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.

Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

Neutrophilic phagocytosis by tumor cells. A feature to consider in the differential diagnosis in fine needle aspiration smears.

OBJECTIVE: To analyze neutrophilic phagocytosis by tumor cells in fine needle aspirate (FNA) smears from different types of tumor. STUDY DESIGN: A retrospective review of a total of 7 cases showing prominent neutrophilic phagocytosis by tumor cells in FNA smears during the period July 2003-December 2004. RESULTS: This feature was seen in malignant fibrous histiocytoma and poorly differentiated renal cell carcinoma in addition to giant cell carcinoma of the lung. CONCLUSION: Neutrophilic phagocytosis by tumor cells is seen in FNA smears and on cytomorphology. The differential diagnoses should include both pleomorphic sarcomas and carcinomas.

Pulmonary giant cell carcinoma: pathological entity or morphological phenotype?

AIMS: To evaluate the morphological spectrum and clinical significance of giant cell carcinoma and to assess the frequency of tumour giant cell production in a consecutive series of primary (non-giant cell) lung tumours. METHODS AND RESULTS: Forty-six cases of giant cell carcinoma of the lung were collated from two centres over a 12-year period. Giant cell carcinoma was found to be associated with areas of clear cell carcinoma, spindle cell carcinoma and showed trophoblastic differentiation (syncytiotrophoblastic giant cells and beta-human chorionic gonadotrophin immunopositivity) in 57%, 34% and 26% cases, respectively. 'Pure' giant cell carcinoma was identified in five (11%) cases. Eleven of the tumours contained diastase-resistant periodic acid-Schiff positive material and were separately designated as giant cell adenocarcinomas. Areas of squamous cell and neuroendocrine differentiation (as determined by chromogranin A and Leu-7 immunopositivity) were not found. The median survival for giant cell carcinoma (excluding the giant cell adenocarcinomas) was 18 months. Median survival was not adversely affected by the extent of tumour giant cell formation or by the presence of trophoblastic differentiation. Of 200 consecutive non-small cell lung carcinomas, tumour giant cells constituting < 10% of the tumour were identified in 32% of adenocarcinomas and 26% of squamous cell carcinomas. CONCLUSIONS: The presence of tumour giant cells in lung carcinoma does not, in itself, indicate a more aggressive tumour type, Giant cell carcinoma of the lung does not appear to be a distinct entity but a morphological phenotype expressed by a heterogenous group of tumours. We support and advocate the use of an encompassing term such as 'pleomorphic' or 'anaplastic' carcinoma for those tumours showing no specific differentiation pattern but which express diverse morphological features such as giant cell formation, clear or spindle cell change.

[Human tumor xenografted into SCID mice and human immune function reconstitution].

OBJECTIVE: In order to observe (1) The behavior of growth and metastasis of PG and PGPTS7 in SCID mice and human immune function reconstituted mice; (2) The ability of interleukin-6 autosecreted from PGTS7 in enhancing the anti-tumor activity of the peripheral blood lymphocytes (PBL). METHODS: Xenografting of PG and PGTS7 into the subepithelial space of the SCID mice, and in some of these animals, human PBL were administrated simultaneously into the peritoneal cavities. The latent period, taken rate, growth speed, volume of the grafted tumor, incidences of metastasis in lungs and lymph nodes and serum level of human immunoglobulin of the immunity reconstituted mice were examined. RESULTS: Although tumor growth had been detected in all the experimental animals, the latent period of grafted PGTS7 was postponed and the volume of tumor mass as well as the incidence of lymph node metastasis all became lower in the immunity reconstituted mice accompanied simultaneously with a higher serum level of human immunoglobulin (HIg). CONCLUSIONS: (1) The SCID mice are good as an appropriated hosts in studying the behavior of growth and metastasis of PG and PGTS7. (2) IL-6 autosecreted from PGTS7 stimulates the proliferation and promotes the activating of PBL. It seems also able to enhance the liberation of human immunoglobulin: to suppress the growth of tumor cells and to reduced the rate of lymph node metastasis.