Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors.

The levels of sPD-1 and sPD-L1 were analyzed in blood serum of 132 patients (age 14-70 years) with primary bone tumors: osteosarcoma (N=39), chondrosarcoma (N=42), Ewing sarcoma (N=9), chordoma (N=12), giant-cell bone tumor (GCBT) (N=16), benign neoplasms (N=14) and in and practically healthy subjects (age 19-58 years; N=27). sPD-L1 levels in all studied bone neoplasms were significantly higher than in the control. Serum sPD-1 level in GCBT patients was significantly higher than in the control, benign neoplasms, chondrosarcoma, and chordoma patients, but did not differ from osteosarcoma group. sPD-1 concentration in Ewing sarcoma was significantly higher than in chordoma and chondrosarcoma, but did not differ from the control. sPD-1 level in chondrosarcoma patients was also lower than in osteosarcoma, Ewing sarcoma, and in the control. Both sPD-1 and sPD-L1 concentrations were not significantly associated with the type of affected bone, process localization, disease stage, tumor histological grade, patients' age and sex. These results suggest the possibility of using these biological markers for preliminary assessment of the character of the process in the bone.

[Osteochondroma in children and adolescents].

Osteochondroma is called a benign cartilage-forming tumor arising from an aberrant subperiosteal cartilage. Multiple osteochondromas syndrome (MOS) is an autosomal dominant disease, the basis for which is mutations in the EXT (EXT1 or EXT2) genes. Osteochondroma is one of the most common benign bone tumors. According to the WHO data, it is detectable in 35% of benign bone tumors and 8% of all surgically removed bone tumors. A total of 491 cases of bone tumors were analyzed in the children and adolescents diagnosed at the Department of Pathoanatomy, Russian Children's Clinical Hospital, Moscow, in 2009 to 2014. All the patients with osteochondroma were divided into 2 groups: 1) sporadic cases (n = 63) and 2) tumors included in MOS (n = 33). Both groups showed a preponderance of boys (39 boys and 24 girls in Group 1 and 21 boys and 12 girls in Group 2). Clinical, radiological, and morphological criteria for the diagnosis and differential diagnosis of osteochondromas in children and adolescents are given.

[Classical osteosarcoma in children and adolescent].

Classical osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. It more frequently occurs in the areas of the highest growth plate proliferation: limb long bones particularly in the distal femur (30%), proximal tibia (15%), and proximal humerus (15%). In the long bones, the tumor is located usually in the metaphysis (90%), less frequently in the diaphysis (9%), and very rarely in the epiphysis. This paper considers the clinical, radiological, and histological diagnosis, and prognosis in this pathology.

Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

Endostatin, placental growth factor, and fibroblast growth factors-1 and -2 in the sera of patients with primary osteosarcomas.

Serum levels of endostatin, placental growth factor (PlGF), and fibroblast growth factors-1 and -2 (FGF-1 and FGF-2) were measured in 58 patients with primary osteosarcomas before therapy and in 21 healthy subjects. The incidence of serum FGF-1 in bone tumors was 2.5 times higher than in healthy individuals (p=0.004); significant levels of FGF-2, PlGF, and endostatin were detected in all examined subjects. The mean serum level of endostatin in healthy individuals was significantly lower than in the total group of patients with bone tumors (p=0.005). The level of FGF-1 in osteosarcomas was significantly higher than in chondrosarcomas (p<0.05). No appreciable differences in FGF-2 levels were detected in patients with tumors of different histological structure. The mean serum content of PlGF was virtually the same in healthy individuals and patients with bone tumors. A significant relationship between serum PlGF level and maximum tumor size (p=0.008) was detected in osteosarcoma. No relationships between the levels of FGF-1, FGF-2, PlGF, and endostatin were detected in healthy subjects and patients with primary tumors of the bones. Differences in 3-year overall survival values of patients with bone sarcomas with different initial serum levels of FGF-1 and endostatin were detected.

[Dedifferentiated chondrosarcoma: problems of diagnosis and treatment].

In 2001-2007, Moscow cancer hospital sixty-two examined 77 patients with chondrosarcoma (including consultative cases). The dedifferentiated form of the tumor was confirmed in 10 (13%) cases. Recurrences and metastases were observed in 3 patients. Radical surgery could be performed in 5 patients, including interileoabdominal exarticulation in 4 patients. Immunohistochemical studies provide a way of specifying the nature of one of the tumor components. Ultrastructural data on the components of dedifferentiated chondrosarcoma are first presented in the Russian literature. Fine-needle biopsy and trepan-biopsy may give an incorrect guide to choosing treatment policy. The experience in performing combined therapy for this unusual tumor is first presented in the Russian literature and drug pathomorphism has been studied. Radical surgery remains to be the method of choice in treating patients with dedifferentiated chondrosarcoma; however, the capabilities of multidrug therapy and irradiation should not be ignored in this form of the tumor.

[Soft tissue chondroma].

The paper gives a rare case of soft tissue chondroma in a 55-year-old female woman who has unsuccessfully received physiotherapeutic procedures for more than 6 months due to misdiagnosis. The patient detected the tumor herself. Clinical and X-ray diagnostic difficulties are considered. Differential diagnosis was made between synovial chondromatosis and chondrosarcoma. A correct diagnosis could be established only at open tumor biopsy. The neurovascular fascicle, tendons, and an intrinsic group of shoulder muscles could be preserved during radical surgery. The problems in the morphological diagnosis of extraskeletal chondroma are discussed in detail. The results of organ-preserving resection are presented.

[Osteocartilaginous exostoses (osteochondromas)].

Osteochondroma is the most common true bone neoplasm formed by a cartilage capped bony projection arising on the external surface of a bone containing a marrow cavity that is continuous with that of the underlying bone. Osteochondromas generally arise in the bones preformed by cartilage. Osteochondromas may be solitary and multiple. Most reported cases have been in the first 3 decades with no known sex predilection. The lesion has three layers - perichondrium, cartilage and bone. The cartilage cap is usually less than 2.0 cm thick, superficial chondrocytes are clustered, the ones close to the transition to the bone resemble a growth plate, they are organized into chords and undergo enchondrial ossification. Loss of the architecture of cartilage, wide fibrous bands, myxoid change, increased chondrocyte cellularity, mitotic activity, significant chondrocyte atypia and necrosis are all features that may indicate secondary malignant transformation.

[Abnormal (bizarre) paraostial osteochondromatous proliferation (Nora's disease)].

Bizarre paraostial osteochondromatous proliferation (BPOP) is a reactive process composed of bone and cartilage attached to the surface of a bone, the condition was first described by Nora et al. as a reactive proliferation involving small bones. A case of a 76-year-old male represents the first description of BPOP in the Russian literature. The patient has a history of trauma, the duration of symptoms being more than a year. Xray study shows suspected secondary chondrosarcoma. The benign space-occupying lesion BPOP is verified after wedge resection of the phalanx. The described condition seems to occur more frequently than reported in the literature. Current imaging techniques and histological study permit avoidance of diagnostic errors and correct choice of the scope of treatment.

[Osteochondrosarcoma: clinical and morphological comparisons].

A total of 109 patients with chondrosarcoma were operated on in 2005-2007. Classical primary chondrosarcoma was verified in 77 cases; secondary and periosteal chondrosarcomas were confirmed in 28 and 4 patients, respectively. By analyzing their findings and the data available in the literature, the authors considered the current problems in the classification and diagnosis of the most common types of cartilaginous malignancies. New techniques, including cytogenetic assay, significantly alleviate this problem. However, the most precise cytogenetic assays are expensive and not always accessible for usual oncological care. The principal criteria in practice are a clinical picture, the results of radiation studies, and the standard histological method that establishes the differentiation of chondrosarcoma, the extent of a process, and the specific features of tumor growth. Immunohistochemical assay are of no crucial importance. In some cases, fine-needle biopsy may provide useful information to make a decision on treatment policy.

[Chondromas (enchondroma, periosteal chondroma, enchondromatosis)].

Chondromas combine a group of benign cartilaginous tissue tumors with common histological manifestations. The tumors (enchondroma, periosteal chondroma, and enchondromatosis) differ in sites and clinical manifestations. Chondromas are generally hypocellular, avascular tumors with an abundance of hyaline cartilage matrix and chondrocytes located diffusely, in clones or lobules. Small bone chondromas, Ollier's disease, and Mafucci's syndrome are characterized by the tumor tissue containing a large number of cells and by greater cytological atypia. Enchondroma is successfully treated by surgical methods.

[Chondroblastoma].

Chondroblastom, benign cartilage tissue neoplasm, accounts for 1% of all bone tumors. It is encountered in any skeletal bones mainly in persons aged 10 and 25 years. Morphologically, it is represented as large homogenous cells--well-defined oval polygonal chondroblasts with a fine eosinophilic cytoplasm, and a round-to-oval nucleus. Cartilaginous portions of chondroblastoma form lobular structures. The tumor always comprises single-to-multiple multinucleate giant cells. The pathognomonic sign of chondroblastoma is intercellular reticular basophilically stained calcifications as a mesh. Mitotic cells, rather than abnormal ones, are present. There are cases of primary malignant chondroblastomas.

[Chondromyxoid fibroma].

Chondromyxoid fibroma is a benign chondroid tissue tumor characterized by the lobular overgrowth of stellate or elongated cells in the myxoid or chondroid intracellular matrix. There may be giant multinucleate cells. They may be encountered in any skeletal bones, mainly at the age of 20-30 years. A positive reaction with S-100 protein, d smooth muscle actin, and CD 34 was immunohistochemically detected in chondromyxoid fibroma tissue. In chondromyxoid fibroma, the prognosis is favorable. Recurrence of the tumor is observed in 15% of the surgically treated cases.

[Chondrosarcoma of the larynx].

Patients with chondrosarcoma of the larynx are diagnosed at the III-IV stages. Nevertheless, they have a relatively good prognosis. The tumor grows lowly, metastases develop late.

[Intraarticular chondromatosis].

Intraarticular chondromatosis is subdivided into primary (synovial) and secondary one. Synovial chondromatosis is a benign, focal proliferation of cartilaginous tissue within the synovial membrane of a joint, articular bursa and tendons. More often synovial chondromatosis is present in the synovial membrane. Some nodules loose a bond to the synovial membrane and form chondromal intraarticular bodies that are freely located within the joint cavity. Secondary intraarticular chondromatosis develops in the presence of a pre-existing process, such as injury, degenerative joint diseases including osteoarthrosis. In secondary intraarticular chondromatosis, loose intraarticular bodies are most commonly formed on the basis of a small disconnected fragment of hyaline articular cartilage.

[Ossifying fibromyxoid tumor].

Ossifying fibromyxoid tumor (OFMT) is a rare tumor of unknown histogenesis. It consists of chains and trabecules of ovoid cells in the fibromyxoid stroma (ICD code 8842/0). Tumor is frequently surrounded in part by a capsule of laminar bone. It is more frequent in males 14-79 years of age, mean 44 years. Soft tissues of extremities is a preferable location, but body, neck, oral cavity, mediastinum and retroperitoneal tissue can also be the site of OFMT. More than 100 OFMT cases are reported abroad. It is frequently masked by other tumors of soft tissues. We describe 3 cases in our country: 2 in 65 and 66 year old females and in a 44 year old male. Lipoma and soft tissue sarcoma were suspected clinically. Fibroblasts were found cytologically before operation in one case. Diagnosis was established after total biopsy of the tumor. One of the females is under observation after the operation without recurrence during more than two years. Preoperative diagnosis is sometimes possible when characteristic osteoblastic foci are observed.

[Gangliocytic paraganglioma of the duodenum].

Gangliocytic paraganglioma in a female of 64 years of age with stones in the gall bladder, atrophic liver cirrhosis and gastro-intestinal polyposis is described in the Russian literature for the first time. Polyps of the rectum and sygmoid were removed within 15 years. The same pathology was described by other authors. It is possible that the occurrence of paraganglioma and polyps was of genetical nature. The tumor was detected at gastroduodenoscopy. Biopsy diagnosis varied from polymorphocell liposarcoma and malignant fibrous histiocytoma. Endoscopic tumor electroexcision was complicated by intestinal bleeding that followed by an urgent laparatomy, duodenotomy and suture of the bleeding vessel in the duodenal wall. Bleeding zone in the duodenum was 3 cm from papilla Vateri. Analysis of difficulties in clinical and morphological differential diagnosis is performed.

[Adamantinoma of long tubal bones].

Four cases of adamantinomas of the long tubular bones, ulna and femur among them which rarely occur in patients aged 18-64 years (one female) are reported. A late metastasis to the sacrum was observed in one case. Typical diagnostic errors are described. Electron microscopy data are provided. Immunohistochemistry helps in differential diagnosis of this tumor. Histology does not give too much for the prognosis, radical resection does not influence the incidence of recurrences and metastases. The surgeons should be warned against enucleation of the tumor.

[Extraovarian malignant Brenner tumor]. / Ekstraovarial'naia zlokachestvennaia opukhol' Brennera.

Extraovarian malignant Brenner tumour in a female of 35. Rapid infiltrating growth with the destruction of tumour. All extraovarian tumours described so far were benign, located in the mesosalpinx, uterus or vagina. In this case the starting point of the tumour was in the vagina wall or in the recto-vaginal septum. Histological picture produced difficulties in establishing histogenesis of malignancy. The true nature of the tumour was established only immunohistochemically.

[Short-term preservation of venous transplants and evaluation of their viability]. / Nedlitel'naia konservatsia venoznykh transplantov i otsenka ikh zhiznesposobnosti.

A method for short-term (7 days) storage of venous grafts was developed. The grafts were stored in 2% solution of neutral formaldehyde and isotonic buffer solution (Henks' solution). The viability and tissue metabolism were studied in grafts taken from 54 patients who underwent operation for primary varicosity of the lower limb veins without trophic disorders. Light and electron microscopy as well as biochemical tests showed that grafts stored in Henks' solution maintain viability for up to 7 days, while those stored in a 2% neutral formaldehyde solution for 2 days cannot be used as allografts in reconstructive operations on the lower limbs.