Poorly-differentiated Squamous Cell Carcinoma Research Articles

Evaluation of Serum β2-Microglobulin Levels in Histologically Diagnosed Oral Squamous Cell Carcinoma Patients

Introduction: Oral cancer presents challenging and unresolved problems for the human population, accounting for as much as 30-40% of all carcinomas in India. The current research focuses on the use of the tumour marker β2-microglobulin as a surrogate marker in patients with Oral Squamous Cell Carcinoma (OSCC) for early detection of cancer. Aim: To evaluate the level of serum β2-microglobulin in histologically diagnosed OSCC patients and compare it with age- and sex-matched healthy controls. Materials and Methods: This was a cross-sectional study conducted in the Department of Pathology at SN Medical College, Agra, over a period of one year and six months. The study included 50 histologically diagnosed OSCC cases and 40 age- and sex-matched healthy controls. Blood samples were taken from the healthy controls and OSCC patients, and the level of serum β2-microglobulin was measured using Enzyme Linked Immunosorbent Assay (ELISA). Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 11. Z test and ANOVA test were used to compare various parameters. A p-value of <0.05 was considered significant. Results: In the 50 cases of OSCC, the mean±SD of serum β2-microglobulin was 2.99±0.85 μg/mL, while in the healthy controls, it was 1.30±0.10 μg/mL, with a p-value <0.001, which was statistically significant. The mean±SD of serum β2-microglobulin in cases of Well Differentiated Squamous Cell Carcinoma (WDSCC) was 2.40±1.59 μg/mL, whereas it was 3.09±1.52 μg/mL in Moderately Differentiated Squamous Cell Carcinoma (MDSCC) and 3.46±0.03 μg/mL in Poorly Differentiated Squamous Cell Carcinoma (PDSCC), with a p-value of <0.05, which was statistically significant. Increased levels of serum β2-microglobulin were observed among all cases of OSCC. Loss of differentiation in Squamous Cell Carcinoma (SCC) was associated with an increase in levels of serum β2- microglobulin. Conclusion: Due to its minimally invasive nature and quick availability of results, serum β2-microglobulin can be used for diagnosis of OSCC. Therefore, it is recommended to monitor levels of serum β2-microglobulin in patients with OSCC.

Carcinosarcoma: a rare sinonasal malignancy with atypical behaviour

Carcinosarcoma is an extremely rare neoplasm in the nasal cavity and in the paranasal sinus, with rapid growth and extensive local destruction. We report a case of a 61-year-old man with progressive left-side nasal obstruction and epiphora for six months. Imaging showed a massive mass lesion, mainly located in the left nasal cavity and ethmoid sinus, with no intracranial or orbital extension. Biopsy of the nasal mass revealed a poorly-differentiated squamous cell carcinoma associated with sarcomatous elements. Patient underwent an endoscopic transnasal resection. Definitive histopathologic analysis revealed a carcinosarcoma. Postoperative radiotherapy was, then, performed. After five years of follow-up, there is no evidence of tumor recurrence. This report highlights that even though despite the lack of optimal treatment protocol, long term disease control can be achieved through endoscopic transnasal resection complemented with radiotherapy.

Immunohistochemical evaluation of superficial and invasive front of oral squamous cell carcinoma using epithelial membrane antigen as a marker.

Epithelial membrane antigen (EMA) has been used as a marker for the expression of tumour margins in various glandular neoplastic lesions. Histopathologically, oral squamous cell carcinoma (OSCC) may exhibit several features within the same tumour cells, portraying that these cells at the invasive margins commonly display certain features that differ from those of the superficial part of the tumour. To identify and study the invasive tumour front and also to recognise any micrometastases in an OSCC lesion. A retrospective study of 30 OSCC cases with superficial and most invasive parts were sectioned at 4 μm. Routine H&E staining and immunohistochemical staining with mouse antihuman EMA were done. The OSCC cases were graded into well differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (MDSCC) and poorly differentiated squamous cell carcinoma (PDSCC). The EMA-stained slides were observed and analysed under higher magnification to identify the individual EMA-stained cells. Analysis of Variance (ANOVA) analysis revealed that when comparing the superficial and invasive fronts of OSCC, it was evident that the P values were significant across the groups. In WDSCC, positive predictive value was 70.6% and sensitivity was 100% when the same slide was analysed for large and small islands to individual cells in an EMA-stained section, while MDSCC and PDSCC showed both sensitivity and positive predictive value to be 100%. EMA could be considered a useful prognostic marker for describing the nature of the neoplastic epithelium as well as recognising the typical anaplastic cells in cases of OSCC.

MUC4 Expression in Oral Dysplastic Epithelium and Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

MUCIN4 (MUC4) glycosylation is linked to the oncogenesis and progression of a neoplastic process. It can suggest information pertaining to tumor progression, management and its natural properties. Thus, MUC4 can play a pivotal role in prognostic diagnosis. This study aimed to analyze the MUC4 expression in oral cell squamous carcinoma and oral dysplastic epithelium. The research included 45 samples of oral epithelial dysplasia (OED) and 45 cases of oral squamous cell carcinoma (OSCC). In order to carry out the investigation, tissue blocks of previously diagnosed cases of OED and OSCC were retrieved from the relevant archives. Forty-five OED cases were categorized into three group's mild, moderate and severe dysplasia, with 15 cases in each respective category. Forty-five OSCC cases were categorized into three groups: well differentiated, moderately differentiated, and poorly differentiated OSCC with 15 cases in each respective category. Ten tissue biopsies of normal oral mucosa were obtained from subjects in the control group. The chi-square test and one-way ANOVA were used for statistical analysis. There was an absence of MUC4 expression in normal mucosa, whereas the OED and OSCC groups had a significant amount of observable variance. Within the OED category of cases, a consistent progression from mild to severe dysplasia was seen in terms of the staining pattern. Cases with severe dysplasia displayed a staining pattern that covered the complete thickness of the tissue in the epithelium. Expression of MUC4 was shown to be lower in moderate differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC) as compared to well differentiated squamous cell carcinoma (WDSCC). It showed decreasing pattern across all grades of OSCC. In WDSCC, an intense highest staining response was noticed, particularly among the cells that are highly differentiated and take the form of a honeycomb pattern. Analysis of the expression profile of MUC4 and the aberrant expression of this gene in OSCC suggests that it may serve as a useful diagnostic marker. Therefore, it is possible to draw the conclusion that MUC4 plays a very significant part in the pathogenesis of OSCC and also acts as a marker that may be taken into consideration for the accurate diagnosis of OED and OSCC.

Epithelial-Mesenchymal Transition Marker Brachyury Is Not Expressed in Spindle Cell Carcinoma of the Head & Neck

Introduction. Epithelial-mesenchymal transition (EMT) is a complex biologic process by which epithelial cells lose their cytomorphologic characteristics and assume the phenotype of mesenchymal cells. EMT is essential to normal human embryogenesis, and also occurs in wound healing, tissue repair and cancer progression. Acquisition of a mesenchymal phenotype via EMT enhances the migratory capacity of carcinoma cells, increasing their metastatic capability and worsening prognosis for patients. One emerging marker of EMT is brachyury, a T-box transcription factor protein. Recent studies have demonstrated upregulation of brachyury in several carcinoma types, includ- ing squamous cell carcinoma (SCC). Spindle cell carcinoma (SpCC) is a variant of SCC in which cancer cells have a predominantly spindled phenotype. Whether brachyury is expressed in SpCC and contributes to this pheno- typic change is not clear. Objective.To examine brachyury expression by immunohistochemistry in SpCC of the head & neck, hypothesizing that brachyury expression is increased in SpCC, as compared with other forms of SCC. Methods.Immunohistochemical staining for brachyury was performed on 20 head and neck carcinoma cases per group in each of four groups: SpCC; moderately- to well-differentiated SCC; moderately- to poorly-differentiated SCC; and verrucous carcinoma (VC). Uninflamed fibroma was the negative control; and human chordoma, along with a 14.5-day-old mouse embryo, were positive controls. Evaluation of brachyury reactivity was completed by light microscopy. Results.Brachyury expression was not seen in any of the experimental groups. Nuclear reactiv- ity was present in both positive controls, including within chordoma cells, and within the nucleus pulposus of the mouse embryo. Conclusions.Brachyury does not appear to be involved in the cytomorphologic changes present in SpCC, nor is it expressed in any head & neck SCC variants. Our results are contrary to those found in previous reports. This result supports the hypothesis that an alternate mechanism contributes to the phenotype of SpCC.

Association of IHC p16INK4a expression and ELISA Plasma p16INK4a Protein in Squamous Cell Carcinoma of Uterine Cervix: A Concept of Liquid Biopsy

Introduction: Cervical cancer is the 3rd most common cancer among women worldwide. p16 biomarker is the surrogate marker in cervical cancer and can be detected by Immunohistochemistry (IHC). Aim: To evaluate the association of IHC p16INK4a expression in tissue sections and Enzyme-linked Immunosorbent Assay (ELISA) p16INK4a protein in plasma of paired samples in Squamous Cell Carcinoma (SCC) of uterine cervix. Materials and Methods: This laboratory-based observational, pilot study was conducted at Sri Devaraj Urs Medical College (tertiary health care centre) in South India from June 2020 to May 2021. Total 17 new cases of SCC of cervix diagnosed by histopathology were considered for the study. The cases were staged as per International Federation of Gynecology and Obstetrics (FIGO) staging system and classified by histopathology as keratinising and non keratinising types. IHC p16INK4a evaluation was done on tissue sections and classified as block positivity, ambiguity and negative. ELISA p16INK4a estimation was done using plasma from Dipotassium Ethylenediaminetetraacetic Acid (K2-EDTA) blood sample of same cases. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 22.0 software. Results: The age ranged from 30-80 years with mean of 54.3±12.0 years. Plasma ELISA p16INK4a level ranged from 3.4-19.6 ng/ mL with a mean of 7.2±2.35 ng/mL in SCC of cervix. The plasma p16INK4a ELISA levels of 5.1 to 6.2 ng/mL, 6.0 to 6.6 ng/mL and 5.5 to 9.7 ng/mL predicts negative, ambiguity and block positivity of IHC p16INK4a expression respectively in corresponding tissue biopsy. Plasma ELISA p16INK4a levels were maximum in Non Keratinising Squamous Cell Carcinoma (NKSCC) followed by Well Differentiated Squamous Cell Carcinoma (WDSCC), Moderately Differentiated Squamous Cell Carcinoma (MDSCC) and Poorly Differentiated Squamous Cell Carcinoma (PDSCC). Conclusion: The plasma ELISA p16INK4a levels and IHC p16INK4a expression were maximum in higher disease stage compared to lower stage. This was a pilot study to evaluate the association between tissue IHC p16 expression and plasma ELISA p16 levels. Further study has to be done on larger study population with standardised procedure to prove the hypothesis.

Expression of Cyclin D1 in Oral Squamous Cell Carcinoma

Background: Cyclin D1 expression regulates normal cell cycle. Its deregulation or overexpression may cause disruption in the normal cell cycle control and lead to cancer progression. In this study, we aimed to study the expression of cyclin D1 in oral squamous cell carcinoma (OSCC) and find its association with the different grades of oral tumors, if any. 
 Methods: This cross-sectional study included 40 formalin-fixed paraffin-embedded tissue blocks specimens of OSCC with variable grades. The expression of cyclin D1 was evaluated through immunohistochemical (IHC) staining.
 Results: There were 9 female and 31 male samples, with a male-to-female ratio of 3.4:1. The age ranged between 25 and 90 years with an average age of 65.5 years. Twenty-five (62.5%) samples were diagnosed as well-differentiated squamous cell carcinoma (WDSCC) and fifteen (37.5%) as poorly differentiated squamous cell carcinoma (PDSCC). No cases of moderately differentiated squamous carcinoma were included in the study. The expression of cyclin D1 was detected in the cases of WDSCC and a lesser expression was seen in the PDSCC with a P-value of 0.0003, OR 1581 and 95% CI (29.8239 to 83810.7113).
 Conclusion: Cyclin D1 is expressed in OSCC and stronger expression was detected in WDSCC.

Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Surgical delays of less than 1 year in Mohs surgery associated with tumor growth in moderately- and poorly-differentiated squamous cell carcinomas but not lower-grade squamous cell carcinomas or basal cell carcinomas: A retrospective analysis

Evidence is controversial and limited concerning whether surgical delays are associated with tumor growth for cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas. Identify tumor subpopulations that may demonstrate an association between tumor growth and surgical delay. We retrospectively analyzed 299 SCCs and 802 basal cell carcinomas treated with Mohs surgery at a single institution. Time interval from biopsy to surgery represented surgical delay. Change in major diameter (ΔMD) from size at biopsy to postoperative defect represented tumor growth. Independent predictors of ΔMD were identified by multivariate analysis. Linear regression was then utilized to assess for whether the ΔMD from these independent predictors trended with surgical delay. Surgical delays ranged from 0 to 331days. Among SCCs, histologic subtype and prior treatment were identified as independent predictors of ΔMD. Significant associations between ΔMD and surgical delay were found for poorly- and moderately-differentiated SCCs, demonstrating growth rates of 0.28cm and 0.24cm per month of delay, respectively. The ΔMD for SCCs with prior treatment and basal cell carcinoma subgroups did not vary with surgical delay. Retrospective design, single center. Surgical delays of less than a year were associated with tumor growth for higher-grade SCCs, with effect sizes bearing potential for clinical significance.

Comparative Analysis of Clinicopathological Characteristics, Survival Features, and Protein Expression Between Basaloid and Squamous Cell Carcinoma of the Esophagus.

BackgroundBasaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma (SCC) of the esophagus. This study aimed to assess the discrepancy in clinicopathological characteristics and protein expression between esophageal BSCC and typical esophageal SCC.Study DesignWe reviewed 40 cases of esophageal BSCC. As controls, 63 well-differentiated SCC (WSCC) patients, 70 moderately differentiated SCC (MSCC) patients, and 51 poorly differentiated SCC (PSCC) patients were selected. The clinicopathologic characteristics and immunoreactivity of Ki-67, p53, p63, and epidermal growth factor receptor (EGFR) were then evaluated in the BSCC and typical SCC patients.ResultsThe 5-year survival rates for the BSCC patients were 27.5%. The prognostic outcomes of the BSCC group were similar to those of the PSCC and MSCC groups but worse than that of the WSCC group, with a significant difference (P=0.045). Ki-67 expression was significantly higher in the BSCC group than that in the WSCC group (P < 0.05). Meanwhile, there were no significant differences in the expression of the other molecular markers (p53, p63, and EGFR) between the typical SCC and BSCC groups (P > 0.05). The median survival time of esophageal the BSCC patients with low p53 expression was significantly longer than that of the patients with high p53 expression (P=0.026). Further, the median survival time of the esophageal BSCC patients with high p63 expression was significantly longer than that of the patients with low p63 expression (P=0.041). Meanwhile, Ki-67 and EGFR expressions were not correlated with OS in the BSCC group.ConclusionEsophageal BSCC has a more clinically virulent course. Notably, p53 and p63 expression are associated with prognosis in BSCC. These findings conject that evaluation of multiple cancer biomarkers might be a promising auxiliary diagnostic indicator in BSCC.

Immunohistochemical Expression of the Epithelial to Mesenchymal Transition Proteins E-cadherin and ß-catenin in Grades of Oral Squamous Cell Carcinoma.

Background:E-Cadherin/β-Catenin protein complexes play a major role in epithelial to mesenchymal transition (EMT) and vice versa. Such types of EMT are implicated physiologically during embryonic development and pathologically in tissue fibrosis and tumorigenesis.Aims:The aim was the evaluation of E-Cadherin and β-Catenin immunoreactivity in various grades of oral squamous cell carcinoma (OSCC) and to correlate their pattern of expression.Materials and Methods:Immunohistochemical expression of E-Cadherin/β-Catenin was evaluated in a total n = 30 tissue samples comprising of n = 10 well-differentiated squamous cell carcinoma (WDSCC), n = 10 moderately differentiated squamous cell carcinoma (MDSCC), and n = 10 poorly differentiated squamous cell carcinoma (PDSCC). Based on the intensity of staining, an immunoreactivity scoring was calculated.Statistical Analysis:The scorings obtained were subjected to independent t-test, paired t-test, Chi-square test, and ANOVA test using SPSS version 20.0 statistical analysis software. P < 0.05 was considered statistically significant.Results:A significant difference was observed in the expression of β-Catenin between normal mucosa and WDSCC; normal mucosa and MDSCC. A gradual decrease in the immunoreactivity score of E-Cadherin is seen in WDSCC, MDSCC, and PDSCC.Conclusion:Therefore, dysregulation of these proteins can lead to tumor progression, invasion, and metastasis. Further studies are warranted to specify the role of these EMT proteins as prognostic/therapeutic markers in patients suffering from OSCC.

Epidemiological trends of oral squamous cell carcinoma – An institutional study

Background: Oral squamous cell carcinoma (OSCC) is an important cause of morbidity and mortality worldwide with an incidence rate that varies widely by geographic location. Even within one geographic location, the incidence varies among groups categorized by age, gender or race. Aims and Objectives: The purpose of this retrospective study was to identify the trends in the age, gender, habits, sites involved and the histopathological grading which are given to patients diagnosed with OSCC in D.Y. Patil University School of Dentistry, Navi MumbaI. Materials and Methods: The study covered a period from July 2003 to July 2019. OSCC cases were retrospectively analysed for age, gender, habit, site of the lesion and histopathological grading given to patients diagnosed with OSCC. Charts were made, analysis was done and the results were formulated. Correlation was also done comparing gender vs habit, gender vs site of the lesion and gender vs histopathological grading given to the OSCC cases to check for statistical significance. Results: The study revealed a male to female ratio of ~ 0.7 : 0.3 with the largest number of OSCCs developing in the fourth and sixth decades of life. Overall, Buccal Mucosa (40%) was the most common site involved while floor of the mouth (2.8%) showed the least incidence. Other sites involved were gingiva (34%), tongue (12%), palate (4%) and labial mucosa (3%) respectively. Smokeless tobacco habit was more prevalent than smoking tobacco in both men as well as women. We even observed that 58% of cases were diagnosed with Well differentiated squamous cell carcinoma (WDSCC), 39% with Moderately differentiated squamous cell carcinoma (MDSCC) and 2% with Poorly differentiated squamous cell carcinoma (PDSCC). Correlation between gender vs habit, gender vs site of the lesion and gender vs histopathological grading of OSCC was done using chi square test and all the three parameters turned out to be statistically significant. Conclusion: An alarming rise in the number of OSCC cases over the years was observed from this 15-year retrospective study. Measures must be taken to make people aware about the ill effects of tobacco and the prolonged usage & the availability of treatment options should be made known to the affected individuals. Race, ethnicity and age cannot be altered; however, lifestyle behaviour such as use of tobacco and alcohol are amenable to change.

Avian Papilloma and Squamous Cell Carcinoma: a Histopathological, Immunohistochemical and Virological study

In this retrospective study, we describe the histopathological findings in seven papillomas and 45 squamous cell carcinomas (SCCs) from psittacine birds, raptors and domestic fowl. The age of affected birds ranged from 3 to 40 years, with median age significantly higher in psittacines (P=0.014). The majority of tumours were located in the skin (24/52, 46.2%) or uropygial gland (10/52, 19.2%). Thirty of the SCCs (66.7%) were well differentiated and 15 (33.3%) were poorly-differentiated. SCCs exhibited a significantly higher degree of nuclear pleomorphism (P=0.005) and a greater proportion were ulcerated (P=0.001) compared with papillomas; however, there was no significant difference in mitotic count (MC) or inflammation score. The expression of cyclo-oxygenase (COX)-2 and E-cadherin was investigated by immunohistochemistry. The COX-2 total score (TS) was significantly higher in SCCs compared with papillomas (P=0.002), but the difference between COX-2 TS of well- and poorly-differentiated SCCs was not significant. COX-2 labelling was predominantly cytoplasmic, but some tumours had concurrent membranous and/or perinuclear labelling. SCCs with membranous labelling had a significantly higher MC (P=0.028). A significantly higher proportion of SCCs were negative for E-cadherin compared with papillomas (P=0.042), but there was no significant difference between well- and poorly-differentiated SCCs. Fourteen papillomas and SCCs from psittacines were also tested by polymerase chain reaction for the presence of Psittacus erithacus papillomavirus 1 and Psittacid herpesvirus 1, but all samples tested negative. We demonstrate for the first time the expression of COX-2 and E-cadherin in avian tissues, and suggest that these markers may be useful in differentiating papillomas from SCCs, particularly when sample size is small.

Abdominal Pain, Hypotension With Rectal Bleeding: A Unique Presentation of Emphysematous Cholecystitis From Squamous Cell Carcinoma of Gallbladder (GB)

Carcinoma of GB is a rare tumor which presents significant diagnostic challenges. We present a case of an elderly woman who presented with abdominal pain and hematochezia was found to have septic shock from emphysematous cholecystitis in the setting of squamous cell carcinoma of the gallbladder. A 70 year old woman with past medical history of hypertension, anemia, CKD Stage III and DVT on warfarin presented with diffuse abdominal pain and bright red rectal bleeding. Her initial blood pressure was 74/38 mm hg with significant epigastric tenderness on exam. Rectal exam revealed hematochezia. Labs revealed hemoglobin of 9.7 g/dL. Initially believed to have lower GI bleed in the setting of supratherapeutic INR (3.1) she was transfused fresh frozen plasma and packed red blood cells. In view of significant epigastric tenderness CT scan of abdomen was done which revealed a markedly distended stone-containing GB with wall thickening, fat stranding and gas anteriorly dependent within the GB concerning for emphysematous cholecystitis. She was treated with IV antibiotics with emergent cholecystectomy. Pathology of the GB was significant for poorly-differentiated squamous cell carcinoma with positive cystic duct lymph node and acute cholecystitis with cholelithiasis. Cancer of the GB is an uncommon malignancy comprising just 0.6% of all new cancer diagnoses, and just 3.7% of all new digestive system cancer diagnoses in 20161. Histologic subtypes include adenocarcinoma, and squamous/adenosquamous carcinoma with an incidence of 90% and 1.7-12% respectively. Occurring primarily in the elderly with a 3:1 predominance in women3,4, GB carcinoma is a highly aggressive disease entity. Due to the lack of typical presenting symptoms GB cancer is usually diagnosed in advanced stages. In certain instances, patients may present with complaints of abdominal pain, nausea and vomiting and are eventually diagnosed with cholecystitis as the tumor obstructs outflow of bile. Aim of treatment is surgical resection when possible. Our case was clinically challenging as the initial presentation was consistent with massive lower GI bleeding but the CT scan of the abdomen helped us reach to the correct diagnosis and treatment. It is important for physicians to think of a broad differential diagnosis as sometimes the disease presentation is not straight forward like in our case where in the presenting complaint of rectal bleeding eventually led to a diagnosis of squamous cell cancer of GB.1241_A.tif Figure 1: Axial view of emphysematous gallbladder with foci of anteriorly dependent air.1241_B.tif Figure 2: Coronal view of markedly distended gallbladder with multiple stones, irregularly thickened wall and pericholecystic fluid.

The importance of ctokeratins in the early detection of oral squamous cell carcinoma.

Background:Oral cancer is usually diagnosed at advanced stages. The pattern of keratin expression in normal epithelia and the change in their expression in premalignant lesions and carcinomas have suggested the possibilities of improving diagnosis. The aim of this study is to determine the use of acidic cytokeratins (CKs) as biomarkers of histopathological progression in oral carcinogenesis.Materials and Methods:A total of 50 paraffin blocks of histological specimens diagnosed as hyperplastic epithelium, dysplastic epithelium, well-differentiated squamous cell carcinoma (SCC) and poorly-differentiated SCC (10 specimens each) were included in this study, in addition to 10 normal oral mucosal samples. All samples were stained immunohistochemically with CKs (10-ab1, 14, 16-ab1, 18-dc10 and 19-abs10) using Ventana Medical Systems (Arizona-USA). The expression of CKs antigen was evaluated as absent, mild, moderate and severe.Results:CK10-ab1 was found to be positive in the suprabasal layers of all specimens in normal and hyperplastic epithelium, while it was moderate in dysplastic epithelium and mild in well-differentiated SCC. CK10-ab1 was negative in all samples with poorly-differentiated SCC (P < 0.005). CK14 was positive in all specimens of all groups whereas CK16-ab1 was negative in all specimens of all groups. The stain of CKs 18-dc10 and 19-abs10 was restricted to the basal cells only in normal, hyperplastic and dysplastic epithelium, while it was mild in well-differentiated and poorly-differentiated SCC (P < 0.01).Conclusion:CK10-ab1 disappeared gradually with the progression of malignant changes of squamous cells whereas CKs 18-dc10 and 19-abs10 increased gradually at the same time. Such changes in the protein mapping of squamous cells need more investigation for a better understanding of oral SCC.

Evaluation of Tumor-associated Tissue Eosinophilia in Different Stages of Oral Squamous Cell Carcinoma using Special Stains: Anin vitroHistopathological Study

To evaluate the tissue eosinophilia in different stages and grades of oral squamous cell carcinoma (OSCC) and correlate its possible role as a prognosticator in primary OSCC using special stains like Congo red and carbol chromotrope. Forty-five intraoral histopathologi-cally proven cases of OSCC were selected (15 cases each of well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC)). Three sections of 4 pm were taken for each case. All slides were stained using routine stain, i.e., hematoxylin and eosin (H&E), and special stains, i.e., carbol chromotrope and Congo red respectively, for studying tissue eosinophils in all these groups. Histopathological evaluation was performed on paraffin sections for calculating the quantitative eosinophil distribution by two separate observers who were blinded to clinical and histopathological data. Tumor-associated tissue eosinophilia (TATE) was calculated using the density method. An increase in the degree of TATE from stage I to stage IV suggested that elevated tissue eosinophilia was seen with an increasing size of primary tumor. Also an increase in TATE was observed with an increasing grade of OSCC. Chromotrope stain was found to be a much better and more specific stain for eosinophils, and gave more accurate eosinophil count compared with H&E and Congo red. The findings of the present study highlight the significance of eosinophil counting and that it can be used as an additional morphological parameter in the grading of OSCC which can also be included in the biopsy report.

A case of poorly-differentiated squamous cell carcinoma following dental extractions

Gingival squamous cell carcinomas (SCC) are relatively rare and make up approximately 10% of oral squamous cell carcinomas. 1 The initial signs and symptoms of a gingival SCC can resemble common dental and periodontal infections and hence it is usually diagnosed late with a relatively poor prognosis. This report presents a case of a healthy 39-year-old patient who attended for routine wisdom teeth extractions, and returned to the emergency department complaining of progressive trismus and paraesthesia of the lower lip. A provisional diagnosis of osteomyelitis was made. However, further clinical, radiographic and histopathological investigations resulted in the diagnosis of poorly-differentiated SCC. CPD/Clinical Relevance: A series of misdiagnoses were made by specialists and by general dental and medical practitioners; this case highlights the importance of recognizing the signs and symptoms of oral carcinoma and appropriate subsequent management.

Recurrent maxillary sinus cancer with only adrenal metastasis.

Maxillary sinus cancer is rare, and often presents as a locally advanced disease. Recurrence commonly occurs locoregionally, while fewer patients present with distant metastasis; the most common sites involved are the lung and bone. This report discusses the case of a 64-year-old male who presented with a mass in the left submandibular area. Biopsy was performed and histological analysis identified a poorly differentiated squamous cell carcinoma. After staging work up, it was concluded the patient had a maxillary sinus squamous cell carcinoma at clinical stage IVA. The patient received a left partial maxillectomy and left radical neck dissection followed by postoperative chemoradiotherapy. After three months of CRT, the patient developed a left adrenal gland metastasis without locoregional failure. The patient subsequently received a laparoscopic left adrenalectomy and the results of histological analysis revealed a poorly-differentiated squamous cell carcinoma. Within one month of surgery, the patient had developed multiple metastases at the left adrenalectomy site and succumbed to the disease four months later.

Evaluation of paxillin expression in patients with oral squamous cell carcinoma: An immunohistochemical study.

Background:Oral squamous cell carcinoma (OSCC) is the tenth most common cancer in the world. The diagnosis of OSCC remains problematic, especially in advanced-stage tumors.Aims:The present study was conducted to understand the pattern of expression of paxillin in varying grades of carcinomas and also to ascertain whether its expression has an association with increasing grades.Methods:A total of ninety formalin-fixed paraffin-embedded tissues of OSCC were included in the study comprising thirty cases of each of well-differentiated squamous cell carcinomas, moderately differentiated squamous cell carcinomas (MDSCCs) and poorly differentiated squamous cell carcinomas (PDSCCs). The tissue sections were subjected to immunohistochemical staining of paxillin using super polymer-sensitive polymer 3,3’ diaminobenzidine detection kit. All the three groups were analyzed on various parameters including staining intensity, location and percentage of staining. SPSS 19.0 was used to analyze the data.Results:Paxillin stain positivity was observed in 95.5% of the cases. Predominant intense paxillin staining was demonstrated in 17 (56.6%) cases of well-differentiated squamous cell carcinoma, 28 (93.3%) cases of moderately differentiated squamous squamous cell carcinoma and 15 (50%) cases of PDSCC. A predominant cytoplasmic staining was observed in 21 (70%) cases of PDSCC and cytoplasmic plus membrane staining in 14 (46.6%) cases of MDSCC.Conclusion:The present study provides evidence that paxillin may be involved in the development and progression of OSCC. Thus, paxillin could be considered a useful biomarker for patient management and prognosis.

Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma

The aims of this study were to clarify the usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma with a solid growth pattern [solid epithelioid mesothelioma (SEM)] and poorly differentiated squamous cell carcinoma (PDSCC), and to confirm the validity of a specific type of antibody panel. Additionally, we aimed to clarify the pitfalls of immunohistochemical analyses. Formalin-fixed paraffin-embedded specimens from 36 cases of SEM and 38 cases of PDSCC were immunohistochemically examined for calretinin, podoplanin (D2-40), Wilms' tumour gene product (WT1), cytokeratin (CK) 5/6, p40, p63, carcinoembryonic antigen (CEA), epithelial-related antigen (MOC31), claudin-4, thyroid transcription factor-1 (TTF-1), and napsin A. WT1 showed the highest diagnostic accuracy (85.1%) as a mesothelial marker, and CEA, p40 and claudin-4 showed higher diagnostic accuracies (95.9%, 94.6%, and 93.2%, respectively) as carcinoma markers. Calretinin (diagnostic accuracy: 75.7%), D2-40 (diagnostic accuracy: 67.6%), CK5/6 (diagnostic accuracy: 63.5%), TTF-1 (diagnostic accuracy: 55.4%) and napsin A (diagnostic accuracy: 52.7%) could not differentiate between SEM and PDSCC. Among these markers, the combination of calretinin and WT1 showed the highest diagnostic accuracy (86.5%) as a positive marker, and the combination of p40 and CEA showed the highest diagnostic accuracy (97.3%) as a negative marker. The combination of CEA and claudin-4 also showed relatively high diagnostic accuracy (94.6%) as a negative marker. We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.