Background: Urothelial carcinoma is common urinary malignancy responsible for a significant proportion of cancer morbidity and mortality. We carried out the present study to demonstrate the clinicohistopathological features and to correlate the p53 and Ki-67 immunoexpression with grade and stage of bladder carcinomas. Materials and Methods: We investigated 110 cases of bladder tumor. Grading and staging were done according to the WHO-2004 and American Joint Committee on Cancer-TNM staging recommendations. Immunohistochemical staining for p53 and Ki-67 was performed in all the cases, categorized as high and low expression taking 20% positivity as cutoff value. Statistical analysis was done using McNemar's Chi-square test and Fisher's exact test. Results: There were 61 cases of high grade and 49 cases of low grade exhibiting urothelial carcinoma as the most common variant (97.3%). Muscle invasive carcinomas (pT2) noted in 29 cases whereas 23 and 58 cases revealed stage pTa and pT1, respectively. Evaluation of p53 and Ki-67 immunoexpression showed a significant association with histological grade and stage individually and also in combination (P

Role of p53 and Ki-67 immunomarkers in carcinoma of urinary bladder.

The morphological spectrum of gallbladder carcinoma is broad and variable. Most of these tumors are tubular adenocarcinomas. There are some tumors with unusual morphology that may be difficult to classify due to their rarity. One of such tumors is the signet-ring cell carcinoma, which is a highly aggressive, mucin producing variant of gallbladder adenocarcinoma predominantly or exclusively composed of signet-ring cells. Histologically, these tumors are similar to their counterparts in other organs such as stomach, colon and breast, and should not be misinterpreted as metastatic carcinoma from one of these primary sites. The literature about this variant of carcinoma is sparse and little is known about it. We found only three cases of signet-ring cell carcinoma of the gallbladder previously reported. We present the case of an 86-year-old woman with signet-ring cell carcinoma of the gallbladder and discuss the potential diagnostic dilemmas

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A case of signet-ring cell carcinoma of the gallbladder: immunohistochemistry and differential diagnosis.

To the Editor: Primary signet-ring cell carcinoma of the cervix is extremely rare in the literature. We report a case of primary signet-ring cell carcinoma of the cervix, and discuss its cytology, immunohistochemical profile, HPV DNA results obtained with in situ hybridization (ISH) and polymerase chain reaction (PCR), and clinical course. The patient was a 31-year-old Japanese woman, gravida 4 para 2, without history of malignancy who visited a hospital for abnormal vaginal bleeding. Cytologic examination of cervical smears revealed agglomeration of atypical cells with intracellular mucinous vacuoles. Clusters of cells with a signet-ring appearance were observed in the mucus (Fig. 1a). It was categorized as atypical glandular cells. A 15-mm tumor was observed on the dorsal wall of the uterine cervix with magnetic resonance imaging; therefore, conization was performed. The histological diagnosis was signet-ring cell carcinoma. The tumor marker levels (carbohydrate antigen [CA] 125, 18.9 U/mL; CA 19-9, 12.2 U/mL; squamous cell carcinoma-related antigen, 0.7 ng/mL; carcinoembryonic antigen [CEA], 2.2 ng/mL) were not elevated. No other lesion was identified via a gastrointestinal endoscopic examination. An abnormal accumulation of fluorodeoxyglucose was observed only at the uterine cervix with positron emission tomography-computed tomography. Because no other tumor was identified, it was diagnosed with cervical cancer (International Federation of Gynecologic Oncologists [FIGO] stage IB1). A radical hysterectomy with pelvic lymphadenectomy and bilateral salpingooophorectomy was performed. No macroscopic lesions were identified during the radical hysterectomy except those in the conization scar. Microscopically, signet-ring cells infiltrated the superficial to the muscular layers of the cervix, and extended to less than one-third from the bottom of the vaginal wall, but not to the pelvic wall or parametrium. The tumor invaded the deeper part of the cervical wall (invasion depth, 20 mm). Total tumor size was 60 × 30 × 20 mm. There was lymphatic involvement (1/29, external iliac nodes). No histological type other than proliferating signet-ring cells was observed (Fig. 1b). Signet-ring cells were stained blue with alcian blue stain and periodic acid-Schiff reaction (Fig. 1c). Immunohistologically, the signet-ring cells tested positive for mucin 2 (MUC2), CDX2, CEA, and cytokeratin 7 (CK7), and negative for MUC1, MUC5AC, MUC6, p53, CK20, thyroid transcription factor 1 (TTF-1), gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, estrogen receptor (ER), progesterone receptor (PgR), chromogranin A, p16, and HIK1083. ISH showed the presence of HPV DNA (Human Papillomavirus Type 16/18 Biotinylated DNA probe [Y1412]; Dako, Japan) in the nuclei of Signet-ring cells (Fig. 1d). The nonneoplastic cervical glandular epithelium tested positive for HPV. DNA samples from the tumor lesions were selectively captured from 10-μm dewaxed sections with a laser capture microdissection (LCM) system (LM200; Olympus Co. Ltd, Tokyo, Japan). DNA isolation from LCM specimens was performed with a PicoPure DNA Extraction kit (Arcturus Engineering, Mountain View, CA, USA) according to the manufacturer’s protocol. PCR was performed according to the manufacturer’s protocol with HPV16 (E6 forward, 5′-CTGCGACGTGAGGTATATGACTTT-3′; E6 reverse, 5′-ACATACAGCATATGGATTCCCATCT-3′) and HPV18 (E6 forward, 5′-AAACCGTTGAATCCAGCAGAA-3′; E6 reverse, 5′-GTCGTTCCTGTCGTGCTCG-3′). DNA of our sample was HPV18-positive on agarose gel electrophoresis. The histological diagnosis was primary signet-ring cell carcinoma of the cervix; the pathological stage was FIGO stage IIA (TNM category, pathological T2aN1M0). Postoperative chemotherapy consisting of six courses of paclitaxel and carboplatin was administered. The patient is currently alive with no evidence of disease 41 months after the surgery. Sixteen cases of primary cervical carcinoma containing signet-ring cells were reported in the English literature (Table 1). In most cases of previous reports, the signet-ring cell components is included in a part of histological types. The occurrence of the pure form of primary signet-ring cell carcinoma, a subtype of mucinous adenocarcinoma of the cervix, is extremely rare. Signet-ring cell carcinoma of the cervix commonly represents a metastasis, usually from the stomach but less frequently from the colon, breast, lungs, appendix, gallbladder, bladder, or ovary. Therefore, it is necessary to combine clinical, imaging, and endoscopic findings to identify other primary sites. Immunohistochemical and molecular studies have often provided critical information for the origin of a tumor. Six previous cases were tested for immunohistochemical expression of ER and PgR; only one case was positive for ER and PgR. Three cases reported positive reaction for CK7 as well as negative reaction for CK20, TTF-1, GCDFP-15, mammaglobin, vimentin, and MUC5AC. The previous two cases were negative for CDX2; however, our case was positive. Negative CDX2 expression is not sufficient to reject the diagnosis of primary cervical cancer. Pathology International 2015; 65: 393–395 doi:10.1111/pin.12275 bs_bs_banner

Diagnosis of primary pure signet-ring cell carcinoma of the cervix.

AIM The conjunctival nevus affecting children and adolescents is a rare condition and the literature showed only few reports on this issue. The aim of this article is to determine the histopathological features for the correct diagnosis of an inflammatory juvenile compound nevus of the conjunctiva (IJCNC) in order to make the difference between this tumor and other lesions, like conjunctival melanoma or lymphoma, very similar from a gross point of view. This article is a clinical pathological study of two cases of IJCNC with particular histopathological characteristics, who were admitted at the 2nd Ophthalmology Clinic, "Prof. Dr. Nicolae Oblu" Emergency Clinical Hospital, Iasi, Romania, over a period of five years (from July 1, 2012 to June 30, 2017). Both patients were adolescents, a boy (13-year-old) and a girl (12-year-old). Both lesions were bulbar juxtalimbal located and grew in size over one year. Seen at slit-lamp biomicroscopy, the first one presented as a non-pigmented lesion, while the second was a pigmented nevus, but their dimensions did not exceed 10 mm in diameter. From a histopathological point of view, both of them showed a nested junctional growth pattern, along with intra- and subepithelial location, of the nevomelanocytes. Tumoral cells demonstrated different degrees of atypical cytology, but in the second case, it was more obvious. Microscopic examination also revealed epithelial cystic inclusions, and prominent inflammation in the stroma of these two nevi. One of the cases presented heavy inflammation that took the form of lymphoid follicles and sheets of eosinophils, but the other showed only diffuse inflammation with lymphocytes plasma cells, and eosinophils within its stroma. The immunohistochemical characterization (anti-melan A, anti-S100 protein and anti-cytokeratin AE1÷AE3 antibodies) of the tumoral cells helped to the diagnosis. CONCLUSIONS IJCNC represent a small group of nevi that develop in adolescents and have some particular histopathological features. The pathological diagnosis is difficult as the microscopic features are very similar to a conjunctival melanoma, but a detailed microscopic examination, immunohistochemical stainings and the young age of the patient could help in establishing the benign nature of these lesions.

Inflammatory juvenile compound conjunctival nevi. A clinicopathological study and literature review.

Background: Many women can be saved from carcinoma of cervix by detecting and treating its precancerous stage Pap smear is cheap and easily available in majority of institutes The objective of this study is to determine the frequency of abnormal Pap smear and role of Pap smear in detecting precancerous stage of cancer cervix in women Methods: This is retrospective descriptive study was conducted in gynaecology outpatient department of Isra University Hospital, Hyderabad, Sind from Nov 2006 to Oct 2009 All women who presented in OPD with gynaecological complaints were included in the study Pregnant women were excluded from the study Smear was collected with an Aryes spatula and relevant information was obtained from the patient’s record and recorded on pre-designed Performa Slides were then sent to pathology department Data were analysed through SPSS-15 and presented as frequency and percentage Results: Total 981 women underwent Pap smear screening Majority (633%) of the patients belonged to age group of 31–40 years One hundred and eighty (1834%) smears were normal and 792 (807%) were abnormal Among these abnormal smears, 739 (7533%) smears were inflammatory while 4 (040%) women had Ca in situ and 4 (040%) had squamous cell carcinoma Conclusion Pap smear is an important screening tool to detect precancerous stage of carcinoma of cervix It should be done periodically in all married and high risk women for early detection of a precancerous stage Keywords: Pap smear, inflammatory, cancer cervix, malignancy, gynaecological tumour, diagnosis

Pap smear, an important screening tool to detect precancerous stage of carcinoma of cervix.

Results: Out of 57 cases of bone marrow aspiration, erythroid hyperplasia was seen in 12 cases (21%). Megaloblastic anemia was seen in 7 cases (12.3%) and microcytic anemia was seen in 4 cases (7%). There were 6 cases (10.5%) of Idiopathic Thrombocypenic Purpura. Acute leukemia was diagnosed in 7 cases (12.3%) and among this acute myeloid leukemia (10.5%) was more common than acute lymphoid leukemia (1.8%). Myelodysplastic syndrome and multiple myeloma was seen in 3.5 % cases each. Aplastic anemia and kalaazar was seen in 5.3% and 1.8% cases respectively.

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Interpretation of bone marrow aspiration in hematological disorder

Carcinoma of the gall bladder is the most common biliary tract tumor with higher incidence in females and increasing age The risk is significantly higher in cholelithiasis Signet ring cell carcinoma is a rare form of mucinous adenocarcinoma and has a worse prognosis Early diagnosis is rare We report a case of signet ring cell carcinoma of the gall bladder in a 70 years old female patient The gross finding was yellowish white mass measuring 4 x 35 cm on cut surface of the gall bladder along with thickened wall Histopathological examination of the specimen shows the sheets of signet ring cells with lateral spread through the lamina propria and large amount of extracellular mucin There was metastasis in the retroperitoneum and mesenteric lymph node The tumor was stage IV (according to TNM staging) Patient died 20th post operative day Since very few cases have been reported, information regarding the behavior and prognosis of gall bladder carcinoma is limited However it has been seen that stage III and IV carcinoma usually have worse prognosis

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Signet ring cell carcinoma of the gallbladder: a case report.

Urothelial carcinoma is the most common tumor of the bladder and is a major cause of morbidity and mortality. Cystitis constitutes an important source of clinical signs and symptoms. In this study 31 cystoscopic biopsies subjected for histopathological examination were taken. The study was conducted in the department of Pathology of Nepal Medial College Teaching Hospital over a period of two years (October 2012 to September 2014). The mean age of the patient undergoing cystoscopic biopsy was 61.3 years, most of the patients being elderly male. 51.6% cases were clinically malignant. The most common histopathological diagnoses were cystitis (29%) and non invasive papillary urothelial carcinoma, low grade (29%). 58% are neoplastic lesions. 51.6% of the case was malignant lesions on histopathology. Among the malignant lesion of urinary bladder 93.7% were urothelial tumor and 6.3% were glandular neoplasm (adenocarcinoma, signet ring cell). There was no detrusor muscle in 33.3% cases of urothelial tumor to assess the muscle invasion. 26.7% cases of urothelial tumor shows muscle invasion. Histopathological study of cystoscopic biopsy helps in early detection of tumor and its management.

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Cystoscopic bladder biopsies: a histopathological study.

Background: Cervical cancer is a leading cause of mortality and morbidity among women worldwide and most common gynaecological cancer in developing countries. Papanicolaou smear is a simple and cost effective screening test for cervical cancer. The aim of this study is to evaluate and interpret the cervical pap smear cytology in a tertiary hospital. The interpretation and reporting of the pap smear is based on 2001Bethesda system. Materials and methods: This is a prospective study conducted in a tertiary hospital, Nepal Medical College over a period of two and a half years (January 2013 to June 2015). All cervical pap smears received in the department of Pathology in the study period were included. Results: A total of 4160 cervical pap smears were reported in the study period. Majority of the cases were Negative for Intraepithelial lesion or malignancy (87.9%). Bacterial vaginosis, atrophy and reactive cellular changes associated with inflammation were seen in 5.3%, 2.4% and 1.5% cases respectively.   Epithelial cell abnormalities (0.5%) include Atypical squamous cells of undetermined significance, Low grade squamous intraepithelial lesion and High grade intraepithelial lesion. 88% of Low grade squamous intraepithelial lesion was seen in reproductive age group (20-45 years). Conclusion: Cervical cancer is the most common gynaecological cancer in the developing countries. Pap smear is the simple and cost effective screening tool to detect pre invasive cervical epithelial lesions.

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Cervical pap smear- A prospective study in a tertiary hospital

Ophthalmic lesions include a wide spectrum of conditions ranging from benign lesions to precancerous lesions and malignant lesions. The diagnosis of these lesions is based on the clinical as well as histopathological features. This was a prospective study of ophthalmic lesions conducted in the department of pathology of Nepal Medial College teaching hospital over a period of one year (September 2012 - August 2013). In this study period, we received total 11 ophthalmic biopsies. Out of these, 54.5% cases were conjunctival lesions and 45.5% cases were eye lid lesions. The age range was from 8 years to 40 years with the mean age of 25.5 years. All the cases were benign lesions, papilloma being the most common clinical and histopathological diagnosis. Other lesions like inclusion cyst, dermoid cyst, seborrheic keratosis, pilomatrixoma, nevus and molluscum contagiosum are also included in our study.

Kbr Prasad

Papers

Interpretation of bone marrow aspiration in hematological disorder

Signet ring cell carcinoma of the gallbladder: a case report.

Cystoscopic bladder biopsies: a histopathological study.

Cervical pap smear- A prospective study in a tertiary hospital

A histopathological study of ophthalmic lesions