Venkateswaran K. Iyer

Diffusion-weighted MRI in renal cell carcinoma: A surrogate marker for predicting nuclear grade and histological subtype:

Background Though previous investigators have attempted to evaluate its utility in characterization of focal renal lesions, diffusion-weighted MR imaging (DW MRI) in renal diseases is still an evolving field and its role in predicting the aggressiveness of renal cell carcinoma (RCC) is yet to be established. Purpose To assess whether apparent diffusion coefficient (ADC) values can be used to determine the nuclear grade and histological subtype of RCCs and to identify the tumor attributes contributing to variation in ADC values. Material and Methods The institutional ethics committee waived the requirement of informed consent for this retrospective study. The study cohort consisted of 33 patients who underwent MRI (with diffusion-weighted imaging at b values of 0 and 500 s/mm2) and were found to have 36 pathologically-proven RCCs. ADC values were determined for solid portions of RCC, cystic/hemorrhagic areas, and normal renal parenchyma. Histological subtype, nuclear grade, and cell count were determined for each lesion. ADC values were compared between different grades and subtypes and correlation with cell count was investigated. Receiver operating characteristic curves were drawn to establish cut-off ADC values. Results There were 23 low grade (grades I and II) and 13 high grade tumors (grades III and IV). There were 32 clear-cell and four non-clear-cell RCCs. A decreasing trend of ADC values was seen with increasing grade and mean ADC of high grade RCC was significantly lower than low grade (1.3145 vs 1.6982 × 10−3 mm2/s) (P = 0.005). Mean ADC for clear-cell RCC was significantly higher than non-clear-cell RCC (1.6245 vs. 1.0412 × 10−3 mm2/s) (P = 0.005). ADC values higher than 1.7960 × 10−3 mm2/s were seen only with low grade and values greater than 1.4904 × 10−3 mm2/s were seen only with clear-cell RCC. Conclusion ADC values provide a non-invasive means to predict the nuclear grade and histological subtype of RCC. Cellularity and morphology are other tumor attributes contributing to the variation in ADC values of RCCs.

Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries

Background The frequencies of various causes of pulmonary granulomas in pathological material are unknown, as is the influence of geographical location on aetiology. The aim of this study was to identify the causes of pulmonary granulomas in pathological specimens, to define their frequencies, and to determine whether these causes vary by geographical location. Methods 500 lung biopsies and resections containing granulomas were reviewed retrospectively by expert pulmonary pathologists from 10 institutions in seven countries. Fifty consecutive cases from each location were assigned a diagnosis based on histological features and available clinical/microbiological data. Results A specific cause was identified in 58% of cases (290/500), most commonly sarcoidosis (136, 27%) and mycobacterial or fungal infections (125, 25%). Mycobacteria were identified in 19% of cases outside the USA versus 8% within the USA. In contrast, fungi accounted for 19% cases in the USA versus 4% in other locations. Fungi were mostly detected by histology, whereas most mycobacteria were identified in cultures. In 42% of cases (210/500) an aetiology could not be determined. Conclusions Across several geographical settings, sarcoidosis and infections are the most common causes of pulmonary granulomas diagnosed in pathological specimens. Fungi are more commonly identified than mycobacteria in the USA, whereas the reverse is true in other countries. A definite aetiology cannot be demonstrated in more than a third of all cases of pulmonary granulomas, even after histological examination. These findings highlight the need to submit material for histology as well as cultures in all cases in which granulomatous disease enters the differential diagnosis.

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

BACKGROUND To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. METHODS This was a cross-sectional study of 546 sexually active women aged > or =30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (kappa) and Chi-square test. RESULTS Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (kappa=76.31%, 95% confidence interval [CI]: 64.97-82.29%, p=0.04)-complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (kappa=63.7%, 95% CI: 55.2-72.2%) and 95.3% for physician-collected samples (kappa=80.4%, 95% CI: 71.8-89.0%). CONCLUSIONS Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.

Human papillomavirus-type distribution in women with and without cervical neoplasia in north India.

Our objective was to determine the human papillomavirus (HPV)-type prevalence in cervical samples in women with and without cervical neoplasia in an opportunistic hospital-based cancer-screening program. A cross-sectional study of 524 women presenting from January 2003 through June 2005 with symptoms of persistent vaginal discharge, intermenstrual bleeding, and postcoital bleeding or detected to have an unhealthy cervix underwent HPV genotyping by consensus polymerase chain reaction and reverse line-blot hybridization assay, conventional Pap smear, and colposcopy, with directed biopsy from all lesions detected. The prevalence rates of HPV infection among women with normal, low-grade cervical neoplasia (CIN 1) and high-grade CIN (>CIN2) were found to be 7.6%, 42.3%, and 87.5%, respectively. Seventeen high-risk and 6 low-risk HPV types were identified by the reverse line-blot assay. Multiple infections were seen in 20% of women. In normal women, the 6 commonest types were HPV-16, HPV-89, HPV-39, HPV-52, HPV-62, and HPV-18, whereas in high-grade disease, these were all high-risk types HPV-16, HPV-18, HPV-33, HPV-39, HPV-35, and HPV-56. HPV-16 was the commonest type in all groups, seen in 49.4% cases overall and in 74.3% of high-grade squamous intraepithelial lesion. It was followed by HPV-18 (7.4%) and HPV-33 and HPV-39 (4.9% each). HPV-89 was the commonest low-risk type (9.9%). HPV-16/18 were associated with 34.3% of normal, 45.4% of low-grade and 65.7% of high-grade lesions. A wide spectrum of HPV types is seen in north Indian women, with the majority being HPV-16 in all grades of histology. A vaccine against HPV-16 and HPV-18 could prevent two thirds of cases of high-grade cervical neoplasia.

Imaging of paediatric liver tumours with pathological correlation

Paediatric hepatic tumours are relatively rare with malignant lesions being twice as frequent as benign neoplasms and are mostly metastases. Imaging has a significant role in the evaluation of most paediatric liver tumours. Differentiating benign from malignant tumours is important as it significantly affects treatment decisions. We present the characteristic radiological and pathological features of the most common paediatric liver tumours.

Fine Needle Aspiration Cytology of Hepatoblastoma

Objective To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). Study Design Papanicolaou- and May-Grunwald-Giemsa-stained smears of aspirates from 26 cases of HRL were analyzed by 2 observers, Histologic material, available in 15 cases, was correlated. A cytology group-ing system was proposed on the basis of which all cases were classified. Results The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was ≤ 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of ≥ 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respective-ly). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in I case. Conclusion Epithelial HBL can be easily diagnosed in aspirates and further classified into fetal and embryonal subtypes, -which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.

Cytologic Diagnosis of Pulmonary Nocardiosis

Background Nocardiosis is an uncommon infection and presents as an opportunistic infection in an immunocompromised host. Pulmonary infection by Nocardia may be difficult to diagnose based on clinical and radiologic features, as these are not specific. Sputum examination, bronchoalveolar lavage and transthoracic ultrasound/ computed tomography-guided fine needle aspiration cytology offer a simple means of procuring material for diagnostic evaluation. Very few articles have described the morphologic appearance of this uncommon pathogen in cytologic material. Cases Three cases occurred in patients with an underlying immunocompromised state. Patient 1 was on steroid therapy for nephrotic syndrome, patient 2 was on immunosuppressant therapy after renal transplantation, and patient 3 was HIV positive. A diagnosis of pulmonary nocardiosis was suspected on Papanicolaou stain. Modified Ziebl-Neelsen stain and silver methanamine stains were useful in confirming the diagnosis. Conclusion A high index of suspicion for nocardiosis must be maintained while assessing cytologic material in immunosuppressed individuals as it may be masked by the intense inflammatory exudate associated with this infection. A meticulous search may reveal the presence of delicate, thin, faintly stained, branching filaments of Nocardia on routine Papanicolaou stain. Special stains and culture studies are useful in confirming the diagnosis.

Fine Needle Aspiration Cytology of Dermatopathic Lymphadenitis

OBJECTIVE To delineate and describe the cytomorphologic features of dermatopathic lymphadenitis on fine needle aspirated material. STUDY DESIGN Thirteen cases of previously diagnosed dermatopathic lymphadenitis (DLN) and 10 cases of reactive lymphadenitis (RLN) (5 each of sinus histiocytosis and follicular hyperplasia) were reexamined by two independent observers. The cytologic features were semiquantitated (0-3+). Histology was available in two cases. RESULTS A variable amount of melanin pigment was seen in all 13 cases of DLN and in only 3 cases of RLN. DLN had large histiocytic collections with blood vessels at the center (12/13). The histiocytic cells had an elongated nucleus (13/13) with nuclear grooves (13/13) and pseudonucleoli (11/13). Many of these nuclei had a convoluted and crumpled appearance (11/13). On immunocytochemistry these cells were S-100 positive (six cases) and CD68 negative (one case). In contrast, in RLN with sinus histiocytosis, the histiocytes were polygonal and had rounded nuclei. Spindle-shaped histiocytes were rare, while pseudonucleoli and nuclear grooves were absent. Sinus histiocytes were CD68 positive and S-100 negative on histologic sections. Tingible body macrophages were rare (2/13) in DLN and prominent (8/10) in RLN. Mitoses were seen in DLN (6/13) and RLN (9/10). CONCLUSION The morphologic features found to be helpful in the diagnosis of DLN on fine needle aspiration cytology are melanin-laden macrophages with variable pigment; large, histiocytic clusters with blood vessels at the center; characteristic histiocytes, with elongated vesicular nuclei, nuclear grooves, crumpled and convoluted nuclei and pseudonucleoli; and absence of or very few tingible body macrophages. Positivity on immunostaining for S-100 and negativity for CD68 aid in the diagnosis.

Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases

S. Kaushal, V. K. Iyer, S. R. Mathur and R. Ray
Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases

Gallbladder carcinoma: An attempt of WHO histological classification on fine needle aspiration material.

Background: Carcinoma of the gallbladder (CaGB) is common in India and its prognosis depends primarily on the extent of the disease and histological type. We aim to study the role of guided fine needle aspiration cytology (FNAC) for diagnosis of CaGB and to evaluate the feasibility of applying world health organization (WHO) classification on fine needle aspiration (FNA) material to predict the outcome of the tumor. Materials and Methods: Retrospective cytomorphologic analysis was performed in all cases of CaGB diagnosed by ultrasound (US) guided FNAC over a period of 2 years. A specific subtype was assigned according to WHO classification based on characteristic cytologic features. These included papillary or acinar arrangement, intra and extracellular mucin, keratin, rosettes and columnar, signet ring, atypical squamous, small, clear, spindle and giant cells. Correlation with histopathology was performed when available. Results: A total of 541 aspirations with clinical or radiological suspicion of primary CaGB were studied. Of these, 54 aspirates were unsatisfactory. Fifty cases were negative for malignancy. Remaining 437 aspirates were positive for carcinoma. Histopathologic diagnosis was available in 32 cases. Adenocarcinoma was the most frequent diagnosis in 86.7% of cases. Mucinous, signet ring, adenosquamous, squamous, small cell, mixed adenoneuroendocrine and undifferentiated carcinoma including spindle and giant cell subtypes were diagnosed identifying specific features on FNAC. Correlation with histopathology was present in all, but one case giving rise to sensitivity of 96.8%. No post-FNA complications were recorded. Conclusions: US guided FNAC is a safe and effective method to diagnose CaGB. Although, rare, clinically and prognostically significant variants described in WHO classification can be detected on cytology.