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BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma sometimes presents as large pulmonary nodules composed of small nodular opacities (galaxy sign) on computed tomography (CT). The aim of this study was to assess the presence, usefulness, and pathological characteristics of the galaxy sign on CT of pulmonary MALT lymphoma. METHODS: From January 2011 to December 2021, chest CTs of 43 patients with pulmonary MALT lymphoma were reviewed by two radiologists for the galaxy sign and various other findings. Interreader agreement to characterize the galaxy sign and factors associated in making a correct first impression on CT prior to pathological diagnosis were assessed. Resected specimens were reviewed by two pathologists, and the proportion of peripheral lymphoma infiltrates was compared between lesions with and without the galaxy sign. RESULTS: Of 43 patients, 22 patients (44.2%) showed the galaxy sign (κ = 0.768, p < 0.0001). The galaxy sign (p = 0.010) was associated with making a correct first impression on CT prior to pathological diagnosis. On pathological examination, lesions showing the galaxy sign on CT demonstrated a significantly higher proportion of peripheral lymphoma infiltrates (p = 0.001). CONCLUSION: The galaxy sign can be seen on CT of pulmonary MALT lymphoma with a higher proportion of peripheral lymphoma infiltrates and may be useful in making a correct diagnosis of pulmonary MALT lymphoma.
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Neoplasias de los Bronquios , Linfoma de Células B de la Zona Marginal , Humanos , Linfoma de Células B de la Zona Marginal/diagnóstico , Radiografía , Tejido Linfoide/patología , Membrana MucosaRESUMEN
Nevus sebaceous (NS) is a congenital hamartoma associated with an increased risk of secondary neoplasms in approximately 10%-20% of patients. However, additional genomic alterations underlying tumorigenesis in NS lesions have not been clarified. We performed whole-exome sequencing of archived tumor tissues (n = 8; six basal cell carcinomas and two trichoepitheliomas) and matched germline tissues (n = 7) with from seven patients with secondary tumors arising from NS. We also analyzed NS lesions without secondary tumors (n = 8). Somatic mutations and copy number alterations (CNAs) were analyzed. We identified a median of 129 somatic mutations (corresponding to 2.6/Mb in target regions, range 26-336) for eight tumors, while a median of 118 somatic mutations (2.3/Mb, range 1-196) for eight NS lesions. Known RAS hotspot mutations were found in seven of the eight tumors (six for HRAS p.G13R and one for HRAS p.Q61R) and in six of the eight NS lesions (four for HRAS p.G13R, one for KRAS p.G12C, and one KRAS p.G12D). Except RAS mutations, several putative driver mutations were detected in tumors: TP53 p.F134L/p.R213*, MYCN p.P59L, OR2Z1 p.P167S, PTPN14 p.Q768*, and SMO p.W535L. As for CNAs, two tumors harbored copy-loss in regions encompassing PTCH1 gene. However, eight NS lesions did not harbor both putative driver mutations and CNAs. In conclusion, our study revealed that secondary tumors arising from NS harbor known RAS hotspot mutations and additional genomic alterations, including putative driver mutations and PTCH1 copy-loss. These results could help to define the high-risk group for tumor development in patients with NS and provide evidence for prophylactic resection.
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Nevo , Neoplasias Cutáneas , Humanos , Secuenciación del Exoma , Proteínas Proto-Oncogénicas p21(ras)/genética , Mutación , Nevo/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Genómica , Proteínas Tirosina Fosfatasas no Receptoras/genéticaRESUMEN
Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer-related genes with a median coverage of 515× for AK (N = 9), CIS (N = 9), cSCC lesions (N = 13), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK/CIS. Driver mutations were found in TP53 (81%), NOTCH1 (32%), RB1 (26%) and CDKN2A (19%). All AK/CIS and cSCC lesions (93.5%), except two, harboured TP53 or NOTCH1 mutations, some of which were known oncogenic mutations or reported mutations in normal skin. RB1 driver mutations were found in CIS/cSCC (36.4%) but not in AK. CDKN2A driver mutations were found more frequently in cSCC (30.8%) than in AK/CIS (11.1%). Among recurrent (≥3 samples) CNAs (gain in MYC and PIK3CA/SOX2/TP63; loss in CDKN2A and RB1), MYC (8q) gain and CDKN2A (9p) loss were more frequently detected in cSCC (30.8%) than in AK/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK/CIS and cSCC. Our study revealed that AK/CIS lesions harbour prevalent TP53 or NOTCH1 mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK/CIS lesions.
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Carcinoma de Células Escamosas , Queratosis Actínica , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Queratosis Actínica/genética , Queratosis Actínica/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Genómica , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
The genomic landscape of Bowen's disease (BD), with multiple manifestations, has not yet been determined. This study aimed to investigate the genomic alterations in multiple BD. We performed whole-exome sequencing of BD lesions (n = 9) and matched germlines collected from three patients with multiple (≥3) BD to detect somatic and germline mutations. We found a median of 64 somatic mutations in each sample (range 20-267). UV-signature mutations accounted for 64.9% (median, range 26.0%-82.1%) of point mutations. Putative driver mutations were found in five BDs (RB1 p.R445*, ARID2 p.R274*, TP53 p.Y163D/p.Y205D/p.R342*, KMT2C p.R4549C) but not in the other four lesions. Somatic mutations were not shared between multiple BD lesions collected from the same patient, indicating a different clonal origin. We also found no known pathogenic germline mutations in cancer-related genes. The mutational signature analysis revealed that UV signatures (SBS7a/7b) and age-related signatures (SBS1/5) were the main active signatures. Copy number alterations (CNAs) were found in two BDs: one with extensive CNA regions (21.7% of the genome), including driver genes (PIK3CA/SOX2/TP63 and MYC gain, and CDKN2A loss), and the other with 1q gain. Our study revealed that multiple BD lesions harbor distinct genomic landscapes, suggesting that they have different risks of malignant progression.
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Enfermedad de Bowen , Neoplasias Cutáneas , Humanos , Mutación , Secuenciación del Exoma , Enfermedad de Bowen/genética , Genómica , Neoplasias Cutáneas/genéticaRESUMEN
The mechanism underlying the progression of actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) in situ (SCCIS) to SCC remains unclear. To investigate this, we performed regional microdissection and targeted deep sequencing in SCC (n = 10) and paired adjacent sun-damaged epidermis (SE)/AK/SCCIS (n = 13) samples to detect mutations and copy number alterations. Most (11/13) SE/AK/SCCIS tissues harbored ≥1 driver alterations, indicating their precancerous nature. All pairs except one showed genome architectures representing the genomic progression of SE/AK/SCCIS to SCC with common trunks and unique branches (seven parallel and five linear progression cases). SE/AK/SCCIS tissues tended to harbor lower mutation/copy number alteration burdens than SCC tissues, but most of them had driver mutations, including NOTCH1 and TP53 mutations. SCC-specific genomic alterations included TP53, PIK3CA, FBXW7, and CDKN2A mutations and an MYC copy number gain, but they were heterogeneous among cases, suggesting that a single gene or pathway does not explain the progression of AK to SCC. In multiregion analyses of AK lesions, only some AK samples were related to SCC. In conclusion, the SE/AK/SCCIS genomes may have previously acquired truncal driver alterations, such as NOTCH1 and TP53 mutations, which promote parallel or linear progression to SCC on an acquisition of additional genomic alterations.
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Carcinoma de Células Escamosas , Queratosis Actínica , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Genómica , Humanos , Queratosis Actínica/genética , Queratosis Actínica/patología , Mutación , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality for response evaluation in FDG-avid lymphoma, but the prognostic value is not established in follicular lymphoma (FL). This study investigated the prognostic value of Deauville 5-point scale (D5PS) from paired interim PET/CT (PETInterim) and end-of-induction therapy PET/CT (PETEOI) in patients with FL. METHODS: FL staging and response assessment PET/CT images from 2013 to 2015 were retrospectively reviewed. PETInterim was performed 3 or 4 cycles after chemotherapy and PETEOI after 6 or 8 cycles. D5PS scores of 1, 2, and 3 were considered as negative (-), and scores 4 and 5 were considered as positive (+). Statistical analysis was done using Cox regression analysis, Kaplan-Meier survival analysis, and the log-rank test. RESULTS: Thirty-three patients with set of baseline, interim, and end-of-induction therapy PET/CT studies were included. Ten patients (30.3%) had progression. The median progression-free survival (PFS) was 38.8 months (range 3.5-72.7 months). On PETInterim, 23 patients were negative and 10 were positive. On PETEOI scans, 29 patients were negative, and 4 were positive. On multivariate analysis, PETEOI(-) was associated with longer PFS. PETInterim(+) and PETEOI(+) patients had a significantly shorter PFS than PETInterim(-) patients (39.9 months, 95% confidence interval [CI] 23.0-56.9, versus 55.5 months, 95% CI 49.7-61.2, p = 0.005) and PETEOI(-) patients (14.2 months, 95% CI 8.5-19.8, versus 60.5 months, 95% CI 52.1-69.0, p < 0.001). CONCLUSION: For patients with FL, PETInterim and PETEOI response is predictive of PFS, and PETEOI(+) is an independent prognostic factor for progression of FL.
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PURPOSE: To report the clinical manifestations of 199 patients with suspected conjunctival lymphoma, the associations between these features and the pathological diagnoses, and the prognosis of conjunctival lesions during long-term follow-up. METHODS: We conducted a retrospective chart review of 199 patients who underwent conjunctival biopsy on suspicion of conjunctival lymphoproliferative disease between January 2008 and June 2015. We focused on slit-lamp findings in the conjunctiva and the pathological diagnoses. RESULTS: In total, 261 specimens of 199 patients were included in this study. The median age of patients was 42 years (range, 16-87 years), and those over 60 years of age constituted 17.1% of all patients. The proportion finally diagnosed with mucosa-associated lymphoid tissue (MALT) lymphomas was 58.2%. In these patients, the most common slit-lamp findings were the 'salmon patch' appearance (73.7%), followed by a follicular appearance (14.5%) and a nodular or subconjunctival mass (6.6%). Bilateral ocular manifestations were more common in patients with disease with the follicular appearance, as compared with patients with the salmon-patch appearance. CONCLUSION: Conjunctival MALT lymphoma presents in various ways, not only with the salmon-patch appearance. Therefore, biopsy should be considered if suspicion is raised, even though the conjunctival lesion does not exhibit the typical appearance of MALT lymphoma. In cases of follicular lesions responding poorly to topical steroids, a conjunctival MALT lymphoma may be suspected, given that chronic inflammation may precede neoplasia in patients with extranodal marginal zone lymphoma.
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Neoplasias de la Conjuntiva/diagnóstico , Inflamación/diagnóstico , Linfoma de Células B de la Zona Marginal/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias de la Conjuntiva/metabolismo , Neoplasias de la Conjuntiva/cirugía , Conjuntivitis/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Pronóstico , Estudios Retrospectivos , Microscopía con Lámpara de HendiduraRESUMEN
Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments.
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Antígeno B7-H1/inmunología , Inmunoterapia/métodos , Leucemia Mieloide Aguda/terapia , Células Progenitoras Mieloides/efectos de los fármacos , Receptores CXCR4/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencilaminas , Línea Celular Tumoral , Ciclamas , Citarabina/uso terapéutico , Modelos Animales de Enfermedad , Compuestos Heterocíclicos/uso terapéutico , Humanos , Inmunomodulación , Leucemia Mieloide Aguda/inmunología , Ratones , Ratones Endogámicos C57BL , Células Progenitoras Mieloides/fisiología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Whether hematopoietic cell-restricted distribution of antigens affects the degree of thymic negative selection has not been investigated in detail. Here, we show that T cells specific for hematopoietic cell-restricted antigens (HRA) are not completely deleted in the thymus, using the mouse minor histocompatibility antigen H60, the expression of which is restricted to hematopoietic cells. As a result, low avidity T cells escape from thymic deletion. This incomplete thymic deletion occurs to the T cells developing de novo in the thymus of H60-positive recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific thymic deletion escapee CD8+ T cells exhibit effector differentiation potentials in the periphery and contribute to graft-versus-leukemia effects in the recipients of H60-mismatched BMT, regressing H60+ hematological tumors. These results provide information essential for understanding thymic negative selection and developing a strategy to treat hematological tumors.
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Linfocitos T CD8-positivos/inmunología , Células Madre Hematopoyéticas/inmunología , Antígenos de Histocompatibilidad Menor/inmunología , Timo/inmunología , Animales , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Trasplante de Médula Ósea/métodos , Linfocitos T CD8-positivos/metabolismo , Citometría de Flujo , Células Madre Hematopoyéticas/metabolismo , Ratones Noqueados , Ratones Transgénicos , Antígenos de Histocompatibilidad Menor/genética , Antígenos de Histocompatibilidad Menor/metabolismo , Timocitos/inmunología , Timocitos/metabolismo , Timo/metabolismo , Inmunología del Trasplante/inmunologíaAsunto(s)
Enfermedades del Pie/patología , Pie , Hemangioendotelioma Epitelioide/patología , Neoplasias Cutáneas/patología , Adulto , Diagnóstico Diferencial , Femenino , Enfermedades del Pie/cirugía , Granuloma Piogénico/patología , Hemangioendotelioma Epitelioide/cirugía , Humanos , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: To report six cases of CD34+ fibroblastic mesenchymal tumours, which are uncommon neoplasms in the orbit. CASE PRESENTATION: Six patients presenting with proptosis and palpable mass who were later diagnosed with fibrous solitary tumours, fibrous histocytoma or haemangiopericytoma in the orbit were included. All patients received radiologic examinations and surgical excision for histopathology and immunohistochemistry examinations. Five patients had no recurrence after a minimum follow-up of 12 months. One patient (case 6) experienced recurrence twice, and had debulking surgeries each time. At present, the patient still has remnant tumour in the orbit, but no growth has been detected during the past two years. The tumour size will be closely monitored. CONCLUSIONS: Even though fibroblastic tumours are rarely found in the orbit, they can present as a palpable mass with proptosis. Complete surgical excision is important for long-term prognosis, and immunohistochemical study is helpful for confirming pathologic diagnosis.
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Angiofibroma/diagnóstico , Antígenos CD34/inmunología , Hemangiopericitoma/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Órbita/patología , Neoplasias Orbitales/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico , Adulto , Angiofibroma/complicaciones , Angiofibroma/inmunología , Exoftalmia/diagnóstico , Exoftalmia/etiología , Femenino , Hemangiopericitoma/complicaciones , Hemangiopericitoma/inmunología , Histiocitoma Fibroso Benigno/complicaciones , Histiocitoma Fibroso Benigno/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Orbitales/complicaciones , Tumores Fibrosos Solitarios/complicaciones , Tumores Fibrosos Solitarios/inmunología , Adulto JovenRESUMEN
PURPOSE: Although each Waldeyer's ring sub-site is considered an independent prognostic factor, few studies have assessed the prognosis and treatment of tonsillar lymphoma. Treatment outcomes were analyzed in patients with primary tonsillar lymphoma who were treated with chemotherapy and radiotherapy (RT). MATERIALS AND METHODS: Nineteen patients with diffuse large B-cell lymphoma were evaluated, with a median follow-up of 53 months. Age, sex, and histology, amongst other factors, were reviewed. Progression-free survival (PFS) and overall survival (OS) rates were analyzed. RESULTS: Most patients had Ann Arbor stage I-II (94.7%), IPI score of 0 (89.5%), and complete remission after chemotherapy (89.5%). The 5-year PFS and OS rates were 74.6% and 80%, respectively. In univariate analysis, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen resulted in a better PFS than the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (88.9% vs. 50.0%; p = 0.053). RT dose was related to the survival outcome (p = 0.010 for PFS, p = 0.044 for OS). Patients were classified into the CHOP + RT (>40 Gy) group and R-CHOP + RT (≤40 Gy) group. The 5-year PFS rates were 50% in the CHOP + RT group, and 100 % in the R-CHOP + RT group (p = 0.018). The 5-year OS rates were 66.7% and 100%, respectively (p = 0.087). CONCLUSION: Primary tonsillar lymphoma patients typically have favorable outcomes. Chemotherapy (R-CHOP) combined with relatively lower dose consolidative RT may be safe and effective for primary tonsillar lymphoma.
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Glioblastoma stem cells (GSCs) are a subpopulation of highly tumorigenic and stem-like cells that are responsible for resistance to conventional therapy. Bcl-2-intreacting cell death suppressor (BIS; also known as BAG3) is an anti-apoptotic protein that is highly expressed in human cancers with various origins, including glioblastoma. In the present study, to investigate the role of BIS in GSC subpopulation, we examined the expression profile of BIS in A172 and U87-MG glioblastoma cell lines under specific in vitro culture conditions that enrich GSC-like cells in spheres. Both BIS mRNA and protein levels significantly increased under the sphere-forming condition as compared with standard culture conditions. BIS depletion resulted in notable decreases in sphere-forming activity and was accompanied with decreases in SOX-2 expression. The expression of STAT3, a master regulator of stemness, also decreased following BIS depletion concomitant with decreases in the nuclear levels of active phosphorylated STAT3, while ectopic STAT3 overexpression resulted in recovery of sphere-forming activity in BIS-knockdown glioblastoma cells. Additionally, immunoprecipitation and confocal microscopy revealed that BIS physically interacts with STAT3. Furthermore, BIS depletion increased STAT3 ubiquitination, suggesting that BIS is necessary for STAT3 stabilization in GSC-like cells. BIS depletion also affected epithelial-to-mesenchymal transition-related genes as evidenced by decrease in SNAIL and MMP-2 expression and increase in E-cadherin expression in GSC-like cells. Our findings suggest that high levels of BIS expression might confer stem-cell-like properties on cancer cells through STAT3 stabilization, indicating that BIS is a potential target in cancer therapy.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias Encefálicas/patología , Glioblastoma/patología , Células Madre Neoplásicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/fisiología , Glioblastoma/metabolismo , Humanos , Células Madre Neoplásicas/patologíaRESUMEN
OBJECTIVE: According to lymphoma guidelines, gastric diffuse large B cell lymphoma (DLBCL) patients should undergo regular computed tomography (CT) and/or positron emission tomography (PET) examinations to assess treatment response. Endoscopic examinations are not indicated in the guidelines. The aim of this study was to investigate the utility of endoscopic examinations during and after treatment for DLBCL. METHODS: We reviewed the patients diagnosed with gastric DLBCL at Seoul St. Mary's Hospital. All patients underwent endoscopy and radiologic examinations at every follow-up appointment. Radiologic response was defined according to World Health Organization criteria and endoscopic response was determined based on the Groupe d'Etude des Lymphomes de l'Adult grading system that is widely used in post-treatment evaluation of gastric MALT lymphoma. RESULTS: Forty-five patients were analyzed. Within a median follow-up period of 34 months, 35 patients achieved both radiologic and endoscopic complete remission (CR). The median times to endoscopic and radiologic CR were not significantly different (21 versus 16 weeks, p = 0.118). However, in 25 patients with stage I disease, endoscopic CR [median (range), 20 (11-36)] was achieved later than radiologic CR [median (range), 13 (8-36)] (p = 0.027). Among 40 patients who achieved radiologic CR, 35 patients who also achieved endoscopic CR maintained remission during the follow-up. Two of the five patients who achieved radiologic CR without endoscopic CR experienced recurrence. CONCLUSIONS: In gastric DLBCL patients, endoscopic response does not always correlate with radiologic response and might predict disease recurrence. We suggest that follow-up endoscopic examination with biopsy should be performed in addition to radiologic examination.
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Endoscopía/estadística & datos numéricos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/terapia , Adulto , Anciano , Antibacterianos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Estudios de Seguimiento , Infecciones por Helicobacter/epidemiología , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Masculino , Persona de Mediana Edad , Radioterapia/métodos , Inducción de Remisión , Estudios Retrospectivos , Seúl , Neoplasias Gástricas/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Bis, also known as BAG3, has been identified as a Bcl-2-interacting protein that enhances cellular anti-apoptotic activity. It is involved in cellular differentiation, angiogenesis, migration, and invasion in various tumors. The purpose of this study was to investigate the Bis expression pattern, and the clinical significance thereof, in patients with resected lung cancer. METHODS: We studied 121 lung cancer patients who underwent curative surgical resection. Patient clinicopathological characteristics were reviewed retrospectively from medical records, including tumor recurrence and survival. The expression of Bis protein in lung cancer tissues was evaluated by immunohistochemical staining and was assessed using a four-tiered intensity score system (negative, weak, moderate, strong). Enhanced Bis expression at the periphery of a tumor facing the adjacent nontumor region was referred as "marginal activity." RESULTS: Although Bis expression was higher in squamous cell carcinoma than in adenocarcinoma, marginal activity was higher in adenocarcinoma than in squamous cell carcinoma. All of the small cell carcinomas and lung cancer with neuroendocrine differentiation examined were negative for Bis expression. Compared with stage I lung cancer, patients with stage II and IIIA lung cancer exhibited higher Bis protein levels in lung tissues. Recurrence and survival rates did not differ significantly according to Bis expression intensity score or marginal activity. CONCLUSIONS: Our study demonstrated that Bis expression differed according to the histological type and pathological stage of the lung cancer. Further studies are needed to assess its use as a biomarker and its role in the molecular pathogenesis of lung cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/cirugía , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
Liquid-based cytology (LBC) has been progressively used for evaluating fine needle aspiration (FNA) specimens. However, limited studies have examined LBC in FNA of parathyroid lesions. We retrospectively reviewed 24 FNA specimens of parathyroid lesions, including 6 specimens prepared by conventional smear, 12 specimens prepared using ThinPrep method, and 6 specimens prepared using SurePath method. The 18 LBC specimens were also used for cell block preparation and immunostaining for parathyroid hormone (PTH). LBC specimens more frequently showed variable cellularity; microfollicular structure; bubbly or vacuolated cytoplasm; and small, round cells with distinct borders compared to specimens prepared by conventional smear. ThinPrep specimens showed a clean background and fewer isolated cells and naked nuclei compared to specimens prepared using the other methods. SurePath specimens showed many white blood cells in the background and more scattered single cells and naked nuclei compared to ThinPrep specimens. Specimens prepared using the 3 methods often showed colloid-like material but did not contain dense globular colloidal structures. White blood cells in the background of LBC specimens serve as useful indicators for estimating cell size. The nuclear size of parathyroid cells was similar to or smaller than that of inflammatory cells in the background. Cell block sections showed definite histological features of the parathyroid tissue and strong positive immunostaining for PTH. Awareness of these cytologic features of parathyroid FNA specimens prepared using ThinPrep and SurePath methods may help in preventing misdiagnosis. Cell block preparation and PTH immunostaining should be performed for the definitive diagnosis of parathyroid lesions.
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Citodiagnóstico/métodos , Enfermedades de las Paratiroides/diagnóstico , Biopsia con Aguja Fina , Humanos , Inmunohistoquímica , Estudios RetrospectivosRESUMEN
A 57-year-old woman presented with cough and dyspnea for 2 months. Computed tomography of the chest showed diffuse ground-glass opacities in both lungs. Histologic examination via thoracoscopic lung biopsy revealed atypical lymphoproliferative lesion. Her symptoms and radiologic findings of the chest improved just after lung biopsy without any treatment. Therefore, she was discharged and monitored at an outpatient clinic. Two months later, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection of API2-MALT1 translocation in fluorescent in situ hybridization analysis. Although the lung lesions resolved spontaneously, she received chemotherapy due to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is rare. Nodular or consolidative patterns are the most frequent radiologic findings. Although the disease has an indolent growth, it rarely resolves without treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse interstitial abnormalities on image and spontaneous regression on clinical course.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Tejido Linfoide/patología , Linfoma/diagnóstico , Mucosa Respiratoria/patología , Antineoplásicos/uso terapéutico , Médula Ósea , Femenino , Humanos , Neoplasias Pulmonares/patología , Linfoma/tratamiento farmacológico , Linfoma/patología , Persona de Mediana Edad , Remisión EspontáneaRESUMEN
The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (≥20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor.
Asunto(s)
Carcinoma Papilar/secundario , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Sustitución de Aminoácidos , Carcinoma Papilar/genética , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Proto-Oncogenes Mas , Estudios Retrospectivos , Neoplasias de la Tiroides/genética , Adulto JovenRESUMEN
The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>G mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>G mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma. [Corrected]