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.

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.

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.

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.

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.

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.

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.

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.

Expression of cytokeratin 20 in urine cytology smears: a potential marker for the detection of urothelial carcinoma.

BACKGROUND: Urine cytomorphology is one of the oldest methods for screening and monitoring patients with transitional cell carcinoma (TCC). Sensitivity of urine cytology is relatively low. Ancillary techniques on urine sample may increase the sensitivity. AIM: To explore the utility of cytokeratin 20 (CK20) immunostaining in identifying malignant cells in urine cytology smears. MATERIALS AND METHODS: Fourteen cases each of confirmed TCC and benign urinary cytology along with five cases of atypical cells in urine were immunostained with a monoclonal CK20 antibody. Of 14 cases of TCC, 12 showed strong positive staining with the antibody. All benign cases were negative except for a few cases in which the umbrella cells were weakly to moderately positive. In all five cases of atypical urine cytology the atypical cells stained positive with the antibody. These cases were later confirmed as TCC on histopathology of bladder wall biopsy. CONCLUSION: CK20 is an important biomarker that can be used to identify TCC in urine cytology smears. It is particularly useful in those cases where malignancy cannot be confirmed by morphology alone.

Cytopathological spectrum of unusual malignant pleural effusions at a tertiary care centre in north India.

BACKGROUND: Cytological examination of pleural fluid is one of the most informative laboratory procedures in the diagnosis of pleural effusions. Although tuberculosis is the commonest cause of pleural effusions in developing countries, tumours, including grade ones, can present with effusions. OBJECTIVE: The aim of the present study was to evaluate the uncommon causes of malignant pleural effusion. METHODS: A 2-year retrospective analysis of pleural fluid cytological specimens submitted to the Department of Cytopathology, PGIMER, Chandigarh between January 2003 and December 2004 was performed to retrieve unusual metastases. Out of a total of 898 samples reviewed, 710 were negative for malignancy and 24 cases were suspicious for malignancy. The remaining 164 cases were positive for malignancy, out of which 38 cases revealed malignancies other than adenocarcinoma. RESULTS: The 38 unusual malignancies metastasizing to the pleural cavity included 29 haematological malignancies (non-Hodgkin's lymphoma, acute lymphoid leukaemia, multiple myeloma and chronic myeloid leukaemia) and nine non-haematological malignancies (Ewing's sarcoma, neuroblastoma, Wilms' tumour, squamous cell carcinoma, small-cell carcinoma and malignant fibrous histiocytoma). CONCLUSION: Although metastatic adenocarcinoma was the commonest aetiology of malignant pleural effusions, a significant number of unusual causes of malignant pleural effusion were also encountered.

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.

Fine needle aspiration of epididymal nodules in Chandigarh, north India: an audit of 228 cases.

BACKGROUND: Epididymal nodules are not infrequently encountered in surgical practice. These are generally small and slippery and fine needle aspiration cytology (FNAC) is not easy. But as it is rapid and less traumatic than a biopsy, this is a favoured technique in the assessment of epididymal nodules. PATIENTS AND METHODS: In the present study, all the cases of epididymal nodules aspirated from January 1998 to August 2004 were retrieved from the cytology files of the Department of Cytology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. RESULTS: A total of 228 cases were retrieved and divided as follows: tuberculous epididymitis 70 (30.7%), non-specific inflammation 10 (4.4%), microfilaria 2 (0.9%), hydrocele 26 (11.4%), spermatocele 42 (18.4%), spermatic granulomas 12 (5.3%), adenomatoid tumour 3 (1.3%), leiomyosarcoma 1 (0.4%) and lipoma 1 (0.4%). Thirty-six (15.8%) cases were labelled as benign aspirate not otherwise specified. FNAC material was inadequate for opinion in 22 (9.65%) cases and three (1.3%) cases revealed evidence of a haematoma. CONCLUSIONS: FNAC was useful in the diagnosis of 90.3% of cases, thereby avoiding surgical biopsy and other investigations. Therefore, FNAC has an important role in the differential diagnosis of epididymal nodules as it can detect malignancy and benign conditions such as tuberculosis and acute and chronic epididymo-orchitis.

Pathology of supraclavicular lymphadenopathy in Chandigarh, north India: an audit of 200 cases diagnosed by needle aspiration.

OBJECTIVE: Fine needle aspiration cytology (FNAC) of lymph nodes can be used routinely as a first-line diagnostic test. The majority of studies reveal a malignant cause for palpable supraclavicular lymph nodes. The present audit further emphasizes the use of FNAC as a first-line investigation for the evaluation of enlarged supraclavicular lymph nodes. METHODS: A total of 200 cases of palpable supraclavicular lymph node(s) were included in the present study. RESULTS: Left supraclavicular lymph nodes were found to be more commonly involved (59.5% cases). Sixty-four per cent cases showed metastatic deposits and 13.5% cases were diagnosed as tuberculosis. Ten per cent cases showed reactive lymphoid hyperplasia; 0.5% (one) case showed only necrosis and on autopsy, a microscopic focus of choriocarcinoma was found in the testis. In 7.5% cases, diagnostic material could not be aspirated despite repeated attempts. Common metastatic tumours were from lung (22% cases), breast (16.4% cases), cervix (11% cases) and oesophagus (8.6% cases). In 13.3% cases the primary site was unknown and the diagnosis of malignancy first came from FNAC. CONCLUSION: The present study further highlights the importance of FNAC as a first-line diagnostic modality in the evaluation of supraclavicular lymphadenopathy. A full history, radiological findings and immunochemistry in difficult cases can help to arrive at a definitive diagnosis.

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.