Significance of epithelial cell clusters in pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterised by distension of the peritoneum by jelly-like ascites. Cytological evaluation of peritoneal fluid is often an initial diagnostic test for possible ovarian and/or appendiceal primary tumours. AIMS AND OBJECTIVES: The present work was conducted to study the usefulness of peritoneal fluid cytomorphology in the early diagnosis of PMP and to evaluate the significance of the presence of epithelial cell (EC) clusters and their prognostic implications. MATERIALS AND METHODS: We evaluated the detailed cytological features of 21 cases of PMP retrospectively. Both conventional and liquid-based cytology smears of peritoneal fluid were reviewed, cytological features were compared with histological findings and cases were classified into disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). RESULTS: In our study, the common causes of PMP were primary gastrointestinal malignancies (appendix and colorectal, 57.14%), followed by primary ovarian mucinous neoplasms (28.57%) and synchronous ovarian and appendicular tumours (14.28%). Thick mucinous material was present in all cases (100%). ECs were present in 18 of 21 (85.17%) patients, with mild nuclear atypia in the majority of cases. Histiocytes, mesothelial cells and fibroblast-like, spindle-shaped cells with entrapped mucin were also noted in the background. The cases of PMCA showed greater numbers of EC clusters in cytology smears and these patients had recurrent episodes of PMP. CONCLUSION: On cytomorphology, high-grade tumours were more cellular and frequently showed EC clusters with moderate to severe atypia, prominent nucleoli and mitosis, and were more prone to PMCA.

Solitary fibrous tumour: a diagnostic challenge for the cytopathologist.

BACKGROUND: Solitary fibrous tumour (SFT) is an uncommon spindle cell tumour that can occur in a variety of locations. Cytological features of this tumour have only rarely been reported in the literature. We describe the cytomorphological features of SFT with an emphasis on diagnostic pitfalls. METHODS: We retrieved nine cases of histopathologically proven SFT. Three cases had sampling error with inadequate smears and, therefore, six cases with adequate cellularity were analysed for cytological findings. The cytomorphological features and the differential diagnoses on fine needle aspiration cytology (FNAC) are discussed. RESULTS: No definitive cyto-diagnosis of any of these cases was possible because of the morphological overlap with various soft tissue tumours and other tumour types. There was one false-positive case, in which the possibility of sarcoma was suggested due to the presence of scattered atypical cells. Cytologically, the smears from the SFTs showed spindle to plump cells embedded in metachromatically staining dense ropy collagen material. The cells usually had oval to spindle shaped nuclei, bland chromatin and wavy elongated pale staining cytoplasm. CONCLUSION: A diagnosis of SFT on cytology smears is challenging. Careful attention given to certain cytological features in an appropriate clinicoradiological setting and application of immunochemistry, including CD34 and CD99 immunostaining on cytological samples, can help in the diagnosis of SFT in some cases. It is important to consider cytological overlaps of this tumour in order to avoid false-negative or false-positive results.

Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases.

OBJECTIVE: To assess the diagnostic value of fine needle aspiration cytology (FNAC) in ovarian lesions. METHODS: This was a retrospective study of ultrasound-guided (US) FNAC of 584 ovarian lesions from January 1998 to July 2010. The lesions were categorized into non-neoplastic lesions, neoplastic lesions and inadequate aspirates. The results were compared with the corresponding histopathology whenever available. RESULTS: Of the 584 lesions, 180 (30.8%) were reported as non-neoplastic (48 non-specific inflammation, 11 tuberculosis, 63 functional cysts and 58 endometriotic cysts), 249 (42.6%) as neoplastic (81 benign lesions/tumours and 168 malignant) and 155 (26.5%) as inadequate. Based on the subsequent histopathology, which was available in 121 (20.7%), the cases were divided into those that were concordant and discordant. Concordant cases comprised 92/121 (76%), including 28 non-neoplastic lesions (seven non-specific inflammation, nine functional cysts and 12 endometriotic cysts), 42 surface epithelial tumours (13 benign and 29 malignant), 10 germ cell tumours (five mature cystic teratomas and five mixed germ cell tumours), seven sex-cord stromal tumours (three granulosa cell tumours, one sclerosing stromal tumour, one strümal leutoma, one Sertoli Leydig cell tumour and one malignant Sertoli cell tumour) and five miscellaneous lesions (one plasma cell tumour, two leiomyosarcomas and two cases of necrosis). Discordant cases comprised 29/121 (24%) (21were inconclusive or inadequate on cytology), including four endometriotic cysts, 14 surface epithelial tumours (one cystadenofibroma, one borderline mucinous tumour and 12 carcinomas), five germ cell tumours (two immature teratomas and three mature cystic teratomas), two thecomas, one fibroma, one sclerosing stromal tumour, one fibrosarcoma and one myxoma. FNAC sensitivity for a diagnosis of malignancy was 85.7%, specificity 98.0%, positive predictive value 97.7%, negative predictive value 87.7% and accuracy 92.0%, if 21 inconclusive/inadequate FNACs were excluded; with the latter taken as false negatives, sensitivity was 73.7% and accuracy 76.0%. CONCLUSION: FNAC has a high specificity for diagnosis of ovarian/adnexal lesions but greater experience is required for the accurate subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate results.

The role of micronucleus scoring in fine needle aspirates of ductal carcinoma of the breast.

AIMS AND OBJECTIVES: Micronucleus (MN) scoring was carried out in benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) breast lesions to evaluate the role of MN as a biomarker in breast carcinomas. We also compared MN scores among different cytological grades of breast carcinoma. MATERIALS AND METHODS: A total of 31 archival cases of fibroadenoma (FA) and 40 cases of infiltrating ductal carcinoma (IDC) were selected. The best May-Grünwald-Giemsa (MGG) stained fine needle aspiration cytology (FNAC) smear of each case was selected. The MN scoring was carried out independently by two observers on 1000 epithelial cells in oil immersion magnification (100× objective). The MN scores in FA and IDC were compared. The IDC cases were graded and the MN scores in different cytological grades of IDC were compared. RESULTS: The mean MN scores (± standard deviation) in FA and IDC were 0.6 (± 1.1) and 13.6 (± 12.8), respectively, which were significantly different (P < 0.0001). There were seven grade 1, 13 grade 2, and 20 grade 3 IDCs. The mean MN scores (± standard deviation) of grade 1, 2 and 3 IDC were 4.3 (± 2.3), 11.95 (± 9.2) and 21.1 (± 16.7), respectively. An analysis of variance (anova) test showed a significant difference in MN score between all the grades of IDC (P < 0.05). However, there was no significant difference between fibroadenoma and grade 1 IDC. The Pearson's correlation coefficient showed positive correlations between MN scoring in the different grades of IDC. CONCLUSIONS: MN scoring on routinely stained smears of IDCs was significantly higher than in fibroadenoma and was relatively easy, reliable and reproducible. As MN scoring of grade 1 IDC was similar to fibroadenoma, a larger study should be conducted to compare grade 1 IDC with other benign breast lesions.

Atypical squamous cells and low-grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low-resource setting.

OBJECTIVES: To perform an audit of all cervical smears reported as atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL) as in the Bethesda system (TBS) 2001, and determine their histological follow-up and outcome when available, in order to define the threshold for colposcopic referral. MATERIAL AND METHODS: A total of 25,203 cervical smears were screened over a period of 3 years (January 2006 - December 2008) and all ASC and LSIL smears were reviewed with the corresponding histological follow-up. All cervical intraepithelial neoplasia (CIN) grade 2 lesions and above (CIN2+) were considered as clinically significant lesions for analysis. RESULTS: Out of 25,203 cervical smears, 424 (1.7%) were reported as ASC and 113 (0.4%) as LSIL. Additionally, three were reported as atypical cells, not otherwise specified. The ASC : SIL ratio was 2.18 : 1. Follow-up histology was available in 153 (36.8%) of the ASC cases and revealed CIN2+ lesions in 22 (14.4%). Follow-up histology was available in 50 (44.2%) of LSIL cases and revealed clinically significant abnormalities in five (10%), all of which were CIN2. CIN3 and invasive squamous carcinomas were seen in 5.9% and 1.4%, respectively, of cases of ASC, and not seen in LSIL. Reclassification of ASC smears into ASC-US (ASC-undetermined significance) and ASC-H (ASC- high grade SIL not excluded) revealed ASC-H in 2.6% of all ASC smears, with a clinically significant outcome in 45.4%. CONCLUSION: In a low-resource setting where human papillomavirus testing is unaffordable, the threshold for colposcopic referral and follow-up histology should be ASC rather than SIL.

Histoplasmosis: cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology.

BACKGROUND: Human infection with Histoplasma capsulatum runs the gamut from asymptomatic to disseminated disease. In immunocompromised patients, a tiny inoculum can lead to widespread disseminated infection. Early diagnosis and initiation of treatment is therefore important. OBJECTIVE: To review the cases of histoplasmosis diagnosed on fine needle aspiration cytology (FNAC) and to discuss the clinical presentation, associated inflammatory response, load of organisms and differential diagnosis on cytomorphology in these cases. METHODS: Retrospective review of seven cases of histoplasmosis at a tertiary-care centre during the period from 1998 to 2009 was performed. Clinical presentation along with cytomorphological features were studied and discussed in detail. RESULTS: The mean age of patients was 48.6 years and six out of seven were male. History of immunodeficiency (HIV) was available in five cases. Six patients presented with peripheral and/or abdominal lymphadenopathy. One patient had nodular shadows in both lungs and two also had skin lesions. On cytological smears, a variable load of uniform round to oval, about 2-4 microm in diameter, budding yeasts were seen intracellularly (within histiocytes) as well as extracellularly. In one case (HIV positive), these organisms were also seen within neutrophil polymorphonuclear leucocytes. In two cases, an inflammatory response in the form of epithelioid cell granulomas along with multinucleated giant cells was seen. CONCLUSIONS: FNAC is a reliable tool to recognize infection with H. capsulatum in tissues. This infection can cause a variable inflammatory response, which should be considered while reporting on such cases.

Advanced germ cell malignancies of the ovary: should neo-adjuvant chemotherapy be the first line of treatment?

Malignant germ cell tumours of the ovary, though classically known for 'young age' and 'early stage' at presentation, are not uncommonly identified at advanced stages. Little is available in literature on the role of neo-adjuvant chemotherapy (NACT) in this group of tumours. Two patients with advanced stage ovarian germ cell tumours, including one with 45XO/46XY chromosomal mosaicism, were treated at our Institute with neo-adjuvant chemotherapy with Bleomycin, Etoposide and Cisplatin followed by surgery. Besides marked clinical improvement, intraoperatively both the patients presented no difficulty otherwise expected with widespread tumours, and histopathology report revealed no evidence of viable tumour. The article discusses the experience and suggested course of management of these tumours with NACT, which could be offered to patients with advanced malignancy in whom high surgical morbidity is anticipated or in whom only an operative biopsy was performed at laparatomy. Behaviour and management guidelines of dysgenetic gonads with XY mosaicism have also been discussed.

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting.

OBJECTIVES: To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001. METHODS: A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out. RESULTS: AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old (P = 0.010). CONCLUSION: The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.

Changing objects lead briefly flashed ones.

Continuous, predictable events and spontaneous events may coincide in the visual environment. For a continuously moving object, the brain compensates for delays in transmission between a retinal event and neural responses in higher visual areas. Here we show that it similarly compensated for other smoothly changing features. A disk was flashed briefly during the presentation of another disk of continuously changing color, and observers compared the colors of the disks at the moment of flash. We also tested luminance, spatial frequency and pattern entropy; for all features, the continuously changing item led the flashed item in feature space. Thus the visual system's ability to compensate for delays in information about a continuously changing stimulus may extend to all features. We propose a model based on backward masking and priming to explain the phenomenon.

Prevalence of high--risk human papillomavirus infections in women with benign cervical cytology: a hospital based study from North India.

INTRODUCTION: Cervical cancer is the commonest cancer among Indian women. High-risk human papillomavirus (HPV) detection holds the potential to be used as a tool to identify women, at risk for subsequent development of cervical cancer. There is a pressing need for identifying prevalence of asymptomatic cervical HPV infection in the local population. OBJECTIVE: To determine the prevalence of high-risk HPV DNA in women with benign cervical cytology. MATERIALS AND METHODS: Women visiting the gynecology outpatient with varied complaints were subjected to Pap smear. Four hundred and seventy two samples were subjected to polymerase chain reaction, using consensus primers for low and high-risk HPV (types 6, 11, 16, 18, 31 and 33). The samples that were positive for HPV DNA were subsequently assessed for high-risk consensus primers, types 16, 18, 31 and 33 as well as for HPV type 16 and 18. RESULTS: One hundred and seventy four (36.8%) women tested positive for HPV DNA. Thirty nine (8.2%) of the entire cohort tested positive for high-risk HPV. Fifteen samples were positive for type 16, 22 for type 18 and two for both types 16 and 18. A statistically higher prevalence of high-risk HPV was observed in poorly educated and rural groups. No association of HPV prevalence was noted with age, parity and age at marriage. CONCLUSION: The study generates epidemiological data of prevalence of sub-clinical HPV in the women visiting a tertiary care institute as well as peripheral health centres. The data generated will be useful for laying guidelines for mass screening of HPV, treatment and prophylaxis in the local population.

Rosai-Dorfman disease: unusual cause of diffuse and massive retroperitoneal lymphadenopathy.

Rosai-Dorfman disease (RDD), originally described as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. Patients usually present with massive cervical lymphadenopathy. However other nodal sites (mediastinal and inguinal) are also frequently involved. The retro-peritoneum is an infrequent site of involvement. This uncommon entity should also be included in the list of differential diagnoses of diffuse and massive lymphadenopathy, which includes includes infectious/granulomatous conditions, lymphomatous and metastatic disease.

Fine-needle aspiration cytology of extramammary neoplasms metastatic to the breast.

Fine-needle aspiration (FNA) biopsy is the first-line investigation in any breast lump and hence cytomorphological recognition of nonmammary metastatic tumors to the breast and their distinction from primary tumors is important. Metastatic breast neoplasms diagnosed over a 6-yr period from 1997 to 2002 were retrieved from the database of the Department of Cytopathology and the clinical, cytopathological, histochemical, and immunohistochemical findings were correlated with the histopathology of the primary tumor. Fifteen cases of metastatic breast neoplasms were encountered constituting 1.47% of all malignant tumors of the breast diagnosed on FNA. There were 14 female patients and one male patient aged 13-80 yr. The preaspiration clinical diagnosis was either a benign breast lump or a malignancy (primary vs. metastatic). The breast lump was the initial presentation in four cases and the cytodiagnosis of a metastatic malignancy lead to the subsequent detection of the primary malignancy. These included one case each of melanoma, myeloma, rhabdomyosarcoma, and small-cell carcinoma of the lung. There were five pediatric cases that included four cases of rhabdomyosarcoma and one case of leukemic deposit. The adult cases included two cases each of melanoma, small-cell carcinoma, and myeloma; one case of choriocarcinoma; and three cases of soft-tissue sarcomas. These included two cases of malignant fibrous histiocytoma (MFH) and one case of leiomyosarcoma. The presence of unusual cytomorphological patterns on breast FNA should alert the cytopathologist to the possibility of a metastatic breast neoplasm, even if not suspected clinically. A detailed history of the patient, clinical correlation, and immunocytochemistry helps in establishing an accurate diagnosis, which avoids unnecessary surgery and ensures appropriate treatment.

Rhabdomyosarcoma of vulva in a young lady: A rare case report with review of literature.

A 21-year-old lady presented with a rapidly progressive vulvar swelling with inguinal lymphadenopathy for 7 months. Pathological evaluation revealed it as a case of rhabdomyosarcoma. The disease behaved aggressively and she was treated with multimodality treatment.

T cell subsets in acute rheumatic fever, rheumatic heart disease and acute glomerulonephritis cases.

T cell subsets were studied in 45 patients, 15 each of acute rheumatic fever, rheumatic heart diseases, and acute glomerulonephritis and compared with 10 normal control in the same age group. A significant depression in the OKT1 and OKT4 +ve cells and insignificant increase in the OKT8 +ve cells was noted in all these groups of cases.

Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels.

Somatosensory evoked potentials (SEPs) following median nerve stimulation were abnormal in 7 patients with sensory impairment due to vitamin B12 deficiency. Extensor plantar reflexes indicated a central sensory pathway lesion in 4 cases and absent tendon jerks suggested peripheral neuropathy in 4, but median nerve SEPs indicated a predominantly central lesion without marked peripheral nerve involvement in 6 and an axonal neuropathy without CNS involvement in 1. The latter had evidence of central slowing of conduction in SEPs following posterior tibial nerve stimulation. Consequently, it is suggested that the brunt of sensory pathway involvement usually falls on the CNS, although peripheral neuropathy may occur as the major abnormality in some cases. In 2 patients SEPs showed a marked improvement following treatment with vitamin B12 injections, one consistent with restored central conduction and the other with recovery from peripheral neuropathy. No peripheral or central SEP abnormalities were seen in 18 dairy-produce eating vegetarians with low vitamin B12 levels, although 6 reported mild sensory symptoms suggestive of peripheral neuropathy and 3 had corroborative clinical signs.

Regression to egocentrically determined description of form under conditions of inattention.

Although, ordinarily, upright objects are readily recognized by observers who are tilted, it is hypothesized that this is achieved by a process of correction. The first stage of that process is held to be a description of the object in relation to the biologically more primitive system of retinal coordinates. In order to test this hypothesis, tilted subjects were required to view figures under conditions of inattention (Experiment 1) or divided attention (Experiment 2). Under such conditions description may not proceed beyond that first stage. The results showed that recognition was higher for figures that maintained their orientation with respect to the retina (although they were then tilted in the environment) than for figures that remained upright in the environment (although they were then disoriented with respect to the retina). This outcome is the very opposite of what occurs under conditions of attention.

Antiepileptic drugs, hepatic enzyme induction and raised serum alkaline phosphatase isoenzymes.

Thirteen patients with epilepsy on long-term antiepileptic drug therapy and who had a persistently raised serum alkaline phosphatase (ALP) activity were investigated biochemically. Twelve patients had a raised liver ALP-isoenzyme activity and in nine of these the bone ALP-isoenzyme activity was normal. Gamma-glutamyl transferase (gamma GT) levels were raised in 12 patients. Two patients were hypoglycaemic. One patient fitted the biochemical parameters for subclinical osteomalacia. The resultant clinical picture showed 75% of patients with borderline hypocalcaemia, raised liver ALP, raised gamma GT and normal bone ALP activities in whom 1,25 dihydroxy-cholecalciferol (1,25-DHCC; vitamin D) therapy would be inappropriate, whilst 1,25-DHCC therapy might be considered for those with borderline hypocalcaemia and a raised bone ALP activity (three patients). No evidence was found of hepatotoxicity or drug induced cholestasis. It is considered that the induction of liver microsomal enzymes by antiepileptic drugs could include liver ALP (as opposed to bone ALP) as well as gamma GT and the inactivation pathways for 1,25 DHCC.

Ameloblastoma of the mandible: diagnosis by fine-needle aspiration cytology.

The fine needle aspiration cytologic findings of 3 cases of histologically proven ameloblastoma of the mandible are described. Tightly packed clusters of basaloid epithelial cells with palisading are a characteristic feature. Squamous differentiation was noted in all cases but was marked in one case seen as larger cells with central nucleus and abundant cytoplasm showing keratohyaline granules and whorls. A careful examination of the centrifuged sediment is important when fluid is aspirated as it may reveal a few characteristic clusters enabling a cytodiagnosis when supplemented by radiologic findings.