Bilateral Auricular Squamous Cell Carcinomas with Perineural Invasion

BACKGROUND: Bilateral squamous cell carcinoma (SCC) of the external ears is a rare phenomenon, and we are unaware of instances of bilateral perineural involvement. OBJECTIVE: To describe bilateral auricular SCCs, each with perineural invasion. METHODS: Case report and literature review. RESULTS: Histopathologic examination revealed perineural invasion in both tumors. CONCLUSION: This appears to be an unusual presentation of bilateral auricular SCCs with perineural invasion in an elderly immunocompromised patient.     

膀胱鳞状细胞癌的诊治

目的：探讨膀胱鳞状细胞癌的发病、诊断、治疗及预后。方法：回顾性分析8例膀胱鳞状细胞癌患者的临床资料,结合国内外文献进行分析讨论。结果：8例患者年龄44～7串岁。行膀胱全切术3例,膀胱部分切除5例。7例患者随访1～10年,2年和5年生存率分别为43％（3／7）和14％（1／7）。结论：膀胱鳞状细胞癌是一种高度恶性肿瘤,预后差,早期诊断和治疗对患者来说非常重要。膀胱根治性切除仍是目前较好的治疗办法。     

Multiple Primary Carcinomas with Esophageal Squamous Cell Cancer: Clinicopathologic Outcome

The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of early-stage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.     

Aggressive Squamous Carcinomas of the Scalp

BACKGROUND: Squamous cell carcinomas of the scalp sometimes exhibit unusually aggressive behavior. OBJECTIVE: To describe a series of 11 cases of extraordinarily aggressive squamous cell carcinomas of the scalp. METHODS: These cases were selected based on a number of criteria including their tendency to recur after Mohs surgery, their propensity to develop satellite lesions, their tendency to invade bone, and their tendency to metastasize to regional nodes and systemically. A chart review was performed for each patient. RESULTS: Five of 11 patients have succumbed to their disease. Of note is that the patients all had significant long-standing alopecia or thinning of their hair with marked actinic damage. Initial biopsies of the tumors revealed them to be either moderate or well-differentiated. Four of 11 patients developed satellite lesions and experienced recurrences despite obtaining clear margins with Mohs micrographic surgery. CONCLUSION: Squamous cell carcinomas of the scalp may metastasize and cause death. Thus, early diagnosis and treatment of these neoplasms is mandatory. In the setting of satellitosis, it is believed that it is best to perform a wide excision with margin control followed by split-thickness grafting and postoperative irradiation. The employment of radiation therapy, however, should be done with appropriate caution owing to the significant risk of osteoradionecrosis.     

Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.     

Identification and Validation of DNA Methylation Markers to Predict Lymph Node Metastasis of Esophageal Squamous Cell Carcinomas

Background

The presence of lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patients is a critical factor for decision of treatment strategy. However, there have been no molecular markers to assess lymph node metastasis. In this study, we aimed to identify CpG islands (CGIs) whose DNA methylation statuses are associated with the presence of lymph node metastasis.

Materials and Methods

A total of 96 ESCCs were divided into a screening set (n = 48) and a validation set (n = 48). Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation-CGI microarray analysis. Methylation levels were analyzed by quantitative methylation-specific PCR (qMSP).

Results

Genome-wide methylation analysis identified 25 CGIs differentially methylated between 8 ESCCs with lymph node metastasis and 4 without. In the screening set, 7 CGIs had significantly different methylation levels (P < 0.05) between the ESCCs with and without lymph node metastasis, and cut-off methylation levels for these CGIs were determined. The validation set was analyzed with the prefixed cut-offs, and methylation statuses of 2 CGIs in the vicinities of PAX6 and ENST00000363328 were validated to be associated with the presence of lymph node metastasis. Using these 2 markers, the presence was predicted with a sensitivity of 93% and specificity of 57%. In addition, the methylation statuses of the 2 CGIs were significantly associated with disease-free survival (P = 0.006).

Conclusions

Methylation statuses of these 2 CGIs were significantly associated with the presence of lymph node metastasis of ESCCs. These CGIs are promising markers to predict the presence of lymph node metastases.     

High Rates of Ultraviolet-Signature Mutations in Squamous Cell Carcinomas of the Parotid Gland and Prognostic Implications

In the absence of clear pathologic differences, clinical history may differentiate potential primary parotid squamous cell carcinomas (SCC) from metastases. The presence of an ultraviolet (UV) signature can distinguish between tumors of cutaneous and non-cutaneous origin. This study aimed to investigate rates of UV signature mutations in squamous cell carcinomas of the parotid gland as well as differences in clinical features between tumors of cutaneous and non-cutaneous origin. Clinical and pathologic data were collected from 71 patients with SCC involving the parotid gland, of which 48 had cutaneous, 10 had mucosal, and 13 had no history of SCC. In 34 available cases, genomic DNA was isolated from formalin-fixed paraffin-embedded tissue specimens and sequenced using a targeted hybrid capture 1213 gene panel. Tumor mutational burden and COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signatures were calculated. Most (74%) were UV-positive. Patients with UV-positive tumors were significantly older, white, and had higher rates of sun exposure. Patients with UV-negative tumors had a significantly higher mortality rate and shorter time to death: 6 (67%) died of disease with a median time to death of 9 months compared to 5 (20%) UV-positive patients who died of disease with a median time to death of 32 months. Pathologic features did not significantly vary by clinical history or UV status. The presence of a UV-signature combined with clinical history can be used to determine the primary source of SCC involving the parotid gland. UV-positivity may reflect a less aggressive disease course in an older population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12105-021-01349-x.     

Relevance of Level IIb Neck Dissection in Patients with Head and Neck Squamous Cell Carcinomas

World Journal of Surgery - Cervical nodal metastasis is the most important prognostic factor in patients with head and neck cancers. Unfortunately, nodal dissection at level IIb carries a risk of...     

Letter to the Editor: Relevance of Level IIb Neck Dissection in Patients with Head and Neck Squamous Cell Carcinomas

World Journal of Surgery -     

苦参碱对喉鳞癌细胞株Hep-2侵袭转移的影响

目的:研究不同浓度苦参碱对喉鳞癌细胞株Hep-2侵袭和转移的影响及其作用机制。方法:Hep-2细胞体外培养,经0g/L、0.1g/L、0.2g/L和0.3g/L苦参碱分别处理1h、8h及48h,细胞黏附实验检测细胞黏附力,细胞迁移实验检测细胞运动力,细胞侵袭实验检测细胞侵袭力,RT-PCR法检测Hep-2细胞MMP-2和MMP-9mRNA的表达。结果:不同浓度苦参碱与对照组比较,苦参碱能有效抑制Hep-2细胞的黏附力、运动力和侵袭力(P<0.01),且能下调Hep-2细胞MMP-2和MMP-9mRNA的表达(P<0.01)。结论:苦参碱能抑制Hep-2细胞的浸润转移能力,其机制可能与下调MMP-2和MMP-9mRNA的表达使Hep-2细胞的黏附力、运动力和侵袭力下降有关。     

Survival Factors in Patients with Recurrence After Curative Resection of Esophageal Squamous Cell Carcinomas

Background  

Approximately half of patients who undergo curative resection for esophageal cancers develop recurrence postoperatively. The factors affecting survival after such recurrence remain largely unknown.     

KRAS and BRAF Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Head and Neck Squamous Cell Carcinomas in HIV-Positive Patients: A Preliminary Investigation of Viral Associations

Oncogenic human papillomaviruses (HPVs) are associated with oropharyngeal squamous cell carcinoma (SCC). Infection with human immunodeficiency virus (HIV) increases susceptibility to opportunistic infections and viral-promoted cancers. The prevalences of HPV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human herpesvirus-8 (HHV-8) have not been established for head and neck squamous cell carcinoma in HIV-positive patients (HIV+ HNSCC). We have observed that HIV+ HNSCC tend to contain numerous multinucleated tumor giant cells, this finding has not been described previously. The goal of this study is to test for these oncogenic viruses in a small cohort of retrospectively identified patients with HIV infection, and to compare histologically these cancers to a control group of HNSCC patients. Tumors were reviewed histologically and compared to a control group of 102 patients with HNSCC (serologically untyped or HIV negative). Polymerase chain reaction (PCR) was performed on formalin-fixed, paraffin-embedded HIV+ HNSCC samples from combined 25 patients in two institutions. In situ hybridization was performed to identify EBV (EBER) and immunohistochemistry was performed to detect HSV-1, HSV-2, HHV-8, and HIV-related proteins (Nef, p24). The study sample consisted of 34 HIV+ patients with HNSCC from Montefiore Medical Center, and six HIV+ HNSCC patients from Hospital Clinic, University of Barcelona; 24 (60%) men and 16 (40%) women. The larynx was most commonly involved (65%, n = 26); followed by the oropharynx (22.5%, n = 9). Four carcinomas arose from the oral cavity (10%) and one from the nasal cavity (2.5%). Histologically, multinucleated tumor giant cells were more common in the HIV+ group (39/40, 97.5%) than the control group (27/102, 26%, p 0.001, chi-square). HPV was detected in 6 of 25 (24%) HNSCC tumors by PCR, five were typed as HPV 16 and one as HPV 26/69; five of these tumors (83%) were located in the oropharynx. EBV, HSV-1, HSV-2, and HHV-8 were detected only infrequently in tumor cells. Nef protein was detected in tumor cells in 7 of 21 (33.3%) cases; p24 was not detectable in 6 tumors studied. There were no significant associations between HPV positive tumors and co-infections with other viruses. This study is consistent with other reports that suggest an increased incidence of laryngeal carcinoma for HIV+ patients. HPV was detected in 24% of HIV+ HNSCC, however, the number of tumors with amplifiable DNA (n = 25) is too small to allow for conclusions. EBV, HSV-1, HSV-2, and HHV-8 are uncommon in HIV+ HNSCC; it is unlikely that these viruses have a promoting effect. MNTCG are significantly common in HIV+ HNSCC, but there is overlap in MNTCG counts with the control group and therefore this finding cannot be used as a biomarker of HIV infection.     

External Carotid Artery Ligation in Squamous Cell Carcinomas of the Oral Cavity and Oropharynx: an Oncological Emergency

The purpose of this study is to investigate the outcomes of emergency external carotid artery ligation in head and neck cancer patients. It is a retrospective observational study of 11 patients with oral cavity and oropharynx cancers who underwent external carotid ligation as an emergency procedure. Prior tracheostomy was done in all the patients as part of the procedure. Parameters studied were the efficacy and safety of the procedure in the form of control of haemorrhage, any postoperative neurological deficit, morbidity and mortality. The study evaluates the efficacy of the intervention purely as an emergency procedure, and oncological outcomes have not been reported. Analysis was done using simple frequencies and proportions. The oropharynx is the most common site of tumour bleeding in head and neck malignancies. Bleeding following external carotid ligation stopped in all the patients immediately without any postoperative mortality or morbidity. No patient had any neurologic deficits postoperatively. There was one case of rebleeding. Emergency external carotid ligation in tumours of the oral cavity and oropharynx is a life-saving and simple procedure with limited morbidity. Prior tracheostomy is recommended in all the patients.     

Screening Cystoscopy and Survival of Spinal Cord Injured Patients With Squamous Cell Cancer of the Bladder

Purpose

Yearly cystoscopy has been advocated in spinal cord injured patients with chronic or recurrent urinary tract infections secondary to the increased risk of squamous cell cancer of the bladder. We examined the effectiveness of this protocol in our patients.

Materials and Methods

The medical records of all spinal cord injured patients with squamous cell cancer of the bladder between 1980 and 1996 were reviewed for the method of detection of the lesion. Screened patients (those presenting with chronic or recurrent urinary infections) were considered asymptomatic and were compared to symptomatic patients (those presenting with overt signs or symptoms of the bladder lesion) with respect to age, latency since spinal cord injury, treatment of neurogenic bladder, therapy, pathological stage and survival.

Results

Of 14 patients (9 symptomatic at presentation) 13 underwent cystoprostatectomy, while 1 presented with metastatic disease and was treated with supportive care only. Three symptomatic patients received adjuvant radiation therapy for positive lymph nodes or margins. Pathological stage was more advanced in the symptomatic group, including 7 patients (78%) with stage pT3a or pT3b (4 had positive lymph nodes), 1 with stage pT1N0M0 and 1 with stage pT2N0M0 cancer. In the asymptomatic group 3 patients had stage pT2N0M0, 1 had stage pT2aN0M0 and 1 had pT3bN0M0 disease. Overall and cancer specific survival rates for symptomatic patients were 44 and 50%, respectively, with a median of 40 months to death. In the asymptomatic group there was 1 noncancer related death, while the remaining patients were alive at a mean followup of 8.2 years.

Conclusions

Cystoscopy to screen for squamous cell cancer of the bladder in spinal cord injured patients with chronic or recurrent urinary tract infection results in an earlier stage at diagnosis and appears to convey a survival advantage. Such a protocol should be strictly followed and careful prospective studies must be performed to ascertain if this will become significant.