Tall Cell Carcinoma with Reversed Polarity: Case Report of a Rare Special Type of Breast Cancer and Review of the Literature.

Background: Tall cell carcinoma of the breast with reversed polarity (TCCRP) is a rare type of invasive breast cancer with overlapping features with papillary thyroid carcinoma and a characteristic molecular profile. Few cases have been reported in the literature since the first case was described in 2003. Case presentation: We present the case of a 41-year-old female with a symptomatic left breast lump. Image-guided core biopsy was diagnosed as triple-negative apocrine carcinoma. Surgical excision revealed an invasive carcinoma with solid papillary pattern, nuclei arranged away from the basement membrane (reversed polarity) and luminal eosinophilic colloid-like material. The tumour was GATA3-, CK5-, CK14- and CK7-positive and TTF1-negative. Specialist opinion and the identification of hotspot mutations in the IDH2 p.Arg172 gene via PCR confirmed the diagnosis of TCCRP. Conclusions: TCCRP is a relatively recently recognised papillary epithelial neoplasm with characteristic morphological features and molecular profile. Due to its rarity, TCCRP can be diagnostically challenging, and features can be mistaken for benign and malignant lesions. Accurate diagnosis is important in effective treatment of this indolent malignant triple-negative breast cancer, which carries an excellent prognosis.

Factors That Influence Time to Operating Room for Geriatric Hip Fractures: A Quality Improvement Initiative.

Background: For geriatric hip fractures, the current American College of Surgeons guideline recommends surgery within 48 hours. We sought to identify which factors delayed a patient's progression to definitive surgery at 2 associated level II trauma centers using chart abstraction. Methods: We reviewed all geriatric patients who underwent a surgical procedure for a hip fracture. Data regarding age, length of stay, procedure, and minutes from emergency department arrival to operating room (OR) were evaluated. Chart abstraction determined if cardiac or medical clearance and an echocardiogram were obtained. For patients that entered the OR over 24 hours, a reason was identified for the delay. Analysis of variance was used to compare continuous data, and chi-squared tests were used for categorical data. Results: Of 477 patients, 288 (60%) presented to the OR in under 24 hours, 114 (24%) between 24 and 36 hours, and 75 (16%) over 36 hours. There was a significant increase in length of stay for patients, over 36 hours. Patients presenting to the OR between 24 and 36 hours were often delayed due to facility reasons such as OR or surgeon availability while patients presenting over 36 hours were delayed due to medical comorbidities. Of all patients in the under-24-hours group, 34.7% had an echocardiogram compared with 56.1% and 69.3%, respectively. Similarly, 17.7% of patients received cardiac clearance in the under-24-hours group, compared with 31.8% and 48%, respectively. Conclusions: The timeliness of presentation of hip fractures to the OR is a multidisciplinary effort and requires cooperation between a variety of services to increase safety and efficiency as well as to control costs.

Does sentinel lymph node biopsy for screening high-grade ductal carcinoma in situ of the breast cause more harm than good?

PURPOSE: Ductal carcinoma in situ (DCIS) of the breast does not metastasize to axillary lymph nodes. Yet high-grade DCIS (HgDCIS) is often subjected to Sentinel Lymph Node Biopsy (SLNB) concomitant with definitive surgery. This is to avoid further axillary surgery in the event of upstaging to invasive carcinoma, which often entails Axillary Lymph Node Dissection (ALND). We wished to examine the validity of this approach. METHODS: This study includes a retrospective analysis of consecutive pre-operatively diagnosed HgDCIS patients from a single screening unit between December/2014 and August/2016. The main outcomes were the overall incidence of upstaging and the independent predictors of upstaging on multivariable analysis. The rates of various complications of SLNB vs ALND in four RCTs were used to calculate the upstaging rate below which SLNB could be safely omitted. RESULTS: There were 224 eligible patients of whom 26 (11.6%) were upstaged. Axillary metastasis (pN1) occurred in two patients (0.9%). On Univariable analysis, upstaged patients were significantly younger (median (IQR) = 56.0 (51.0-63) vs 60.0 (54.0-65.0); p = 0.019). Radiological size, pathological size, type of biopsy, type of operation, and comedo-necrosis were not significant (p > 0.05). On multivariable analysis, age as a continuous variable (OR 0.93; p = 0.031) and core biopsy (OR 2.62; p = 0.036) were the only independent predictors of upstaging. Chi-square test showed that patients < 55 years whose pre-operative diagnosis was made on core biopsy were at significantly higher risk of upstaging than the others (31.8% vs 9.4%; p = 0.002). CONCLUSION: Upstaging of HgDCIS is infrequent. According to the known rates of complications of SLNB relative to ALND, routine SLNB concomitant with surgery seems to be more harmful than its routine omission. A selective approach based on age and type of biopsy could be considered.

A rare case of symptomatic hyperparathyroidism in an elderly patient with dual pathology.

Primary hyperparathyroidism secondary to true sporadic synchronous parathyroid cancer (PTCa) and adenoma (PTa) is rare. This is a case of an 80-year-old female admitted with symptomatic hypercalcaemia, raised serum calcium (Ca) of 3.39 mmol/L and raised parathyroid hormone (PTH) of 44.3 pmol/L. Ultrasonic evaluation of the neck revealed a mass posterior to the right thyroid lobe. Imaging of the left neck was unremarkable. Subsequent sesta-MIBI and single-photon emission computed tomography-computed tomography (SPECT-CT) scanning highlighted conspicuous activity over the right lower neck consistent with the neck ultrasound scan findings. Pre-operatively, PTa was suspected. Intra-operatively, malignancy was suspected due to infiltration of the parathyroid tumour into the thyroid. The right inferior parathyroid and right thyroid gland were resected. Histology confirmed PTCa. Despite surgical treatment, she was found to have persistently high Ca and PTH levels. Further investigation with a repeat sesta-MIBI and SPECT-CT suggested a left inferior parathyroid tumour. Excision of this mass revealed a PTa. Recovery was unremarkable and serum biochemistry returned to normal ranges.

A technique for marking oncological breast tissue specimens.

With new breast conserving oncological surgical techniques, accurate identification of specimen margins is important to allow for the re-excision of margins. The accurate identification of margins is crucial is the success of the patients treatment if further margins are required. NHS Breast Screening Programme (NHSBSP) guidelines recommend the excised specimen is labelled accurately to correctly identify the margins and allow for X-ray examination. This method has been proven to be cheap, it uses equipment and materials readily available in the operating theatre. Furthermore, if any of the methods fails as there is more than one way to identifying your margins. For example if a clip were to fall off, the type/length of suture and the orientation on the board will still allow you to identify the correct margin. If the sample was to fall off the board, the sutures and clips will still allow the pathologist to orientate the sample. In summary this method is easy to apply, logical and uses equipment readily available within the theatre, i.e. silk sutures, and the needle protection board. It ensures all relevant radiological and surgical criteria are met for enabling orientation of the specimen when removed from the breast tissue. It is an easily taught technique that is easy to remember. A national survey showed a lack and wide variation of specimen orientation protocols. (Volleamere et al., 2013) This technique could be used as the national standard for breast specimen marking and as a national marking system for the NHS.

A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients.

AIMS: Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs. METHODS AND RESULTS: RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB). CONCLUSIONS: Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.

Dietary glucoraphanin-rich broccoli sprout extracts protect against UV radiation-induced skin carcinogenesis in SKH-1 hairless mice.

Feeding broccoli sprout extracts providing daily doses of 10 micromol of glucoraphanin to SKH-1 hairless mice with prior chronic exposure to UV radiation (30 mJ cm(-2) of UVB, twice a week, for 17 weeks) inhibited the development of skin tumors during the subsequent 13 weeks; compared to the controls, tumor incidence, multiplicity, and volume were reduced by 25, 47, and 70%, respectively, in the animals that received the protective agent.

Rapid body weight gain increases the risk of UV radiation-induced skin carcinogenesis in SKH-1 hairless mice.

Although it is well known that caloric restriction reduces the risk of chronic diseases including cancer, the role of weight gain in the development of UV light-induced tumors has not, to our knowledge, been investigated. In view of the increase in obesity worldwide, we asked the question whether there is any relationship between body weight gain and skin tumor development. We subjected 3 groups, each composed of 30 SKH-1 hairless female mice, to UV radiation (30 mJ/cm(2), twice weekly for 17 weeks) and observed tumor formation over the ensuing 8 to 13 weeks: group 1 received pelleted diet; group 2 received pellets during the irradiation period and was then switched to powder; and group 3 received powder exclusively. At the end of the experiment, the mean body weight of group 1 was 32.1 +/- 0.5 g, whereas that of groups 2 and 3 was 39.0 +/- 1.5 and 39.5 +/- 1.4 g, respectively. Tumor incidence reached 90% at 8 weeks after completion of irradiation for the animals in group 3 and at 13 weeks for the animals in group 2. Similarly, at 8 weeks after irradiation when all animals of group 3 were euthanized, tumor multiplicity was 0.8, 1.2, and 3.2 for groups 1, 2, and 3, respectively. Thus, in comparison with the mice consuming pellets, the powder-fed mice gained weight more rapidly and developed tumors much faster. Considering the escalating numbers of individuals worldwide who are overweight or obese, our findings provide further impetus for advocating healthier diets and maintenance of constant body weight in adults.

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice.

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality.

Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts.

The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light-induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm(2) increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans.

Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts.

Aerobic life, UV solar radiation, genetic susceptibility, and immune status contribute collectively to the development of human skin cancers. In addition to direct DNA damage, UV radiation promotes the generation of reactive oxygen intermediates that can cause oxidative damage and inflammation, and ultimately lead to tumor formation. Treatment of murine and human keratinocytes with the isothiocyanate sulforaphane elevated phase 2 enzymes and glutathione and protected against oxidant toxicity. Topical application of sulforaphane-containing broccoli sprouts extracts induced the phase 2 response in mouse skin in vivo. Sulforaphane inhibited cytokine-dependent (gamma-interferon or lipopolysaccharide) induction of iNOS in RAW 264.7 macrophages. The UV-radiation-induced skin carcinogenesis in "initiated high-risk mice" was substantially inhibited by broccoli sprout extracts containing sulforaphane. After completion of the UV irradiation schedule (30 mJ/cm(2)/session twice a week for 20 weeks), groups of approximately 30 mice were treated topically on their backs (5 days a week for 11 weeks) with broccoli sprout extract containing either the equivalent to 0.3 micromol (low dose) or 1.0 micromol (high dose) sulforaphane, respectively. At this time point, the tumor incidence had reached 100% in the control mice. Tumor burden, incidence, and multiplicity were reduced by 50% in the animals that received the high dose of protector. Tumor incidence and multiplicity did not differ between the low dose-treated and the control groups, but the low dose treatment resulted in a substantial reduction of the overall tumor burden. Thus, topical application of sulforaphane-containing broccoli sprout extracts is a promising strategy for protecting against skin tumor formation after exposure to UV radiation.