Non-keratinizing Squamous Cell Carcinoma Research Articles

Lumbar metastases in nasopharyngeal carcinoma (NPC) patient with uncomplete chemoradiation

Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. In Indonesia, NPC is the 4th most prevalent. Nasopharyngeal Carcinoma stage IVB as distant metastasis. The therapy in nasopharyngeal carcinoma (NPC) is Chemoradiotherapy. Concurrent chemoradiotherapy is either an established treatment modality or actively being investigated. Chemoradiotherapy have demonstrated decreased incidence of distant metastases compared with radiation only, however only if its treatment done completely. Here we present a rare case of unfinished chemoradiotherapy that caused metastases nasopharyngeal carcinoma patient. A 41-years-old consulted to ENT-HN department with main complaints of progressive cancer pain for 3 month and got worse in past 1 month. Patient also complaints for the pain at the waist, chest and headache currently. However, there was formal history of nasopharyngeal carcinoma for this patient since 2019 that had been treated with 3 cycles of chemotherapy and 26 cycles of radiotherapy. The patient was diagnosed with recurrent nasopharyngeal carcinoma post chemotherapy and radiotherapy with metastatic process. Unfortunately, the treatment underwent was not complete. A nasopharyngeal biopsy was performed and the histopathology result revealed a non-keratinizing squamous cell carcinoma nasopharynx. Lumbar CT-scan showed distant metastatic to lumbar vertebrae I-V. Nasopharyngeal carcinoma (NPC) represents a rare disease that showed as carcinoma that appears in the nasopharynx. The unfinished treatment of NPC leads to recurrent NPC and metastatic process to lumbar vertebrae I-V. Nevertheless, 20% of patients are radioresistant and experience a recurrence, which in most cases manifests with distant metastases.

Sinonasal DEK-rearranged Papillary Non-keratinizing Squamous Cell Carcinoma: Expanding the Emerging Entity.

The newly emerging sinonasal carcinomas have demonstrated diverse morphologies and specific molecular mutations along with deviant clinical behavior from conventional counterparts. Also, many sinonasal malignancies turned to be SMARCB1/SMARCA4-deficient. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) from DEK::AFF2 SNSCC, the two lesions are not distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK-rearranged papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. The tumor and locoregional lymph nodes were surgically resected, followed by adjuvant radiotherapy.

Sinonasal neoplasms: Update from the WHO 2022

The pathology of poorly differentiated sinonasal malignancies has undergone adynamic evolution during the last decade, resulting in arefined, mostly genetically or etiologically oriented classification of neoplasms in the historical spectrum of sinonasal undifferentiated carcinoma (NUT carcinoma, SWI-/SNF-deficient carcinomas, and others). Moreover, some new entities have been established, while others could be further delineated and better characterized. Ahighlight of the new classification is the inclusion of SWI/SNF (SMARCB1 or SMARCA4)-deficient carcinomas into aseparate category. In addition, carcinomas with DEK::AFF2 fusions have been included as aprovisional entity in the spectrum of nonkeratinizing squamous cell carcinoma. This review addresses the major changes in the classification of sinonasal tract neoplasms in the new WHO classification.

Treatment trends and prognostic factors related to histology of squamous cell carcinoma of the prostate: A SEER review.

e17120 Background: Excluding skin cancers, prostate cancer is the most common malignancy in males. Over 93% of prostate cancers are adenocarcinomas, and as such, an abundance of literature exists with regards to its screening, treatment, and prognosis. Often overlooked, however, data is lacking with regards to squamous cell carcinoma (SCC) of the prostate, a rare alternative form of prostatic cancer comprising fewer than 1% of malignancies. Given the rarity of SCC of the prostate there are neither accepted treatment guidelines nor consistent characterizations of the disease’s histogenesis and histopathology. This study seeks to improve existing guidelines on the treatment of prostate SCC by supplementing current literature with a novel method of longitudinal data collection in the form of the SEER database. Methods: This was a retrospective cohort study utilizing the Surveillance, Epidemiology and End Results (SEER) database sponsored by the National Cancer Institute (NCI). Investigated variables entailed patient demographics such as race and age, tumor characteristics including grade, tumor type, and histopathologic characteristics. Treatment modalities (surgical resection, radiation therapy, and systemic therapy) as well as disease characteristics were considered in generating Kaplan Meier overall survival (OS) curves compared using log rank test. Results: The most abundantly utilized treatment was surgery (58.6%), either alone or in conjunction with systemic and radiotherapy. Surgery alone was utilized for 24 patients and chemotherapy alone was utilized for 7 patients. Interestingly, only 14% of patients received multimodality treatment. Prostatic squamous cell carcinoma was the ultimate cause of death in 63.8% of cases. Kaplan Meier analysis demonstrated a median OS of 13 months. When stratifying by histopathologic characteristics, our results showed a significant difference in overall survival between patients with papillary carcinoma, with the median survival time of four years, and non-keratinizing squamous cell carcinoma, with a median survival time of one year (p = 0.005). Conclusions: Further studies are warranted regarding this exceedingly rare and understudied malignancy. The current analysis suggests subclassification of SSC of the prostate into papillary versus non-keratinizing squamous cell carcinoma may yield valuable prognostic information. Further research may emphasize this distinction as well as the role of multimodal treatment which appears to be underrepresented in SSC of the prostate when compared to other similar malignancies.

Bilateral infiltrative kidney metastasis due to non-keratinizing squamous cell carcinoma of the lung: lesson for the clinical nephrologist.

Bilateral infiltrative kidney metastasis due to non-keratinizing squamous cell carcinoma of the lung: lesson for the clinical nephrologist.

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus

ObjectivesKnowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. Materials and MethodsThis multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. ResultsThe 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients’ OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. ConclusionsEBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

Spatial genomic diversity associated with APOBEC mutagenesis in squamous cell carcinoma arising from ovarian teratoma.

Although the gross and microscopic features of squamous cell carcinoma arising from ovarian mature cystic teratoma (MCT-SCC) vary from case to case, the spatial spreading of genomic alterations within the tumor remains unclear. To clarify the spatial genomic diversity in MCT-SCCs, we performed whole-exome sequencing by collecting 16 samples from histologically different parts of two MCT-SCCs. Both cases showed histological diversity within the tumors (case 1: nonkeratinizing and keratinizing SCC and case 2: nonkeratinizing SCC and anaplastic carcinoma) and had different somatic mutation profiles by histological findings. Mutation signature analysis revealed a significantly enriched apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC) signature at all sites. Intriguingly, the spread of genomic alterations within the tumor and the clonal evolution patterns from nonmalignant epithelium to cancer sites differed between cases. TP53 mutation and copy number alterations were widespread at all sites, including the nonmalignant epithelium, in case 1. Keratinizing and nonkeratinizing SCCs were differentiated by the occurrence of unique somatic mutations from a common ancestral clone. In contrast, the nonmalignant epithelium showed almost no somatic mutations in case 2. TP53 mutation and the copy number alteration similarities were observed only in nonkeratinizing SCC samples. Nonkeratinizing SCC and anaplastic carcinoma shared almost no somatic mutations, suggesting that each locally and independently arose in the MCT. We demonstrated that two MCT-SCCs with different histologic findings were highly heterogeneous tumors with clearly different clones associated with APOBEC-mediated mutagenesis, suggesting the importance of evaluating intratumor histological and genetic heterogeneity among multiple sites of MCT-SCC.

A nomogram for predicting survival in patients with skin non-keratinizing large cell squamous cell carcinoma: A study based on the Surveillance, Epidemiology, and End Results database.

This study aimed to develop and validate a nomogram for predicting cancer-specific survival (CSS) in patients with non-keratinized large cell squamous cell carcinoma (NKLCSCC) at 3, 5, and 8 years after diagnosis. Data on SCC patients were collected from the Surveillance, Epidemiology, and End Results database. Training (70%) and validation (30%) cohorts were generated using random selection of patients. Independent prognostic factors were selected using the backward stepwise Cox regression model. To predict the CSS rates in patients with NKLCSCC at 3, 5, and 8 years after diagnosis, all of the factors were incorporated into the nomogram. Indicators such as the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration curve, and decision-curve analysis (DCA) were then used to validate the performance of the nomogram. This study included 9,811 patients with NKLCSCC. Twelve prognostic factors were identified by Cox regression analysis in the training cohort, which were age, number of regional nodes examined, number of positive regional nodes, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, surgery status, chemotherapy status, radiotherapy status, summary stage, and income. The constructed nomogram was validated both internally and externally. The nomogram had good discrimination ability, as indicated by the comparatively high C-indices and AUC values. The nomogram was properly calibrated, as indicated by the calibration curves. Our nomogram was superior to the AJCC model, as illustrated by its superior NRI and IDI values. DCA curves indicated the clinical usability of the nomogram. The first nomogram for prognosis predictions of patients with NKLCSCC has been developed and verified. Its performance and usability demonstrated that the nomogram could be utilized in clinical settings. However, additional external verification is still required.

Programmed death ligand-1 expression and its association with the degree of differentiation and the presence of necrosis in non-small cell lung carcinoma

The mechanisms underlying the expression of programmed death ligand-1 (PD-L1) in non-small cell lung carcinoma (NSCLC) are not yet fully clarified. In this study, surgical resections of 730 lung cancer patients with diagnosed NSCLC were analyzed. Results of PD-L1 immunohistochemistry (using clone 22C3) were correlated with clinicopathological variables including the degree of tumor differentiation and the presence of confluent areas of coagulative necrosis. PD-L1 immunohistochemistry was analyzed in tumor cells, whereas PD-L1 positivity was defined as membranous staining in ≥1 of tumor cells. A significantly higher proportion of PD-L1 positive cases was noted in poorly differentiated (grade 3) adenocarcinomas compared to better differentiated (grade 1 and grade 2) subtypes (63.8% vs. 28.7%; p<0.001). Contrary to this, better differentiated (keratinizing) and less differentiated (non-keratinizing) squamous cell carcinoma subtypes were found to have a similar proportion of PD-L1 positive cases (51.4% vs. 55.8%; p=0.570). High levels of PD-L1 expression significantly correlated with the presence of necrosis in NSCLC: seventy-nine of 109 NSCLC cases with the presence of necrosis were PD-L1 positive compared to 256 out of 621 NSCLC without necrosis (72.5% vs. 41.2%; p<0.001). High PD-L1 expression was not positively correlated with age, gender, and advanced T stage but a significant association between PD-L1 positivity and higher N stage was observed (p<0.001) in NSCLC patients. In conclusion, the proportion of PD-L1 positive cases is higher only in poorly differentiated NSCLC of the adenocarcinoma type. A significantly higher overall rate of PD-L1 positive cases was noted in NSCLC with the presence of necrosis. Further investigation is suggested to elucidate the intricated interconnections between the plethora of hypoxic biomarkers and immunological factors in different types and subtypes of NSCLC.

MTA1 as negative prognostic marker in vulvar carcinoma

PurposeVulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis.MethodsA total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters.ResultsMTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan–Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1.ConclusionsMTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma.

Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

Epidemiology and Histopathology of Nasopharyngeal Neoplasms in Iran.

This study aimed to study the trend, histologic pattern, geographical distribution, and characteristics of nasopharyngeal carcinoma (NPC) and nasopharyngeal neoplasms (NPN) from 2003 to 2017 in Iran. The Ministry of Health and Medical Education collected NPN cases from the corresponding university in each province and stored them in Iran National Cancer Registry (INCR) database. The Joinpoint program calculated the average annual percent change (AAPC) and its 95% confidence interval (CI). The jump model minimized the interfering effect of INCR transformation. 3653 NPN cases were reported between 2003-2010 and 2014-2017, with a mean age of 49.04 ± 18.31 years and a male-to-female ratio of 2.15. The age-standardized incidence rate (ASIR) per 100,000 person-years was 0.30 for females and 0.68 for males in 2017. Although the ASIR/100,000 of NPN raised from 0.35 to 0.49 during 2003-2017, the trend was constant with an AAPC of -2% (95% CI: -4.8% to 0.9%). The age-specific incidence rate was highest in the older than 70 population (1.56/100,000). NPC formed 77.1% of NPNs and showed a constant pattern (AAPC CI: -5.7% to 0.2%), in contrast to the significant increase of non-keratinizing squamous cell carcinoma (AAPC CI: 2.3%to 24.5%). Nasopharynx cancer is rare in Iran, and NPC incidence remained constant from 2003 to 2017, unlike previously reported rising trend. However, non-keratinizing squamous cell carcinoma exhibited a significant increase, and future studies are needed to examine the role of the Epstein-Barr virus on this growth rate.

Survival comparison of different histological subtypes of oropharyngeal squamous cell carcinoma: A propensity-matched score analysis based on SEER database.

The purpose of this study was to analyze the difference of survival rates in paitents with oropharyngeal keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), basaloid squamous cell carcinoma (BSCC), and papillary squamous cell carcinoma (PSCC). Patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2015 were collected from the SEER database. Cox proportional hazards models and Kaplan-Meier curves were used for survival analysis. Propensity score matching (PSM) was performed to adjust for the effect of confounding variables. Due to the small sample size of PSCC, this study did not perform PSM between it and other subtypes. The 5-year cancer-specific survival (CSS) rate of PSCC was higher than that of KSCC, NKSCC, and BSCC (0.627 vs. 0.812 vs. 0.789 vs. 0.875, P < 0.05); And the CSS rate of KSCC was lower than that of other subtypes both before and after PSM. In addition, the 5-year and 10-year CSS rates of BSCC were not different from NKSCC (P > 0.05), but not as good as NKSCC in the long term (P = 0.028). After PSM, the 5-year, 10-year, and long-term prognosis of BSCC were significantly worse than those of NKSCC (P < 0.001). The 5-year CSS of PSCC was better than the other three subtypes. The short-term prognosis of BSCC was not significantly different from NKSCC, but the long-term survival was lower than that of NKSCC, and the difference was more obvious after PSM. Meanwhile, the prognosis of KSCC was worst.

AN UNUSUAL CASE OF CHRONIC RHINOSINUSITIS

<h3>Introduction</h3> We present a case of long-standing nasal symptoms initially suggestive of chronic rhinosinusitis with nasal polyposis (CRSwNP) but later found to be an atypical etiology. <h3>Case Description</h3> A 30 year-old female with past medical history of tobacco use disorder presented with two years of nasal congestion, rhinorrhea, and lost of taste and smell. She was trialed on diphenhydramine, loratidine, fexofenadine, cetirizine, and intranasal budesonide without significant relief. She had history of ENT provocation testing positive for tree, weeds, grass pollen, mold, dust mite and pet dander and was started on subcutaneous allergy immunotherapy without improvement. Additional history was notable for mild eosinophilia of 300 cells/μL and vomiting and nasal congestion to tramadol and naproxen - though tolerated other NSAIDs. She was evaluated by ENT where she was found to have large nasal polyps via rhinoscopy and diagnosed with CRSwNP. A referral to Allergy was made for consideration of dupilumab therapy. However, CT scan showed large mass eroding into nearby facial sinuses. There was also notable increased bone growth along right middle turbinate initially suggestive of inverted papilloma. Pathology showed invasive poorly differentiated non-keratinizing squamous cell carcinoma positive for HPV. Definitive treatment involved multiple debulking procedures and adjuvant radiation. <h3>Discussion</h3> This case highlights the typical treatment of chronic rhinosinusitis with nasal polyposis as well as the broad differential required of her presenting symptoms. Her symptoms were very suggestive of chronic sinusitis with nasal polyposis, but treatment was resistant. Other etiologies of nasal polyps, including malignancy, should be on differential of recalcitrant nasal symptoms.

Clinicopathological Challenges in Tumors of the Nasal Cavity and Paranasal Sinuses: Our Experience.

Background and objectiveNasal and paranasal lesions are one of the most common otorhinolaryngological presentations encountered in clinical practice. Common presenting symptoms of these lesion range from nasal blockades, facial swellings, pain, nasal discharge, and epistaxis to orbital and ear symptoms. Diagnosis can be tricky as these symptoms are common in inflammatory conditions and tumors. The aim of our study was to observe the epidemiology and clinical pathological findings in patients with nasal and paranasal masses presenting to our institute and discuss the challenges in proper diagnosis and management due to similar presentations, and the role of histopathological examination (HPE) and immunohistochemistry (IHC) in overcoming these challenges.MethodsThe IPD records of 396 patients were taken up for the study. All the specimens were sent in 10% neutral buffered formalin for examination as biopsy for diagnosis or after surgical excision. After adequate fixation, the biopsy specimen was submitted for routine processing, followed by paraffin embedding, and stained with hematoxylin and eosin (H&E). Special stains like periodic acid-Schiff (PAS) and Ziehl-Neelsen (ZN) stains for acid-fast bacilli (AFB) were used as required. IHC was performed in the required samples. IHC markers were performed on representative paraffin-embedded sections according to the streptavidin-biotin immunoperoxidase technique as needed. The findings were noted, and histology was correlated with clinical presentations and investigations, tabulated, and statistically analyzed using SPSS Statistics (IBM, Armonk, NY).ResultsOf note, 67.92%% were non-neoplastic lesions whereas 18.18% came out to be benign neoplasms and 13.88% were malignant lesions on HPE. Nasal obstruction was the most common presenting symptom (73.23% of patients) followed by nasal mass (64.14% of cases). Inflammatory sinonasal polyps were the most prominent cases in our study, accounting for 41.16% of all lesions; 18.68% fungal RS (mucormycosis) were seen in our study and 4.54% were cases of juvenile nasopharyngeal angiofibroma (JNA). The majority of benign neoplasms encountered were Schneiderian papilloma or inverted papilloma (06.81%). Eighteen (4.54%) cases of squamous cell carcinomas (SCC) were seen in our study and 2.77% (n=11) cases were of adenoid cystic carcinoma. Of 18 cases of SCC, moderately differentiated SCC carcinoma accounted for 10 cases followed by poorly differentiated SCC (5/18) and nonkeratinizing SCC (3/18). IHC for p40 was performed in all the cases of nonkeratinizing SCC, which showed strong and diffuse nuclear positivity.ConclusionThe nasal cavity is the site of the most varied presentation of tumors in the upper respiratory tract. Mass in the nose and paranasal sinus (PNS) form a heterogeneous group of lesions with varied histopathological features. The proximity of the area to the eyes and brain warrants early definitive diagnosis so that the lesion is treated before it can involve important and vital centers. Even though malignant nasal tumors have a very low incidence, they cause a lot of morbidity due to their long course and frequent local recurrences. Nasal tumors tend to become polypoidal. Epithelioid papilloma of the nasal cavity often resembles a nasal polyp. Clinical diagnosis can be challenging due to similar presentations and appearances, and hence histological examination is a vital tool for the timely diagnosis of such patients.

Relationship between Age and Gender with Histopathological Type of Nasopharyngeal Carcinoma

BackgroundNasopharyngeal carcinoma (NPC) is a malignancy with a high incidence in Indonesia. Recent studies had found several factors that influence the incidence and prognosis of NPC including age, sex, and histopathological type. This study aimed to determine the relationship between age and sex with the histopathological type of NPC.MethodsSubjects were NPC patients diagnosed by the Anatomical Pathology Department of Dr. Kariadi General Hospital Medical Center (RSUP Dr. Kariadi) from 1st January 2017-31st December 2019. Data were collected from the medical record. The relationship between age and sex with the histopathological type of NPC was examined. ResultsThere were 201 NPC patients during 2017-2019 in RSUP Dr. Kariadi. The highest number of NPC incidence was in the range of 54-59 years old. There were more males than females at the ratio of 2.24:1. Undifferentiated non-keratinizing cell carcinoma type NPC was the most common type (90.5% of NPC patients), followed by differentiated non-keratinizing cell carcinoma and squamous cell carcinoma consecutively. Both age and sex had no significant relationship with the histopathological type of NPC (p&gt;0.05).ConclusionThere was no relationship between age and sex with the histopathological type of NPC.

A combined microinvasive trans-submandibular and nasendoscopy surgical approach to dissect recurrent or radiotherapy-insensitive nasopharyngeal carcinoma.

ObjectiveTo investigate a novel combined microinvasive trans-submandibular and nasendoscopy surgical approach for nasopharyngeal carcinoma involving the parapharyngeal space.MethodsSeven patients diagnosed with nasopharyngeal carcinoma involving the parapharyngeal space between May 2018 and April 2021, two males and five females, aged 37–63 years.Six of the 7 patients underwent submental flap preparation and dissection of the lymph nodes in the upper neck and parapharyngeal space on the lesion side. The nasopharynx lesions and tumor margins were dissected under nasal endoscopy. The medial boundary of internal carotid artery separated by open cervical approach was used as the lateral boundary of the tumor to realize en bloc resection of the tumor.ResultsThe patients were preoperatively diagnosed with T2~3N0M0 nasopharyngeal carcinoma, including mucoepidermoid carcinoma (n=2), papillary adenocarcinoma (n=1), and nonkeratinizing squamous cell carcinoma (n=4). The tumors were removed completely, and patients achieved primary healing of the incision. No recurrence and no serious complications were recorded during the 13–48 month follow-up.ConclusionComplete resection of the tumor was obtained in the 7 patients without recurrence and serious complications during the follow-up. The findings of this cohort study suggest that, patients with recurrent nasopharyngeal carcinoma after radiotherapy and radiotherapy-insensitive types of nasopharyngeal carcinoma, the combined microinvasive trans-submandibular and nasendoscopy surgical approach may be considered as an surgical options. The results of this study provide an additional option for surgical treatment of NPC in the clinic.

A Novel Prognostic Risk Model for Cervical Cancer Based on Immune Checkpoint HLA-G-Driven Differentially Expressed Genes.

Human leukocyte antigen G (HLA-G) is a potential checkpoint molecule that plays a key role in cervical carcinogenesis. The purpose of this study was to construct and validate a prognostic risk model to predict the overall survival (OS) of cervical cancer patients, providing a reference for individualized clinical treatment that may lead to better clinical outcomes. HLA-G-driven differentially expressed genes (DEGs) were obtained from two cervical carcinoma cell lines, namely, SiHa and HeLa, with stable overexpression of HLA-G by RNA sequencing (RNA-seq). The biological functions of these HLA-G-driven DEGs were analysed by GO enrichment and KEGG pathway using the “clusterProfiler” package. The protein-protein interactions (PPIs) were assessed using the STRING database. The prognostic relevance of each DEG was evaluated by univariate Cox regression using the TCGA-CESC dataset. After the TCGA-CESC cohort was randomly divided into training set and testing set, and a prognostic risk model was constructed by LASSO and stepwise multivariate Cox regression analysis in training set and validated in testing set or in different types of cervical cancer set. The predictive ability of the prognostic risk model or nomogram was evaluated by a series of bioinformatics methods. A total of 1108 candidate HLA-G-driven DEGs, including 391 upregulated and 717 downregulated genes, were obtained and were enriched mostly in the ErbB pathway, steroid biosynthesis, and MAPK pathway. Then, an HLA-G-driven DEG signature consisting of the eight most important prognostic genes CD46, LGALS9, PGM1, SPRY4, CACNB3, PLIN2, MSMO1, and DAGLB was identified as a key predictor of cervical cancer. Multivariate Cox regression analysis showed that this signature is an independent risk factor for the overall survival of CESC patients. Kaplan-Meier survival analysis showed that the 5-year overall survival rate is 23.0% and 84.6% for the high-risk and low-risk patients, respectively (P<0.001). The receiver operating characteristic (ROC) curve of this prognostic model with an area under the curve (AUC) was 0.896 for 5 years, which was better than that of other clinical traits. This prognostic risk model was also successfully validated in different subtypes of cervical cancer, including the keratinizing squamous cell carcinoma, non-keratinizing squamous cell carcinoma, squamous cell neoplasms, non-squamous cell neoplasms set. Single-sample gene set enrichment (ssGSEA) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis confirmed that this signature influence tumour microenvironment and immune checkpoint blockade. A nomogram that integrated risk score, age, clinical stage, histological grade, and pathological type was then built to predict the overall survival of CESC patients and evaluated by calibration curves, AUC, concordance index (C-index) and decision curve analysis (DCA). To summarize, we developed and validated a novel prognostic risk model for cervical cancer based on HLA-G-driven DEGs, and the prognostic signature showed great ability in predicting the overall survival of patients with cervical cancer.

MDM2 is a useful diagnostic marker for nasopharyngeal carcinoma

BackgroundThe MDM2 gene appears to be involved in the development of nasopharyngeal carcinoma. The aim of this study was to examine MDM2 expression in a series of nasopharyngeal carcinoma biopsies to explore its potential diagnostic significance. MethodsThe study cohort consisted of 26 nasopharyngeal carcinomas, including 22 EBV positive non-keratinizing squamous cell carcinomas (NKSCC), 1 EBV negative NKSCC and 3 EBV negative keratinizing SCC. For comparison, we selected 48 oropharyngeal carcinomas, including 17 HPV positive SCC (14 non-keratinizing and 3 keratinizing) and 31 HPV negative SCCs (28 keratinizing and 3 non-keratinizing). In addition, we examined MDM2 expression in a group of 26 cervical lymph node metastases, including 5 with EBV positive nasopharyngeal NKSCC and 21 from oropharyngeal carcinoma (18 non keratinizing HPV positive, 1 keratinizing HPV positive, 1 keratinizing HPV negative and 1 non-keratinizing HPV negative). Finally, 2 bone metastases from EBV positive nasopharyngeal NKSCC were also included. A tissue microarray was constructed from formalin-fixed paraffin embedded tumor tissue specimens. Sections were immunostained for MDM2 and in situ hybridization for EBER and CISH analysis for the MDM2 gene were also conducted in all cases. ResultsOverall, MDM2 positivity was detected in 28 of 102 SCCs (27.2 %). MDM2 positivity was significantly more frequent in EBV positive NKSCC (80 %) than in oropharyngeal HPV positive NKSCC (6.1 %) and keratinizing SCCs (9.4 %) (p < 0.001, Pearson chi square). Considering only the primary tumors, 86.4 % of the nasopharyngeal carcinomas were positive, versus 13.5 % of the oropharyngeal carcinomas (p < 0.001, Pearson chi square). Considering the lymph node metastases, 3 of 5 EBV positive carcinomas with nasopharyngeal primary were positive, whereas only one of the HPV positive carcinomas was positive. Finally, both the bone metastases from EBV positive nasopharyngeal carcinoma were positive for MDM2. No amplification of the MDM2 gene was identified by in situ hybridization analysis. ConclusionsOur data indicate that MDM2 could be a valuable diagnostic marker to support the diagnosis of nasopharyngeal EBV positive NKSCC.

CORRELATION INDEX PERITUMORAL BUDDING TUMOUR WITH GRADING HISTOPATHOLOGY CERVICAL SQUAMOUS CELL CARCINOMA NOS

Background: Cervical squamous cell carcinoma NOS cervix It is an invasive epithelial tumor with varying degrees of differentiation. The prognostic grading system based on WHO (2020) is assessed from nuclear pleomorphism, mitosis, tumor cell invasion, keratin, and necrosis. Tumor budding is an isolated tumor cell bud 5 cells.1 This tumor budding phenomenon is considered the histological basis for the formation of metastases and further tumor invasion which is an independent prognostic, especially in cervical squamous cell carcinoma NOS.15 Research purposes: Analyze the relationship between tumor index peritumoral budding with grading histopathology in patients squamous cell carcinoma NOS cervix. Materials and Methods: This research is an analytic research approach cross-sectional in 36 samples of paraffin blocks of patients diagnosed histopathologically with Cervical SCC. Then, the paraffin block was re-cut, followed by staining slides with H&E. Conducted an assessment of peritumoral budding tumor categorized as no buds (low grade) and 15buds (intermediate grade), also 15buds (high grade), rating relationship peritumoral budding tumor with grading histopathology squamous cell carcinoma NOS cervix as a prognostic independent on Cervical SCC statistically tested. Results: Most were in the age group >51 years and a few were aged 31-35 years. Most parity 2x parturition, and most nonkeratinizing squamous cell carcinoma compared keratinizing squamous cell carcinoma, the correlation between grading histopathology squamous cell carcinoma NOS cervix with age, there was no significant relationship. Relationship between grade with parity constant and unrelated. Conclusion: Significant relationship between tumor index peritumoral budding with grading histopathology in cases squamous cell carcinoma NOS cervix