Ovarian fibroma/fibrothecoma with elevated serum CA125 level: A cohort of 66 cases.

Ovarian fibroma/fibrothecoma with elevated serum OC125 antigen (CA125) is rarely encountered in clinical practice, and also easily misdiagnosed as epithelial ovarian carcinoma (EOC). The aim of this study was to investigate the clinicopathological features of ovarian fibroma/fibrothecoma with elevated serum CA125.In total, 580 patients who underwent primary surgery and pathologically diagnosed as ovarian fibroma/fibrothecoma were retrospectively analyzed. The clinicopathological parameters were collected and compared between the patients with elevated serum CA125 (>35 U/mL) and without. The immunoreactivity for CA125 in ovarian fibroma/fibrothecoma and epithelial cancer tissues was detected and compared by immunohistochemistry. Univariate and multivariate analyses were performed to identify factors associated with elevated serum CA125 level. The correlation between the immunoreactivity of CA125 in tissue and serum CA125 level was examined by Pearson correlation analysis.Elevated serum CA125 level (range 36.7-1848 u/m) was found in 66 of 580 (11.3%) ovarian fibroma/fibrothecoma patients. Univariate analysis showed that the elevated serum CA125 level was significantly correlated with tumor diameter ≥10 cm (P < .001), ascites (P < .001), and hydrothorax (P < .001). Multivariate analysis revealed that tumor diameter ≥10 cm and ascites were independently associated factors (P < .001 and < .001 respectively). Immunohistochemical staining showed that the expression of CA125 was negative in all fibroma/fibrothecoma tissues, but positive in all EOC tissues, and the immunoreactivity for CA125 was positively correlated with serum CA125 level in the EOC patients (P = .005).The elevated serum CA125 level in ovarian fibroma/fibrothecoma is nontumor originated and occurs more frequently in those with larger size tumor or Meigs syndrome.

[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.

Vestibulodynia: A Multifactorial Syndrome: A Case Report.

BACKGROUND: Vulvodynia is a difficult-to-treat, chronic, multifactorial malady that drastically lowers the quality of life of afflicted patients. CASE: A 68-year-old woman, who had been treated successfully for vulvodynia years before with medication, returned with a recurrence of vulvodynia symptoms that this time did not respond to treatment. She now had biopsy-confirmed lichen sclerosis and was found to have markedly elevated serum testosterone levels. An imaging study detected an ovarian lesion that, on removal, proved to be afibrothecoma. Postoperatively the testosterone rapidly dropped to normal levels. What was unexpected and unusual was that the vulvar pain disappeared and the lichen sclerosis markedly regressed. CONCLUSION: This case demonstrates a hormonal trigger for the development of vulvodynia.

Mitotically active cellular fibroma of the ovary: a case report and a review of the literature.

Mitotically active cellular fibroma (MACF) is characterized by increased cellularity, mitotic activity, and less frequently, nuclear atypia, which comprises 10% of ovarian fibromatous tumors. The authors report the case of a 76-year-old woman who presented at the present hospital with a two-month pelvic mass. B ultrasound disclosed a 75 x 52 x 41 mm mass in the right accessories. A hysterectomy and bilateral salpingo-oophorectomy was performed. Histologically, the tumor was composed of a densely cellular proliferation of fibrolastic-like cells with bland nuclear features and arranged in a fascicular pattern. There were more than four mitotic figures per ten high-power fields (HPFs). The histological diagnosis for the mass of the right ovary was MACF. MACF should be distinguished from ovarian fibrosarcoma. MACF is a recent histopathologic entity. Despite the high count of mitotic figures, the clinical course of the tumor is typically uneventful. Long-term clinical follow-up is recommended.

PTCH1 gene polymorphisms in ovarian tumors: potential protective role of c.3944T allele.

In this study we investigated the types and role of different genetic changes of PTCH1 gene in three different types of ovarian tumors: carcinomas, fibromas and dermoids. LOH of the PTCH1 region was detected in 27.3% ovarian carcinoma samples, 18.18% ovarian fibroma samples and 55.56% ovarian dermoid samples. No point mutations were detected in any of the three types of ovarian tumors. SNP c.3944C>T showed significant differences between ovarian carcinoma and control samples with the minor T allele being significantly higher in controls compared to ovarian carcinomas. Interestingly, a new polymorphism c.-1184G>A was found only in tumor samples and further analyses should be performed in order to elucidate its potential role in ovarian tumors.

Mitotically active cellular ovarian fibroma with Meigs' syndrome and elevated CA-125: towards fertility preservation.

BACKGROUND: Meigs syndrome is rare in women under 30 years of age and even more if associated with an elevated CA-125. In this case, malignancy was suspected and raised concerns about fertility preservation. CASE: A 13-year-old girl presented with a 4-month amenorrhea, abdominal enlargement and dyspnea. Ultrasonography showed a 14-cm solid mass with ascites, bilateral pleural effusion and, analytically, elevated serum CA-125. Unilateral salpingo-oophorectomy was performed, with a 19 × 15 × 12 cm mass being disclosed from the right ovary. Final pathology diagnosed a mitotically active cellular ovarian fibroma (MACF), with no significant nuclear atypia. CONCLUSION: MACF is a recent histopathologic entity. Despite the high count of mitotic figures, it is not associated with atypia, which contributes to favorable outcome. Although initial suspicions of malignancy, a conservative surgical intervention allowed fertility preservation. This was clinically appropriate and with no implications on survival and prognosis of these patients.

Ovarian fibroma with marked ascites and elevated serum levels of CA-125 in a young girl.

We report a case of ovarian fibroma with marked ascites and elevated serum CA-125 levels in a young girl. Ovarian fibromas are rare in children. They usually present as a solid mass and may be associated with ascites and elevated serum CA-125 levels. Because of their solid nature and these associations, they can be mistaken for a malignant tumor, resulting in unnecessary oophorectomy. Ovarian fibromas are benign neoplasms, and the prognosis is extremely good. Surgical management should be an ovarian-sparing tumor excision. Although uncommon in pediatric patients, ovarian fibromas should be included in the differential diagnosis of ovarian mass in children.

Hematological profile of Chelonia mydas (Testudines, Cheloniidae) according to the severity of fibropapillomatosis or its absence / Perfil hematológico de Chelonia mydas (Testudines, Cheloniidae) de acordo com o grau de acometimento pela fibropapilomatose e sua ausência

The green turtle Chelonia mydas feeds and nests in the Brazilian coastal area and is considered an endangered species by the World Conservation Union (IUCN 2009) and threatened by the Red List of Brazilian Fauna (Ministério do Meio Ambiente 2009). Fibropapillomatosis is a disease characterized by benign skin tumors (fibropapillomas), and it is one of the main threats to the survival of this species. Studies suggest the involvement of viruses as infectious agents associated with environmental and genetic factors. Blood samples were collected from 45 turtles captured in the coastal area of the state of Sao Paulo, Brazil. From these, 27 were affected by fibropapillomas and 18 were tumor free. Biometrical data on the turtles, size, location and quantity of tumors were recorded. The area occupied by fibropapillomas per animal was calculated and four groups were determined according to severity of the disease or its absence. The objective of the study was to compare hemogram results of the sea turtles classified in these four groups. The lowest hematocrit value was observed in severely affected animals. In the hemoglobin assay, the highest value was observed in the group of tumor free turtles and the lowest, in animals severely affected. Lymphocyte counts and curved carapace length were on the verge of statistical significance.

Chelonia mydas, denominada tartaruga verde, é uma tartaruga marinha que frequenta o litoral brasileiro para alimentação e nidificação e é considerada em perigo de extinção pela IUCN (World Conservation Union, 2009) e ameaçada pela Lista Vermelha da Fauna Brasileira (Ministério do Meio Ambiente, 2009). A fibropapilomatose, doença caracterizada por tumores cutâneos benignos (fibropapilomas), é uma das mais importantes ameaças à sobrevivência dessa espécie. Pesquisas sugerem o envolvimento de agentes infecciosos virais em associação com fatores ambientais e genéticos. Foram colhidas amostras sanguíneas de 45 tartarugas provenientes do litoral do estado de São Paulo, Brasil, sendo 18 sem fibropapilomas e 27 acometidas. Dados de biometria das tartarugas, quantidade, localização e tamanho dos tumores foram anotados. Foi realizado o cálculo da área de fibropapilomas por animal e foram estipulados 4 grupos de acordo com o grau de acometimento e sua ausência. O objetivo foi realizar uma comparação entre os hemogramas das tartarugas marinhas classificadas nos 4 grupos. Animais de grau grave apresentaram o menor valor para hematócrito. Para dosagem de hemoglobina, observou-se que o maior valor foi para o grupo de tartarugas sem fibropapilomas e o menor para o de grau grave. Os valores de linfócitos e comprimento curvilíneo da carapaça beiraram a significância estatística.

[Correlation of peripheral blood micrometastasis to distant metastasis of breast cancer].

BACKGROUND & OBJECTIVE: Breast cancer, a whole body disease, can metastasize at early stage. This study was to explore the correlation of peripheral blood cancer cell (PBCC) content to distant metastasis of breast cancer. METHODS: The PBCC content of 65 breast cancer patients and 8 healthy donors was detected by multi-parameter flow cytometry (FCM) with CD45 and cytokeratin staining. RESULTS: Cancer cells were detected in peripheral blood samples from 57 of the 65 patients; the positive rate was 87.7%. No cancer cell was found in peripheral blood samples from healthy donors. The positive rate of PBCCs was correlated to T stage (r=0.271,P=0.017) and N stage (r=0.393, P=0.002). The patients were followed for 5 years; 2 were lost. Distant metastasis was found in 25 patients with PBCCs. In contrast, no metastasis was found in 8 patients without PBCCs (P<0.05). CONCLUSION: Preoperative PBCC content is closely related to distant metastasis of breast cancer. The detection of PBCCs might be useful for individual treatment decision for breast cancer.

Pre-operative differentiation of pediatric ovarian tumors: morphological scoring system and tumor markers.

OBJECTIVE: To investigate the importance of morphological scoring systems in differentiation of ovarian tumors in childhood. METHODS: Morphological assessment using DePriest's index was performed for all patients with histopathological confirmation of ovarian tumor, with evaluation of tumor markers, from January 1997. RESULTS: Fifty-three girls (age range 13 months to 19 years) were surgically treated for 59 ovarian tumors, including six bilateral. All lesions with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and four of ten solid tumors were also benign. Stage of malignant disease was as follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive predictive value and accuracy by DePriest's and Ueland's indexes for benign tumors (score <7) were: 0.88, 0.79; 0.89; and 0.94, 0.84; 0.93; respectively. Elevated levels of tumor markers were observed in 17 patients, including four patients with endocrine manifestations. In 24 patients ovaries were successfully preserved, including two patients with foci of immature teratoma in a dermoid cyst. CONCLUSION: Ultrasonographic assessment with morphological analysis recommended by DePriest and Ueland is a very useful procedure for differentiating benign from malignant ovarian tumors in children. Tumor markers and endocrinological investigation are also useful for preoperative evaluation.

Serum concentration of AMDL DR-70 for the diagnosis and prognosis of carcinoma of the tongue.

The aim of this study was to discover the clinical value of the tumour marker AMDL DR-70 in a group of patients with cancer of the tongue. Serum concentrations of AMDL DR-70 were estimated by enzyme linked immuno-sorbent assay in 52 patients with carcinoma of the tongue and compared with 40 controls and 42 patients with benign lesions in the tongue. Thirty-nine patients with carcinoma of the tongue had results above 6 mg/L (75%), compared with 3/40 (7%) in healthy controls and 4/42 (10%) in those with benign tumours. The concentration of AMDL DR-70 in serum correlated significantly with 3-year survival.

Biochemical responses to fibropapilloma and captivity in the green turtle.

Blood biochemical parameters were compared for green turtles (Chelonia mydas) with and without green turtle fibropapillomatosis (GTFP) from both captive and wild populations in Hawaii (USA) and from a captive population from California (USA), during the period between 1994 and 1996. Statistical analysis did not detect an influence of disease in any of the blood parameters for free-ranging turtles; however, captive turtles in Hawaii with GTFP had significantly higher levels of alkaline phosphatase and significantly lower levels of lactate compared to non-tumored captive turtles. Multivariate analysis found that biochemical profiles could be used to accurately predict if turtles were healthy or afflicted with GTFP. Discriminant function analysis correctly classified turtles as being with or without GTFP in 89% of cases, suggesting that diseased animals had a distinct signature of plasma biochemistries. Measurements of blood parameters identified numerous differences between captive and wild green turtles in Hawaii. Levels of corticosterone, lactate, triglyceride, glucose, and calcium were significantly higher in wild green turtles as compared to captive turtles, while uric acid levels were significantly lower in wild turtles as compared to captive turtles. Additionally, turtles from Sea World of California (San Diego, California, USA), which had been in captivity the longest, had higher levels of alanine aminotransferase and triglycerides as compared to nearly all other groups. Differences in diet, sampling methods, environmental conditions, and turtle size, help to interpret these results.

Tumor-related osteomalacia followed after treatment by hyperparathyroidism.

Tumor-induced osteomalacia is due to renal phosphate wasting in response to a humoral factor produced by a tumor, usually a benign mesenchymal tumor. Removal of the tumor is followed by resolution of the metabolic disorder. Physicians should be aware that sporadic renal phosphate wasting in an adult should prompt a search for a tumor. A case of tumor-induced osteomalacia due to a nonossifying fibroma of the radius is reported. After removal of the tumor, renal phosphate excretion returned to normal, but the patient developed tertiary hyperparathyroidism. Eight years elapsed between symptom onset and the diagnosis of the tumor. The pathogenesis of tumor-induced osteomalacia and the role of treatment for renal phosphate wasting on the subsequent development of hyperthyroidism are discussed.

Study of serum big-insulin-like growth factor (IGF)-II and IGF binding proteins in two patients with extrapancreatic tumor hypoglycemia, using a combination of Western blotting methods.

Extrapancreatic tumor hypoglycemia (EPTH) is associated with increased amounts of high-molecular-weight precursor forms of insulin-like growth factor (IGF)-II ('big-IGF-II') that have a primary role in the pathophysiology of hypoglycemia. In the present study, using Western ligand and immunoblotting methods, we investigated IGF-binding proteins (IGFBPs), IGFBP-3 proteolysis and big-IGF-II in pre- and postoperative serum from two patients with EPTH due to benign pleural fibroma. In the preoperative serum, IGFBP-3 was reduced and IGFBP-2 was increased compared with that from an age-matched healthy control. IGFBP-3 proteolysis was dramatically reduced in one patient, whereas no major alteration was observed in the other (9% and 120% of control serum, respectively). IGFBPs progressively returned to a subnormal pattern in postoperative serum, whereas IGFBP- 3 proteolysis remained greater than in preoperative serum in both patients at days 14 and 90 after surgery. High-molecular-weight forms of IGF-II predominate in EPTH serum (65% and 57% of total IGF-II immunoreactivity in patients 1 and 2, respectively, compared with 2 5% in control serum). Two forms, of molecular mass 10 and 12 kDa ('standard big-IGF-II') were present in both EPTH and control sera, whereas two additional forms, of molecular mass 15 and 18 kDa ('big big-IGF-II') were observed in EPTH sera only. Big big-IGF-II represented 72% and 55% of total high-molecular-weight forms of IGF-II in the two EPTH sera, respectively. All big forms of IGF-II disappeared from the serum as early as 6 h after surgery. This study shows that combination of simple Western blotting methods, available routinely in most laboratories, should prove useful in providing reliable physiopathological information in EPTH.

Gonadotrophins and prolactin rise after bilateral oophorectomy for benign conditions.

The aim of this study was to analyse the changes in follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin concentrations in the 3 months following oophorectomy in pre-menopausal women operated on for benign gynaecological conditions. Included in this analysis were 21 women (mean age 47 years, range 46-52) who underwent bilateral oophorectomy plus hysterectomy for fibroids or ovarian cysts. Plasma concentrations of FSH, LH and prolactin were measured before and on days 2, 4, 6, 14 and 30 after surgery; in 10 cases measurements were made on day 60, and in five cases on day 90 after surgery. Hormone concentrations were measured in duplicate daily samples, and immunoenzymatic assay kits were used for all the immunoassays. The FSH and LH concentrations increased constantly after surgery. Mean prolactin concentrations also increased from 12.1 ng/ml before surgery to 31.5 ng/ml on day 14 after bilateral oophorectomy, but decreased thereafter to 18.2 ng/ml on day 30, 10.9 ng/ml on day 60 and 6 ng/ml on day 90. In conclusion, transient (2-3 weeks) increased prolactin concentrations are observed after surgical castration.

Identification of antibodies against human papillomavirus type 16 E4 and E7 proteins in sera of patients with cervical neoplasias.

Sera from 35 women (patients with various clinical diagnosis: cervical dysplasia, benign and malignant tumors of the uterine cervix) were tested by immunodot blot for the presence of antibodies to E4 and E7 HPV16 proteins. A number of 26 sera displayed positivities for at least one antibody type. The mean absorbance for anti-E antibody in positive cases was higher in cancer patients (15 from 16 sera) as compared with other diagnoses (2 from 5 in dysplasia or one from 4 in uterine fibroma). Interestingly, most sera were reactive for both proteins. The high prevalence rates and high absorbance values for HPV16 E7 antibodies in association with malignant transformation suggest that the detection of these antibodies may be a useful diagnostic aid for cervical cancer--associated HPV16.