Frozen section is not cost beneficial for the assessment of margins in oral cancer.

BACKGROUND: Routine use of frozen section (FS) is a costly procedure and sparsely available in resource poor countries. A proper cost benefit analysis may help to reduce its routine use and would empower surgeons to perform oral cancer surgeries without having FS facility. FS is performed to identify microscopic spread beyond gross disease that cannot be assessed clinically. OBJECTIVE: Our primary aim was to determine the cost benefit analysis of FS in the assessment of margins in oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Retrospective study of prospectively collected data of 1311 consecutive patients who were operated between January 2012 and October 2013. The gross and microscopic margin status of each patient was extracted from the patient's chart. The cost estimates were performed to calculate the financial burden of FS as well as expenses incurred on adjuvant treatment resulting from inadequate margins. RESULT: Microscopic spread changed the gross margin status in 5.2% (65/1237) patients. Of this entire cohort of 1237 patients, FS helped 29 (2.3%) patients to achieve tumor free margin, and it changed the adjuvant treatment plan in 9 (0.7%) patients. The cost of FS for each patient was INR 11052. The cost-benefit ratio of FS was 12:1. Gross examination alone could have identified majority of the inadequate margins. CONCLUSION: Frozen section for assessment of margin status bears poor cost-benefit ratio. Meticulous gross examination of the entire surgical specimen is sufficient to identify majority of inadequate margins.

An algorithmic approach to overcome diagnostic challenges in FNAC in large-cell poorly differentiated thyroid carcinomas.

INTRODUCTION: Poorly differentiated thyroid carcinoma (PDTC) is a distinct entity and a rare carcinoma of thyroid follicular origin with an intermediate prognosis. It is defined by the Turin criteria set in 2007. Although this entity is well known, with widely available literature on histological features, specific studies describing the cytological features of PDTC (especially the large cell type) are lacking. In this study, we describe the cytological and clinical features of PDTC showing large cells (PDTC-LC) with abundant cytoplasm. MATERIALS: Twelve cases of PDTC showing abundant cytoplasm between 2007 and 2016 were retrieved from the departmental archives and studied. RESULTS: The cases occurred predominantly in women with a mean age of 54.3 years. The mean tumor size was 4.3 cm. Fine-needle aspiration cytology (FNAC) smears showed singly scattered large cells with abundance of cytoplasm admixed with microfollicular and insular pattern. Lymph node metastasis was noted in 7 cases and distant metastasis to bone and visceral organs were also seen in 7 cases. CONCLUSIONS: Microfollicular pattern may lead to these cases being misinterpreted as a differentiated follicular neoplasm on FNAC, and the dissociated large cells may mimic Hürthle cell neoplasm. Immunocytochemistry is not helpful in this scenario, although it does resolve the diagnostic dilemma when the differential diagnoses include medullary thyroid carcinoma and metastatic tumors. It is important to identify these tumors on FNAC as this facilitates proper management.

Phosphaturic mesenchymal tumor of the nasal cavity and paranasal sinuses: A clinical curiosity presenting a diagnostic challenge.

Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated with tumor-induced osteomalacia (TIO) and elevated serum FGF-23. Common in extremities, PMT rarely occurs in sinonasal region. We report a series of sinonasal PMT diagnosed at our institute over a 6-year period. Six cases of sinonasal PMT were identified during this period, of which five presented with features of TIO. Median age of patients was 45.5 years. All six tumors were composed of stellate to spindled cells, with prominent staghorn vasculature in four cases. Typical smudgy matrix was seen in all cases, but only focally; grungy calcification was absent. Accurate diagnosis of PMTs is imperative, as complete excision leads to dramatic resolution of TIO symptoms. Lack of knowledge of this entity prevents clinicians from ordering relevant investigations. Absence of specific morphological features, like grungy calcification, and presentation at atypical locations makes the diagnosis challenging. Awareness of this entity is essential in order to suspect PMT in patients presenting with a soft tissue mass and features of TIO, however unusual the location may be.

Thyroid Mass: Metastasis from Nasopharyngeal Cancer - An Unusual Presentation.

Thyroid gland is an uncommon site of metastasis, and metastasis to the gland secondary to nasopharyngeal carcinoma is seldom seen. We were only able to identify eight reported cases in the literature. A 61-year-old man, diagnosed case of nasopharyngeal cancer-second primary ( first primary-oropharynx), was found to have a thyroid nodule on routine follow-up positron emission tomography-computed tomography (PET-CT) scan. There was no evidence of metastases at any other sites. The thyroid nodule was confirmed as metastatic carcinoma by fine needle aspiration cytology. He was treated with multimodal treatment comprising of surgery followed by reirradiation with concurrent chemotherapy. Subsequently, at the first follow-up (2 months after completion of all treatment), the patient remained asymptomatic, but the response assessment with PET-CT scan was suggestive of lung metastases with no evidence of locoregional disease. Although thyroid parenchymal metastasis is an uncommon occurrence and signifies a poor prognosis, in appropriately selected patients, aggressive therapy with reirradiation and chemotherapy may improve local control and quality of life.

Cytomorphological findings and histological correlation of papillary cystadenocarcinoma of the parotid: Not always a low-grade tumor.

Papillary cystadenocarcinoma (PCAC) is a rare salivary gland tumor characterized by a predominantly cystic growth that often exhibits intraluminal papillary growth without specific histologic features of other cystic salivary gland tumors. The preoperative cytological diagnosis can pose a diagnostic challenge as it has to be differentiated from other cystic papillary tumors such as mucoepidermoid carcinoma, papillary cystic variant of acinic cell carcinoma, and low-grade cribriform CAC. It is considered to be a low-grade malignant salivary gland tumor with an indolent biological behavior. We report a case of PCAC of the parotid in a 55-year-old male diagnosed on fine needle aspiration cytology. Although it showed mild atypia cytologically, on excision tumor showed vascular and perineural invasion with regional node metastasis indicating a wider morphologic spectrum than what is described. This prompted us to write a case report describing the cytological and histological features of this rare tumor and also discuss the diagnostic challenges.

Isolated Metastasis in Male Breast from Differentiated Thyroid Carcinoma - Oncological Curiosity. A Case Report and Review of Literature.

Papillary carcinomas are the most common thyroid malignancy accounting for approximately 80 % of thyroid cancers (Rosenbaum and McHenry Expert Rev Anticancer Ther 9:317-329, 2009). They generally manifest as solitary nodules in the thyroid with or without cervical lymphadenopathy. Distant metastases though rare, are commonly seen in lungs and bones, other rare sites are parotid, skin, brain, ovary, adrenal, kidney, Pancreas and breast. We herein present an unusual case of breast lump as an initial presentation of a well differentiated thyroid cancer in a male patient. Our case is unique since it presented with isolated breast metastasis in a male patient in the absence of primary diagnosis. This prompted us to report the case with review of literature. A brief review of literature follows.

Epidermal growth factor receptor (EGFR) gene amplification in high-grade gliomas: Western Indian tertiary cancer center experience.

BACKGROUND: EGFR gene amplification is the hallmark of primary glioblastomas; however, its frequency in patients of Indian origin remains sparsely investigated. AIMS: The aim of this study was to explore the frequency of EGFR amplification in high grade gliomas (HGGs) in Indian patients and to study its correlation with p53 protein overexpression. METHODS AND MATERIALS: 324 cases of HGGs, where EGFR gene amplification was evaluated by fluorescence in-situ hybridization formed the study group. Ratio of >2 was considered as EGFR gene amplification. Immunohistochemically, p53 overexpression was evaluated and graded as positive for strong intensity staining in more than 50% of tumour cells. RESULTS: 249 patients were male and 75 female (M: F-3.3:1); their age range was 8-91 years [paediatric glioblastoma (pGBM; 8-18yrs; n = 24)], adult HGGs [>18yrs; n = 300]}. 258 patients were having a GBM [including 31 with a GBM with oligodendroglioma component (GBM-O)], 31 with a gliosarcoma, 13 with an anaplastic astrocytoma (AA), 12 with an anaplastic oligodendroglioma (AO), and 10 with an anaplastic oligoastrocytoma (AOA). 79/233 cases (34%) with an adult GBM, (including 10/31 with a GBM-O [32.2%]), 1/31 (3.2%) with a GS and 1/10 (10%) with an AOA showed EGFR gene amplification. None of the pGBMs (n = 24) showed amplification. Amplification was seen in 19/81 (23.4%) of diffuse p53 protein positive cases and 53/143 (37%) of cases with focal or negative p53 protein expression. CONCLUSIONS: 34% of our adult GBM patients showed EGFR gene amplification. The amplification was uncommonly associated with a strong diffuse p53 protein expression.

Cytologic diagnostic approach to poorly differentiated thyroid carcinoma: a single-institution study.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a well-established technique for the preoperative evaluation of thyroid nodules because it is minimally invasive, cost-effective, quick, efficient, and safe. Various articles have discussed differences in the cytomorphology of different types of thyroid cancer. However, review articles on the cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) are scarce as PDTC are rare tumors. Although the histologic diagnostic criteria are well standardized, the cytologic diagnostic criteria are not yet standardized. This prompted us to study the cytomorphological features of PDTC and assess features of distinction from differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). METHODS: This was a retrospective study of thyroid FNAC smears from 44 PDTC cases retrieved from the database of a single tertiary cancer institute (2009-2013). Papanicolaou and Giemsa smears were evaluated for 21 cytomorphologic features. Immunocytochemistry was available for 6 cases only. RESULTS: The frequencies of cytomorphologic features in the 44 cases were as follows: hypercellularity, 84.1%; insular pattern, 79.5%; small cell size, 93.2%; high nuclear-cytoplasmic ratio, 93.2%; granular chromatin pattern, 95.45%; nuclear overlapping, 88.64%; mild pleomorphism, 86.36%; grooves/inclusions, 22.7%; binucleation/multinucleation, 9.1%; abrupt nucleomegaly, 34.1%; apoptosis, 45%; mitosis, 25%; necrosis, 34.1%; and colloid, 22.7%. CONCLUSION: A high index of suspicion is necessary for an upfront diagnosis of PDTC on FNAC. Although PDTC, DTC, and MTC have overlapping features, there are distinguishing features also. The cytologic diagnostic criteria for PDTC need to be standardized by collaborative efforts among tertiary cancer centers. A prompt diagnosis is the key feature for planning multimodality treatment.

Prospective study of ultrasound-guided fine-needle aspiration cytology and sentinel node biopsy in the staging of clinically negative T1 and T2 oral cancer.

BACKGROUND: The purpose of this study was to compare sentinel node biopsy (SNB) and ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative evaluation of the N0 neck in T1 to T2 oral cavity squamous cell carcinoma (SCC). METHODS: Fifty-one consecutive patients with T1 to T2 N0 oral cavity SCC were included in this study. Preoperative ultrasound was performed in all patients. Ultrasound-guided FNAC was performed in patients in whom the ultrasound result was reported as indeterminate or positive. SNB was done in all patients followed by elective neck dissection (END). Histopathology of END was considered as the gold standard for all statistical analysis. RESULTS: The incidence of occult metastasis was 26.4%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.4%, 100%, 100%, and 90.2% for SNB and 14.3%, 100%, 100%, and 76.5% for ultrasound-guided FNAC. CONCLUSION: Ultrasound-guided FNAC lacked sufficient accuracy to detect occult metastases. SNB is a reliable method to detect occult metastasis that has potential to replace END.

The role of squash cytology in rapid on-site adequacy checking and rapid diagnosis in image-guided gun biopsy at a tertiary cancer center.

OBJECTIVE: To evaluate the role of squash cytology in rapid on-site adequacy checking (ROSAC) of image-guided gun biopsy and to determine its diagnostic accuracy at a tertiary cancer center. STUDY DESIGN: This was a prospective study on 183 patients undergoing image-guided biopsy. Squash smears were prepared from biopsy cores and checked for adequacy by cytotechnologists. When adequate, more cores were sampled from the same area for histopathology. If inadequate, the procedure was repeated at the same sitting on a different area. The squash smears were reported by cytopathologists within 4 h after staining with conventional Papanicoloau stain. The results were compared with the final histopathology report. RESULTS: The sampling was representative in 95.6% cases with concordance for adequacy in 97.3% cases. The sensitivity, specificity, positive predictive value and negative predictive value of squash cytology for diagnosis of the lesion were 99.4, 92.7, 97.7 and 97.4%, respectively. CONCLUSIONS: Squash cytology is an ideal and cost-effective technique for ROSAC of image-guided biopsies, which ensures adequacy, avoids repeat procedures and prevents delay in diagnosis. It can be effectively performed by trained cytotechnologists in radiology clinics. Squash cytology is also a cost-effective tool offering rapid diagnosis which expedites planning of treatment.

Proteomic profile of keratins in cancer of the gingivo buccal complex: consolidating insights for clinical applications.

Keratins play a major role in several cellular functions. Each tissue type expresses a specific set of keratins. The immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. Oral cancer is the fifteenth most common cancer worldwide. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. A few recent proteomic studies have reported the identification of keratins in head and neck cancer. Majority of the studies have used tissues from the head and neck region without specifying subsites. This study reports the analysis of enriched preparations of keratins from cancer of the gingivo buccal complex (GBC) using MS, 2DE, WB, silver staining of 2DE gels and IHC. Our study reveals the absence of K4 and K13 and presence of K14, K16, and K17, in cancers of the GBC and combination of these expression patterns in the cut margins. This report also shows that K13 is glycosylated. This well characterized profile of keratins may have potential to be used in clinics. BIOLOGICAL SIGNIFICANCE: In recent years the immense potential of keratins as diagnostic and prognostic markers for different cancers is emerging. However, comprehensive information on the profile of keratins in the oral cavity is not available. Several independent reports have identified keratins using only antibody based techniques which have pitfalls due to the cross reactivity of the antibodies to this set of very homologous proteins. This study reports the analysis of enriched preparations of keratins from a subsite of the oral cavity, the gingivo buccal complex (GBC) using mass spectrometry, 2DE, western blotting, silver staining of 2DE gels and IHC. The proteomic analysis shows the absence of K4 and K13 and presence of K14, K16, and K17 in cancers of the GBC and combination of these expression patterns in the cut margins. This well characterized profile of keratins from the gingivo buccal complex provides defined markers which may have potential to be used in the clinics.

Prognostic utility of autoantibodies to α-enolase and Hsp70 for cancer of the gingivo-buccal complex using immunoproteomics.

PURPOSE: Studies from our laboratory have reported 14 tumor antigens that elicit an autoantibody response in patients with cancer of the gingivobuccal complex (GBC) In this study, utility of the autoantibody response has been evaluated for prognosis of cancer of the GBC. EXPERIMENTAL DESIGN: Autoantibody response was evaluated using immunoproteomics and the prognostic significance was assessed by Kaplan-Meier survival and multivariate analysis. RESULTS: Autoantibody response against α-enolase isoforms a, b, and c and Hsp70 was detected in 27, 53, 64, and 26% of the 78 patients, respectively. Patients positive for autoantibody response to α-ENO and Hsp70 individually and in combination, showed significantly reduced disease-free survival (DFS) compared to those who do not show autoantibody response to either of them. Further the patients, who exhibit autoantibody response to α-ENO and Hsp70 in combination with nodal involvement and/or differentiation status, have significantly lowered DFS. The relative risk of recurrence is 3.41 for patients who exhibit autoantibody response to both the antigens. CONCLUSIONS AND CLINICAL RELEVANCE: Autoantibody response against α-ENO and Hsp70 provides an additional parameter and may be utilized along with nodal involvement and differentiation status for better prognosis of cancer of GBC.

Keratins in oral cancer: necessity of mass spectrometry for validation of antibody based identifications.

Keratins are intermediate filament family proteins which are predominantly expressed in the epithelial cells. Most of the studies which evaluate the status of keratins in clinical samples of the oral cavity are based on the identification of their presence and localization by immunohistochemistry using monoclonal antibodies. It is very well known that many monoclonal/polyclonal antibodies show cross-reactivity with the other closely related or non-related proteins. This cross-reactivity might be the result of epitope similarity, but it is not always necessary. Therefore studies done with only antibody based techniques can mislead interpretation unless they are validated with additional techniques like mass-spectrometry. In this investigation we have evaluated the status of keratin 18 in cancer of buccal mucosa using 1DE, 2DE and western blotting with monoclonal antibody to keratin 18. The patterns emerging showed aberrant as well as differential expression of K18 in adjacent normal versus tumor tissue samples of buccal mucosa. Mass spectrometry analysis of the immunodetected spots however revealed that it is keratin 13. Thus this study emphasizes the necessity of validation of antibody based findings when dealing with proteins of a large family having similarity/homology in amino acid sequence.

Utility of frozen section in assessment of margins and neck node metastases in patients undergoing surgery for carcinoma of the tongue.

OBJECTIVE: The aims of this study are to evaluate the impact of frozen section in achieving adequate surgical margin and to study the accuracy of frozen section in detection of occult metastases. MATERIALS AND METHODS: This was a retrospective review of prospectively collected data of 877 patients with squamous cell carcinoma of the tongue who underwent surgery and intra-operative frozen section at our center from January 2007 to June 2010. RESULTS: Frozen section was found to have very high accuracy in assessment of margin as well nodal status. On frozen section, 2% of our patients had positive margins and 21% had close margins. Most of these underwent intra-operative revision and at final pathology, 1.2% patients had positive margins and 11% were close. Of the 651 supraomohyoid neck dissections performed, one third were found to have occult metastases on frozen section. Of those reported positive on frozen section, 68% got additional removal of level 4 ± 5. Interestingly, 11% of these additionally removed nodes harbored metastases at final pathology. However, 7% of the patients were wrongly declared negative on frozen section. Tumor thickness was predictor of margin positivity as well as occult metastases. Tumor volume did not correlate with occult metastases or margin status. CONCLUSIONS: Frozen section nearly halves the rates of positive margin and close margins which certainly translates into clinical benefits. The incidence of 11% positive nodes in the frozen section guided removal of lower levels is an important finding in our study that questions the ability of supraomohyoid neck dissection to completely eradicate the nodal burden in such patients.

Minor salivary gland tumors of the sinonasal region: results of a retrospective analysis with review of literature.

BACKGROUND: Minor salivary gland tumors of the sinonasal region are rare. Minor salivary gland tumors of this region behave differently from other subsites in the head and neck. The objective of our study was to analyze the survival and prognostic factors in patients with minor salivary gland tumors of the sinonasal region. METHODS: We carried out a retrospective review of patients with minor salivary gland tumors of the sinonasal region. All slides were reviewed by an independent pathologist. Survival was analyzed using the Kaplan-Meier method and Cox multivariate regression to identify prognostic factors. RESULTS: In all, 163 patients were identified from our registry. The 5-year disease-free and overall survival rates were 48.3% and 83.3%, respectively. Tumor grade, nodal status, and adjuvant radiotherapy were significant predictors of disease-free survival (DFS), on multivariate analysis. CONCLUSIONS: Minor salivary gland tumors have a good overall survival in spite of high recurrence rates. Tumor grade, nodal status, and adjuvant radiotherapy are independent predictors of DFS.

A study of pathologic risk factors in postchemoreduced, enucleated specimens of advanced retinoblastomas in a developing country.

CONTEXT: Advanced cases of retinoblastoma are treated with chemoreduction followed by enucleation. Further adjuvant therapy is recommended in patients with known pathologic risk factors (PRFs). OBJECTIVES: To determine the PRFs in enucleated specimens after chemoreduction and their association for adverse events of recurrence, metastasis, or death. DESIGN: This was a retrospective study of 77 enucleation specimens from patients treated between January 2000 and September 2008 with prior chemoreduction that were accessioned in the pathology department of a tertiary referral cancer center with an average follow-up of 24 months. Various PRFs were noted and their association with the development of an adverse event was recorded. RESULTS: Of 77 patients, (male to female ratio, 51∶26), the incidence of overall PRF was 51.9%, and retrolaminar optic nerve invasion (32.5%), optic nerve cut margin (12.9%), massive choroidal invasion (26%), scleral invasion (23.4%), vitreous seedings (44.2%), and anterior segment invasion (20.8%). Undifferentiated tumor (>60%) was seen in 60.3% of cases (41 of 68 patients with differentiation available). Adverse event occurred in 18 of 72 patients with available follow-up (25%). Retrolaminar optic nerve invasion, optic nerve cut margin involvement, and scleral invasion were independent prognostic factors predicting the occurrence of an adverse event. Undifferentiated tumor (>60%) was a significant risk factor in univariate analysis, which is the unique feature in this study. CONCLUSIONS: Classic PRF with the addition of a predominant presence from the undifferentiated component were associated with adverse outcomes in retinoblastoma treated with anterior chemotherapy. The latter may represent chemoresistant clones and more intensive adjuvant chemotherapy may be warranted in these patients.

Case report of renal cell carcinoma diagnosed in voided urine confirmed by CD10 immunocytochemistry.

BACKGROUND: Preoperative diagnosis of renal cell carcinoma (RCC) by exfoliative urine cytology is difficult, as infiltration of RCC into the pelvicalyceal system is uncommon. The exfoliation of RCC cells in urine is a rare phenomenon and when it does occur, it is likely to be missed. Cytologic examination of the urine coupled with ancillary immunocytochemistry can clinch the diagnosis leading to appropriate clinical management. CASE: A 50-year-old man presented with complaints of hematuria and abdominal pain of 6 months' duration. Ultrasonographic examination of the abdomen and pelvis showed a well-defined mass lesion in the upper pole of the left kidney, suggestive of neoplastic etiology. In the given clinical context of renal mass, urine cytology was suggestive of RCC and biopsy confirmation was suggested. One cytology smear subjected to immunocytochemistry with anti-CD10 antibody which showed strong diffuse cytoplasmic positivity in these cells confirmed the diagnosis of RCC. Subsequently, fine needle aspiration cytology of the kidney mass was reported as RCC. CONCLUSIONS: RCC has distinct cytologic features that facilitate a diagnosis in urine in an appropriate clinical and radiological context. Their recognition in the urine smear is important to avoid costly and invasive modalities like image-guided needle biopsy.

Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 51 cases in a tertiary cancer center.

OBJECTIVE: To analyze the importance of unique cytoarchitectural patterns and the immunohistochemical profile in the diagnosis of myoepithelial carcinomas. DESIGN: Retrospective case analysis. SETTING: Tertiary cancer center. PATIENTS: A total of 51 patients with myoepithelial-rich carcinomas diagnosed over a 14-year period were studied for demographic data and tumor histologic characteristics and biologic behavior. MAIN OUTCOME MEASURES: We analyzed various histopathologic parameters and an immunohistochemical profile consisting of pan-cytokeratin (Pan-CK), epithelial membrane antigen (EMA), CD10, smooth-muscle actin (SMA), S-100 protein, p63, calponin, and carcinoembryonic antigen (CEA). RESULTS: The parotid gland (n = 15) and the palate (n = 15) were common sites involved. The cell types encountered were epithelioid, stellate, plasmacytoid, spindle, clear, and mixed with myxoid, hyaline, or myxohyaline stroma. Immunohistochemical analysis revealed vimentin (100%), CK (74%), EMA (27%), CD10 (62%), SMA (35%), S-100 protein (82%), p63 (28%), and calponin (98%) positivity and CEA (100%) negativity. Cervical node dissection was performed in 17 cases: 7 showed nodal metastasis, 2 with pure spindle-cell morphologic characteristics and 3 with spindle cells mixed with other cells. Distant metastasis was noted in 3 of these 7 cases: 2 of these 3 cases showed spindle-cell morphologic characteristics. CONCLUSIONS: Myoepithelial carcinomas showed varied cell types and patterns leading to a wide range of differential diagnoses. Immunohistochemical analysis helped determine the diagnosis. Spindle morphologic characteristics were observed with nodal and distant metastasis.