RESUMO
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare dendritic cell tumor with slightly more than 100 cases reported in the English literature. This report discusses a case of localized IDCS involving cervical lymph nodes and provides a literature review of clinicopathologic aspects and treatment outcomes.
Assuntos
Sarcoma de Células Dendríticas Interdigitantes/diagnóstico , Sarcoma de Células Dendríticas Interdigitantes/terapia , Idoso de 80 Anos ou mais , Biópsia , Terapia Combinada , Fluordesoxiglucose F18 , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Masculino , Tomografia por Emissão de Pósitrons , Resultado do TratamentoRESUMO
The presentation of two 19-year-old male subjects with stage I non-Hodgkin lymphoma in the proximal tibia prompted an extensive review of institutional and national databases to assess whether there is any statistical evidence that these reflected a previously overlooked syndromic pattern of presentation. The institutional records of a single institution were reviewed for presentation of non-Hodgkin lymphoma in the bone. The records of two additional institutions were reviewed for all reports of non-Hodgkin lymphoma in the tibia. Analysis was performed on data from Surveillance, Epidemiology, and End Results (SEER) dichotomized to bone presentation in the lower extremity versus other bones. Institutional databases included 20 patients with tibial presentation of lymphoma with a median age of 22.5 years (versus 42 for all bone lymphomas; P<0.001). Eighteen out of twenty patients had diffuse large B-cell lymphoma, and all patients aged ≤40 achieved remission and apparent cure. Distinctive and unusual features were a tendency for bilateral involvement of the tibia and sclerotic changes on X-ray. SEER data included 808 cases of bone lymphoma; the fraction of cases presenting in the lower extremity versus other bone sites is higher at ages ≤40 years (38% versus 19%; P<0.0001). Presentation in the lower extremity, as compared with other bone sites, confers 97% overall survival in patients aged ≤40 (versus 82%; P=0.01). This survival effect was independent of stage. In contrast, no significant difference in overall survival was identified for lower extremity versus non-lower extremity site for age >40. These data show a previously undescribed syndromic pattern of disease presentation: bone lymphoma in young patients is likely to present in the lower extremity-specifically the proximal tibia-has atypical sclerotic features on X-ray, is often bilateral, and has an excellent prognosis compared with bone lymphomas at other sites matched for stage and age.
Assuntos
Neoplasias Ósseas/patologia , Linfoma/patologia , Tíbia/patologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/análise , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Ósseas/química , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Linfoma/química , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia , Indução de Remissão , Fatores de Risco , Programa de SEER , Tíbia/química , Tíbia/diagnóstico por imagem , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition.
RESUMO
Chronic lymphocytic leukemia (CLL) involving skin is a rare but well-documented occurrence, mainly reported in advanced disease. In contrast, CLL presenting with skin lesions is exceedingly rare, only few reports existing to date. We report a 70-year-old man who presented with two non-pruritic, papular lesions on the lower abdomen and proximal thigh. Biopsies showed dense lymphohistiocytic infiltrates involving the reticular dermis and subcutis without epidermotropism consisting mostly of small, CD20 and PAX-5-positive B-cells expressing CD5, CD23, CD43 and BCL2. Numerous large B-cells were present in a T-cell, histiocyte-rich background. A staging bone marrow biopsy showed a clonal B-cell proliferation with typical CLL flow cytometry immunophenotyping but neither lymphadenopathy nor absolute lymphocytosis was present. Numerous B and T-cell cutaneous lymphoproliferative disorders can be associated with increased numbers of histiocytes occasionally masquerading as benign disorders. This was the case with our patient's lesions, originally interpreted as cutaneous Rosai-Dorfman disease. A high index of suspicion from both the pathologist and the dermatologist is essential in identifying these rare but probably underrecognized occurrences of early systemic lymphoproliferative disorders presenting as cutaneous lesions with an unexpected cellular composition.
Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Citometria de Fluxo , Histiocitose Sinusal/patologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismoRESUMO
Integrase interactor 1 (INI1)-deficient carcinomas, recently described in several sites including the head and neck, are associated with basaloid or rhabdoid histology and aggressive behavior irrespective of origin. INI1-deficient thyroid carcinoma is extremely rare. We present here the phenotype and genotype of an INI1-deficient thyroid carcinoma and report on the INI1 protein expression in various thyroid lesions. Case report with clinicopathologic and molecular characterization and INI1 assessment in 184 thyroid lesions. A 67-year-old woman presented with globus sensation due to a large thyroid mass with extrathyroid extension, focal necrosis and cervical and mediastinal nodal involvement. Histologically, tumor cells had a solid, alveolar and pseudopapillary architecture in a myxoid stroma, exhibited monomorphic epithelioid and focal rhabdoid/plasmacytoid morphology and lacked glandular, squamous or follicular cell differentiation. Tumor cells were positive for AE1/AE3 and CK18 but negative for TTF1, thyroglobulin and PAX8. INI1 nuclear expression was absent. A frameshift SMARCB1/INI1 mutation was detected. In addition, TET2 and Notch1 mutations were present but alterations of BRAF, RET, PAX8/PPAR8 or RAS were not identified. Patient death occurred 14 months after diagnosis from post-therapeutic complications. None of the 184 benign and malignant thyroid lesions tested, including 12 poorly and undifferentiated thyroid carcinomas, were INI1-deficient. INI1-deficient thyroid carcinoma shares the phenotype, genotype and biology of other INI1-deficient tumors. Epithelioid and plasmacytoid/rhabdoid changes are most frequent whereas basaloid morphology is not reported, in contrast with sinonasal tumors. Poorly differentiated and undifferentiated thyroid tumors with epithelioid or rhabdoid morphology should be tested for INI1 protein expression to better characterize these aggressive neoplasms and identify patients eligible for targeted therapy.
Assuntos
Carcinoma/genética , Carcinoma/patologia , Proteína SMARCB1/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Idoso , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Feminino , Mutação da Fase de Leitura , Genótipo , Humanos , Metástase Linfática , Fenótipo , Receptor Notch1/genéticaRESUMO
Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson's trichrome) and vascular (CD31) markers. All PDX models retained the HPV/p16 status of the original patient tumor. Immunohistochemical evaluation revealed the presence of multiple vessel phenotypes (tumor, stromal or mixed) in the PDX panel. Vascular phenotypes identified in the PDX models were validated in a tissue microarray of human HNSCC. Treatment with a microtubule targeted vascular disrupting agent (VDA) resulted in a heterogeneous antivascular and antitumor response in PDX models. The PDX with the tumor vessel phenotype that exhibited higher CD31+ vessel counts and leaky vasculature on magnetic resonance imaging (MRI) was sensitive to VDA treatment while the PDX with the stromal vessel phenotype was resistant to therapy. Collectively, our results demonstrate the phenotypic and functional vascular heterogeneity in HNSCC and highlight the impact of this heterogeneity on response to antivascular therapy in PDX models of HNSCC.
RESUMO
Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ligação a DNA/genética , Fusão Gênica , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Neoplasias da Língua/genética , Fatores de Transcrição/genética , Actinas/análise , Adolescente , Adulto , Biomarcadores Tumorais/análise , Desmina/análise , Feminino , Predisposição Genética para Doença , Proteína Glial Fibrilar Ácida/análise , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/química , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Fenótipo , Estudos Retrospectivos , Proteínas S100/análise , Análise de Sequência de RNA , Neoplasias da Língua/química , Neoplasias da Língua/patologia , Adulto JovemRESUMO
OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.
Assuntos
Doenças da Medula Óssea/patologia , Medula Óssea/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Doenças da Medula Óssea/diagnóstico , Exame de Medula Óssea/normas , Canadá , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
OBJECTIVES/HYPOTHESIS: Examine the accuracy of sentinel lymph node biopsy (SNB) in scalp melanoma (SM), patterns of nodal metastases, patient outcomes, and the utility of immunohistochemistry (IHC) in SNB evaluation. STUDY DESIGN: Retrospective. METHODS: There were 22 patients, 4 females and 18 males. Sentinel lymph nodes (SLN) were localized via preoperative lymphoscintigraphy, intraoperative gamma probe, and Lymphazurin injection. SLNs were stained with hematoxylin-eosin, S-100, HMB-45, Melan-A, micropthalmia transcription factor, and tyrosinase. SLNs were grouped into cervical (levels 1-5) and extracervical (parotid, suboccipital, retroauricular) regions. RESULTS: There were 13 posterior and 9 anterior SMs. The first SNB were mapped to the extracervical regions in 77% of posterior and 78% of anterior lesions. SLN number ranged from 1 to 5. Ten patients had positive SLNs (PSLN). Forty percent of the PSLN group had SLNs mapped in both cervical and extracervical sites. Six underwent completion lymphadenectomy, with no additional positive nodes identified. No significant difference between PSLN and negative sentinel node (NSLN) patients was seen when compared by SLN number, Breslow's thickness, tumor ulceration, and clinical outcomes. Mean follow-up was 35 months. One patient died of disease. One isolated regional recurrence occurred. Sixty percent of PSLN and 92% of NSLN patients were recurrence free at last follow-up. One distant metastasis occurred in the NSLN group, and one local, one regional, and two patients with distant metastases were in the PSLN group at the time of last follow-up. Additional IHC did not detect other metastases in the NSLN group. CONCLUSIONS: SM is aggressive, as demonstrated by the high rate of SLN metastases, and there were no significant histopathologic factors in the primary tumor that predicted the presence of SLN metastases. SNB was accurate. The majority of first SLNs were localized in extracervical basins.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Melanoma/secundário , Couro Cabeludo , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Criança , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Antígeno MART-1 , Masculino , Melanoma/imunologia , Melanoma/metabolismo , Antígenos Específicos de Melanoma , Fator de Transcrição Associado à Microftalmia/metabolismo , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/metabolismo , Pescoço , Proteínas de Neoplasias/metabolismo , Prognóstico , Estudos Retrospectivos , Proteínas S100/metabolismo , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismoRESUMO
OBJECTIVES: To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue. MATERIALS AND METHODS: Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n=124), TBM were obtained before examination of the glossectomy specimen. RESULTS AND CONCLUSIONS: Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32% sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Glossectomia/normas , Margens de Excisão , Neoplasias da Língua/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. MATERIALS AND METHODS: Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (pâ¯<â¯0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; pâ¯<â¯0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; pâ¯=â¯0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high (pâ¯<â¯0.05) and CD31high/SDF1high (pâ¯=â¯0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant disorders and may hence be used in identifying high-risk OPMD.
Assuntos
Progressão da Doença , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Quimiocina CXCL12/metabolismo , Estudos de Coortes , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores CXCR4/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. METHODS: A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. RESULTS: Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. CONCLUSION: HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016.
Assuntos
Carcinoma in Situ/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Laríngeas/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES/HYPOTHESIS: The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN: Retrospective review. METHODS: Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS: Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS: Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2733-2738, 2016.
Assuntos
Quimiorradioterapia , Neoplasias Orofaríngeas/terapia , Abandono do Hábito de Fumar , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Blast phase (BP) in chronic myelogenous leukemia (CML) frequently is accompanied by cytogenetic abnormalities in addition to t(9;22)(q34;q11.2). We describe 5 patients with CML in blast phase (CML-BP) in which t(9;22) and inv(16)(p13q22) were identified by conventional cytogenetics, with confirmation of BCR-ABL and CBFss-MYH11 by fluorescence in situ hybridization. The morphologic findings at the time of BP resembled de novo acute myeloid leukemia (AML) carrying inv(16)(p13q22), with abnormal eosinophils in the bone marrow and monocytosis in the peripheral blood in all cases. In 1 patient, inv(16)(p13q22) and abnormal eosinophils were detected in the bone marrow 2 months before CML-BP. The clinical course of these patients was similar to patients with CML-BP without evidence of inv(16)(p13q22). These cases illustrate that inv(16)(p13q22) is a form of cytogenetic evolution that rarely occurs in patients with CML at the time of BP. In this setting, unlike de novo AML, inv(16)(p13q22) in CML-BP is not associated with a favorable prognosis.
Assuntos
Crise Blástica/genética , Inversão Cromossômica , Cromossomos Humanos Par 16 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Adulto , Feminino , Humanos , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, targeting EGFR for chemoprevention of head and neck squamous cell carcinomas (HNSCC) has received considerable attention. In the present study, we examined the impact of 1,25(OH)2D3, the active metabolite of the nutritional supplement vitamin D on the chemopreventive efficacy of the EGFR inhibitor, erlotinib, against HNSCC. Experimental studies were conducted in patient-derived xenografts (PDX) and the 4-nitroquinoline-1-oxide (4NQO) carcinogen-induced model of HNSCC. Short-term treatment (4 weeks) of PDX-bearing mice with 1,25(OH)2D3 and erlotinib resulted in significant inhibition of tumor growth. Noninvasive MRI enabled longitudinal monitoring of disease progression in the 4NQO model with 100% of control animals showing evidence of neoplastic lesions by 24 weeks. Among the experimental groups, animals treated with the combination regimen showed the greatest reduction in tumor incidence and volume (P < 0.05). Combination treatment was well tolerated and was not associated with any significant change in body weight. Histopathologic assessment revealed a significant reduction in the degree of dysplasia with combination treatment. Immunoblot analysis of whole tongue extracts showed downregulation of phospho-EGFR and phospho-Akt with the combination regimen. These results highlight the potential of 1,25(OH)2D3 to augment the efficacy of erlotinib against HNSCC. Further optimization of schedule and sequence of this combination regimen along with investigation into the activity of less calcemic analogues or dietary vitamin D is essential to fully realize the potential of this approach.
Assuntos
Anticarcinógenos/administração & dosagem , Calcitriol/administração & dosagem , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Bucais/prevenção & controle , 4-Nitroquinolina-1-Óxido , Animais , Antineoplásicos/administração & dosagem , Carcinógenos , Carcinoma de Células Escamosas/prevenção & controle , Progressão da Doença , Regulação para Baixo , Esquema de Medicação , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/prevenção & controle , Humanos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Transplante de Neoplasias , QuinolonasRESUMO
Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5' G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation.
RESUMO
BACKGROUND: The survival rates and prognostic factors for salivary duct carcinoma (SDC) are not clear. METHODS: Survival estimates and prognostic factors were evaluated for 228 patients with SDC identified from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Median overall survival (OS) duration for patients with SDC was 79 months and 5-year disease-specific survival (DSS) rate was 64%. Among patients with SDC with lymph node involvement, larger primary tumor size (>3 cm) was associated with twice the risk of death (p < .03). Factors predictive of improved DSS were age (p = .01), tumor size (p = .006), tumor grade (p = .02), and lymph node involvement (p < .001). Adjuvant radiotherapy did not improve survival when compared to surgery alone for early-stage (I-II) disease (p = .28). CONCLUSION: Younger patients with SDC (<50 years) showed a better prognosis. Primary tumor size and lymph node involvement were independent and additive risk factors for poor prognosis. The role of adjuvant radiotherapy in the treatment of SDC needs to be explored further.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Medição de Risco , Programa de SEER , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Taxa de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. EXPERIMENTAL DESIGN: Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. RESULTS: Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. CONCLUSION: HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction.