POU2F3-Expressing Small Cell Lung Carcinoma and Large Cell Neuroendocrine Carcinoma Show Morphologic and Phenotypic Overlap.

Considering the differences in protein expression in small cell lung carcinoma (SCLC) by molecular classification, it is likely that there are differences in morphology, but the relationship between molecular classification and morphology has not been examined. Furthermore, there are limited reports concerning this molecular classification for large cell neuroendocrine carcinoma (LCNEC) and SCLC simultaneously. Therefore, we investigated the relationship between immunohistochemistry-based molecular classification and morphology, protein expression, and clinical features of 146 consecutive resection specimens of pulmonary neuroendocrine carcinoma (NEC), focusing mainly on POU2F3, the master transcription factor involved in tuft cell generation. POU2F3-dominant SCLC (n=24) and LCNEC (n=14) showed overlap in cytomorphology, while non-POU2F3-dominant SCLC (n=71) and LCNEC (n=37) showed distinct differences in cytomorphology. In addition, POU2F3-dominant NEC exhibited significantly more abundant tumor stroma, more prominent nest formation, more frequent bronchial intraepithelial involvement, and less frequent background fibrosis than non-POU2F3-dominant NEC. Immunohistochemically, POU2F3-dominant SCLC and LCNEC were characterized by lower expression of TTF-1, CEA, and neuroendocrine markers and higher expression of bcl-2, c-Myc, and c-kit. Clinically, POU2F3-dominant NEC had a significantly better prognosis than non-POU2F3-dominant NEC for recurrence-free survival. POU2F3-dominant NEC had a higher smoking index than non-POU2F3-dominant NEC. POU2F3-dominant NEC forms a unique population, exhibiting intermediate morphologic features between SCLC and LCNEC, with distinct protein expression as tuft cell-like carcinoma. Recognition of this unique subtype may provide clues for solving the long-standing issues of NEC and appropriate therapeutic stratification. It is important to accurately identify POU2F3-expressing carcinomas by immunohistochemistry and to analyze their clinicopathological features.

Implication of cytoplasmic p53 expression in pulmonary neuroendocrine carcinoma using next-generation sequencing analysis.

AIMS: Cytoplasmic p53 expression indicates a high frequency of TP53 abnormalities in gynaecological carcinoma. However, the implication of this expression in pulmonary neuroendocrine carcinoma (NEC) remains unclear. Thus, our study aimed to fill this research gap. METHODS AND RESULTS: Immunohistochemistry (IHC) of p53 was performed on 146 cases of resected small-cell lung carcinoma and large-cell NEC, and next-generation sequencing was conducted on cases showing cytoplasmic and wild-type p53 expression. IHC revealed overexpression in 57% of the cases (n = 83), complete absence in 31% (n = 45), cytoplasmic expression in 8% (n = 12) and wild-type expression in 4% (n = 6) of the cases. TP53 mutations were identified in nine of the 13 cases with available genetic analysis. The TP53 mutation rates in cases with cytoplasmic and wild-type p53 expression were 88% (seven of eight) and 40% (two of five), respectively. All seven cases showing cytoplasmic expression with TP53 mutations harboured loss-of-function type mutations: four had mutations in the DNA-binding domain, two in the nuclear localisation domain and one in the tetramerisation domain. Clinically, cases with cytoplasmic p53 expression had a poor prognosis similar to that in cases with p53 overexpression or complete absence. CONCLUSIONS: Cytoplasmic p53 expression in patients with pulmonary NEC suggests a high TP53 mutation rate, which is associated with a poor prognosis similar to that in patients with p53 overexpression or complete absence. This cytoplasmic expression should not be misidentified as a wild-type expression. This is the first report, to our knowledge, that demonstrates the implication of cytoplasmic p53 expression in pulmonary NEC.

Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma.

BACKGROUND: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts. CASE PRESENTATION: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma. CONCLUSION: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.

Diagnostic yield and the number of tumor cells of ultrathin bronchoscopy for peripheral lung lesions: A comparison with thin bronchoscopy.

Ultrathin bronchoscopy has been reported to have a higher diagnostic yield than thin bronchoscopy for small peripheral lung lesions in transbronchial biopsy under radial endobronchial ultrasonography (EBUS). However, data comparing the number of tumor cells in non-small cell lung cancer (NSCLC) are limited. We retrospectively compared the number of NSCLC tumor cells in peripheral lung lesions obtained using an ultrathin bronchoscope and a thin bronchoscope with radial EBUS between April 2020 and October 2021. In all patients, we used virtual bronchoscopic navigation (VBN) software, and guide sheaths were used in thin bronchoscopy cases. A total of 175 patients were enrolled in this study. Ultrathin bronchoscopy cases (n = 69) had lesions with a smaller diameter that are more peripherally located compared to thin bronchoscopy cases (n = 106) (median, 25.0 vs. 26.5 mm, mean bronchial generations accessed by bronchoscopy; 4.4±1.2 vs. 3.8±1.0, respectively; p<0.010). There were no significant differences in the overall diagnostic yield (ultrathin vs. thin bronchoscopy cases, 68.1% vs. 72.6%, p = 0.610) or diagnostic yield in only lung cancer cases (78.6% vs. 78.5%, p = 1.000). In histologically NSCLC cases (n = 102), the maximum number of tumor cells per slide as the primary endpoint was similar (average, 307.6±246.7 vs. 328.7±314.9, p = 0.710). The success rate of the Oncomine™ analysis did not differ significantly (80.0% vs. 55.6%, p = 0.247). The yield of NSCLC tumor cells was not different between the samples obtained by the ultrathin bronchoscope and those obtained by the thin bronchoscope.

Programmed death ligand-1 expression and occult lymph node metastasis in non-small cell lung cancer.

BACKGROUND: Identifying the preoperative risk factors for lymph node upstaging could contribute to the development of individualized perioperative treatment for patients with non-small cell lung cancer (NSCLC). The current study aimed to evaluate the risk factors for lymph node upstaging, including gene mutation and programmed death ligand-1 expression in patients with resectable NSCLC. METHODS: Data on the clinicopathological characteristics of patients who underwent lobectomy for clinical N0 NSCLC at our institution were collected. The clinicopathological findings of the pathological N0 and lymph node upstaging groups were then analyzed. Univariate and multivariate analyses were performed to examine the predictive factors for nodal upstaging. RESULTS: Of 291 patients, 40 had postoperative nodal upstaging (n = 25, N1; n = 15, N2). Large tumor size and high maximum standardized uptake value were significantly associated with nodal upstaging. The nodal upstaging group had a higher proportion of patients with solid adenocarcinoma and lymphatic, vascular, and pleural invasion than the pathological N0 group. Further, the nodal upstaging group had a higher proportion of patients with positive programmed death ligand-1 expression than the pathological N0 group. Univariate and multivariate analyses showed that tumor size and positive programmed death ligand-1 expression were associated with nodal upstaging. CONCLUSION: The appropriate therapeutic strategy including preoperative treatment and resection should be cautiously considered preoperatively in patients with clinical N0 NSCLC who have large tumors and positive programmed death ligand-1 expression.

Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Effect of myasthenia gravis on the surgical outcomes of patients with thymoma.

BACKGROUND: Myasthenia gravis (MG) is the most common paraneoplastic syndrome in thymoma. However, the association between MG and postoperative outcomes is controversial. Therefore, we examined the effect of MG on the surgical outcomes of patients with thymoma. METHODS: This study enrolled 145 consecutive patients with thymoma who underwent surgical resection at our institution between January 2000 and December 2020. The patients were classified into thymoma with MG (MG group) and without MG (non-MG group). Data about characteristics of patients, surgical outcomes, and prognostic factors were compared between the two groups. RESULTS: Of 145 patients, 47 (32%) presented with MG and 98 (68%) did not. There was no significant difference in terms of the incidence of postoperative complications, overall survival (OS), and recurrence-free survival (RFS) between the two groups. The deaths were not caused by thymoma. Among the patients aged >60 years, the MG group had a lower survival rate than the non-MG group. In the univariate analysis, age ≥60 years was a poor prognostic factor for OS, whereas in the multivariate analysis, Masaoka stage III and IV classifications were poor prognostic factors for RFS. CONCLUSION: The incidence of postoperative complications did not differ between patients with thymoma and without MG. In the MG group, age ≥60 years was a poor prognostic factor for OS. The postoperative follow-up of patients aged ≥60 years with thymoma with MG should focus on not only recurrence but also progression of diseases other than thymoma.

Annexin A10 Expression as a Novel Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma. MATERIALS AND METHODS: ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction. RESULTS: High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines. CONCLUSION: ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

Immunohistochemical analysis revealed the expression of bone morphogenetic proteins-4, 6, 7, and 9 in human induced membrane samples treated with the Masquelet technique.

BACKGROUND: Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. METHODS: This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. RESULTS: The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. CONCLUSIONS: This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM.

Sarcomatoid mesothelioma originating from mesothelioma in situ: are methylthioadenosine phosphorylase loss and CDKN2A homozygous deletion poor prognostic factors for preinvasive mesothelioma?

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches. Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.

Chloride Intracellular Channel 1 Expression Is Associated With Poor Prognosis of Lung Adenocarcinoma.

BACKGROUND/AIM: Chloride intracellular channel 1 (CLIC1) is a member of the chloride channel protein family. The aim of this study was to clarify the role of CLIC1 in lung adenocarcinoma. PATIENTS AND METHODS: The expression levels of CLIC1 in 74 patients with completely resected lung adenocarcinoma were analyzed by immunohistochemistry. Overall survival was assessed in relation to the expression level of CLIC1. Moreover, in the lung cancer cell lines A549 and PC9, CLIC1 expression was inhibited by small interfering RNA. The function of CLIC1 was analyzed in these cell lines. RESULTS: High expression of CLIC1 was associated with short overall survival compared to low expression (p=0.0327). Multivariate analysis revealed that CLIC1 expression was an independent prognostic factor. Knockdown of CLIC1 inhibited cell proliferation and migration through suppression of the p38 MAPK signaling pathway in A549 and PC9 cells. CONCLUSION: CLIC1 may be a useful prognostic factor in lung adenocarcinoma.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated with Atypical Thymic Carcinoid: A Case Report.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.

Yield of tumor samples with a large guide-sheath in endobronchial ultrasound transbronchial biopsy for non-small cell lung cancer: A prospective study.

BACKGROUND: Adequate tumor tissue is required to make the best treatment choice for non-small cell lung cancer (NSCLC). Transbronchial biopsy (TBB) by endobronchial ultrasonography with a guide sheath (EBUS-GS) is useful to diagnose peripheral lung lesions. The data of tumor cell numbers obtained by two different sizes of GSs is limited. We conducted this study to investigate the utility of a large GS kit to obtain many tumor cells in patients with NSCLC. METHODS: Patients with a peripheral lung lesion and suspected of NSCLC were prospectively enrolled. They underwent TBB with a 5.9-mm diameter bronchoscope with a large GS. When the lesion was invisible in EBUS, we changed to a thinner bronchoscope and TBB was performed with a small GS. We compared the tumor cell number prospectively obtained with a large GS (prospective large GS group) and those previously obtained with a small GS (small GS cohort). The primary endpoint was the tumor cell number per sample, and we assessed characteristics of lesions that could be obtained by TBB with large GS. RESULTS: Biopsy with large GS was performed in 55 of 87 patients (63.2%), and 37 were diagnosed with NSCLC based on histological samples. The number of tumor cells per sample was not different between two groups (658±553 vs. 532±526, estimated difference between two groups with 95% confidence interval (CI); 125 (-125-376), p = 0.32). The sample size of the large GS group was significantly larger than that of the small GS cohort (1.75 mm2 vs. 0.83 mm2, estimated difference with 95% CI; 0.92 (0.60-1.23) mm2, p = 0.00000019). The lesion involving a third or less bronchus generation was predictive factors using large GS. CONCLUSIONS: The sample size obtained with large GS was significantly larger compared to that obtained with small GS, but there was no significant difference in tumor cell number. The 5.9-mm diameter bronchoscope with large GS can be used for lesions involving a third or less bronchus generation.

Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus­positive head and neck squamous cell cancer through upregulation of Ror2 expression.

Ror2 (receptor tyrosine kinase like orphan receptor 2) is highly expressed in various types of cancers; in the majority of these cancers, Ror2 expression is associated with more aggressive disease states. Recently, it has been reported that Ror2 is highly expressed in human papilloma virus (HPV)­positive head and neck squamous cell cancer (HNSCC) cell lines, presumably indicating that Ror2 plays a critical role in HPV­related cancers. However, the function of Ror2 in HPV­positive HNSCC is currently unknown. Here, we first examined the expression levels of Ror2 in clinical specimens from patients with HPV­negative and HPV­positive oropharyngeal squamous cell cancer (OPSCC) via immunohistochemical analysis. We found that Ror2 was expressed in both HPV­negative and HPV­positive OPSCC tissues. We then confirmed that HPV­positive HNSCC cell line, UPCI:SCC152 cells, express Ror2 higher than HPV­negative cell lines as previously reported. Suppressed expression of HPV E6/7 resulted in reduced expression levels of Ror2. We also revealed that Ror2 downregulation significantly inhibited the proliferation of UPCI:SCC152 cells without inducing apoptosis. Moreover, Ror2 knockdown decelerated G1/S phase progression and abrogated invasive migration of UPCI:SCC152 cells. These results provide strong evidence that E6 and/or E7 oncoproteins regulate the progression of HPV­positive HNSCC by upregulating Ror2 expression, suggesting that Ror2 could potentially be a novel target in HPV­related cancers.

Homology-Based Image Processing for Automatic Classification of Histopathological Images of Lung Tissue.

The purpose of this study was to develop a computer-aided diagnosis (CAD) system for automatic classification of histopathological images of lung tissues. Two datasets (private and public datasets) were obtained and used for developing and validating CAD. The private dataset consists of 94 histopathological images that were obtained for the following five categories: normal, emphysema, atypical adenomatous hyperplasia, lepidic pattern of adenocarcinoma, and invasive adenocarcinoma. The public dataset consists of 15,000 histopathological images that were obtained for the following three categories: lung adenocarcinoma, lung squamous cell carcinoma, and benign lung tissue. These images were automatically classified using machine learning and two types of image feature extraction: conventional texture analysis (TA) and homology-based image processing (HI). Multiscale analysis was used in the image feature extraction, after which automatic classification was performed using the image features and eight machine learning algorithms. The multicategory accuracy of our CAD system was evaluated in the two datasets. In both the public and private datasets, the CAD system with HI was better than that with TA. It was possible to build an accurate CAD system for lung tissues. HI was more useful for the CAD systems than TA.

Histological analysis of induced membranes in patients whose bone defects were treated with the Masquelet technique to identify factors affecting the vascularity of induced membranes.

BACKGROUND: Rich vascularity of the induced membrane (IM) is important for Masquelet reconstruction surgery. The factors affecting IM vascularity are not completely understood. This study aimed to investigate these factors using histological samples of human IMs. METHODS: We retrospectively evaluated 36 patients whose bone defects were treated using the Masquelet technique. Two clinical pathologists analyzed histological sections of IM pieces (1 cm2). The number of blood vessels per 1 mm2 was counted and compared among men and women, femur or tibia, with and without free flap surgery, antibiotic impregnation to the cement, osteogenesis inside the membrane, smoking, and diabetes mellitus. The number of blood vessels within the same patient was compared among different time points. Correlation analysis was performed among blood vessel numbers and patient age, duration of cement spacer placement, and histological grading scales (inflammation, foreign body reaction, and fibrosis). RESULTS: IM formation with rich vascularity and some inflammation, foreign body reaction, and fibrosis were histologically confirmed in all patients. We found 37.4 ± 19.1 blood vessels per 1 mm2. The number of blood vessels was significantly lower in patients with than in those without free flap surgery; it was higher in patients with osteogenesis inside the IM. No significant correlations were found in any of the analyses. CONCLUSION: Sex, patient age, smoking, diabetes mellitus, femur or tibia, duration of cement spacer placement, and antibiotic impregnation to the cement did not affect IM vascularization. IM vascularization was reduced in patients with than in those without free flap surgery.

Hybrid Schwannoma/Perineurioma: Morphologic Variations and Genetic Profiles.

To clarify the morphologic spectrum and molecular profiles of hybrid schwannoma/perineurioma (HSP), we investigated 15 tumors clinicopathologically and cytogenetically. HSP was classified into 2 morphologic types: mixed cellular and combined tumor types. The former comprising of 14 tumors mostly arose in the subcutaneous tissue of the extremities and the trunk of middle-aged adults. They were well-circumscribed and composed of elongated spindle-shaped tumor cells arranged in storiform and whorl patterns. Immunostaining revealed a mixed cellular proliferation of S-100 protein-positive and SOX10-positive Schwann cells and epithelial membrane antigen-positive, claudin 1-positive, and GLUT1-positive perineurial cells. During follow-up, no tumors were found to have recurred in any cases. In contrast, in the combined tumor type arising in the mediastinum of a young male with neurofibromatosis type 2, the intraneural perineurioma-like areas, characterized by small whorl-like structures, were present in plexiform schwannoma-like areas. No recurrence was noted in the case. Molecular analyses (array comparative genomic hybridization and fluorescence in situ hybridization) revealed LOH 22q in 2 tumors of 5 studied: one each of the mixed cellular and combined tumor types. Although the same diagnostic term, HSP, has been applied to both mixed and combined types, they should be separated from each other.

Relationship between PDGFR expression and the response to pazopanib in intimal sarcoma of the pulmonary artery: A case report.

Intimal sarcoma of the pulmonary artery (PAIS) is a rare disease with a poor prognosis. Pazopanib, which has been indicated in metastatic non-adipocytic soft-tissue sarcomas and is expected to be active in PAIS, is a multi-kinase inhibitor that targets the tyrosine kinase activity of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor. The present study reports findings related to two cases of PAIS with PDGF and VEGF expression following treatment with pazopanib. A case with a moderate to strong expression of PDGFR-α and -ß presented a long-term stable disease when treated with pazopanib (progression-free survival, 5.8 months). In a second case with a weak expression of PDGFR-α and -ß, the disease progressed rapidly on pazopanib (progression-free survival, 1.1 months). VEGFR-2 was not expressed in the tumors of both cases. The level of PDGFR expression in the tumor tissue may therefore be predictive of pazopanib efficacy.

Chondrolipoma of the finger in a child: A case study.

Chondrolipoma is, based on the limited case reports available, an extremely rare histological variant of lipoma with the proliferation of mature adipocytes containing an area of true hyaline cartilage. Chondrolipoma is characterized by adult onset and is often identified in the breast, pharynx and tongue. The current study presents a case of chondrolipoma of the finger in an 11 year-old girl. Physical examination indicated a well-defined elastic soft mass, measuring 2.5x2 cm, on the dorsal aspect of the proximal phalanx of the left middle finger. Magnetic resonance imaging (MRI) revealed a well-circumscribed lesion with heterogeneous signal intensity. On T1- and T2-weighted images, the lesion indicated a predominantly marked hyperintense signal containing linear hypointense regions, and on fat-suppressed short-tau inversion recovery sequences, the lesion indicated a predominant hypointensity, with linear regions displaying hyperintensity. Marginal excision of the tumor was performed. Histologically, the major component of the tumor was mature adipose tissue containing a limited area of mature hyaline cartilage matrix, without lipoblasts or malignancy. The postoperative course of the patient was excellent, with no local recurrence three years after surgery. To the best of our knowledge, the current study outlines the first pediatric case of chondrolipoma arising in the finger.