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Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.
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Although classic morphology is the cornerstone for the diagnosis of bone tumors, the rapidly developed molecular pathology based on Next Generation Sequencing (NGS) has evolved current diagnostic techniques. At the same time, new disease entities based on molecular abnormalities were constantly reported, which converted the morphological pathological classifications into molecular categories. At present, bone tumors could be roughly classified as tumors with simple karyotypes and those with complex karyotypes by molecular alterations. The previous classification can be subclassified as tumors that carry specific translocations, somatic gene mutations, or those with specific amplifications. However, the later groups usually lack specific alterations. The present review discusses various updates on molecular pathology in detail based on new categories of bone tumors proposed by World Health Organization (WHO) in 2019 aiming to further provide guidance for evidenced-based treatment. Some examples are included, such as giant cell tumor of bone (H3F3A p.G34W), chondroblastoma (H3F3B p.K36M), chondrosarcoma (IDH1/2 mutation), aneurysmal bone cyst (USP6 rearrangements) and so on. All mutual alterations play an increasingly important role in reaching a diagnosis and in patients management.
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Objective:To investigate the clinical manifestations, imaging features, histopathological features, diagnostic pitfalls, treatment and prognosis of clear cell chondrosarcoma (CCCS).Methods:23 cases of CCCS admitted and operated from January 2010 to January 2020 were analyzed retrospectively. Among the 23 cases, 21 were males and 2 were females. There were 8 cases (35%) aged 21-40, 10 cases (43%) aged 41-60 and 5 cases (23%) aged 61-80. There were 8 femurs, 7 pelvis, 4 thoracolumbar spine, 3 sacrum and 1 tibia. The specimens were fixed with 10% phosphate-buffered formalin, decalcified with 5% nitric acid, embedded in paraffin and stained with hematoxylin and eosin (HE) and immunohistochemistry (Envision). The preoperative imaging and clinical symptoms, and the postoperative histopathological and immunophenotype under the microscope were collected. And the relevant literature was reviewed to summarize the clinical, imaging and pathomorphological characteristics of CCCS.Results:23 cases of CCCS showed bone destruction in imaging, some cases were well-circumscribed lytic lesions, some cases had sclerotic margin. The serum alkaline phosphatase was increased in 7 patients before operation. The tumor tissue was gray-white and gray-red in general and some cases showed porcelain white cartilage-like areas. Microscopically, the tumor cells are round or polygonal, some of them have clear cytoplasm and boundary, some of them are eosinophilic, some of them have round and centrally located nuclei, and mitotic image is rare. It is often seen that there are nodular distribution of cartilage-like matrix and immature woven bone, multinucleated osteoclast-like giant cell scattered in those components. Immunohistochemical staining: S-100, D2-40, EMA, Vimentin, p16, SATB2 can be positive in varying degrees. The surgical treatment is mainly through en bloc excision. 10 patients had recurrence and no distant metastasis.Conclusion:CCCS is a rare subtype of chondrosarcoma, which has low-grade malignant biological behavior and is easy to be misdiagnosed clinically and pathologically. Pathological diagnosis needs to be careful. Careful observation of microscopic histology is necessary in order to avoid over-diagnosis of osteosarcoma leading to clinical treatment errors. Once the biopsy is confirmed, it needs en bloc excision in order to reduce the recurrence rate. Long-term follow-up is needed after the operation, the overall prognosis was good.
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Objective: To evaluate whether clinical imaging findings of sarcomas after preoperative chemotherapy correlate with tumor responses by pathological evaluation using the rate of necrosis, so as to develop reliable and quantitative evaluation of clinical re-sponse. Methods: We retrospectively reviewed the medical records of 190 patients with high-grade sarcomas (mainly osteosarcomas and Ewing's sarcomas) that originated from the bone and who received neoadjuvant chemotherapy from June 1, 2014 to March 1, 2017 at Peking University People's Hospital. Finally, 157 lesions were evaluated by clinical imaging, including X-ray, computed tomogra-phy, magnetic resonance imaging, and bone scans or PET/CT. All patients underwent surgery at our center and pathological evaluation by tumor necrosis rates, which were graded by Huvos'classification, where gradeⅠis 0 to 49%, gradeⅡis 50% to 89%, gradeⅢis 90% to 99%, and gradeⅣis 100% necrosis. Statistical diversity analysis was performed by different pathological groups and receiver operating characteristic (ROC) curves. ROC curves were generated to determine the dividing clinical parameters (cut-off values) to dis-tinguish different pathological groups. Results: The cut-off values of the rate change in maximum diameters of tumors located in the extremities were 86%, 50.7%, and 0.02% for Huvos'Ⅳ,Ⅲ,Ⅱ, andⅠgroups, respectively. The differentiation was not obvious using bone scans to distinguish different pathological responses. The cut-off value for SUVmax for Huvos'Ⅲ,Ⅱ, andⅠgroups were 60.7% and 31.4%, respectively. We did not identify any valuable clinical parameters to evaluate the lesion restricted inside the bone. For sar-comas that originated from the axial skeleton, because of the small size of the sample, the differentiation was not so obvious. Conclu-sions: This study clearly defined the measuring methods for sarcomas primarily originating from the bone and attempted to determine meaningful cut-off values for multiple pathological response groups. A prospective multicenter trial is warranted to expand the sample size to make this clinical evaluation more precise and practical.
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Purpose To evaluate the correlations between high resolution CT (HRCT) findings and IASLC/ATS/ERS pathological classification of ground glass nodule (GGN). Materials and Methods 121 patients with confirmed GGN were selected, and divided into benign group (22 cases), PIL group (21 cases), microinvasive carcinoma group (26 cases) and invasive carcinoma group (52 cases), then the imaging, pathology and prognosis data of patients with pulmonary GGN were reviewed, and the differences among GGN of different pathological types were analyzed.Results Maximum diameter, margin, vacuole sign, solid component, shape and blood vessels through of GGN were significantly different among the four groups (χ2=9.945-31.068,P<0.05). Maximum diameter and margin were significantly different between invasive adenocarcinoma and other groups (P<0.008); vacuole sign of the benign group was significantly different with other groups (P<0.008); the existence of solid component and shape were significantly different between invasive adenocarcinoma and minimally invasive adenocarcinoma (P<0.008); there was significant difference of blood vessels through between invasive adenocarcinoma and benign lesions (P<0.008). Among the 121 lesions, no metastasis except one invasive adenocarcinoma case complicated with distant metastasis.Conclusion Maximum diameter of GGN greater than 16.35 mm, with spiculation or lobulation represent invasive adenocarcinoma; vacuole sign within the GGN represent malignancy; with solid component and irregular shape can be used to identify invasive adenocarcinoma from minimally invasive adenocarcinoma; while blood vessels through can be used to identify invasive adenocarcinoma from benign lesions; the prognosis of GGNs is well with only 0.83% probability of distant metastasis.
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Objective To investigate the clinicopathologic features of sclerosing polycystic adenosis(SPA)of salivary gland.Methods The clinical and pathologic profiles of 2 SPA cases were evaluated.Immunohistochemical study was performed on fixed tissues.The biologic behavior was analyzed with follow-up data.Results The main clinical manifestation of patients was parotid painless nodules.Histological features were embedded cystic dilatation of ducts and alveoli as hyaline sclerosis collagen tissue background,catheter see apocrine metaplasia,focal areas of ductal epithelial hyperplasia and dysplasia.Immunohistochemical staining for calponin and SMA staining showed that the catheter had a layer of myoepithelial cells.Conclusion Sclerosing polycystic sialadenopathy of parotid is a rare disease,the cause and course of the disease are not very clear,but the literature reports are atypical ductal epithelial remarkable phenomenon,thus strengthen the follow-up to patients.
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Objective To investigate colonoscopic presentation and explore biopsy style of lower gastrointestinal graft-versus-host disease (GI-GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The endoscopic findings including mucosa erythema,edema,erosion,ulcer,tortoiseshell-pattern and sloughing were observed in 36 patients with GI-GVHD and the rate of apoptotic cell yields in colon and end-ileum was calculated.Results Mucosa lesions were found in almost all of the patients both in colorectal and end-ileum (97.2％ vs 94.1％,P =0.609).Mucosa erythema was more often seen in end-ileum (47.2％ vs 79.4％,P =0.007) and tortoiseshell-pattern was mainly in colorectal mucosa (63.9％ vs 5.9％,P =0.000).Mucosa edema,erosion and oozing bleeding were the same prevalence in large intestine and end-ileum (97.2％ vs 94.1％,80.6％ vs 79.4％,47.2％ vs 47.1％,P ＞ 0.05,respectively).Sloughing was found in 76.5％ (26/34) GI-GVHD patients,and it was almost the same prevalence in large intestine and end-ileum (52.8％ vs 47.1％,P ＞0.05).Almost all of the colorectal mucosa sloughing located in the tortoiseshell-pattern mucosa.Rates of apoptotic cell in rectal,colonic and end-ileal mucosa were 88.9％,91.3％ and 75.9％,respectively,and the rates were 88.2％ and 93.9％ in ileum plus rectum and ileum plus colon respectively,showing that biopsy only in ileum was not sufficient for the pathologic diagnosis of GI-GVHD (93.9％ vs 75.9％,P =0.070).Conclusion Endoscopic presentations of GI-GVHD after allo-HSCT are not the same between colorectal and end-ileal mucosa.Sloughing with GIGVHD feature is not rarely seen in lower GI.Tortoiseshell-pattern mucosa should also be pathognomonic feature of colorectal GVHD in endoscopy.Pathologic tissue should not only be biopsied in end-ileum,but also in colorectal mucosa in the same time.
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Objective To explore the expression of N-myc downstream regulated gene 1 (NDRG1) in gastric carcinoma and the relationship with clinicopathological parameters and prognosis. Methods The expression of NDRGI was detected by immunohisto chemistry in formalin-fixed and paraffin-embedded sections with a total of 220 specimens including 110 gastric carcinoma and 110 corresponding paraneoplastic tissue. The correlation between clinicopathological parameters and the expression of NDRG1 in gastric carcinoma were also analyzed. Results Low expression of NDRG1 was detected in most gastric carcinoma sections. Among the gastric cancer tissues, NDRG1 protein expression was significantly lower in tumors with more advanced pathological stage, local tumor invasion and lymphatic metastases. There was no significant difference in sex, age, tumor differentiation and gross types of the tumor. The 1-, 3- and 5 year survival and disease free survival in patients with low NDRG1 protein expression was 84.2%, 53.9%, 21.1%, and 60.5%, 31.6%, 19.7%, respectively, which was signifivantly poorer when compared with patients with high NDRG1 protein expression. Conclusion The expression of NDRG1 is low in the majority of patients with gastric carcinoma, which was in a close relationship with advanced stage, local invasion and lymphatic metastases of gastric carcinoma. NDRG1 may be a candidate metastasis suppressor gene.