[CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases]. / Mutatsii v gene CDC73 u molodykh patsientok s pervichnym giperparatireozom (opisanie dvukh klinicheskikh sluchaev).

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

Hyperparathyroidism-jaw Tumor Syndrome: An Overlooked Cause of Severe Hypercalcemia.

Ossifying fibromas of the maxillofacial bones are an uncommon form of benign neoplasm usually treated by surgical excision. Up to 30% of patients with hyperparathyroidism-jaw tumor syndrome, a rare form of multiple endocrine neoplasia resulting from autosomal dominant inactivating mutation of the Hrpt2 tumor suppressor gene, initially present with ossifying fibromas. Coincident hypercalcemia because of the presence of parathyroid adenoma is common in these patients, of whom 15% may have or may develop parathyroid carcinoma. The authors present a case of severe postsurgical hypercalcemia after removal of a large maxillary ossifying fibroma in a patient with previously unrecognized hyperparathyroidism-jaw tumor AU3 syndrome.

Two cases of multiple ossifying fibromas in the jaws.

BACKGROUND: The clinicopathologic characteristics of multiple ossifying fibroma (OF) are unclear due to the condition's rarity, making diagnosis challenging. Sporadic multiple OFs must be distinguished from hyperparathyroidism-jaw tumour syndrome (HPT-JT) related OF and other fibro-osseous lesions. METHODS: Multiple OF cases were identified from ossifying fibroma cases. Clinical data including age, sex, anatomic site, radiographic features, clinical impression, treatment and available follow-up data as well as serum calcium, phosphorus, and parathyroid hormone (PTH) were recorded. GNAS and HRPT2 genetic mutations were examined in the two present cases. Case reports of sporadic multiple ossifying fibroma and HPT-JT-related OF were also reviewed. RESULTS: The two present cases were confirmed as sporadic multiple OF, with no genetic GNAS and HRPT2 mutations found. The incidence of sporadic multiple ossifying fibroma was 2.0% (2/102). The total 18 sporadic multiform OF cases were characterized as followed: 13 (72.2%) female; 5 (27.8%) male; mean age 28.6 years; 2/16 (11.1%) cases only in the mandible; 4/18 (22.2%) cases only in the maxilla; and 12/18 (66.7%) cases in both the maxilla and mandible. Radiographically, the lesions were radiolucent in 5/18 (27.8%) cases and mixed density in 13/18 (72.2%) cases. Along with 24 cases of HPT-JT related OF were reviewed, sixteen (66.7%) patients were diagnosed with a single lesion, and 8 patients (33.3%) were diagnosed with multiple jaw lesions. CONCLUSIONS: Sporadic multiple OFs are very rare, but must be distinguished from HPT-JT related OF. We strongly recommend that patients diagnosed with multiple ossifying fibromas receive serum PTH testing and mutation screening of HRPT2. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/1194507146115753.

The oxidant/antioxidant status and cell death mode in oral squamous cell carcinoma.

OBJECTIVE: Oxidative stress and imbalance in the oxidant/antioxidant system have a critical role in carcinogenesis by affecting necrosis and apoptosis. The aim of this study is to evaluate the oxidant/antioxidant status and cell death modes in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Twenty-nine patients with OSCC and 29 control subjects were included in the study. The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP) were determined in plasma samples of all subjects. The necrotic and apoptotic cell death modes were evaluated with M65 ELISA and M30 ELISA, respectively. RESULTS: MDA and AOPP values as oxidative stress markers were higher in patients with OSCC than in the control group. FRAP values evaluating plasma antioxidant status increased in OSCC patients. M65 and M30 levels indicating necrosis and apoptosis were significantly higher in OSCC patients compared to controls. There were significant correlations between MDA, AOPP and FRAP; M65 and M30 values. CONCLUSIONS: The elevated levels of oxidative stress markers together with the increase of antioxidant capacity and the presence of a strong correlation between MDA, AOPP and FRAP suggest an activation of antioxidant defense against accentuated oxidative stress determined in OSCC. Enhanced oxidation of lipids and proteins may cause decomposition of cell membranes with subsequent leakage of cytoskeletal cytokeratins as CK18 and caspase-cleaved CK18 (evaluated as M65 and M30, respectively) in the circulation, suggesting that both cell death modes are affected in OSCC.

Comparative study of inhibitory effects by murine interferon gamma and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK).

The inhibitory effect of murine interferon gamma (muIFN gamma) on humoral hypercalcemia in nude mice bearing lower-jaw cancer (LJC-1-JCK), in which parathyroid-hormone(PTH)-related protein is responsible for causing humoral hypercalcemia by activating bone resorption, was examined in comparison with that of a new bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). muIFN gamma was injected into tumor-bearing nude mice for 5 days before the establishment of hypercalcemia. The increase of plasma calcium concentration was delayed and this effect continued for more than 6 days even after the injection was stopped. Alendronate markedly suppressed hypercalcemia in tumor-bearing nude mice but this inhibitory effect continued for less than 6 days. Neither muIFN gamma nor alendronate affected the tumor volume or serum PTH-related protein concentration. Injection of muIFN gamma into mice for 3 days almost completely abolished the formation of multinucleated osteoclast-like cells from bone marrow cells in vitro, whereas injection of alendronate into mice had no effect. These findings suggested that muIFN gamma suppressed the formation of osteoclasts, resulting in the prolonged decrease of plasma calcium concentration in hypercalcemic tumor-bearing nude mice, whereas alendronate is cytotoxic to functionally mature osteoclasts and inhibited osteoclastic bone resorption, resulting in a marked decrease in the plasma calcium concentration in tumor-bearing hypercalcemic nude mice.

Applicability of the general nutritional status score to patients with oral and maxillofacial malignancies.

The general nutritional status (GNS) score was used to assess the nutritional status of 127 consecutive patients with oral and maxillofacial malignancies. Forty-six of our patients (36.2%) were undernourished (group 2), while 81 (63.8%) were in good nutritional condition (group 1). Comparison of nutritional laboratory tests between these two groups showed that the differences in serum albumin, transferrin, and creatinine-height index (CHI) had statistical significance, yielding an excellent correlation between the GNS score and the nutritional laboratory test. Undernourished patients had a significantly higher postoperative complication incidence (48.3%) than well-nourished patients (19.4%) (chi 2 = 6.637; P < 0.01), indicating that the GNS score can be used as a prognostic index.

[Hemostatic changes in patients with tumors of the maxillofacial area]. / Izmeneniia gemostaza u bol'nykh s opukholiami cheliustno-litsevoi oblasti.

To study hemostatic impairments in patients with maxillofacial tumors, 131 patients and 30 healthy subjects were examined. The patients were found to develop early hemostatic changes which appeared as a latent DIC syndrome. The mobility of the physiological system of PASA permits the equilibrium of coagulative and anticoagulative mechanisms to be preserved to a definite extent and fairly long. The changes were detected during the formation of prothrombinase, thrombin and during fibrin formation and stabilization in the fibrinolytic system. Hypercoagulation typical of the DIC syndrome at the early stages of tumor was followed by consumption coagulopathic signs and profuse bleeding risk at the T4 and N3 stages.

[The use of blood phosphatidylinositol indices for the diagnosis of tumorous diseases of the maxillofacial area]. / Ispol'zovanie pokazatelei fosfatidilinozitov v krovi dlia diagnostiki opukholevykh zabolevanii cheliustno-litsevoi oblasti.

Phosphatidyl inositol levels were measured by flow thin-layer chromatography in red cells, platelets, lymphocytes, plasma, and whole blood of 198 patients with maxillofacial malignant and benign tumors and in 50 donors. Phosphatidyl inositol levels in the blood and its fragments were found reduced twofold in the patients with malignant tumors as against controls. Reduction of blood phosphatidyl inositol level to 185 +/- 11.0 mol of phosphatidyl inositol phosphorus per liter evidences the presence of a malignant tumor in the maxillofacial area in 97.6% of cases, this being confirmed by x-ray and histologic findings.

Fibrinolytic activity in cystic lesions of jaw bones.

The fibrinolytic activity in the tissues of cystic lesions of jaw bones was investigated by the semiquantitative method of Astrup. The specimens examined were ameloblastoma (9 cases), follicular cyst (8 cases) and radicular cyst (14 cases). High fibrinolytic activity was observed in ameloblastoma, while in radicular cyst the activity was variable. It is suggested that in radicular cyst inflammatory episodes play an important role in activating local fibrinolysis, while in ameloblastoma the tissue itself has a great capacity to induce locally activated plasmin.