Keratinizing Squamous Cell Carcinoma Research Articles

Case – Late Presentation of Invasive Keratinizing Squamous Cell Carcinoma

Penile cancer, a rare but highly morbid disease, primarily manifests as squamous cell carcinoma (PSCC) originating from the squamous cells of the glandular and preputial skin. Late-stage diagnosis is common due to social stigma, psychological barriers, and nonspecific initial symptoms, resulting in poor overall survival rates, especially in metastatic cases. This case report illustrates a 38-year-old man with advanced metastatic PSCC, showcasing severe systemic manifestations and delayed presentation of the disease. Despite aggressive treatment options, the patient opted for palliative care, succumbing to the disease months after his diagnosis. Risk factors for PSCC include HPV infection, phimosis, chronic inflammation, and lifestyle factors, with higher prevalence in regions of low socioeconomic status. The psychological and sexual burden of penile cancer is significant, impacting patients’ well-being, mental health, and quality of life. In conclusion, efforts to reduce the stigma associated with penile cancer are crucial to prompt early diagnosis and treatment initiation. Encouraging seeking medical attention for symptoms can enhance the chances of recovery and minimize the need for invasive treatments. Addressing the psychosocial impact of the disease is imperative for holistic patient care.

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.

THE CORRELATION BETWEEN PRESENCE OF EOSINOPHIL WITH HISTOPATHOLOGICAL SUBTYPES IN NASOPHARYNGEAL CARCINOMA

Background: Nasopharyngeal carcinoma is a malignancy shows squamous differentiation, incidence rate was 5% in Indonesia. Eosinophils are granulocytic leukocytes residing in blood and tissues, has been related as a prognostic indicator for cancers. Whether an increase in eosinophils leading to favorable or unfavorable prognosis still remains controversial and depends on many factors including the type of cancer. Objective: This study was aimed to analyze correlation the presence of eosinophil with histopathologic subtypes in nasopharyngeal carcinoma Material and Methods: This study was analytic, with cross-sectional approach, which were enrolled 72 slides of NPC biopsy, and assessed by accounting eosinophils in 10 high power field (HPF) with 40X magnification. The result with 0 is nothing eosinophil, 1-4 is mild infiltration, 5-19 is moderate infiltration, ?20 is severe infiltration. Result: There were more males than females, with the highest age group being 51-60 years and the most common histopathological subtype was non-keratinizing squamous cell carcinoma (NKSCC). In NKSCC subtype, the most common eosinophil infiltration category groups were mild and moderate infiltration as many as 25 (39.7%) samples, and in keratinizing squamous cell carcinoma (KSCC) subtype the most common samples were obtained in mild infiltration category group 5 (55.6%) samples. Mann Whitney U test was performed on this variable and obtained p-value 0.025 (p ? 0.05). Conclusion: There was correlation between presence of eosinophil with histopathological subtypes in nasopharyngeal carcinoma.

Detection of human papilloma virus (HPV) in parafin block of cervical cancer patients using multiplex polymerase chain reaction (PCR) and reverse line blot methods

ObjectivesThe aim of this study is to detect human papilloma virus (HPV) especially types 16 and 18 through DNA expression from paraffin block preparations of cervical cancer and pre-cancer. MethodsThis study was conducted at the Anatomical Pathology Laboratory and Molecular biology Hasanuddin University Medical Research Center (HUMRC) Laboratory. The samples that used were came from cervical specimens which had been processed into paraffin blocks and had been diagnosed as Cervical Intra-epithelial Neoplasia (CIN) and Cervical carcinoma. HPV DNA was extracted from paraffin blocks using DNA extraction reagents from FFPE (Qiagen). DNA extraction products were then propagated by the polymerase chain reaction (PCR) method. HPV genotyping is done by a reverse line blot method using Ampliquality HPV-Type Express (AB Analitica). ResultsTotally 67 cervical samples from paraffin blocks preparations were diagnosed in Squamous Cell Carcinoma (SCC) and Cervical Intra-epithelial Neoplasia (CIN). The large number of cancer patients was more than 40 years old (42 patients/67.7%), with most of which are in the periods 41–50 years old (25 patients/40.3%). The most common cancer type was Non Keratinizing Squamous Cell Carcinoma (NK-SCC) with 50 (74.6%) samples. The most infectious strains are HPV strains 16, which were found in 53 (79.1%) samples both in single infection and co-infection with other HPV strains. Three of four HPV strains found were 16, 18 and 52 strains that belonging to High Risk strain of HPV, while strain 67 was included in the low risk group. There was also co-infection of 2 different HPV strains which involved 16 & 67 HPV Co-infection and 52 & 67 HPV Co-infection. ConclusionCervical cancer patients were more commonly found in women with more than 30 years old, which the most common type was Non keratinizing squamous cell carcinoma (NK-SCC). HPV infection is strongly associated with cervical cancer. HPV 16 infection was found in many cervical cancer lesions both as a single infection and co-infection with other types of low risk HPV.

Comprehensive Molecular Characterizations of Chinese Patients With Different Subtypes of Lung Squamous Cell Carcinoma.

BackgroundThis study aims to profile integrative genomic spectra of Chinese patients with different subtypes of lung squamous cell carcinoma (LUSC) and explore potential molecular prognosis factors.MethodsWe retrospectively identified 204 surgically resected LUSC patients in Shanghai Chest Hospital who underwent capture-based targeted next-generation sequencing (NGS) with a panel of 68 lung cancer‐related genes from September 2017 to January 2019. NGS was used to profile comprehensive molecular characterizations.ResultsOf 204 cases, 114 (55.9%) were keratinizing squamous cell carcinoma (KSCC), 77 (37.7%) were non-keratinizing squamous cell carcinoma (NKSCC), 13 (6.4%) were basaloid squamous cell carcinoma (BSCC), respectively. All subtypes presented similarly high proportions of mutations, including TP53, CDKN2A, and NOTCH1. A comparable prevalence of FGFR1 amplifications was identified between KSCC and NKSCC (11.4 versus 26.9%, p = 0.007). Compared with NKSCC, IGF1R amplifications were more frequent in BSCC (0 versus 15.4%, p = 0.019). We found cases with TP53 alterations had less EGFR alterations in KSCC (P = 0.013, OR = 0.158). Compared with TCGA cohorts, our Chinese cohorts exhibited statistic differences in both somatic mutations and signaling pathways. We found that STK 11 alterations and TOP2A alterations were significantly associated with higher risk of recurrence in patients with LUSC.ConclusionsSignificant differences exist among three subtypes of LUSC in molecular characterizations.

S1971 Femur Fracture as Initial Presentation of Esophageal Squamous Cell Carcinoma

INTRODUCTION: Squamous Cell Carcinoma (SCC) of the esophagus is a highly malignant tumor that can progress rapidly without treatment. Given the highly malignant potential of SCC, approximately 50% of patients are found to have metastatic disease at initial diagnosis. However, according to one study, esophageal adenocarcinoma is 3 times more likely to metastasize to the bone than SCC. Our patient presented uniquely with a bone metastasis from SCC resulting in a pathologic femur fracture. CASE DESCRIPTION/METHODS: A 65-year-old male presented to the emergency department with complaints of severe left leg pain. He reports being woken up from a nightmare with the pain at which point he noticed an obvious deformity of his left upper leg. Radiographs of his left leg were concerning for a pathologic fracture of the distal femur within a large underlying lytic lesion. Interestingly, he had presented to the ED two months prior with complaints of left leg pain and had a normal femur radiograph at that time. Given concerns for metastatic disease a CT Chest/Abdomen/Pelvis was obtained and revealed central esophageal wall thickening with mediastinal lymphadenopathy and right sided pleural effusion. He also had additional lytic bone lesions of the right 8th rib and left iliac bone. Esophagogastroduodenoscopy was performed given esophageal thickening and revealed malignant appearing esophageal stenosis suspicious for squamous cell carcinoma. Biopsies were taken and confirmed the diagnosis of Invasive Keratinizing Squamous Cell Carcinoma. CT Guided bone biopsy of left femur lesion revealed the same pathology (Figure 9) confirming the diagnosis of metastatic esophageal squamous cell carcinoma. Intramedullary nail fixation of his left femur was performed along with placement of PEG tube and port for initiation of chemotherapy with Carboplatin/Paclitaxel. He eventually passed away from complications of his disease. DISCUSSION: Historically, esophageal SCC accounted for most cases of esophageal cancer, however over the past few decades esophageal adenocarcinoma has taken over as the most common esophageal malignancy. Given our patient's recent history of stroke, his previous complaints of dysphagia were not worked up further. Two months prior to this presentation he reported left leg pain and had an unremarkable radiograph of the left femur. This case highlights the importance of obtaining a timely and detailed history and physical examination to avoid delaying diagnostic and therapeutic measures for esophageal cancer.Figure 1.: Pathologic distal femur fracture with underlying lytic bone lesion.Figure 2.: Femur biopsy showing metastatic squamous cell carcinoma with malignant squamous cells forming keratin pearls and invading fibrous stroma surrounding the bone.Figure 3.: Malignant appearing esophageal stenosis.

Survival comparison of Three histological subtypes of lung squamous cell carcinoma: A population-based propensity score matching analysis

ObjectivesThis study is aimed to analyze the survival differences among patients with lung basaloid squamous cell carcinoma (BSCC), keratinizing squamous cell carcinoma (KSCC), and nonkeratinizing squamous cell carcinoma (NKSCC), and explore the prognostic factors of patients with lung BSCC. Materials and MethodsWe searched the information of 4743 patients with lung SCC between 2005 and 2014 from the SEER database. Propensity score matching (PSM) was used to adjust confounding factors. The overall survival (OS), cancer-specific survival (CSS), and cumulative incidence of cancer-specific mortality (CSM) were estimated with a comparative analysis. A competing risks regression model was conducted to identify the prognostic factors of lung BSCC. ResultsAfter PSM, patients with lung BSCC had a higher CSS rate than those with lung KSCC or NKSCC (5-year CSS rate: 50.4 % vs. 37.7 % vs. 38.5 %, p = 0.033 and p = 0.033). The cumulative incidence of CSM was lower for patients with lung BSCC than those with lung KSCC or NKSCC (5-year CSM rate: 46.4 % vs. 56.9 % vs. 56.4 %, p = 0.046 and p = 0.042), which were similar to the results before PSM. As for patients with lung KSCC and NKSCC, there was no survival differences between them (5-year CSS rate: 37.7 % vs. 38.5 %, p = 0.997). The competing risks regression analysis showed that T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC (all p < 0.05). ConclusionsPatients with lung BSCC had a better survival than those with lung KSCC or NKSCC, while no survival differences were found between lung KSCC and NKSCC. T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC.

The effect of histological subtypes on survival outcome in nasopharyngeal carcinoma after extensive follow up.

No consensus exists regarding the follow-up of nasopharyngeal carcinoma (NPC) patients stratified by different histological subtypes. The purpose of this study was to determine the hazard function of disease-related death and assess the prognostic effect of early and late disease-related death in NPC according to histological subtypes. We included non-metastatic NPC patients between 2004 and 2014 using the Surveillance, Epidemiology and End-Results (SEER) program. Life-table methods, Kaplan-Meier methods, and a multivariate Cox regression model were used in the analysis. We identified 2,845 patients in this study including 1,218 (42.8%), 849 (29.8%), and 778 (27.3%) patients with keratinizing squamous cell carcinoma (KSCC), differentiated non-keratinizing carcinoma (DNKC), and undifferentiated non-keratinizing carcinoma (UNKC), respectively. Most NPC-related death (89.8%) occurred within 5 years of diagnosis. In the entire cohort, the hazard curve for NPC-related death peaked at 2 years. It peaked at 1 year, 2- and 5-year, and 2- and 6-year in patients with KSCC, DNKC, and UNKC, respectively. Within the follow-up period over 5 years, patients with DNKC had poorer NPC-specific survival (NPC-SS) compared to UNKC, and had comparable NPC-SS between the two subtypes after more than 5 years of follow-up. Moreover, within the follow-up period of 1, 2, and 3 years, patients with KSCC experienced poorer NPC-SS compared to UNKC but there was comparable NPC-SS between KSCC and UNKC patients after more than 3 years of follow-up. The hazard rate patterns for NPC-related mortality significantly differed between histological subtypes. Tailored surveillance and follow-up strategies should be designed in NPC patients according to histological subtypes.

Lymph Node Status and Outcomes for Nasopharyngeal Carcinoma According to Histological Subtypes: A SEER Population-Based Retrospective Analysis.

We aimed to investigate the clinical effect of histological subtypes on survival in nasopharyngeal carcinoma (NPC), and assess the effect of nodal stage on outcome according to histological subtypes. Patients with non-metastatic NPC were identified from the Surveillance, Epidemiology and End-Results (SEER) database between 2004 and 2014. Statistical analysis was performed using the chi-squared test, Kaplan-Meier methods, and multivariate Cox regression models. We identified 2845 patients in this study including 1218 (42.8%), 849 (29.8%), and 778 (27.3%) patients with keratinizing squamous cell carcinoma (KSCC), differentiated non-keratinizing squamous cell carcinoma (DNKSCC), and undifferentiated non-keratinizing squamous cell carcinoma (UNKSCC), respectively. The multivariate analysis indicated that patients with UNKSCC subtype had better NPC-specific survival (NPC-SS) (P < 0.001) compared to KSCC (P < 0.001) and DNKSCC (P < 0.001) patients. The 5-year NPC-SS was 75.2%, 77.9%, and 88.9% in patients with KSCC, DNKSCC, UNKSCC, respectively (P < 0.001). Subgroup analysis showed that advanced nodal stage was related to lower NPC-SS in patients with DNKSCC and UNKSCC but not in patients with KSCC. Histology is an independent prognostic factor in patients with NPC. However, advanced nodal stage is not associated with lower survival in KSCC.

Adenoid Basal Carcinoma of the Uterine Cervix in Association with Keratinizing Squamous Cell Carcinoma: a Rare Diagnosis.

Adenoid Basal Carcinoma of the Uterine Cervix in Association with Keratinizing Squamous Cell Carcinoma: a Rare Diagnosis.

Lung squamous cell carcinoma: A postoperative recurrence analysis of keratinizing and nonkeratinizing subtypes

BackgroundThere is currently no definite clinical implication for the subtypes of lung squamous cell carcinoma according to the 2015 WHO classification. This study aimed to investigate postoperative recurrence of the two major subtypes of lung squamous cell carcinoma: keratinizing squamous cell carcinoma (KSCC) and nonkeratinizing squamous cell carcinoma (NKSCC). MethodsWe identified the patients with KSCC and NKSCC who had undergone complete resection in Shanghai Chest Hospital between April 2015 and June 2016. Disease-free survival (DFS) was compared using Kaplan-Meier statistical analysis. Variables selected by univariate analysis were evaluated in multivariate analysis using the Cox proportional hazard model. ResultsA total of 334 patients included 231 (69.2%) cases with KSCC and 103 (30.8%) cases with NKSCC. There were more smokers in keratinizing than nonkeratinizing subtype (84.8% versus 72.8%, p = 0.009). The percentage of stage Ⅲ was higher in NKSCC than that in KSCC (35% versus 22.9%, p = 0.012). The 2-year DFS rates of stage Ⅰ, stage Ⅱ and stage Ⅲ were 90.1%, 66.4% and 37.7% in KSCC, 83.3%, 67.7% and 52.8% in NKSCC, respectively. There were no significant differences of 2-year DFS rates between KSCC and NKSCC. Furthermore, KSCC and NKSCC had no significant differences in recurrence patterns and metastatic sites. ConclusionThere were no significant differences of postoperative recurrence between KSCC and NKSCC.

Correlation of clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification

AimsThis study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma (LSCC) subtypes according to the 2015 WHO classification. MethodsWe identified 824 operable LSCC patients undergoing a complete surgical resection at Shanghai Chest Hospital between April 2015 and January 2017. Immunohistochemistry was used to investigate the clinicopathologic features. ResultsAmong them, the percentages of LSCC subtypes were 66.1% (545/824), 28.6% (236/824), and 5.2% (43/824) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more males, more smokers, and more pneumonectomy surgeries in KSCC patients (p = 0.008, p = 0.000, p = 0.043). There were more N2 lymph node involvement and pathological stage III in NKSCC patients (p = 0.01, p = 0.03). BSCC did not demonstrate specificity to anything, but expressed adenocarcinoma markers more frequently. No significant difference existed between pathological subtypes and other clinicopathologic features, such as age, location type, visceral pleural involvement and lymphovascular invasion. The frequencies of EGFR sensitive mutations and ALK rearrangements were not significantly different among three subtypes. ConclusionSignificant relationships exist between some clinicopathologic features and LSCC subtypes.

Global trends in nasopharyngeal cancer mortality since 1970 and predictions for 2020: Focus on low-risk areas.

Nasopharyngeal cancer (NPC) mortality shows great disparity between endemic high risk areas, where non-keratinizing carcinoma (NKC) histology is prevalent, and non-endemic low risk regions, where the keratinizing squamous cell carcinoma (KSCC) type is more frequent. We used the World Health Organization database to calculate NPC mortality trends from 1970 to 2014 in several countries worldwide. For the European Union (EU), the United States (US) and Japan, we also predicted trends to 2020. In 2012, the highest age-standardized (world standard) rates were in Hong Kong (4.51/100,000 men and 1.15/100,000 women), followed by selected Eastern European countries. The lowest rates were in Northern Europe and Latin America. EU rates were 0.27/100,000 men and 0.09/100,000 women, US rates were 0.20/100,000 men and 0.08/100,000 women and Japanese rates were 0.16/100,000 men and 0.04/100,000 women. NPC mortality trends were favourable for several countries. The decline was -15% in men and -5% in women between 2002 and 2012 in the EU, -12% in men and -9% in women in the US and about -30% in both sexes in Hong Kong and Japan. The favourable patterns in Europe and the United States are predicted to continue. Changes in salted fish and preserved food consumption account for the fall in NKC. Smoking and alcohol prevalence disparities between sexes and geographic areas may explain the different rates and trends observed for KSCC and partially for NKC. Dietary patterns, as well as improvement in management of the disease, may partly account for the observed trends, too.

PUB094 Correlation of Clinicopathologic Features and Lung Squamous Cell Carcinoma Subtypes According to the 2015 WHO Classification

This study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification. We identified 368 operable lung squamous cell carcinoma patients who had undergone a complete surgical resection at Shanghai Chest Hospital between April 2015 and March 2016. Among all patients, the percentages of lung squamous cell carcinoma subtypes were: 68.5% (252/368), 26.2% (97/368), and 5.1% (19/368) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more smokers in patients with KSCC than in patients with other subtypes (p=0.004). There were no significant relationships between pathological subtypes and other clinicopathologic features, such as gender, age, location type, type of resection, stage, visceral pleural involvement, lymphovascular invasion, and lymph node involvement. The expressions of P40, CK5/6, TTF-1, Napsin A, and CK7 were also not significantly different in three subtypes. Our study revealed that there were no significant relationships between clinicopathologic features and lung squamous cell carcinoma subtypes.

A Primary Keratinizing Squamous Cell Carcinoma of the Pancreas: Endosonography and Confocal Endomicroscopy of an Unusual Pancreatic Cystic Lesion

Case Report: A 79-year-old woman presented with abdominal discomfort and unintentional weight loss. A computed tomography scan demonstrated a 7 cm complex pancreatic cystic lesion (PCL) along with multiple hepatic cystic lesions. Endoscopic ultrasound (EUS) demonstrated a 7.1 x 6.7 cm anechoic cystic lesion with an irregularly thick wall and multiple mural nodules in the pancreatic body without obvious communication with the main pancreatic duct. On protocol, EUS-guided needle-based confocal laser endomicroscopy (nCLE) with an AQ-Flex 19 miniprobe (Cellvizio, Mauna Kea Technologies, Paris, France) revealed large cells of unequal shapes and sizes (> 20 μ) suggestive of a malignant process. Fine needle aspiration (FNA) confirmed a diagnosis of pancreatic keratinizing squamous cell carcinoma (SCC) metastatic to liver with demonstration of irregular spindle-like cells, hyperchromatic cells, and dense keratin material from both the primary pancreatic and metastatic liver lesions. Discussion: A primary pancreatic SCC constitutes a rare diagnosis with very few reports described in the literature. One large case series reviewed 5075 patients and reported the incidence of pure squamous cell carcinoma 0.5% of the total pancreatic ductal carcinomas1. Moreover, this case is unique for being an unusual presentation of a PCL where the diagnosis of malignancy was suspected by EUS-nCLE and confirmed with FNA. This adds to the growing literature of intracystic nCLE image patterns in the diagnosis of PCLs. 1) Baylor SM, Berg JW. Cross-classification and survival characteristics of 5,000 cases of cancer of the pancreas. J Surg Oncol 1973;5:335-358.

Carcinoma Ex-Pleomorphic Adenoma of the Parotid Gland Comprised of High Grade Salivary Duct Carcinoma and Keratinizing Squamous Cell Carcinoma

Carcinoma Ex-Pleomorphic Adenoma of the Parotid Gland Comprised of High Grade Salivary Duct Carcinoma and Keratinizing Squamous Cell Carcinoma

Discovery of invasion routes for nasopharyngeal adenoid cystic carcinoma.

The aim of this study is to discover regional invasion routes for nasopharyngeal adenoid cystic carcinoma (NACC) through analyses of the magnetic resonance (MR) images and comparison with keratinizing squamous cell carcinoma (KSCC). Both MR results and clinical records were retrospectively reviewed for 18 patients with NACC and 182 patients with KSCC. The metastasis routes of NACC were identified by analysis of MR images of patients who underwent magnetic resonance imaging (MRI). There were significant differences in skull base invasion and cavernous sinus invasion (p = 0.020 and 0.028, respectively) while parapharyngeal space invasion rate was not. The laryngopharynx invasion rate and external pterygoid muscle invasion rate were higher in NACC patients than that in KSCC patients (16.7% vs. 0.5 %, p = 0.002; 27.8% vs. 11.0%, p = 0.040, respectively). Paralysis of the cranial nerves had a significant higher incidence in the NACC group compared to the KSCC group (66.7% vs. 8.2%, p < 0.001). There was significant difference in invasion to the neural foramen between the NACC and KSCC groups (66.7% vs. 36.3%, p = 0.020). Foramen ovale was a common invasion site, significantly higher in NACC patients than in KSCC patients (50.0% vs. 24.1%, p = 0.018). Based on the MRI findings, a regional invasion model of NACC with two possible routes has been built, including aggressive local infiltration along submucosa to laryngopharynx or external pterygoid muscle, and extension from pharyngonasal cavity, through cranial nerve canal to cavernous sinus. The significant difference in overall survival (OS) time between the two different invasion routs and the recurrent rates in different regions also supported the validity of the invasion model.

Nasopharyngeal carcinoma risk by histologic type in central China: Impact of smoking, alcohol and family history

The role of cigarette smoking, alcohol use, family history of cancer and the interaction of cigarettes and family history in the etiology of Nasopharyngeal carcinoma (NPC) in general and within each histologic type are unclear. We conducted a case-control study among 1,044 Han Chinese patients with NPC and 1,095 Han Chinese cancer-free control subjects. Logistic regression was used to analyze the association between histologic type of NPC and cigarette smoking, alcohol drinking and family history. The results indicated that NPC was significantly associated with cigarette smoking [adjusted odds ratio (OR) = 2.97, 95% confidence interval (CI), 2.38-3.70], and the association exhibited a dose-response relationship for intensity, duration, and cumulative consumption of cigarettes (p(trend) < 0.0001 for intensity, duration and cumulative consumption of cigarettes). Positive family history of cancer led to a significant 12-fold elevated risk of NPC (adjusted OR = 12.95, 95% CI, 7.12-23.54) and acted jointly with cigarettes in contributing to NPC risk (adjusted OR = 56.68, 95% CI, 17.25-186.19). The association of NPC risk with cigarettes was stronger for nonkeratinizing carcinoma than for keratinizing squamous cell carcinoma (KSCC), whereas family history was more closely associated with KSCC. NPC risk was not associated with alcohol consumption. Our study demonstrated that cigarette smoking and family history of cancer could serve independently and jointly as risk factors for etiology of NPC and might affect the risk of histology-specific NPC differently. This knowledge may help facilitate comprehension of NPC etiology in general as well as within each histologic type, and thereby improve prevention efforts.

Histologic Identification of Human Papillomavirus (HPV)-Related Squamous Cell Carcinoma in Cervical Lymph Nodes: A Reliable Predictor of the Site of an Occult Head and Neck Primary Carcinoma

Patients with head and neck squamous cell carcinoma (SCC) often present with cervical lymph node metastasis. Occasionally the primary tumor site remains unknown even after thorough investigation. Management of such cases is problematic and may result in over-treatment and consequent increased morbidity. High risk HPV has been advocated recently as an important etiologic factor for a subset of head and neck SCC. These are believed to have a special predilection for the oropharyngeal tonsils and are characterized by nonkeratinizing basaloid morphology, and a strong reactivity to p16 immunostain. Identifying HPV-related SCC in the lymph nodes may thus provide a means for localizing the primary tumor site. Ninety-three cases of SCC metastatic to the neck from known primary tumors were classified morphologically into conventional keratinizing SCC (KSCC) and non-keratinizing SCC (NKCa). In situ hybridization (ISH) for high risk HPV as well as immunostaining for p16 were performed on all metastsatic and primary tumors. Of the 93 cases of metastatic carcinomas 32 were oropharyngeal, 35 oral, and 26 arose in the laryx/hypopharynx. Twenty-three cases were found to be HPV+ by ISH, of which 22/23 had oropharyngeal origin (P < 0.0001), with 95.7% sensitivity and 85.7% specificity. Twenty-one of these HPV+ oropharyngeal tumors were NKCa (P < 0.0001). The remaining case showed overlapping NKCa/KSCC hybrid morphology. All NKCa were HPV+ and stained diffusely and strongly with p16 antibodies. We have demonstrated that HPV status of the lymph node metastasis can be assessed not only by ISH and p16 immunoreactivity but also histomorphologically. In addition, a positive microscopic identification of HPV-related carcinoma is a reliable predictor of oropharyngeal origin.

Detection of human papillomavirus-related squamous cell carcinoma cytologically and by in situ hybridization in fine-needle aspiration biopsies of cervical metastasis

Fine-needle aspiration (FNA) biopsy often is the first diagnostic procedure performed in patients with head and neck masses. When squamous cell carcinoma (SCC) is diagnosed, proper management and improved prognosis depends on identification of the primary tumor. Recent studies have indicated that human papillomavirus (HPV) infection is associated closely with oropharyngeal SCC and that these tumors have a distinct nonkeratinizing morphology. In this study, the authors explored the value of identifying HPV-related tumors in neck metastases to determine the origin of occult primary head and neck squamous cell carcinoma (HNSCC). Thirty FNA biopsies of neck metastases from patients with HNSCC were recovered from the authors' files from 2004 to 2005. The primary sites included 13 oropharynx, 13 oral cavity, and 4 larynx/hypopharynx. All patients had corresponding tissue samples from the neck mass and the primary carcinoma. The FNA specimens and corresponding tissue samples were classified as either nonkeratinizing SCC (NKSCC) or keratinizing SCC (KSCC). In situ hybridization for HPV (HPV-ISH) was performed using ethanol-fixed, Papanicolaou-stained smears. A positive signal was defined as dark blue or black nuclear dots. Corresponding formalin-fixed, paraffin-embedded tissue sections also were processed for HPV-ISH. Twenty of the 30 FNA specimens were KSCC, and 10 were NKSCC. Eight of the 10 NKSCCs originated in the oropharynx, and 2 had nonoropharyngeal origin. HPV was detected in 7 of 10 NKSCCs. Ten of 30 (33%) FNA biopsies were positive for HPV, and 9 of those biopsies were metastatic from the oropharynx. Nonkeratinzing morphology or HPV-positive ISH in FNA samples significantly predicted oropharyngeal origin (P < .0069 and P < .0004, respectively). NKSCC in metastatic cervical lymph nodes predicted positive HPV-ISH and was strongly suggestive of an oropharyngeal primary tumor.