Immune characterization of thyroid neoplasm's and its variants using immunohistochemical markers: CK-19, Galectin-3 and Hector Battifora mesothelial-1.

BACKGROUND: Nodular lesions of the thyroid are amongst the common palpable lesions that are encountered by the pathologists in the fine needle aspiration clinics and not only aspiration smears, but even biopsy sections pose significant challenges in their characterization and further classification. Neoplastic lesions of the thyroid have shown a steady rise worldwide and are diagnosed at age younger than most other cancers. Histopathology remains the gold standard in diagnosis and classification of thyroid neoplasms, with variable sensitivity and specificity of immunohistochemical markers, also attributed to variation in the inclusion criteria. We classified the thyroid neoplasms based on WHO Classification (2017) and aimed to study the diagnostic utility of immunohistochemical markers - CK-19, Galectin-3 and Hector Battifora mesothelial-1 performed on manual tissue microarray sections to differentiate various variants of papillary carcinoma from its mimickers, specifically follicular patterned papillary neoplasms from other follicular patterned lesions. METHOD: Prospective study of neoplastic lesions of thyroid from July 2018 to August 2020. Authors describe the clinico-radiological, cytological, histo-morphological and immunohistochemical features of neoplastic nodular lesions of the thyroid. RESULTS: Prospective analysis of nodular thyroid lesions yielded 76 cases, of which 38 were neoplastic. Cytology showed discordance in 10/24 cases, amongst the discordant cases, 70% were confirmed as papillary carcinoma. CK-19 showed high expression in all variants of papillary carcinomas (24/24), low expression in well differentiated tumor of uncertain malignant potential (WD-TUMP) and medullary carcinoma. It was negative in follicular and Hurthle cell neoplasms. Galectin-3 showed 100% specificity and HBME-1 showed 100% sensitivity in diagnosis of papillary carcinoma and its variants. Adenomatoid nodules did not express Gal-3 which helped in their differentiation from FVPTC. CONCLUSIONS: Gal-3 in combination either with CK-19 or HBME-1 improves the sensitivity and specificity of detection of papillary carcinoma, its variants and its differentiation from follicular patterned lesions to 100% with a significant p value.

Expression of TP53 in oral squamous cell carcinoma and its correlation with adverse histopathological features.

Background: This study aimed to evaluate the expression of TP53 in oral squamous cell carcinoma (OSCC) and to correlate its expressions with adverse histopathological features like depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), extranodal extension (ENE), and margin status which significantly affect the prognosis. Methodology: This cross-sectional study included 48 patients of OSCC who underwent surgical resection. All the histopathological adverse features such as DOI, LVI, PNI, ENE, margin status were noted. Immunohistochemical expression of TP53 was noted and a correlation of TP53 with histopathological adverse features was done. Statistical analysis was performed using SPSS software. Results: TP53 immunopositivity was seen in 45.83% (22/48) of cases. TP53 has a statistically significant correlation with margin status (P = 0.002). Similarly, TP53 expression is more in cases with LVI (100% cases) though the value is not statistically significant. TP53 expressions are more in positive margin cases and less if the margin is >5 mm. Similarly, TP53 expression is more in cases with LVI (100% cases) though the value is not statistically significant. Conclusion: Few parameters that did not show the correlation of TP53 with adverse histopathological features could be attributed to a small sample size. Further studies with a large number of cases and using other ancillary molecular diagnostic techniques would throw further light on the exact alteration of TP53 in our population and their association with histopathological prognostic features.

Effect of megaloblastic anemia on hemoglobin A2 and diagnosis of ß-thalassemia trait.

Context: ß-thalassemia trait is usually diagnosed by raised hemoglobin A2 (HbA2). The presence of megaloblastic anemia can cause an increase in HbA2 and create a diagnostic dilemma. Here, we have analyzed the effect of vitamin B12 and folic acid supplementation on HbA2 and diagnosis of ß-thalassemia trait in cases of megaloblastic anemia with raised HbA2. Materials and Methods: Cases of megaloblastic anemia with raised HbA2 on high-performance liquid chromatography (HPLC) were supplemented with vitamin B12 and folic acid. Post-treatment evaluation was done after 2 months. Cases showing adequate hematological response were subjected to statistical analysis. Based on post-treatment HbA2 value, the cases were diagnosed as normal, borderline raised HbA2, or ß-thalassemia trait. Pre- and post-treatment values of red cell parameters and HbA2 were analyzed. Results: There was a significant decrease in HbA2 value after vitamin B12 and folic acid supplementation. The diagnosis was changed in 70.97% of the cases after treatment. The chance of inconclusive diagnosis was decreased from more than 50% to less than 10%. Pre-treatment mean corpuscular volume (MCV) and HbA2% showed a significant difference between the thalassemic and normal groups. Conclusions: Megaloblastic anemia can lead to false-positive diagnosis of ß-thalassemia trait on HPLC. Repeat HPLC should be done after adequate supplementation of vitamin B12 and folic acid in cases of megaloblastic anemia with raised HbA2. Red cell parameters are not helpful to suspect ß-thalassemia trait in presence of megaloblastic anemia. However, HbA2% on HPLC can be a useful parameter to suspect or exclude ß-thalassemia trait in cases of megaloblastic anemia.

Accuracy of cytological grading in the carcinoma breast and its correlation with pathological prognostic parameters.

BACKGROUND: Breast carcinoma is a significant contributor to cancer deaths worldwide. Tumor grade is an important parameter in planning out the treatment. Histology is the gold standard for grading the carcinoma breast. However, fine-needle aspiration cytology (FNAC) is still an important first-line diagnostic procedure in many parts of the world. Grading on cytology will help in pre-operative management. Although cytological grading of the carcinoma breast is a topic of research for many years, it is not yet included as a part of routine cytology reports. MATERIALS AND METHODS: A prospective study was conducted over a period of 1 year at Kalinga Institute of Medical Sciences. A total of 42 cases of carcinoma breast, diagnosed on FNAC and subsequently confirmed on histology, were included. Cytological grading was performed using Robinson's grading system, and the results were compared with the histological grade. Also, the cytological grades were correlated with various pathological prognostic parameters such as tumor size, lymph node status, lympho-vascular invasion, estrogen and progesterone receptor status, Her-2-neu expression, and Ki-67 index. The kappa measure of agreement and Fisher's exact test were used for statistical analysis. RESULTS: A moderate kappa measure of agreement (k = 0.415) was found between cytological and histological grades with an overall concordance rate of 66.67%. The accuracy of cytological grading was higher with increasing cytological grade. Except for estrogen receptor expression, none of the other prognostic parameters have a statistically significant correlation with cytological grade. CONCLUSIONS: Tumor grading on cytology can be helpful in planning treatment, especially in resource-constrained settings. Subjective variation in assessing different parameters and non-inclusion of mitosis in this system might be the reasons behind wrong grading in some cases. Inclusion of mitosis in the scoring system can improve the accuracy of cytological grading and its importance in prognosis.

Tumour budding in invasive breast carcinoma and its correlation with histopathological prognostic parameters and hormone receptor status.

INTRODUCTION: Tumor Budding (TB) is emerging as an important sensitive indicator of aggressiveness over traditional histopathological variables such as lymph node metastasis and lymphovascular invasion because TB at the invasive front was postulated as the first step of invasion and metastasis. But the role of TB in breast carcinoma is not yet standardized. AIM: This study aims to assess the prognostic significance of TB in breast carcinoma. OBJECTIVES: To study and grade TB in invasive breast carcinoma and correlate it with known histopathological prognostic markers and hormone receptor status. MATERIALS AND METHODS: In this ambispective study, 51 cases of invasive breast carcinoma undergoing radical surgery were studied from September 2017 to September 2021. Tumor buds were defined as a single or cluster of up to four tumor cells at the invasive front of the tumor and were counted by using IHC Pancytokeratin in 200X and graded into a three-tier grading system. The correlation between TB with established histopathological parameters and hormone receptor status was studied. A Chi-square test was used and a P value < 0.05 was considered significant. RESULTS: TB was seen in all cases of invasive breast carcinoma. Grade 1 TB was seen in 37.26% (19/51) of cases and Grade 2 TB and Grade 3 TB in 31.37% (16/51) of cases each. There was a lack of significant correlation between TB with histologic grade, lymph node status, and HER2 neu. Correlation between TB with Estrogen receptor (ER), Progesterone receptor (PR), and American Joint Committee on Cancer (AJCC) Prognostic stage group was noted but it was not statistically significant. CONCLUSION: Although several studies have confirmed the prognostic value of TB in breast carcinoma, they had used several different methods of assessment. So, there is a need for a standardized method for the assessment of TB in breast carcinoma. Further standardization of TB may add its value as a prognostic factor.

Role of neonatal cerebrospinal fluid cytology in correlation to C-reactive protein, blood culture, risk factors and clinical outcomes in neonatal intensive care.

Introduction: The number of neonatal cerebrospinal fluid (CSF) samples sent from the neonatal intensive care unit (NICU) for cytologic examination is rising, warranting accurate analysis and interpretation of the same. This study was taken up to assess the usefulness of CSF cell count and cytology in NICU settings, as it can be used even in a resource-limited setting. Aim and Objective: 1) To study the prevalence of cell count and cytologic changes in CSF from NICU and assess their usefulness in correlation to C-reactive protein, CSF neutrophil percentage, blood, CSF culture, and other biochemical parameters. 2) To correlate cell counts and cytology with age, period of gestation, presence, and absence of sepsis, seizures, intracranial hemorrhage, and their clinical follow-up. Materials and Methods: A retrospective study was done on neonatal CSF samples submitted for cytology over one year (January-December 2016) in the Department of Pathology. CSF cell counts were retrieved, and cytosmears were reviewed for cellularity, cell type, proportion, and background and correlated with the biochemical, microbiological, and clinicoradiological findings. Results: A total of 213 samples were included with 140 males and 73 females with an age range of 0-28 (mean: 7.3) days. The mean CSF cell count was 5.48/cu.mm (0-90 cells/cu.mm). The most frequent cytologic finding was occasional lymphocytes or acellular CSF (63.9%). The CSF leucocyte count and protein levels showed a significant correlation with s C-reactive protein. The CSF cytology showed a significant correlation between the age of the neonate and blood neutrophil percentage (P = 0.0158). History of intracranial hemorrhage showed a significantly higher frequency of the presence of red blood cells (P = 0.0147). Conclusion: Accurate cell counts, cytology of neonatal CSF, and biochemical and microbiological workup can help diagnose and manage neonates in intensive care.

Non-Hodgkin Lymphoma of Cauda Equina: A Diagnostic Conundrum: Case Report.

Primary central nervous system lymphoma (PCNSL) is uncommon with scarce cases having involvement of the spinal cord. Cauda equina is unique in its location and shows very rare involvement by diseases pathologies. When the same occur, they pose a lot of diagnostic difficulties as the location is difficult to access with overlapping radiologic abnormalities. It is an unusual location for lymphomas to occur with only few cases reported in literature. The cauda equina lymphomas may mimic other entities which occur at that site. Histopathology is the gold standard for the same. Here, we report an unusual case of cauda equina lymphoma mimicking a myxopapillary ependymoma in a 50-year-old male.

Expression of Claudin-4 and D2-40 and their significance in prostatic adenocarcinoma.

BACKGROUND: Claudins are a clan of proteins that are the most important component of tight junctions. The claudin-4 expression has been linked to tumour cell invasion and progression in a variety of primary malignancies. Evaluation of lymphovascular density (LVD) correlates with tumour aggressiveness and may correlate with prognosis. D2-40 is a highly specific marker of lymphatic vessels. AIMS: To evaluate the claudin-4 expression in relation to LVD by D2-40 expression and with clinicopathological parameters in prostatic adenocarcinoma. SETTINGS AND DESIGN: Prospective study. MATERIALS AND METHODS: 39 cases of prostatic adenocarcinoma were taken, the D2-40 and claudin-4 immunohistochemical stains were performed and correlation was done with clinicopathological parameters. STATISTICAL ANALYSIS USED: Statistical analyses such as mean, median, standard deviation, Mann-Whitney U test, Fischer exact test, Spearman's rank-order correlation coefficient, Chi-square test and T-test were used. RESULTS: The claudin-4 expression was seen higher in cases with higher Gleason score but it was statistically non-significant (P = 0.778). The claudin-4 expression did not correlate with any clinicopathological parameters. LVD in the peritumoral area was significantly higher as compared to the intratumoral area (P = 0.005). Intratumoral LVD and perineural invasion were found to be statistically significant (P = 0.048). CONCLUSION: The claudin-4 expression may correlate with adverse prognostic parameters. Higher lymphatic vessels can be responsible for the higher metastatic potential of prostatic adenocarcinomas.

Primary lymphangioma of palatine tonsil.

Lymphangiomas are benign congenital tumors of the lymphatic system. Tonsillar lymphangiomas are extremely rare. Histopathological confirmation is essential to make the correct diagnosis. We report a case of primary lymphangioma of the left tonsil in a 17-year-old male patient who presented with difficulty in swallowing and was clinically diagnosed as a tonsillar cyst.

Neutrophil-to-lymphocyte ratio as a prognostic factor in oral squamous cell carcinoma - A single-institutional experience from a developing country.

BACKGROUND: Cell-mediated inflammatory response, neutrophils, lymphocytes and monocytes are being recognized as an important role in carcinogenesis. Neutrophil-to-lymphocyte ratio (NLR) has been used as an independent prognostic factor in varieties of cancers. NLR can be easily determined from complete blood count, and it could be considered as a simple and inexpensive prognostic marker. AIM: In this study, we evaluate the prognostic significance of NLR in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Clinical and epidemiological data of all biopsy-proven nonmetastatic OSCC treated between 2014 and 2018 were taken into consideration. Pretreatment absolute neutrophil and lymphocyte counts were used to get NLR. Using univariate and multivariate analysis, the impact of NLR on overall survival (OS) and progression-free survival (PFS) was investigated. RESULTS: A total of 50 patients of OSCC with median pretreatment NLR ratio of 2.52 were identified. Based on the median NLR as a cutoff, patients were classified into two groups, i.e., high NLR and low NLR. Elevated NLR was significantly associated with lymph node metastasis (P = 0.01). Four-year OS and PFS were significantly better for patients with low NLR when compared with high NLR group (51.4% vs. 100%, P = 0.001). Four-year PFS for high and low NLR groups was 38.8% and 87.8% (P = 0.002). Multivariate analysis confirmed that NLR is an independent prognostic factor (P = 0.003). CONCLUSION: Pretreatment NLR provides a simple, cheap and early predictor of outcome in this group of patients. However, an optimal cutoff value of NLR should be determined, for which larger sample size and prospective studies are required.

Salivary amylase crystalloids in Warthin's tumor: An aspiration cytodiagnosis.

Crystalloids may be seen in a variety of salivary gland lesions, but their presence is not common. Among various types of crystalloids, amylase crystalloids are usually found in benign lesions of the salivary gland. Here, we report a case of a 76-year-old male with swelling on the angle of the mandible left side for 15 days. Local examination showed a solitary soft-to-firm swelling of size 4.7 cm × 4.1 cm × 2.8 cm. Ultrasonography (USG) showed a well-defined cystic lesion with the solid component. Fine-needle aspiration cytology cytosmears showed predominantly mixed inflammatory cells; few epithelial cell clusters with numerous crystalloids which are rectangular to rhomboid shape with nonparallel sides. Cytological features are suggestive of benign cystic sialadenitis with amylase crystalloids. However, after 3 months of follow-up, as the swelling did not subside, excisional biopsy was done and histopathology showed features of Warthin's tumor with crystalloids. The presence of amylase crystalloids in any type of salivary gland lesion with cystic change; multiple aspirations followed by histopathological examination should be done to rule out neoplastic etiology.

Pancreatic collision tumor of ductal adenocarcinoma and neuroendocrine tumor-A rare case report.

A collision tumor is composed of two adjacent histological distinct neoplasms without the histological admixture of cell types in the same organ or tissue. It is rare in pancreas. Herein we report an unusual case of a mixed malignant neuroendocrine tumor (NET) and ductal adenocarcinoma of pancreas in a 24 year old male who presented with history abdomen pain. A clinicoradiological diagnosis of chronic calcific pancreatitis with carcinoma body of pancreas was made. Distal pancreaticosplenectomy specimen showed a grey white, nodular growth measuring 2 x 2 x 1.2 cm on the cut surface of pancreas. Histopathology revealed a composite tumor consisting of ductal and neuroendocrine origin. Immunohistochemistry showed complementary staining for CK7 in adenocarcinoma and chromogranin A in NET areas confirming a collision tumor. Accurate evaluation of the radiologic pointers, histomorphologic evaluation to recognize and quantitate the individual components, appropriate immunohistochemical evaluation and correlation is essential for diagnosis.

Angiomyofibroblastoma of the Vulva: A Rare Case Report with Brief Review of Literature.

Angiomyofibroblastoma is an unusual tumor of pelvic and vulval region. It is often diagnosed in the middle-aged women. Although benign owing to its location and morphology, it has a few benign and malignant mimics. Here, we present such a case where a 42-year-old female presented with a vulval mass.