半乳糖凝集素-9和T细胞免疫球蛋白黏蛋白分子3在口腔扁平苔藓和口腔鳞状细胞癌组织中的表达及临床意义

目的探讨半乳糖凝集素-9(Galectin-9)和T细胞免疫球蛋白黏蛋白分子3(TIM3)在口腔扁平苔藓和口腔鳞状细胞癌组织中的表达及临床意义。方法收集42例口腔扁平苔藓组织、25例口腔鳞状细胞癌组织及30例正常口腔黏膜组织,采用免疫组织化学染色法检测3种组织中Galectin-9和TIM3的表达情况,分析Galectin-9和TIM3表达情况与口腔扁平苔藓和口腔鳞状细胞癌患者临床特征的关系,采用Pearson相关分析法分析口腔扁平苔藓及口腔鳞状细胞癌患者中Galectin-9和TIM3表达的相关性。结果口腔鳞状细胞癌组织中Galectin-9的阳性表达率低于口腔扁平苔藓组织和正常口腔黏膜组织,TIM3的阳性表达率高于正常口腔黏膜组织,差异均有统计学意义(P﹤0.05);口腔扁平苔藓组织中Galectin-9的阳性表达率低于正常口腔黏膜组织,TIM3的阳性表达率高于正常口腔黏膜组织,差异均有统计学意义(P﹤0.05)。糜烂型口腔扁平苔藓患者口腔扁平苔藓组织中Galectin-9的阳性表达率低于非糜烂型口腔扁平苔藓患者,TIM3的阳性表达率高于非糜烂型口腔扁平苔藓患者,差异均有统计学意义(P﹤0.05)。不同分化程度、淋巴结转移情况口腔鳞状细胞癌患者口腔鳞状细胞癌组织中Galectin-9的表达情况比较,差异均有统计学意义(P﹤0.05);不同分化程度口腔鳞状细胞癌患者口腔鳞状细胞癌组织中TIM3的表达情况比较,差异有统计学意义(P﹤0.05)。Pearson相关分析结果显示,口腔扁平苔藓和口腔鳞状细胞癌患者中Galectin-9和TIM3的表达均呈负相关(r=-0.415、-0.437,P﹤0.01)。结论Galectin-9和TIM3可能参与口腔扁平苔藓及口腔鳞状细胞癌的发生发展,并可能与口腔扁平苔藓的癌变有关。     

Expression of matrix metalloproteinases (MMP-1 and -2) and their inhibitors (TIMP-1, -2 and -3) in oral lichen planus, dysplasia, squamous cell carcinoma and lymph node metastasis.

Although matrix metalloproteinases (MMPs) are among the potential key mediators of cancer invasion, their involvement in premalignant lesions and conditions is not clarified. Therefore, we studied, using in situ hybridization, immunohistochemistry and zymography the expression and distribution of MMP-1 and -2, and their tissue inhibitors (TIMPs -1, -2 and -3) in oral squamous cell carcinomas (SCC) and lymph node metastases as well as in oral lichen planus, epithelial dysplasias and normal buccal mucosa. In oral SCC and lymph node metastasis, MMP-1 mRNA was detected in fibroblastic cells of tumoral stroma. In two out of ten carcinomas studied, the peripheral cells of neoplastic islands were also positive. MMP-2 mRNA expression was noted in fibroblasts surrounding the carcinoma cells, and no signal in carcinoma cells was detected. A clear TIMP-3 mRNA expression was seen in stromal cells surrounding the neoplastic islands in all SCCs and lymph node metastases studied. TIMP-1 mRNA was detected in some stromal cells surrounding the neoplastic islands, whereas the mRNA expression for TIMP-2 was negligible. On the other hand, expression of MMPs and TIMPs was consistently low in oral epithelial dysplasias, lichen planus and normal mucosa. In certain epithelial dysplasias and lichen planus, MMP-1 and -2 mRNA expressions were detected in few fibroblasts under the basement membrane zone, but normal mucosa was completely negative. In SCC and lymph node metastasis, a detectable immunostaining for MMP-1 in stromal cells and in some carcinoma cells was observed. MMP-2 immunoreactivity was detected in the peripheral cell layer in neoplastic islands and in some fibroblast-like cells of tumoral stroma. Immunostaining for TIMP-3 was detected in stromal cells surrounding the neoplastic islands. A weak positive staining for TIMP-1 was located in tumoral stroma, whereas the immunostaining for TIMP-2 was negative. Using zymography, elevated levels of MMP-2 and MMP-9 were observed in carcinoma samples in comparison with lichen planus or normal oral mucosa. Our results indicate that the studied MMPs and TIMPs are clearly up-regulated during invasion in oral SCC. However, there was also a clear, although weak, up-regulation of the expression of the MMPs but not TIMPs in some of the lichen planus and dysplastic lesions.     

口腔癌、癌前病变及癌前状态中抑癌基因PTEN的表达及其临床意义的研究

目的研究PTEN蛋白在口腔鳞状细胞癌、癌前病变及癌前状态组织中的表达及其与口腔鳞状细胞癌的临床病理及预后的关系。了解PTEN蛋白表达在口腔癌发生、发展中的作用。方法免疫组织化学法检测10例正常口腔粘膜、14例口腔扁平苔癣、20例口腔白斑、30例癌旁组织及46例口腔鳞状细胞癌组织中PTEN蛋白的表达水平,并进行半定量分析。结果正常口腔粘膜、口腔扁平苔癣、口腔白斑、癌旁组织及鳞状细胞癌组织中PTEN蛋白表达总阳性率分别为70．00％（7／10）、57．14％（8／14）、45．00％（9／20）、73．3％（22／30）及19．57％（9／46）。口腔白斑、扁平苔癣及鳞状细胞癌组织中VrEN蛋白表达水平显著低于正常口腔粘膜（P〈0．05）。口腔鳞状细胞癌组织中PTEN蛋白表达水平显著低于患者自身癌旁组织（P〈0．01）。结论PTEN蛋白表达水平降低或缺失在口腔鳞状细胞癌的发生发展过程中可能起重要作用。免疫组织化学法检测PTEN蛋白的表达对口腔癌早期诊断和预后判断的价值有待进一步研究。     

Salivary MMP-1, MMP-2, MMP-3 and MMP-13 Levels in Patients with Oral Lichen Planus and Squamous Cell Carcinoma

The aim of present study was to evaluate salivary matrix metalloproteinase-1 (MMP-1) , MMP-2, MMP-3 and MMP-13 levels in patients with oral lichen planus (OLP) and squamous cell carcinomas (SCC) as well as in healthy controls. Thirty cases of OLP (bilateral lesions, papular and reticular lesions, and Wickham lines) clinically and histopathologically (group A), 30 with oral SCCs (group B), and 30 with no history of oral cancer, other lesions or lichen planus (group C) were enrolled at the Department of Oral Medicine School of Dentistry, Zahedan, Iran. Unstimulated whole saliva was collected and laboratory measurement of salivary concentration of MMP-1, MMP-2, MMP-3 and MMP-13 was conducted by immuno-sorbent enzyme-linked methods. Data analysis was performed with Kruskal-Wallis and Mann-Whitney tests and Pearson’s correlation coefficients. In the present study, MMP-2 and MMP-13 levels were higher in oral SCC patients than in OLP cases  and healthy individuals. More research is required to assess MMP links with tumor invasion.     

Oral lichenoid contact reactions may occasionally transform into malignancy.

The purpose was to identify cases of squamous cell carcinoma (SCC) of the tongue, in which a biopsy taken at the site preceding the cancer could be verified to show a lichenoid contact type of reaction (LCR). We retrieved all 724 SCC of the tongue from the Swedish Cancer Registry in the period 1995-2000. These cases were cross-searched with our own oral biopsy data files from 1988 to 1994, in order to identify biopsies with LCR-type lesions preceding the cancer. We found four verified and some additional tentative cases. The study demonstrated that there is a low incidence of malignant transformation in LCR-type oral lesions, not much different from what has been previously reported in oral lichen planus.     

TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva

Non-neoplastic epithelial lesions of the vulva (NNEDV) lichen sclerosus (LS) and squamous hyperplasia (SH) have been implicated in the pathogenesis of squamous cell carcinoma of the vulva (SCC). To date, there have been no recognisable precursor lesions for SCC associated with NNEDV. TP53 is the most frequent genetic change in human cancers and can indicate both aetiology and molecular pathogenesis of tumours. A total of 27 SCC patients underwent immunohistochemistry (IHC) and TP53 mutational analysis using microdissection and direct sequencing. There were 19 patients with areas of adjacent epidermis: 17 had NNEDV (four SCCs had more than one adjacent lesion) and two had normal epidermis. In all, 70.4% of the SCCs, 40% LS and 22.2% SH demonstrated overexpression of p53. In total, 77.8% of SCCs, 46.7% of LS and 22.2% SH demonstrated mutations in TP53, with the majority of lesions having a mutation in codon 136. Eight cases were identified where the same mutation was identified in the SCC and in the adjacent area. These data suggest that TP53 mutations develop in NNEDV and are intrinsic to the clonal evolution that leads to SCC. The type of mutation detected is more likely to occur due to endogenous cellular changes rather than exogenous carcinogen exposure.     

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

The prognosis of locally advanced or recurrent squamous cell carcinoma （SCC） of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with Iocoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months （range, 10-50 months）. Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in Iocoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC shouJd be prospectively investigated.     

Cytokeratin fragment 19 and squamous cell carcinoma antigen for early prediction of recurrence of squamous cell lung carcinoma

Sixty patients with squamous cell carcinoma (SCC) of the lung, including 25 cases with recurrence and 35 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of cytokeratin fragment 19 (CYFRA 21-1) and SCC antigen were measured before operation and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after operation for early detection of recurrence. The results revealed that 1) mean serum values of CYFRA 21-1 were significantly higher at early and any times after operation in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC; and 2) mean serum values of SCC antigen were significantly higher until 9 and 12 months after operation, in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC. We conclude that CYFRA 21-1 is a better marker than SCC antigen for early prediction of SCC recurrence in the lung.     

Basaloid squamous carcinoma of oral cavity: a histologic and immunohistochemical study

Basaloid squamous carcinoma (BSC) is an aggressive variant of squamous cell carcinoma (SCC) with a predilection for the upper aerodigestive tract. In the English literature, approximately 40 cases of BSC have been described in the oral cavity. BSC has frequently been confused with adenoid cystic carcinoma (ACC), basal cell adenocarcinoma, and undifferentiated SCC. The purpose of the investigation was to examine the histological features and immunohistochemical expression of differentiation-related substances, including cytokeratin (CK) subtypes, vimentin, S-100, chromogranin, laminin, and type IV collagen, for the characterization of biological features of these tumours. We studied three cases of BSC of the oral cavity, three cases of ACC, and one case of basal cell adenocarcinoma. Well-differentiated and undifferentiated SCCs were also studied for comparison. The BSCs showed many histopathologic similarities to cases previously reported. Among the CK subtypes analyzed, CK14 was the only subtype expressed by all basaloid cells of BSC. Potentially useful for the differential diagnosis was the finding of CKs 7 and 19 expression in the basaloid cells of ACC, and CKs 7 and 8 in basal cell adenocarcinoma. In BSCs, laminin and type IV collagen were found in the microcystic spaces between basaloid cells, but neither ACCs nor basal cell adenocarcinoma showed this feature. These data suggest that immunohistochemical findings are helpful in distinguishing BSC of the oral cavity from other histopathologically similar tumours.     

Serum squamous cell carcinoma antigen levels in invasive squamous vulvar cancer.

Squamous cell carcinoma (SCC) antigen levels were studied in 34 patients with primary (N = 27) or recurrent (N = 7) SCC of the vulva. In primary disease, the SCC antigen level was greater than 2.5 ng/ml in only four patients (15%). Elevated antigen levels ranged from 2.7-18.0 ng/ml. All of these patients had advanced disease by either clinical or surgical staging systems. Four of twelve patients with inguinal metastasis had elevated SCC antigen levels. In two of these patients the inguinal nodes were abnormal to palpation. No association of the SCC level and the degree of tumor differentiation was observed. SCC antigen levels were increased slightly (2.7-4.5 ng/ml) in three of six patients with locally recurrent disease. In one patient with distant recurrence the SCC antigen was 15.3 ng/ml. In both primary and recurrent disease all elevated SCC antigen levels decreased with effective therapy. Vulvar cancer is primarily a local disease that is easily assessed by physical examination. An effective tumor marker in vulvar cancer would benefit only the rare patient with distant but not local disease.     

High tumoral maspin expression is associated with improved survival of patients with oral squamous cell carcinoma

Maspin, a member of the serpin family of protease inhibitors, is known to have tumor-suppressor functions. However, the association between its expression level and survival has not been demonstrated in human cancer. Using the immunohistochemical technique to examine the expression levels of maspin in 44 cases of oral squamous cell carcinoma (SCC), we found that 66% of the cases expressed low to intermediate levels of maspin and 34% of the cases expressed high levels of maspin. We further examined maspin protein expression in a series of six SCC cell lines from the head and neck, and found that all but one expressed low or no maspin protein. We also compared the clinicopathological features of the oral SCC cases with the maspin expression level, and found that high maspin expression was associated with the absence of lymph node metastasis. More importantly, we showed that higher maspin expression was significantly associated with better rates of overall survival, suggesting that high maspin expression may be a favorable prognostic marker for oral SCC.     

放疗对口腔粘膜白斑和扁平苔癣的作用观察

目的　对伴有口腔粘膜慢性病变的 2 4例口腔鳞癌术后放疗病例进行观察 ,了解 6 0钴 (γ—射线 )对口腔粘膜白斑和扁平苔癣是否具有抑制发展和治疗作用。方法　选择上海市第九人民医院口腔颌面外科放疗室 1994年 3月到 1999年 3月间进行放疗的 2 4例伴有慢性口腔粘膜疾病的口腔鳞癌病例 ,分放疗、放疗后、康复期 3个阶段进行观察 (其中粘膜白斑 16例、扁平苔癣 8例 ) ,另选 2 4例口腔鳞癌病例作对照观察。结果　放疗阶段两组病例相比 ,观察组放射耐受性比对照组差 ,表现在口腔粘膜溃疡出现早持续时间长 ;放疗结束后两组相比 ,对照组口腔粘膜修复过程快 ,观察组内相比口腔粘膜白斑比扁平苔癣恢复快 (包括全身和口腔内粘膜反应 ) ;康复期内观察口腔粘膜白斑比扁平苔癣复发率高。结论　 6 0钴 (γ—射线 )对口腔粘膜白斑和扁平苔癣具有一定的抑制和减缓发展的作用。     

Squamous cell carcinoma of the colon with an elevated serum squamous cell carcinoma antigen responding to combination chemotherapy

Primary squamous cell colorectal carcinomas are uncommon, and their characteristics are not well known. They seem to occur most commonly in the fifth decade of life with a slight predominance for men. The most commonly reported anatomic locations are the rectum and the proximal colon. Clinical features and common diagnostic methods do not easily differentiate squamous cell colorectal carcinomas from adenocarcinomas. Because of their extremely rare occurrence, it is difficult to study their natural course, clinical behavior, and response to therapy. This report presents the case of a pure squamous cell colorectal cancer and provides a brief review of the literature, which includes 60 previously published cases. The case of a patient with T3N2M0 primary squamous cell carcinoma of the rectosigmoid colon, which was initially treated with abdominoperineal resection followed by adjuvant chemotherapy and radiation, is presented. During the follow-up, an elevated squamous cell carcinoma antigen (SCC Ag) level led to restaging computed tomography scans, which confirmed recurrent metastatic disease in the liver. Response to chemotherapy with a decrease in tumor size correlated with a decrease in the serum SCC Ag level. Although SCC Ag has been used as a tumor marker for squamous cell cancers of the lung, head and neck, uterine cervix, and esophagus, this is the first reported case of a squamous cell colon carcinoma presenting with an elevated SCC Ag at the time of recurrence. In addition, this patient showed an objective partial response to combination chemotherapy, with a decrease in the serum level of this tumor marker.     

Mitochondrial DNA mutations in oral squamous cell carcinoma

It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations within the ND2 gene of histologically normal parotid salivary gland tissue of smokers may be molecular biomarkers for smoking-induced mtDNA damage. Oral squamous cell carcinoma (SCC) is strongly related to cigarette smoking; therefore, we used PCR and direct sequencing to establish whether mtDNA mutations were also present in oral SCC which could be used as additional biomarkers for smoking-associated DNA damage. In addition to searching for mutations in the ND2 gene, the mitochondrial D-Loop was also analysed. Three mutation hotspots were observed in the D-Loop at nt 146, 152 and 186, two of which (nt 146 and 152) have also been implicated in oesophageal SCC, another smoking-related cancer. The mutation hotspot observed at nt 186 has not previously been reported in other tumours. Furthermore, we show that the mutations previously reported within the ND2 gene in normal parotid tissue of smokers were not evident in these samples, but that a mutation hotspot occurs at nucleotide 4917 in oral SCC. We also show that D-Loop mutations occur predominantly in male smokers and female non-smokers and that this association with gender is statistically significant (P = 0.003). We conclude that the mtDNA mutation hotspots found in this study, in particular nt 186, are potential biomarkers for oral SCC. However, owing to gender-specific differences in occurrence in smokers and non-smokers, and a lack of environmental smoking history, in general, it is difficult to associate these mutations with mtDNA damage induced by smoking. If the mutations observed in the subset of male patients are smoking induced, given our previous findings, mutation hotspots in the ND2 gene may be tissue specific suggesting the causative mutagens for mtDNA damage within these tissues are likely to be different.     

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n=66) detected by immunohistochemistry and (b) cetuximab- and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the (51)Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR- and HER-2 expression. Out of both EGFR- and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.     

Malignant transformation of oral lichen planus.

AIMS: To investigate the malignant potential of oral lichen planus (OLP), a common mucocutaneous disease of unknown aetiology. The malignant potential of OLP is still controversial, with studies reporting malignant transformation rates of between 0 and 5.6%. We also aimed to identify factors that might be associated with malignant transformation. METHODS: We retrospectively reviewed the records of 832 patients with histologically confirmed OLP treated at the Dental Hospital, Newcastle upon Tyne during the period 1983-1996. RESULTS: Of these 832 patients, a total of seven (0.8%) developed intra-oral squamous cell carcinoma (SCC), including three cases of carcinoma in situ. It was noted that OLP patients with SCC are more likely to be women, relatively young and have a low tobacco and alcohol intake. However, they had a good long-term prognosis. CONCLUSIONS: We conclude that the risk of malignant transformation in OLP is real but not high. Clinicians should have a higher index of suspicion of the possibility of malignancy developing in OLP, because such patients are different from typical patients who develop oral malignancy. Follow-up for at least 6 years is recommended.     

Contemporary management of penile squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common tumor of the penis. The natural history and its proclivity to spread via regional lymphatics has been well defined. Laser ablation of the primary tumor has a prominent role in patients with a superficial tumor as a penis-conserving approach. Patients with deeper infiltrating tumors, should undergo (partial) penile amputation. For patients presenting with proven metastatic nodes complete (ilio-) inguinal lymphadenectomy should be performed. During the last two decades, the management of penile carcinoma patients with impalpable regional lymph nodes has improved due to better knowledge of risks for metastases, the introduction of modified lymphadenectomy, and sentinel node biopsy. Future perspectives in penile cancer comprises continuing research to reduce mutilation without jeopardizing clinical outcome.     

Multiple high-grade bronchial dysplasia and squamous cell carcinoma: concordant and discordant mutations.

Loss of heterozygosity (LOH) involving chromosomes 3p, 5q, 9p, or 17p and aberrant expression or mutation of p53 are reported previously in selected bronchial dysplasias and squamous cell cancers (SCCs). Yet, comprehensive analyses of LOH patterns at these chromosomal sites and of p53 alterations are not reported for histologically normal bronchial epithelium, high-grade bronchial dysplasia, and SCC present in the same pulmonary resections. Whether concordant or discordant genetic changes are detected in these bronchial tissues, especially when multiple high-grade dysplastic bronchial lesions are present, was studied. Genomic DNA was microdissected from eight pulmonary SCCs and high-grade dysplastic lesions that were associated with SCC. In four cases, two independent high-grade dysplastic bronchial lesions were identified. When available, histologically normal bronchial epithelium was microdissected. Germ-line genomic DNA was isolated from normal lymph nodes. LOH was assessed for 15 microsatellite markers on chromosomes 3p, 5q, 9p, or 17p, sites frequently deleted in lung cancers. Immunohistochemical p53 expression was studied and correlated with p53 DNA sequence analyses. Progressive LOH for these markers was found when SCCs were compared with high-grade dysplasia and histologically normal bronchial epithelium present in the same resections. Histologically normal bronchial specimens had LOH in up to 27% of informative markers. High-grade dysplastic lesions exhibited LOH for 18-45% and SCC had LOH for 18-73% of the markers. Common regions of LOH were found in some dysplasias compared with SCCs. In other dysplasias, discordance was found relative to SCCs, especially for p53 mutations. In cases with a single or second high-grade dysplasia associated with SCC, heterogeneity in LOH markers was detected. These concordant and discordant changes were consistent with convergent and divergent clonal selection pathways in pulmonary squamous cell carcinogenesis. Some histologically normal bronchial epithelial tissues had genetic changes more similar to those in the SCCs than in dysplastic lesions. DNA loss or mutations accumulate in SCC, but discordant genetic changes can exist in the same carcinogen-exposed bronchial tissues. These findings have implications for lung cancer prevention trials.     

Trisomy 12 in a Case of Multiple Cutaneous Squamous Cell Carcinoma in Association with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukaemia （CLL）, which shares clinical and morphological overlap with small lymphocytic lyjmphoma （SLL）, is a low-grade clonal B-cell lymphoproliferative disorder that accounts for 25% of all cases of leukaemia in Western countries, while it is considered rare in Oriental patients and is thought to constitute only 2% of all leukemias in these patients. CLL is associated with an increased incidence of secondary malignant neoplasms, such as brain tumors, melanomas, and gastrointestinal-tract carcinomas. However, the simulataneous occurrence of CLL and cutaneous squamous cell carcinoma （SCC） is rarely reported. We present here a case of CLL with multiple SCC on the face. Subsequent studies demonstrated the patient to have a trisomy 12 identified in bone marrow specimen.     

Metastasis to the penis in a patient with squamous cell carcinoma of the lung with a review of reported cases

Metastasis to the penis is very rare in lung cancer. We describe a patient with squamous cell carcinoma of the lung who developed a metastatic lesion in the penis. A 75-year-old Japanese male visited a local hospital complaining cough and bloody sputum. A chest plain radiograph and computed tomographic (CT) scans of the chest demonstrated a right hilar mass. He was diagnosed with squamous cell carcinoma of the lung at stage IIIB (T4N2M0). Then he was treated with concurrent chemoradiotherapy consisting of cisplatin, docetaxel, and thoracic irradiation, and after the chemoradiotherapy, he achieved a partial response. However, 6 months later, he visited an urologist complaining of firm mass in the penis with slight pain. A biopsy of the corpus cavernosum penis was performed, which provided a histological diagnosis of squamous cell carcinoma. The histology of the specimen was consistent with that of previous lung cancer, so he was considered to have penile metastasis from squamous cell carcinoma of the lung. Radiotherapy was given to the metastatic tumor in the penis. The penile tumor was diminished and the pain was completely relieved. In addition, we review reported cases to investigate the clinical characteristics and appropriate management of this rare involvement.