Multiple Primary Squamous Cell Carcinomas Research Articles

Multiple Primary Squamous Cell Carcinomas of the Oral Cavity

There is a subset of patients who develop multiple primary squamous cell carcinomas (SCCs) of the oral cavity. The aim of this study was to better characterize this group of patients and determine whether there are any associated risk factors. This is a retrospective review of all patients treated for oral SCCs at the University of Maryland Department of Oral and Maxillofacial Surgery from November 1989 to February 2013. The inclusion criteria were patients who developed at least 3 primary oral cancers. Lesions were considered separate primaries if they involved different anatomic regions within the oral cavity and were more than 2 cm apart or if they occurred more than 5 years apart. Of 1,478 patients treated during this time frame, 20 met the inclusion criteria. There were 14 women and 6 men (female-to-male ratio, 2.3:1). Nineteen were Caucasian and 1 was of Indian ethnicity. The average number of primaries per patient was 3.9 (range, 3 to 6 primaries). The mean age at first diagnosis was 63.3 years (44 to 86 yr). The mean interval between the different primaries was 32 months (0 to 228 months). The most common site involved was the gingiva (45% of cases), followed by the tongue, buccal mucosa, retromolar fossa, and soft or hard palate. The mean follow-up was 118 months (22 to 342 months). Eleven patients developed nodal disease. Of those 11 patients, 9 died of the disease (<20% survival). The average time to neck involvement was 66.4 months. The average time from last neck involvement to death was 11.5 months. More than half the patients were nonsmokers or had quit more than 10 years before the first diagnosis. All patients quit smoking during the course of their treatment yet continued to develop multiple primaries. Three patients had proliferative verrucous leukoplakia (PVL), and 4 patients had biopsy-proved lichen planus. The incidence of multiple primary SCCs within the oral cavity appears to more commonly involve Caucasian women without risk factors, although lichen planus and PVL might play a role. The gingiva appears to be the most commonly involved primary site, and subsequent primaries tend to be restricted to the oral cavity. Close observation and early expectant treatment appear to improve prognosis and survival in these patients. Cervical nodal metastases adversely affected survival (P = .02) as did the development of more than 4 primary carcinomas (P = .04).

A rare presentation of multiple primary squamous cell carcinoma of the tongue in a patient with recurrent hepatitis C infection

Hepatitis C virus (HCV) infection has been implicated as a risk factor for development of oral squamous cell carcinoma (SCC). Multiple primary sites of oral SCC associated with HCV infection occurs infrequently. This case report describes a rare presentation of multiple primary SCCs of the tongue in a patient with recurrent HCV cirrhosis status post liver transplant that required interdisciplinary medical and surgical management. It is important for oral health care providers to understand the local and systemic implications of HCV infection and perform routine clinical examinations to monitor for development of oral lesions and associated complications.

PP022: EMT-associated genes are predictive markers in multiple primary oral squamous cell carcinoma

Although multiple primary carcinomas in the head and neck are not uncommon, the exact prevalence is controversial, and its clinicopathological features remain unknown. Deregulation of Epithelial–Mesenchymal-Transition (EMT) proteins’ has been related to malignant transformation and tumor progression. The present study evaluated the relationship among immunohistochemical expression of EMT molecular markers and associated proteins with clinicopathological characteristics and overall survival probability in OSCC patients presenting multiple primary tumors in comparison with patients without second tumors or metastatic disease. Immunohistochemistry reactions for E-cadherin, catenin (α, β, and γ), APC, collagen IV, Ki-67, and cyclin D1 were performed in a tissue microarray containing 102 representative areas in duplicate from OSCC patients followed at least by 10 years. Clinical and treatment data were obtained from medical records and histopathological features revised. Significant correlation was found among multiple OSCC and protein expression of E-cadherin ( P = 0.002), α-catenin ( P = 0.056), β-catenin ( P = 0.047), APC ( P = 0.017), and cyclin D1 ( P = 0.001). Positive associations were found between lymph nodes metastasis and Ki-67 staining ( P = 0.021). OSCCs presenting vascular embolization were associated with negative β-catenin expression ( P = 0.050). There was a significantly lower survival probability for patients with multiple OSCC (log-rank test, P < 0.0001), which tumors showed negative protein expression for E-cadherin (log-rank test, P = 0.003), α-catenin (log-rank test, P = 0.053), and β-catenin (log-rank test, P = 0.031). Taken together, our results show alterations in EMT protein expression involved in invasive phenotype related to patients with multiple OSCC with significant importance in the prognostic features.

Multiple Primary Squamous Cell Carcinomas of the Oral Cavity

There is a subset of patients that develop multiple primary squamous cell carcinomas (SCCA) of the oral cavity. The aim of this study is to characterize this group of patients and determine whether there are any associated risk factors.

The haptoglobin phenotype influences the risk of cutaneous squamous cell carcinoma in kidney transplant patients

Cutaneous squamous cell carcinoma (SCC) is the most frequent skin cancer after organ transplantation. Currently, the pre-identification of transplant patients at increased risk for non-melanoma skin cancer remains difficult. To investigate the Hp polymorphism as a marker for the identification of a subset of patients with an increased susceptibility to develop SCC/Bowen's disease. Haptoglobin phenotyping was performed with haemoglobin-supplemented starch gel electrophoresis in 300 kidney transplant patients. High-performance gel permeation chromatography was used in case of low serum haptoglobin concentration. Cox regression analysis (adjusted for age, gender and Mediterranean origin) showed a significant association of the Hp 1-1 phenotype with a higher risk of SCC/Bowen's disease (P = 0.035) and multiple primary SCCs (P = 0.002). No significant difference between the Hp phenotypes was found for the development of Bowen's disease and SCCs in the first 10 years following renal transplantation. However, after a follow-up of >10 years, a significant association between the Hp 1-1 phenotype and the occurrence of Bowen's disease and SCC was reported (P = 0.002 and P = 0.001 respectively). This study shows an increased risk for the development of (multiple) SCCs in kidney transplant patients with the Hp 1-1 phenotype. This finding points to the role of Hp 1-1 phenotype as an important predictor in identifying a subset of patients with an increased need for preventive measures and is in agreement with the decreased anti-inflammatory capacity of this phenotype.

Multiple primary cancer, including basal and squamous cell carcinomas of the skin with loss of mismatch-repair protein expression in a HNPCC family member – Case report

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited disease characterized by onset at an early age, an excess of synchronous and metachronous tumors and a variety of extracolorectal malignancies. Basal and squamous cell carcinomas of the skin are not customarily included in the tumor spectrum of HNPCC. HNPCC is caused by a germline mutation in one of the DNA mismatch repair (MMR) genes, most commonly MSH2 or MLH1, and typically presents with genomic instability and frequent loss of MMR protein expression in the tumor tissue.

Multiple Primary Cutaneous Squamous Cell Carcinomas of the Extremities-Case Report

Multiple primary cutaneous squamous cell carcinomas (CSCCs) are common in the head and neck region, but synchronous CSCCs of the extremities have not been frequently reported in the literature. Multiple CSCCs carry a high risk of subsequent primary skin cancer. CSCCs arising in a scar have higher rate of recurrence or metastasis than those occurring in actinic keratoses. A patient presented with primary CSCCs on the ankle and wrist. She had a 14-year history of a scar on her ankle which became ulcerated 2 years prior to presentation, as well a numerous cancer precursors on her palms, fingers, and extremities that had been investigated several years earlier. Although the ankle lesion was consistent with Marjolin's ulcer, the synchronous wrist lesion and multiple precancerous lesions raise the possibility of other etiologies, including cancer arising in actinic keratoses and/or chronic arsenism.

Clinical analysis of multiple primary malignancies of the hypopharynx and esophagus

Purpose: Because the capability to control squamous cell carcinomas of the head and neck has improved recently, the phenomenon of multiple primary malignancies of that region is now recognized with increasing frequency. We reviewed cases of multiple primary squamous cell carcinomas of the hypopharynx and esophagus with regard to their frequency, incidence, and prognosis. Patients and Methods: We reviewed 104 cases of hypopharyngeal cancer to determine (1) if and when esophageal cancer occurred, (2) the classification of multiple tumors as metachronous or synchronous, and (3) tumor histology. Results: In most cases of the metachronous type, esophageal cancer followed hypopharyngeal cancer within less than 3 years. Most cases of hypopharyngeal cancer were at an advanced stage, in contrast to esophageal cancer, which were all early stage. These cases had a poor prognosis despite various treatments causing local disease to be well controlled. Endoscopic esophageal mucosal resection was found to be an effective treatment for esophageal cancer, especially in superficial types. Conclusions: The prognosis and mild systemic damage after endoscopic esophageal mucosal resection compare favorably with surgery, radiation, or systemic chemotherapy. (Am J Otolaryngol 2001;22:107-110. Copyright © 2001 by W.B. Saunders Company)

Experience in the treatment of synchronous and metachronous carcinoma of the oesophagus and the head and neck.

Treatment of multiple primary squamous cell carcinomas of the head and neck and oesophagus is controversial. The poor prognosis of these 2 types of carcinoma taken individually and their anatomic proximity complicate the therapeutic strategy and limit the treatment choices for each location. From 1986 to 1998, 43 patients received curative treatment for multiple synchronous (n = 30) or metachronous (n = 13) primary neoplasms of the oesophagus and head and neck. For synchronous cancers, the therapeutic strategy consisted of first curing the head and neck cancer and then planning oesophagectomy according to the type of head and neck cancer therapy. Ten total oesopharyngolaryngectomies and 33 subtotal oesophagectomies were performed. The postoperative mortality rate was 9.3% (4/43). The rate of anastomotic leakage was 30% (13/43), and all such leaks were cervical. Pulmonary infection occurred in 19% of cases (8/43). A past history of cervical radiation therapy or cervicotomy did not appear to be a significant risk factor for anastomotic leakage or pulmonary complications. Oesophagectomy did not affect the functional results in the 31 patients whose larynx could be preserved. Oesophagectomy after head and neck cancer treatment is possible with a low mortality rate and acceptable morbidity.

Six primary squamous cell carcinomas of the head and neck

The chronic irritation to mucosa of the head and neck area by carcinogen, commonly stemming from heavy usage of betel nuts, tobacco and alcohol, leads to dysplastic mucosal changes and eventually, multiple primary squamous cell carcinomas. With improvements in locoregional control, the problem of multiple primary malignancies of the head and neck is becoming apparent. We reported a unique case of six primary squamous cell carcinomas in the head and neck area. We attribute the success of controlling cancer in this patient to our alert attitude and prompt management. Surgery remains one of the best options in treating multiple head and neck malignancies, as surgery offers an effective, quick and low morbidity approach, and does not take the chance of inducing another cancer.

414 Treatment of multiple primary squamous cell carcinoma of the lung

Background. The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy. Materials. We treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3~ of all squamous cell carcinoma patients undergoing resection. Results. Two patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IliA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation. Conclusions. The surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.

Analysis of the p53 gene mutations in patients with multiple primary cancers of the oesophagus

We investigated genetic alterations of the p53 gene in two patients with multiple primary oesophageal squamous cell carcinomas (ESCs). We found that each primary tumour could be distinguished by mutation of p53. Moreover, mutations detected in the p53 gene in metastatic lymph nodes were the same as those detected in at least one of the primary tumours. Our results presented the possibility of: (1) discrimination of primary and metastatic legions in patients with multiple primary ESCs; (2) determination of metastatic pathway to regional lymph nodes; and (3) application for the development of a better clinical management of patients with multiple primary ESCs.

Treatment of multiple primary squamous cell carcinomas of the lung

Treatment of multiple primary squamous cell carcinomas of the lung

Treatment of multiple primary squamous cell carcinomas of the lung

The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy. We treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3% of all squamous cell carcinoma patients undergoing resection. Two patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation. The surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.

Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus.

A review of data on 205 patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy revealed 30 cases (14.6%) and 32 lesions with multiple primary squamous cell carcinomas. The incidence of this multiplicity was 11.7% and 25.6% in those with and without preoperative irradiation treatment, respectively. Among the 32 second lesions, there were 17 intraepithelial carcinomas, eight restricted to the mucosa, five invading the submucosa, one invading down to the proper muscular layer, and one involving the entire thickness of the esophageal wall. These second lesions were in the relatively early stage. Moreover, incidence of the coexistence of intraepithelial carcinoma contiguous to the main lesion was 42.1% and 100.0% in those with multiple cancers, with and without preoperative irradiation, respectively. The values were 7.6% and 53.1% in patients with a solitary carcinoma, respectively. These findings show the close relationship between multiplicity and intraepithelial carcinoma contiguous to the main lesion, and support the concept of multicentric or field carcinogenesis of esophageal squamous cell carcinoma.

Multiple primary squamous cell carcinomas in the upper digestive tract

Multiple squamous cell carcinomas are common and patients carry a constant and excessive risk of developing a new cancer at any time (13–21 X the normal). Among 6,203 cases of primary squamous carcinoma of the upper digestive tract, 648 patients (10.4%) developed two or more independent tumors. Altogether, 761 additional malignancies were observed, with up to five cancers being seen in individual patients. There were 279 patients with a prior or synchronous cancer and 409 patients who developed 462 metachronous tumors. There was a substantial risk for developing a second primary cancer in the upper aerodigestive tract. Overall the observed to expected ratio was 2.48, specifically 2.32 for males and 2.89 for females.