Morphological markers of chromosomal instability as predictors of malignancy in pleural effusion.

BACKGROUND: Malignancy in pleural effusion is an indication of poor prognosis. The distinction between malignant cells and reactive mesothelial cells in effusion cytology is sometimes difficult and requires ancillary techniques. Evaluation of morphological indicators of chromosomal instability (CI) like micronuclei (MN), chromatin bridging (CB), nuclear budding (NB), and multipolar mitosis (MM) on routine cytology smears is a promising tool to distinguish malignant from benign ascitic fluids. However, it has been scarcely evaluated in pleural effusions. The present study was conducted to evaluate the diagnostic value of these markers in differentiating between malignant and benign pleural fluids. METHODS: It is a cross sectional study in which a total of 72 pleural fluid samples over a period of 2 years received in the cytology department of the hospital were evaluated. The cytological analysis was done by two independent cytopathologists and interpreted as either malignant or benign. Four morphological markers of CI were counted in the May-Grünwald Giemsa (MGG) stained smears of all the cases and the score was compared with the conventional cyto-morphological diagnosis. RESULTS: Out of 72 cases, there were 42 malignant and 30 benign effusions on cytological examination. The mean score of micronuclei count, nuclear budding, chromatin bridging and multipolar mitosis in malignant effusions were 7.26 ± 2.74, 9.55 ± 5.53, 1.83 ± 1.17, and 2.21 ± 1.62 respectively that was significantly higher than the benign effusions (1 ± 0.71, 1.1 ± 0.86, 0.38 ± 0.50, and 0.15 ± 0.37 respectively) (p < .05). On Receiver operating characteristic (ROC) curve analysis, a cut-off of 5 for the MN count had a sensitivity of 88% and specificity of 100% in detecting malignant pleural effusion [Area under curve (AUC) 95.8%, p < .001]. CONCLUSION: Evaluation of morphological indicators of CI on routine MGG stained smears is a simple and cost-effective method to differentiate between benign and malignant pleural fluids.

Iodine-125 brachytherapy for choroidal melanoma by using Ocuprosta seeds with indigenous non-collimated plaques: Our initial experience.

PURPOSE: Brachytherapy is the gold-standard treatment for choroidal melanoma. This study evaluated iodine-125 brachytherapy by using Ocuprosta seeds with indigenous non-collimated plaques in Asian patients. METHODS: Retrospective single-center study in a tertiary care hospital of 12 eyes with choroidal melanoma in 12 Asian patients who underwent brachytherapy with Ocuprosta seeds fixed on non-collimated plaques and had a follow-up of at least 32 months (mean: 42.4 ± 9.5 months; median: 40 months). Radiotherapy was planned after developing the digital 3D model of the tumor within the eye by using radiological images and clinical pictures. Ocuprosta iodine-125 seeds were used on indigenous non-collimated gold plaques to deliver the radiation for precalculated time. "Successful outcome" was taken as a decrease in the volume of the tumor, and "unsuccessful outcome" was defined as no change in the tumor volume or increase in the tumor volume at 24 months after brachytherapy. RESULTS: The mean decrease in tumor volume was 21% (914.5 ± 912.2 mm3 to 495.7 ± 633.6 mm3) after brachytherapy, which correlated with the baseline volume of the tumor. Ten eyes (83.3%) showed a reduction in tumor volume, whereas two eyes showed an increase in the volume of the tumor after brachytherapy. One of the cases with a reduction in tumor size developed neovascular glaucoma. Enucleation was done in three eyes. A globe salvage rate of 75% and tumor regression rate of 83% were seen in the present study using Ocuprosta seeds. CONCLUSIONS: Iodine-125 brachytherapy with uncollimated indigenous gold plaques is an effective treatment modality for choroidal melanomas in Asian patients.

Vocal Cord Nodule with Stromal Atypia: Case Report and Review of Literature.

Vocal cord nodule is a common reactive transformation of the laryngeal mucosa encountered routinely. Although benign, rare instances of stromal atypia have been demonstrated, which can often be confused with other spindle cell lesions. There is a dearth of literature explaining this peculiar transformation. Hence, the diagnosis of these lesions can be put-forth only after histopathological evaluation and appropriate immunohistochemical analysis. Herein, we report a case of a 55-year-old male who presented with vocal cord nodule with stromal atypia.

Comparative Analysis of Conventional Cytology and Liquid-Based Cytology in the Detection of Carcinoma Cervix and its Precursor Lesions.

Context: The conventional smears (CS) and Liquid based cytology (LBC) are important tools to detect carcinoma cervix and its precursor lesions. Aims: The present study was done to compare the cytomorphological features of cervical lesions using both techniques and compare with the histopathological diagnosis. Settings and Design: This was a prospective observational study over a period of 1.5 years at a tertiary care hospital. Methods and Material: A total of 969 women in the age group of 21-65 years presenting with either routine screening or complaints of vaginal bleeding, discharge, or pelvic pain were enrolled for the study. Both the CS and LBC smears were analyzed and compared with the corresponding histopathology diagnosis. The data was analyzed using Statistical Package for the Social Sciences (SPSS) software and P values <0.05 were considered significant. Results: There were 8.57% unsatisfactory smears in CS as compared to 0.5% in LBC smears. Liquid-based cytology was superior to conventional preparations in terms of smear adequacy, lesser hemorrhagic and inflammatory background, and presence of more endocervical cells. Liquid-based cytology showed a better yield in detecting all the types of epithelial cell lesions with a concordance rate of 73.9% between the two techniques. On histopathology correlation of these lesions, LBC had a higher sensitivity (96.67%) and diagnostic accuracy (99.08%) as compared to CS (73.33% and 92.66%, respectively). Conclusions: Liquid-based cytology is superior to conventional cytology for the detection of epithelial cell lesions. Reduction in the unsatisfactory smears, a cleaner background, and better representation of the sample are more significantly appreciated on LBC in contrast to CS.

The Fallacies of the Breast MRI: A Case Study.

Magnetic resonance imaging (MRI) of breasts using diffusion-weighted imaging and dynamic contrast enhancement is now well-established imaging for the evaluation and characterization of suspicious breast lesions, where it has become a problem-solving tool. Breast lesions are characterized according to their morphological features and enhancement characteristics. Breast MRI is helpful in the evaluation of breast lesions in patients with dense breasts and women with breast implants and to differentiate scars and recurrence. However, this technique has its own limitations, a few of which are elucidated in the present case report.

Role of Magnetic Resonance Mammography in the Evaluation of Indeterminate Breast Lesions.

Background: Malignancy of the breast is one of the most common cancers among females worldwide. Magnetic resonance mammography (MRM) is a valuable complement to conventional methods for the early diagnosis of disease, thereby providing patients with a better prognosis. The number of unnecessary biopsies and repeated excisions in cases of indeterminate breast lesions detected on conventional imaging is high. Aims: The purpose of this study was to evaluate the role of MRM in the evaluation of indeterminate breast lesions [Breast Imaging Reporting and Data System (BIRADS) 3/4] found in conventional mammography and ultrasonography (USG), taking the histopathological examination (HPE) as the gold standard. Materials and methods: A total of 38 patients with conventional radiological imaging diagnosis of indeterminate breast lesions (BIRADS 3/4) were included in this study and evaluated using contrast-enhanced MRM according to the MR-BIRADS lexicon (5th edition). Morphological characteristics of lesions were evaluated to determine the probability of malignancy. Histopathology was kept as the gold standard for comparing all the statistical parameters. Results: There were a total of 40 lesions, 35 masses, and five nonmass enhancement (NME) available for evaluation out of the 38 patients. The sensitivity of margins to detect malignancy approached 100%; however, it had a slightly lower specificity of 66.67%. Magnetic resonance imaging (MRI) showed good diagnostic performance with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85, 90, 89.47, 85.71, and 87.50%, respectively. Conclusion: The MRI has been shown to be useful as a problem-solving tool in breast cancer screening, clarifying indeterminate findings and avoiding unnecessary short follow-ups and percutaneous biopsies. How to cite this article: Mishra E, Kaur N, Kaur R, et al. Role of Magnetic Resonance Mammography in the Evaluation of Indeterminate Breast Lesions. J Assoc Physicians India 2023;71(11):76-84.

Clinico-pathological Spectrum of Primary Skin Malignancies in an Indian Tertiary Care Hospital.

Background: Skin malignancies are the most common form of malignant disease in the western world, predominantly affecting older age groups. The majority of skin cancers are basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma, which account for more than 95% of total skin malignancies. However, in India, these constitute only 1-2% of all cancers. There is an increase in incidence in India over 10 years of period. There is scarcity of data on the clinico-pathological profile of these tumours from this geographical region. Materials and Methods: This was a retrospective study conducted in a tertiary care teaching hospital in which archival records and histopathology sections of all patients of skin carcinomas diagnosed over a period of 5 years (January 2016 to December 2020) were analysed. The clinical parameters and histopathological features of the cases were analysed and correlated for any possible association. Results: Out of the 230 skin malignancies studied, SCC constituted the most common type (n = 148), followed by BCC (n = 70) and malignant melanoma (n = 12). The tumour commonly presented in the 6th decade of life with slightly higher male preponderance (M: F =1.6:1). Sun-exposed areas were the most common sites, and the common presentations included non-healing ulcer, fungating/cauliflower/polypoidal growth, and hyperpigmented or nodular plaque. In SCC, previous history of diabetes and burns was noted in 10% and 3.4% of the patients, respectively. Conclusion: SCC is likely the most common histological type of skin malignancies in India. The clinico-pathological profile of skin malignancies of patients depends on multiple factors, notably the skin colour and the geographical location.

Hepatocyte paraffin-1, CD10, and CD34 immunostaining as a diagnostic aid in cytologic diagnosis of hepatic cancer.

Background: Cytomorphological distinction between hepatocellular carcinoma and metastatic tumors to the liver may be difficult, especially when these have poor differentiation. The present study was done to assess the diagnostic utility of hepatocyte paraffin-1 (HepPar-1), CD10, and CD34 in differentiating hepatocellular carcinoma from metastatic carcinoma. Materials and Methods: Ultrasound-guided fine-needle aspiration was performed on 50 patients with space-occupying lesions of liver suspicious for malignancy on clinical/radiologic findings. The cytological assessment was done on smears stained with May-Grünwald-Giemsa and hematoxylin and eosin. Cell blocks were prepared, and immunostaining for HepPar-1, CD10, and CD34 was done. Results: In these 50 patients, hepatocellular carcinoma was diagnosed in 7 and metastatic tumors in 43 cases. The sensitivity of smears in diagnosing hepatocellular carcinoma was 100% and the specificity was 95.3%, while the sensitivity and specificity of cell block were 100%. A canalicular pattern of CD10 immunoreactivity had a 100% positive predictive value for diagnosing hepatocellular carcinoma. CD10 had a sensitivity of 57.1% and 41.9% in identification of HCC and metastatic tumors, respectively. For the diagnosis of hepatocellular carcinoma, the sensitivity of CD34 was 85.7% and the specificity of sinusoidal pattern of immunoreactivity was 100%. The sensitivity and specificity of granular cytoplasmic staining pattern of HepPar-1 were 100% in hepatocellular carcinoma. Conclusions: The staining patterns of HepPar-1, CD10, and CD34 are highly specific in distinguishing hepatocellular carcinoma from metastasis. These three immunomarkers should be included in the immunocytochemical panel for differentiating hepatocellular carcinoma from metastatic carcinoma to the liver.

Fine-needle aspiration cytology in soft tissue tumors-5-year institutional experience.

INTRODUCTION: Fine-needle aspiration cytology (FNAC) forms one of the first-line investigations in the evaluation of tumors in modern era. Its role in diagnosing soft tissue tumors (STT) has been well established. However, the morphological overlap and biological heterogeneity of STT pose a morphological diagnostic challenge. AIMS: To evaluate the scope of FNAC in diagnosis and categorization of STT and to correlate the cytological features with histological findings wherever available, and to analyze the reasons for discordance, if any. MATERIALS AND METHODS: All FNAs of cytologically diagnosed STT during 5-year period were retrospectively analyzed. FNAC smears stained using May-Grünwald Giemsa, Pap- and hematoxylin and eosin, were evaluated and interpreted inconjunction with clinical details. Cellblock and immunocytochemistry (ICC) was done, wherever required to render the final diagnosis. RESULTS: Of the total 15,844 FNAC done in 5 years, 1319 (8.3%) cases were diagnosed as STT. Benign tumors comprised the majority (94.2%), whereas 5.8% were diagnosed to be malignant. These were further grouped according to the cytomorphological features into adipocytic (82.2%), benign spindle cell lesions (10.8%), vascular (1.4%), spindle cell sarcoma/sarcoma NOS (2.2%), myxoid (0.3%), round cell tumors (0.9%), metastatic tumors (1.9%), and others (0.3%). The cytological findings were corelated with histopathological findings, which were available in 316 cases. The specificity and sensitivity calculated for detecting malignancy was 99.2% and 95.4%, respectively. The overall diagnostic accuracy for diagnosing malignancy was 98.7%. Among the group of non-adipocytic tumors, the sensitivity, specificity, PPV, NPV calculated for diagnosing a malignant tumor (irrespective of exact sub-categorization) is 95.2%, 100%, 100%, and 96.4%, respectively. The overall diagnostic accuracy in non-adipocytic tumors is 97.92%. CONCLUSION: FNAC is a simple, cost effective, and minimally invasive method in diagnosing STT with good sensitivity and specificity. It is of utility not only in primary lesions, but also for metastatic tumors, and for the documentation of locally recurrent soft tissue neoplasms.

Correlation of Morphological Features of Chromosomal Instability and Flow Cytometric DNA Ploidy Analysis in Aspirates of Breast Carcinoma.

OBJECTIVE: Morphological indicators of chromosomal instability (CI), including multipolar mitoses, chromatin bridges (CB), strings, nuclear buds (NB), micronuclei (MN), and deoxyribonucleic acid (DNA) ploidy analysis help in prognostication of breast carcinoma. The present study was done to evaluate CI in breast carcinoma and correlate with DNA ploidy and tumor grade. STUDY DESIGN: Fifty cases of carcinoma breast diagnosed by fine-needle aspiration cytology were included. Robinson's grading method was used on smears to grade breast carcinoma. To assess the morphological features of CI, the best May-Grünwald Giemsa stained smear was chosen. At least 1,000 epithelial cells on oil immersion magnification (×100 objective) were counted. DNA ploidy on the aspirates was done by flow cytometry. RESULTS: All the patients were female, diagnosed as infiltrating ductal carcinoma on cytology. Eight tumors were grade I, 32 were grade II, and 10 were grade III. MN was seen in 48 cases, NB in 45, and CB in 12 cases. Mean MN, NB, and CB scores in aneuploid (24) cases were 9.96 ± 8.42, 5.29 ± 4.71, and 1.08 ± 1.84 while 6.19 ± 6.67, 1.92 ± 1.79, and 0.11 ± 0.33 were seen in diploid (26) cases. Statistically significant positive correlation was observed between CI and DNA ploidy. CONCLUSIONS: Morphological evaluation of CI by light microscopy on routinely stained breast aspirates is feasible, although a meticulous search is required. Cytomorphological features of CI and ploidy have a positive correlation with increasing tumor grade.

Fine needle aspiration cytology of dermatofibrosarcoma protuberans arising in a burn scar.

Tumours developing after a protracted period of time in burn scars are a notable complication with carcinomas forming a major share. The occurrence of burn scar sarcomas is scarce with dermatofibrosarcoma protuberans (DFSP) being an uncommon entity having only three prior reported cases. The authors report a case of a 32-year-old male patient with a 5 year prior history of thermal burn who presented with an expanding painless swelling for 2 years in the right flank region, diagnosed as DFSP on fine needle aspiration cytology and subsequently confirmed on histopathology.

Role of Intraoperative Pathology Consultation by Imprint and Scrape Cytology in Soft Tissue Tumors and Tumor-Like Lesions.

Intraoperative pathologic consultation plays an essential role in therapeutic decision making, possibly avoiding under or overtreatment of the patient. Common indications for intraoperative consultation include obtaining a diagnosis in an unknown pathology, ruling out malignancy, confirming a provisional diagnosis, and assessing margin status. Fifty patients undergoing surgery for soft tissue tumors or tumor-like lesions were included in the present prospective study to evaluate the role of intraoperative pathologic consultation by imprint and scrape cytology. Careful and quick gross examination of the specimen was performed, followed by processing for imprint and scrape smears. The prepared smears were evaluated by three pathologists and the cytological diagnosis compared subsequently with final histopathological diagnosis. Intraoperative consultation was primarily requested to make or confirm preoperative diagnosis. In 44.0% cases, no previous tissue/cytological diagnosis was available. In 56.0% cases, previous pathological diagnosis was available, but the reports were inconclusive or were reported from outside our institute. The diagnostic yield of imprint smears was 24% (5 malignant, 6 benign, and 1 inconclusive), and scrape smears was 100% (10 malignant, 38 benign, and 2 inconclusive). Paraffin-embedded sections yielded diagnosis in 100% cases (11 malignant, 38 benign, and 1 nonneoplastic). Imprint smears alone were not of much help in intraoperative diagnosis. Scrape smears were found to be superior to imprint smears in terms of diagnostic yield and accuracy. Combined imprint and scrape smear cytology did not provide any advantage in intraoperative provisional tissue diagnosis in soft tissue tumors.

Isolation and morphology of circulating tumor cells by cell block technique in breast cancer.

BACKGROUND: Circulating tumor cells (CTCs) are cells present in the blood stream that are antigenically or genetically similar to a specific tumor type and are markers of tumor diagnosis, prognosis, residual disease and metastasis. The ever-increasing burden of breast cancer globally warrants the incorporation of this all-inclusive marker in the diagnostic repertoire using the simplest of techniques. AIMS: To identify CTCs in peripheral blood by cell block (CB) technique in cases of breast cancer diagnosed on fine-needle aspiration (FNA) or core needle biopsy (CNB) and to correlate their presence with nodal metastasis. MATERIAL AND METHODS: This study was conducted in the Department of Pathology, at a tertiary care hospital. Peripheral blood samples from a total of 30 cases of primary breast carcinoma diagnosed on FNA or CNB without prior neoadjuvant chemotherapy were analyzed using the CB technique. RESULTS: The age ranged between 29-74 years with the most common presenting complaint being a palpable, single, unilateral breast lump. CTCs were detected in 2 (6.7%) cases with a <5 cell cluster with both the cases being grade I breast carcinomas and also displaying nodal metastasis.

Evaluation of DNA ploidy and S-phase fraction in fine needle aspirates from breast carcinoma.

BACKGROUND: The use of fine-needle aspiration (FNA) as a primary tool in the diagnosis of breast carcinoma provides opportunity for early proliferative characterization of the tumor. This study was undertaken to assess DNA ploidy and S-phase (SPF) fraction by flow cytometry in fine needle aspirates of patients with breast cancer. METHOD: Fifty patients of breast cancer diagnosed on fine needle aspiration cytology (FNAC) and who subsequently underwent either mastectomy or lumpectomy were included. Material obtained by FNAC was subjected to DNA ploidy and SPF analysis. Immunohistochemical estimation of Ki-67 was done on histopathology sections. The proliferation markers (SPF and Ki-67) were compared with each other and with the histopathologic parameters. RESULTS: On DNA flow cytometry, 27 (54%) cases were aneuploid and 23 (46%) cases were diploid. The median SPF was 12.43% and 4.03% in aneuploid and diploid tumors respectively. Median Ki-67 among aneuploid tumors was 28.6% compared to 8.7% among diploid tumors. Aneuploid tumors were significantly associated with higher values of SPF and Ki-67, with Kappa 0.437 and agreement of 72%. Diploid tumors showed lower values of SPF and Ki-67, with Kappa 0.455 and agreement of 72.7%. Correlation among SPF and Ki-67 was highly significant with Kappa value 0.446, P value of .002 and agreement of 72.3%. CONCLUSION: DNA ploidy and proliferative activity by flow cytometric SPF estimation on fine needle aspirates from breast cancer can provide valuable prognostic and predictive information at the time of diagnosis in patients with breast cancer. This might help in selection of appropriate treatment modality.

Diagnostic utility of p16 immunocytochemistry in metastatic cervical lymph nodes in head and neck cancers.

BACKGROUND: Human papilloma virus (HPV) testing can be useful in work-up of patients presenting with cervical node metastasis, suspected to be of head and neck origin as HPV positive tumors show better response to therapy. The current study was planned to detect HPV in aspirates from metastatic cervical nodes using p16 immunocytochemistry in head and neck squamous cell carcinoma (HNSCC). Further correlation of HPV status between node metastasis and primary tumor was done. METHODS: The prospective study included 50 patients diagnosed as metastatic SCC in cervical nodes on fine needle aspiration with either known head and neck primary or primary detected post cytodiagnosis. Immunostaining for p16 was carried out on both smears and tissue sections. RESULTS: Forty-three patients were male and seven were female. Age of the patients ranged from 35 to 80 years. Primary sites of HNSCC were oropharynx (25), oral cavity (14), and larynx (11). Immunocytochemistry for p16 on smears showed positivity in 28 cases. Immunohistochemistry for p16 in primary tumors was positive in 34. There was substantial agreement between p16 immunocytochemistry and immunohistochemistry (Kappa value: 0.823). The sensitivity of p16 immunocytochemistry for the detection of HPV in metastatic HNSCC was 82.4% while the specificity was 100%. The positive and negative predictive values were 100% and 72.7%, respectively. CONCLUSIONS: P16 immunocytochemistry in HNSCC metastatic to cervical node mirrors the HPV status of the corresponding primary tumor. Hence in tumors of unknown origin presenting as cervical node metastasis, p16 immunocytochemistry can be employed for localization of the primary.

Unusual presentation of Retinoblastoma.

Most cases of retinoblastoma are diagnosed before the age of 5 years. The cases in older age groups can have variable presentations leading to misdiagnosis and management challenges. We report a case of retinoblastoma in an 8-year-old female who was primarily referred as a case of sympathetic ophthalmia due to a co-incidental misleading history of penetrating eye injury to other eye 3 weeks prior. The patient complained of decreased vision in the left eye after 3 weeks of repair of the corneo-scleral laceration in the right eye. Visual acuity in the right and left eye was 3/60 and light perception respectively. The anterior segment examination showed moderate sized keratic precipitates, intense inflammatory cellular reaction with large fluffy cells, hypopyon and dense vitreous exudates. Ultrasonography showed abundant hyperechoic contents within the vitreous cavity in the left globe. The retino-choroid was thickened. The possibility of endophthalmitis and sympathetic ophthalmia was considered. Diagnostic vitrectomy was planned. Intraoperatively, after clearing the exudates, a yellowish white mass lesion was seen superiorly. Post- operatively contrast-enhanced MRI scan confirmed the presence of an enhancing mass lesion in the globe consistent with the diagnosis of intraocular retinoblastoma. Enucleation of left globe was done after chemotherapy. Thus, a high risk of suspicion has to be kept for this malignant tumour in children with unexplained visual loss.