Diane L Carlson

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

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Publications (37)175.27 Total impact

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    ABSTRACT: To describe the outcome of patients with poorly differentiated thyroid cancer (PDTC) presenting with gross extrathyroidal extension (ETE). After IRB approval we performed retrospective review of consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at MSKCC from 1986-2009. Out of 91 PDTC patients, 27 (30%) had gross ETE (T4a) and they formed the basis of our study. Of 27 patients, 52% were female. The median age was 70 (range 27-87). Ten patients (37%) presented with distant metastases; four to the bone, three to lung and three had both bone and lung metastases. All patients had extended total thyroidectomy except two who had subtotal thyroidectomy. 20 patients (74%) had central compartment neck dissection and 11 also had lateral neck dissection. Four patients had pN0, 6 (30%) pN1a and 10 (50%) pN1b neck disease. 21 patients (77%) had adjuvant therapy: 15 (55%) RAI only, 3 (11%) postoperative external beam radiation (PORT) only and 3 (11%) had both RAI and PORT. Overall survival (OS), disease specific survival (DSS), local recurrence free survival (LRFS) and regional recurrence free survival (RRFS) were calculated by the Kaplan Meier method. Median follow-up time was 57 months (range 1-197 months). The 5 year OS and DSS were 47% and 49% respectively. This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further 6 developed distant metastases during follow up. Locoregional control was good with 5 year LRFS and RRFS of 70% and 62% respectively. Overall, 8 patients (30%) had recurrences: 2 had distant alone, 2 regional, 2 regional and distant, 1 local and distant, and 1 had local, regional and distant recurrence. Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control. Due to the small proportion of patients who received PORT (22%), it is not possible to analyze its benefit on locoregional control. Of significance is the observation that the majority of patients (60%) who presented with or subsequently developed distant metastases eventually died of distant disease. New systemic therapies to target distant metastatic disease are required for improvements in outcome.
    Thyroid: official journal of the American Thyroid Association 01/2013; · 2.60 Impact Factor
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    ABSTRACT: BACKGROUND: The objectives of this study were to determine the incidence of locoregional failure in patients with low-risk, early stage oral tongue squamous cell cancer (OTSCC) who undergo partial glossectomy and ipsilateral elective neck dissection without receiving postoperative radiation. METHODS: A combined database of patients with OTSCC who received treatment at Memorial Sloan-Kettering Cancer Center and Princess Margaret Cancer Center from 1985 to 2005 was established. In total, 164 patients with pathologic T1-T2N0 OTSCC who underwent partial glossectomy and ipsilateral elective neck dissection without postoperative radiation were identified. Patient-related, tumor-related, and treatment-related characteristics were recorded. Local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. RESULTS: At a median follow-up of 66 months (range 1-171 months), the 5-year rates of local recurrence-free survival, regional recurrence-free survival, and disease-specific survival were 89%, 79.9%, and 85.6%, respectively. Regional recurrence was ipsilateral in 61% of patients and contralateral in 39% of patients. The regional recurrence rate was 5.7% for tumors <4 mm and 24% for tumors ≥4 mm. Multivariate analysis indicated that tumor thickness was the only independent predictor of neck failure (regional recurrence-free survival, 94% vs 72% [P = .02] for tumors <4 mm vs ≥4 mm, respectively). Patients who developed recurrence in the neck had a significantly poorer disease-specific survival compared with those who did not (33% vs 97%; P < .0001). CONCLUSIONS: Patients with low-risk, pathologic T1-T2N0 OTSCC had a greater than expected rate of neck failure, with contralateral recurrence accounting for close to 40% of recurrences. Failure occurred predominantly in patients who had primary tumors that were ≥4 mm thick. Cancer 2013. © 2013 American Cancer Society.
    Cancer 11/2012; · 5.20 Impact Factor
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    ABSTRACT: Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB. Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients. Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.
    Journal of neurological surgery. Part B, Skull base. 06/2012; 73(3):208-20.
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    ABSTRACT: For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high-dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. Planned treatment consisted of definitive intensity-modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m(2) on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2-year progression-free survival (PFS), and overall survival (OS) was a secondary endpoint. Forty-two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27-75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment-related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow-up was approximately 31.8 months (range, <3 to 51 months). The 2-year PFS rate was 75.9% (95% confidence interval, 63.9%-90.1%), and the 2-year OS rate was 88% (95% confidence interval, 78.6%-98.4%). Among 32 patients for whom post-treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients. The addition of bevacizumab to high-dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging. Cancer 2012. © 2012 American Cancer Society.
    Cancer 03/2012; 118(20):5008-14. · 5.20 Impact Factor
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    ABSTRACT: The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the "endogenous marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not show significant correlation. The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.
    Oral Oncology 02/2012; 48(8):717-22. · 2.70 Impact Factor
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    ABSTRACT: The objective of this study was to determine the prognostic significance of viable tumor in postchemoradiation neck dissection specimens in patients with squamous cell carcinoma of the laryngopharynx. Retrospective analysis identified 181 patients treated with primary concurrent chemoradiation for carcinoma of the laryngopharynx at Memorial Sloan-Kettering Cancer Center between the years 1995 and 2005. Of these, 56 patients had a comprehensive neck dissection either as a planned or salvage procedure. Neck dissection specimens were analyzed by a single pathologist for the presence of viable tumor. The presence of viable tumor was correlated to the timing of neck dissection after chemoradiation and to tumor response. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by the Kaplan-Meier method, and correlation to tumor viability was determined with the log-rank test. Nineteen (33%) patients had viable tumor in their neck dissection specimens. Viable tumor was higher in patients who had a less-than-complete response to chemoradiation compared with those who had a complete response (42% vs 25%, p = .1). There was no correlation to timing of neck dissection. The 5-year OS, DSS, and RFS were significantly lower in patients who had viable tumor in their neck dissection specimens (OS 49% vs 93%, p = .0005; DSS 56% versus 93%, p = .003; RFS 40% vs 75%, p = .004). Patients with viable tumor in postchemoradiation neck dissection specimens had a poorer outcome compared with patients with no viable tumor.
    Head & Neck 10/2011; 33(10):1387-93. · 2.83 Impact Factor
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    ABSTRACT: Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.
    Pediatric Blood & Cancer 05/2011; 57(4):693-5. · 2.35 Impact Factor
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    ABSTRACT: Saracatinib (AZD0530) is an orally available Src kinase inhibitor. A phase II study was conducted to evaluate saracatinib in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This was an open-label, single-arm, phase II study. Patients received 175 mg saracatinib daily either orally or by percutaneous gastrostomy tube. Radiologic imaging for response was planned at the end of each eight-week cycle. Nine patients were enrolled. All patients had received prior radiotherapy and six patients had received prior chemotherapy for recurrent or metastatic disease. The most common adverse event was fatigue. Eight patients had progression of disease by response evaluation criteria in solid tumors (RECIST) within the first eight-week cycle and one patient was removed from the study after 11 days due to clinical decline with stable disease according to the RECIST criteria. Median overall survival was six months. The study was closed early due to lack of efficacy according to the early stopping rule. Single-agent saracatinib does not merit further study in recurrent or metastatic HNSCC.
    Anticancer research 01/2011; 31(1):249-53. · 1.71 Impact Factor
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    ABSTRACT: We report a case of functional vagal paraganglioma to illustrate the biochemical and radiological imaging tests important in diagnosis and to highlight the importance of a multidisciplinary team approach to manage the preoperative, perioperative, and postoperative effects of catecholamine secretion from these tumors.
    Skull Base 11/2010; 20(6):491-6. · 0.66 Impact Factor
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    ABSTRACT: Preclinical studies suggest that additive or synergistic effects are achieved with the combination of pemetrexed plus gemcitabine. A phase 1 study of pemetrexed plus gemcitabine given every 2 weeks demonstrated encouraging preliminary efficacy against head and neck squamous cell cancer (HNSCC). This was an open-label, single-institution, single-arm, phase 2 study for patients who had received no more than 2 cytotoxic regimens for recurrent and/or metastatic HNSCC. All patients received pemetrexed 500 mg/m² intravenously plus gemcitabine 1250 mg/m² intravenously every 2 weeks with vitamin B12 and folate support. The primary endpoint was the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST); secondary endpoints were to estimate overall survival and to evaluate safety and tolerability. Twenty-five patients received therapy. All patients had received prior radiotherapy, and half had received prior cytotoxic chemotherapy for recurrent and/or metastatic disease. Neutropenia (grade ≥ 3) occurred in 24% of patients. Four patients (16%) had a partial response (PR) according to RECIST, and 5 additional patients (20%) had objective tumor reductions of > 20 but < 30% did not meet RECIST criteria for a PR. The median overall survival for all treated patients was 8.8 months. Treatment with pemetrexed plus gemcitabine every 2 weeks with vitamin support generally was well tolerated. The results of this study provided further evidence that pemetrexed may have significant palliative activity against advanced HNSCC.
    Cancer 10/2010; 117(4):795-801. · 5.20 Impact Factor
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    ABSTRACT: Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a(-/-) mice, whereas its expression in Ink4a(-/-)/PTEN(-/-) background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-beta) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-beta alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers.
    Neoplasia (New York, N.Y.) 06/2010; 12(6):476-84. · 5.48 Impact Factor
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    ABSTRACT: Carcinoma ex pleomorphic adenoma is a rare salivary gland neoplasm, especially when the malignant component is only intracapsular/minimally invasive. Moreover, only few studies have assessed the behavior of carcinoma ex pleomorphic adenoma according to the histologic subtype. Forty-three cases of carcinoma ex pleomorphic adenoma were identified over a 27-year period and subjected to a detailed histopathologic analysis. There were 13 intracapsular/minimally invasive and 30 widely invasive carcinomas. There were 15 myoepithelial carcinomas, 25 salivary duct carcinomas, 2 adenocarcinomas not otherwise specified, and 1 carcinosarcoma. There was a trend toward a higher frequency of myoepithelial carcinomas in widely invasive tumors (13/30, 43%) than in intracapsular/minimally invasive (2/13, 15%) carcinoma ex pleomorphic adenoma (P = .095). Adequate follow-up was available for 38 patients. Vascular invasion and distant metastases correlated with decreased disease-free survival and disease-specific survival (P < .05), whereas the extent of invasion and the presence of a high mitotic rate or atypical mitoses correlated with decreased disease-free survival only (P < .05). There was a trend toward worse disease-free survival and disease-specific survival in patients with myoepithelial carcinoma (P = .08). Within the intracapsular/minimally invasive carcinoma ex pleomorphic adenoma group, both myoepithelial carcinoma (2/2, 100%) had metastatic disease, whereas only 1 of 11 nonmyoepithelial carcinoma relapsed (P = .038). Vascular invasion, high mitotic rate, and histologic subtype were found to correlate with recurrence in carcinoma ex pleomorphic adenoma. Patients with intracapsular/minimally invasive tumor have a more favorable outcome than patients with widely invasive neoplasm, but intracapsular/minimally invasive carcinoma ex pleomorphic adenoma can recur and cause death. The presence of myoepithelial carcinoma subtype increases the risk of recurrence in carcinoma ex pleomorphic adenoma, especially within the group of intracapsular/minimally invasive tumors.
    Human pathology 03/2010; 41(7):927-34. · 3.03 Impact Factor
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    ABSTRACT: The ability of cancer to infiltrate along nerves is a common clinical observation in pancreas, head and neck, prostate, breast, and gastrointestinal carcinomas. For these tumors, nerves may provide a conduit for local cancer progression into the central nervous system. Although neural invasion is associated with poor outcome, the mechanism that triggers it is unknown. We used an in vitro Matrigel dorsal root ganglion and pancreatic cancer cell coculture model to assess the dynamic interactions between nerves and cancer cell migration and the role of glial cell-derived neurotrophic factor (GDNF). An in vivo murine sciatic nerve model was used to study how nerve invasion affects sciatic nerve function. Nerves induced a polarized neurotrophic migration of cancer cells (PNMCs) along their axons, which was more efficient than in the absence of nerves (migration distance: mean = 187.1 microm, 95% confidence interval [CI] = 148 to 226 microm vs 14.4 microm, 95% CI = 9.58 to 19.22 microm, difference = 143 microm; P < .001; n = 20). PNMC was induced by secretion of GDNF, via phosphorylation of the RET-Ras-mitogen-activated protein kinase pathway. Nerves from mice deficient in GDNF had reduced ability to attract cancer cells (nerve invasion index: wild type vs gdnf+/-, mean = 0.76, 95% CI = 0.75 to 0.77 vs 0.43, 95% CI = 0.42 to 0.44; P < .001; n = 60-66). Tumor specimens excised from patients with neuroinvasive pancreatic carcinoma had higher expression of the GDNF receptors RET and GRFalpha1 as compared with normal tissue. Finally, systemic therapy with pyrazolopyrimidine-1, a tyrosine kinase inhibitor targeting the RET pathway, suppressed nerve invasion toward the spinal cord and prevented paralysis in mice. These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer.
    CancerSpectrum Knowledge Environment 01/2010; 102(2):107-18. · 14.07 Impact Factor
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    ABSTRACT: The impact of lymph node metastases on prognosis in patients with oral cavity squamous cell carcinoma (OSCC) has been well recognized. However, accurate stratification of risk for recurrence among patients with lymph node metastases is difficult based on the existing staging systems. In the current study, the utility of lymph node density (LND) was evaluated as an alternative method for predicting survival. Three hundred eighty-six patients who underwent neck dissection were included. The median follow-up was 67 months. Five-year overall survival (OS), disease-specific survival (DSS), and locoregional failure (LRF) rates were calculated using the Kaplan-Meier method. LND (number of positive lymph nodes/total number of excised lymph nodes) and tumor-node-metastasis (TNM) staging variables were subjected to multivariate analysis. Using the median (LND=0.06) as the cutoff point, LND was found to be significantly associated with outcome. For patients with LND<or=0.06, the OS was 58 percent versus 28 percent for patients with LND>0.06 (P<.001). Similarly, the DSS for patients with LND<or=0.06 was 65 percent and was 34 percent for those with LND>0.06 (P<.001). On univariate analysis, pathologic T and N classification, extracapsular spread, and LND were found to be significant predictors of outcome (P<.001). However, on multivariate analysis, LND remained the only independent predictor of OS (P=.02; hazards ratio, 2.0), DSS (P=.02; hazards ratio, 2.3), and LRF (P=.005; hazards ratio, 4.1). LND was also found to be the only significant predictor of outcome in patients receiving adjuvant radiotherapy (P<.05). Within individual subgroups of pN1 or pN2 patients, LND reliably stratified patients according to their risk of failure (P<.05). After surgery for OSCC, pathologic evaluation of the neck using LND was found to reliably stratify the risk of disease recurrence and survival.
    Cancer 08/2009; 115(24):5700-10. · 5.20 Impact Factor
  • Diane L Carlson
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    ABSTRACT: Necrotizing sialometaplasia is a benign, self-limited lesion of both major and minor salivary glands, although more commonly the latter. It can represent a diagnostic dilemma and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. A major causal relationship has been ascribed to ischemia. Bulimia, an eating disorder with increasing prevalence in our society, may also be an underlying underreported cause. To discuss the potential pathogenesis, diagnostic pitfalls, and the application of immunohistochemistry as an aid in the diagnosis of necrotizing sialometaplasia. This report uses a previously published case history for illustrative purposes and a review of the current literature. The diagnosis of necrotizing sialometaplasia may be difficult and is reliant upon a well-oriented biopsy section and a complete clinical history. Diagnosis may be further supplemented via immunohistochemistry, demonstrating focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells. Interpreted in context collectively, these findings may be helpful adjuncts in the diagnosis of necrotizing sialometaplasia; nonetheless, to date, hematoxylin-eosin staining remains the gold standard.
    Archives of pathology & laboratory medicine 06/2009; 133(5):692-8. · 2.78 Impact Factor
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    ABSTRACT: To characterize the incidence and pattern of neural invasion (NI) in patients with cancers of the paranasal sinuses and anterior skull base. Retrospective study. A tertiary referral cancer center. The study included 208 patients with cancer of the paranasal sinuses. Patients with brain invasion or neurogenic tumors were excluded. Analysis of clinical and pathologic data on patients with cancer of the paranasal sinuses. Forty-one specimens (20%) had evidence of NI. Sinonasal undifferentiated, adenoid cystic, and squamous cell carcinoma had a high propensity for NI, whereas melanoma and sarcoma rarely invaded nerves. Intraneural invasion was found in 32% of these cases, and 34% invaded more than 1 cm distal to the tumor. Neural invasion was associated with a high rate of positive margins, maxillary origin, and previous surgical treatment (P < .04) but not with stage, orbital invasion, or dural invasion. Patients with NI were more likely to undergo adjuvant radiotherapy (P = .003), which significantly improved survival in patients with minor salivary gland carcinomas (P = .04). Multivariate analysis showed that pathologic evidence of NI was not an independent predictor of outcome. Paranasal carcinomas have high propensity for NI, whereas melanoma and sarcoma rarely invade nerves. Patterns of NI include both perineural and intraneural invasion. Neural invasion is associated with positive margins, maxillary origin, and previous surgery.
    Archives of otolaryngology--head & neck surgery 02/2009; 135(2):173-9. · 1.92 Impact Factor
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    ABSTRACT: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR. Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.
    BMC Cancer 01/2009; 9:11. · 3.33 Impact Factor
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    ABSTRACT: This article reports the case of a 59-year-old patient with an 8-year history of chronic lymphocytic leukemia (CLL), prostate carcinoma, and squamous cell carcinoma who developed an ALK-positive anaplastic large cell lymphoma (ALCL). Lymph node and bone marrow biopsies showed 2 distinct morphologic populations: (a) the CLL component showing a diffuse monomorphous infiltrate of small lymphocytes with the typical immunophenotype showing positive CD20, CD5, CD23, and κ light chain restriction and (b) the ALCL component showing large anaplastic pleomorphic cells positive for CD30, CD45, ALK, CD45Ro, CD4, and vimentin. Polymerase chain reaction performed on the lymph node for immunoglobulin heavy chain and T-cell receptor γ and β showed gene rearrangements after macrodissection of morphologically distinct populations, indicating confirmed genetically distinct populations. Despite intensive chemotherapy, the patient died. This case represents the rare occurrence of an ALK-positive ALCL developing in a patient with CLL.
    International Journal of Surgical Pathology 10/2008; 18(5):424-8. · 0.76 Impact Factor
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    ABSTRACT: Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past 5 years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate (IVBP) therapy, but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. To further categorize risk factors associated with ONJ and potential clinical outcomes of this condition, we performed a retrospective study of patients with metastatic bone disease treated with intravenous bisphosphonates who have been evaluated by the Memorial Sloan-Kettering Cancer Center Dental Service between January 1, 1996 and January 31, 2006. We identified 310 patients who met these criteria. Twenty-eight patients were identified as having ONJ at presentation to the Dental Service and an additional 7 patients were subsequently diagnosed with ONJ. Statistically significant factors associated with increased likelihood of ONJ included type of cancer, duration of bisphosphonate therapy, sequential IVBP treatment with pamidronate followed by zoledronic acid, comorbid osteoarthritis or rheumatoid arthritis, and benign hematologic conditions. Our data do not support corticosteroid use or oral health as a predictor of risk for ONJ. Clinical outcomes of patients with ONJ were variable with 11 patients demonstrating improvement or healing with conservative management. Our ONJ experience is presented here.
    The Oncologist 09/2008; 13(8):911-20. · 4.10 Impact Factor
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    Journal of Clinical Oncology 09/2008; 26(24):4037-8. · 18.04 Impact Factor