Characterization of the c.793-1G > A splicing variant in CHEK2 gene as pathogenic: a case report.

BACKGROUND: CHEK2 is involved in the DNA damage repair response Fanconi anemia (FA)-BRCA pathway. An increased risk for breast and other cancers has been documented in individuals who carry a single pathogenic CHEK2 variant. As for other genes involved in cancer predisposition, different types of pathogenic variants have been observed, including single nucleotide variations, short insertions/deletions, large genomic rearrangements and splicing variants. Splicing variants occurring in the splicing acceptor or donor site result in alternative mature mRNA produced and can cause intron retention, exon skipping, or creation of alternative 3' and 5' splice site. Thus, the pathogenicity of this type of alterations should always be explored experimentally and their effect in the mRNA and consequently the protein produced, should be defined. The aim of this study was the delineation of the effect of a splicing variant in the CHEK2 gene. CASE PRESENTATION: A healthy 28-year-old woman with a family history of breast and ovarian cancer was referred for genetic testing. The variant c.793-1G > A (rs730881687) was identified by Next Generation Sequencing (NGS) using a solution-based capture method, targeting 33 cancer predisposition genes (SeqCap EZ Probe library, Roche NimbleGen). Experimental analysis in patient-derived leukocytes using RT-PCR of mRNA followed by cDNA sequencing revealed the deletion of one base from the alternative transcript created (r.793del). This resulted in a frameshift leading to premature termination codon within exon 7 (p.(Asp265Thrfs*10)). CONCLUSIONS: This finding suggests that the CHEK2 splicing variant c.793-1G > A is a deleterious variant. Our case shows that RNA analysis is a valuable tool for uncharacterized splice site variants in individuals referred for testing and facilitates their personalized management.

Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Many Faces of Adrenal Lesions in a Large Patient Cohort: What Has Changed Over the Last Two Decades?

OBJECTIVE: To review the presentation characteristics, clinical and hormonal evaluations, and histopathological results of patients with adrenal lesions over a 21-year period and evaluate the changes across the two decades. METHODS: This single-center, retrospective study included 1003 patients with adrenal lesions who presented to our department between 2000 and 2021. Clinical, metabolic, hormonal, radiological, and pathological data of the patients were collected. RESULTS: Forty-seven percent of the lesions were non-functioning adrenal adenomas. Possible autonomous and autonomous cortisol secretion were detected in 22.2% of the patients. The percentages of the patients diagnosed with pheochromocytoma, primary hyperaldosteronism, adrenal Cushing syndrome, adrenocortical carcinoma, and adrenal metastasis were 7.4%, 4.8%, 4.7%, 0.9%, and 5.6%, respectively. Adrenalectomy was performed in 31.3% of the patients. Functional adrenal lesions were the leading cause of surgery (46.5%), followed by large size and/or suspicious imaging features (38.6%). Among the patients referred to surgery due to large size (≥6 cm), the diagnosis in 19% was metastasis, and in 12.1%, it was primary adrenocortical carcinoma. In patients with adrenal lesions with a size of 4-6 cm and suspicious imaging properties, the rates of metastasis and primary adrenocortical carcinoma were 44.4% and 4.8%, respectively. From the first to the second decade, major differences in presentation characteristics were increased detection of bilateral lesions and increased prevalence of possible autonomous and autonomous cortisol secretion. CONCLUSIONS: Adrenal lesions are common in the adult population, and while it is important to avoid overtreatment, hormone secretion, and malignancy should not be overlooked.

The new normal for breast cancer surgery during COVID-19 pandemic: An international survey conducted by SENATURK.

PURPOSE: The COVID-19 pandemic has changed the way many health institutions approach their workload. Physicians managing patients with cancer now have to deal not only with the disease but also the restrictions and limitations imposed because of the global pandemic. We aimed to determine how surgical preferences in breast cancer management were affected globally using a questionnaire-based survey. METHODS: Under the auspices of the Turkish Senology Society (SENATURK) we asked 122 surgeons from 27 countries to reply to a 26-question survey designed to measure the impact of COVID-19 on their surgical practice when treating patients with breast cancer. RESULTS: The characteristics of participant surgeons were statistically similar when comparing the participants' answers from Turkey and other countries. From the responses given to our questionnaire, it was understood that breast cancer surgery decreased by 25% (p<0.05) in institutions all over the world, including Turkey, but there was no change in the approach technique to the axilla. CONCLUSIONS: Globally breast surgeons have adapted to the new normal due to the COVID-19 pandemic. Many surgical approaches and some follow up protocols have been changed, although the degree of change has varied from country to country. In addition, the availability of multidisciplinary case conferences has been reduced in some centers which may affect the quality of services provided to patients.

Pathologic nipple discharge in patients with radiologically invisible mass: review of 28 consecutive sub-areolar explorations.

The carcinoma frequency of clinically and radiologically negative pathologic nipple discharges (PNDs) and the optimum management strategy of these cases are still unclear. In this study, the frequency of cancer and the situation of the classic surgical intervention in patients with PND and invisible mammographic and ultrasonographic results are reviewed. The data pertaining to the cases of sub-areolar exploration and major duct excision in a surgery clinic of university hospital from December 2002 to June 2007 have been examined in detail. In 28 cases with PND, which did not have any findings during conventional radiologic examinations, 21% of cases had malignant, and 7% of cases had atypical ductal hyperplasia. The frequency of invasive or in situ carcinoma is not low in clinically and radiologically negative PNDs. Sub-areolar exploration and major duct excision seems to be an appropriate and definitive diagnostic and therapeutic option in this special patient group.

Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis.

INTRODUCTION: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-gamma ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear. AIM AND METHODS: The present study aimed to investigate the chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200 microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their combination on a DMBA-induced rat mammary carcinogenesis model. RESULTS: In the rosiglitazone group, no malignant tumour developed, apart from the lowest proliferative mammary lesions. In the fenretinide group, 30% developed a malignant tumour but there were no benign tumours. Cancer incidences were 61.5% and 10% in the control and combination groups respectively. CONCLUSIONS: Our results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid fenretinide have potent chemopreventive properties against in vivo mammary carcinogenesis; however, the efficacies were not enhanced by their combination.

Comparison of irisin hormone expression between thyroid cancer tissues and oncocytic variant cells.

Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto's thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls (p<0.05). In addition, mild immunoreactivity was observed in the thyroid tissues of patients with papillary carcinoma while significantly increased irisin immunoreactivity was observed tissues of patients with oncocytic papillary carcinoma (p<0.05). There was no difference in irisin immunoreactivity in thyroid tissues between patients with follicular carcinoma and controls. However, irisin immunoreactivity was higher in tissues of patients with oncocytic follicular carcinoma than in tissues of patients with follicular carcinoma (p<0.05). No irisin immunoreactivity was observed in tissues of patients with medullary carcinoma, a malignant tumor the thyroid; however, irisin expression was significantly increased in tissues of patients with anaplastic carcinoma compared with that in tissues of controls (p<0.05). Furthermore, in all thyroid tissues with irisin expression, irisin immunoreactivity was observed in follicular cells, indicating that irisin is produced by these cells. Conclusion: Irisin is a novel potential immunohistochemical marker for differentiating oncocytic variants of papillary and FTCs from papillary and follicular thyroid cancers.

Exposure of surgical staff in surgical probe applications in radioguided parathyroidectomy.

The aim of this study is to calculate the exposure of surgical staff during radioguided parathyroidectomy. Two parathyroidectomy operations on patients with parathyroid adenoma were selected. Fifty-centimeter spaced circles were drawn surrounding the operation bed on the floor of the operation room. During the operation, radiation dose was measured according to the drawn circles at distances of 50-200 cm from the side of patient's head, bilateral neck and abdomen while the patient lied on the operation bed. All the operations were recorded throughout with a video camera. Three physicians watched all records. The time spent at each distance for every staff during the operation was recorded. Whole body dose to senior surgeon was calculated as 8.78-11.00 microSv which means that a senior surgeon can perform 91-114 procedures per year to reach the annual International Commission on Radiological Protection (ICRP) radiation dose limit for a member of the public. We concluded that radiation risk to the surgical staff is low from radioguided parathyroidectomy.

Metastatic tumors in the breast: a report of 5 cases and review of the literature.

Breast cancer is the most common malignancy in women. However, metastases to the breast from nonmammary malignant neoplasms are rare and were detected at a rate of 0.28% in our series. Clinical and pathologic findings in 5 cases of metastatic tumors (malign mesenchymal tumor, squamous cell carcinoma of the tongue, non-Hodgkin lymphoma, and Sézary syndrome) in the breast are presented and discussed with respect to the literature. Detailed clinical history and a multidisciplinary approach are useful in establishing correct diagnosis and preventing unnecessary radical surgery.

Porcine Dermal Collagen Prevents Seroma Formation After Mastectomy and Axillary Dissection in Rats.

OBJECTIVE: Seroma occurs as a result of accumulation lymphovascular liquid in the dead space forming after tissue dissection. It is the most common complication after breast surgery. Collagens are the common component of extracellular matrix and have an important role in wound healing. In this study, we aimed to investigate the efficiency of the Porcine Dermal Collagen in preventing Seroma. MATERIALS AND METHODS: Eighteen young female Wistar rats were used and divided into three groups. Mastectomy and axillary dissection were performed in each group. No other procedures were performed in Group 1 (Control group). Porcine dermal collagen was applied to 50% of the mastectomy field in Group 2 and to 100% of the mastectomy field in Group 3. RESULTS: Seroma volume was significantly decreased in Group 3 in contrast to Groups 1 and 2 (p<0.001) and in Group 2 in contrast to Group 1 (p<0.001). Vascular proliferation, granulation tissue formation and congestion were significantly increased in Group 3 (p<0.05). CONCLUSION: We conclude that the use of Porcine Dermal Collagen reduces the formation of seroma in the model of experimental mastectomy and axillary dissection. As the amount of Porcine Dermal Collagen applied increases the formation of seroma reduces.

Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer.

AIMS: The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. MATERIALS AND METHODS: The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer+NS); Group III (5mg/kg sildenafil citrate, low dose); Group IV (10mg/kg sildenafil citrate, high dose); Group V (0.6mg/kg heparin, low dose); Group VI (6mg/kg heparin, high dose); Group VII (20nmol/kg des-acyl ghrelin); Group VIII (40nmol/kg des-acyl ghrelin); Group IX (4nmol/kg acyl ghrelin); Group X (8nmol/kg acly ghrelin); Group XI (20pmol/kg Nesfatin-1); Group XII (15nmol/kg Obestatin) and Group XIII (5nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. KEY FINDINGS: The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. SIGNIFICANCE: Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer.

The incidence of 18F-FDG PET/CT thyroid incidentalomas andthe prevalence of malignancy: a prospective study.

BACKGROUND/AIM: To determine the prevalence of malignancy in thyroid incidentalomas (TIs) detected by fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: 18F-FDG PET/CT images were evaluated prospectively for the presence of thyroid uptake. The patients with a TI were evaluated by an endocrinologist according to the predefined diagnostic algorithm. The final diagnosis was obtained clinically and/or by pathology. RESULTS: TI was detected in 4.2% of 4204 patients. A malignant thyroid nodule was diagnosed in 29% and 33% of the focal and diffuse-focal uptake groups, respectively. However, no malignancy was detected in the diffuse uptake group. The standardized maximum uptake values (SUVmax) of the nodules were significantly higher in patients with thyroid malignancy than in patients with benign nodules (P = 0.006). The calculated cut-off value of SUVmax for malignancy was 3.5. In 2 patients in whom the cytopathological diagnosis was benign, malignancy was diagnosed after total thyroidectomy. CONCLUSION: A malignant nodule was present in one-third of the patients with focal or diffuse-focal uptake. A SUVmax value of 3.5 was considered as a cut-off value for the differentiation of a malignant lesion. Benign cytology in fine-needle aspiration biopsy for 2 patients underestimated a thyroid malignancy.

Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats.

7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer.

BACKGROUND: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells. METHODS: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels. RESULTS: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM. CONCLUSION: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells.

The effects of pentoxifylline on bacterial translocation after intestinal obstruction.

Bacterial translocation (BT) occurs mainly in preseptic conditions such as intestinal obstruction, trauma, and burn, and the underlying mechanisms are still unclear. Pentoxifylline (PTX) is a derivative of methyl xanthine and has several beneficial effects in sepsis. We investigated the effects of PTX on a rat BT model. Simple intestinal obstruction (IO) was choosen to create high BT rates. Rats were divided in to five groups of 10 rats. Either 50 mg/kg PTX or placebo (3 mg/100 g saline) was administered subcutaneously following IO, either by single injection or twice with a 12-h interval. All rats were sacrificed 12 or 24 h after the procedure, and mesenteric lymph nodes (MLN), liver, and blood samples were obtained under aseptic conditions for bacterial cultures. The samples were obtained 12 h following IO in the first two groups, and the same samples were obtained 24 h after IO in last three groups. Groups IV and V were the PTX treatment groups. PTX was re-injected 12 h after IO only in group IV. As a result, BT rates in MLNs and liver were found to be significantly low, blood specimens remained sterile in PTX-pretreated and -treated rats, and BT rates were high in control groups and group V (once treatment late specimen group). We conclude that simple intestinal obstruction causes BT, and PTX reduces BT in rats with IO during the first 12-h period if PTX is given once immediately following IO. PTX reduces BT during the first 24-h after IO provided that is injected twice with a 12-h interval. More experimental studies are need to explain the exact mechanism of this beneficial effect.

Warthin-like papillary carcinoma of the thyroid: a case series and review of the literature.

Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant.

Interobserver and intraobserver agreement in parathyroid scintigraphy: How can parathyroid scintigraphy be made more reliable?

OBJECTIVE: To determine the intraobserver and interobserver agreement levels in the evaluation of technetium Tc 99m sestamibi parathyroid scintigraphic images. METHODS: Ninety-eight patients with hyperparathyroidism were included in the study, and their parathyroid images were evaluated by 4 experienced nuclear medicine observers. The 98 cases were evaluated twice by each observer within an interval of 2 weeks. The evaluations were performed directly on workstations with use of digital images. A questionnaire was completed by each observer. The presence of a lesion, the number and the localizations of the lesions, and whether the lesion was clear or doubtful were all evaluated. Cohen kappa statistics and total agreement percentages were calculated by using SPSS version 11.0 software. RESULTS: The 4 observers performed 8 different evaluations and identified a minimum of 38 and a maximum of 43 cases with a parathyroid lesion (or lesions). Both the intraobserver and the interobserver agreements were "very good" for the presence of a parathyroid lesion. The intra-observer agreement was also "very good" and the interobserver agreement was "good" (for only 1 pair of observers) or "very good" for the evaluation of the number of parathyroid lesions. The intraobserver agreement was "very good" or "good" and the interobserver agreement was "good" for the lesion localization and for the presence of a doubtful lesion. CONCLUSION: Parathyroid scintigraphy seems to be an observer independent method in the detection of a parathyroid lesion, in the determination of the number of lesions, and in the localizations of the lesions. The measured high agreement between observers increases the reliability of parathyroid scintigraphy.

Factors predicting non-sentinel lymph node involvement in sentinel node positive breast carcinoma.

OBJECTIVE: In routine practice, axillary lymph node dissection is performed in early invasive breast cancer patients with positive sentinel node biopsy. However, sentinel node is the only involved axillary node in 40-70% of patients, and determining factors that predict axillary non-sentinel node involvement will therefore prevent unnecessary axillary lymph node dissection and decrease morbidity. MATERIAL AND METHOD: In this study, 119 invasive breast cancer patients with sentinel node metastasis who underwent axillary lymph node dissection between 1998-2009 at our institution were studied. Primary tumor characteristics and features of the metastatic tumors in sentinel nodes, such as microanatomic location, size of metastasis, and the ratio of metastatic tumor area to the total sentinel node area were evaluated. Student's t-test and multivariate logistic regression were used for statistical analysis. RESULTS: The mean age of the patients was 50.7 years (28-80). Forty-three patients (36%) had invasive ductal and 25 patients (21%) had invasive lobular carcinoma. Most of the patients had either pT1 (44%) or pT2 (54%) tumors. Fifty-four patients (45%) had no further positive nodes in the axilla. The metastatic deposits in the sentinel node were subcapsular in 16 patients (13%). The percent area of sentinel node occupied by tumor (p < 0.001), number of sentinel nodes (p=0.041), and microanatomic location of metastatic tumor (p=0.002) were significantly associated with non-sentinel node metastasis in univariate analysis. The percent area of sentinel node occupied by tumor (p < 0.001) and number of sentinel nodes (p=0.033) remained significantly associated with non-sentinel node involvement in multivariate analysis. CONCLUSION: In patients with invasive breast cancer and positive sentinel node, area percent of sentinel node occupied by tumor, and the number of sentinel nodes removed are independently predictive of non-sentinel node involvement.

Papillary carcinoma arising in subhyoid ectopic thyroid gland with no orthotopic thyroid tissue.

Ectopic thyroid gland with no orthotopic thyroid tissue is extremely rare. The authors present a case of a follicular variant of papillary carcinoma developed from an ectopic thyroid gland with no orthotopic thyroid tissue.