Cytomegalovirus induces sialyl Lewis(x) and Lewis(x) on human endothelial cells

BACKGROUND: Cytomegalovirus (CMV) is the primary viral cause of complications in transplant recipients. We sought to understand the mechanisms of its dissemination and induction of vascular disease, which may lead to transplant complications. Sialyl Lewis(x) (sLe(x)) and Lewis(x) (Le(x)) are known for their roles in mediating cell adhesion and as tumor-associated carbohydrate antigens. Herein we explore whether CMV induces surface expression of these important molecules in endothelial cells (EC). METHODS: Flow cytometry was used to detect surface expression of sLe(x) and Le(x) on CMV-infected human umbilical vein endothelial cells (HUVEC), with or without ultraviolet inactivation of the virus. To elucidate mechanisms of CMV-mediated induction, mRNA coding for predominant HUVEC sialyltransferases (ST) and fucosyltransferases (FT), key enzymes in sLe(x) and Le(x) synthesis, was analyzed by Northern blot. Dual immunohistochemical staining for sLe(x) and Le(x) expression of human colon and placental tissue was performed to investigate in vivo relevance. RESULTS: sLe(x) expression on CMV-infected HUVEC was strongly up-regulated by 8 days after inoculation. Le(x) expression was detectable earlier and increased steadily over time. In contrast, ultraviolet-inactivated CMV did not induce expression of these molecules. Northern blot assays demonstrated higher levels of important EC glycosyltransferases ST-IV, FT-III, and FT-IV in CMV-infected EC. Finally, high levels of sLe(x) and Le(x) were expressed in CMV-infected EC in vivo. CONCLUSIONS: Given the known biologic functions of sLe(x) and Le(x), we suggest that CMV induction of these molecules may have widespread consequences ranging from CMV dissemination to induction of CMV-associated vascular disease, including thrombosis.     

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

Objective 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. Design 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. Results 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. Conclusion 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.     

Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma

BACKGROUND: Interaction between tumor cells and endothelium plays a major role in cancer invasion and metastasis. Among various cell adhesion molecules, the cognate interaction between sialyl Lewis antigen expressed in the tumor cell surface and E-selectin expressed on endothelial cells is considered to be crucial for the tumor cell adhesion to the endothelium. METHODS: The sialyl Lewis X (sL(X)) expression in 45 specimens from renal cell carcinoma patients was examined using immunohistochemistry. RESULTS: In this study, we demonstrate that the immunoreactivity for sL(X) in renal cell carcinoma specimens not only correlates with conventional histopathologic parameters but also serves as a useful indicator for the prognosis of renal cell carcinoma. CONCLUSION: Since beneficial effect of cimetidine has been reported and ascribed to its inhibitory action on the expression of E-selectin, a ligand molecule of sialyl Lewis antigen, cimetidine may also show inhibitory effect on the tumor recurrence and metastasis of renal cell carcinoma with high level of sL(X) expression.     

大肠癌唾液酸化Lewis X表达的临床意义

目的 :探讨大肠癌组织中细胞粘附分子唾液酸化LewisX表达状况与肿瘤发生、分化、转移及预后的关系。方法 :应用免疫组织化学催化信号放大法 (catalyzedsignalamplification ,CSA)和计算机图像分析技术 ,对 90例大肠癌原发癌灶、距肿瘤边缘 2cm的癌旁粘膜组织、远离癌组织 10cm以上的非癌大肠粘膜以及 5 1例转移淋巴结进行唾液酸化LewisX表达和反应强度进行比较 ,并对其中 5 3例患者进行随访。结果 :唾液酸化LewisX阳性物质在远离癌组织的非癌大肠粘膜中阳性率为 16 .7% (15 / 90 ) ,主要位于腺腔缘游离面 ;癌旁粘膜组织阳性率为 83.3% (75 / 90 ) ,主要位于细胞浆和 /或腺腔缘游离面 ;大肠癌组织中唾液酸化LewisX阳性表达率为 94 .4 % (85 / 90 ) ,主要分布于癌组织腺管细胞膜、细胞浆以及粘液腺癌的粘液湖内。转移淋巴结中唾液酸化LewisX阳性率为 96 .1% (49/ 5 1)。图像分析 :唾液酸化LewisX阳性细胞平均积分光密度值在低分化腺癌中显著高于高、中分化腺癌和粘液癌 (P <0 .0 1) ;有淋巴结转移者显著高于无淋巴结转移者 (P <0 .0 1) ;5年内死亡病例显著高于生存病例 (P <0 .0 1)。结论 :唾液酸化LewisX表达阳性率和反应强度对反映大肠癌组织发生发展、判断恶性程度、预测转移和评估患者预后具有重要意     

唾液酸化Lewis X 在大肠癌中的表达研究

目的探讨大肠癌组织中唾液酸化LewisX(sialyl-LewisX)的表达状况和分布特点,以及与肿瘤发生发展、转移的关系.方法应用免疫组化微波-LSAB法,对90例大肠癌及30例正常粘膜组织进行Sialyl-LewisX检测,并进一步用胶体金免疫电镜技术对阳性物质的分布特征进行观察.结果大肠癌组织中83例呈Sialyl-LewisX阳性表达,阳性率为92.2%;正常大肠粘膜中5例呈弱阳性表达,阳性率仅为16.7%.Sialyl-LewisX表达阳性率在伴有淋巴结转移的大肠癌中为100%,显著高于无淋巴结转移者(82.1%)(P<0.01).免疫电镜显示,在阳性癌细胞中Sialyl-LewisX主要分布于细胞浆的界膜、内质网、高尔基体及近细胞核膜处,而在正常粘膜则主要分布于细胞浆的界膜处.结论Sialyl-LewisX表达与大肠癌的发生发展及其生物学行为有关,它可能是通过改变糖链的糖基及其构型而参与肿瘤的侵袭和转移过程.     

Primary squamous cell carcinoma of the breast presenting as a breast abscess

Primary squamous cell carcinoma (SCC) of the breast is a very rare neoplasm, with only 75 cases reported in the English literature. Herein, we report four new cases and discuss the diagnostic and therapeutic challenges of this unusual tumor in a retrospective review of all cases of SCC of the breast at our institution from 1990 to 1998. Four patients with breast SCC were identified, with a mean age of 70 years. Two patients with "pure" SCC (no features of ductal carcinoma) were initially treated for breast abscess. Two other patients with features of both SCC and ductal carcinoma had skin erythema associated with an underlying mass, and infectious etiology was considered in each case. Mean tumor size was 4.9 cm. Both patients with pure SCC underwent extensive evaluation for primary tumors at other sites. Two patients developed early systemic metastasis. SCC of the breast is often diagnosed at an advanced stage and may be confused with breast abscess. For this reason, breast biopsy should be considered in cases of breast abscess. Treatment of primary SCC of the breast is similar to that of more common types of breast cancer (i.e., breast conservation is possible and lymph node dissection is recommended). Because metastasis to the breast from other primary tumor sites has been reported (lung, cervix, skin, and esophagus), patients with pure SCC should undergo evaluation to exclude this possibility.     

Increased expression of inducible nitric oxide synthase for human buccal squamous-cell carcinomas: immunohistochemical,reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR studies

BACKGROUND: The inducible nitric oxide synthase (iNOS) is involved primarily in inflammatory and carcinogenesis processes. An enhanced expression of iNOS at the protein level has been reported previously for human oral squamous cell carcinoma; however, the expression of iNOS at the mRNA level has not yet been demonstrated. Furthermore, no studies have addressed whether iNOS expression at mRNA level correlates with cervical lymph node metastasis. METHODS: Specimens of the squamous cell carcinoma of the buccal mucosa obtained from tissue samples of surgically resected tumors from 25 male patients were evaluated with immunohistochemical assessment of iNOS protein and IS-RT-PCR, as well as RT-PCR for iNOS mRNA. We also analyzed the iNOS expression status with clinical parameters to determine whether it had any prognostic significance in this homogenous population. RESULTS: Inducible NOS protein (16 of 25, 64%) and mRNA (13 of 25, 53%) activities were detected for the oral carcinoma specimens examined in this study. Cytoplasmic and/or nuclear stainings were observed in the specimens of both well-differentiated SCC (10 of 15, 67%), and moderately to poorly differentiated SCC (6 of 10, 60%). The cellular location of iNOS mRNA was noted to be consistent with the finding using immunohistochemical technique (cytoplasm and/or nuclei stainings of the tumor islands). Using in situ RT-PCR, iNOS mRNA activity was detected in nine specimens of well-differentiated squamous cell carcinoma (9 of 15, 60%) and four specimens of moderately to poorly differentiated squamous cell carcinoma (4 of 10, 40%). With RT-PCR, an electrophoretic band corresponding to a 907-bp PCR product was observed for nine specimens of well-differentiated squamous cell carcinoma (9 of 15, 60%) and four specimens of moderately to poorly differentiated squamous-cell carcinoma (4 of 10, 40%). Neither iNOS protein nor mRNA was noticed in the samples of normal buccal mucosa or in the negative control samples. There was a significant relationship between iNOS expression (at both protein and mRNA levels) and whether patients had nodal disease. CONCLUSIONS: We have demonstrated an enhanced expression of iNOS protein and mRNA in a number of human buccal carcinomas compared with normal buccal mucosa. Such an observation suggests that the iNOS protein and mRNA expression is chiefly derived from a subset of oral cancerous tissues. Our observation also indicates that iNOS expression correlates with cervical lymph node metastasis in oral squamous cell carcinomas. Therefore, it may also indicate that a subset of oral cancers with greater metastatic potential, as evidenced by increased expression iNOS protein and mRNA, is identified.     

Expression of SSEA-1 carbohydrate antigen correlates with stage, grade and metastatic potential of transitional cell carcinoma of the bladder.

Expression of stage-specific embryonic antigen-1 (SSEA-1) was immunohistochemically analyzed in primary cancerous regions from transitional cell carcinoma of the bladder. Lymph node metastasis occurred in 14 (50%) of 28 patients with high expression of SSEA-1 antigen, but in only one (4%) of 23 patients with low or no expression. Of 36 invasive bladder carcinoma patients with no metastasis at operation, 8 (57%) of 14 with high expression of SSEA-1 antigen died of cancer or had metastasis, whereas 4 (18%) of 22 with low or no expression had progression of the disease. In addition, stage pT3b-4 tumors more frequently reacted with SSEA-1 MAb than stage pT1 tumors (p less than 0.01). Grade 2 or 3 tumors were also more reactive than grade 1 tumors, which were all unreactive except for one (p less than 0.01, respectively). Our data suggest that SSEA-1, which is a Le(x) antigen, correlates with stage and grade as well as metastatic phenotype of transitional cell carcinoma of the bladder.     

Expression of Ki-67 in squamous cell carcinoma of the penis

OBJECTIVE: To investigate the Ki-67 labelling index (LI) as a prognostic factor for the outcome of penile carcinoma, as in squamous cell carcinoma (SCC) of the larynx the expression of this marker correlates with histological features indicative of prognosis. PATIENTS AND METHODS: We retrospectively analysed the records of 44 patients in whom primary SCC of the penis was treated with amputation and bilateral lymphadenectomy (pT1, in 24, pT2 in 20, pN+ in 10; G1 in 12, G2 in 28 and G3 in four). During a mean follow-up of 35.6 months, four patients had disease progression. Tumour tissue was stained immunohistochemically using the streptavidin-biotin method. The mean Ki-67 LI was defined as the percentage of total tumour cells that were Ki-67-positive. The results were compared with pathological tumour stage, grade, nodal status and clinical disease progression. RESULTS: The mean (range) Ki-67 LI was 40.5 (6.4-93.0)%; a high mean Ki-67 LI was significantly inversely correlated with tumour differentiation (P < 0.005) and there was a tendency for a high Ki-67 LI to be associated with advanced local tumour stage, nodal metastasis and clinical disease progression, but these correlations were not statistically significant (P = 0.07, 0.07 and 0.06, respectively). CONCLUSIONS: The Ki-67 LI is correlated with tumour grade in penile cancer, and may indicate a greater risk of nodal metastasis.     

Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source.

OBJECTIVE: To demonstrate an oncologic basis for the recommendation to perform bilateral tonsillectomy as a routine measure in the search for a primary mucosal lesion in patients presenting with cervical nodal metastasis of squamous cell carcinoma (SCC). STUDY DESIGN: A case series of individuals selected from a 3-year period is reported. SETTING: Academic medical center. RESULTS: Each individual presented with metastatic squamous cell carcinoma in a cervical lymph node from an unknown primary source. In each case, the primary source was identified in a tonsillectomy specimen, either located contralateral to the node, or in both tonsils. CONCLUSIONS: The rate of contralateral spread of metastatic cancer from occult tonsil lesions appears to approach 10%. For this reason, bilateral tonsillectomy is recommended as a routine step in the search for the occult primary in patients presenting with cervical metastasis of SCC and palatine tonsils intact.     

Maspin expression in stage I and II oral tongue squamous cell carcinoma.

BACKGROUND: A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. METHODS: We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. RESULTS: Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p =.01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p =.03). CONCLUSIONS: Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs.     

Studies on antigen associated with human squamous cell carcinoma (SCC antigen) in patients with esophageal carcinoma

The authors studied on SCC antigen in patients with esophageal carcinoma. Serum SCC antigen was found in 9 (40.9%) of 22 patients with esophageal squamous cell carcinoma and 5 (55.5%) of 9 patients with lung squamous cell carcinoma, but was not found in other malignant diseases, such as gastric cancer, hepatoma, colon cancer, pancreas cancer and biliary try tract cancer. SCC antigen positive cases increased in association with progression of histological invasion, grade of nodal metastasis and clinical stage. However, in early esophageal carcinoma, SCC antigen was rarely positive. There was no positive case in patients with poorly differentiated squamous cell carcinoma regardless of clinical stage. Positive rate of SCC antigen increased in association with progression of clinical stage in patients with moderately and well differentiated squamous cell carcinoma. Immunoreactivity of SCC, which was investigated immunohistologically with TA-4 rabbit serum, was not found in cases with poorly differentiated squamous cell carcinoma, but was found in keratinized portion and cytoplasm of moderately and well differentiated carcinoma. From the above, SCC antigen is intimately related with keratinization of squamous cell carcinoma, and it was thought that it could be useful as a good marker for diagnosis of moderately and well differentiated squamous carcinoma of the esophagus.     

Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy

BACKGROUND: To develop novel therapeutic approaches for patients with head and neck malignancies, poorly immunogenic murine models of squamous cell carcinoma (SCC) need to be defined. METHODS: The phenotype, growth characteristics, and responsiveness to tumor-specific T-cell transfer of a spontaneously arising murine SCC (SCC VII) were characterized. RESULTS: SCC VII expresses major histocompatibility complex (MHC) class I molecules yet is resistant to tumor-specific T-cell killing and relatively insensitive to killing mediated by lymphokine-activated killer (LAK) cells. Intradermal tumors are reproducibly established after vaccination of 5 x 10(4) cells, and systemic micrometastases are apparent after intravenous administration of 2.5 x 10(4) cells. Immunotherapy of 3-day lung metastases using tumor-specific T cells and systemic interleukin-2 (IL-2) was ineffective in reducing the number of metastases in vivo. CONCLUSIONS: SCC VII is a poorly immunogenic murine squamous cell cancer, which represents an ideal model for preclinical testing of immunotherapeutic approaches for patients with SCC of the upper aerodigestive tract.     

Metastatic Cutaneous Squamous Cell Carcinoma: An Update

BACKGROUND: Squamous cell carcinoma (SCC) is the second most common type of skin cancer in the United States. Cutaneous SCC has the potential to metastasize and cause morbidity and mortality. OBJECTIVE: Our purpose was to review and summarize the literature on metastatic cutaneous SCC, including risk factors for metastasis, data from clinical studies, and current management. RESULTS: Multiple studies confirm that even well-differentiated and small tumors (<2 cm) may metastasize. Over the past two decades, additional literature on the risk factors for metastatic cutaneous SCC, including immunosuppression, has been published. In addition, new staging systems have been proposed that may influence management of these tumors. Chemotherapy regimens are numerous, but remain limited in ability to improve overall survival. CONCLUSION: Although we know more about the risk factors, survival for patients with metastatic cutaneous SCC depends on extent of nodal involvement. Therefore, emphasis should remain on prevention and aggressive treatment of cutaneous SCC and vigilant observation for signs and symptoms of metastasis.     

Basaloid squamous cell carcinoma of the penis with papillary features: a clinicopathologic study of 12 cases

There are 3 distinct variants of penile squamous cell carcinoma frequently associated with human papillomavirus (HPV): basaloid, warty-basaloid, and warty carcinomas. Considering the high incidence rates of penile cancer in some countries, a large international study was designed to evaluate the presence of HPV, its genotype distribution, and its association with histologic types of penile cancer. In this international review of >900 cases, we found a group of highly distinct papillary neoplasms composed of basophilic cells resembling urothelial tumors but frequently associated with HPV. Macroscopically, tumors were exophytic or exoendophytic. Microscopically, there was a papillomatous pattern of growth with a central fibrovascular core and small basophilic cells lining the papillae. Positivity for HPV was present in 11 of 12 tumors (92%). Single genotypes found were HPV-16 in 9 tumors and HPV-51 in 1 tumor. Multiple genotypes (HPV-16 and HPV-45) were present in another case. Overexpression of p16 was observed in all cases. Uroplakin-III was negative in all cases. The differential diagnosis was with basaloid, warty-basaloid, warty, and papillary squamous cell carcinoma and with urothelial carcinomas. Local excision (4 cases), circumcision (3 cases), or partial penectomy (5 cases) were preferred treatment choices. Tumor thickness ranged from 1 to 15 mm (average, 7 mm). Two patients with tumors invading 11 and 15 mm into the corpus spongiosum developed inguinal nodal metastasis. Of 11 patients followed up (median 48 mo), 7 were alive with no evidence of metastatic disease, 3 died from causes other than penile cancer, and another died postoperatively. This morphologically distinct tumor probably represents a papillary variant of basaloid carcinomas (papillary-basaloid carcinomas). Unlike typical basaloid carcinomas, the overall prognosis was excellent. However, deeply invasive tumors were associated with regional nodal metastasis indicating a potential for tumor-related death.     

Squamous cell carcinoma of the floor of the mouth: tumour thickness and the rate of cervical metastasis

BACKGROUND: Increased thickness of oral cavity squamous cell carcinoma (SCC) has been shown to be associated with higher rates of cervical metastasis. Most of the previous studies have focused on SCC of the oral tongue. There are few studies that have examined solely carcinoma of the floor of the mouth and these studies differ in the thickness of tumour that is associated with significantly increased rates of cervical metastasis. METHODS: Patients with SCC of the floor of the mouth of all stages who were treated with excision and neck dissection were identified. Primary tumour thickness and other pathological features were determined in the pathological specimens and were correlated to the incidence of pathological cervical lymph node metastasis. Fisher's exact test and the unpaired t-test were used for statistical analysis. RESULTS: Fifty-three patients were studied (43 men and 10 women). The median age was 56.5 years (range 43-86 years). The median tumour thickness in patients with lymph node metastases (14.6 mm) differed significantly from those without metastases (8.6 mm) (P = 0.004). When T1 and T2 cases were looked at in isolation, the median tumour thickness of cases with lymph node metastases (11.1 mm) again was significantly greater than those without metastases (4.6 mm) (P = 0.04). Subgrouping tumours into those > or =7.5 mm or < 7.5 mm showed a significantly increased rate of lymph node metastasis (57% compared with 12%, P = 0.001). There was no statistically significant association between perineural invasion or tumour differentiation and the presence of lymph node metastases. CONCLUSION: Tumour thickness has been shown to be directly related to rates of cervical lymph node metastasis in floor of mouth SCC. The primary tumour thickness associated with significantly increased rates of metastasis is similar to that shown in previous studies examining SCC of the oral tongue.     

Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma: A Systematic Review of the English Literature

BACKGROUND: Although most cutaneous squamous cell carcinoma (SCC) is curable by a variety of treatment modalities, a small subset of tumors recur, metastasize, and result in death. Although risk factors for metastasis have been described, there are little data available on appropriate workup and staging of patients with high-risk SCC. OBJECTIVE: We reviewed reported cases and case series of SCC in which sentinel lymph node biopsy (SLNB) was performed to determine whether further research is warranted in developing SLNB as a staging tool for patients with high-risk SCC. METHODS: The English medical literature was reviewed for reports of SLNB in patients with cutaneous SCC. Data from anogenital and nonanogenital cases were collected and analyzed separately. The percentage of cases with a positive sentinel lymph node (SLN) was calculated. False negative and nondetection rates were tabulated. Rates of local recurrence, nodal and distant metastasis, and disease-specific death were reported. RESULTS: A total of 607 patients with anogenital SCC and 85 patients with nonanogenital SCC were included in the analysis. A SLN could not be identified in 3% of anogenital and 4% of nonanogenital cases. SLNB was positive in 24% of anogenital and 21% of nonanogenital patients. False-negative rates as determined by completion lymphadenectomy were 4% (8/213) and 5% (1/20), respectively. Most false-negative results were reported in studies from 2000 or earlier in which the combination of radioisotope and blue dye was not used in the SLN localization process. Complications were reported rarely and were limited to hematoma, seroma, cutaneous lymphatic fistula, wound infection, and dehiscence. CONCLUSIONS: Owing to the lack of controlled studies, it is premature to draw conclusions regarding the utility of SLNB in SCC. The available data, however, suggest that SLNB accurately diagnoses subclinical lymph node metastasis with few false-negative results and low morbidity. Controlled studies are needed to demonstrate whether early detection of subclinical nodal metastasis will lead to improved disease-free or overall survival for patients with high-risk SCC.     

Squamous cell carcinoma of the buccal mucosa: one institution's experience with 119 previously untreated patients

BACKGROUND: Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC. METHODS: We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded. RESULTS: Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p <.05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful. CONCLUSIONS: SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites.     

Management of contralateral N0 neck in oral cavity squamous cell carcinoma

BACKGROUND: The purpose of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in squamous cell carcinomas of the oral cavity to form a rational basis for elective contralateral neck management. METHODS: We performed a retrospective analysis of 66 patients with cancer of the N0-2 oral cavity undergoing elective neck dissection for contralateral clinically negative necks from 1991 to 2003. RESULTS: Clinically negative but pathologically positive contralateral lymph nodes occurred in 11% (7 of 66). Of the 11 cases with a clinically positive ipsilateral node neck, contralateral occult lymph node metastases developed in 36% (4 of 11), in contrast with 5% (3 of 55) in the cases with clinically N0 ipsilateral necks (p < .05). Based on the clinical staging of the tumor, 8% (3 of 37) of the cases showed lymph node metastases in T2 tumors, 25% (2 of 8) in T3, and 18% (2 of 11) in T4. None of the T1 tumors (10 cases) had pathologically positive lymph nodes. The rate of contralateral occult neck metastasis was significantly higher in advanced-stage cases and those crossing the midline, compared with early-stage or unilateral lesions (p < .05). Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5-year disease-specific survival rate was 79% vs. 43%, p < .05). CONCLUSIONS: The risk of contralateral occult neck involvement in the oral cavity squamous cell carcinomas above the T3 classification or those crossing the midline with unilateral metastases was high, and patients who presented with a contralateral metastatic neck had a worse prognosis than those whose disease was staged as N0. Therefore, we advocate an elective contralateral neck treatment with surgery or radiotherapy in patients with oral cavity squamous cell carcinoma with ipsilateral node metastases or tumors, or both, whose disease is greater than T3 or crossing the midline.     

Is there a role for positron emission tomography with 18F-fluorodeoxyglucose in the initial staging of nodal negative oral and oropharyngeal squamous cell carcinoma

BACKGROUND: The aim of our study was to assess the value of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) for the staging of clinically nodal negative necks in oral and oropharyngeal squamous cell carcinoma (SCC) using sentinel lymph node (SLN) biopsy and elective neck dissection (END) as "gold standard" for comparison. METHODS: Twelve patients (10 men, 2 women) with oral or oropharyngeal squamous cell carcinoma and no evidence of lymph node metastasis in the physical and radiologic examinations were eligible. At least 24 hours before surgery PET with FDG were performed. The SLN was localized by preoperative lymphoscintigraphy with 99m-Tc-Nanocoll and intraoperative use of a hand-held gamma-probe and selectively excised. All patients then underwent END. RESULTS: SLN and END revealed occult metastasis in 5 of 12 cases. SLN biopsy was accurately feasible in all 12 patients and diagnosed all 5 cases of occult metastasis (sensitivity and specificity of 100%). PET suggested two patients having occult metastasis, of which one turned out to be false positive (sensitivity 25%, specificity 88%). The mean size of the micrometastasis was 1.4 mm (range, 1.2-1.5 mm). CONCLUSIONS: PET with FDG turned out to have a poor sensitivity and specificity in revealing occult metastasis and has no role for the evaluation of otherwise clinically N0 necks. The failure to detect micrometastasis by PET is due to the technical limitations of resolution (4-5 mm). SLN biopsy, with END in cases of positive SLN, provides a highly accurate staging of N0 necks in oral and oropharyngeal carcinoma. Patients with negative SLN could be spared the risks and the morbidity of END.