant tumor was benign serous cystadenoma (18.8%) and serous carcinoma (9.9%), respectively. CONCLUSION: In the present study, ovarian tumors were classified according to the WHO classification, epithelial and germ cell tumors were the major types of ovarian tumors. Benign epithelial tumor formed the majority with 46.2% cases. Serous cystadenoma and mature cystic teratoma were the predominant type of epithelial and germ cell tumors, respectively.

Pharmacological application of barium containing bioactive glass in gastro-duodenal ulcers.

Peptic ulcer is prevalent in about 4% of the world population and nearly 10% of people have been affected by peptic ulcer at some point in their life. Therefore, there is a need for newer efficient and safe anti-ulcer agents. In the present strategy, we have prepared a novel bioactive glass containing 1.3 mol% of barium oxide (BaBG) and evaluated its antiulcer potential in gastroduodenal ulcer models. Prophylactic effect of BaBG pretreatment was evaluated for 5 days in ethanol, aspirin and pyloric ligation-induced gastric ulcer and cysteamine-induced duodenal ulcer models. Repeated treatment of 10 days of BaBG was evaluated in the healing ulcer model of acetic acid. BaBG significantly reduced the ulcerative damage against all the five tested ulcer models. Scanning electron microscope (SEM) images have shown that BaBG forms a physical protective barrier over the gastro-duodenal epithelium cell. In the pyloric-ligation, ethanol and aspirin models, BaBG showed significantly increased in gastric pH, indicating antacid like activity. BaBG treatment significantly increased cell proliferation in the pyloric model. Thus, BaBG mediates antiulcer action by forming a protective physical barrier against harsh luminal factors, acid neutralization and cell proliferation.

Indole-3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model.

Stroke is one of the most common causes of death worldwide and also responsible for permanent disability. Ischemic stroke has been found to affect 80% of stroke patients. Recombinant tissue plasminogen activator (rtPA) is the widely used drug for the ischemic stroke with narrow therapeutic window. Indole-3-carbinol (I3C) is a natural compound obtained from brassica species having antithrombotic activity. Middle cerebral artery occlusion (MCAO) model was used followed by reperfusion after 2 h of ischemia for the evaluation of the I3C against ischemic stroke. After reperfusion, I3C (12.5, 25, and 50 mg/kg) was given by oral route once daily and continued up to the 14th day. Behavioral studies including postural reflex, forelimb placing, and cylinder tests showed I3C attenuated the MCAO-induced increase in average score and asymmetry score efficiently. Mean cerebral blood flow (CBF) was improved by treatment with I3C (12.5 mg/kg) by 60% of baseline at 6 h. I3C inhibited ADP-induced platelet aggregation and reduced ischemic volume significantly. It also inhibited in vitro the ADP-induced platelet aggregation in healthy human volunteers. I3C improves behavioral scores and mean CBF after focal cerebral ischemia in rats. Furthermore, I3C showed prophylactic anti-thrombotic activity against carrageenan induced tail thrombosis. Therefore, preclinical evidence points to I3C as a potential candidate for use in cerebral ischemic stroke.

Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 (HER2) and p53 in Gastric Adenocarcinoma: A Pilot Study from Northern India.

INTRODUCTION: After the recent approval of Trastuzumab (anti-HER2 antibody) for the treatment of HER2 overexpressed Gastric Adenocarcinoma (GA), importance of HER2 testing is increasingly recognized. However, there is paucity of studies for HER2 overexpression in the Indian patients of GA. Similarly, study of p53 expression in the Indian patients of GA is infrequent. AIM: To study immunohistochemical expression of HER2 and p53 in GA biopsy samples. MATERIALS AND METHODS: This was a cross-sectional observational study. The expression of HER2 and p53 by immunohistochemistry were analyzed in 50 cases of GA. The HER2 expression was scored as negative (0 and 1+), equivocal (2+), and overexpression (3+). The p53 expression was quantified as negative (0-9% tumour cells) and positive (≥10% tumour cells). The intensity of p53 expression was assessed as strong and weak. RESULTS: Mean age of the patients was 56.8±14.8 years. Male:female ratio was 2:1. Histological types of adenocarcinoma were intestinal (68%), diffuse (28%), and indeterminate (4%). HER2 overexpression and equivocal results were present in 10% cases, each. Overall, a positive expression of p53 was seen in 72% (strong and weak intensities: 66.7% and 33.3% cases, respectively). CONCLUSION: As compared to HER2 overexpression, a higher incidence of p53 expression was seen (10% vs.72%) in GA.

Invasive Papillary Carcinoma of the Male Breast Misdiagnosed as Fibroadenoma on FNAB.

Male breast cancers constitute less than 1% of all the breast cancers. Papillary carcinoma is a very rare tumour of the male breast. Due to rarity, Fine Needle Aspiration Biopsy (FNAB) findings of papillary carcinoma in male breast are seldom reported. A 55-year-old male presented with a lump in the left breast of two years' duration. FNAB was reported as fibroadenoma. Histopathological examination of the excised breast lump revealed invasive papillary carcinoma. Immunohistochemistry showed expression of pancytokeratin, oestrogen receptor, and progesterone receptor. Negative immunostaining was seen for HER2, p53, 34ßE12, and CD34. Ki-67 proliferative index was 5%. We have discussed cytological findings of invasive papillary carcinoma and its differential diagnoses. Cytopathologists must be aware of cytologic findings of invasive papillary carcinoma of the male breast.

Performance of nested multiplex PCR assay targeting MTP40 and IS6110 gene sequences for the diagnosis of tubercular lymphadenitis.

The conventional methods for diagnosis of tubercular lymphadenitis (TBLN) such as - fine needle aspiration cytology, Ziehl-Neelsen staining and culture have limitations of low sensitivity and/or specificity. So, it becomes essential to develop a rapid, sensitive, and specific method for an early diagnosis of TBLN. Therefore, the present study was conducted to evaluate nested multiplex polymerase chain reaction (nMPCR) targeting MTP40 and IS6110 gene sequences of Mycobacterium tuberculosis and Mycobacterium tuberculosis complex, respectively in 48 successive patients of TBLN and 20 random patients with non-tubercular lymph node lesions. Out of the 48 cases of TBLN, 14 (29.2%) were found to be positive by Ziehl-Neelsen staining, 15 (31.2%) were positive by culture and 43 (89.6%) cases were positive after first round of PCR while 48 (100%) cases were positive by nMPCR assay. The sensitivity and specificity of nMPCR was found to be 100% for the diagnosis of TBLN. The results thus obtained indicate that nMPCR assay is a highly sensitive and specific tool for the diagnosis of TBLN.

Diagnostic Utility of PAX5 in Hodgkin and Non-Hodgkin Lymphoma: A Study from Northern India.

INTRODUCTION: PAX5 is an immunomarker of B-cell origin and useful in the diagnosis of lymphoma. There is hardly any study on PAX5 expression in Indian patients with lymphoma. AIM: To evaluate the diagnostic utility of PAX5 as an adjunct immunohistochemical marker in the diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL). MATERIALS AND METHODS: Immunohistochemistry was performed against CD20, CD3, CD15, CD30, and PAX5 on formalin fixed paraffin embedded tissue of 71 cases of lymphoma and CD20, CD3 and PAX5 in control samples of reactive lymph nodes. Frequency, mean values, and percentage were calculated. Fisher's-exact test and test for analysis of variance were applied. RESULT: For 24 cases of HL and 47 cases of NHL, the mean age of patients was 17.6±14.8 years and 44.1±21.6 years, respectively. The male: female ratio for both HL and NHL were 1.7:1. Among NHL cases, the numbers of B-cell and T-cell types were 39/47 (83%) and 8/47 (17%), respectively. In comparison to control samples, PAX5+ expression was seen in 23/24 (95.8%) cases of HL (p=1.000) and 32/39 (82%) cases of B-NHL (p=0.0834). All the cases of T-NHL showed negative expression of PAX5 (p<0.0001). Analysis of variance between NHL, HL and control samples was statistically significant (p<0.0001). CONCLUSION: PAX5 staining between control samples and cases of classical HL and B-NHL was statistically not significant, whereas, statistically significant difference was observed with T-NHL. Thus, PAX5 may be used as an adjunct marker in the diagnosis of classical HL and B-NHL.

PCR and Genotyping for HPV in Cervical Cancer Patients.

AIMS: To devise nested multiplex polymerase chain reaction (NMPCR) protocol for detection of mucosal human papilloma viruses (HPVs) and typing of HPV-16 and -18 in formalin-fixed, paraffin-embedded (FFPE) tissues of carcinoma cervix (CaCx). SETTINGS AND DESIGN: Cross-sectional observational study. MATERIALS AND METHODS: NMPCR was done for simultaneous detection of HPV, targeting 134 bp L1 capsid gene employing GP+/mGP+ primers and typing of genotypes-16 and -18, targeting E6/E7 gene from 34 FFPE tissue blocks of CaCx and cervical intraepithelial neoplasia (CIN). Detection of 142 bp consensus sequence of L1 capsid gene was performed by nested PCR employing MY/GP+ primers. Sequencing of selected PCR amplicons of the later protocol obtained from control cell line DNA and 5 select samples were done for validation of the NMPCR protocol. STATISTICAL ANALYSIS USED: Calculation of percentage from the Microsoft Excel Software. RESULTS: Of 26 FFPE samples of CaCx, 17 (65.3%) samples were found positive for HPV by NMPCR. Amplicons of 142 bp L1 capsid gene employing MY/GP+ primers were observed in 11 (42.3%) samples of CaCx. Nearly 25% samples of CIN were positive for HPV. On sequence analysis, it was observed that the sample typed as HPV-16 by NMPCR was found to be the same on sequencing of amplicons obtained after MY/GP+ nested PCR. CONCLUSIONS: This study indicates the usefulness of our NMPCR protocol for detection of mucosal HPVs and typing of HPV-16 and -18 from FFPE tissue samples of CaCx. The NMPCR protocol may be used to detect HPV and type common genotypes-16 and -18 in fresh tissue of cervical biopsy or scrape samples for screening of CaCx.

Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery.

The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). d-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC50 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P<0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™.

Capillary Hemangioma of the Fallopian Tube.

Neoplastic lesions of the fallopian tube are rarely seen by surgical pathologists. Haemangioma of the fallopian tube is an extremely rare benign neoplasm. A 30-year-old lady with polymenorrhea and dysmenorrhea underwent hysterectomy and bilateral salpingo-oophorectomy. Her left fallopian tube showed a 2mm sized solid nodule in the wall. Histopathological examination revealed a well-defined vascular lesion in the left fallopian tube, consistent with capillary haemangioma. The vascular endothelium was highlighted by CD34 immunostaining. Our literature review has identified 10 cases of cavernous haemangioma of the fallopian tube. To the best of our knowledge, we report the first ever case of capillary haemangioma of the fallopian tube. This is also the smallest detected haemangioma in the fallopian tube.

Non-Functional Paraganglioma of the Urinary Bladder Treated by Transurethral Resection: Report of Two Cases.

Paraganglioma of the urinary bladder is a rare tumour derived from chromaffin tissue of the sympathetic nervous system. Paraganglioma of the urinary bladder especially the non-functional type is often misdiagnosed as urothelial cancer. Two female patients aged 32 years and 45 years presented with painless haematuria without any symptoms of catecholamine excess. Radiological investigations revealed urinary bladder tumour. The tumour was removed by transurethral resection in both the patients. Histopathological diagnosis was paraganglioma, which was confirmed by immunohistochemistry. Complete resection of tumour by transurethral approach is curative in paraganglioma of the urinary bladder. We hereby, also discuss the salient features of nonfunctional paraganglioma of the urinary bladder.

Primary Eosinophilic Gastritis in a Child with Gastric Outlet Obstruction.

A 3-year-old girl presented with multiple episodes of vomiting, fever, and hematemesis for the past 2 months. Except for hemoglobin, her rests of the laboratory tests were unremarkable. Her barium X-ray showed absence of the duodenal bulb and the C-loop. Her endoscopy showed deformed stomach with multiple ulcers and diverticuli. The gastric outlet was not visualized. Distal gastrectomy with gastro-duodenal anastomosis was performed. Histopathological findings revealed transmural dense infiltrates of eosinophils, consistent with eosinophilic gastritis.

Renal-type clear cell carcinoma of the prostate: a diagnostic challenge.

A 72-year-old male presented with urinary symptoms. His serum prostate specific antigen level was 65.2 ng/ml. His radical prostatectomy specimen showed clear cell lesion reminiscent of the clear cell renal cell carcinoma along with acinar type of prostatic adenocarcinoma, Gleason score 4 + 4. The lesional clear cells were positive for pancytokeratin, epithelial membrane antigen, CD10, vimentin, and AMACR while negative for 34ßE12, CK7, prostate specific antigen, and PAX8. The final diagnosis was renal-type clear cell carcinoma of the prostate. A follow-up of 20 months did not show metastasis. We herein report fifth case of renal-type clear cell carcinoma of the prostate.

Cutaneous metastases of prostatic adenocarcinoma.

Prostatic adenocarcinoma (PA) is a common visceral malignancy of elderly men. Cutaneous metastasis of PA is rare. The incidence is <1%. A 55-year-old man presented with urinary symptoms and multiple cutaneous nodules around suprapubic region, inner aspect of both thighs and scrotum. Fine-needle aspiration cytology (FNAC) of cutaneous nodules was suggestive of metastatic adenocarcinoma. Skin and prostatic biopsies confirmed the cytological diagnosis. Serum level of prostate specific antigen was raised. Total prostatectomy revealed adenocarcinoma of Gleason's score 7 (3 + 4). Though rare, cutaneous metastases of PA must be known to cytopathologists. Meticulously performed FNAC in such cases may help in early diagnosis.

Langerhans cell histiocytosis diagnosed by FNAC of lymph nodes.

Langerhans cell histiocytosis (LCH) is a rare clonal disorder of unknown etiology and characterized by the proliferation of dendritic cells. LCH most commonly involves the bone followed by the skin and the lymph nodes. Recently, only a few cases of LCH with predominant lymph node involvement have been diagnosed by fine-needle aspiration cytology (FNAC). A 2-year-old boy presented with generalized lymphadenopathy, fever, and cough. The patient had hepatosplenomegaly, anemia, and lytic lesions in the skull. FNAC from the largest submandibular lymph node showed features of LCH. The large cells of LCH showed positive immunostaining for S-100 protein on FNAC smears. Later, lymph node biopsy and immunohistochemistry against S-100 protein and CD1a confirmed the diagnosis of LCH. The patient was treated with chemotherapy and he is under regular follow-up. This case report highlights the importance of FNAC as a rapid and accurate investigation in the diagnosis of lymph node predominant LCH.