Well-differentiated Squamous Cell Carcinoma Research Articles

Follicular Carcinoma Thyroid with Focus of Squamous Cell Carcinoma - A Case Report

Collision tumors of the thyroid gland are a rare entity. Primary squamous cell carcinoma of the thyroid (PSCCT) is a malignant epithelial tumor, composed entirely of cells with squamous differentiation and accounting for less than 1% of all malignancies of the thyroid gland. PSCCT arises from other thyroid diseases such as Hashimoto’s thyroiditis, tall cell variant papillary carcinoma, follicular carcinoma, and anaplastic carcinoma1. We describe a patient with the combination of a well-differentiated squamous cell carcinoma and follicular carcinoma of the thyroid.

Squamous Cell Carcinoma Arising From Odontogenic Cyst Epithelium or Oral Mucosa Epithelium After Marsupialization of Odontogenic Radicular Cyst in Posterior Mandible?

Squamous cell carcinomas (SCCs) are common malignant tumors in the oral and maxillofacial region. However, SCCs secondary to marsupialization of odontogenic radicular cysts are extremely rare. The authors report an unusual case of a 43-year-old male presented with dull pain in the right molar region of the mandible without numbness of lower lips, who had a long history of smoking, alcohol consumption, and betel nut chewing. Computerized tomography revealed a round well-defined unilocular radiolucent at the apex of lower right premolars, 2 nonvital teeth. The clinical diagnosis was the radicular cyst of the right mandible. The patient was initially treated with root canal therapy of the teeth followed by marsupialization with a mandibular vestibular groove incision. While the patient did not follow the instruction of irrigation of the cyst and had no regular follow-up. The reexamination of computerized tomography indicated a round well-defined unilocular radiolucent at the apex of lower right premolars and filled with a soft tissue without clear boundary with buccal muscles at 31 months follow-up. There were no masses or ulcer around the mandibular vestibular groove incision and the patient had no sign of numbness of lower lips. The clinical diagnosis was the radicular cyst of right mandible with infection. A curettage was performed. However, the pathologic diagnosis was well-differentiated SCC. An extended radical surgical resection including segmental resection of the right mandible was performed. The histopathology was well-differentiated SCC without the cyst epithelium and invasion of bone, which can be distinguished from primary intraosseous SCC. The case indicates that marsupialization performed in patients with a history of smoking, alcohol consumption, and betel nut chewing, has a risk of suffering from oral SCC.

External Auditory Canal Mass: A Case Series of Squamous Cell Carcinoma

Introduction: Squamous cell carcinoma of the temporal bone is extremely rare comprising 0.2% of all tumors of head and neck. Symptoms are nonspecific and may be mistaken for other more benign conditions as otitis, cholesteatoma and polyp. Hence, this condition may present as a diagnostic challenge. Case Discussion: We describe a case series of three patients who presented with external auditory canal (EAC) mass. The most common signs and symptoms are pruritus, decreased hearing and yellowish discharge. They were initially treated with otic antibiotics which afforded no relief. The first case is a 51 year-old female who underwent wide excision of the right ear canal and middle ear mass and right temporal craniotomy. Histopathology showed moderately differentiated squamous cell carcinoma with temporal tumor and subdural extension consistent with metastasis. The second case is a 53 year-old male who refused surgical management. He was non-compliant with work-up and follow-up and later on presented with left facial asymmetry and headache. CT scan showed a left inner and middle ear canal mass with extension to the auditory canal and protrusion into the left cerebellar hemisphere. Punch biopsy of the left EAC mass was done and pathologic report showed well-differentiated squamous cell carcinoma. Lastly, a 54 year old male who underwent Radical mastoidectomy with histopathology reports of a moderately differentiated squamous cell carcinoma. Conclusion: Standard treatment modality is still unclear because of the rarity of this condition. However, surgical resection with negative margins followed by concurrent chemotherapy and radiation is the most commonly performed approach1. For the above-mentioned patients, concurrent chemotherapy and radiation therapy was given which showed significant treatment response.

Cutaneous Verrucous Carcinomas: A Review.

Verrucous carcinoma (VC) is a relatively rare locally aggressive, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential and is most frequent in the mucosa. Although rarely reported on the skin, cutaneous verrucous carcinomas (CVC) can appear anywhere, most commonly on the feet. However, clinical and pathologic diagnosis of CVC has been confusing and challenging. It can easily be mistaken for benign or more malignant conditions such as giant condyloma acuminata, keratoacanthoma, and pseudoepithelioma-like hyperplasia or squamous cell carcinoma, resulting in inappropriate management. In this review, we describe the different aspects associated with CVC, including its pathogenesis and clinicopathologic features. The available evidence for the differential diagnosis and treatment of CVC is discussed, and specific management recommendations are made. After the treatment, careful follow-up examinations of the excised area should be performed at regular intervals.

Quality of Life Assessment With European Organisation for Research and Treatment of Cancer Questionnaire (Head and Neck Module 43) and Its Clinicopathological Correlation Among Patients Treated for Oral Squamous Cell Carcinoma: An Exploratory Study.

Introduction Oral cancer has a great impact on quality of life (QOL). Many risk factors influence the overall QOL. Our study was performed to evaluate the QOL among patients with oral cancer and to correlate it with age, gender, tobacco usage, and clinicopathological details. Methods We have used the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43) and the Quality of Life Questionnaires for Core 30 (QLQ-C30) among the patients diagnosed with oral cancer after reporting to our institution. The Gpower calculation based on differences between two independent means reported by Meera et al. had a total sample size of 28 with an actual power of 0.9616. Thirty-five patients were included in the present study. Ethical clearance for this study was obtained, and there were no gender or age limits for enrollment. The patient demographic details and case history with relevant treatment information were collected from the DIAS (Dental Information Archival Software) of Saveetha Dental College, Chennai. After obtaining informed consent from the patients, the EORTC QLQ-HN43 and QLQ-C30 questionnaires were given to them. It was used both in Tamil and English. Various domains such as pain, appearance, and oral function were documented. The findings were correlated with clinical and histopathological findings. The collected data were tabulated and statistically analyzed with IBM Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., USA). The mean ± SD were calculated for continuous variables, and frequency with percentage was determined for categorical parameters. Results The study included both men (57%) and women (43%)in the age range of 30-70 years, with a mean age of 50 years. Study samples included tobacco users (82%) and non-tobacco users (18%). Out of the 35 patients, 15 patients had lesions involving the buccal mucosa (42%) and 10 involving the tongue (28%). Oral squamous cell carcinoma (OSCC) was the most common type of lesion, and it was mostly treated surgically with resection and excision (82%), or just excision (18%). Seventy percent of our patients underwent reconstruction, while primary closure was done in only 30% of cases. All of the patients underwent neck dissection, including supraomohyoid neck dissection (52%), modified radial neck dissection (40%), and radial neck dissection (8%). Histopathology revealed that 49% had well-differentiated squamous cell carcinoma, 23% had moderately differentiated squamous cell carcinoma, and 28% had poorly differentiated squamous cell carcinoma. Out of the 35 included cases, five patients had died (14%). The primary site was buccal mucosa in all five cases, and surprisingly, three patients also had recurrences post-surgery or post-radiotherapy. We observed that the average rating of overall health and overall QOL at the time of diagnosis was 5.4. After one year of follow-up, the average rating of overall health and overall QOL was found to be 3.4. Conclusion The administration of EORTC QLQ-HN43 was found to be efficacious in our study on patients with OSCC. We could identify baseline data regarding the QOL of our patients treated for OSCC. We have identified critical domains of oral function that need to be focused upon to improve the overall QOL of OSCC patients through adjunctive therapies. We have also identified higher mortality and overall poorer QOL in patients with OSCC involving the buccal mucosa.

Images in haematology: Primary cutaneous diffuse large B cell lymphoma, leg type with an unusual presentation: A diagnostic challenge.

An 83-year-old woman with a history of arterial hypertension treated with amlodipine, and a well-differentiated cutaneous squamous cell carcinoma completely excised during the past year, was referred to dermatology consultations for the progressive appearance of indurated nodular skin lesions over the last two months, which began on the right lower extremity and progressed to the upper extremities, trunk and buttocks, with no other symptoms associated. With the differential between cutaneous lymphoma versus subcutaneous metastases, a punch biopsy of one of the lesions was performed. Histopathological examination demonstrated a dense hypodermal infiltrate composed of atypical large lymphocytes showing a round-shaped nucleus with vesicular chromatin and prominent single or multiple nucleoli. The immunohistochemical study showed positivity in neoplastic cells for CD79a, CD20, Bcl-2, MUM-1, c-myc and IgM, along with a high expression of Ki-67; and negativity for CD3, CD10, Bcl-6, CD30, p53, PD-L1 and Epstein-Barr Virus Encoded RNA. Molecular analyses were then performed without detecting BCL-2, BCL-6 or c-MYC rearrangements by fluorescence in situ hybridization, as well as the absence of p.L265P mutation in MYD88 through a quantitative polymerase chain reaction. Taking into account both histopathological and clinical findings, a primary cutaneous diffuse large B cell lymphoma, leg type (PCDLBCL-LT) and skin involvement in the course of a systemic DLBCL were considered, so blood tests and a positron emission tomography (18-FDG PET/CT) were then solicited. Blood tests showed a haemoglobin value of 12.5 g/dl with a normal white blood cell count and a slight β-2-microglobulin elevation (3.33 mg/L) in the context of a decreased renal function (54.38 ml/min/1.73m2). 18-FDG PET/CT revealed 23 hypermetabolic subcutaneous nodules distributed predominantly in the right arm and lower extremities, with no sign of disease in other locations (Figure 1), confirming the primary cutaneous origin of the disease and the final diagnosis of a PCDLBCL-LT. The patient underwent treatment with 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, with progressive improvement of the skin lesions and complete resolution of them, and is currently being followed up by haematology and dermatology departments. Although the majority of PCDLBCL-LT, arise in the lower limbs (80%–85%), some patients can develop the disease in other areas, but in those cases, the lesions are usually individual or few in number, contrary to our case. PET imaging tests have a major role in the initial staging of the disease and treatment response evaluation, and they could even avoid bone marrow biopsy in selected patients. The double expression of bcl-2 and c-myc is frequent in PCDLBC-LT, although the prognostic value of this dual expression is yet unclear, whereas the absence of the MYD88 mutation could be associated with both better response to lenalidomide as well as better prognosis. For these reasons, immunohistochemical and molecular techniques can be helpful in defining prognosis and deciding therapeutic options in patients with PCDLBCL-LT and should be performed in routine practice. In conclusion, we present an extremely rare 18-FDG PET/CT image of a PCDLBCL-LT with 23 subcutaneous nodules, underlying the importance of this test for the study of these patients. Lucía Prieto-Torres – Attending the case and performing clinical research and manuscript revision. Pablo Villagrasa-Boli – Attending the case, revising existing literature and manuscript writing. Luis Ignacio Sancho-Val – Attending the case and manuscript revision. Pedro Paul – Attending the case and manuscript revision. Ana Leticia Tardin-Cardoso – Performing the imaging tests and their clinical interpretation. Mar García-García – Pathology diagnosis, taking microscopic images and manuscript revision. Mariano Ara-Martín – Proof checking. The authors have nothing to report. The authors declare that they have no conflict of interest. No funding has been received for this article.

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study

Background Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. Objective To compare the prognosis of early-stage glottic cancer among SCC variants Methods We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan–Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. Results HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). Conclusions The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

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.

Evaluation of the Role of Neck Dissection in Patients with Verrucous Squamous Cell Carcinoma of the Oral Cavity: A Cohort Study

Introduction: Verrucous Carcinoma (VC), a well-differentiated Squamous Cell Carcinoma (SCC), commonly presents in the oral cavity, accounting for 2-16% of oral carcinomas. Though rare, it poses a challenge in establishing a pathological diagnosis, even in adequate biopsies, as 20% of Oral Cavity Verrucous Carcinoma (OVC) contains concomitant SCC. VC is primarily treated by surgery, similar to oral SCC. The role of neck dissection in oral SCC is well-established, but there is limited data on VC. Aim: To evaluate the role of neck dissection in the management of OVC. It also aimed to evaluate the clinicopathological demographics of OVC and identify predictors for survival outcomes. Materials and Methods: A retrospective cohort study was conducted using medical records of 2312 patients with oral carcinoma treated from January 2010 to December 2020 at Department of Surgical Oncology, Malabar Cancer Centre, Kannur, Thalassery, Kerala, India, a tertiary cancer centre under the Government of Kerala. Among 116 patients identified with VC, 49 patients met the inclusion criteria. The collected data was analysed using Statistical Package for Social Sciences (SPSS) version 20.0. The primary outcomes were overall survival rate and disease-free survival rate. Kaplan-Meier curves were constructed based on the survival data and compared using the log-rank test. Results: The mean age of the entire population was 62.8 years, with an age range of 40-90 years. Among the 2312 patients who underwent surgery for oral carcinoma, 49 (2.11%) patients were diagnosed with VC based on the final histopathology report. The majority of patients were diagnosed with early-stage disease on histopathological examination 36/49 (73.5%). A total of 34 patients received neck dissections, of which 13 patients (38.3%) had palpable nodes on presentation. All patients were node negative (PN0). On univariate analysis, neck dissection was not found to be a predictor of mortality or locoregional recurrence. There was no significant difference in overall survival rate (p=0.160) or disease-free survival rate (p=0.67) when comparing patients who underwent primary resection with neck dissection to those whose necks were kept under observation. Conclusion: The OVC has an excellent prognosis, and surgery remains the mainstay of treatment. The decision on neck dissection and the extent of neck dissection should be judiciously made based on the surgical approach and the procedure’s morbidity.

Immunohistochemical Expression of E-cadherin in Premalignant and Malignant Squamous Lesions of the Oral Cavity: A Cross-sectional Study

Introduction: Squamous Cell Carcinoma (SCC) constitutes 90% of the malignancies of the oral cavity, making it the 6th most common cancer worldwide. Premalignant lesions of the oral cavity carry an increased risk for the development of oral SCC, which is a multistage process. Numerous molecules are involved in this process, and E-cadherin is one of them. E-cadherin is a 120 kDa glycoprotein and a calcium-dependent molecule involved in cell adhesion. Altered expression of E-cadherin has been described in preinvasive lesions and malignancies of the cervix, oesophagus, and head and neck. Aim: The aim of this study was to observe the immunohistochemical (IHC) expression pattern of E-cadherin in premalignant and malignant lesions of the oral cavity and to correlate E-cadherin immunoexpression between different grades of dysplasia and malignancy. Materials and Methods: This cross-sectional, ambispective study was conducted at Sri Dharmasthala Manjunatheshwara College of Medical Sciences and Hospital, Dharwad, Karnataka, India. The study duration was two and a half years, with one year being retrospective from July 2014 to June 2015, and the remaining period being prospective from July 2015 to December 2016. Systematic random sampling was done to select 60 cases. Premalignant and malignant lesions of the oral squamous epithelium were classified according to the 2017 World Health Organization (WHO) classification and subjected to E-cadherin immunohistochemistry. Grading of expression was based on the percentage of cells showing continuous homogenous membranous staining: 0 (negative)=0 to 10%, 1+ (loss)=11-25%, 2+ (weak)=26% to 50%, 3+ (strong)=51% to 75%, 4+ (intense)=&gt;75% of cells. Results were analysed using the Statistical Package for Social Sciences version 20.0. Results: The expression of E-cadherin between the different grades of premalignant lesions varied significantly (p-value=0.003), ranging from intense expression in mild dysplasia to weak expression in high grades of dysplasia. Immunoexpression was intense (4+) in 50% of cases, strong (3+) in 39.28%, and weak (2+) in 7.14% of cases. The expression of E-cadherin between the different grades of malignant lesions also varied significantly (p-value=0.002), ranging from negative expression in poorly differentiated SCC to strong expression in well-differentiated SCC. Immunoexpression was negative (0) in 31.25% of cases, strong (3+) in 31.25%, weak (2+) in 15.62%, and (1+) in 21.87% of cases. The pattern of expression was also significant between premalignant and malignant lesions (p-value&lt;0.0001). Conclusion: As the grades of dysplasia and malignancy increase, the expression of E-cadherin reduces. Hence, there is a negative correlation between E-cadherin expression and the grades of dysplasia and malignancy.

To evaluate an association between prognostic significance of Moesin with histopathological grading of oral squamous cell carcinoma: A systematic review.

The aim of the present Aetiology/Risk type and Prognostic type of systematic review is to evaluate the value of Moesin as a biomarker of invasiveness in Oral Squamous Cell Carcinoma patients and to review/assess the available evidence regarding the prospective prognostic association between Moesin and histopathological grading of OSCC to enhance the quality of life and survival rate of oral cancer patients. A systematic wide-range literature search was performed by authors (BS, KS, and DK) till October 2022 using both, electronic search media and manual search by hand, searching appropriate journals as per the focussed guiding question and inclusion/exclusion criteria. Major databases such as Scopus, EMBASE, Web of Science, Cochrane central register for controlled trials, PubMed & Google Scholar were conducted by two calibrated reviewers independently to gauge the association between the prognostic significance of Moesin with histopathological grading of oral squamous cell carcinoma. As this study is based on tissue samples of oral squamous cell carcinoma patients, all the selected studies were mostly, cross-sectional studies, and retrospective in nature. The studies were integrated with this review to gauge the association between the prognostic significance of Moesin with histopathological grading of oral squamous cell carcinoma (OSCC). The review included a total of 7 studies with tissue samples of 645 cases. The prime outcome was to assess the immunoexpression of Moesin among the different histopathological grades i.e well-differentiated SCC, moderately differentiated SCC, and poorly differentiated SCC and the subordinate outcome was to consider the extent of strong immunoexpression characteristics (cytoplasmic, membranous and mixed type) in different grades of OSCC as well as to correlate with morbidity, mortality, and/or 5 years or 10 years survival rate. The results were analyzed and presented narratively using the Critical Appraisal Tools developed by the University Of Oxford; Risk of Bias - Cochrane Risk of Bias tool - RoB 2.0, and GRADE-pro (Grading of Recommendations, Assessment, Development, and Evaluations) which rates the features of the evidence as high, moderate, low and very low. The risk of mortality expressed in terms of Hazard ratio has been elicited as a 1.37 times higher rate of mortality in the advanced histopathological stages of the OSCC cases. As the sample size of this review was insignificant, therefore, the authors have incorporated hazard ratios of some other studies of carcinomas in diverse sites in the body to give a flavor of prognostic outcomes of Moesin. It was observed that Moesin expression in Breast cancer and UADT carcinomas have a higher mortality rate as compared to OSCC and lung carcinoma cases and this decree strengthens our conviction that Moesin expression in the cytoplasm of advanced histopathological stages of cancer can be assumed as a sign of poor prognosis in all carcinomas including OSCC patients. A sample of seven studies is inadequate as definite evidence for claiming that Moesin is a strong biomarker of invasiveness in OSCC cases and more clinical trials need to be conducted on the prognostic efficacy of Moesin expression in the various histopathological grades of OSCC cases.

Does a well-differentiated oral squamous cell carcinoma always behave well? A case series

Does a well-differentiated oral squamous cell carcinoma always behave well? A case series

Extensive Eccrine Squamous Syringometaplasia Mimicking Squamous Cell Carcinoma on Histopathology

Eccrine Squamous Syringometaplasia (ESSM) is a histologically distinctive skin eruption occurring predominantly in acral or intertriginous areas presenting as erythematous macules, papules or patches. It is a response of eccrine ducts and glands to any injury or inflammation. The cuboidal epithelium of eccrine ducts and glands undergoes metaplasia and transforms to keratinised squamous epithelium in ESSM. Other types of metaplastic changes encountered are squamous, mucinous and adenomatous. In squamous syringometaplasia, the metaplastic squamous cells form lobules and florid types can pose a diagnostic dilemma, which if not well understood may lead to an erroneous diagnosis of neoplasia. Literature suggests ESSM as a condition associated with another pathogenic stimuli or therapy; however florid ESSM is very rare. Hereby, the authors present a case report of a 43- year- old male who presented florid ESSM mimicking well-differentiated Squamous Cell Carcinoma (SCC). The present case presented with a non healing elevated lesion on anterior aspect of right leg with itching. Similar lesions were not present in any other part of the body. The patient did not have history of any systemic disease or drug intake. The lesion was excised and sent for histopathology. On gross examination the skin showed irregular thickening and foci of erosion. Microscopy showed acanthotic, hyperkeratotic epidermis and dermal ESSM. There were irregular clusters of metaplastic squamous cell in dermis, resembling invasive islands of SCC. Meticulous examination revealed lobulated architecture of ESSM, lack of individual cell keratinisation/significant atypia or mitosis. The present report highlights the significance of histopathological diagnosis of benign squamous proliferations which can mimic malignancy and cause undue stress to the patient.

A specimen out of the blue, case of squamous cell carcinoma demonstrating various patterns of perineural Invasion

Oral squamous cell carcinoma (OSCC) is the fifth most frequent cancer in the world and about 3% of all malignant neoplasms are usually spread by lymphatic or rarely hematogenous spread. Perineural invasion (PNI) is an alternate method of tumor spread and an important prognostic factor for further treatment plans in OSCC. The patterns of PNI are categorized, according to various research articles and studies conducted, some of the common ones are complete encirclement, incomplete “crescent-like” encirclement, sandwiching, onion skin, partial invasion, and neural permeation. We received a hemiglossectomy specimen of a 62-year-old male diagnosed with squamous cell carcinoma (SCC) on a small biopsy with an ulceroproliferative lesion in the left lateral border of tongue. Microscopy showed an invasive tumor showing features of well-differentiated SCC with extensive various patterns of PNI such as complete encirclement, incomplete encirclement, sandwich pattern, onion skinning, crescenting and neural permeation. PNI indicates and predicts the local recurrence and also regional nodal metastasis in patients with OSCC. PNI should be searched and included in the histopathology report in every OSCC case including recurrent cases.

A TNFR1–UBCH10 axis drives lung squamous cell carcinoma dedifferentiation and metastasis through a cell-autonomous signaling loop

Tumor necrosis factor receptor 1 (TNFR1), encoded by TNFRSF1A, is a critical transducer of inflammatory pathways, but its physiological role in human cancer is not completely understood. Here, we observed high expression of TNFR1 in many human lung squamous cell carcinoma (SCCs) samples and in spontaneous lung SCCs derived from kinase-dead Ikkα knock-in (KA/KA) mice. Knocking out Tnfrf1a in KA/KA mice blocked lung SCC formation. When injected via tail vein, KALLU+ lung SCC cells that highly expressed TNFR1/TNF, Sox2, c-Myc, Twist1, Bcl2, and UBCH10, generated dedifferentiated spindle cell carcinomas with epithelial–mesenchymal transition markers in mouse lungs. In contrast, KALLU+ cells with silenced TNFR1 and KALLU- cells that expressed low levels of TNFR1 generated well-differentiated lung SCCs and were less tumorigenic and metastatic. We identified a downstream effector of TNFR1: oncogenic UBCH10, an E2 ubiquitin-conjugating enzyme with targets including Twist1, c-Myc, and Sox2, which enhanced SCC cell dedifferentiation. Furthermore, Tg-K5.TNFR1;KA/KA mice, which expressed transgenic TNFR1 in keratin 5-positve epithelial cells, developed more poorly differentiated and metastatic lung SCCs than those found in KA/KA mice. These findings demonstrate that an overexpressed TNFR1–UBCH10 axis advances lung carcinogenesis and metastasis through a dedifferentiation mechanism. Constituents in this pathway may contribute to the development of differentiation-related therapies for lung SCC.

Squamous Cell Carcinoma Arising from Chronic Osteomyelitis in the Extremities: Treatment Approach and Oncological Outcomes-A Systematic Review of the Literature.

Aims In chronic osteomyelitis-derived squamous cell carcinoma, what are the demographic and clinical variables, risk factors associated with worse outcomes, and results of treatment modalities used? Methods A systematic review was performed using PubMed and EMBASE. Articles were evaluated for inclusion and exclusion criteria, and for quality analysis. PRISMA guidelines were applied. Demographic and clinical data and therapeutic approaches were presented narratively and in descriptive statistics registered at PROSPERO. Results Most patients were male (40/49), trauma was the most common etiology (27/36), and about half of all SCC were in the tibia (25/48). Amputation was the main definitive treatment (42/47). Adjuvant treatments were not analyzed. Well-differentiated SCC accounted for 58.3% (21/36) of all tumors. Bone invasion was described in 82.8% (24/29); recurrence, in 7.7% (3/39); and metastasis, in 7.7% (3/39). Recurrence and metastasis occurred more frequently when bone invasion was present (p = 0.578 and p = 0.646, respectively). SCC with lymph node involvement showed a higher tendency to metastasize (p = 0.377). Compared with limb salvage, amputation was associated with a tendency for less recurrence (p = 0.312) and longer survival (p = 0.219). Conclusions COM-derived SCC mostly occurs after trauma and is usually located in the tibia. Bone invasion is common, and patients predominantly undergo amputation. This treatment is associated with a trend toward higher survival, compared to limb salvage.

Plasma cells in oral lesion: A clue to diagnosis or a diagnostic dilemma.

Plasma cells can just represent a part of host inflammatory response or form the cornerstone of diagnosis such as IgG4-related disease (IgG4RD) and plasma cell dyscrasias and sometimes create a diagnostic dilemma. The study aims to discuss a series of plasma cell lesions which we encountered in the oral cavity, discuss the diagnostic conundrum of plasma cell lesions. We also propose a working classification for their interpretation. All plasma cell lesions affecting the oral and maxillofacial region were retrieved from the archives of the Department of Oral and Maxillofacial Pathology. The cases were analyzed on the basis of histomorphology and immunohistochemical markers along with clinical, imaging and laboratory findings. Thirteen (0.64%) of 2026 oral lesions were diagnosed with plasma cell lesions. Out of 13 cases, 9 were plasma cell gingivitis, 2 IgG4-RD, 1 plasma cell myeloma and 1 plasmablastic lymphoma. Representative case from each category is discussed along with one case of well-differentiated squamous cell carcinoma (WDSCC) masquerading as plasma cell dyscrasias. We discuss the practical difficulties faced during the diagnosis of these oral plasma cell entities along with a working classification and propose an efficient diagnostic scheme for the correct characterization of these lesions.

Genistein anticancer efficacy during induced oral squamous cell carcinoma: an experimental study

BackgroundAbout 7 million people die from various types of cancer every year representing nearly 12.5% of deaths worldwide. This fact raises the demand to develop new, effective anticancer, onco-suppressive, and chemoprotective agents for the future fighting of cancers. Genistein exhibits pleiotropic functions in cancer, metabolism, and inflammation. It functions as an antineoplastic agent through its effect on the cell cycle, apoptotic processes, angiogenesis, invasion, and metastasis.Aim of the studyThe current study aimed to study the genistein onco-suppressive effects during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters’ buccal pouch utilizing flow cytometry analysis (FMA), as a fast-diagnosing tool, in addition to the histopathology.Material and methodsThe buccal mucosa of adult male Syrian hamsters was painted with paraffin oil only (group 1), DMBA mixed in mineral oil (group 2), or orally administrated genistein along with painting DMBA (group 2B). The buccal mucosa was utilized for flow cytometric analysis and histopathological examination.ResultsGrossly, DMBA-induced carcinogenesis started at the 9th week. Progressive signs appeared in the following weeks reaching to large ulcerative oral masses and exophytic nodules at the 21st week. Histologically, invasive well-differentiated oral squamous cell carcinoma (OSCC) appeared in the underlying tissues from the 12th week, showing malignant criteria. Genistein had delayed clinicopathological change, which started 6 weeks later, than the DMBA-painted hamsters, as mild epithelial dysplastic changes. This became moderate during the last 6 weeks, without dysplastic changes. Flow cytometry revealed that DMBA led to considerable variation in DNA proliferation activity, aneuploid DNA pattern, in 47.22% of hamsters and significantly raised the S-phase fragment (SPF) values, which drastically reduced after genistein treatment.ConclusionTaken together, genistein could be employed as an onco-suppressive agent for carcinogenesis. Moreover, FMA could be used as an aiding fast tool for diagnosis of cancer.

35007 An unusual clinical presentation of a squamous cell carcinoma mimicking mycetoma

Mycetoma is a chronic granulomatous infection of subcutaneous tissue caused by bacteria or fungi. It is endemic to tropical areas and leads to tissue swelling, ulcerated nodules, and draining sinus tracts. We present the case of a patient with an atypical squamous cell carcinoma (SCC), whose clinical presentation was consistent with mycetoma. Our patient is a 39-year-old Guatemalan male without past medical history who presented with a 20-year history of nonresolving swollen and ulcerated lesions on his left buttock. Upon examination, he had a large, edematous, and indurated mass with multiple circular ulcers and sinus tracts draining yellowish, malodorous discharge. Punch biopsies were performed for histology and tissue cultures. Tissue cultures for bacteria, atypical mycobacteria, nocardia, actinomyces, and fungi only grew polymicrobial bacterial organisms for which he was treated with antibiotics and had minimal improvement. Unexpectedly, histology revealed a well-differentiated SCC, and a left inguinal lymph node biopsy was positive for SCC. A wide excision was performed and hematology/oncology and surgery departments are currently following the patient for further management. This case demonstrates the importance of including SCC in the differential diagnosis when there is clinical suspicion of a long-standing infectious process such as mycetoma, especially when dealing with areas of chronic inflammation. The development of SCC has long been associated with non-healing wound ulcers. Even when solely an infectious process is suspected, clinicians should perform biopsies for both tissue cultures and histopathology to ensure prompt diagnosis, since malignancies such as SCC have the potential to masquerade as an infection.

Histomorphology and Molecular Profiling of Well-Differentiated Squamous Cell Carcinoma of the Esophagus Including its Unusual Variants

Esophageal verrucous squamous cell carcinoma and esophageal carcinoma cuniculatum are rare variants of extremely well-differentiated squamous cell carcinoma. These rare tumors share similar risk factors and clinical presentations with conventional esophageal squamous cell carcinoma. However, these tumors have distinct morphological features, molecular mutation profiles, and clinical outcomes. Diagnosis of esophageal verrucous squamous cell carcinoma and esophageal carcinoma cuniculatum can be challenging, requires high clinical suspicion, and often can only be diagnosed on a deep mucosal biopsy or resection specimen. Surgical treatment or endoscopic resection can be curative in early disease. This review presents the histomorphology and molecular profiling of the conventional type and the rare variants of the esophageal well-differentiated squamous cell carcinoma.