Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients.

BACKGROUND: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. PATIENTS AND METHODS: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P=0.03), lymph nodal involvement (P=0.002), and PML expression (P=0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P=0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P=0.003) and the only statically significant prognostic factor for OS (P=0.009). CONCLUSIONS: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.

Characteristics at haematoxylin and eosin staining of ruptures of the long head of the biceps tendon.

OBJECTIVE: To examine the relative prevalence of histological changes that have been found to be associated with the process of tendinopathy in lesions of the tendon of the long head of the biceps brachii and to evaluate the reliability of histopathological evaluation of tendon tissue in lesions of the tendon of the long head of the biceps. DESIGN: Tendon samples were taken from 51 patients (31 men, 20 women; mean age 63.2 years) who underwent arthroscopic release of the long head of the biceps tendon because of refractory biceps tendinopathy and from 5 male patients who died of cardiovascular events (mean age 69.6 years). Histological examination was performed using haematoxylin and eosin staining of sections, which were interpreted using a semiquantitative grading scale assessing fibre structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen staining and hyalinisation. RESULTS: The mean (SD) pathological sum score of ruptured tendons was greater than that of control tendons (15.76 (3.11) vs 3.4 (1.9), p<0.001). Within each specific category of tendon abnormalities, the chi(2) test showed significant differences between the control and ruptured tendons; all the variables were significantly different (Mann-Whitney U test 0.05, p<0.001). Using the kappa statistic, the agreement between the two readings ranged from 0.53 to 0.85. CONCLUSIONS: Unruptured tendons of the long head of the biceps, even at an advanced age and ruptured tendons of the long head of the biceps are clearly part of two distinct populations.

Human equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.

BACKGROUND: Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. MATERIALS AND METHODS: We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. RESULTS: In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor-node-metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). CONCLUSIONS: hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux. AIM: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter. METHODS: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year. RESULTS: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls. CONCLUSIONS: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.

Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer.

AIMS: The histological modification produced by neoadjuvant chemoradiation on primary rectal cancer has been investigated by many authors, and a prognostic value of tumor regression grade (TRG) has been identified. Tumor regression grade on metastatic mesorectal lymphnodes has been never evaluated. The purpose of this study is to analyse the TRG on mesorectal lymphnodes (lymphnode regression grade, LRG) after preoperative chemoradiation in rectal cancer patients and to determine the correlation with TRG of primary tumor. METHODS: Surgical specimens from 35 patients who underwent chemoradiation were included. LRG on mesorectal lymphnodes was assessed by immunohistochemistry. Response to treatment was evaluated by a 5-point LRG based on the ratio of residual tumor to fibrosis. RESULTS: Complete pathologic response (LRG 1) was observed in 18 patients (51%). In 4 patients (11%) no regression was observed (LRG 5). In 4 cases only reactive lymphnodes were found. LRG on lymphnodes significantly correlated with TRG on primary tumor (p<0.05). CONCLUSIONS: Neoadjuvant chemoradiation determines a tumor regression on mesorectal lymphnodes as on primary tumor; further studies are needed to evaluate the prognostic value of LRG.

COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables.

BACKGROUND: There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis. OBJECTIVE: To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas. METHODS: Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies. RESULTS: COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density. CONCLUSIONS: COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.

Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer.

BACKGROUND: Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks. AIM: To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas. METHODS: Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70-Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls. RESULTS: A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins. CONCLUSIONS: Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.

Complementary use of local excision and transanal endoscopic microsurgery for rectal cancer after neoadjuvant chemoradiation.

BACKGROUND: Neoadjuvant therapies have significantly improved local control and survival of patients with rectal cancer. Nevertheless, although a complete pathologic response can be achieved in 30% of cases, a transabdominal surgical resection is always required. This study aimed, for the first time, to test in the literature the feasibility of local excision combined with transanal endoscopic microsurgery (TEM) as a surgical option for patients treated with neoadjuvant chemoradiation. METHODS: Between July 1997 and December 2002, 30 patients with rectal cancer affected by an extraperitoneal tumor entered a protocol consisting of neoadjuvant chemoradiation followed by surgery. The surgical treatment, consisting of open surgery, local excision, or TEM, was planned according to the patient's clinical response after chemoradiation and distance from the anal verge. RESULTS: A significant clinical downstaging was observed in eight patients. Five of these patients underwent TEM, and three had local excision. Consequently, open surgery was performed for 22 patients. Histology showed six cases of complete pathologic response: three in the open surgery group and three in the transanal excision group. After a mean follow-up period of 47 months, the disease-free survival rate was 77% in the open surgery group and 100% in TEM or local excision group. CONCLUSIONS: The findings suggest the complementary feasibility of TEM and local excision after neoadjuvant chemoradiation. However, randomized trials are needed to confirm the oncologic safety of this approach.

Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.

To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies.

The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80 DNA-binding activity in human tumors. Heterodimer DNA-binding activity and protein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers. Corresponding normal tissues of the same patients were used as controls. Ten out of 15 tumors showed nuclear Ku-binding activity 3-10 times higher than in the normal tissues, irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and in all the metastatic nodes analysed, nuclear Ku-activity was 1.5-4.5-fold lower than in the corresponding normal tissues. Cytoplasmic heterodimer activity significantly differed between tumor and normal tissues, displaying a 2-10-fold increase in neoplastic tissues. Three different patterns combining both Ku expression and activity with tumor characteristics were identified. In low aggressive breast tumors p70/p80 proteins were expressed in tumor but not in normal tissues. The heterodimer binding-activity matched the protein levels. In non-invasive bladder carcinomas no significant differences in protein expression between tumor and the corresponding normal tissues were found, however heterodimer binding-activity was increased in tumor samples. In breast and bladder tumors, at the advanced stage and in node metastases, the binding activity was strongly reduced in tumor biopsies, however no differences were demonstrated between normal and tumor protein levels. Our results suggest a different modulation of Ku70/80 DNA-binding activity in human neoplastic tissues, possibly related to tumor progression. Findings provide further data on tissue-specific protein expression and post-translational regulation of heterodimer activity.

Tumour proliferation, angiogenesis, and ploidy status in human colon cancer.

AIMS: Tumour angiogenesis is essential for carcinogenesis and facilitates the process of tumour development and metastasis. Vascular endothelial growth factor (VEGF) is a well characterised angiogenetic factor and is known to play a crucial role in new vessel development. To gain further insight into the effects of microvessel density and VEGF expression in colon cancer, their relation with tumour proliferation, ploidy status, and p53 expression was investigated in colon cancer. METHODS: Tissue samples of 50 archived colon cancers were analysed by immunohistochemistry for VEGF, p53, and the endothelial cell marker, von Willebrand factor (VWF), using specific antibodies. The same samples were re-cut for flow cytometric studies to obtain S phase fraction (SPF) and ploidy status. RESULTS: A positive significant correlation was found between SPF and angiogenesis. The median microvessel count in high SPF tumours was significantly higher than in low SPF ones. No association was found between VEGF expression and SPF. A positive correlation was found between ploidy status and p53 expression and microvessel count. Furthermore, a positive correlation was established between DNA ploidy, VEGF expression, and microvessel count. CONCLUSION: This study provides evidence that in colon cancer, tumour growth may be stimulated by vascular supply, and the lack of a correlation between tumour cell proliferation and VEGF expression indicates that these two parameters may be regulated by separate mechanisms. Furthermore, the positive correlation between microvessel density, VEGF expression, and ploidy status provides more evidence that genetic alterations are involved in tumour angiogenesis.

Cutaneous lymphoadenoma: a rare clinicopathological entity.

Cutaneous Lymphadenoma (Benign Lymphoepithelial tumour of the skin) is a rare tumour, with distinctive clinical and histological features. To date, very few cases of this entity have been reported. We present a case of cutaneous lymphoadenoma in a 52-year-old man and a short review of the literature, summarizing the principal clinical and morphological characteristics of this rare tumour.

A rare case of solitary fibrous tumour of the pre-sacral space: morphological and immunohistochemical features.

A 28-year-old woman presented with abdominal pain. Ultrasonograhic examination showed a pre-sacral mass, with complex structure and well delimitated cystss with thick walls. The resected specimen was 7.5 x 6 x 4 cm in size, well circumscribed and yellow in colour, with cysstic change containing mucoid-like material. Histologically, the lesion was composed of spindle cells with high cellularity and rich vascularization with a haemangiopericytoma-like pattern. The diagnosis of solitary fibrous tumour (SFT) was made. The differential diagnosis for SFT of the pre-sacral spaace involves haemangiopericytoma, GIST, malignant mesothelioma, synovial sarcoma, leiomyomatous tumours and granulosa cell tumour. Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2, but no staining for desmin, inhibin, c-kit, EMA, CK, SMA, S-100 and CD31, confirming a diagnosis of SFT. Although SFT is usually associated with a favourable prognosis, close follow-up is recommended because of the limited information on its long-term behaviour.

Thyroid cancer in suppressed contralateral lobe of patients with hot thyroid nodule.

We studied 60 patients with thyrotoxicosis due to single toxic nodule. At surgery in 3 patients (5%) a papillary carcinoma has been detected in the contralateral suppressed lobe. Thyroid function tests and thyroid scan confirmed thyrotoxicosis. Thyroid stimulating hormone (TSH) was undetectable in all patients. It is common opinion that differentiated thyroid tumour growth is TSH dependent. On the basis of our study two hypotheses are possible: (1) the development of thyroid carcinoma precedes the adenoma and suppressed TSH levels inhibit tumour growth; (2) suppressed TSH levels do not protect patients from the occurrence of cancer. In the evaluation of hot thyroid nodule we suggest careful ultrasonographic control in order to look for nodules outside the adenoma. A complete surgical examination of the whole thyroid gland is required and intraoperative biopsies are advocated in abnormal areas.

Correlation of p53 and bcl-2 expression with vascular endothelial growth factor (VEGF), microvessel density (MVD) and clinico-pathological features in colon cancer.

This study was designed to elucidate the possible relationship between tumour related genes and angiogenesis in colon cancer. The protein expression of p53, bcl-2, Von Willebrand factor and vascular endothelial growth factor (VEGF) were analysed by immunohistochemistry in 57 paraffin-embedded colon cancer. The results showed that microvessel density (MVD) was lower in VEGF negative tumours than in VEGF positive ones (P<0.0001). MVD and VEGF in p53 negative tumours were significantly lower than in p53 positive tumours (respectively, P=0.003 and P<0.0001). Moreover, positive correlations were recorded between VEGF expression and MVD, and bcl-2 expression (respectively, P<0.0001 and P=0.009). Our data confirm the central role of VEGF in angiogenesis and suggest direct correlations among p53, bcl-2 and VEGF expression in colon cancer.

Collection of 'normal' blood repopulating cells during early hemopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukemia.

Twenty-five patients with CML (chronic phase (CP): 15 patients; accelerated phase (AP): 10 patients) at a median of 40 months after diagnosis and ineligible for allogeneic BMT, received an intensive chemotherapy regimen consisting of idarubicin, intermediate-dose ara-C and etoposide (ICE protocol). All patients had previously received alpha-interferon and only two patients had had partial cytogenetic response. During recovery from chemotherapy-induced aplasia, blood progenitors cells (BPC) were harvested by leukapheresis. All metaphases were found to be Ph-negative in the collection of 12 of 25 (48%) patients (CP: 9 of 15 (60%), AP: 3 of 10 (30%)) and a decrease of < 50% Ph-positive metaphases was seen in an additional five (CP: 4 patients; AP: 1 patient). The percentage of complete Ph-disappearance was 66% in patients receiving this procedure within the first 2 years of diagnosis and 30% in those treated after the second year of diagnosis. So far, the Ph-negative collections have been used in 9 patients (CP: 8 patients; AP: 1 patient) as autograft after conditioning with total body irradiation/etoposide/CY. Seven of 9 patients engrafted and 5 are alive and well, Ph-negative at 2+, 3+, 6+, 10+ and 18+ months.

Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer.

AIMS: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB-IIA non-small cell lung cancer (NSCLC). METHODS: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105. RESULTS: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p = 0.04). Univariate analysis showed that those patients with VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression (p = 0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p = 0.0002). CONCLUSIONS: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC. This may be because these factors are more closely related to the metastatic process.

Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

[Coexistence of hyperthyroidism and thyroid carcinoma. Description of a clinical case]. / Coesistenza di ipertiroidismo-carcinoma tiroideo. Segnalazione di un caso clinico.

The association of hyperthyroidism and thyroid carcinoma, especially multicentric forms, is an unusual event. We present the case of a 49-year-old woman with clinical and radiological findings of hyperfunctioning thyroid nodule that showed, after a subtotal thyroidectomy, histologic evidence of multicentric carcinoma in one lobe and adenoma in the other lobe. The interest of this clinical case is in the coexistence of an independent adenoma with a multicentric carcinoma, revealed by radical surgery that was necessary for the occurrence of a multinodular goiter. The incidence of this situation could be underestimated in consequence of the current surgical approach to the single "hot" nodule and suggests we pay attention to these patients for the possible presence of malignancy in functionally-inhibited thyroid tissue.

Biovularity and "coalescence of primary follicles" in ovaries with mature teratomas.

Several theories have been postulated regarding the origin of ovarian teratomas, including incomplete twinning, neoplastic proliferation of sequestered totipotent blastomeres or primordial cells, derepression of totipotent genetic information in the nuclei of somatic cells, and parthenogenetic development of germ cells. At present parthenogenetic development of ova is the most widely accepted theory, primarily because of the presence of a 46 XX karyotype in almost all mature teratomas. However, some authors have raised the possibility of fusion of ova in the mechanism of formation of ovarian teratomas. We report the results of a study on ovarian tissue adjacent to 31 teratomas to assess the frequency of biovularity, which could provide evidence favoring the last theory. On the whole we found biovularity in 26 ovaries of young patients (mean age, 27 years) with variable numbers of biovular follicles ranging from 1 in 4 cases to more than 10 in 2 cases; the number of biovular follicles depended on the quantity of ovarian tissue examined as well as on the total number of ova in the tissue. In multiple occasions 2 ova were included within a single follicle; in 24 ovaries the biovularity was correlated with coalescence of primary follicles characterized morphologically by an ovoid or hourglass-like shape that resulted from cohesion of 2 follicles. As control cases, 30 ovaries of patients with an average age of 28 years were examined (12 removed for endometriosis, 8 for serous cystadenoma, 7 for tubal pregnancy, and 3 for acute salpingo-oophoritis). Only 1 ovary with endometriosis contained a single biovular follicle. The results suggest that ovarian teratoma development may result from fusion of ova in ovaries containing biovularity and phenomena of coalescence of primary follicles.