Spatiotemporal pattern of thyroid cancer incidence in South Kerala: A population-based study.

Background: Thyroid cancer (TC) is the most common endocrine cancer and has been increasing over the past decades worldwide. A notable finding is that Kerala's capital Thiruvananthapuram ranks the first among men and the second highest among women in the incidence of TC in India. Reasons for this increase have not been established. Objectives: Here, we investigated the spatiotemporal pattern of TC incidence in Thiruvananthapuram. Materials and Methods: TC incidence data (n = 1937) of Population Based Cancer Registry Thiruvananthapuram, Kerala, India, between 2012 and 2016, were analyzed for identifying geographical patterns by spatial methods, temporal methods for studying spatial variation in TC incidence, distribution of age, gender, and histology in lowland (coastal), midland, and highland. Results: Spatial clustering of TC incidence was identified consistently near the coastal region based on all geospatial analyses. 56.9%, 23.9%, and 19.2% of TC cases were observed in the coastal, midland, and highland areas, respectively. A significant clustered pattern of TC incidence was revealed by Moran's index I (0.49), high-high clusters by local Moran's, hotspot by Getis-Ord-Gi* (P < 0.05), point pattern analysis by nearest neighbor ratio and kernel density estimation. The relative risk of the significant cluster was obtained as 1.60 (95% confidence interval: 1.03-1.84) by SaTScan analysis. Conclusion: This study identified spatial variations in the pattern of TC cases with significant clusters near the coastal region of Thiruvananthapuram. This would help to pinpoint the high-risk geographical areas of TC and for more effective cancer control programs.

Novel mutations and expression alterations in SMAD3/TGFBR2 genes in oral carcinoma correlate with poor prognosis.

Transforming growth factor beta (TGF-ß) signaling is a pleiotropic cytokine signaling pathway, which controls cellular activities ranging from embryogenesis to apoptosis. Although many molecular alterations in this pathway have been described in cancers, the central point of concern, that is how these alterations influence the treatment outcome, has been addressed to a lesser extent. In this study, we have characterized the alterations of TGF-ß-SMAD signaling in 97 oral squamous cell carcinoma (OSCC) samples and assessed the association between these alterations and the outcome of the treatment. Genomic level alteration analysis using reverse transcriptase polymerase chain reaction-single-strand conformation polymorphism/sequencing revealed that there were 25% samples harboring genomic level alterations in this pathway. Altogether, 21% samples showed TGFBR2 mutations, whereas three cases were found to harbor novel SMAD3 mutations. Notably, 14 out of 24 TGFBR2 mutations are of one type (c.*6C>A), which supplemented complementarity for hsa-miR-3189-5p. These samples showed significantly low TGFBR2 transcript levels (P = 0.026). In addition, transcript level studies using quantitative real-time PCR revealed a strong association between low TGFBR2 transcript levels and poor disease-free survival (P = 0.028) as well as poor overall survival (P = 0.013). In brief, our results showed that oral cancers with TGFBR2 downregulation comprise a different group with more aggressive nature. These results suggest that in OSCCs, TGFBR2 transcript levels may be developed as a promising prognostic biomarker. Furthermore, for the first time, this study reports SMAD3 mutations in oral carcinoma.

Initial presentation of hepatocellular carcinoma as pharyngeal mass mimicking advanced hypopharyngeal carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of patients with HCC and indicates a dismal prognosis. The head and neck region is an extremely uncommon site of metastatic HCC. Extrahepatic metastasis at first presentation, although uncommon, indicates advanced disease with a poor prognosis. Herein, we present the case of a 68-year-old male patient with a neck mass. Clinical examination and initial radiology were suggestive of an advanced primary pharyngeal malignancy. Biopsy showed neoplasm with large polygonal cells with clear/granular cytoplasm. The neoplastic cells showed positivity for Hep Par1, CD10, and CEA. A diagnosis of metastatic HCC was given. Subsequently, serum alpha-fetoprotein level was found to be markedly elevated and further imaging showed multiple mass lesions in the liver. It is necessary to recognize that the pharyngeal region is a potential site of HCC metastasis. Accurate diagnosis and risk stratification can help in avoiding unnecessary costs and delay in treatment.

Ewing's sarcoma in adolescents and adults - 10-year experience from a tertiary cancer center in India.

BACKGROUND: Ewing's sarcoma (EWS) is an aggressive small round cell tumor, affecting bone and soft tissues and is mostly seen in childhood and second decade of life. EWS accounts for 10-12% of bone tumors in more than 15 years age group and is even rarer after 40 years of age. MATERIALS AND METHODS: This retrospective analysis was conducted among patients aged more than 15 years with histologically proven EWS. RESULTS: Among 240 cases of EWS treated at our center during 2001-2010, 130 (54%) were more than 15 years of age. The median age was 20 years with a male: female ratio of 2.4:1. Ninety percent had skeletal EWS, 10% had extra skeletal EWS, and 37% patients were metastatic at presentation. Eighty-two received curative treatment with chemotherapy (vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide (VAC/IE)) along with local treatment, radiotherapy (RT) in 61, surgery alone in seven, and RT plus surgery in 14. Two- and 5-year overall survival (OS) was 43.3% and 25.5%, respectively, for the entire series. The OS for the non-metastatic group was 63.2% at 2 years and 36.5% at 5 years, and the progression free survival was 53.7% at 2 years and 37.8% at 5 years. High lactate dehydrogenase was found to be a significant poor prognostic factor (P = 0.001). Median OS for localized central EWS was 49.2 months and that for peripheral EWS was 24 months. Patients more than 20 years of age with non-metastatic disease had better OS compared to those with 15-20 years of age. CONCLUSION: Treatment of EWS requires a multidisciplinary approach with radical surgery and/or radiation to control local disease and multiagent chemotherapy to control systemic disease. Long-term follow-up is essential because of disease relapse and treatment-related complications.

Identification of salivary metabolic biomarker signatures for oral tongue squamous cell carcinoma.

OBJECTIVE: To identify the salivary metabolites associated with squamous cell carcinoma of the tongue to develop easy and non-invasive potential biomarkers for disease diagnosis. DESIGN: Initially, the study utilized untargeted metabolomics to analyze 20 samples of tongue squamous cell carcinoma and 10 control samples. The objective was to determine the salivary metabolites that exhibited differential expression in tongue squamous cell carcinoma. Then the selected metabolites were validated using targeted metabolomics in saliva samples of 100 patients diagnosed with squamous cell carcinoma of the tongue, as well as 30 healthy control individuals. RESULTS: From the analysis of untargeted metabolomics, 10 metabolites were selected as potential biomarkers. In the subsequent targeted metabolomics study on these selected metabolites, it was observed that N-Acetyl-D-glucosamine, L-Pipecolic acid, L-Carnitine, Phosphorylcholine, and Deoxyguanosine exhibited significant differences. The receiver operating characteristic curve analysis indicates a combination of three important metabolites such as N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine provided the best prediction with an area under the curve of 0.901. CONCLUSIONS: The present result reveals that the N-Acetyl-D-glucosamine, L-Pipecolic acid and L-Carnitine are the signature diagnostic biomarkers for oral tongue squamous cell carcinoma. These findings can be used to develop a rapid and non-invasive method for disease monitoring and prognosis in oral tongue cancer.

The Milan system for reporting salivary gland cytopathology - Assessment of utility and the risk of malignancy.

BACKGROUND: Cytological diagnosis of salivary gland lesions furnishes several challenges to pathologists and clinicians owing to their diverse morphology and varying reporting terminology. The Milan system for reporting salivary gland cytopathology was proposed to overcome these defects. The aim of this study was to grade histopathologically diagnosed cases of salivary gland pathology using Milan system and to correlate Milan system with histopathological diagnosis. The study aims to assess the utility of the Milan system and the risk of malignancy in each category. MATERIALS AND METHODS: This is a retrospective study of 4 years duration. All the cases of salivary gland pathology with fine-needle aspiration cytology findings from January 2015 to December 2018 were retrieved and classified according to the Milan system. Histopathology follow-up of these cases were reviewed from the archives, and risk of malignancy was calculated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated using histopathological diagnosis as the gold standard. RESULTS: Cytology slides of 151 cases were reviewed, and the Milan system was applied. Histopathology follow-up was obtained in 94 cases (attrition rate = 37.74%). The percentage of cases in each category were as follows: nondiagnostic = 9.27%, nonneoplastic = 4.64%, atypia of undetermined significance = 3.97%, benign neoplasm = 23.84%, neoplasm of uncertain malignant potential = 8.61%, suspicious for malignancy = 11.92%, and malignant = 37.75%. Sensitivity, specificity, positive predictive value, and negative predictive value of the Milan system were 94.20%, 96.00%, 98.48%, and 85.71%, respectively. CONCLUSION: The Milan system has high sensitivity and specificity in comparison with histopathology. This system proves helpful to the pathologist as well as the clinician in achieving uniformity of reporting terminology by classifying salivary gland lesions into subcategories with prognostic relevance.

Immunohistochemical expression of PD-L1 and MDR1 in breast tumors: association with clinico-pathological parameters and treatment outcome.

Antitumor immune evasion is a hallmark for the development and progression of cancer. Tumor cells adopt various mechanisms to escape the host immune system recognition. One such mechanism is the over expression of programmed death ligand (PD-L1), a negative T cell regulatory molecule. Because PD-L1 overexpression causes resistance to chemotherapeutic response in many cancers, herein we explored the relationship between PD-L1 and multidrug resistance protein MDR1 in breast cancer. Immunohistochemical evaluation of PD-L1 and MDR1 proteins in 194 breast cancer tissue samples were carried out. The relationship between PD-L1 and MDR1 expression on cancer cells with clinicopathological factors and prognosis was investigated. IHC showed a significant correlation between PD-L1 and MDR1 expression on tumor cells. Increased PD-L1 expression was also associated with lymph node status and tumor grade of the patient. Our results also revealed that the expression of PD-L1 and MDR1 was higher in TNBC subtype compared to other breast cancer subtypes. Therefore, a better understanding of the molecular mechanism through which PD-1/PD-L1 pathway contribute to the chemoresistance might bring forth the prognostic significance of PD-L1 and selection of patients who may benefit from immunotherapy.

The gray zone squamous lesions: ASC-US / ASC-H.

The unequivocal and easily recognizable entities of LSIL and HSIL pose no diagnostic problems for a trained eye. However, when the defining morphologic features are either qualitatively or quantitatively insufficient, it is then that the borderline category of "Atypical Squamous cells" (ASC) may have to be used. Scant and suboptimal preparations (mainly in conventional smears) are the common causes that hinder confident decision-making. The binary classification of the ASC category has been retained in The Bethesda System 2014. It includes ASC of undetermined significance (ASC-US) when the atypia is seen in mature cells and ASC-cannot rule out high-grade lesion (ASC-H) when borderline changes are seen in less mature, smaller metaplastic cells or smaller basaloid cells. There are many criticisms of the ASC category. The major one is its subjective and inconsistent applications and the low interobserver and intraobserver reproducibility. However, studies have shown that if we eliminate ASC-US, the LSIL rate will increase. If ASC-H is eliminated, the chances of detecting true lesions are reduced. Hence, there are strong reasons to retain the ASC category. The usual problems leading to the categorization of such cells as atypical are hyperchromasia beyond that acceptable as reactive change; abnormal chromatin pattern that is not overt dyskaryosis; minor variations in nuclear shape; and membrane outlines. Qualifying the atypical cells precisely in one of the categories has bearing on the clinical management and follow-up of the patient. Surveillance of women under the ASC-US category is either by repeat smear at 6 months and 1 year or by reflex human papillomaviruses DNA testing. Women with a Pap smear interpretation of ASC-H are directed to undergo immediate colposcopy. This article describes in detail the morphologic features of the ASC category, doubts about the correct interpretation of the chromatin pattern of the cells in question, and the differential diagnosis between normal, reactive, or inflammatory conditions, and LSIL/HSIL.

Limited utility of intraoperative frozen sections in primary malignant tumours involving long bones - A multicenter analysis of 475 cases.

BACKGROUND: In the surgical removal of primary malignant tumours involving long bones, intraoperative frozen sections are used to ascertain the adequacy of tumour clearance. However, with the improved imaging modalities that provide better foreknowledge of the tumour extent, it is possible that the arduous task of performing frozen sections can be safely avoided. This would not only save procedural time but also reduce hospital costs. Presently, there are no clear guidelines regarding the modality required intraoperatively to assess tumour margins in these cases. Hence, in our retrospective multicentre analysis, we aimed at determining the usefulness of frozen sections in these cases. MATERIALS AND METHODS: Our study is a 3-centre retrospective analysis of 475 cases (513 tumour margins) involving the surgical removal of primary malignancies of long bones. The preoperative Magnetic Resonance Imaging (MRI) and intraoperative assessment of the split specimen of the tumours were used to determine marginal clearance in all the cases in addition to frozen sections in 410 of the margins. RESULTS: Of the 410 frozen sections (centres 1 and 2), only one margin was reported positive and another reported indeterminate. All other margins were reported negative. In the first case, a 2 cm additional bone-cut was done whereas in the second, the procedure was proceeded based on the intraoperative agreement without re-cutting the margin. All these margins were negative in the final histopathology. In addition, in Centre 3, where frozen sections were not available, all the 103 cases had negative margins in the final histopathology. CONCLUSION: In primary malignancies involving long bones, intraoperative decision making with the aid of MRI has been sufficiently accurate in identifying the required tumour margin without frozen sections. Hence, the added time and cost incurred by doing an additional procedure can be avoided in these cases.

Mesenchymal Chondrosarcoma-A Retrospective study.

INTRODUCTION: Mesenchymal chondrosarcoma is a rare high grade malignant neoplasm that accounts for 3-10% of all chondrosarcomas. Histopathologically, it shows biphasic population composed of small round to ovoid with occasional spindle cells and islands of well differentiated cartilage. The study aimed at retrospectively analysing the clinical, pathological, radiological features of these cases in our institution. MATERIALS AND METHODS: This is a retrospective descriptional study. All the cases of mesenchymal chondrosarcomas were retrieved from our archives of pathology over a period of 10 years .The demographic details including the age, clinical presentation including skeletal/extraskeletal along with radiology were noted for all these cases. The treatment details along with the follow up of the patients were archived from the medical records. RESULTS: A total of 13 cases of mesenchymal chondrosarcoma were retrieved for our study. The mean age of presentation was 33 years with a slight male predilection. Extra skeletal soft tissue origin was noted in 3 of our cases (3/13), one case in forearm, another in pelvis. The third case was intracranial origin which presented as a dural based parieto-occipital mass and rest all had bony origin .The radiological and clinical correlation was done for all these cases. CONCLUSION: Mesenchymal chondrosarcoma presents multiple diagnostic challenges, most common include inadequate biopsy samples which may result in errors in diagnosis, namely with small blue round cell tumours .A better understanding of this entity may help the pathologists in conferring an accurate diagnosis to the clinicians.

Grossing and reporting of a soft tissue tumor specimen in surgical pathology: Rationale, current evidence, and recommendations.

Soft tissue tumors, including sarcomas are complex and diagnostically challenging tumors. This is as a result of their heterogeneity and overlapping clinicopathological, immunohistochemical and also molecular features, the latter to some extent. More than 80 types of sarcoma have been described. Current management, which is best offered at centers with active multidisciplinary care, is based on balancing oncologic and functional outcomes in such cases. This has transcended into the types of specimens received for grossing these rather uncommon tumors. Over the years, diagnostic specimens have reduced in their sizes from, open biopsies to core needle biopsies. These specimens need to be adequately and judiciously triaged for ancillary techniques, such as molecular testing. Conservative surgeries have led to resected specimens for marginal assessment. Lately, post neoadjuvant (chemotherapy or radiation therapy)-treated resection specimens of soft tissue sarcomas are being submitted for surgical pathology reporting. This article focuses on the grossing of soft tissue tumors, including sarcomas, in terms of types of specimens, grossing techniques including rationale, tissue triage, reporting, and recommendations from the surgical pathologists actively engaged in reporting musculoskeletal tumors, based on current evidence.

MiRNA expression profiling and emergence of new prognostic signature for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancers, is associated with high recurrence, metastasis, low long-term survival rates and poor treatment outcome. As deregulated miRNA expression plays a crucial role in malignant transformation and cancer progression, the present study is aimed at profiling the miRNA expression pattern in OSCC and developing a new miRNA prognostic signature for oral cancer. MiRNA expression profiling was performed using MiRNA microarray in 30 tumor and 18 normal samples. MiRNA signature obtained was validated with quantitative real time PCR (qRT-PCR) in 144 tumor and 36 normal samples. The potential targets, clinical implications and prognostic value of the miRNA signature were elucidated by various bioinformatics and statistical analyses. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were validated by qRT-PCR. In silico analysis revealed the signature miRNAs to be involved in various cancer associated pathways. Up-regulation of miR-196a, miR-21, miR-1237 and downregulation of miR-204, miR-144 was associated with poor prognosis of OSCC patients. The mir-196a/miR-204 expression ratio emerged as best predictor for disease recurrence and patient survival. Altogether, our study identified a miRNA signature for OSCC with prognostic significance.

Grossing and reporting of bone tumor specimens in surgical oncology: Rationale with current evidence and recent updates.

Primary bone tumors, including sarcomas, are rare tumors and require a multidisciplinary approach, including inputs from a radiologist, pathologist, medical oncologist, and surgical and radiation oncologist, for optimal management. Over the years, there has been a paradigm shift toward the treatment of bone sarcomas, from radical resections to conservative surgical procedures, to achieve improved clinical and functional outcomes. This has led to receiving and processing various types of specimens in orthopedic oncopathology. Grossing and reporting of bone tumors require expertise. This review focuses upon the types of biopsies, grossing techniques of various specimens in orthopedic oncology and reporting, with rationale and recommendations from pathologists, actively involved in reporting and pursuing a special interest in bone tumors, based on current evidence. Furthermore, there is a section on some of the updates in the diagnosis of bone tumors, based on the recent fifth edition of the World Health Organization classification of tumors of soft tissues and bone.

Pediatric Primary Ovarian Angiosarcoma: From Rarity to a Realization.

BACKGROUND: Angiosarcoma is an uncommon high-grade sarcoma in children. Visceral angiosarcoma involving the ovary is extremely rare. Because of the lack of recurrent cytogenetic alterations, histopathological identification of this uncommon tumor in unusual sites like the ovary demands pathologic expertise. Complete surgical resection and radiotherapy are the chief treatment modalities determining survival, with chemotherapy contributing a minor role. CASE: We discuss a 11-year-old prepubertal girl who presented with primary angiosarcoma of the ovary. SUMMARY AND CONCLUSION: Early realization of such exceptional presentations of these tumors is needed to achieve the best treatment outcome.

Multiple cardiac metastases from Ewing's sarcoma.

Ewing's sarcoma commonly arises from bone and sometimes from extraskeletal soft tissues. It commonly metastasizes to the lungs, bone, bone marrow and brain. Cardiac metastasis is extremely uncommon. The present report discusses a case of Ewing's sarcoma metastasizing to the heart at the time of initial presentation.

Odontogenic ghost cell carcinoma with pulmonary metastasis.

Odontogenic ghost cell carcinoma (OGCC) is an exceptionally rare malignant odontogenic epithelial tumor. It is characterized by ameloblastic-like islands of epithelial cells with aberrant keratinization in the form of ghost cells with varying amounts of dysplastic dentin. Malignant histological characteristics include infiltration, cellular pleomorphism, numerous mitosis and necrosis. Its biological behavior varies from slow-growing locally invasive lesions to rapidly growing highly aggressive tumors. OGCC metastasizing to distant sites is extremely rare. Only three cases of metastasis have been reported in literature. We are reporting the case of a 54-year-old male patient who presented with tender swelling in the malar region. Histopathological examination revealed OGCC and he received postoperative radiotherapy. Two years later, he presented with a lung mass. Biopsy from the lung lesion showed the same morphology as that of maxillary tumor with scattered ghost cells. This case points to the aggressive behavior of OGCC and its metastatic potential. It also highlights the need for long-term follow-up of these patients.

Meningioma presenting as temporal region swelling: Diagnosis by cytopathology and immunohistochemical confirmation on cell block preparation.

Meningiomas are common intracranial neoplasms. Meningomas are rarely subjected to fine-needle aspiration (FNA) studies. However, intraoperative squash preparations are commonly done. FNA of meningiomas are usually performed incidentally for cases with a clinical suspicion of some other disease such as metastatic carcinoma. We are reporting two cases, which were referred to our center with a diagnosis of metastatic carcinoma on FNA from swelling of the temporal region. We are discussing the characteristic cytomorphological features, which help in diagnosing meningiomas, the common cytological differentials, and the utility of immunohistochemistry (IHC) on cell block preparations in confirming the diagnosis, especially when there is a clinical differential diagnosis.

Malignant melanoma of breast: a unique case with diagnostic dilemmas.

Melanomas arising in the skin, mucous membranes, and eye are encountered commonly than melanomas involving the breast. Melanomas in the breast are usually metastatic. Primary melanoma of the breast is extremely rare. We report a case of malignant melanoma of breast (primary/metastatic) that presented as a breast lump in a patient with no detectable cutaneous, mucosal or ocular lesion and who is a known case of squamous cell carcinoma of the oral cavity and had relapsed twice. The unexpected challenges faced during the diagnosis prompted us to report this case.

Solitary plasmacytoma of the metacarpal bone in an adolescent.

Solitary plasmacytoma of the bone (SPB) is a plasma cell neoplasm that usually presents as a lytic lesion mainly localized within the axial skeleton. The occurrence of SPB in young individuals is exceedingly rare, but has been sporadically reported before. We report a case of SPB involving metacarpal bone in a 16-year-old male with a prior history of trauma at the same site.