The poor prognosis factors in G2 neuroendocrine tumor.

BACKGROUND: The G2 neuroendocrine tumors (NET) or well-differentiated neuroendocrine carcinomas (2010 WHO Classification of Tumours of the Digestive System) embrace different types of evolution despite the fact that they actually are included in the same group of prognosis based on mitotic count and the Ki-67 proliferation index. AIM: We studied the pathological and clinical aspects in patients with G2 NET. MATERIALS AND METHODS: This is a retrospective pilot observational study in patients admitted between January 2008 and January 2013 in "Constantin I. Parhon" National Institute of Endocrinology, Bucharest, Romania. They were evaluated based on the pathological report, imagistic scan, and neuroendocrine markers. RESULTS: Nine patients (female/male ratio: 5/4) with G2 NET were included (mean age at diagnosis 54.11 years). Surgery was performed in 66.66% of cases. 44.44% of tumors had unknown origin. 22.22% of patients had negative immunostain for chromogranin A. Synaptophysin was positive in all cases. Neuronal specific enolase (NSE) was performed in 44.44% of cases and it was positive in all these situations. 88.88% of patients had high neuroendocrine markers. Multiple tumors were found in two cases (follicular thyroid adenoma, and a carcinoma of the port vein, respective bilaterally pheochromocytomas). The youngest patient (39-year-old) had atypical onset with bilateral adrenal tumors (positive for CHROMO, EMA, CK-19, CK-20, negative for SOMATO, CK-7, S-100, glucagon, CD57, and a Ki-67 of 15%). Death was registered in two cases, both with bone metastases. DISCUSSION: Some poor prognosis factors may be taken into account as lack of CHROMO immunostain, young age at diagnosis, genetic background, and lack of therapy options as surgery. Larger databases will provide more information. CONCLUSIONS: It is possible that the G2 NET group of tumors actually includes some different subtypes or in fact, a late diagnosis of the tumor might be associated with a poor diagnosis.

The dedifferentiation of neuroendocrine tumor metastases: myth or reality?

Dedifferentiation is a process that may be found in metastasis from the neuroendocrine tumors. We present the case of a female within the seventh decade of life incidentally diagnosed with a mature teratoma with element of cartilages, bronchia, mucinous glands, and a poorly differentiated neuroendocrine carcinoma (Ki67 of 30%). After six months of chemotherapy and another six months of disease free interval, a metastasis of the great omentum was removed. The dedifferentiation was diagnosed based on much higher Ki67 (of 70%). The loss of estrogen receptor of 40% from the initial site to 3% into metastasis indicates an exclusive neuroendocrine aggressive pattern. The ovarian carcinoid is a rare situation, and metastasis to the great omentum with dedifferentiation is even seldom.

Well-differentiated neuroendocrine tumor and osteoporosis: incidental findings?

The neuroendocrine tumors (NETs) have an increased incidence related to the age. Secondary osteoporosis might be found in patients with bone metastases and in those with NETs associated Cushing's disease or primary hyperparathyroidism. Primary osteoporosis might be found in postmenopausal women, but in case with non-metastatic NET as G1 NET it is difficult to establish the NET contribution to the bone loss. We present the case of a 53-year-old female accidentally diagnosed with G1 lung NET after surgery of the tumor. The immunohistochemistry pointed positive reaction for CHROMO, SYN and negative for CK7 and TTF1, and a Ki67 of 1-2% (well-differentiated neuroendocrine tumor). The central Dual X-Ray Absorptiometry (DXA) showed osteoporosis based on a T-score of -3. The patient had normal neuroendocrine markers and she was asymptomatic. She remained so for one year and the only therapy provided was weekly alendronate with adequate vitamin D and calcium supplements. Based on the pathological and immunohistochemistry profile, the low risk NET was diagnosed. We encourage the skeletal status assessment as central DXA in postmenopausal women with NETs, regardless clinical evidence of bone loss. The future will provide more epidemiological and pathogenic connections between the two dynamic fields of medicine as neuroendocrine tumors and osteoporosis.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

The value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis.

Thyroid metastasis is atypical. We present a 70-year-old female case that was first diagnosed as gastric cancer after surgical approach. Two years later a thyroidectomy was performed and the immunohistochemistry (IHC) profile revealed a neuroendocrine tumor (NET): poorly differentiated neuroendocrine carcinoma (with small cells), with positive reaction for SYN, CROMO, negative for calcitonin, TTF1 and thyreoglobulin. The Ki-67 index was 25%. Considering the unusual metastasis, the IHC exam of the stomach tumor was performed pointing the same features as the thyroid findings. This proved that the thyroid tumor was a metastasis from a primary gastric neoplasia. This is an unusual case of NET because of the thyroid involvement. Nevertheless, the IHC exam played the major role in elucidating the diagnosis and the prognosis of the case.

Contributions to myometrium study in uterine-tubal junction.

Complex coordinated contractions of the tubal musculature are thought to be important for movement of the ovum from the distal end to the proximal end of the tube, while at the same time aiding in the movement of sperm from the proximal end to the distal end of the oviduct. Studies of the anatomy and the physiology of the uterine-tubal junction (UTJ), with a main concern for the muscular pattern and the secretory activity of this part of the tube, in relation with the hormonal and nervous control, can play an important role in understanding and impairment of infertility. Related to these aspects, the purpose of our research is mainly to identify the determining factors in maintaining a morphological and structural balance between contractile items and extracellular matrix items within uterine myometrium, particularly uterine-tubal junction. For this reason, the present study includes analyses of anatomical sections within uterus and uterine tubes extracted from patients during therapeutic surgeries. Thirty anatomical pieces from patients aged 23-37-year-old (uterus and tubes) were used to perform microanatomical sections, 10 pieces for each pathology identified, namely leiomyofibroma, leiomyofibroma with pregnancy, ectopic pregnancies. At the same time, the study proposes a statistic and mathematic analysis of the cases with uterine-tubal junction pathology in Oltenia region within a period of 10 years. The novelty of the study is represented by the identification of certain continuity ratios between myocyte fascicles and average tunica of arteries and arterioles, which explains the existence of "vascular units" determined by myometrial structures. Moreover, the stereo-distribution of "vascular myometrial units" explains the existence of a plexiform cavernous network, which enables many authors to describe numerous barely individualized myometrial tunicas. These units are rich in orthosympathetic vegetative innervations that might be responsible for the unfavorable evolution of circulatory myometrial system in postpartum. Considering all these observations, it is highly necessary to reconsider the structure of the uterine wall and, particularly of uterine-tubal junction.