Role and significance of HER-2/neu as a biomarker in the premalignant and malignant lesions of uterine cervix.

Cancer of uterine cervix is the most common cancer among Indian females. Surgery is the main modality of treatment along with radiation and chemotherapy depending upon clinical stage of the tumor and surgical findings. However, patients with advanced or recurrent disease have a poor survival despite the use of cisplatin-based combination chemotherapy. Hence, there is an increasing need for developing novel therapeutic target that can replace or be added to the current therapy for these patients. The present study was conducted to evaluate the presence of Her-2/neu expression. Two hundred cervical specimens were included in this study. These comprised cases with diagnosis of cervical intraepithelial neoplasia, squamous cell carcinoma, adenocarcinoma. HER-2/neu immunostaining was performed by using BioGenex monoclonal mouse anti-human HER-2/neu Receptor IgG1 antibody. Higher expression of HER-2/neu was noted in malignant lesions as compared to premalignant lesions. Intensity of staining also correlated with grade of malignant tumor, clinical stage and lymph node metastasis. The over-expression of HER-2/neu oncoprotein is found to be associated with poor prognosis, metastatic potential and aggressive biological behaviour.

Clinicopathological study of role of CD34 expressions in the stroma of premalignant and malignant lesions of uterine cervix.

CD34 is a transmembrane glycoprotein that is thought to be involved in the modulation of cell adhesion and signal transduction. The connective tissue stroma of virtually all human organs contain large amounts of resident CD34+ fibrocytes, which are involved in multiple functions such as wound healing, secretion of cytokines and also participate in stromal remodeling. It has been seen in various studies that absence of CD34+ fibrocytes within the stroma is associated with invasive carcinomas. In our study, we also investigated the presence and distribution of CD34+ fibrocytes in cervical intraepithelial neoplasia, invasive cervical carcinoma and adjacent normal cervical stroma. It was seen that normal cervical stroma and the stroma adjacent to cervical intra epithelial lesions harbours a dense meshwork of CD34+ fibrocytes, whereas the stroma of invasive carcinoma was nearly devoid of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34+ fibrocytes. This can be used as a sensitive tool in detecting tiny foci of stromal invasion in early cancer.

Peripheral Neutrophil to Lymphocyte Ratio (NLR), a cogent clinical adjunct for Ki-67 in breast cancer.

BACKGROUND: Clinical utility of Ki-67 immunohistochemistry (IHC) in breast cancer (BC) is mainly limited to decide for the use of chemotherapy and estimate prognosis in patients with either Ki-67 index < 5% or > 30%; however, lacunae still exists pertaining to its analytical validity. Neutrophilia is common in cancer with accompanying lymphocytopenia. Neutrophil to lymphocyte ratio (NLR) captures the intricate balance between pro-tumor neutrophilia and anti-tumor lymphocyte immunity. This study aimed to correlate cellular proliferation in breast cancer with NLR. METHODS: An observational study was carried out including 73 cases of BC; pre-treatment NLR and Ki-67 grading were performed. NLR < 3 was considered low, while ≥ 3 was high. The Ki-67 expression was graded as low ≤ 5%, intermediate 6-29%, or high ≥ 30%. Various clinico-pathological variables were studied, and the association of categorical variables was analyzed using Pearson's chi-square test, and a p-value of < 0.05 was taken as significant. RESULTS: Ki-67 correlated significantly with modified Scarff-Bloom-Richardson (SBR) grade (p < 0.01), and tumor-node-metastasis (TNM) stage (p < 0.001). Correlation of NLR was not significant with SBR grade (p > 0.05) and molecular subtype (p > 0.05); however, NLR was found to be significantly correlated with TNM stage (p < 0.001) and Ki-67 (p < 0.001). CONCLUSION: NLR is fast emerging as a personalized theranostic marker in breast cancer. Instead of determining a generalized cut-off value, individual baseline NLR and its dynamics with disease progression will help manage patients better, obviating some of the drawbacks associated with Ki-67.

Rapid Cytological Diagnosis With Evaluation of Pre- and Post-Therapeutic Fungal Morphological Characteristics in Mucormycosis.

Background: Mucormycosis necessitates rapid diagnosis and treatment. Microscopy and culture have been considered the gold standard for diagnosis but both take time of 3 - 5 days. KOH mount is another method for fungal identification that takes 1 - 2 h, but it has its own limitations. This study evaluated crush smear as a means of rapid cytological diagnosis. Methods: Biopsy tissue (pre-treatment) from clinically suspicious mucormycosis patients (n = 52) was received in normal saline and crush/imprint smears were prepared; the remaining tissue was processed as routine biopsy specimen. After the rapid initial cytological identification, the patients were managed according to the standard clinical protocol. Random post-therapeutic biopsy samples of some of these patients (n = 19) were also obtained and again evaluated cytologically. Results: Crush smears showed sensitivity/specificity of 77.7%/75.0% with histopathology and 72.2%/62.5% with culture, respectively, while KOH mount had values of 71.4%/70.5% with histopathology and 79.3%/69.5% with culture, respectively. Degenerative fungal morphological characteristics and cellular inflammatory infiltrate (predominantly neutrophilic) in the vicinity of fungal hyphae were compared in pre- and post-treatment groups, and we found a statistically significant difference (P < 0.05) between them. Conclusion: Our preliminary results suggest that crush smear cytology is a simple, rapid, cost-effective and easily available method for diagnosing mucormycosis. Moreover, crush smears also demonstrated morphological alteration in hyphal structure and accompanying immune cell infiltration which may provide valuable insights into mechanism of therapy/host immune response against fungal pathogen.

A study on antioxidant and apoptotic effect of Azadirachta Indica (neem) in cases of cervical cancer.

PURPOSE: To study the anti-oxidant properties of neem (Azadirachta indica) in inducing apoptosis of cervical cancer cells and estimation of caspase activity and TNF-α and IFN-γ levels in monocytes of cervical cancer patients and controls. METHODS: Monocytes were cultured from blood samples of 65 study cases and 30 controls for the estimation of caspase 3, 8 and 9 with specific inhibitors and TNF-α and IFN-γ levels in culture supernatant of monocytes. Two cervical biopsies were taken from 18 cases of moderately differentiated SCC. One biopsy was formalin fixed for histopathology and the other for tissue culture was kept in RPMI-1640 medium to evaluate the apoptotic effect of neem extract on malignant cells. RESULTS: Neem-treated monocytes from cervical cancer patients showed high activity levels of caspase 3, 8, and 9. A decrease in TNF-α and an increase in IFN-γ levels was seen in culture supernatant of monocytes. Cyto- and histomorphology of neem-treated cervical cancer cells exhibited increased apoptosis. CONCLUSION: Neem is a potent inducer of apoptosis in biopsies of cervical cancer patients.

Scrotal calcinosis: idiopathic or dystrophic?

Scrotal calcinosis is a rare benign local process characterized by multiple, painless, hard scrotal nodules in the absence of any systemic metabolic disorder. Histological examination reveals extensive deposition of calcium in the dermis, which may be surrounded by histiocytes and an inflammatory giant cell reaction. Numerous theories have been propounded to explain the pathogenesis of this condition, but the principal debate revolves around whether the calcium is deposited at the site of previous epithelial cysts or the calcified nodules are purely idiopathic. This is the largest study of scrotal calcinosis to date with 100 cases, on which clinical, biochemical, radiological, cytopathological, and histopathological examinations were conducted. The histological picture shows a continuous spectrum of changes ranging from intact epithelial cysts (41.0%) - both normal and inflamed; through inflamed cysts containing calcific material in the lumen but with intact cyst wall (53.0%); calcified inflamed cysts with partial epithelial lining (11.0%); to 'naked' calcium deposits lying in the dermis (100%), sometimes compressing surrounding collagen fibres to form a pseudocyst (56.0%). The presence of normal values of calcium and phosphorus along with this spectrum of changes in histology both support the theory that these form by dystrophic calcification of epithelial cysts in a progression that involves inflammation, rupture, calcification and obliteration of the cyst wall.

Advanced presentation of gallbladder cancer: epidemioclinicopathological study to evaluate the risk factors and assess the outcome.

OBJECTIVE: To evaluate the risk factors and assess the short-term prognosis and independent prognostic factors of cases of gallbladder cancer. METHODS: A retrospective analysis of the data of 52 patients of gallbladder cancer was done. Clinical presentation, laboratory investigations, treatment given, operative findings and histopathological findings were reviewed. RESULTS: Forty-four patients were unresectable at presentation. A 2-year survival rate for early gallbladder cancer was 100% while it was only 29.2% in the advanced stage group. CONCLUSION: The overall 2-year survival rate was 39.58%. The TNM stage was the most important factor affecting the survival.

Microfilariae in thyroid aspiration smear--an unexpected finding.

Lymphatic filariasis is a major health problem in tropical countries including India. Despite its high incidence it is difficult to find microfilariae in blood and fine-needle aspirates due to the nocturnal periodicity of species endemic in India. Lymphatic filariasis can manifest as asymptomatic microfilaremia, hydrocele, lymphangitis, and lymphadenitis. The presence of microfilariae in thyroid aspirates is a rare finding. A case of microfilariae in a thyroid aspirate is being reported to emphasize the significance of careful screening of smears in endemic areas.

Evaluation of gelatin/resorcinol/aldehyde as a hemostatic agent and tissue adhesive: an experimental study in rat.

Use of gelatin/resorcinol/formaldehyde glue as a tissue adhesive and hemostatic agent was evaluated experimentally after modification of the aldehyde component. Gelatin/ resorcinol/aldehyde (GRA) glue was prepared by mixing gelatin and resorcinol and cross-linking with a blend of formaldehyde/glutaraldehyde. After wedge resection of the liver of 28 albino rats, bleeding was controlled, and the cut surfaces were joined with GRA. Liver biopsy was done at 7, 14, 21, and 28-day intervals. Hemostasis was excellent in 71.4%, satisfactory in 25.0%, and poor in 3.6%. Mean time for tissue adhesion was 2.6 minutes. No necrosis or bile leakage was seen. Visibility of site of repair decreased from 50.0% on day 7 to 14.3% on day 28. Residual glue was seen microscopically on day 28 in 43% cases. GRA is safe and good hemostatic, tissue adhesive, and sealant in rat liver.

Utility of Cytospin and Cell block Technology in Evaluation of Body Fluids and Urine Samples: A Comparative Study.

BACKGROUND: Cytologic examination of body fluids commonly involves the use of direct or sediment smears, cytocentrifuge preparations, membrane filter preparations, or cell block sections. Cytospin and cell block techniques are extremely useful in improving cell yield of thin serous effusions and urine samples, and ensure high diagnostic efficacy. MATERIALS AND METHODS: We studied cytospin preparations and cell block sections prepared from 180 samples of body fluids and urine samples to compare the relative efficiency of cell retrieval, preservation of cell morphology, ease of application of special stains, and diagnostic efficacy. Samples were collected and processed to prepare cytospin smears and cell block sections. RESULTS: We observed that overall, cell yield and preservation of individual cell morphology were better in cytospin preparations as compared to cell blocks, while preservation of architectural pattern was better in cell block sections. The number of suspicious cases also decreased on cell block sections, with increased detection of malignancy. It was difficult to prepare cell blocks from urine samples due to low cellularity. CONCLUSIONS: Cytospin technology is a quick, efficient, and cost-effective method of increasing cell yield in hypocellular samples, with better preservation of cell morphology. Cell blocks are better prepared from high cellularity fluids; however, tissue architecture is better studied, with improved rate of diagnosis and decrease in ambiguous results. Numerous sections can be prepared from a small amount of material. Special stains and immunochemical stains can be easily applied to cell blocks. It also provides a source of archival material.

Prostatic adenocarcinoma metastasizing to the parietal bones.

Prostate cancer metastasis to the axial skeleton occurs at high frequency in patients with advanced disease causing significant morbidity and mortality. Apart from bone, brain is also a common site of metastasis but the involvement of the parietal bones is extremely unusual. Parietal bone metastasis from prostatic adenocarcinoma was the initial presentation seen in our patient. This is the first case of its kind in the literature where the prostatic carcinoma had metastasized to the parietal bones of the skull without any symptomatology of prostatic involvement. The report is intended to alert the reader of this rare site of metastasis from the prostate.

Glomus tumor of lesser omentum--a case report.

A case of glomus tumor of lesser omentum occurring in a 24 years old male is being reported for its rarity.

Cerebriform nevus sebaceus: a rare entity.

We present a case of cerebriform nevus sebaceus in an 18-year-old boy. This form of nevus sebaceus is quite rare, in contrast to the relatively common linear variant.

Granulomatous Response with Breast Cancer: A Case Report.

Granulomatous response in association with breast cancer and within the cancer draining lymph nodes is an extremely rare phenomenon. Granulomatous inflammation is an immune response commonly seen against infectious agents and certain non-neoplastic conditions. The etiopathogenesis of granulomas associated with malignancies is not clear but it may be because of an immunologic reaction to tumour antigens. We hereby report a 50-yr-old postmenopausal female presented to Surgical Outpatient Department, Aligarh Muslim University, India, with complaints of lump and pain in her left breast for 6 months. We have also discussed about its etiopathogenesis, final diagnosis, treatment & patient outcome.

A Comparative Evaluation of Different Diagnostic Modalities in the Diagnosis of Typhoid Fever Using a Composite Reference Standard: A Tertiary Hospital Based Study in Central India.

INTRODUCTION: Enteric fever, caused by Salmonella spp. is a major cause of morbidity and mortality worldwide and endemic in many developing countries including India and other South-East Asian countries. Blood culture is regarded as the gold standard for diagnosis. Currently, the standard serological method is tube agglutination with moderate sensitivity and specificity. Dot blot assay detecting IgM and IgG antibodies to a specific 50kD Outer Membrane Protein (OMP) antigen of Salmonella spp. is a simple, reliable, affordable and rapid test which can help in the early diagnosis of typhoid fever. AIM: To systematically evaluate the different diagnostic modalities against a composite reference standard for the better diagnosis of typhoid fever in clinically suspected cases of typhoid fever. MATERIALS AND METHODS: This cross-sectional, prospective analytical study was carried out at a tertiary care hospital attached to Medical College in central India from November 2011 to June 2013. A total of 163 blood samples, collected aseptically from patients clinically diagnosed of enteric fever, were tested using various component tests like blood culture, Tube Widal and Dot Enzyme Immuno Assay (Dot EIA) for IgG and/or IgM. Composite Reference Standard (CRS) was created for defining the confirmed cases of typhoid fever using the component tests, wherein culture positive and in absence of culture positivity any two component test positive patients were taken as confirmed cases. All the component tests were evaluated against the CRS for sensitivity, specificity, PPV and NPV and their significance in relation to the duration of illness using statistical tests of significance. RESULTS: Blood culture was positive in 16 (9.81%) whereas, Tube Widal, IgM, IgG and IgM+IgG in combination were positive in 88(54%), 58(35.58%), 30 (18.40%) and 75 (46.01%) respectively. Using a two test criteria of CRS framed, a total of 104 patients were considered as confirmed cases. Though specificity of blood culture was 100%, the sensitivity was low with significant detection rate in 1st week of illness. Tube Widal showed a sensitivity of 65.38% and specificity of 89.83% with significant detection rate in 2nd week. Dot blot assay for IgM, IgG and Combined IgM and IgG showed a sensitivity of 71.15%, 65.28% and 51.72% respectively whereas, the specificity was 10.16%, 47.45% and 74.57% respectively with significant detection rate in 2nd and 3rd week of illness. CONCLUSION: It can be concluded that though blood culture is still the gold standard, Dot blot assay found to have high sensitivity and good specificity might be a practical alternative test for the rapid diagnosis of typhoid fever if interpreted with care particularly using a composite reference standard. Further, it is reliable, simple to perform and rapid; results being available in 1 hour when compared to 48 hours for blood culture and 18 hours for Tube Widal test.

Kikuchi-Fujimoto disease--a case report.

The etiology of cervical lymphadenopathy is multifactorial including infections and tumoral lesions. Histiocytic necrotising lymphadenitis or Kikuchi-Fujimoto's disease is a rare cause of cervical lymphadenopathy which does not have specific clinical signs. We report herewith a case of Kikuchi's disease (KD) diagnosed by histopathology.

A case of coexisting carcinoma and tuberculosis in one breast.

Coexistent carcinoma and tuberculosis in a breast is a rare entity. It poses problems right from the diagnosis and staging of carcinoma to treatment and patient compliance. Proper clinical examination and investigations should be performed in such cases as both carcinoma and tuberculosis are major diseases with no definite symptoms or signs to distinguish the two. Herein, we report the case of a 45-year-old female who presented with complaints of a lump and pain in left breast, weight loss and weakness for the past 4 months. Fine needle aspiration cytology from the breast lump showed clusters of malignant cells along with many loose clusters of epithelioid cells on a background showing caseous necrosis. A diagnosis of coexisting breast carcinoma and tuberculosis of the breast was made and antitubercular treatment was started. The patient was operated and histopathology confirmed the diagnosis.

A large proliferating trichilemmal cyst masquerading as squamous cell carcinoma.

Proliferating trichilemmal cyst (PTC), a rare benign tumor, is a fascinating follicular neoplasm. It occurs on head and neck region of elderly women and its histologic hallmark is trichilemmal keratinization. A 70-year-old female presented to skin outpatient department with complaints of a slowly growing mass on scalp for the past 2 years. On examination, the lesion was firm, mobile, painless, and measured 6 × 5 × 3 cm and was not fixed to the underlying bone. Laboratory investigations were unremarkable. Excisional biopsy was done. Histopathology revealed well-demarcated tumor with variably sized lobules of squamous epithelium undergoing an abrupt change into eosinophilic amorphous keratin without granular cell layer (trichilemmal keratinization). PTC should be differentiated from trichilemmal cyst as it has potential for malignant transformation. Thus, complete excision is recommended for all benign proliferating variants owing to their potential for locally aggressive behavior and malignant transformation.

Low Grade Appendiceal Mucinous Neoplasm with Pseudomyxoma Peritonei: An Enigma for Pathologist.

Malignant mucinous neoplasms of the appendix is an infrequently encountered entity. Extra-appendiceal spread of these tumor is one of the commonest etiology of pseudomyxoma peritonei, which demands a hightened vigilance in their early diagnosis. Although low-grade appendiceal mucinous neoplasms (LAMNs) largely stay confined to the appendix, but they can spread to the peritoneum as pseudomyxoma peritonei leading to an unpredictable outcome. Due to the rare occurrence of low-grade appendiceal neoplasm only tenuous and limited information is present in the medical literature. We report a case of LAMN with pseudomyxoma peritonei in a 45-year-old male, who presented with the complaints of abdominal distension associated with abdominal pain and constipation. Clinical examinations and computed tomography (CT) scan were suggestive of pseudomyxoma peritonei. Peroperative findings and histopathological examination rendered a conclusive diagnosis of low-grade appendiceal neoplasm. How to cite this article: Qadri S, Alam K, Alam F, Maheshwari V. Low Grade Appendiceal Muci-nous Neoplasm with Pseudomyxoma Peritonei: An Enigma for Pathologist. Euroasian J Hepato-Gastroenterol 2014;4(2):113-116.

Incidentally discovered giant mucocele of the appendix.

Mucocele of the appendix is a rare but well-recognized entity that can mimic several common clinical conditions or present as an incidental radiological or surgical finding at laparotomy. Mucoceles are characterized by distension of the lumen due to accumulation of mucoid substance. They can result from mucosal hyperplasia, mucinous cystadenoma, or mucinous cystadenocarcinoma. If untreated, they may rupture producing the potentially fatal entity Pseudomyxoma peritonei, which is difficult to treat both surgically or medically. Appendectomy is used for simple mucocele or for cystadenoma. Preoperative diagnosis of a mucocele is helpful at the time of surgical intervention with careful mobilization, particularly of large lesions reducing the possibility of rupture and complications. The authors report a case of a 65-year-old man presenting with peritonitis due to a pre-pyloric gastric perforation also having an incidental giant mucocele of the appendix.