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BACKGROUND: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. METHODS: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. RESULTS: Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. CONCLUSIONS: We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.
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Carcinoma de Células Grandes , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Femenino , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/mortalidad , Estudios Retrospectivos , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/cirugía , Carcinoma de Células Grandes/mortalidad , Tasa de Supervivencia , Persona de Mediana Edad , Anciano , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/terapia , Pronóstico , Estudios de Seguimiento , Estadificación de Neoplasias , Quimioterapia AdyuvanteRESUMEN
INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for the efficacy of anti-programmed cell death receptor-1/PD-L1 antibodies in advanced non-small cell lung cancer (NSCLC). Although several assays have been approved for evaluating PD-L1 expression status, inter-assay discordance has been observed between some assays. The clinical significance of these discrepancies is still unclear. METHODS: We retrospectively reviewed treatment-naïve NSCLC patients whose PD-L1 expression was evaluated using both 22C3 and SP142 assays. Among those, efficacy analysis was performed for patients with PD-L1 tumor proportion score (TPS) ≥ 50 % (22C3), who had received first-line pembrolizumab monotherapy. Additionally, transcriptome analysis was conducted in the available tumors with TPS ≥ 50 % to investigate the distinct immune profiles that accompany inter-assay discordance. RESULTS: In total, 611 patients were eligible. Among 198 patients with TPS ≥ 50 %, 91 (46 %) had tumor cell score ≤ 1 (SP142, i.e., inter-assay discrepancy). In the 52 patients who received first-line pembrolizumab monotherapy, treatment efficacy was significantly lower in patients with the discrepancy than that in those without (objective response rate: 18 % vs. 83 %, p < 0.001; median progression-free survival [months]: 3.2 vs. 8.3, p < 0.001). Transcriptome analysis revealed significantly more CD274 splice variants with aberrant 3'-terminal sequences in tumors with the inter-assay discrepancy than in those without. CONCLUSION: The inter-assay discrepancy in the PD-L1 status of tumor cells between the 22C3 and SP142 assays, reflecting an imbalance in the CD274 splice variants, could be a biomarker for primary resistance against pembrolizumab monotherapy in high PD-L1-expressing NSCLCs.
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Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Masculino , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Adulto , Relevancia ClínicaRESUMEN
Background: Cryobiopsy is recently being promoted for biopsy of tumors in the lung periphery in precision medicine for lung cancer; the obtained tissue samples have been reported to be more useful compared to those obtained using forceps, because of the larger volume and higher quality. However, the influence of freezing and thawing of tissues when performing cryobiopsy on the results of immunohistochemistry (IHC) has not been completely understood. Methods: In this study, consecutive patients who underwent diagnostic bronchoscopy with cryobiopsy for peripheral pulmonary lesions (PPLs) at our institution between June 2017 and November 2021 were reviewed retrospectively. Specimens of diagnosed cases of unresectable or recurrent non-small cell lung carcinoma (NSCLC) were selected. We compared the results of IHC assessment for programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and human epidermal growth factor receptor 3 (HER3) in cryobiopsy specimens versus conventional forceps biopsy specimens from the same site in the same procedure. Results: Twenty-four of 40 patients were male (60%). The most frequent histologic type of cancer was adenocarcinoma (n=31, 77.5%), followed by NSCLC (n=4, 10%), squamous cell carcinoma (n=3, 7.5%), and others (n=2, 5%). The concordance rates of the tumor proportion scores (TPSs) for PD-L1, IHC score for HER2 and, IHC scores for HER3 were 85%, 72.5%, and 75%, respectively; the weighted kappa were 0.835, 0.637, and 0.697, respectively. Conclusions: Freezing and thawing associated with cryobiopsy had virtually no effect on the results of IHC. We suggest that cryobiopsy specimens would therefore be ideal for precision medicine and translational research.
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Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.
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Tumor del Seno Endodérmico , Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Teratoma , Neoplasias Testiculares , Adolescente , Humanos , Masculino , Mediastino/patología , Secuenciación del Exoma , Teratoma/genética , Teratoma/patología , Neoplasias del Mediastino/genética , Tumor del Seno Endodérmico/patología , Neoplasias Testiculares/patologíaRESUMEN
Thymic squamous cell carcinoma (TSC) presents distinct immunohistochemical features with its expression of CD5 and CD117, both of which are rarely expressed in squamous cell carcinoma in other organs. We found insulinoma-associated-1 (INSM1) expression in some TSCs; thus, a series of thymic tumors were examined retrospectively. Using surgically resected thymic tumors (TSC, n = 35; thymic atypical carcinoid [TAC], n = 4; and thymoma, n = 112) and non-neoplastic thymic tissue (n = 26), we evaluated immunohistochemically the expressions of INSM1, ASCL1, SOX2, NE markers (synaptophysin, chromogranin A, and CD56), and conventional TSC markers (CD5 and CD117). INSM1 was expressed in 22 TSCs (63%), whereas the positive frequencies of synaptophysin, chromogranin A, and CD56 were limited to 13, 10, and 1 cases, respectively. The discordance was highly contrasted with concordantly positive TACs. INSM1 and NE makers were rarely expressed in thymomas. INSM1 expression in TSCs was also associated with CD5 expression, which was significantly less frequent in INSM1-negative TSCs. INSM1, ASCL1, and SOX2 expressions were correlated with one another, but none of the single transcription factors or their combinations is associated with NE expression. The non-neoplastic medullary thymic epithelium was dispersedly positive for INSM1, particularly around Hassall's corpuscles. Despite positive INSM1, a significant decrease in the frequency of NE maker expression may present as a diagnostic pitfall in TSCs. Furthermore, the discordance, which was inherent in the non-neoplastic thymic epithelium, might be a characteristic feature in TSCs.
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Carcinoma de Células Escamosas , Timoma , Neoplasias del Timo , Humanos , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Estudios Retrospectivos , Proteínas Represoras/metabolismo , Carcinoma de Células Escamosas/patología , Cromogranina A/metabolismoRESUMEN
Invasive mucinous adenocarcinoma (IMA) of the lung shares some clinicopathological features with mucinous carcinoma of other organs, such as the ovary. Sarcoma-like lesions, called mural nodules, have been reported in the cystic walls of ovarian mucinous tumors. In this study, we analyzed 213 surgically resected cases of IMA of the lung to determine whether similar mural nodule-like lesions were present. We considered abrupt discrete lesions composed of dedifferentiated tumor cells as mural nodule-like lesions. Of 213 IMAs, we identified 11 tumors with mural nodule-like lesions that were histologically categorized into three subtypes similar to those in the ovary. The sarcomatoid and anaplastic carcinoma-like nodules were composed of spindle cell proliferations and polygonal undifferentiated carcinoma, respectively. Sarcoma-like lesions mimicked sarcomatoid nodules, but the spindle cell proliferations were considered a fibroblastic reaction to the scattered, isolated clusters of tumor cells. Molecular analysis of the components of differentiated IMAs and mural nodule-like lesions revealed a clonal relationship, suggesting a spectrum of tumors with different histology. Clinicopathologically, an older age, the male sex, and smokers were significantly associated with IMAs with mural nodule-like lesions. Notably, patient outcomes were unaffected by the presence or absence of these lesions. Our findings demonstrated that IMA of the lung rarely develops mural nodule-like lesions (11 of 213, 5%). Despite a histological impression of clinical aggressiveness, there was no clear trend in patient outcomes, suggesting that pathologists should avoid overstating this mural nodule-like lesion.
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Adenocarcinoma Mucinoso , Neoplasias Ováricas , Sarcoma , Neoplasias de los Tejidos Blandos , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Femenino , Humanos , Pulmón/patología , Masculino , Neoplasias Ováricas/patología , Sarcoma/patologíaRESUMEN
Treatment for small cell lung cancer (SCLC) has not changed significantly compared to the overwhelming development of targeted therapies for non-small cell lung cancer. However, recent epigenetic and expressional analyses have revealed that SCLC can be divided into four distinct subtypes, which may lead to precision treatments. The situation appears slightly similar to the "four-color problem," a classic mathematical problem stating that no more than four colors are required to color the regions so that no two adjacent areas have the same color. This review introduces the framework for subtyping SCLC into four molecular subtypes and the promising targeted treatment for each subtype.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/terapia , Inmunoterapia , BiologíaRESUMEN
INTRODUCTION: The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the histologically predominant subtype and high-grade component. Because the predominant subtypes are associated with characteristic subsets, unique subsets can be identified by this grading system. METHODS: We analyzed the clinicopathologic, genotypic, and prognostic features of a cohort of 781 consecutive patients with invasive nonmucinous adenocarcinoma of the lung. RESULTS: Grade 3 tumors were associated with younger age, male sex, a higher smoking dose, and aggressive features (tumor size, lymph node metastasis, stage, lymphovascular invasion, and pleural invasion). Recurrence-free survival and 3-year overall survival were well-stratified according to tumor grade, and the differences were confirmed with multivariate analysis using the Cox proportional hazard model. Radiologically, most grade 3 tumors exhibit a solid nodular pattern on computed tomography images and a high maximum standardized uptake value with positron emission tomography. Genotypically, 43% of the grade 3 adenocarcinomas lacked any driver mutations, although one of the driver mutations was detected in 79% of grade 1 or 2 tumors. Patient age, positive smoking history, solid nodule on computed tomography image, and higher maximum standardized uptake value were identified as significant preoperative predictive factors of grade 3 tumors, with a prediction rate greater than 90%. CONCLUSIONS: Besides stratifying the patient outcomes, the new grading system characterized unique clinicopathologic subsets and this study suggested that grade 3 tumors could be predicted using the preoperative variables.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosAsunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma Papilar , Carcinoma Papilar , Neoplasias Pulmonares , Neoplasias de la Tiroides , Adenocarcinoma Papilar/diagnóstico , Adenocarcinoma Papilar/patología , Carcinoma Papilar/patología , Humanos , Neoplasias Pulmonares/patología , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patologíaRESUMEN
INTRODUCTION: Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance. METHODS: We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images. RESULTS: Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19-1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point. CONCLUSIONS: Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC.
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Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported. METHODS: METex14 skipping results from three assays (Oncomine DxTT, ArcherMET, and laboratory-developed reverse-transcriptase polymerase chain reaction test [LDT RT-PCR]) were compared in a relatively small series of the specimens diagnosed as advanced NSCLC (n = 50). RESULTS: The ArcherMET and LDT RT-PCR results were identical for all 50 samples, but eight samples had discordant results between Oncomine DxTT and the other two assays. All eight samples had METex14 skipping with Oncomine DxTT and wild-type signals with ArcherMET and LDT RT-PCR. The discordance might be caused by the homopolymeric error of the splice donor site with Oncomine DxTT, and false positives could be distinguished by relatively low read counts. CONCLUSIONS: Although the caution in detecting METex14 skipping focuses on false negatives in the literature, false positives were first noted at a relatively high frequency (8 of 26, 30.8%) in this study. According to the results of previous clinical trials using the other tyrosine kinase inhibitors, it could be surmised that MET inhibitor treatment in patients without METex14 skipping is detrimental. Clinicians need to be alert to the false positives that can lead to harmful treatments.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/genética , Exones/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas c-met/genéticaRESUMEN
BACKGROUND: Miliary pulmonary metastasis characterized by tiny nodules is a rare metastatic pattern in advanced non-small cell lung cancer (NSCLC) and is usually seen in patients harboring an EGFR mutation, and amylase-producing lung cancer is highly uncommon and rarely reported in NSCLC patients who have an EGFR mutation. CASE: A 32-year-old Japanese female was found to have miliary pulmonary nodules throughout both lung fields on a chest x-ray examination during an annual health check-up. Further examination by computed tomography (CT) revealed diffuse, bilateral, miliary nodules. Blood tests showed no increased tumor marker levels, but there was a significantly increased serum amylase level. A diagnosis of ALK-rearranged adenocarcinoma was made based on the results of a mediastinal lymph node biopsy obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Treatment with alectinib resulted in rapid regression of the CT shadows and a reduction in the patient's serum amylase level. CONCLUSION: We have reported a case of ALK-rearranged NSCLC with a miliary pulmonary metastasis pattern that was sensitive to alectinib and in which the serum amylase level decreased in response to treatment with alectinib. Young patients with miliary pulmonary metastasis should be checked for all driver mutations.
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INTRODUCTION: The WHO classification of lung tumors defines adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) as cancers with no or limited histologic invasive components. The probability of patients with AIS or MIA being recurrence free for 5 years postoperatively has been found to be 100%. This study aimed to analyze the prognosis of patients with AIS or MIA after more than 5 postoperative years. METHODS: We reviewed the pathologic findings of 4768 patients who underwent resection for lung cancer between 1998 and 2010. Of these, 524 patients with curative resection for AIS (207 cases, 39.5%) and MIA (317 cases, 60.5%) were included. Postoperative recurrence, survival, and development of secondary primary lung cancer (SPLC) were analyzed. RESULTS: Of the included patients, 342 (65.3%) were of female sex, 333 (63.5%) were nonsmokers, and 229 (43.7%) underwent sublobar resection. Average pathologic total tumor diameter was 15.2 plus or minus 5.5 mm. Median postoperative follow-up period was 100 months (range: 1-237). No recurrence of lung cancer was observed for either AIS or MIA cases. Estimated 10-year postoperative disease-specific survival rates were 100% and 100% (p = 0.72), and overall survival rates were 95.3% and 97.8% (p = 0.94) for AIS and MIA cases, respectively. Estimated incidence rates of metachronous SPLC at 10 years after surgery were 5.6% and 7.7% for AIS and MIA, respectively (p = 0.45), and these were not correlated with the EGFR mutation status. CONCLUSIONS: Although the development of metachronous SPLC should be noted, the risk of recurrence is quite low at more than 5 years after resection of AIS and MIA. This finding strengthens the clinical value of distinguishing AIS and MIA from other adenocarcinomas of the lung.
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Adenocarcinoma in Situ , Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/cirugía , Adenocarcinoma in Situ/cirugía , Adenocarcinoma del Pulmón/cirugía , Femenino , Humanos , Pulmón , Neoplasias Pulmonares/cirugía , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
CD70 - a ligand protein of CD27 on lymphocytes - is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with expression of programmed death ligand-1 (PD-L1) and CD27+ tumor-infiltrating lymphocytes (TIL) in formalin-fixed paraffin-embedded (FFPE) tissues of thymic tumors. FFPE tissues of thymic squamous cell carcinoma (TSCC) (operative specimens, n = 31; biopsy specimens, n = 11), thymoma (n = 60), thymic carcinoid (n = 3), and lung squamous cell carcinoma (LSCC) (n = 30) were analyzed immunohistochemically. Immunoreactivity for CD70 was semi-quantitatively scored according to the proportion of positive tumor cells. Moreover, the densities of CD27-positive intratumoral TIL (iTIL) and stromal TIL of TSCC were assessed and survival was compared. Most TSCC cases (87%; 27/31) were CD70-positive. In contrast, all thymoma and thymic carcinoid cases were CD70-negative. In LSCC cases, CD70-positivity was significantly lower than TSCC cases (20%; 6/30). Biopsy and resected specimens obtained from the same patients demonstrated a consistent staining pattern (6/6 patients). The proportion of CD70-positive TSCC was comparable with those of CD5 (87%) and CD117 (90%). Correlation between CD70 and PD-L1 expression score was observed. There was no significant difference in survival between the CD70-high and CD70-low expression groups. Meanwhile, patients with CD27-positive iTIL-high tumors exhibited better survival than those with iTIL-low tumors. This tendency was weaker in the CD70-high subset. CD70 immunohistochemistry is useful in diagnosing TSCC. CD70 may prevent anti-tumor immunity via CD27. Immunotherapy targeting the CD70-CD27 axis may be a promising option for the treatment of TSCC.
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Originally described as a systemic self-limiting disease in infancy, the spectrum of ALK-positive histiocytosis has recently been broadened to include localized diseases in older children and young adults. Despite different manifestations, these tumors share histologic characteristics and a highly recurrent KIF5B-ALK fusion. ALK-positive histiocytosis is poorly characterized in the breast. In this study, we report 3 cases of ALK-positive histiocytosis of the breast. The patients were Asian women, aged 16 to 45 years. Two patients presented with an isolated breast mass, while 1 exhibited multiorgan involvement. The latter patient received ALK inhibitor after surgery, which led to complete remission. Histologically, well-circumscribed tumors displayed fascicular and storiform growth of uniform, nonatypical spindle cells admixed with lymphocytic infiltrates. Fewer conventional epithelioid histiocytes with lobulated or clefted nuclei were observed within the same breast tumors in 2 cases or within a concomitant brain tumor in the third case. Touton-type giant cells were focally present in 2 cases. Immunohistochemically, tumor spindle, and epithelioid cells were diffusely positive for CD163 and ALK in all cases and focally positive for S100 protein in 1 of the cases. CD1a and langerin were negative. Actin-positive myofibroblasts were admixed within the tumor in 2 cases, and their reactive nature was highlighted using double immunostaining. Break-apart fluorescence in situ hybridization assay demonstrated gene rearrangements involving KIF5B and ALK in all the 3 cases. ALK-positive histiocytosis rarely occurs as a spindle cell breast tumor, and should be distinguished from other diseases such as inflammatory myofibroblastic tumors and spindled histiocytic reaction.
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Quinasa de Linfoma Anaplásico/análisis , Enfermedades de la Mama/enzimología , Histiocitosis/enzimología , Adolescente , Adulto , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/genética , Biomarcadores/análisis , Enfermedades de la Mama/genética , Enfermedades de la Mama/patología , Enfermedades de la Mama/terapia , Quimioterapia Adyuvante , Femenino , Reordenamiento Génico , Histiocitosis/genética , Histiocitosis/patología , Histiocitosis/terapia , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Cinesinas/genética , Mastectomía , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoAsunto(s)
Carcinoma , Neoplasias Pulmonares , Biomarcadores de Tumor , Humanos , Inmunohistoquímica , Isoformas de ProteínasRESUMEN
INTRODUCTION: Interaction of OX40 and OX40 ligand (OX40L) is associated with immune activation. OX40-OX40L axis is also suggested to play a role in immunity against several solid malignancies. OBJECTIVE: In this study, serum OX40 and OX40L levels in patients with advanced lung adenocarcinoma were assessed and their correlation with survival and clinicopathologic parameters was determined. METHODS: Serum samples were collected from patients with advanced lung adenocarcinoma, then OX40 and OX40L were quantified via enzyme-linked immunosorbent assay. Immunohistochemical (IHC) analysis of OX40 and OX40L in resected primary lesions was also performed. The association between OX40 and OX40L levels and clinicopathologic status and patient survival was retrospectively analyzed. RESULTS: A total of 56 patients were analyzed. Median serum OX40 and OX40L levels were 156.2 pg/mL and 186.6 pg/mL, respectively. IHC analysis in 5 patients indicated high positivity of OX40 in tumor-infiltrating lymphocytes and of OX40L in tumor cells in mucinous adenocarcinoma. Patients with a high OX40 level (≥152.2 pg/mL) had poorer prognosis than those with a low serum OX40 level (median survival, 7.36 vs. 21.19 months, respectively, p = 0.04). Patients with a high OX40L level (≥207.3 pg/mL) had poorer prognosis than those with a low serum OX40L level (median survival, 7.36 vs. 14.26 months, respectively, p = 0.04). In the subset of patients treated with immune checkpoint inhibitors (ICIs) (n = 12), those with a high OX40L level were found to have longer survival from ICI initiation than those with a low OX40L level (p = 0.023). CONCLUSIONS: High OX40 and OX40L levels are associated with poor prognosis and may reflect the immune-exhausted status against lung adenocarcinoma.
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Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/mortalidad , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Ligando OX40/sangre , Receptores OX40/sangre , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Soluble CD27 (sCD27) is associated with somatic immune reaction status. Moreover, sCD27 level is associated with the prognosis of patients with prostate cancer who receive immunotherapy. OBJECTIVE: In this study, we assessed sCD27 levels in patients with advanced lung cancer and determined their correlation with survival and clinicopathologic parameters. METHODS: Serum samples were collected from patients with advanced lung cancer, and sCD27 was quantified via enzyme-linked immunosorbent assay. The association between sCD27 levels and clinicopathologic status and patient survival was retrospectively analyzed. RESULTS: Of 96 patients analyzed, 73 had adenocarcinoma, 7 had squamous cell carcinoma, and 15 had small cell carcinoma. Median serum sCD27 level was 36.54 U/mL (range, undetectable-104.47); this is lower than that previously reported for patients with lung cancer, including those with localized stages. Patients with squamous cell carcinoma had higher sCD27 levels (p = 0.010). Age, performance status, and serum albumin levels were significantly correlated with serum sCD27 level. Patients with high serum sCD27 levels (≥32.52 U/mL; n = 58) had poorer prognosis than those with low serum sCD27 levels (<32.52 U/mL, n = 38; median survival, 7.3 vs. 21.8 months, respectively, p< 0.0001). CONCLUSIONS: High sCD27 level is associated with poor prognosis and may reflect the immune-exhausted status of patients with advanced lung cancer.
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Neoplasias Pulmonares/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/sangre , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
Pathological diagnosis of dermal melanocytic tumors is often problematic owing to histological resemblance. Recently, cutaneous melanocytoma with CRTC1-TRIM11 (CMCT) was added to this category. However, only six cases have been reported so far. We herein present a case of a 77-year-old Japanese man with CMCT. The patient presented a nodule in the right thigh and underwent surgical resection. Histological examination indicated a well-demarcated 6 × 5 mm-sized tumor nodule in the dermis and subcutis. The tumor was amelanotic, consisting of uniform nests and fascicles of spindled, or epithelioid cells. The melanocytic nature was evident by immunohistochemistry. The CRTC1-TRIM11 fusion was detected by TRIM11 immunostaining, chromogenic in situ hybridization, and RT-PCR/direct sequencing. He has been free from the tumor for 1 year after additional resection. The main differential diagnosis of CMCT includes primary and metastatic dermal malignant melanomas (MM) and dermal/subcutaneous clear cell sarcoma (CCS). Additionally, histological overlap with paraganglioma-like dermal melanocytic tumor was considered. Although some investigators argue that CMCT is a variant of CCS, we think it should be separated from CCS, and subcutaneous/dermal CCS should be confined to tumors with EWSR1-ATF1/ CREB1 fusion. However, longer follow-up and more case studies are needed for revealing the true prognosis of CMCT.